Publications

<![CDATA[ %0 Book %A Brower, RG %D 1998 %T Future clinical trials of mechanical ventilation in ARDS and ALI %E Marini, J. J. %E Evans, T. W. %B Acute Lung Injury %C Belrin %I Springer-Verlag %! Future clinical trials of mechanical ventilation in ARDS and ALI %0 Journal Article %A Wheeler, AP %A Bernard, GR %A Schoenfeld, DA %A Steinberg, KP %D 1998 %T Methylprednisolone for Unresolving ARDS %B JAMA %V 280 %N 24 %P 2074 %8 12/1998 %9 Letter %! Methylprednisolone for Unresolving ARDS %U http://jama.jamanetwork.com/article.aspx?articleid=1154074 %0 Conference Paper %A Brower, RG %A ARDSNet, NIH / NHLBI %D 1999 %T Assessment of protocol conduct in a trial of ventilator management of acute lung injury (ALI) and ARDS %B ATS %X 159:A %0 Conference Paper %A Krishman, JA %A Thompson, DA %A Diette, G %A Brower, RG %A ARDSNet, NIH / NHLBI %D 1999 %T ALI/ARDS survival after hospital discharge sampling interval and accuracy of patient exposure in ARDS %B ATS %X 159:A %0 Conference Paper %A Krishman, JA %A Thompson, DA %A Diette, G %A Brower, RG %A ARDSNet, NIH / NHLBI %D 1999 %T PaO2/FiO2 predicts mortality in patients with ALI/ARDS sampling interval and accuracy of patient exposure in ARDS %B ATS %X 159:A %0 Conference Paper %A Morris, AH %A ARDSNet, NIH / NHLBI %D 1999 %T Data sampling interval and acuracy of patient exposure in ARDS %B ATS %8 1999 %X 159:A %0 Conference Paper %A Morris, AH %A Orme, JF %A Clemmer, T %A Grissom, CK %A Weaver, L %A Young, MP %A East, T %A Uhler, J %A Funlinson, K %A ARDSNet, NIH / NHLBI %D 1999 %T Hemodynamic computerized protocol development %B ATS %8 1999 %X 159:A %0 Conference Paper %A Parsons, PE %A ARDSNet, NIH / NHLBI %D 1999 %T The incidence of non-pulmonary organ failure is independent of Pao2/FiO2 ratio %B ATS %8 1999 %X 159:A %0 Conference Paper %A Parsons, PE %A ARDSNet, NIH / NHLBI %D 1999 %T Low tidal volume ventilation is routinely used in patients with early acute lung injury %B ATS %8 1999 %X 159:A %0 Generic %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 1999 %T Results on the Study on mechanical ventilation %C Berlin, Germany %P 65-59 %8 10/1999 %! Results on the Study on mechanical ventilation %0 Conference Paper %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 1999 %T Baseline physiologic assessment and outcome in 234 patients with acute lung injury (ALI) %B ATS %8 1999 %X 159:A %0 Conference Paper %A Abraham, E %A ARDSNet, NIH / NHLBI %D 2000 %T Lisofylline versus placebo for ALI and ARDS %B ATS %8 2000 %X 161:A %0 Conference Paper %A Abraham, E %A Bursten, S %A Schoenfeld, DA %D 2000 %T Free fatty acids as predictors of outcome in ARDS %B ATS %8 2000 %X 161:A %0 Book %A Brower, RG %A Fessler, HE %D 2000 %T Mechanical ventilation in acute lung injury and acute respiratory distress syndrome %E Wiedemann, H. P. %E Matthay, M. A. %B Clinic in Chest Medicine %V 21 %P 491-510 %! Mechanical ventilation in acute lung injury and acute respiratory distress syndrome %0 Journal Article %A Brower, RG %A Matthay, MA %A Wheeler, AP %D 2000 %T Ventilation with lower tidal volumes as compared with traditional volumes for acute lung injury (letter) %B New Engl J Med %V 343 %P 812-814 %! Ventilation with lower tidal volumes as compared with traditional volumes for acute lung injury (letter) %U http://www.nejm.org/doi/full/10.1056/NEJM200009143431113 %0 Conference Paper %A Eisner, MD %A Thompson, BT %A Hudson, LD %A Luce, JM %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2000 %T Low tidal volume ventilation reduces mortality independent of the clinical risk factor for ALI/ARDS %B ATS %8 2000 %X 161:A211 %0 Conference Paper %A Ely, EW %A Wheeler, AP %A Thompson, BT %A Steinberg, KP %A Ancukiewicz, M %A Bernard, GR %D 2000 %T Age is an independent predictor of outcomes in ARDS %B ATS %8 2000 %X 161:A210 %0 Conference Paper %A Gottlieb, JE %A Park, PK %A Girod, A %A Ancukiewicz, M %A Hayden, D %A Schoenfeld, DA %D 2000 %T Comparison of neuromusclar blocker and sedative use among patients with ARDS treated with lows versus high tidal volume %B ATS %8 2000 %X 161:A506 %0 Conference Paper %A Klein, D %A Morris, AH %A ARDSNet, NIH / NHLBI %D 2000 %T Variations in tidal volume due to predicted body weight equations %8 2000 %X 161:A %0 Book %A Knudsen, N %A Fulkerson, WF %D 2000 %T Ventilator induced lung injury %E MacIntyre, N. R. %E Branson, R. %B Mechanical Ventilation %C Philadelphia %I WB Saunders %P 212-221 %! Ventilator induced lung injury %0 Conference Paper %A Krishman, JA %A Hayden, D %A Schoenfeld, DA %A Bernard, GR %A Brower, RG %A ARDSNet, NIH / NHLBI %D 2000 %T Outcome of participants vs eligible non-participants in a clinical trial of critically ill patients %B ATS %8 2000 %X 161:A %0 Conference Paper %A Lanken, PN %A Schoenfeld, DA %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 2000 %T Evaluation of early changes in PaO2/FiO2 (P/F) or Oxygenation index (01) as surrogate markers for survival in patients with acut %B ATS %8 2000 %X 161(3):A209 %0 Book %A MacIntyre, NR %D 2000 %T Mechanical ventilation strategies for lung protection %E MacIntyre, N. R. %B Innovations in Mechanical Ventilation, Seminars in Resp and Crit Care Med %V 21 (3) %P 215-222 %! Mechanical ventilation strategies for lung protection %0 Book %A MacIntyre, NR %D 2000 %T Mechanical ventilation strategies for parenchymal lung injury %E MacIntyre, N. R. %E Branson, R. %B Mechanical Ventilation %C Philadelphia %I WB Saunders %P 330-339 %! Mechanical ventilation strategies for parenchymal lung injury %0 Book %A MacIntyre, NR %D 2000 %T Principles of Mechanical Ventilation %E Murray, J. %E Nadel, J. %E Mason, R. %E Boushey, H. %B Textbook of Respiratory Medicine %C Philadelphia %I WB Saunders %P 2471-2485 %! Principles of Mechanical Ventilation %0 Conference Paper %A Morris, AH %D 2000 %T Oscillation and damping in human decision-making systems %B ATS %8 2000 %X 161:A %0 Journal Article %A Morris, AH %D 2000 %T Developing and Implementing Computerized Protocols for Standardization of Clinical Decisions %B Ann Int Med %V 132 %P 373-383 %! Developing and Implementing Computerized Protocols for Standardization of Clinical Decisions %X #### Abstract Humans have only a limited ability to incorporate information in decision making. In certain situations, the mismatch between this limitation and the availability of extensive information contributes to the varying performance and high error rate of clinical decision makers. Variation in clinical practice is due in part to clinicians' poor compliance with guidelines and recommended therapies. The use of decision-support tools is a response to both the information revolution and poor compliance. Computerized protocols used to deliver decision support can be configured to contain much more detail than textual guidelines or paper-based flow diagrams. Such protocols can generate patient-specific instructions for therapy that can be carried out with little interclinician variability; however, clinicians must be willing to modify personal styles of clinical management. Protocols need not be perfect. Several defensible and reasonable approaches are available for clinical problems. However, one of these reasonable approaches must be chosen and incorporated into the protocol to promote consistent clinical decisions. This reasoning is the basis of an explicit method of decision support that allows the rigorous evaluation of interventions, including use of the protocols themselves. Computerized protocols for mechanical ventilation and management of intravenous fluid and hemodynamic factors in patients with the acute respiratory distress syndrome provide case studies for this discussion. %U http://annals.org/article.aspx?articleid=713297 %0 Conference Paper %A Morris, AH %A ARDSNet, NIH / NHLBI %D 2000 %T Evaluating and refining a hemodynamic protocol for use in a multicenter ARDS clinical trial %B ATS %8 2000 %X 161:A %0 Journal Article %A NHLBI ARDS Clinical Trials Network, the %D 2000 %T Ketoconazole for Early Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial %B JAMA %V 283 %N 15 %P 1995-2002 %8 04/2000 %! Ketoconazole for Early Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial %X ####CONTEXT: Three clinical studies have suggested that ketoconazole, a synthetic imidazole with anti-inflammatory activity, may prevent the development of acute respiratory distress syndrome (ARDS) in critically ill patients. However, the use of ketoconazole as treatment for acute lung injury (ALI) and ARDS has not been previously studied. ####OBJECTIVE: To test the efficacy of ketoconazole in reducing mortality and morbidity in patients with ALI or ARDS. ####DESIGN: Randomized, double-blind, placebo-controlled trial conducted from March 1996 to January 1997. ####SETTING: Twenty-four hospitals associated with 10 network centers in the United States, constituting the ARDS Network. ####PATIENTS: A total of 234 patients with ALI or ARDS. ####INTERVENTION: Patients were randomly assigned to receive ketoconazole, 400 mg/d (n = 117), or placebo (n = 117), initiated within 36 hours of fulfilling study entry criteria and given enterally for up to 21 days. ####MAIN OUTCOME MEASURES: Primary outcome measures were the proportion of patients alive with unassisted breathing at hospital discharge and the number of days of unassisted breathing (ventilator-free days) during 28 days of follow-up. Secondary outcome measures included the proportion of patients achieving unassisted breathing for 48 hours or more, the number of organ failure-free days, and changes in plasma interleukin 6 (IL-6) and urinary thromboxane A2 metabolites (thromboxane B2 [TXB2] and 11-dehydro-TXB2). ####RESULTS: In-hospital mortality (SE) was 34.1% (4.3%) for the placebo group and 35.2% (4.3%) for the ketoconazole group (P=.85). The median number of ventilator-free days within 28 days of randomization was 9 in the placebo group and 10 in the ketoconazole group (P=.89). There were no statistically significant differences in the number of organ failure-free days, pulmonary physiology, or adverse events between treatment groups. The median serum ketoconazole level was 1.25 microg/mL and serum levels greater than 0.5 microg/mL were detected in 96% of patients assayed. Plasma IL-6, urinary TXB2, and 11-dehydro-TXB2 levels were unaffected by ketoconazole. ####CONCLUSIONS: In these patients with ALI or ARDS, ketoconazole was safe and bioavailable but did not reduce mortality or duration of mechanical ventilation or improve lung function. These data do not support the use of ketoconazole for the early treatment of ALI or ARDS. %U http://jama.jamanetwork.com/article.aspx?articleid=192592 %0 Conference Paper %A Schoenfeld, DA %A Thompson, BT %A Wheeler, AP %A Lanken, PN %A ARDSNet, NIH / NHLBI %D 2000 %T Early changes in IL-6 as a surrogate marker (SM) for survival in patients with acute lung injury (ALI) or ARDS %B ATS %8 2000 %X 161:A %0 Conference Paper %A Suchyta, M %A Lawton, C %A Morris, AH %D 2000 %T ARDS mortality in randomized controlled trials using methods is the same in two different hospitals %B ATS %8 2000 %X 161:A %0 Conference Paper %A Suchyta, M %A Morris, AH %A ARDSNet, NIH / NHLBI %D 2000 %T Outcomes of ALI/ARDS patients randomized vs excluded for >36 duration of ARDS %B ATS %8 2000 %X 161:A %0 Conference Paper %A Suchyta, M %A Morris, AH %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 2000 %T Attributes and outcomes of randomized versus excluded patients in ALI/ARDS trials %B ATS %8 2000 %X 161:A %0 Conference Paper %A Suchyta, M %A Orme, JF %A Morris, AH %D 2000 %T ARDS patient mortality is lower and depends on P/F %B ATS %8 2000 %0 Journal Article %A The Acute Respiratory Distress Syndrome Network %D 2000 %T Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome %B N Engl J Med %V 342 %N 18 %P 1301-1308 %! Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome %X #### BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. #### METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. #### RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively. #### CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. %U http://www.nejm.org/doi/full/10.1056/NEJM200005043421801 %0 Conference Paper %A Wheeler, AP %A Wickersham, N %A Ancukiewicz, M %A Brower, RG %A Thompson, BT %A Bernard, GR %A ARDSNet, NIH / NHLBI %D 2000 %T Low tidal volume ventilation reduces plasma cytokines in human acute lung injury %B ATS %8 2000 %X 161:A %0 Book %A Wiedemann, HP %A Matthay, MA %D 2000 %T Acute Respiratory Distress Syndrome %E Wiedemann, H. P. %E Matthay, M. A. %B Clinics in Chest Medicine %C Philadelphia %I WB Saunders and Co %V 21 %! Acute Respiratory Distress Syndrome %0 Journal Article %A Betesky, RA %A Schoenfeld, DA %D 2001 %T Nonparametric estimation in a cure model with random cure times %B Biometrics %V 57 %N 1 %P 282-6 %8 03/2001 %! Nonparametric estimation in a cure model with random cure times %X Acute respiratory distress syndrome (ARDS) is a life-threatening acute condition that sometimes follows pneumonia or surgery. Patients who recover and leave the hospital are considered to have been cured at the time they leave the hospital. These data differ from typical data in which cure is a possibility: death times are not observed for patients who are cured and cure times are observed and vary among patients. Here we apply a competing risks model to these data and show it to be equivalent to a mixture model, the more common approach for cure data. Further, we derive an estimator for the variance of the cumulative incidence function from the competing risks model, and thus for the cure rate, based on elementary calculations. We compare our variance estimator to Gray's (1988, Annals of Statistics 16, 1140-1154) estimator, which is based on counting process theory. We find our estimator to be slightly more accurate in small samples. We apply these results to data from an ARDS clinical trial. %0 Journal Article %A Brower, RG %D 2001 %T New ARDS Network Guidelines: Which of your patients will benefit? (Letter) %B J Crit Illness %V 16 %N 6 %P 277 %! New ARDS Network Guidelines: Which of your patients will benefit? (Letter) %0 Journal Article %A Brower, RG %D 2001 %T Ventilation in acute lung injury and ARDS 6 ml.kg: end of story? %B Minerva Anestesiologica %V 67 %N 4 %P 248-251 %! Ventilation in acute lung injury and ARDS 6 ml.kg: end of story? %0 Conference Paper %A Brower, RG %A Clemmer, T %A Lanken, PN %A MacIntyre, NR %A Matthay, MA %A Morris, AH %A Schoenfeld, DA %A Thompson, BT %D 2001 %T Effects of recruitment maneuvers (RMs) in acute lung injury (ALI) patients ventilated with lower tidal volumes and higher positi %B ATS %8 2001 %X 163:A %0 Journal Article %A Brower, RG %A Ware, LB %A Berthiaume, Y %A Matthay, MA %D 2001 %T Treatment of ARDS %B Chest %V 120 %N 4 %P 1347-1367 %8 10/2001 %! Treatment of ARDS %X Improved understanding of the pathogenesis of acute lung injury (ALI)/ARDS has led to important advances in the treatment of ALI/ARDS, particularly in the area of ventilator-associated lung injury. Standard supportive care for ALI/ARDS should now include a protective ventilatory strategy with low tidal volume ventilation by the protocol developed by the National Institutes of Health ARDS Network. Further refinements of the protocol for mechanical ventilation will occur as current and future clinical trials are completed. In addition, novel modes of mechanical ventilation are being studied and may augment standard therapy in the future. Although results of anti-inflammatory strategies have been disappointing in clinical trials, further trials are underway to test the efficacy of late corticosteroids and other approaches to modulation of inflammation in ALI/ARDS. %U http://journal.publications.chestnet.org/article.aspx?articleid=1080010 %0 Conference Paper %A Eisner, MD %A Hayden, D %A Thompson, BT %A Matthay, MA %D 2001 %T Airway pressure and the risk of early barotrauma in ALI/ARDS %B ATS %8 2001 %X 163:A %0 Journal Article %A Eisner, MD %A Thompson, BT %A Hudson, LD %A Luce, JM %A Hayden, D %A Schoenfeld, DA %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2001 %T Efficacy of Low Tidal Volume Ventilation in Patients with Different Clinical Risk Factors for Acute Lung Injury and the Acute Respiratory Distress Syndrome %B Am J Resp Crit Care Med %V 164 %P 231-236 %! Efficacy of Low Tidal Volume Ventilation in Patients with Different Clinical Risk Factors for Acute Lung Injury and the Acute Respiratory Distress Syndrome %X In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS. %U http://www.atsjournals.org/doi/abs/10.1164/ajrccm.164.2.2011093?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed %0 Conference Paper %A Girod, A %A Gottlieb, JE %A Yannarell, L %A Park, PK %D 2001 %T Critical care nursing perceptions of pulmonary artery catheter competency and clinical relevance: do nurses know what they know? %B ATS %8 2001 %X 163:A134 %0 Conference Paper %A Goss, CH %A Rubenfeld, GD %A Brower, RG %A Hudson, LD %D 2001 %T Incidence of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) in the United States %B ATS %8 2001 %X 163:A %0 Conference Paper %A Kallet, RH %A Alonso, JA %A Martin, L %A Eisner, MD %A Luce, JM %A ARDSNet, NIH / NHLBI %D 2001 %T Characteristics of acute lung injury patients exhibiting respiratory distress or dyssynchrony during low tidal volume ventilatio %B Respir Care %X 46(10):1122 %0 Conference Paper %A Kallet, RH %A Alonso, JA %A Martin, L %A Eisner, MD %A Luce, JM %A ARDSNet, NIH / NHLBI %D 2001 %T Incidence of respiratory distress or patients ventilator dyssynchrony during low tidal volume ventilation in patients with acute %B Respir Care %X 46(10):1122 %0 Conference Paper %A Kallet, RH %A Corral, W %A Hayden, D %A Silverman, HJ %A Luce, JM %A ARDSNet, NIH / NHLBI %D 2001 %T Does high level minute ventilation VE Demand limit implementation of the acute respiratory distress syndrom (ARDS) network low V %B Respir Care %X 46(10):1122 %0 Journal Article %A Kallet, RH %A Corral, W %A Silverman, HJ %A Luce, JM %D 2001 %T Implementation of a Low Tidal Volume Ventilation Protocol for Patients with Acute Lung Injury or Acute Respiratory Distress Synd %B Respir Care %V 46 %N 10 %P 1024-1037 %! Implementation of a Low Tidal Volume Ventilation Protocol for Patients with Acute Lung Injury or Acute Respiratory Distress Synd %X The ARDS (acute respiratory distress syndrome) Network study found 22% lower mortality in acute lung injury and ARDS patients ventilated with low tidal volumes (V(T)) than in those ventilated with traditional V(T) ventilation. Several points should be considered when using the low V(T) protocol for clinical practice. Prior to implementation, hemodynamic and acid-base status, minute ventilation, and adequacy of sedation should be assessed to minimize the potential for intolerance. The volume-preset, assist-control mode is recommended for better control of V(T), and the respiratory rate should be increased as V(T) is reduced, so as to maintain minute ventilation and prevent acute hypercapnia. When unavoidable, hypercapnia should be induced slowly. Ventilator inspiratory flow (V(I)) and trigger sensitivity settings should be optimized to limit the increase in work of breathing and dyspnea. When dyspnea results in double-triggered breaths, V(T) can be titrated to 7-8 mL/kg, provided end-inspiratory plateau pressure is < or = 30 cm H(2)O. In severe acidosis (pH < 7.15) V(T) also can be increased. However, every effort should be made to maintain plateau pressure and V(T) goals by buffering severe acidosis and treating patient-ventilator asynchrony with sedation. Evaluation for weaning should occur when adequate oxygenation can be maintained on 40% oxygen and a positive end-expiratory pressure of 8 cm H(2)O. Pressure support levels between 5 and 20 cm H(2)O (above 5 cm H(2)O positive end-expiratory pressure) are used for weaning and titrated to keep the respiratory rate < 35 breaths/min. Pressure support levels should be weaned aggressively, as long as the protocol's weaning tolerance criteria can be maintained. %0 Conference Paper %A Kallet, RH %A Eisner, MD %A Luce, JM %A ARDSNet, NIH / NHLBI %D 2001 %T Sedation and neuromuscular blocking agent requirements during initiation of low tidal volume ventilation in patients with acute %B Respir Care %X 46(10):1122 %0 Conference Paper %A Lee, CM %A Neff, MJ %A Steinberg, KP %A Raniery %A Slutsky, AS %A Hudson, LD %D 2001 %T Effects of low tidal volume ventilation on intrinsic PEEP in patients with acute lung injury %B ATS %8 2001 %X 163:A %0 Journal Article %A Morris, AH %D 2001 %T Rational Use of Computerized Protocols in the ICU %B Crit Care %V 5 %P 249-254 %! Rational Use of Computerized Protocols in the ICU %X Excess information in complex ICU environments exceeds human decision making limits, increasing the likelihood of clinical errors. Explicit decision-support tools have favorable effects on clinician and patient outcomes and can reduce the variation in clinical practice that persists even when guidelines based on reputable evidence are available. Computerized protocols used for complex clinical problems generate, at the point-of-care, patient-specific evidence-based therapy instructions that can be carried out by different clinicians with almost no inter-clinician variability. Individualization of patient therapy is preserved by these explicit protocols since they are driven by patient data. Computerized protocols that aid ICU decision-makers should be more widely distributed. %U http://ccforum.com/content/5/5/249 %0 Journal Article %A Silverman, HJ %A Hull, SC %A Sugarman, J %D 2001 %T Variability Among Institutional Review Boards' Decisions Within the Context of a Multicenter Trial %B Crit Care Med %V 29 %P 235-241 %! Variability Among Institutional Review Boards' Decisions Within the Context of a Multicenter Trial %X ####BACKGROUND: Institutional review boards (IRBs) are given discretion to interpret and apply the federal regulations governing the protection of human subjects in research. ####OBJECTIVE: To determine the extent of the variability among different IRBs on their approved research practices and informed consent forms within the context of a multicenter trial that used a common protocol. ####DESIGN: Descriptive analysis of survey information and informed consent forms. ####SETTING AND PARTICIPANTS: Sixteen IRBs from the institutions participating in a multicenter trial comparing lower vs. traditional tidal volume ventilation in patients with acute lung injury. ####MEASUREMENTS: Analysis of survey information on IRBs' approved research practices. Analysis of informed consent forms for the presence and the adequacy of description of each basic element of informed consent specified in the federal regulations. Reading levels of informed consent forms. ####MAIN RESULTS: Surveys and IRB-approved consent forms were obtained from all of the contacted IRBs (n = 16). Variability was observed among several of the research practices; one IRB waived the requirement for informed consent, five IRBs permitted telephone consent, and three IRBs allowed prisoners to be enrolled. Three consent forms contained all of the basic elements of informed consent outlined in the federal regulations, and 13 forms had varying numbers of these elements absent (six forms without one element, four without two, one without three, and two without four). Reading levels of the consent forms ranged from grades 8.2 to 13.4 (mean +/- sd was 11.6 +/- 1.2 grade level). ####CONCLUSIONS: Within a multicenter trial, IRBs reviewing a common protocol varied in several of their approved research practices and in the extent to which the basic elements of informed consent were included in their consent forms. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TNXpQRxbLwHR361ZnQpTbLTwLQvGbzvSpl1bnMnyJpXRs00nJJty!1354214353!181195628!8091!-1?issn=0090-3493&volume=29&issue=2&spage=235 %0 Journal Article %A Thompson, BT %A Hayden, D %A Matthay, MA %A Brower, RG %A Parsons, PE %D 2001 %T Clinicians' Approaches to Mechanical Ventilation in Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) %B Chest %V 120 %P 1622-1627 %! Clinicians' Approaches to Mechanical Ventilation in Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) %X ####STUDY OBJECTIVES: To examine clinicians' approaches to mechanical ventilation in patients with acute lung injury (ALI; PaO(2)/fraction of inspired oxygen [FIO(2)] <or= 300) and compare ventilator settings in patients with ARDS (PaO(2)/FIO(2) <or= 200) to settings in patients with milder oxygenation impairment (PaO(2)/FIO(2) of 201 to 300). ####DESIGN: Retrospective analysis of baseline data from prospective randomized trials conducted by the National Institutes of Health ARDS Network between 1996 and 1999. ####SETTING: Ten clinical centers comprising 24 hospitals and 74 medical and surgical ICUs of the ARDS Network. ####MEASUREMENTS AND RESULTS: The most common mode of mechanical ventilation in both groups was volume-assist control (56%). Synchronized intermittent mandatory ventilation (SIMV) or SIMV with pressure support was used more often in patients with PaO(2)/FIO(2) of 201 to 300 than in patients with ARDS. The use of pressure-control ventilation was uncommon (10% overall), as was the use of permissive hypercapnia (6% of patients with ARDS and 3% of patients with PaO(2)/FIO(2) of 201 to 300). The mean +/- SD tidal volume was 10.3 +/- 2 mL/kg of predicted body weight or 8.6 +/- 2 mL/kg of measured weight for patients with ARDS, and was not significantly different for patients with PaO(2)/FIO(2) of 201 to 300. Plateau pressures (Pplats) were lower in the PaO(2)/FIO(2) of 201 to 300 group (27 +/- 7 vs 31 +/- 8 for the ARDS group; p = 0.0003) and were > 35 cm H(2)O in 26% of patients. Seventy-eight percent of patients with ARDS received <or= 10 cm H(2)O of positive end-expiratory pressure. ####CONCLUSIONS: Physicians in ARDS Network centers caring for patients early in the course of ALI/ARDS used volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H(2)O. The average tidal volume was similar for patients with ARDS vs those with milder oxygenation deficits. %U http://journal.publications.chestnet.org/article.aspx?articleid=1080089 %0 Conference Paper %A Thompson, DA %A Hayden, D %A Ringwood, NJ %A Schoenfeld, DA %A Brower, RG %D 2001 %T Clinical outcomes of acute lung injury (ALI) patients with AIDS vs. ALI patients with other comorbid conditions %B ATS %8 2001 %X 163:A %0 Journal Article %A ARDSNet, NIH / NHLBI %D 2002 %T Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome %B Crit Care Med %V 30 %N 1 %P 1-6 %8 2002 %! Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome %X ####OBJECTIVE: To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). ####DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter study. ####SETTING: Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network. ####PATIENTS: A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group). ####INTERVENTIONS: Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing. ####MEASUREMENTS AND MAIN RESULTS: The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure-free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo. ####CONCLUSIONS: In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQjhKvsHGCRmnLZhnRytLH0M3JhGJC2b5JB37Zp4phVV1t37Hllj!-867019713!181195629!8091!-1?issn=0090-3493&volume=30&issue=1&spage=1 %0 Journal Article %A Brower, RG %D 2002 %T Mechanical ventilation in acute lung injury and ARDS. Tidal Volume Reduction %B Crit Care Med %V 18 %N 1 %P 1-13 %! Mechanical ventilation in acute lung injury and ARDS. Tidal Volume Reduction %X Traditional mechanical ventilation practices used generous tidal volumes in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). This approach may have caused overdistention of aerated lung units, thus exacerbating lung injury in some patients. Several recent clinical trials of traditional versus lower tidal volume strategies in ALI/ARDS yielded disparate results. In the largest study, the lower tidal volume approach was associated with lower mortality and more ventilator-free days. This article reviews the rationale for tidal volume reduction in ALI/ARDS and the differences between the studies. Several different interpretations of the recent clinical trial results are addressed. %U http://www.mdconsult.com/das/article/body/443570373-2/jorg=journal&source=&sp=12342628&sid=0/N/414712/1.html?issn=0749-0704 %0 Journal Article %A Brower, RG %A Matthay, MA %A Schoenfeld, DA %D 2002 %T Meta-analysis of acute lung injury and acute respiratory distress syndrome trials %B Am J Resp Crit Care Med %V 166 %N 11 %P 1515-1517 %! Meta-analysis of acute lung injury and acute respiratory distress syndrome trials %U http://www.atsjournals.org/doi/abs/10.1164/ajrccm.166.11.340?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&#.U1Adm1VSjGB %0 Journal Article %A Eisner, MD %A Thompson, BT %A Schoenfeld, DA %A Anzueto, A %A Matthay, MA %D 2002 %T Airway Pressures and Early Barotrauma in Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome %B Am J Resp Crit Care Med %V 165 %N 7 %P 978-982 %! Airway Pressures and Early Barotrauma in Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome %X The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) have not been clearly established. Using data from ARDS Network randomized controlled trials, we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma. We studied airway pressures at three exposure intervals: baseline, one day preceding the barotrauma event (one-day lag), and concurrent with the barotrauma event. During the first four study days, the cumulative incidence of barotrauma was 13% (95% confidence interval [CI] 10.6 to 15.6%). In a forward stepwise Cox proportional hazards analysis using time-dependent variables, higher concurrent positive end-expiratory pressure (PEEP) was associated with an increased risk of early barotrauma (relative hazard [RH] 1.67 per 5-cm H2O increment; 95% CI 1.35-2.07). Once concurrent PEEP was selected into the model, no other airway pressure was related to barotrauma, including plateau pressure. In the multivariate analysis, higher concurrent PEEP was also related to a greater risk of barotrauma (RH 1.93; 95% CI 1.44-2.60), controlling for age, ventilator group (6 versus 12 ml/kg), baseline PEEP, baseline plateau pressure, baseline tidal volume, Acute Physiology and Chronic Health Evaluation score, vasopressor use, serum albumin, hepatic failure, and coagulopathy. When one-day lagged values of PEEP were analyzed, higher PEEP was associated with a greater risk of barotrauma (RH 1.38 per 5-cm H2O increment; 95% CI 1.09-1.76). Controlling for the covariates, higher PEEP was related to an increased risk of barotrauma (RH 1.50; 95% CI 0.98- 2.30). In conclusion, higher PEEP may increase the likelihood of early barotrauma in ALI/ARDS. %U http://www.atsjournals.org/doi/full/10.1164/ajrccm.165.7.2109059#.U1AijVVSjGA %0 Journal Article %A Ely, EW %A Wheeler, AW %A Thompson, BT %A Steinberg, KP %A Ancukiewicz, M %A Bernard, GR %D 2002 %T Recovery Rate and Prognosis in Older Persons who Develop Acute Lung Injury and the Acute Respiratory Distress Syndrome %B Ann Int Med %V 136 %N 1 %P 25-36 %! Recovery Rate and Prognosis in Older Persons who Develop Acute Lung Injury and the Acute Respiratory Distress Syndrome %X ####BACKGROUND: The incidence of acute respiratory failure requiring mechanical ventilation increases 10-fold from the ages of 55 to 85 years, yet the rate of recovery and outcomes in older persons who develop acute lung injury are poorly defined. ####OBJECTIVE: To examine age as an independent risk factor in recovery and intensive care unit discharge after acute lung injury. ####DESIGN: Prospective cohort study. ####SETTING: 10 U.S. university-based medical centers. ####PATIENTS: 902 mechanically ventilated patients enrolled in randomized, controlled trials for the treatment of acute lung injury. All patients were managed according to a standardized protocol for ventilator management and weaning. ####MEASUREMENTS: Frequency and time to achieve well-defined recovery landmarks, duration of ventilation and intensive care unit stay, and survival. ####RESULTS: Median duration of mechanical ventilation was 19 days (interquartile range, 7 to >28 days) for patients 70 years of age or older (n = 173) compared with 10 days (interquartile range, 5 to 26 days) for patients younger than 70 years of age (n = 729) (P < 0.001). The duration of intensive care unit stay was 21 days for the older group (interquartile range, 11 to >28 days) and 16 days for the younger group (8 to >28 days) (P = 0.004). Survival rates decreased across increasing decades of age (P < 0.001): Patients younger than 70 years of age had a greater 28-day survival rate than patients 70 years of age or older (74.6% vs. 50.3%; P < 0.001). The proportion of survivors achieving physiologic recovery landmarks did not differ between the older and younger age groups, and the median time to pass a 2-hour spontaneous breathing trial was similar between both the older and younger patients (4 days vs. 5 days; P > 0.2). After passing a spontaneous breathing trial, however, older patients required 1 more day than younger patients to achieve unassisted breathing (P = 0.002) and 3 more days to leave the intensive care unit (P = 0.005). In a multivariable Cox proportional hazards analysis, age of 70 years or older was a strong predictor of in-hospital death (hazard ratio, 2.5 [95% CI, 2.0 to 3.2]; P < 0.001). ####CONCLUSIONS: Although the survival rate among patients 70 years of age or older was high, these patients were twice as likely to die of acute lung injury compared with their younger counterparts, even after adjustment for covariates. Older survivors recovered from respiratory failure and achieved spontaneous breathing at the same rate as younger patients but had greater difficulty achieving liberation from the ventilator and being discharged from the intensive care unit. %U http://annals.org/article.aspx?articleid=715003 %0 Journal Article %A Kallet, RH %A Luce, JM %D 2002 %T Detection of Patient-Ventilator Asynchrony During Low Tidal Volume Ventilation, Using Ventilator Waveform Graphics %B Respir Care %V 47 %N 2 %P 183-185 %! Detection of Patient-Ventilator Asynchrony During Low Tidal Volume Ventilation, Using Ventilator Waveform Graphics %0 Journal Article %A Morris, AH %D 2002 %T Decision Support and Safety of Clinical Environments %B Quality and Safety in Health Care %V 11 %P 69-75 %! Decision Support and Safety of Clinical Environments %X Safety in the clinical environment is based on structures that reduce the probability of harm, on evidence that enhances the likelihood of actions that increase favourable outcomes, and on explicit directions that lead to decisions to implement the actions dictated by this evidence. A clinical decision error rate of only 1% threatens patient safety at a distressing frequency. Explicit computerised decision support tools standardise clinical decision making and lead different clinicians to the same set of diagnostic or therapeutic instructions. They have favourable impacts on patient outcome. Simple computerised algorithms that generate reminders, alerts, or other information, and protocols that incorporate more complex rules reduce the clinical decision error rate. Decision support tools are not new; it is the new attributes of explicit computerised decision support tools that deserve identification. When explicit computerised protocols are driven by patient data, the protocol output (instructions) is patient specific, thus preserving individualized treatment while standardising clinical decisions. The expected decrease in variation and increase in compliance with evidence-based recommendations should decrease the error rate and enhance patient safety. %U http://qualitysafety.bmj.com/content/11/1/69.long %0 Conference Paper %A Morris, AH %A Sorenson, D %A Orme, JF %A Clemmer, T %A Weaver, L %A Grissom, CK %A Warner, HR %D 2002 %T A frame-based tool set for computerized protocols %B ATS %8 2002 %0 Journal Article %A Schoenfeld, DA %A Bernard, GR %D 2002 %T Statistical Evaluation of Ventilator Free Days as an Efficacy Measure in Clinical Trials of Treatment for Acute Respiratory Distress Syndrome %B Crit Care Med %V 30 %N 8 %P 1772-1777 %! Statistical Evaluation of Ventilator Free Days as an Efficacy Measure in Clinical Trials of Treatment for Acute Respiratory Distress Syndrome %X ####OBJECTIVE: Trials of potential new therapies in acute lung injury are difficult and expensive to conduct. This article is designed to determine the utility, behavior, and statistical properties of a new primary end point for such trials, ventilator-free days, defined as days alive and free from mechanical ventilation. Describing the nuances of this outcome measure is particularly important because using it, while ignoring mortality, could result in misleading conclusions. ####DESIGN: To develop a model for the duration of ventilation and mortality and fit the model by using data from a recently completed clinical trial. To determine the appropriate test statistic for the new measure and derive a formula for power. To determine a formula for the probability that the test statistic will reject the null hypothesis and mortality will simultaneously show improvement. To plot power curves for the test statistic and determine sample sizes for reasonable alternative hypotheses. ####SETTING: Intensive care units. ####PATIENTS: Patients with acute respiratory distress syndrome or acute lung injury as defined by the American-European Consensus Conference. ####MAIN RESULTS: The proposed model fit the clinical data. Ventilator-free days were improved by lower tidal volume ventilation, but the improvement was mostly caused by the improved mortality rate, so trials that expected similar effects would only have modest increase in power if they used ventilator-free days as their primary end point rather than 28-day mortality. Similar results were obtained using the model in two groups segregated by low or high Acute Physiology and Chronic Health Evaluation score. On the other hand, if patients are divided into two groups on the basis of the lung injury score, both the duration of ventilation and mortality are lower in the low lung injury score group. A trial of a treatment that had a similar clinical effect would have a large increase in power, allowing for a reduction in the required sample size. ####CONCLUSIONS: Use of ventilator-free days as a trial end point allows smaller sample sizes if it is assumed that the treatment being tested simultaneously reduces the duration of ventilation and improves mortality. It is unlikely that a treatment that led to higher mortality could lead to a statistically significant improvement in ventilator-free days. This would be especially true if the treatment were also required to produce a nominal improvement in mortality. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQhYnkpZhGHthSzBsJLtYmhX2FrtlfLgd2Sn0SQlHBMdHngfKLG4!1354214353!181195628!8091!-1?issn=0090-3493&volume=30&issue=8&spage=1772 %0 Conference Paper %A Suchyta, M %A Aronsky, DA %A Dean, NC %A Orme, JF %A Jepson, A %A Morris, AH %D 2002 %T Community-acquired pneumonia and the incidence of ARDS %B ATS %8 2002 %0 Conference Paper %A Thompson, BT %A Connors Jr. , AF %A Harabin, AL %A Hite, RD %A Wheeler, AP %A Wiedemann, HP %A ARDSNet, NIH / NHLBI %D 2002 %T Feasibility and safety of the ARDS Network's fluid and catheter treatment trial (FACTT) %B ATS %8 2002 %0 Journal Article %A Ware, LB %A Eisner, MD %A Thompson, BT %A Parsons, PE %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2002 %T Von Willebrand Factor (VWF), a biochemical marker of endothelial injury, predicts outcome in ALI/ARDS and is not modulated by a protective ventilatory strategy %B American Journal of Resp and Crit Care Med %V 165 %8 2002 %! Von Willebrand Factor (VWF), a biochemical marker of endothelial injury, predicts outcome in ALI/ARDS and is not modulated by a protective ventilatory strategy %X 165:A476 %0 Journal Article %A Wiedemann, HP %A Connors Jr. , AF %A Harabin, AL %A Hite, RD %A Thompson, BT %A Wheeler, AP %A ARDSNet, NIH / NHLBI %D 2002 %T Baseline hemodynamic characteristics of patients enrolled in the ARDS Network's fluid and catheter treatment trial (FACTT) %B American Journal of Resp and Crit Care Med %V 101 %8 2002 %! Baseline hemodynamic characteristics of patients enrolled in the ARDS Network's fluid and catheter treatment trial (FACTT) %X 15:A710 %0 Conference Paper %A Brower, RG %A Krishman, JA %A Thompson, BT %A Wheeler, AP %A Wiedemann, HP %A Schoenfeld, DA %A Bernard, GR %D 2003 %T Effects of tidal volume reduction (Vt-R) in Acute Lung Injury (ALI) patients with inspiratory plateau pressures (Pplat) < 32 cm %B ATS 2003 %X C029 %0 Journal Article %A Brower, RG %A Matthay, MA %A Bernard, GR %D 2003 %T Questions about ARDS Network trial of low tidal volume %B Am J Resp Crit Care Med %V 167 %P 1717-1718 %! Questions about ARDS Network trial of low tidal volume %0 Journal Article %A Brower, RG %A Morris, AH %A MacIntyre, NR %A Matthay, MA %A Hayden, D %A Thompson, BT %A Clemmer, T %A Lanken, PN %A Schoenfeld, DA %A ARDSNet, NIH / NHLBI %D 2003 %T Effects of Recruitment Maneuvers in Patients with Acute Lung Injury and Acute Respiratory Distress Syndrome Ventilated with High Positive End-Expiratory Pressure %B Crit Care Med %V 31 %N 11 %P 2592-2597 %8 11/2003 %! Effects of Recruitment Maneuvers in Patients with Acute Lung Injury and Acute Respiratory Distress Syndrome Ventilated with High Positive End-Expiratory Pressure %X ####Objective: Positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. ####Design: Prospective, randomized, crossover study. Setting: Thirty-four intensive care units at 19 hospitals. Patients: Seventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 +/- 3.0 cm H2O and 0.39 +/- 0.10, respectively (mean +/- sd). ####Interventions: We conducted RMs by applying continuous positive airway pressure of 35-40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. ####Measurements and Main Results: Responses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 +/- 0.2 vs. 0.6 +/- 0.3 %, mean +/- SEM, p < .01). Systolic blood pressure decreased more +/- 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. ####Conclusions: In ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQnL0fSGV6dMkXw8jQ04KQtdbcv20Nb7V2SJlRvnb3H72n4pqXm2!-867019713!181195629!8091!-1?issn=0090-3493&volume=31&issue=11&spage=2592 %0 Journal Article %A Brower, RG %A Rubenfeld, GD %A Thompson, BT %D 2003 %T Meta-analysis of tidal volumes in ARDS (comment) %B Am J Resp Crit Care Med %N 168 %P 2 %! Meta-analysis of tidal volumes in ARDS (comment) %U http://www.atsjournals.org/doi/full/10.1164/ajrccm.168.2.950#.U1A1YlVSjGA %0 Journal Article %A Cheng, IW %A Ware, LB %A Greene, KE %A Nuckton, TJ %A Eisner, MD %A Matthay, MA %D 2003 %T Prognostic value of surfactant proteins A and D in patients with acute lung injury %B Critical Care Medicine %V 31 %N 1 %P 20-27 %8 01/2003 %! Prognostic value of surfactant proteins A and D in patients with acute lung injury %X ####OBJECTIVE: The primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes. ####DESIGN: Observational study. ####SETTING: Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital. ####PATIENTS: Thirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference. ####INTERVENTIONS: Undiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients. ####MEASUREMENTS AND MAIN RESULTS: The concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p = .03) and in patients with an absence of intact alveolar fluid clearance (p =.03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p = .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL; p = .02). ####CONCLUSIONS: These results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQ0R9qbGW766kFhT8P0p1KvLSDr0nxg0cnx5W2m1XvXMBR72JSsb!1354214353!181195628!8091!-1?issn=0090-3493&volume=31&issue=1&spage=20 %0 Journal Article %A deBoisblanc, BP %A Girod-Espinoza, A %A Welsh, D %A Taylor, D %D 2003 %T Hemodynamic monitoring in ALI/ARDS %B Respir Care Clin %V 9 %N 4 %P 457-479 %8 12/2003 %! Hemodynamic monitoring in ALI/ARDS %X Hemodynamic monitoring of critically ill patients, especially those who have ALI or ARDS, is a widely practiced compilation of techniques that largely have not been demonstrated to improve patient outcomes. Indeed, some techniques, such as use of the PAC, may actually be harmful. It seems unlikely that monitoring devices themselves are unreasonably risky to use. Rather it seems more likely that operator errors in gathering and interpreting hemodynamic data and in selecting the appropriate treatment strategies are the culprits. There is promise that ongoing clinical trials and better provider education will soon result in evidence-based recommendations for monitoring the circulation in this patient population. %0 Journal Article %A deBoisblanc, BP %A Pellett, AA %A Johnson, RW %A Champagne, MS %A McClarity, E %A Dhillon, G %A Levitzsky, MG %D 2003 %T Estimation of pulmonary artery occlusion pressure by an artificial neural network %B Crit Care Med %V 31 %N 1 %P 261-266 %! Estimation of pulmonary artery occlusion pressure by an artificial neural network %X ####OBJECTIVE: We hypothesized that an artificial neural network, interconnected computer elements capable of adaptation and learning, could accurately estimate pulmonary artery occlusion pressure from the pulsatile pulmonary artery waveform. ####SETTING: University medical center. ####SUBJECTS: Nineteen closed-chest dogs. ####INTERVENTIONS: Pulmonary artery waveforms were digitally sampled before conventional measurements of pulmonary artery occlusion pressure under control conditions, during infusions of serotonin or histamine, or during volume loading. Individual beats were parsed or separated out. Pulmonary artery pressure, its first time derivative, and the beat duration were used as neural inputs. The neural network was trained by using 80% of all samples and tested on the remaining 20%. For comparison, the regression between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure was developed and tested using the same data sets. As a final test of generalizability, the neural network was trained on data obtained from 18 dogs and tested on data from the remaining dog in a round-robin fashion. ####MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between the pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure and measured pulmonary artery occlusion pressure was.75, whereas that for the neural network estimate of pulmonary artery occlusion pressure was.97 (p <.01 for difference between pulmonary artery diastolic pressure and pulmonary artery occlusion pressure estimates). The pulmonary artery diastolic pressure estimate of pulmonary artery occlusion pressure showed a bias of 0.097 mm Hg (limits of agreement -7.57 to 7.767 mm Hg), whereas the neural network estimate of pulmonary artery occlusion pressure showed a bias of -0.002 mm Hg (-2.592 to 2.588 mm Hg). There was no significant change in the bias of the neural network estimate over the range of values tested. In contrast, the bias for the pulmonary artery diastolic pressure estimate significantly increased with the increasing magnitude of the pulmonary artery occlusion pressure. During round-robin testing, the neural network estimate of pulmonary artery occlusion pressure showed suboptimal performance (correlation coefficient between estimated and measured pulmonary artery occlusion pressure.59). ####CONCLUSIONS: A neural network can accurately estimate pulmonary artery occlusion pressure over a wide range of pulmonary artery occlusion pressure under conditions that alter pulmonary hemodynamics. We speculate that artificial neural networks could provide accurate, real-time estimates of pulmonary artery occlusion pressure in critically ill patients. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQtTWqCRlG5ZhQWQLNFMMK7ZqJ5Ycv2gQh8BDTjqM0yLT1QrPbWL!-867019713!181195629!8091!-1?issn=0090-3493&volume=31&issue=1&spage=261 %0 Journal Article %A Eisner, MD %A Parsons, PE %A Matthay, MA %A Ware, LB %A Greene, K %A ARDSNet, NIH / NHLBI %D 2003 %T Plasma Surfactant Protein Levels and Clinical Outcomes in Patients with Acute Lung Injury %B Thorax %V 58 %P 983-988 %! Plasma Surfactant Protein Levels and Clinical Outcomes in Patients with Acute Lung Injury %X ####BACKGROUND: Because injury to the alveolar epithelial barrier is a characteristic feature of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), plasma surfactant protein levels may have prognostic value. To test this hypothesis plasma surfactant proteins A and D (SP-A and SP-D) levels were measured in patients with ALI or ARDS enrolled in the NHLBI sponsored multicentre ARDS Network randomised controlled trial of a 6 ml/kg v 12 ml/kg tidal volume strategy. ####METHODS: Data from 565 participants in the clinical trial were used. Plasma levels of SP-A and SP-D were measured at baseline and on day 3 after the start of the mechanical ventilation protocol. The longitudinal impact of baseline plasma surfactant protein levels on clinical outcomes was examined by multivariate analysis, controlling for mechanical ventilation group, APACHE III score, and other clinical covariates. The effect of 6 ml/kg tidal volume ventilation on plasma SP-A and SP-D levels was evaluated using analysis of covariance. ####RESULTS: Baseline plasma SP-A levels were not related to any clinical outcome. In contrast, higher baseline plasma SP-D levels were associated with a greater risk of death (OR 1.21 per 100 ng/ml increment; 95% CI 1.08 to 1.35), fewer ventilator-free days (mean decrease -0.88 days; p=0.001), and fewer organ failure-free days (mean decrease -1.06 days; p<0.0001). The 6 ml/kg tidal volume strategy had no effect on the rise in plasma SP-A levels (p=0.91) but attenuated the rise in plasma SP-D levels (p=0.0006). ####CONCLUSIONS: Early in the course of ALI/ARDS an increased level of plasma SP-D is associated with a worse clinical outcome. The 6 ml/kg tidal volume strategy attenuated the rise of SP-D early in the clinical course. Taken together, these observations indicate that plasma SP-D, a product of alveolar type II cells, is a valuable biomarker in ALI/ARDS. %U http://thorax.bmj.com/content/58/11/983.long %0 Conference Paper %A Eisner, MD %A Parsons, PE %A Matthay, MA %A Ware, LB %A Greene, K %A ARDSNet, NIH / NHLBI %D 2003 %T Prognostic value of plasma surfactant protein D level for clinical outcomes in patients with acute lung injury %B ATS %X A094 %0 Journal Article %A Goss, CH %A Brower, RG %A Hudson, LD %A Rubenfeld, GD %A ARDSNet, NIH / NHLBI %D 2003 %T Incidence of Acute Lung Injury in the United States %B Crit Care Med %V 31 %N 6 %P 1607-1611 %! Incidence of Acute Lung Injury in the United States %X ####OBJECTIVE: Recent estimates of acute respiratory distress syndrome (ARDS) incidence have varied from 1.3 to 22 per 100,000 person years (105 person.years); the incidence of acute lung injury (ALI) has varied from 17.9 to 34 cases per 105 person.years. Potential reasons for this wide range include differences in the definition of the syndrome, in the populations sampled, and in the assumptions made to estimate incidence. We hypothesized that careful, prospective, protocol-driven case identification that included the milder hypoxemia criterion for ALI would yield incidence numbers greater than previously reported. ####DESIGN: Prospective cohort study with extrapolation to the U.S. population. ####SETTING: National Heart, Lung, and Blood Institute-sponsored ARDS Network composed of 20 hospitals. ####PATIENTS: As part of the National Institutes of Health-sponsored ARDS network, 20 hospitals prospectively identified patients with ALI from 1996 to 1999. Screening logs from this study were used to estimate ALI rates per intensive care unit (ICU) bed per year. We used the registry and data from the American Hospital Association to estimate the incidence of ALI in the United States. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: The ALI per ICU bed incidence in the ARDS network registry varied from 0.7 to 5.8 cases of ALI per ICU bed per year with an average of 2.2 cases of ALI per ICU bed per year. We tested the robustness of the incidence estimate by performing a variety of sensitivity analyses. When we used the conservative assumptions that the ARDS network screening logs were complete at each of the participating hospitals and that ALI cases are limited to academic hospitals with > or =20 adult ICU beds, the incidence of ALI in adults in the United States is 22.4 cases per 105 person.years. Under the less conservative assumption that ALI cases occurred only at hospitals with > or =20 ICU beds, regardless of their academic status, the incidence of ALI in the United States is estimated at 64.2 cases per 105 person.years. ####CONCLUSIONS: Based on this analysis, which used prospective clinical trial screening data and conservative assumptions about where patients with ALI are cared for, the incidence of ALI in the United States appears to be higher than previously reported. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQrb52vPn6TdL1bxwhdyL4ZWsgyl78tS0HthQspd2hMw8Hq2CYWf!1354214353!181195628!8091!-1?issn=0090-3493&volume=31&issue=6&spage=1607 %0 Conference Paper %A Morris, AH %A Silverman, HJ %A Stanholtz, C %A Brower, RG %A Thompson, BT %A Bernard, GR %A ARDSNet, NIH / NHLBI %D 2003 %T Experimental design and ethical issues for non-blinded ICU randomized controlled clinical trials %B ATS %X A015 %0 Conference Paper %A Satsangi, S %A Weir, CF %A Tesseyman, SP %A Morris, AH %D 2003 %T Proposed constructs that predict use of computerized protocols by ICU clinicians %B ATS %X C039 %0 Journal Article %A Suchyta, M %A Orme, JF %A Morris, AH %D 2003 %T The changing face of organ failure in ARDS %B Chest %V 124 %N 5 %P 1871-9 %8 11/2003 %! The changing face of organ failure in ARDS %X ####OBJECTIVE: To study morbidity and mortality in ARDS patients from 1987 to 1999. ####DESIGN: Review of a prospectively collected database of ARDS patients. ####SETTING: Large, community hospital located in Salt Lake City, UT. ####PATIENTS: ARDS patients identified for the years 1987 to 1999. We prospectively identified ARDS patients at LDS Hospital in Salt Lake City, UT, using PaO(2)/fraction of inspired oxygen ratio (P/F) criteria, the presence of bilateral chest radiograph infiltrates, and the absence of left atrial hypertension. ####MEASUREMENTS: We assigned a primary risk factor for ARDS and identified the presence of organ failure before and after ARDS. We compared two temporal groups (ie, 1987 to 1990 vs 1994 to 1999) and used two criteria of arterial hypoxemia (P/F: patients from 1994 to 1999, < or = 105 and < or = 173; patients from 1987 to 1990, < or = 0.2) At 1,500 m (the altitude of Salt Lake City), a PaO(2) of < or = 173 corresponds to an alveolar-arterial oxygen pressure difference of < or = 200 at sea level. We used death at hospital discharge as an end point. ####MAIN RESULTS: We identified 516 ARDS patients with a P/F of < or = 105 (1987 to 1990, 256 patients; 1994 to 1999, 260 patients). Patients who had ARDS between 1994 and 1999 with a P/F of < or = 105 had a lower mortality rate than patients between 1987 and 1990 with a P/F of < or = 105 (44% vs 54%, respectively; p <.05). There were 288 patients with a P/F range of 106 to 173 during 1994 to 1999. Patients from 1994 to 1999 with a P/F of < or = 173 had a lower mortality rate compared to patients from 1987 to 1990 (35% vs 54%, respectively; p <.01). Patients from 1994 to 1999 (for both P/F groups) had statistically fewer total nonpulmonary organ failures (ie, more patients had zero organ failures or single organ failures) and fewer specific organ failures (ie, sepsis, cardiovascular failures, and CNS failures). There were statistically fewer cases of cardiovascular failure, sepsis, and in both periods (ie, prior to ARDS and after the onset of ARDS) for 1994-to-1999 patients with a P/F of < or = 105 compared to 1987-to-1990 patients with a P/F of < or = 105. ####CONCLUSIONS: Mortality from ARDS has decreased and is associated with decreased organ failure prior to and during the course of ARDS. %U http://journal.publications.chestnet.org/article.aspx?articleid=1081971 %0 Book %A Thompson, BT %D 2003 %T Acute Respiratory Distress Syndrome %B Merck Manual of Medical Information %C Whitehouse Station, NJ %I Merck Research Laboratories %! Acute Respiratory Distress Syndrome %0 Generic %A Thompson, BT %D 2003 %T Corticosteroids and Acute Lung Injury %V 31 %P S253-257 %! Corticosteroids and Acute Lung Injury %0 Conference Paper %A Thompson, BT %A Brower, RG %A Wheeler, AP %A Wiedemann, HP %A Schoenfeld, DA %A Bernard, GR %A ARDSNet, NIH / NHLBI %D 2003 %T Standard care prior to entry in ARDS Network studies encompassed wide variation in tidal volumes (Vt) and plateau pressures (Ppl %B ATS %X C097 %0 Conference Paper %A Verberes, L %A Karir, V %A Day, D %A Polissar, N %A Spencer, T %A Cooper, C %A Neff, MJ %A Rubenfeld, GD %D 2003 %T Lung protective ventilation (LPV) for acute lung injury (ALI) does not increase sedation use %B Crit Care Med %X 31(2):A95 %0 Conference Paper %A Ware, LB %A Ancukiewicz, M %A Parsons, PE %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2003 %T Prognostic value of of plasma protein C levels in patients with acute lung injury %B ATS %X C040 %0 Journal Article %A Brower, RG %A Bernard, GR %A Morris, A %A NIH/NHLBI, ARDSNetwork %D 2004 %T Ethics and Standard of Care in Clinical Trials %B Am J Resp Crit Care Med %V 170 %N 2 %P 198-9 %8 07/2004 %9 Letter %! Ethics and Standard of Care in Clinical Trials %U http://www.atsjournals.org/doi/abs/10.1164/ajrccm.170.2.958?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U3JtkIFdWsI %0 Journal Article %A Brower, RG %A Lanken, PN %A MacIntyre, NR %A Matthay, MA %A Morris, AH %A Ancukiewicz, M %A Schoenfeld, DA %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 2004 %T Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome %B New Engl J Med %V 351 %N 4 %P 327-336 %8 07/2004 %! Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome %X ####BACKGROUND: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. ####METHODS: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. ####RESULTS: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). ####CONCLUSIONS: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. %U http://europepmc.org/abstract/MED/15269312 %0 Conference Paper %A Brower, RG %A Thompson, BT %A Ancukiewicz, M %A ARDSNet, NIH / NHLBI %D 2004 %T Clinical trial of mechanical ventilation with traditional versus lower tidal volumes in acute lung injury and acute respiratory %B ATS %X 169:A256 %0 Conference Paper %A deBoisblanc, BP %A Vuchs, B %A Truwit, JD %A Wiedemann, HP %A Hayden, D %A ARDSNet, NIH / NHLBI %D 2004 %T Effect of fluid balance on central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) in patients with acute l %B ATS %X 169:A342 %0 Conference Paper %A Lanken, PN %A Ancukiewicz, M %A Christie, JD %A ARDSNet, NIH / NHLBI %D 2004 %T Baseline risk factors for mortality in 902 subjects with acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) %B ATS %X 169:A18 %0 Journal Article %A O'Brien, JM %A Welsh, CH %A Fish, RH %A Ancukiewicz, M %A Kramer, AM %D 2004 %T Excess Body Weight Is Not Independently Associated with Outcome in Mechanically Ventilated Patients with Acute Lung Injury %B Annals of Internal Medicine %V 140 %N 5 %P 338-345 %8 03/2004 %! Excess Body Weight Is Not Independently Associated with Outcome in Mechanically Ventilated Patients with Acute Lung Injury %X ####Background: Despite an epidemic of obesity among adults, the effect of excess body weight on outcome from critical illness is not well studied. ####Objective: To examine the association between excess body weight and outcome in mechanically ventilated patients with acute lung injury. ####Design: Secondary analysis of participants in trials of therapy for acute lung injury. ####Setting: 10 U.S. medical centers that participate in the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. ####Patients: 902 mechanically ventilated patients who were enrolled in randomized, controlled trials of therapy for acute lung injury. ####Intervention: Assignment to higher (12 mL/kg of predicted weight) or lower (6 mL/kg of predicted weight) tidal volume ventilation strategies with specified weaning protocols. Some patients also received ketoconazole, lisofylline, or placebo by factorial design. ####Measurements: Mortality rate, rate of unassisted ventilation by day 28, and number of ventilator-free days. ####Results: Indirect causes of lung injury, including trauma, were more common in obese patients. Overweight and obese patients had higher peak and plateau airway pressures before enrollment because of higher set tidal volumes. After risk adjustment, excess body weight was not associated with death, achievement of unassisted ventilation, or number of ventilator-free days. This lack of effect persisted with categorical or continuous measures of body mass index (BMI). We found no significant interaction between ventilator protocol assignment and BMI category. ####Conclusions: After risk adjustment, overweight and obese patients with acute lung injury have outcomes similar to those of patients with normal BMI. The lack of interaction between ventilator protocol assignment and BMI suggests that patients with normal, overweight, or obese BMI benefit from lower tidal volume ventilation for acute lung injury. %U http://annals.org/article.aspx?articleid=717254 %0 Journal Article %A Rubenfeld, GD %A Cooper, C %A Carter, G %A Thompson, BT %A Hudson, LD %D 2004 %T Barriers to providing lung protective ventilation to patients with acute lung injury %B Crit Care Med %V 32 %N 6 %P 1289-93 %8 06/2004 %! Barriers to providing lung protective ventilation to patients with acute lung injury %X ####OBJECTIVE: No studies have explored the barriers to implementing lung-protective ventilation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Our objective was to identify barriers to using lung-protective ventilation in patients with ALI/ARDS. ####DESIGN: Survey with content analysis of open-ended responses. ####SETTING: Medical center. ####PARTICIPANTS: Experienced intensive care unit nurses and respiratory therapists network identified through purposive sampling at hospitals from the ARDS Network, a National Institutes of Health-sponsored research consortium. ####INTERVENTIONS: Survey. ####RESULTS: Fifty-five surveys representing all ten ARDS Network sites were received. Twenty-seven (49%) of the respondents were intensive care unit nurses, 24 (44%) were respiratory therapists, and four did not indicate their profession. Clinicians had used lung-protective ventilation in a median of 20 (interquartile range, 10-50) patients with ALI/ARDS. Respondents identified physician willingness to relinquish control of ventilator, physician recognition of ALI/ARDS, and physician perceptions of patient contraindications to low tidal volumes as important barriers to initiating lung-protective ventilation. Important barriers to continuing patients on lung-protective ventilation were concerns over patient discomfort and tachypnea and concerns over hypercapnia, acidosis, and hypoxemia. Techniques for overcoming barriers were identified including specific ventilator setup recommendations, clinician education, and tools to assess patient discomfort. ####CONCLUSIONS: Experienced bedside clinicians perceive important barriers to implementing lung-protective ventilation. Successful strategies to increase use of lung-protective ventilation should target these barriers. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TNvTqwZq9RJ6vvXQ3xTBKDxhlTBg2hqtys5n1XDjTvGymmB9nQYx!-867019713!181195629!8091!-1?issn=0090-3493&volume=32&issue=6&spage=1289 %0 Conference Paper %A Thompson, BT %A Hayden, D %A Schoenfeld, DA %A ARDSNet, NIH / NHLBI %D 2004 %T Safety is not improved with the inclusion of a usual care arm in ICU trials %B ATS %X 169:A256 %0 Journal Article %A Ware, LB %A Eisner, MD %A Thompson, BT %A Parsons, PE %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2004 %T Significance of von Willebrand Factor in Septic and Non-Septic Patients with Acute Lung Injury %B Am J Resp Crit Care Med %V 170 %N 7 %P 766-772 %8 06/2004 %! Significance of von Willebrand Factor in Septic and Non-Septic Patients with Acute Lung Injury %X Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 +/- 265% of normal control plasma) and Day 3 (344 +/- 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 +/- 333%) versus survivors (306 +/- 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4-2.1). Higher VWF levels were also significantly associated with fewer organ failure-free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated. %U http://www.atsjournals.org/doi/full/10.1164/rccm.200310-1434OC#.U1bFnVVdWsI %0 Conference Paper %A Ware, LB %A Eisner, MD %A Wickersham, N %A Olman, MA %A Thompson, BT %A Parsons, PE %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2004 %T Plasminogen activator inhibitor-1 (PAI-1), a marker of impaired fibrinolysis, is associated with higher mortality in patients wi %B ATS %X 169:A115 %0 Journal Article %A Cheng, IW %A Eisner, MD %A Thompson, BT %A Ware, LB %A Matthay, MA %A Network, ARDS %D 2005 %T Acute Effects of Tidal Volume Strategy on Hemodynamics, Fluid Balance, and Sedation in Acute lung Injury %B Critical Care Medicine %V 33 %N 1 %P 63-70; discussion 239-40. %8 01/2005 %! Acute Effects of Tidal Volume Strategy on Hemodynamics, Fluid Balance, and Sedation in Acute lung Injury %X ####OBJECTIVE: To examine the effects of mechanical ventilation with a tidal volume of 6 mL/kg compared with 12 mL/kg predicted body weight on hemodynamics, vasopressor use, fluid balance, diuretics, sedation, and neuromuscular blockade within 48 hrs in patients with acute lung injury and acute respiratory distress syndrome. ####DESIGN: Retrospective analysis of a previously conducted randomized, clinical trial. ####SETTING: Two adult intensive care units at a tertiary university medical center and a large county hospital. ####PATIENTS: One hundred eleven patients who were enrolled in the National Institutes of Health ARDS Network trial at the University of California, San Francisco. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Compared with 12 mL/kg predicted body weight, treatment with a tidal volume of 6 mL/kg predicted body weight had no adverse effects on hemodynamics. There were also no differences in the need for supportive therapies, including vasopressors, intravenous fluids, or diuretics. In addition, there were no differences in body weight, urine output, and fluid balance. Finally, there was no difference in the need for sedation or neuromuscular blockade between the two tidal volume protocols. ####CONCLUSIONS: When compared with ventilation with 12 mL/kg predicted body weight, patients treated with the lung-protective 6 mL/kg predicted body weight tidal volume protocol had no difference in their supportive care requirements. Therefore, concerns regarding potential adverse effects of this protocol should not preclude its use in patients with acute lung injury or the acute respiratory distress syndrome. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TWLFJPkh1v1hGYJnyTLTrrGRLbS2nZbHNhv02nsv6bDyvyZcZC7S!-813027467!181195628!8091!-1?issn=0090-3493&volume=33&issue=1&spage=63 %0 Conference Paper %A Friedman, D %A deBoisblanc, BP %A Arroglia, AC %A Fuchs, BD %A Guntupalli, KK %A Hite, RD %A Truwit, JD %D 2005 %T Accuracy of airway pressure display for identification of end-expiration during the measurement of CVP and PAOP in mechanically %B ATS %X A435 %0 Journal Article %A Hager, DN %A Krishman, JA %A Hayden, D %A Brower, RG %A ARDSNet, NIH / NHLBI %D 2005 %T Tidal Volume Reduction in Patients with acute Lung Injury When Plateau Pressures Are Not High %B Am J Resp Crit Care Med %V 172 %P 1241-1245 %! Tidal Volume Reduction in Patients with acute Lung Injury When Plateau Pressures Are Not High %X Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, “Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?” We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718413/ %0 Journal Article %A Hayden, D %A Pauler, DK %A Schoenfeld, DA %D 2005 %T An Estimator for Treatment Comparisons Among Survivors in Randomized Trials %B Biometrics %V 61 %N 1 %P 305-310 %8 03/2006 %! An Estimator for Treatment Comparisons Among Survivors in Randomized Trials %X In clinical trials of advanced-stage disease it is often of interest to perform treatment comparisons for endpoints which are defined only for survivors. Examples include time on ventilation in ventilation studies, change in quality of life in health-related quality-of-life studies, and duration of response to therapy in therapeutic trials. Randomized treatment comparisons for these endpoints cannot be performed because the outcomes are only defined in the nonrandomly selected subgroup of survivors. We propose a new evaluation of the survivor average causal effect (SACE) for treatment comparisons of this nature. We provide an estimator of SACE in the presence of no unmeasured confounders, a nontestable assumption, which identifies SACE. We also outline a sensitivity analysis for exploring robustness of conclusions to deviations from this assumption. We apply this method to duration of ventilation in a clinical trial of acute respiratory distress syndrome. %U http://onlinelibrary.wiley.com/doi/10.1111/j.0006-341X.2005.030227.x/abstract;jsessionid=533F3CA25ECC1569FBDB763D653B013D.f04t02 %0 Journal Article %A Hough, CL %A Kallet, RH %A Ranieri, VM %A Rubenfeld, GD %A Luce, JM %A Hudson, LD %D 2005 %T Intrinsic Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome (ARDS) Network Subjects %B Crit Care Med %V 33 %N 3 %P 527-32 %8 03/2005 %! Intrinsic Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome (ARDS) Network Subjects %X ####OBJECTIVE: We tested the hypothesis that subjects randomized to the 6 mL/kg predicted body weight tidal volume study group of the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network study had higher levels of intrinsic positive end-expiratory pressure (PEEP) than subjects randomized to the 12 mL/kg predicted body weight tidal volume study group. ####DESIGN: Secondary analysis of a subgroup from a randomized controlled trial. ####SETTING: Hospitals located in San Francisco, CA, and Seattle, WA. ####PATIENTS: Eighty-four patients enrolled in the ARDS Network tidal volume trial in San Francisco, CA, and Seattle, WA, with records of measurement of intrinsic PEEP. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was assessed a median of six times over the first 48 hrs of ARDS Network protocol ventilation in study subjects, with no significant difference in number of measurements between subjects randomized to the tidal volume protocol of 6 mL/kg compared with 12 mL/kg. We found that intrinsic PEEP was higher among subjects randomized to the 6 mL/kg protocol, with a median intrinsic PEEP of 1.3 cm H2O (interquartile range, 0-3.1 cm H2O), compared with a median intrinsic PEEP of 0.5 cm H2O (interquartile range, 0-1.5 cm H2O) among subjects randomized to 12 mL/kg (p = .029). There was no difference in total PEEP between the study groups. ####CONCLUSIONS: In a subgroup of ARDS Network subjects, intrinsic PEEP was statistically significantly higher in subjects randomized to the 6 mL/kg protocol than those in the 12 mL/kg study group. The amount of intrinsic PEEP was very low in both study groups, and difference of median intrinsic PEEP between the groups was <1 cm H2O. It is unlikely that the difference in intrinsic PEEP between the study groups was clinically important in the ARDS Network study of low tidal volume ventilation. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TWNplnNSLMry031LQJNJk7nJjD117GM2nnGr5NQmR5GQSxV8Fr1Z!-867019713!181195629!8091!-1?issn=0090-3493&volume=33&issue=3&spage=527 %0 Conference Paper %A Morris, AH %A Sorenson, D %A Warner, HR %A Day, JA %A Korpak, A %A Orme, JF %A Clemmer, T %A Thompson, BT %A Schoenfeld, DA %D 2005 %T Bedside computerized study protocols for an ARDS Network clinical trial %B ATS %X A436 %0 Journal Article %A Parsons, PE %A Eisner, MD %A Thompson, BT %A Matthay, MA %A Ancukiewicz, M %A Bernard, GR %A Wheeler, AP %D 2005 %T Lower Tidal Volume Ventialtion and Plasma Cytokine Markers of Inflammation in Patients with Acute Lung Injury %B Crit Care Med %V 33 %P 1-6, discussion 230-232 %! Lower Tidal Volume Ventialtion and Plasma Cytokine Markers of Inflammation in Patients with Acute Lung Injury %X ####OBJECTIVES: To evaluate the association between interleukin-6, interleukin-8, and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury. ####DESIGN: Multiple-center, randomized trial. ####SETTING: Intensive care units in ten university centers. ####PATIENTS: The study included 861 patients enrolled in the National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury. ####INTERVENTIONS: Patients were randomized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described. ####MEASUREMENTS AND MAIN RESULTS: Baseline plasma levels of interleukin-6, interleukin-8, and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group (odds ratio 1.63 per log-10 increment, 95% confidence interval 1.33-1.98; odds ratio 2.33 per log-10 increment, 95% confidence interval 1.79-3.03; odds ratio 2.02 per log-10 increment, 95% confidence interval 1.47-2.76, respectively) and multivariate analyses controlling for ventilation strategy, Acute Physiology and Chronic Health Evaluation III score, Pao2/Fio2 ratio, creatinine, platelet count, and vasopressor use (odds ratio 1.63 per log-10 increment, 95% confidence interval 0.93-1.49; odds ratio 1.73 per log-10 increment, 95% confidence interval 1.29-2.34; odds ratio 1.23 per log-10 increment, 95% confidence interval 0.86-1.76, respectively). Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days. Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation. By day 3, the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels. There was a 26% reduction in interleukin-6 (95% confidence interval, 12-37%) and a 12% reduction in interleukin-8 (95% confidence interval, 1-23%) in the 6 mL/kg group compared with the 12 mL/kg group. ####CONCLUSIONS: In patients with acute lung injury, plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality. The severity of inflammation varies with clinical risk factor, suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions. Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TWHG2QB5Hxft5sPkHRmQ80pTS78q6JTwng5npY5Sn3yGjp2QN2M1!-867019713!181195629!8091!-1?issn=0090-3493&volume=33&issue=1&spage=1 %0 Journal Article %A Parsons, PE %A Matthay, MA %A Ware, LB %A Eisner, MD %D 2005 %T Elevated Plasma Levels of Soluble TNF Receptors are Associated with Morbidity and Mortality in Patients with Acute Lung Injury %B Am J Physiol Lung Cell Mol Physiol %V 288 %P L426-431 %! Elevated Plasma Levels of Soluble TNF Receptors are Associated with Morbidity and Mortality in Patients with Acute Lung Injury %X Ventilator-induced lung injury (VILI) is an inflammatory process that can be attenuated by lung protective ventilation strategies. Our objectives to further investigate the pathogenesis of ALI and VILI and the mechanism of lung protection in these syndromes were: 1) to determine if plasma measurements of soluble TNF receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and mortality in a small single center trial; 2) to test the predictive value of these markers and of TNF-alpha in a larger, broader group of patients with ALI; 3) to test the hypothesis that low tidal volume ventilation (LTVV) would be associated with a decrease in plasma levels of TNF-alpha, sTNFRI, and sTNFRII. In the single center study, sTNFRI and II levels were higher in patients at risk for and with ALI, but they did not predict the development of the syndrome. In the multicenter trial sTNFRI and II were strongly associated with mortality (OR 5.76/1 log10 increment in receptor level; 95% CI 2.63-12.6 and OR 2.58; 95% CI 1.05-6.31, respectively) and morbidity measured as fewer nonpulmonary organ failure-free and ventilator-free days. The LTVV strategy was associated with an attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV is associated with a specific decrease in sTNFRI levels. This suggests that one beneficial effect of LTVV may be to attenuate alveolar epithelial injury. %U http://ajplung.physiology.org/content/288/3/L426 %0 Journal Article %A Rizvi, K %A deBoisblanc, BP %A Dhillon, G %A Arroglia, AC %A Fuchs, BD %A Guntupalli, KK %A Hite, RD %A Truwit, JD %A ARDSNet, NIH / NHLBI %D 2005 %T Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome %B Crit Care Med %V 33 %N 1 %P 98-103; discussion 242-3 %8 01/2005 %! Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome %X ####BACKGROUND: Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patients. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions. ####OBJECTIVE: We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration. ####DESIGN: To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. ####SETTING/SUBJECTS/INTERVENTIONS: A total of 459 strip-chart recordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals. ####RESULTS: Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation. ####CONCLUSION: Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TQwJ8Tg5pz14znVPLhpLDmZ13JTx0bpGJrKcrFlTNw5TlvMyQm2m!1354214353!181195628!8091!-1?issn=0090-3493&volume=33&issue=1&spage=98 %0 Journal Article %A Silverman, HJ %A Luce, JM %A Lanken, PN %A Morris, AH %A Oldmixon, CF %A Thompson, BT %A Bernard, GR %A ARDSNet, NIH / NHLBI %D 2005 %T Recommendations for informed consent forms (ICFs) for critical care trials %B Crit Care Med %V 33 %N 4 %P 867-882 %8 04/2005 %! Recommendations for informed consent forms (ICFs) for critical care trials %X ####Background: Many subjects enrolled in research studies have a limited understanding of the research to which they consented. ####Objective: To develop recommendations to enhance comprehensiveness and understanding of informed consent forms used in critical care clinical trials. ####Design: Consensus process. ####Recommendations: We provide recommendations regarding the U.S. federally required basic and additional elements of informed consent as applied to critical care clinical trials. We also identify issues that investigators need to address, if relevant, in the informed consent forms of critical care clinical trials. These include the description, in understandable language, of complex and detailed experimental protocols that are the focus of the clinical trial, disclosure of death as a risk factor if mortality is an outcome variable, and the identification of who can legally serve as the prospective subject’s surrogate. We also offer suggestions to enhance subjects’ understanding of informed consent forms. ####Conclusions: The literature on informed consent forms suggest that shorter informed consent forms written at a lower reading level, when read carefully, might provide better subject understanding. Prospective evaluation is needed to determine whether our recommendations enhance the informed consent process. %U http://journals.lww.com/ccmjournal/Abstract/2005/04000/Recommendations_for_informed_consent_forms_for.27.aspx %0 Journal Article %A Brower, RG %A Thompson, BT %A NIH/NHLBI/ARDSNetwork %D 2006 %T Tidal volumes in acute respiratory distress syndrome--one size does not fit all %B Crit Care Med %V 34 %N 1 %P 263-4 %8 01/2006 %9 Letter %! Tidal volumes in acute respiratory distress syndrome--one size does not fit all %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TynHw2P4cp52Qfrv7Jwssl7dHLhlVyrkz8nxVNh7GZQTyFHQTBGQ!-423127214!181195628!8091!-1?issn=0090-3493&volume=34&issue=1&spage=263 %0 Conference Paper %A deBoisblanc, BP %A Brierre, SP %A Hayden, D %A ARDSNet, NIH / NHLBI %D 2006 %T Discordance of central venous pressure (CVP) vs. pulmonary artery occlusion pressure (PAOP) pressure range assignment in patient %B ATS %X A296 %0 Conference Paper %A Glassberg, AE %A Luce, JM %A Matthay, MA %A ARDSNet, NIH / NHLBI %D 2006 %T The impact of lacking a surrogate on enrollment in NHLBI clinical trials of acute lung injury %B ATS %X A379 %0 Conference Paper %A Grissom, CK %A Morris, AH %A Lanken, PN %A Orme, JF %A Schoenfeld, DA %A Thompson, BT %A ARDSNet, NIH / NHLBI %D 2006 %T Correlation of clinical exam findings and cardiac index in patients with ARDS %B CHEST %0 Journal Article %A Hough, CL %A Steinberg, KP %A Goodman, RB %A et al. %D 2006 %T Incidence, risk factors, serum markers, and outcomes of neuromyopathy in persistent ARDS %B Am J Respir Crit Care Med %V 3 %P A570 %8 2006 %! Incidence, risk factors, serum markers, and outcomes of neuromyopathy in persistent ARDS %0 Journal Article %A McClintock, D %A Starcher, B %A Eisner, MD %A Thompson, BT %A Hayden, D %A Church, GD %A Matthay, MA %D 2006 %T Higher Urine Desmosine Levels are Associated with Mortality in Patients with Acute Lung Injury %B Am J Physiol Lung Cell Mol Physiol %! Higher Urine Desmosine Levels are Associated with Mortality in Patients with Acute Lung Injury %X Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P=0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P=0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury. %U http://ajplung.physiology.org/content/291/4/L566 %0 Journal Article %A Steinberg, KP %A Hudson, LD %A Goodman, RB %A Hough, CL %A Lanken, PN %A Hyzy, R %A Thompson, BT %A Ancukiewicz, M %A ARDSNet, NIH / NHLBI %D 2006 %T Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome %B New Engl J Med %V 354 %N 16 %P 1671-1684 %8 05/2006 %! Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome %X ####BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS. ####METHODS: We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. ####RESULTS: At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness. ####CONCLUSIONS: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.). %U http://www.nejm.org/doi/full/10.1056/NEJMoa051693 %0 Conference Paper %A Trimarchi, T %A Petty, JM %A Young, MP %A Allen, GB %A Parsons, PE %A Suratt, BT %A ARDSNet, NIH / NHLBI %D 2006 %T Plasma G-CSF levels are associated with mortality in ALI/ARDS %B ATS %X A831 %0 Conference Paper %A Truwit, JD %A Korpak, A %A Schoenfeld, DA %A Matthay, MA %A Peterson, M %A Writght, P %A Rock, P %A Anzueto, A %A Hyzy, R %A Steingrub, J %A Douglas, I %A ARDSNet, NIH / NHLBI %D 2006 %T Incidence and impact on mortality of acute renal dysfunction after the onset of acute lung injury %B ATS %X A736 %0 Journal Article %A Wheeler, AP %A Bernard, GR %A Thompson, BT %A Schoenfeld, DA %A Wiedemann, HP %A deBoisblanc, BP %A Connors Jr. , AF %A Hite, RD %A Harabin, AL %A ARDSNet, NIH / NHLBI %D 2006 %T Pulmonary-Artery Versus Central Venous Catheter to Guide Treatment of Acute Lung Injury %B New Engl J Med %V 354 %N 21 %P 2213-2224 %8 05/2006 %! Pulmonary-Artery Versus Central Venous Catheter to Guide Treatment of Acute Lung Injury %X ####BACKGROUND: The balance between the benefits and the risks of pulmonary-artery catheters (PACs) has not been established. ####METHODS: We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a randomized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter (CVC) using an explicit management protocol. Mortality during the first 60 days before discharge home was the primary outcome. ####RESULTS: The groups had similar baseline characteristics. The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent, respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment. There were no significant differences between groups in lung or kidney function, rates of hypotension, ventilator settings, or use of dialysis or vasopressors. Approximately 90 percent of protocol instructions were followed in both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy. Fluid balance was similar in the two groups, as was the proportion of instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC group had approximately twice as many catheter-related complications (predominantly arrhythmias). ####CONCLUSIONS: PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury. (ClinicalTrials.gov number, NCT00281268.). %U http://www.nejm.org/doi/full/10.1056/NEJMoa061895 %0 Journal Article %A Wiedemann, HP %A Wheeler, AP %A Bernard, GR %A Thompson, BT %A Hayden, D %A deBoisblanc, BP %A Connors Jr. , AF %A Hite, RD %A Harabin, AL %A ARDSNet, NIH / NHLBI %D 2006 %T Comparison of Two Fluid-Management Strategies in Acute Lung Injury %B New Engl J Med %V 354 %N 24 %P 2564-2575 %8 05/2006 %! Comparison of Two Fluid-Management Strategies in Acute Lung Injury %X ####BACKGROUND: Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion. ####METHODS: In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology. ####RESULTS: The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent). The mean (+/-SE) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100) and the lung injury score and increased the number of ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06). ####CONCLUSIONS: Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. (ClinicalTrials.gov number, NCT00281268 [ClinicalTrials.gov].). %U http://www.nejm.org/doi/full/10.1056/NEJMoa062200 %0 Journal Article %A Wiedemann, HP %A Wheeler, AP %A Hayden, D %D 2006 %T Fluid-management strategies in acute lung injury %B New Engl J Med %V 355 %N 11 %P 1175-6 %9 Letter %! Fluid-management strategies in acute lung injury %0 Journal Article %A Calfee, CS %A Budev, MM %A Matthay, MA %A Church, G %A Brady, S %A Uchida, T %A Ishizaka, A %A Lara, A %A Ranes, JL %A deCamp, MM %A Arroliga, AC %D 2007 %T Plasma receptor for advanced glycation end-products predicts duration of ICU stay and mechanical ventilation in patients after lung transplantation %B Heart Lung Transplant %V 26 %N 7 %P 675-80 %8 07/2007 %! Plasma receptor for advanced glycation end-products predicts duration of ICU stay and mechanical ventilation in patients after lung transplantation %X ####BACKGROUND: Primary graft dysfunction, formerly termed reperfusion pulmonary edema, is the leading cause of short-term complications after lung transplantation. New evidence shows that alveolar type I epithelial cells play an active role in alveolar fluid transport and are therefore presumed to be critical in the absorption of pulmonary edema. We tested the potential relevance of a novel marker of alveolar type I cell injury, the receptor for advanced glycation end-products (RAGE), to short-term outcomes of lung transplantation. ####METHODS: The study was a prospective, observational cohort study of 20 patients undergoing single lung, bilateral lung or combined heart-lung transplantation. Plasma biomarkers were measured 4 hours after allograft reperfusion. ####RESULTS: Higher plasma RAGE levels were associated with a longer duration of mechanical ventilation and longer intensive care unit length of stay, in contrast to markers of alveolar type II cell injury, endothelial injury and acute inflammation. Specifically, for every doubling in plasma RAGE levels, the duration of mechanical ventilation increased on average by 26 hours, adjusting for ischemia time (95% confidence interval [CI] 7.4 to 44.7 hours, p = 0.01). Likewise, for every doubling of plasma RAGE levels, intensive care unit length of stay increased on average by 1.8 days, again adjusting for ischemia time (95% CI 0.13 to 3.45 days p = 0.04). In contrast, the clinical diagnosis of primary graft dysfunction was not as predictive of these short-term outcomes. ####CONCLUSIONS: Higher levels of plasma RAGE measured shortly after reperfusion predicted poor short-term outcomes from lung transplantation. Elevated plasma RAGE levels may have both pathogenetic and prognostic value in patients after lung transplantation. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741136/ %0 Journal Article %A Calfee, CS %A Eisner, MD %A Ware, LB %A Thompson, BT %A Parsons, PE %A Wheeler, AP %A Korpak, A %A Matthay, MA %A Network, Acute Respiratory Distress Syndrome %A National Heart, Lung %A Institute, Blood %D 2007 %T Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders %B Crit Care Med %V 35 %N 10 %P 2243-50 %8 10/2007 %! Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders %X ####OBJECTIVE: Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. ####DESIGN, SETTING, AND PATIENTS: Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. ####MEASUREMENTS AND MAIN RESULTS: Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24-0.82; p = .01). ####CONCLUSIONS: Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and endothelial injury. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765812/ %0 Journal Article %A Calfee, CS %A Matthay, MA %D 2007 %T Nonventilatory treatments for acute lung injury and ARDS %B Chest %V 131 %N 3 %P 913-20 %! Nonventilatory treatments for acute lung injury and ARDS %X Over the past decade, advances in the ventilatory management of acute lung injury (ALI) and ARDS have improved outcomes; however, until recently the search for other therapies has been less fruitful. Recently, the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial reported that a conservative fluid management strategy, compared with a fluid liberal strategy, increased the mean (+/- SE) number of ventilator-free days in patients with ALI (14.6 +/- 0.5 vs 12.1 +/- 0.5 days, respectively; p < 0.001). In addition to this beneficial effect on outcomes, the study found that the conservative fluid strategy did not increase the incidence of renal failure or the development of shock. Other studies have demonstrated that albumin and furosemide therapy may be beneficial in hypoproteinemic patients with lung injury, though data on outcomes is still lacking. Although several pharmacologic therapies, such as corticosteroids, surfactant, and nitric oxide, have been demonstrated to be ineffective in improving outcomes, several promising new treatments are being investigated in ongoing or upcoming clinical trials. This article reviews these developments and other recent research on the optimal nonventilatory management of patients with ALI. %U http://journal.publications.chestnet.org/article.aspx?articleid=1084992 %0 Journal Article %A Gajic, O %A Afessa, B %A Thompson, BT %A Frutos-Vivar, F %A Malinchoc, M %A Rubenfeld, GD %A Esteban, A %A Anzueto, A %A Hubmayr, RD %A Ventilation, Secondary International Study of Mechanical %A ARDSnet Investigators %D 2007 %T Prediction of death and prolonged mechanical ventilation in acute lung injury %B Critical Care Medicine %V 11 %N 3 %P R53 %8 05/2007 %! Prediction of death and prolonged mechanical ventilation in acute lung injury %X ####INTRODUCTION: Prediction of death and prolonged mechanical ventilation is important in terms of projecting resource utilization and in establishing protocols for clinical studies of acute lung injury (ALI). We aimed to identify risk factors for a combined end-point of death and/or prolonged ventilator dependence and developed an ALI-specific prediction model. ####METHODS: In this retrospective analysis of three multicenter clinical studies, we identified predictors of death or ventilator dependence from variables prospectively recorded during the first three days of mechanical ventilation. After the prediction model was derived in an international cohort of patients with ALI, it was validated in two independent samples of patients enrolled in a clinical trial involving 17 academic centers and a North American population-based cohort. ####RESULTS: A combined end-point of death and/or ventilator dependence at 14 days or later occurred in 68% of patients in the international cohort, 60% of patients in the clinical trial, and 59% of patients in the population-based cohort. In the derivation cohort, a model based on age, oxygenation index on day 3, and cardiovascular failure on day 3 predicted death and/or ventilator dependence. The prediction model performed better in the clinical trial validation cohort (area under the receiver operating curve 0.81, 95% confidence interval 0.77 to 0.84) than in the population-based validation cohort (0.71, 95% confidence interval 0.65 to 0.76). ####CONCLUSION: A model based on age and cardiopulmonary function three days after the intubation is able to predict, moderately well, a combined end-point of death and/or prolonged mechanical ventilation in patients with ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206401/ %0 Journal Article %A Kallet, RH %A Branson, RD %D 2007 %T Respiratory controversies in the critical care setting. Do the NIH ARDS Clinical Trials Network PEEP/FIO2 tables provide the best evidence-based guide to balancing PEEP and FIO2 settings in adults? %B Respir Care %V 52 %N 4 %P 461-75 %8 04/2007 %! Respiratory controversies in the critical care setting. Do the NIH ARDS Clinical Trials Network PEEP/FIO2 tables provide the best evidence-based guide to balancing PEEP and FIO2 settings in adults? %X Positive end-expiratory pressure (PEEP) and inspired oxygen fraction (F(IO(2))) are the primary means of improving P(aO(2)) during mechanical ventilation. Patients with acute respiratory distress syndrome (ARDS) typically present with a large intrapulmonary shunt, which makes even high F(IO(2)) ineffective in improving P(aO(2)). PEEP decreases intrapulmonary shunt by recruiting collapsed alveoli, but PEEP is associated with important adverse effects, whereas prolonged exposure to high F(IO(2)) may cause oxidative lung injury. The improved survival found in the National Institutes of Health's ARDS Network low-tidal-volume study may suggest that their PEEP/F(IO(2)) titration tables represent the best method for adjusting these variables. Based upon an extensive literature review of PEEP and respiratory system mechanics in ARDS, we conclude that: (1) for most patients the therapeutic range of PEEP is relatively narrow, so the ARDS Network PEEP/F(IO(2)) strategy is reasonable and supported by high-level evidence, (2) how best to adjust PEEP to prevent or ameliorate ventilator-associated lung injury is unknown and still under investigation, and (3) in a small subset of patients with severe lung injury and/or abnormal chest-wall compliance, highly individualized titration of PEEP, based upon the respiratory-system pressure-volume curve, PEEP/tidal-volume titration grids, or a recruitment maneuver and a PEEP decrement trial is a reasonable alternative. %U http://rc.rcjournal.com/content/52/4/461.short %0 Journal Article %A Liu, KD %A Glidden, DV %A Eisner, MD %A Parsons, PE %A Ware, LB %A Wheeler, A %A Korpak, A %A Thompson, BT %A Chertow, GM %A Matthay, MA %A NHLBI ARDS Network Clinical Trials Group, the %D 2007 %T Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury %B Critical Care Medicine %V 35 %N 12 %P 2755-2761 %! Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury %X ####OBJECTIVE: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. ####DESIGN: Secondary data analysis from a multicenter, randomized clinical trial. ####SETTING: Intensive care units in ten university medical centers. ####PATIENTS: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. ####INTERVENTIONS: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. ####MEASUREMENTS AND MAIN RESULTS: We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003). ####CONCLUSIONS: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293249/ %0 Journal Article %A McClintock, DE %A Ware, LB %A Eisner, MD %A Wickersham, N %A Thompson, BT %A Matthay, MA %A NHLBI ARDS Network, the %D 2007 %T Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury %B American Journal of Respiratory and Critical Care Medicine %V 175 %N 3 %P 256-62 %! Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury %X ####RATIONALE: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). ####OBJECTIVES: We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury. ####METHODS: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). ####RESULTS: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04). ####CONCLUSIONS: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1899263/ %0 Journal Article %A Rice, TW %A Wheeler, AP %A Bernard, GR %A Hayden, DL %A Schoenfeld, DA %A Ware, LB %A NIH NHLBI ARDS Network, the %D 2007 %T Comparison of the Sp02/FI02 Ratio and the PaO 2/FI02 in Patients with Acute Lung Injury or ARDS %B Chest %V 132 %N 2 %P 410-417 %! Comparison of the Sp02/FI02 Ratio and the PaO 2/FI02 in Patients with Acute Lung Injury or ARDS %X ####BACKGROUND: The diagnostic criteria for acute lung injury (ALI) and ARDS utilize the Pao(2)/fraction of inspired oxygen (Fio(2)) [P/F] ratio measured by arterial blood gas analysis to assess the degree of hypoxemia. We hypothesized that the pulse oximetric saturation (Spo(2))/Fio(2) (S/F) ratio can be substituted for the P/F ratio in assessing the oxygenation criterion of ALI. ####METHODS: Corresponding measurements of Spo(2) (values </= 97%) and Pao(2) from patients enrolled in the ARDS Network trial of a lower tidal volume ventilator strategy (n = 672) were compared to determine the relationship between S/F and P/F. S/F threshold values correlating with P/F ratios of 200 (ARDS) and 300 (ALI) were determined. Similar measurements from patients enrolled in the ARDS Network trial of lower vs higher positive end-expiratory pressure (n = 402) were utilized for validation. ####RESULTS: In the derivation data set (2,613 measurements), the relationship between S/F and P/F was described by the following equation: S/F = 64 + 0.84 x (P/F) [p < 0.0001; r = 0.89). An S/F ratio of 235 corresponded with a P/F ratio of 200, while an S/F ratio of 315 corresponded with a P/F ratio of 300. The validation database (2,031 measurements) produced a similar linear relationship. The S/F ratio threshold values of 235 and 315 resulted in 85% sensitivity with 85% specificity and 91% sensitivity with 56% specificity, respectively, for P/F ratios of 200 and 300. ####CONCLUSION: S/F ratios correlate with P/F ratios. S/F ratios of 235 and 315 correlate with P/F ratios of 200 and 300, respectively, for diagnosing and following up patients with ALI and ARDS. %U http://journal.publications.chestnet.org/article.aspx?articleid=1085326 %0 Journal Article %A Thompson, BT %A Schoenfeld, D %D 2007 %T Usual care as the control group in clinical trials of nonpharmacologic interventions %B Proc Am Thorac Soc %V 4 %N 7 %P 577-582 %8 10/2007 %! Usual care as the control group in clinical trials of nonpharmacologic interventions %X We discuss the pros and cons of including usual care as a control arm in clinical trials of nonpharmacologic interventions. Usual care is a term used to describe the full spectrum of patient care practices in which clinicians have the opportunity (which is not necessarily seized) to individualize care. The decision to use usual care as the control arm should be based on the nature of the research question and the uniformity of usual-care practices. The use of a usual-care arm in a two-arm trial should be considered for trials of investigational drugs or devices, for trials that propose to test interventions that lie well outside usual-care practices, or for trials where the research question per se is to compare a strategy against usual care. Examples of the latter include pragmatic effectiveness trials of clinical pathways or protocolized-care versus usual-care practices. Randomized intervention trials can be safely conducted and monitored using two treatments that lie within the range of usual-care practices if both approaches are considered prudent and good care for the target population. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647648/ %0 Journal Article %A Ware, LB %A Matthay, MA %A Parsons, PE %A Thompson, BT %A Januzzi, JL %A Eisner, MD %D 2007 %T Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome %B Crit Care Med. %V 35 %N 8 %P 1821-8 %8 08/2007 %! Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome %X ####OBJECTIVE: The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking. ####DESIGN: Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. ####SETTING: Ten university medical centers. ####PATIENTS: The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. ####MEASUREMENTS AND MAIN RESULTS: Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. ####CONCLUSIONS: Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764536/ %0 Journal Article %A Arroliga, AC %A Thompson, BT %A Ancukiewicz, M %A Gonzales, JP %A Guntupalli, KK %A Park, PK %A Wiedemann, HP %A Anzueto, A %A NHLBI ARDS Network, the %D 2008 %T Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome %B Critical Care Medicine %V 36 %N 4 %P 1083-8 %8 04/2008 %! Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome %X ####OBJECTIVE: The use of sedatives, opioids, and neuromuscular blocking agents (NMBAs) may delay weaning and prolong intensive care unit length of stay. We hypothesized that in patients on higher positive end-expiratory pressure (PEEP), sedatives, opioids, and NMBAs are used in a higher proportion of patients and in higher doses and that the use of these medications is associated with prolongation of weaning and mortality. ####DESIGN: Retrospective analysis. ####SETTING: The ALVEOLI trial. ####PATIENTS: Five hundred forty-nine patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) who were enrolled in the ALVEOLI trial. ####INTERVENTIONS: We analyzed prospectively collected data regarding the impact of sedatives, opioids, and NMBAs in ALI/ARDS patients on duration of mechanical ventilation, time to weaning landmarks, and mortality. ####MEASUREMENTS AND MAIN RESULTS: Sedatives and opioids were used in >80% of the patients in similar proportion in the two groups. The use of sedatives and opioids, but not the use of NMBAs, was associated with longer time on mechanical ventilation and an increased time to achieve a 2-hr spontaneous breathing trial (p < .0001). Sedatives were also associated with increased time to achieve unassisted breathing. NMBAs were used for a short period of time, in a higher proportion of patients in the lower PEEP group, and for a longer time (0.23 days). ####CONCLUSIONS: Sedatives and opioids use was similar in the higher and lower PEEP groups. The use of sedatives and opioids, but not NMBAs, was associated with a longer time to achieve important weaning landmarks. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TZ2TJnWGBQsLgKqT6nTq6gjpLvzRqkHQ9fW7Q3W6hBf0sxZsfgYL!-867019713!181195629!8091!-1?issn=0090-3493&volume=36&issue=4&spage=1083 %0 Journal Article %A Calfee, CS %A Ware, LB %A Eisner, MD %A Parsons, PE %A Thompson, BT %A Wickersham, N %A Matthay, MA %A NHLBI ARDS Network, the %D 2008 %T Plasma Receptor for Advanced Glycation End-Products And Clinical Outcomes in Acute Lung Injury %B Thorax %V 63 %N 12 %P 1083-9 %! Plasma Receptor for Advanced Glycation End-Products And Clinical Outcomes in Acute Lung Injury %2 PMC2764528 %X ####OBJECTIVES:#### To determine whether baseline plasma levels of the receptor for advanced glycation end products (RAGE), a novel marker of alveolar type I cell injury, are associated with the severity and outcomes of acute lung injury, and whether plasma RAGE levels are affected by lower tidal volume ventilation. ####DESIGN, SETTING AND PARTICIPANTS:#### Measurement of plasma RAGE levels from 676 subjects enrolled in a large randomised controlled trial of lower tidal volume ventilation in acute lung injury. ####MEASUREMENTS AND MAIN RESULTS:#### Higher baseline plasma RAGE was associated with increased severity of lung injury. In addition, higher baseline RAGE was associated with increased mortality (OR for death 1.38 (95% CI 1.13 to 1.68) per 1 log increment in RAGE; p = 0.002) and fewer ventilator free and organ failure free days in patients randomised to higher tidal volumes. These associations persisted in multivariable models that adjusted for age, gender, severity of illness and the presence of sepsis or trauma. Plasma RAGE was not associated with outcomes in the lower tidal volume group (p = 0.09 for interaction in unadjusted analysis). In both tidal volume groups, plasma RAGE levels declined over the first 3 days; however, the decline was 15% greater in the lower tidal volume group (p = 0.02; 95% CI 2.4% to 25.0%). ####CONCLUSIONS:#### Baseline plasma RAGE levels are strongly associated with clinical outcomes in patients with acute lung injury ventilated with higher tidal volumes. Lower tidal volume ventilation may be beneficial in part by decreasing injury to the alveolar epithelium. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764528/ %0 Journal Article %A Checkley, W %A Brower, R %A Korpak, A %A Thompson, BT %D 2008 %T Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury %B Am J Respir Crit Care Med %V 177 %P 1215-1222 %! Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury %2 PMC2408439 %X ####RATIONALE: In a clinical trial by the Acute Respiratory Distress Syndrome Network (ARDSNet), mechanical ventilation with tidal volumes of 6 ml/kg decreased mortality from acute lung injury. However, interpretations of these results generated controversy and it was unclear if this trial would change usual-care practices. ####OBJECTIVES: First, to determine if clinical practices at ARDSNet hospitals changed after the tidal volume trial. Second, to determine if tidal volume and plateau pressure (Pplat) within 48 hours before randomization affected hospital mortality in patients subsequently managed with 6 ml/kg predicted body weight (PBW). ####METHODS: We used preenrollment data from 2,451 patients enrolled in six trials (1996-2005) to describe changes in tidal volume over time. We used logistic regression to determine if preenrollment tidal volume or Pplat affected mortality. ####MEASUREMENTS AND MAIN RESULTS: Median preenrollment tidal volume decreased from 10.3 ml/kg PBW (range, 4.3-17.1) during the tidal volume trial (1996-1999) to 7.3 ml/kg PBW (range, 3.9-16.2) after its completion (P < 0.001). Preenrollment tidal volume was not associated with mortality (P = 0.566). The odds of death increased multiplicatively with each cm H(2)O of preenrollment Pplat (P < 0.001) (e.g., the odds of death was 1.37 times greater when preenrollment Pplat increased by 10 cm H(2)O). ####CONCLUSIONS: Physicians used lower tidal volumes after publication of the tidal volume trial. Preenrollment Pplat was strongly associated with mortality, and may reflect disease severity independent of tidal volume. Pplat measured early in the course of acute lung injury, after accounting for tidal volume, is a respiratory system-specific value with strong prognostic significance. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408439/ %0 Journal Article %A Glassberg, AE %A Luce, JM %A Matthay, MA %A NHLBI Clinical Trials Network, the %D 2008 %T Reasons for Nonenrollment in a Clinical Trial of Acute Lung Injury %B Chest %V 134 %N 4 %P 719-23 %8 10/2008 %! Reasons for Nonenrollment in a Clinical Trial of Acute Lung Injury %2 PMC2789486 %X ####BACKGROUND: Enrolling critically ill patients in clinical trials is challenging. We observed that eligible patients at San Francisco General Hospital (SFGH), a public hospital that cares largely for indigent patients, were less likely to be enrolled in a clinical trial of acute lung injury (ALI) than eligible patients at the University of California, San Francisco (UCSF), a university referral center. We examined the reasons for nonenrollment and the impact of the availability of a surrogate decision maker on critical care clinical trials enrollment. ####METHODS: Data collected from the ARDS Network trial of lower vs traditional tidal volume ventilation for patients with ALI was analyzed. Patient demographics and reasons for nonenrollment were analyzed among 531 consecutively screened patients at the two hospitals: UCSF and SFGH. ####RESULTS: At UCSF, 1% of screened patients were not enrolled because they lacked surrogates, whereas 18% of screened patients were not enrolled at SFGH because they lacked surrogates. Lack of surrogate was the most common reason for nonenrollment among eligible patients at SFGH. ####CONCLUSIONS: Critically ill patients with ALI at a public hospital were less likely to be enrolled in a clinical trial than patients at a university hospital primarily because they lacked surrogates. Lack of a surrogate also was a major factor in nonenrollment in other ARDS Network hospitals. In order to provide all affected patients an opportunity to participate in research, innovative strategies for increasing enrollment in critical care research without compromising protection from research risks are needed. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789486/ %0 Journal Article %A Matthay, MA %D 2008 %T Treatment of acute lung injury: clinical and experimental studies %B Proc Am Thorac Soc %V 15 %N 5 %P 297-9 %8 04/2008 %! Treatment of acute lung injury: clinical and experimental studies %X This presentation at the 2007 Aspen Lung Injury and Repair Conference provided a brief historical perspective from the 1998 Aspen Conference on Acute Lung Injury, highlighting the discussion of clinical definitions. There was also a review of the National Heart, Lung, and Blood Institute ARDS Network clinical trials, with an emphasis on the success of the lung-protective ventilation strategy in reducing mortality. In addition, there was a discussion of the recently completed fluid and catheter treatment trial, which demonstrated no benefit for pulmonary arterial catheterization over central venous catheterization for monitoring patients with acute lung injury (ALI). The trial demonstrated an increase in ventilator-free days with a fluid-conservative protocol. Finally, there was a discussion of recent experimental studies that show promise for cell-based therapy with mesenchymal stem cells for the treatment of endotoxin-induced ALI in mice. There were three objectives for this presentation at the 2007 Lung Injury, Repair, and Remodeling Conference: (1) to provide a brief historical perspective from the 1998 Aspen Conference on Acute Lung Injury; (2) to review major National Heart, Lung, and Blood Institute clinical trials conducted in the past 10 years by the ARDS Network; and (3) to review some of our promising work with cell-based therapy for experimental ALI. %0 Journal Article %A Calfee, CS %A Eisner, MD %A Parsons, PE %A Thompson, BT %A Conner, ER Jr %A Matthay, MA %A Ware, LB %A NHLBI ARDS Network, the %D 2009 %T Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury %B Intensive Care Med %V 35 %N 2 %P 248-57 %8 02/2009 %! Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury %2 PMC2790376 %X ####OBJECTIVE: To determine if levels of soluble intercellular adhesion molecule-1 (sICAM-1), a marker of alveolar epithelial and endothelial injury, differ in patients with hydrostatic pulmonary edema and acute lung injury (ALI) and are associated with clinical outcomes in patients with ALI. ####DESIGN, SETTING, AND PARTICIPANTS: Measurement of sICAM-1 levels in (1) plasma and edema fluid from 67 patients with either hydrostatic pulmonary edema or ALI enrolled in an observational, prospective single center study, and (2) in plasma from 778 patients with ALI enrolled in a large multi-center randomized controlled trial of ventilator strategy. ####RESULTS: In the single-center study, levels of sICAM-1 were significantly higher in both edema fluid and plasma (median 938 and 545 ng/ml, respectively) from ALI patients compared to hydrostatic edema patients (median 384 and 177 ng/ml, P < 0.03 for both comparisons). In the multi-center study, higher plasma sICAM-1 levels were associated with poor clinical outcomes in both unadjusted and multivariable models. Subjects with ALI whose plasma sICAM-1 levels increased over the first 3 days of the study had a higher risk of death, after adjusting for other important predictors of outcome (odds ratio 1.48; 95% CI 1.03-2.12, P = 0.03). ####CONCLUSIONS: Both plasma and edema fluid levels of sICAM-1 are higher in patients with ALI than in patients with hydrostatic pulmonary edema. Higher plasma sICAM-1 levels and increasing sICAM-1 levels over time are associated with poor clinical outcomes in ALI. Measurement of sICAM-1 levels may be useful for identifying patients at highest risk of poor outcomes from ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790376/ %0 Journal Article %A Christie, JD %A Localio, AR %A Bellamy, S %A Gallop, R %A Ancukiewicz, M %A Eisner, MD %A Lanken, PN %A ARDSNet, NIH / NHLBI %A Cooke, CR %A Shah, CV %D 2009 %T A simple clinical predictive index for objective estimates of mortality in acute lung injury (ALI) %B Crit Care Med %V 37 %N 6 %P 1913-20 %8 06/2009 %! A simple clinical predictive index for objective estimates of mortality in acute lung injury (ALI) %2 PMC2731230 %X ####OBJECTIVE: We sought to develop a simple point score that would accurately capture the risk of hospital death for patients with acute lung injury (ALI). ####DESIGN: This is a secondary analysis of data from two randomized trials. Baseline clinical variables collected within 24 hours of enrollment were modeled as predictors of hospital mortality using logistic regression and bootstrap resampling to arrive at a parsimonious model. We constructed a point score based on regression coefficients. ####SETTING: Medical centers participating in the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSnet). ####PATIENTS: Model development: 414 patients with nontraumatic ALI participating in the low tidal volume arm of the ARDSnet Acute Respiratory Management in ARDS study. Model validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury study. Model Validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury trial. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Variables comprising the prognostic model were hematocrit <26% (1 point), bilirubin >or=2 mg/dL (1 point), fluid balance >2.5 L positive (1 point), and age (1 point for age 40-64 years, 2 points for age >or=65 years). Predicted mortality (95% confidence interval) for 0, 1, 2, 3, and 4+ point totals was 8% (5% to 14%), 17% (12% to 23%), 31% (26% to 37%), 51% (43% to 58%), and 70% (58% to 80%), respectively. There was an excellent agreement between predicted and observed mortality in the validation cohort. Observed mortality for 0, 1, 2, 3, and 4+ point totals in the validation cohort was 12%, 16%, 28%, 47%, and 67%, respectively. Compared with the Acute Physiology Assessment and Chronic Health Evaluation III score, areas under the receiver operating characteristic curve for the point score were greater in the development cohort (0.72 vs. 0.67, p = 0.09) and lower in the validation cohort (0.68 vs. 0.75, p = 0.03). ####CONCLUSIONS: Mortality in patients with ALI can be predicted using an index of four readily available clinical variables with good calibration. This index may help inform prognostic discussions, but validation in nonclinical trial populations is necessary before widespread use. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731230/ %0 Journal Article %A Cooke, CR %A Shah, CV %A Gallop, R %A Bellamy, S %A Ancukiewicz, M %A Eisner, MD %A Lanken, PN %A Localio, AR %A Christie, JD %A NHLBI ARDS Network, the %D 2009 %T A Simple Clinical Predictive Index for Objective Estimates of Mortality in Acute Lung Injury %B Critical Care Medicine %V 37 %N 6 %P 1913-20 %8 06/2009 %! A Simple Clinical Predictive Index for Objective Estimates of Mortality in Acute Lung Injury %2 PMC2731230 %X ####OBJECTIVE: We sought to develop a simple point score that would accurately capture the risk of hospital death for patients with acute lung injury (ALI). ####DESIGN: This is a secondary analysis of data from two randomized trials. Baseline clinical variables collected within 24 hours of enrollment were modeled as predictors of hospital mortality using logistic regression and bootstrap resampling to arrive at a parsimonious model. We constructed a point score based on regression coefficients. ####SETTING: Medical centers participating in the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSnet). ####PATIENTS: Model development: 414 patients with nontraumatic ALI participating in the low tidal volume arm of the ARDSnet Acute Respiratory Management in ARDS study. Model validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury study. Model Validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury trial. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Variables comprising the prognostic model were hematocrit <26% (1 point), bilirubin >or=2 mg/dL (1 point), fluid balance >2.5 L positive (1 point), and age (1 point for age 40-64 years, 2 points for age >or=65 years). Predicted mortality (95% confidence interval) for 0, 1, 2, 3, and 4+ point totals was 8% (5% to 14%), 17% (12% to 23%), 31% (26% to 37%), 51% (43% to 58%), and 70% (58% to 80%), respectively. There was an excellent agreement between predicted and observed mortality in the validation cohort. Observed mortality for 0, 1, 2, 3, and 4+ point totals in the validation cohort was 12%, 16%, 28%, 47%, and 67%, respectively. Compared with the Acute Physiology Assessment and Chronic Health Evaluation III score, areas under the receiver operating characteristic curve for the point score were greater in the development cohort (0.72 vs. 0.67, p = 0.09) and lower in the validation cohort (0.68 vs. 0.75, p = 0.03). ####CONCLUSIONS: Mortality in patients with ALI can be predicted using an index of four readily available clinical variables with good calibration. This index may help inform prognostic discussions, but validation in nonclinical trial populations is necessary before widespread use. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731230/ %0 Journal Article %A Erickson, SE %A Martin, GS %A David, JL %A Matthay, MA %A Eisner, MD %A NIH NHLBI ARDS Network, the %D 2009 %T Recent trends in acute lung injury mortality: 1996-2005 %B Crit Care Med %V 37 %N 5 %P 1574-9 %! Recent trends in acute lung injury mortality: 1996-2005 %2 PMC2696257 %X ####OBJECTIVE: Studies from single centers have suggested that mortality from acute lung injury (ALI) has declined over time. However, recent trends in ALI mortality from centers across the United States are unknown. We sought to determine whether recent advances in the treatment of ALI and related critical illnesses have resulted in decreased mortality from ALI. ####DESIGN: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome (ARDS) Network randomized controlled trials. ####SETTING: Adult intensive care units participating in the ARDS Network trials. ####PATIENTS: 2,451 mechanically ventilated patients with ALI enrolled in the ARDS Network randomized controlled trials between 1996 and 2005. ####MEASUREMENTS AND MAIN RESULTS: Crude mortality was 35% in 1996-1997 and declined during each subsequent time period to a low of 26% in 2004-2005 (test for trend p < 0.0005). After adjusting for demographic and clinical covariates, including receipt of lower tidal volume ventilation and severity of illness, the temporal trend persisted (test for trend p = 0.002). When analyzed by individual causes of lung injury, there were not any statistically significant temporal trends in 60-day mortality for the most common causes of lung injury (pneumonia, sepsis, aspiration, and trauma). ####CONCLUSIONS: Over the past decade, there seems to be a clear temporal improvement in survival among patients with ALI treated at ARDS Network centers. Our findings strongly suggest that other advancements in critical care, aside from lower tidal volume ventilation, accounted for this improvement in mortality. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696257/ %0 Journal Article %A Erickson, Sara E. %A Shlipak, Michael G. %A Martin, Greg S. %A Wheeler, Arthur P. %A Ancukiewicz, Marek %A Matthay, Michael A. %A Eisner, Mark D. %D 2009 %T Racial and ethnic disparities in mortality from Acute Lung Injury %B Critical Care Medicine %V 37 %N 1 %P 1-6 %8 01/2009 %! Racial and ethnic disparities in mortality from Acute Lung Injury %2 PMC2696263 %X ####OBJECTIVE: Little is known about the influence of race and ethnicity on mortality from acute lung injury (ALI). We sought to determine whether black race or Hispanic ethnicity is independently associated with mortality among patients with ALI. ####DESIGN: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome Network randomized controlled trials. ####SETTING: Adult intensive care units participating in the Acute Respiratory Distress Syndrome Network trials. ####PATIENTS: A total of 2362 mechanically ventilated patients (1715 white, 449 black, and 198 Hispanic) with ALI. ####MEASUREMENTS AND MAIN RESULTS: The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p = 0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (odds ratio [OR] = 1.42; 95% confidence interval [CI] 1.10-1.84 for blacks; OR = 1.94; 95% CI, 1.36-2.77 for Hispanics; OR = 1.00 for whites). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR = 1.25; 95% CI, 0.95-1.66), whereas the association with Hispanic ethnicity persisted (OR = 2.00; 95% CI, 1.37-2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = -2.3; 95% CI -3.90 to -0.70). ####CONCLUSIONS: Black and Hispanic patients with ALI have a significantly higher risk of death compared with white patients. This increased risk seemed to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696263/ %0 Journal Article %A Grissom, C %A Morris, A %A Lanken, P %A Ancukiewicz, M %A Orme, J %A Schoenfeld, D %A Thompson, T %D 2009 %T Association of Physical Examination with Pulmonary Artery Catheter Parameters in Acute Lung Injury %B Critical Care Medicine %V 37 %N 10 %P 2720-2726 %8 In Press %! Association of Physical Examination with Pulmonary Artery Catheter Parameters in Acute Lung Injury %X ####OBJECTIVE: To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. ####DESIGN: Retrospective study. ####SETTING: Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. ####PATIENTS: Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. ####INTERVENTIONS: Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. ####MEASUREMENTS: We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. ####MEASUREMENTS AND MAIN RESULTS: Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%,specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and high central venous pressure, but these correlations were not found to be clinically useful. ####CONCLUSIONS: In this subset of patients with acute lung injury, there is a high prior probability that cardiac index and mixed venous oxygen saturation are normal and physical examination findings of ineffective circulation are not useful for predicting low cardiac index or mixed venous oxygen saturation. Central venous oxygen saturation <70% does not accurately predict mixed venous oxygen saturation <60%, but a central venous oxygen saturation >or=70% may be useful to exclude mixed venous oxygen saturation <60%. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TflSFfM3m21K2nf40sF0lMq1mhQxM1w1bDnzmWK0h4cF452Fnsmn!-813027467!181195628!8091!-1?issn=0090-3493&volume=37&issue=10&spage=2720 %0 Journal Article %A Hough, CL %A Steinberg, KP %A Thompson, TB %A Rubenfeld, GD %A Hudson, LD %D 2009 %T Intensive care unit-acquired neuromyopathy and corticosteroids in survivors of persistent ARDS %B Intensive Care Medicine %V 35 %N 1 %P 63-8 %! Intensive care unit-acquired neuromyopathy and corticosteroids in survivors of persistent ARDS %2 PMC2861487 %X ####OBJECTIVES: To determine the incidence and outcomes of intensive care unit-acquired neuromyopathy and to investigate the role of methylprednisolone in survivors of persistent acute lung injury. ####DESIGN: Secondary analysis of completed randomized placebo-controlled trial. ####SETTING: Twenty-five hospitals in the NHLBI ARDS Network. ####PATIENTS AND PARTICIPANTS: Patients enrolled in the ARDS Network study of methylprednisolone versus placebo for persistent ARDS who survived 60 days or to hospital discharge. ####MEASUREMENTS AND RESULTS: One hundred and twenty-eight study patients survived 60 days. Forty-three (34%) of these patients had evidence by chart review of ICU-acquired neuromyopathy, which was associated with prolonged mechanical ventilation, return to mechanical ventilation, and delayed return to home after critical illness. Treatment with methylprednisolone was not significantly associated with an increase in risk of neuromyopathy (OR 1.5; 95% CI 0.7-3.2). ####CONCLUSIONS: ICU-acquired-neuromyopathy is common among survivors of persistent ARDS and is associated with poorer clinical outcomes. We did not find a significant association between methylprednisolone treatment and neuromyopathy. Limitations of this study preclude definitive conclusions about the causal relationship between corticosteroids and ICU-acquired neuromuscular dysfunction. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861487/ %0 Journal Article %A Kallet, RH %D 2009 %T What is the legacy of the National Institutes of Health Acute Respiratory Distress Syndrome Network? %B Respir Care %V 54 %N 7 %P 912-24 %8 07/2009 %! What is the legacy of the National Institutes of Health Acute Respiratory Distress Syndrome Network? %X It has been almost 15 years since the National Institutes of Health created the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDS Network) and nearly a decade since the completion of the landmark low-tidal volume (V(T)) trial. In retrospect, the ARDS Network had a profound impact on the design and conduct of clinical trials in critical care. It represented the first time the federal government funded a clinical trials network devoted to Phase-III testing of important, non-pharmacologic therapies. Also the ARDS Network introduced factorial design into critical-care research, which allowed Phase-II testing of promising therapies. Other important contributions from the ARDS Network may not become apparent for many years. These include the ongoing mentoring of a new generation of critical-care researchers, as well as continued testing on an enormous store of biological samples that inevitably will advance our understanding of the pathogenesis of ARDS. Perhaps someday this may lead to another therapeutic breakthrough. Part of the ARDS Network's legacy surely will have been the opening of a dialog regarding the design of clinical trials in critical care, as well as a concerted effort to improve the protection of subjects enrolled into those trials. Finally, the respiratory care profession itself has benefited, owing both to its critical role in the successful implementation of complicated therapist-driven protocols and also to the ARDS Network's novel practice of utilizing respiratory therapists as clinical coordinators. This has raised the profile and enhanced the stature of the respiratory care profession. %U http://rc.rcjournal.com/content/54/7/912.short %0 Journal Article %A Rosenberg, AL %A Dechert, RE %A Park, PK %A Bartlett, RH %A NIH NHLBI ARDS Network, the %D 2009 %T Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort %B Journal of Intensive Care Medicine %V 24 %N 1 %P 35-46 %! Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort %X ####Objective: To evaluate the independent influence of fluid balance on outcomes for patients with acute lung injury. ####Design: Secondary analysis of a prospective cohort study conducted between March 1996 and March 1999. ####Setting: The study involved 10 academic clinical centers (with 24 hospitals and 75 Intensive Care Units). ####Patients: All patients for whom fluid balance data existed (844) from the 902 patients enrolled in the National Heart Lung Blood Institute's ARDS Network ventilator-tidal volume trial. ####Interventions: The study had no interventions. ####Measurements/Results: On the first day of study enrollment, 683 patients were, on average, more than 3.5 L in positive fluid balance compared to 161 patients in negative fluid balance (P < .001). Cumulative negative fluid balance on day 4 of the study was associated with an independently lower hospital mortality (OR, 0.50; 95% CI, 0.28-0.89; P < .001) more ventilator and intensive care unit-free days. ####Conclusions: Negative cumulative fluid balance at day 4 of acute lung injury is associated with significantly lower mortality, independent of other measures of severity of illness. %U http://jic.sagepub.com/content/24/1/35.long %0 Journal Article %A Schoenfeld, DA %A Zheng, H %A Finkelstein, DM %D 2009 %T Bayesian design using adult data to augment pediatric trials %B Clin Trials %V 6 %N 4 %P 297-304 %8 08/2009 %! Bayesian design using adult data to augment pediatric trials %2 PMC3374646 %X ####BACKGROUND:#### It can be difficult to conduct pediatric clinical trials because there is often a low incidence of the disease in children, making accrual slow or infeasible. In addition, low mortality and morbidity in this population make it impractical to achieve adequate power. In this case, the only evidence for treatment efficacy comes from adult trials. Since pediatric care providers are accustomed to relying on evidence from adult studies, it is natural to consider borrowing information from adult trials. ####PURPOSE:#### The goal of this article is to propose a Bayesian approach to the design and analysis of pediatric trials to allow borrowing strength from previous or simultaneous adult trials. ####METHODS:#### We apply a hierarchical model for which the efficacy parameter from the adult trial and that of the pediatric trail are considered to be draws from a normal distribution. The choice of (the variance of) this distribution is guided by discussion with medical experts. We show that with this information, one can calculate the sample size required for the pediatric trial. We discuss how inference of these studies in pediatric populations depends on the parameter that captures the similarity of the treatment efficacy in adults compared to children. ####RESULTS: The Bayesian approach can substantially increase the power of a pediatric clinical trial (or equivalently decrease the number of subjects required) by formally leveraging the data from the adult trial. ####LIMITATIONS: Our method relies on obtaining a value for the inter-study variability, nu, which may be difficult to describe to a clinical investigator. ####CONCLUSIONS:#### The Bayesian approach has the potential of making pediatric clinical trials feasible because it has the effect of borrowing strength from adult trials, thus requiring a smaller pediatric trial to show efficacy of a drug in children. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374646/ %0 Journal Article %A Stewart, RM %A Park, PK %A Hunt, JP %A McIntyre, RC Jr. %A McCarthy, J %A Zarzabal, LA %A Michalek, JE %A NIH NHLBI ARDS Clinical Trials Network, the %D 2009 %T Less Is More: Improved Outcomes In Surgical Patients with Conservative Fluid Administration and Central Venous Catheter Monitoring %B Journal of the American College of Surgeons %V 208 %N 5 %P 725-35 %8 05/2009 %! Less Is More: Improved Outcomes In Surgical Patients with Conservative Fluid Administration and Central Venous Catheter Monitoring %X ####BACKGROUND: The ARDS Clinical Trials Network Fluid and Catheter Treatment Trial (FACTT) addressed fluid management and central monitoring of patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI). Because surgical patients may have been fundamentally different from the overall FACTT cohort, we set out to separately analyze the surgery patients in the trial. ####STUDY DESIGN: We performed a posthoc, surgical subgroup analysis of 1,000 patients enrolled in the FACTT. Patients were randomized using a 2x2 factorial design comparing a conservative (CON) versus a liberal (LIB) strategy of fluid management and the use of a pulmonary artery catheter (PAC) or a central venous catheter (CVC). The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days, ICU-free days, and dialysis-free days until hospital discharge up to day 90. We defined surgical patients as those admitted to a surgical ICU, burn ICU, or cardiac surgical ICU; trauma patients; or those with an APACHE III surgical admission type. ####RESULTS: There were 244 surgical patients. Risk of death within 60 days of randomization did not vary with catheter or fluid management, and a corresponding lack of effect was evident with regard to dialysis-free days. Ventilator-free days were increased in the fluid-conservative group (LIB, 13+/-1 days; CON, 15+/-1 days; p=0.04) at 28 days. CVC patients had more ventilator-free days at 28 and 90 days (28 days: CVC, 16+/-1 days; PAC, 13+/-1 days; p=0.03; 90 days: CVC, 64+/-3 days; PAC, 57+/-4 days; p=0.03). CVC patients had more ICU-free days at 90 days (90 days: CVC, 63+/-3 days; PAC, 55+/-3 days; p=0.04). ####CONCLUSIONS: The risk of death did not vary with fluid management or catheter. A conservative fluid-administration strategy and central venous catheter monitoring resulted in more ventilator-free and ICU-free days in surgical patients with acute lung injury, and conservative fluid administration did not result in more renal failure. %U http://www.mdconsult.com/das/article/body/445168752-2/jorg=journal&source=&sp=22052334&sid=0/N/696636/1.html?issn=10727515&_returnURL=http%3A//linkinghub.elsevier.com/retrieve/pii/S1072751509000490%3Fshowall%3Dtrue %0 Journal Article %A Briel, M %A Meade, M %A Mercat, A %A Brower, R %A Talmor, D %A Walter, S %A Slutsky, A %A Pullenayegum, E %A Zhou, Q %A Cook, D %A Brochard, L %A Richard, J %A Lamontagne, F %A Bhatnagar, N %A Stewart, T %A Guyatt, G %D 2010 %T Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis %B JAMA %V 303 %N 9 %P 865-73 %8 03/2010 %! Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis %X ####CONTEXT: Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences. ####OBJECTIVES: To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups. ####DATA SOURCES: Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010). ####STUDY SELECTION: Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality. ####DATA EXTRACTION: Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects. ####RESULTS: There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar. ####CONCLUSIONS: Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS. %U http://jama.jamanetwork.com/article.aspx?articleid=185447 %0 Journal Article %A Bull, TM %A Clark, B %A McFann, K %A Moss, M %A NIH NHLBI ARDS Network %D 2010 %T Pulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury %B Am J Respir Crit Care Med %V 182 %N 9 %P 1123-8 %8 11/2010 %! Pulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury %2 PMC3001255 %X ####RATIONALE: Despite the recognition that acute lung injury (ALI) can elevate pulmonary artery (PA) pressure and right ventricular afterload, the impact of pulmonary vascular dysfunction on outcomes of these patients is not well defined. ####OBJECTIVES: To investigate the impact of pulmonary vascular dysfunction in patients with acute lung injury. ####METHODS: Secondary analysis of the Fluid and Catheter Treatment Trial. A total of 501 patients who received a PA catheter were evaluated for associations between increases in transpulmonary gradient (TPG) (PA mean pressure - PA occlusion pressure) or pulmonary vascular resistance index (PVRi) and 60-day mortality, ventilator-, intensive care unit (ICU)-, and cardiovascular-free days (days with mean arterial pressure ≥ 60 mm Hg off vasopressor support). ####MEASUREMENTS AND MAIN RESULTS: We were able to measure the TPG in 475 (95%) and the PVRi in 470 (92%) patients. Patients with an elevated baseline TPG had an increased 60-day mortality (30 versus 19%; P = 0.02), and lower numbers of median ventilator- [25-75% quartiles] (15 [0-22] versus 19 [7-24]; P = 0.005), ICU- (14 [0-21] versus 18 [5-22]; P = 0.005), and cardiovascular-free days (23 [12-27] versus 25 [18-27]; P = 0.03). The median PVRi (305 [204-431] dyne s/cm⁵/m²) was elevated early in the course of ALI. PVRi was statistically higher in patients who died (326 [209-518] versus 299 [199-416]; P = 0.01). In individual multivariate models, TPG and PVRi remained independent risk factors for 60-day mortality and decrease in the number of ventilator-, ICU-, and cardiovascular-free days. ####CONCLUSIONS: Pulmonary vascular dysfunction is common in ALI, and is independently associated with poor outcomes. Future trials targeting pulmonary vascular dysfunction may be indicated. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001255/ %0 Journal Article %A Checkley, W %A Brower, RG %A Muñoz, A %A NIH Acute Respiratory Distress Syndrome Network Investigators %D 2010 %T Inference for mutually exclusive competing events through a mixture of generalized gamma distributions %B Epidemiology %V 21 %N 4 %P 557-65 %8 07/2010 %! Inference for mutually exclusive competing events through a mixture of generalized gamma distributions %2 PMC3227544 %X ####BACKGROUND: Time-to-event data with 2 or more types of endpoints are found in many epidemiologic settings. Instead of treating the times for one of the endpoints as censored observations for the other, we present an alternative approach where we treat competing events as distinct outcomes in a mixture. Our objective was to determine if and how the mixture was modified in response to an intervention. ####METHODS: We used a mixture of generalized gamma distributions to concatenate the overall frequency and distribution of the times of 2 competing events commonly observed in critical care trials, namely (1) unassisted breathing followed by discharge home alive and (2) in-hospital death. We applied our proposed methods to data from 2 randomized clinical trials of critically ill patients. ####RESULTS: Mechanical ventilation with lower tidal volumes modified the mixture (P = 0.103) when compared with traditional tidal volumes by lowering the overall frequency of death (P = 0.005), rather than through affecting either the distributions of times to unassisted breathing (P = 0.477) or times to death (P = 0.718). Likewise, use of a conservative versus a liberal fluid management modified the mixture (P < 0.001) by achieving earlier times to unassisted breathing (P < 0.001) and not through affecting the overall frequency of death (P = 0.202) or the distribution of times to death (P = 0.693). ####CONCLUSIONS: A mixture approach to competing risks provides a means to determine the overall effect of an intervention and insights into how this intervention modifies the components of the mixture. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227544/ %0 Journal Article %A Engoren, M %D 2010 %T Does erythrocyte blood transfusion prevent acute kidney injury? Propensity-matched case control analysis %B Anesthesiology %V 113 %N 5 %P 1126-33 %8 11/2010 %! Does erythrocyte blood transfusion prevent acute kidney injury? Propensity-matched case control analysis %X ####BACKGROUND: Acute kidney injury is a common occurrence in intensive care unit patients with a reported incidence of 11-67% and is associated with an increased risk of death. In other patient populations, erythrocyte transfusion has been associated with increased risk of adverse outcomes including sepsis, multisystem organ dysfunction, and death. The purpose of this study was to determine the effect of erythrocyte transfusion on the development of acute kidney injury. ####METHODS: This was a retrospective analysis of prospectively collected data that used propensity matched transfused and nontransfused patients. Propensity matching was done using semiparsimonious logistic regression. McNemar test for nonindependent data sets was used to compare groups. ####RESULTS: Four hundred two patients from a trial on fluid management in patients with acute lung injury were matched. 38% of transfused patients had a rise in creatinine the day after transfusion compared with 33% of their nontransfused matches (P = 0.315). By day 7, creatinine had increased in 51% of transfused patients compared with 52% in nontransfused patients (P = 0.832). The incidences of renal risk, injury, and failure were 39 (19%), 27 (13%), and 11 (5%) in the transfused group and 38 (19%), 24 (12%), and 11 (5%) in the nontransfused group, P = 1.00, 0.785, and 1.00, respectively. ####CONCLUSIONS: Transfusion of erythrocytes to patients with acute lung injury had no effect on the development of acute kidney injury. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=Tf4d3xFxJ81TR3Zfz1vP0lZ4r2hyXKCV2Fvb0zl976029ZTVpnGM!-813027467!181195628!8091!-1?issn=0003-3022&volume=113&issue=5&spage=1126 %0 Journal Article %A Johnson, ER %A Matthay, MA %D 2010 %T Acute lung injury: epidemiology, pathogenesis, and treatment %B J Aerosol Med Pulm Drug Deliv %V 23 %N 4 %P 243-52 %8 08/2010 %! Acute lung injury: epidemiology, pathogenesis, and treatment %2 PMC3133560 %X Acute lung injury (ALI) remains a significant source of morbidity and mortality in the critically ill patient population. Defined by a constellation of clinical criteria (acute onset of bilateral pulmonary infiltrates with hypoxemia without evidence of hydrostatic pulmonary edema), ALI has a high incidence (200,000 per year in the US) and overall mortality remains high. Pathogenesis of ALI is explained by injury to both the vascular endothelium and alveolar epithelium. Recent advances in the understanding of pathophysiology have identified several biologic markers that are associated with worse clinical outcomes. Phase III clinical trials by the NHLBI ARDS Network have resulted in improvement in survival and a reduction in the duration of mechanical ventilation with a lung-protective ventilation strategy and fluid conservative protocol. Potential areas of future treatments include nutritional strategies, statin therapy, and mesenchymal stem cells. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133560/ %0 Journal Article %A Schrier, RW %D 2010 %T Fluid administration in critically ill patients with acute kidney injury %B Clin J Am Soc Nephrol %V 5 %N 4 %P 733-9 %8 04/2010 %! Fluid administration in critically ill patients with acute kidney injury %X Physiologic end points for fluid resuscitation in septic shock patients with acute kidney injury (AKI) have been undertaken in randomized studies using the Early Goal-Directed Therapy (EGDT) approach. These studies have demonstrated a beneficial effect on in-hospital mortality with EGDT. The Saline versus Albumin Fluid Evaluation (SAFE) randomized study in critically ill patients demonstrated no difference in survival when saline versus albumin solutions were used for resuscitation. However, a benefit of albumin has been demonstrated in a randomized study on renal function and survival in cirrhotic patients with spontaneous bacterial periotonitis. On the other hand, recent observational studies have shown a correlation between fluid overload and mortality in AKI patients whether or not they necessitated dialysis. Moreover, the Adult Respiratory Distress Syndrome (ARDS) network performed a randomized study in critically ill patients to compare liberal versus conservative fluid administration. The liberal fluid administration group exhibited worse pulmonary function and no protection of renal function. Constancy of central venous pressure (CVP) measurements in the 12-mmHg range were observed in the liberal fluid group despite a mean increase in positive fluid balance of 7 L, thus suggesting increased interstitial fluid accumulation leading to pulmonary congestion. The review presented here discusses these various aspects of fluid administration in critically ill patients, particularly those with AKI, and indicates the potential deleterious effects of fluid overload on lung, heart, and kidney function that could contribute to increased mortality. %U http://cjasn.asnjournals.org/content/5/4/733.long %0 Journal Article %A Siddiki, H %A Kojicic, M %A Li, G %A Yilmaz, M %A Thompson, BT %A Hubmayr, RD %A Gajic, O %D 2010 %T Bedside quantification of dead-space fraction using routine clinical data in the patients with acute lung injury: secondary analysis of two prospective trials %B Critical Care Medicine %V 14 %N 4 %8 07/2010 %! Bedside quantification of dead-space fraction using routine clinical data in the patients with acute lung injury: secondary analysis of two prospective trials %2 PMC2945122 %X ####INTRODUCTION: Dead-space fraction (Vd/Vt) has been shown to be a powerful predictor of mortality in acute lung injury (ALI) patients. The measurement of Vd/Vt is based on the analysis of expired CO2 which is not a part of standard practice thus limiting widespread clinical application of this method. The objective of this study was to determine prognostic value of Vd/Vt estimated from routinely collected pulmonary variables. ####METHODS: Secondary analysis of the original data from two prospective studies of ALI patients. Estimated Vd/Vt was calculated using the rearranged alveolar gas equation: Vd/Vt=1-[(0.86×VCO2est)/(VE×PaCO2)] where VCO2est is the estimated CO2 production calculated from the Harris Benedict equation, minute ventilation (VE) is obtained from the ventilator rate and expired tidal volume and PaCO2 from arterial gas analysis. Logistic regression models were created to determine the prognostic value of estimated Vd/Vt. ####RESULTS: One hundred and nine patients in Mayo Clinic validation cohort and 1896 patients in ARDS-net cohort demonstrated an increase in percent mortality for every 10% increase in Vd/Vt in a dose response fashion. After adjustment for non-pulmonary and pulmonary prognostic variables, both day 1 (adjusted odds ratio-OR = 1.07, 95%CI 1.03 to 1.13) and day 3 (OR = 1.12, 95% CI 1.06 to 1.18) estimated dead-space fraction predicted hospital mortality. ####CONCLUSIONS: Elevated estimated Vd/Vt predicts mortality in ALI patients in a dose response manner. A modified alveolar gas equation may be of clinical value for a rapid bedside estimation of Vd/Vt, utilizing routinely collected clinical data. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945122/ %0 Journal Article %A Stapleton, RD %A Dixon, AE %A Parsons, PE %A Ware, LB %A Suratt, BT %A NHLBI Acute Respiratory Distress Syndrome Network, the %D 2010 %T The Association Between BMI and Plasma Cytokine Levels in Patients with Acute Lung Injury %B Chest %V 138 %P 568-577 %! The Association Between BMI and Plasma Cytokine Levels in Patients with Acute Lung Injury %2 PMC2940070 %X ####BACKGROUND: Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI. ####METHODS: We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders. ####RESULTS: In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs. ####CONCLUSIONS: Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms. %U http://journal.publications.chestnet.org/article.aspx?articleid=1044973 %> http://www.ardsnet.org/system/files/568%20full.pdf %0 Journal Article %A Ware, LB %A Koyama, T %A Billheimer, DD %A Wu, W %A Bernard, GR %A Thompson, BT %A Brower, RG %A Standiford, TJ %A Martin, TR %A Matthay, MA %A NHLBI ARDS Clinical Trials Network, the %D 2010 %T Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury %B Chest %V 137 %N 2 %P 288-96 %8 02/2010 %! Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury %2 PMC2816641 %X ####BACKGROUND: No single clinical or biologic marker reliably predicts clinical outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of biologic and clinical markers would be superior to either biomarkers or clinical factors alone in predicting ALI/ARDS mortality and would provide insight into the pathogenesis of clinical ALI/ARDS. ####METHODS: Eight biologic markers that reflect endothelial and epithelial injury, inflammation, and coagulation (von Willebrand factor antigen, surfactant protein D [SP-D]), tumor necrosis factor receptor-1, interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C, plasminogen activator inhibitor-1) were measured in baseline plasma from 549 patients in the ARDSNet trial of low vs high positive end-expiratory pressure. Mortality was modeled with multivariable logistic regression. Predictors were selected using backward elimination. Comparisons between candidate models were based on the receiver operating characteristics (ROC) and tests of integrated discrimination improvement. ####RESULTS: Clinical predictors (Acute Physiology And Chronic Health Evaluation III [APACHE III], organ failures, age, underlying cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers and the clinical predictors had an AUC of 0.85. The best performing biomarkers were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar type 2 cells, supporting the concept that acute inflammation and alveolar epithelial injury are important pathogenetic pathways in human ALI/ARDS. ####CONCLUSIONS: A combination of biomarkers and clinical predictors is superior to clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and may be useful for stratifying patients in clinical trials. From a pathogenesis perspective, the degree of acute inflammation and alveolar epithelial injury are highly associated with the outcome of human ALI/ARDS. %U http://journal.publications.chestnet.org/article.aspx?articleid=1086283 %0 Journal Article %A Britos, MF %A Smoot, E %A Liu, KD %A Thompson, BT %A Checkley, W %A Brower, RG %D 2011 %T The value of positive end-expiratory pressure and FiO2 criteria in the definition of the acute respiratory distress syndrome %B Crit Care Med %V 39 %N 9 %P 2025-30 %8 09/2011 %! The value of positive end-expiratory pressure and FiO2 criteria in the definition of the acute respiratory distress syndrome %2 PMC3157575 %X ####OBJECTIVES: The criteria that define acute lung injury and the acute respiratory distress syndrome include PaO₂/Fio₂ but not positive end-expiratory pressure or Fio2. PaO2/Fio2 ratios of some patients increase substantially after mechanical ventilation with positive end-expiratory pressure of 5-10 cm H₂O, and the mortality of these patients may be lower than those whose PaO₂/Fio₂ratios remain <200. Also, PaO₂/Fio₂ may increase when Fio2 is raised from moderate to high levels, suggesting that patients with similar PaO₂/Fio₂ ratios but different Fio₂ levels have different risks of mortality. The primary purpose of this study was to assess the value of adding baseline positive end-expiratory pressure and Fio₂ to PaO₂/Fio₂ for predicting mortality of acute lung injury/acute respiratory distress syndrome patients enrolled in Acute Respiratory Distress Syndrome Network clinical trials. We also assessed effects of two study interventions on clinical outcomes in subsets of patients with mild and severe hypoxemia as defined by PaO₂/Fio₂. ####DESIGN: Analysis of baseline physiologic data and outcomes of patients previously enrolled in clinical trials conducted by the National Institutes of Health Acute Respiratory Distress Syndrome Network. ####SETTING: Intensive care units of 40 hospitals in North America. ####PATIENTS: Two thousand three hundred and twelve patients with acute lung injury/acute respiratory distress syndrome. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Only 1.3% of patients enrolled in Acute Respiratory Distress Syndrome Network trials had baseline positive end-expiratory pressure < 5 cm H₂O, and 50% had baseline positive end-expiratory pressure ≥10 cm H₂O. Baseline PaO₂/Fio₂ predicted mortality, but after controlling for PaO₂/Fio₂, baseline positive end-expiratory pressure did not predict mortality. In contrast, after controlling for baseline PaO₂/Fio₂, baseline Fio₂ did predict mortality. Effects of two study interventions (lower tidal volumes and fluid-conservative hemodynamic management) were similar in mild and severe hypoxemia subsets as defined by PaO₂/Fio₂ ratios. ####CONCLUSION: At Acute Respiratory Distress Syndrome Network hospitals, the addition of baseline positive end-expiratory pressure would not have increased the value of PaO₂/Fio₂ for predicting mortality of acute lung injury/acute respiratory distress syndrome patients. In contrast, the addition of baseline Fio2 to PaO₂/Fio₂ could be used to identify subsets of patients with low or high mortality. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157575/ %0 Journal Article %A Brown, LM %A Calfee, CS %A Matthay, MA %A Brower, RG %A Thompson, BT %A Checkley, W %D 2011 %T A simple classification model for hospital mortality in patients with acute lung injury managed with lung protective ventilation %B Critical Care Medicine %V 39 %N 12 %P 2645-2651 %8 12/2011 %! A simple classification model for hospital mortality in patients with acute lung injury managed with lung protective ventilation %2 PMC3227537 %X ####OBJECTIVE: Despite improvements in the care of critically ill patients, hospital mortality rate for acute lung injury remains high at approximately 40%. We developed a classification rule to stratify mechanically ventilated patients with acute lung injury according to hospital mortality and compared this rule with the Acute Physiology and Chronic Health Evaluation III prediction. ####PATIENTS: We used data of 2,022 participants in Acute Respiratory Distress Syndrome Network trials to build a classification rule based on 54 variables collected before randomization. ####DESIGN: We used a classification tree approach to stratify patients according to hospital mortality using a training subset of 1800 participants and estimated expected prediction errors using tenfold crossvalidation. We validated our classification tree using a subset of 222 participants not included in model building and calculated areas under the receiver operating characteristic curves. ####MEASUREMENTS AND MAIN RESULTS: We identified combinations of age (>63 yrs), blood urea nitrogen (>15 mg/dL), shock, respiratory rate (>21 breaths/min), and minute ventilation (>13.9 L/min) as important predictors of hospital mortality at 90 days. The classification tree had a similar expected prediction error in the training set (28% vs. 26%; p = .18) and areas under the receiver operating characteristic curve in the validation set (0.71 vs. 0.73; p = .71) as did a model based on Acute Physiology and Chronic Health Evaluation III. ####CONCLUSIONS: Our tree-based classification rule performed similarly to Acute Physiology and Chronic Health Evaluation III in stratifying patients according to hospital mortality, is simpler to use, contains risk factors that may be specific to acute lung injury, and identified minute ventilation as a potential novel predictor of death in patients with acute lung injury. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227537/ %0 Journal Article %A Burns, KE %A Adhikari, NK %A Slutsky, AS %A Guyatt, GH %A Villar, J %A Zhang, H %A Zhou, Q %A Cook, DJ %A Stewart, TE %A Meade, MO %D 2011 %T Pressure and volume limited ventilation for the ventilatory management of patients with acute lung injury: a systematic review and meta-analysis %B PLoS One %V 6 %N 1 %P e14623 %8 01/2011 %! Pressure and volume limited ventilation for the ventilatory management of patients with acute lung injury: a systematic review and meta-analysis %2 PMC3030554 %X ####BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS. ####METHODS AND FINDINGS: We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10-15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL [relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05]. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03). ####CONCLUSIONS: This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030554/ %0 Journal Article %A Calfee, CS %A Ware, LB %A Glidden, DV %A Eisner, MD %A Parsons, PE %A Thompson, BT %A Matthay, MA %A ARDS Network, NHLBI %D 2011 %T Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury %B Crit Care Med %V 39 %N 4 %P 711-17 %8 04/2011 %! Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury %2 PMC3260884 %X ####OBJECTIVE: Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury. ####DESIGN: Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury. ####SETTING: Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network. ####PATIENTS: Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort). ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts. ####CONCLUSIONS: When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260884/ %0 Journal Article %A Calfee, CS %A Ware, LB %A NIH/NHLBI/ARDSNetwork %D 2011 %T Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury %B Crit Care Med %V 39 %N 4 %P 711-7 %8 04/2011 %! Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury %2 PMC3260884 %X ####OBJECTIVE: Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury. ####DESIGN: Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury. ####SETTING: Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network. ####PATIENTS: Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort). ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts. ####CONCLUSIONS: When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260884/ %0 Journal Article %A Clermont, G %A Kong, L %A Weissfeld, LA %A Lave, JR %A Rubenfeld, GD %A Roberts, MS %A Connors Jr. , AF %A Bernard, GR %A Thompson, BT %A Wheeler, AP %A Angus, DC %A NHLBI ARDS Clinical Trials Network, the %D 2011 %T The Effect of Pulmonary Artery Catheter Use on Costs and Long-Term Outcomes of Acute Lung Injury %B PLoS ONE %V 6 %N 7 %P e22512 %8 07/2011 %! The Effect of Pulmonary Artery Catheter Use on Costs and Long-Term Outcomes of Acute Lung Injury %2 PMC3141060 %X ####BACKGROUND: The pulmonary artery catheter (PAC) remains widely used in acute lung injury (ALI) despite known complications and little evidence of improved short-term mortality. Concurrent with NHLBI ARDS Clinical Trials Network Fluid and Catheters Treatment Trial (FACTT), we conducted a prospectively-defined comparison of healthcare costs and long-term outcomes for care with a PAC vs. central venous catheter (CVC). We explored if use of the PAC in ALI is justified by a beneficial cost-effectiveness profile. ####METHODS: We obtained detailed bills for the initial hospitalization. We interviewed survivors using the Health Utilities Index Mark 2 questionnaire at 2, 6, 9 and 12 m to determine quality of life (QOL) and post-discharge resource use. Outcomes beyond 12 m were estimated from federal databases. Incremental costs and outcomes were generated using MonteCarlo simulation. ####RESULTS: Of 1001 subjects enrolled in FACTT, 774 (86%) were eligible for long-term follow-up and 655 (85%) consented. Hospital costs were similar for the PAC and CVC groups ($96.8k vs. $89.2k, p = 0.38). Post-discharge to 12 m costs were higher for PAC subjects ($61.1k vs. 45.4k, p = 0.03). One-year mortality and QOL among survivors were similar in PAC and CVC groups (mortality: 35.6% vs. 31.9%, p = 0.33; QOL [scale: 0-1]: 0.61 vs. 0.66, p = 0.49). MonteCarlo simulation showed PAC use had a 75.2% probability of being more expensive and less effective (mean cost increase of $14.4k and mean loss of 0.3 quality-adjusted life years (QALYs)) and a 94.2% probability of being higher than the $100k/QALY willingness-to-pay threshold. ####CONCLUSION: PAC use increased costs with no patient benefit and thus appears unjustified for routine use in ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141060/ %0 Journal Article %A Damluji, A %A Colantuoni, E %A Mendez-Tellez, PA %A Sevransky, JE %A Fan, E %A Shanholtz, C %A Wojnar, M %A Pronovost, PJ %A Needham, DM %D 2011 %T Short-term mortality prediction for acute lung injury patients: External validation of the ARDSNet prediction model %B Crit Care Med %V 39 %N 5 %P 1023-8 %8 05/2011 %! Short-term mortality prediction for acute lung injury patients: External validation of the ARDSNet prediction model %2 PMC3129473 %X ####OBJECTIVE: An independent cohort of patients with acute lung injury was used to evaluate the external validity of a simple prediction model for short-term mortality previously developed using data from Acute Respiratory Distress Syndrome Network (ARDSNet) trials. ####DESIGN: Data for external validation were obtained from a prospective cohort study of patients with acute lung injury. ####SETTING: Thirteen intensive care units at four teaching hospitals in Baltimore, MD. ####PATIENTS: Five hundred and eight nontrauma patients with acute lung injury. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Of the 508 patients eligible for this analysis, 234 (46%) died inhospital. Discrimination of the ARDSNet prediction model for inhospital mortality, evaluated by the area under the receiver operator characteristic curves, was 0.67 for our external validation data set vs. 0.70 and 0.68 using Acute Physiology and Chronic Health Evaluation II and the ARDSNet validation data set, respectively. In evaluating calibration of the model, predicted vs. observed inhospital mortality for the external validation data set was similar for both low-risk (ARDSNet model score = 0) and high-risk (score = 3 or 4+) patient strata. However, for intermediate-risk (score = 1 or 2) patients, observed inhospital mortality was substantially higher than predicted mortality (25.3% vs. 16.5% and 40.6% vs. 31.0% for score = 1 and 2, respectively). Sensitivity analyses limiting our external validation data set to only those patients meeting the ARDSNet trial eligibility criteria and to those who received mechanical ventilation in compliance with the ARDSNet ventilation protocol did not substantially change the model's discrimination or improve its calibration. ####CONCLUSIONS: Evaluation of the ARDSNet prediction model using an external acute lung injury cohort demonstrated similar discrimination of the model as was observed with the ARDSNet validation data set. However, there were substantial differences in observed vs. predicted mortality among intermediate-risk patients with acute lung injury. The ARDSNet model provided reasonable, but imprecise, estimates of predicted mortality when applied to our external validation cohort of patients with acute lung injury. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129473/ %0 Journal Article %A Glavan, BJ %A Holden, TD %A Goss, CH %A Black, RA %A Neff, MJ %A Nathens, AB %A Martin, TR %A Wurfel, MM %A ARDSnet Investigators %D 2011 %T Genetic Variation in the FAS Gene and Associations with Acute Lung Injury %B Am J Respir Crit Care Med %V 183 %N 3 %P 356-63 %! Genetic Variation in the FAS Gene and Associations with Acute Lung Injury %2 PMC3056231 %X ####RATIONALE: Fas (CD95) modulates apoptosis and inflammation and is believed to play an important role in lung injury. ####OBJECTIVES: To determine if common genetic variation in FAS is associated with acute lung injury (ALI) susceptibility, risk of death, and FAS gene expression. ####METHODS: We genotyped 14 single nucleotide polymorphisms (tagSNPS) in FAS in samples from healthy white volunteers (control subjects, n = 294) and patients with ALI (cases, n = 324) from the ARDSnet Fluid and Catheter Treatment Trial (FACTT). FAS genotypes associated with ALI in the discovery study were confirmed in a nested case-control validation study of critically ill patients at risk for ALI (n = 657). We also tested for associations between selected tagSNPS and FAS mRNA levels in whole blood from healthy control subjects exposed to media alone or LPS ex vivo. ####MEASUREMENTS AND MAIN RESULTS: We identified associations between four tagSNPs in FAS (FAS(-11341A>T) [rs17447140], FAS(9325G>A) [rs2147420], FAS(21541C>T) [rs2234978], and FAS(24484A>T) [rs1051070]) and ALI case status. Haplotype-based analyses suggested that three of the tagSNPs (FAS(9325G>A), FAS(21541C>T), and FAS(24484A>T)) function as a unit. The association with this haplotype and ALI was validated in a nested case-control study of at-risk subjects (P = 0.05). This haplotype was also associated with increased FAS mRNA levels in response to LPS stimulation. There was no association between FAS polymorphisms and risk of death among ALI cases. ####CONCLUSIONS: Common genetic variants in FAS are associated with ALI susceptibility. This is the first genetic evidence supporting a role for FAS in ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056231/ %0 Journal Article %A Grams, ME %A Estrella, MM %A Coresh, J %A Brower, RG %A Liu, KD %A NHLBI, the %D 2011 %T Fluid balance, diuretic use, and mortality in acute kidney injury %B Clin J Am Soc Nephrol %V 6 %N 5 %P 966-73 %8 05/2011 %! Fluid balance, diuretic use, and mortality in acute kidney injury %2 PMC3087792 %X ####BACKGROUND AND OBJECTIVES: Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients. ####DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria. ####RESULTS: 306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P=0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased. ####CONCLUSIONS: A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087792/ %0 Journal Article %A Liu, KD %A Thompson, BT %A Ancukiewicz, M %A Steingrub, JS %A Douglas, IS %A Matthay, MA %A Wright, P %A Peterson, MW %A Rock, P %A Hyzy, RC %A Anzueto, A %A Truwit, JD %A NHLBI Acute Respiratory Distress Syndrome Network, the %D 2011 %T Acute kidney injury in patients with acute lung injury: Impact of fluid accumulation on classification of acute kidney injury and associated outcomes %B Crit Care Med %V 39 %N 12 %P 2665-71 %8 12/2011 %! Acute kidney injury in patients with acute lung injury: Impact of fluid accumulation on classification of acute kidney injury and associated outcomes %2 PMC3220741 %X ####OBJECTIVE: It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality. ####DESIGN: Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter. ####SETTING: Acute Respiratory Distress Syndrome Network hospitals. ####PATIENTS: One thousand patients. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: The incidence of acute kidney injury, defined as an absolute rise in creatinine of ≥0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18). ####CONCLUSIONS: Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220741/ http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs046/ovft/live/gv025/00003246/00003246-201112000-00011.pdf %> internal-pdf://1213529710/Liu-2011-Acute kidney injury in patients with.pdf %0 Journal Article %A Matthay, MA %A Brower, RG %A Carson, S %A Douglas, IS %A Eisner, M %A Hite, D %A Holets, S %A Kallet, RH %A Liu, KD %A Macintyre, N %A Moss, M %A Schoenfeld, D %A Steingrub, J %A Thompson, BT %A NHLBI ARDS Network, the %D 2011 %T Randomized, Placebo-Controlled Clinical Trial of an Aerosolized Beta-2 Agonist for Treatment of Acute Lung Injury %B Am J Respir Crit Care Med %V 184 %N 5 %P 561-8. %8 09/2011 %! Randomized, Placebo-Controlled Clinical Trial of an Aerosolized Beta-2 Agonist for Treatment of Acute Lung Injury %2 PMC3175548 %X ####RATIONALE: β₂-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. ####OBJECTIVES: This clinical trial was designed to test the hypothesis that an aerosolized β₂-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). ####METHODS: We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. ####MEASUREMENTS AND MAIN RESULTS: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. ####CONCLUSIONS: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β₂-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993). %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175548/ %0 Journal Article %A Parsons, EC %A Hough, CL %A Seymour, CW %A Cooke, CR %A Rubenfeld, GD %A Watkins, TR %A NHLBI ARDS Network, the %D 2011 %T Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock %B Crit Care %V 15 %N 5 %P R221 %! Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock %2 PMC3334766 %X ####INTRODUCTION: In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock. ####METHODS: We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor use) within 24 hours of randomization. Using multivariable logistic regression, we examined the association between RBC transfusion and 28-day mortality after adjustment for age, sex, race, randomization arm and Acute Physiology and Chronic Health Evaluation III score. Secondary end points included 90-day mortality and ventilator-free days (VFDs). Finally, we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators: hemoglobin < 10.2 g/dL, central or mixed venous oxygen saturation < 70%, central venous pressure ≥ 8 mmHg, MAP ≥ 65 mmHg, and vasopressor use. ####RESULTS: We identified 285 subjects with ALI, sepsis, shock and transfusion data. Of these, 85 also met the above prespecified transfusion criteria. Fifty-three (19%) of the two hundred eighty-five subjects with shock and twenty (24%) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of randomization. We found no independent association between RBC transfusion and 28-day mortality (odds ratio = 1.49, 95% CI (95% confidence interval) = 0.77 to 2.90; P = 0.23) or VFDs (mean difference = -0.35, 95% CI = -4.03 to 3.32; P = 0.85). Likewise, 90-day mortality and VFDs did not differ by transfusion status. Among the subset of patients meeting the transfusion criteria, we found no independent association between transfusion and mortality or VFDs. ####CONCLUSIONS: In patients with new-onset ALI, sepsis and shock, we found no independent association between RBC transfusion and mortality or VFDs. The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334766/ %0 Journal Article %A Randolph, A %A Vaughn, F %A Sullivan, R %A Rubinson, L %A Thompson, BT %A Yoon, G %A Smoot, E %A Rice, T %A Loftis, L %A Helfaer, M %A Doctor, A %A Paden, M %A Flori, H %A Babbit, C %A Graciano, A %A Gedeit, R %A Sanders, R %A Giuliano, J %A Zimmerman, J %A Uyeki, T %A Injury, Pediatric Acute Lung %A Network, Sepsis Investigator's %A the NHLBI ARDS Clinical Trials Network, the %D 2011 %T Critically Ill Children During the 2009-2010 Influenza Pandemic in the United States %B Pediatrics %V 128 %N 6 %8 12/2011 %! Critically Ill Children During the 2009-2010 Influenza Pandemic in the United States %2 PMC3387899 %X ####BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. ####METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. ####RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1-20.6]; P < .0001) remained a mortality risk factor. ####CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387899/ %0 Journal Article %A Rice, TW %A Ware, LB %A Haponik, EF %A Chiles, C %A Wheeler, AP %A Bernard, GR %A Steingrub, JS %A Hite, RD %A Matthay, MA %A Wright, P %A Ely, EW %A NIH NHLBI ARDS Network %D 2011 %T Vascular pedicle width in acute lung injury: correlation with intravascular pressures and ability to discriminate fluid status %B Crit Care %V 15 %N 2 %P R86 %8 03/2011 %! Vascular pedicle width in acute lung injury: correlation with intravascular pressures and ability to discriminate fluid status %2 PMC3219344 %X ####INTRODUCTION: Conservative fluid management in patients with acute lung injury (ALI) increases time alive and free from mechanical ventilation. Vascular pedicle width (VPW) is a non-invasive measurement of intravascular volume status. The VPW was studied in ALI patients to determine the correlation between VPW and intravascular pressure measurements and whether VPW could predict fluid status. ####METHODS: This retrospective cohort study involved 152 patients with ALI enrolled in the Fluid and Catheter Treatment Trial (FACTT) from five NHLBI ARDS (Acute Respiratory Distress Syndrome) Network sites. VPW and central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) from the first four study days were correlated. The relationships between VPW, positive end-expiratory pressure (PEEP), cumulative fluid balance, and PAOP were also evaluated. Receiver operator characteristic (ROC) curves were used to determine the ability of VPW to detect PAOP < 8 mmHg and PAOP ≥ 18 mm Hg. ####RESULTS: A total of 71 and 152 patients provided 118 and 276 paired VPW/PAOP and VPW/CVP measurements, respectively. VPW correlated with PAOP (r = 0.41; P < 0.001) and less well with CVP (r = 0.21; P = 0.001). In linear regression, VPW correlated with PAOP 1.5-fold better than cumulative fluid balance and 2.5-fold better than PEEP. VPW discriminated achievement of PAOP < 8 mm Hg (AUC = 0.73; P = 0.04) with VPW ≤67 mm demonstrating 71% sensitivity (95% CI 30 to 95%) and 68% specificity (95% CI 59 to 75%). For discriminating a hydrostatic component of the edema (that is, PAOP ≥ 18 mm Hg), VPW ≥ 72 mm demonstrated 61.4% sensitivity (95% CI 47 to 74%) and 61% specificity (49 to 71%) (area under the curve (AUC) 0.69; P = 0.001). ####CONCLUSIONS: VPW correlates with PAOP better than CVP in patients with ALI. Due to its only moderate sensitivity and specificity, the ability of VPW to discriminate fluid status in patients with acute lung injury is limited and should only be considered when intravascular pressures are unavailable. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219344/ %0 Journal Article %A Rice, TW %A Wheeler, AP %A Thompson, BT %A deBoisblanc, BP %A Steingrub, J %A Rock, P %A NIH NHLBI ARDS Network of Investigators, the %D 2011 %T Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury %B JAMA %V 306 %N 14 %P 1574-81 %8 10/2011 %! Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury %2 PMC3770348 %X ####CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. ####OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. ####DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. ####INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. ####MAIN OUTCOME MEASURE: Ventilator-free days to study day 28. ####RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). ####CONCLUSIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770348/ %0 Journal Article %A Thompson, BT %A Bernard, GR %D 2011 %T ARDS Network (NHLBI) Studies: Successes and Challenges in ARDS Clinical Research %B Crit Care Clin %V 27 %N 3 %P 459-468 %8 07/2011 %! ARDS Network (NHLBI) Studies: Successes and Challenges in ARDS Clinical Research %2 PMC3143063 %X To hasten the development of effective therapy for acute respiratory distress syndrome (ARDS), in 1994, the National Heart, Lung, and Blood Institute initiated a clinical network to carry out multicenter clinical trials of ARDS treatments. The ARDS Network is a clinical research network of approximately 42 hospitals, organized into 12 clinical sites. The goal of the Network is to efficiently test promising agents, devices, or management strategies to improve the care of patients with ARDS. Comprehensive information regarding all completed and ongoing ARDSNet clinical trials is available at www.ardsnet.org, but a brief summary is provided in this article. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143063/ %0 Journal Article %A Walkey, A %A Weiner, R %D 2011 %T Utilization patterns and patient outcomes associated with use of rescue therapies in acute lung injury %B Crit Care Med %V 39 %N 6 %P 1322-8 %8 06/2011 %! Utilization patterns and patient outcomes associated with use of rescue therapies in acute lung injury %2 PMC3148145 %X ####OBJECTIVES: To investigate the practice patterns and clinical outcomes associated with use of rescue therapies in patients with acute lung injury. ####DESIGN: Secondary analysis of multicentered, randomized, controlled trial data from the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. ####SETTING: Intensive care units of Acute Respiratory Distress Syndrome Clinical Trials Network centers across the United States. ####PATIENTS: Subjects enrolled in six Acute Respiratory Distress Syndrome Clinical Trials Network trials occurring between 1996 and 2005. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: One hundred sixty-six of 2632 (6.3%) subjects received rescue therapy, defined as prone positioning (97 of 166 [58%]), inhaled vasodilators (47 of 166 [28%]), high-frequency ventilation (12 of 166 [7%]), or extracorporeal membrane oxygenation (10 of 166 [6%]). Use of inhaled vasodilators increased whereas use of prone position decreased over time (p for trend = 0.04 and 0.0013, respectively). Multivariate predictors for use of rescue therapy included age (odds ratio per 10 yrs and 95% confidence interval: 0.88; 0.78-0.99; p = .049), positive end-expiratory pressure (odds ratio per 5-cm H2O increase: 1.33; 95% confidence interval, 1.05-1.69; p = .019), Pao2/Fio2; odds ratio per 5-cm H2O increase: 0.98; 95% confidence interval, 0.96-0.99; p = .017), peak airway pressure (odds ratio per 5-cm H2O increase: 1.11; 95% confidence interval, 1.001-1.237; p = .047), and study order (odds ratio per subsequent Acute Respiratory Distress Syndrome Clinical Trials Network study: 1.21; 95% confidence interval, 1.03-1.41; p = .02). Cox proportional hazards analysis of propensity score-matched subjects showed no difference in survival for those who received rescue therapy vs. those who did not (hazard ratio for death after rescue therapy or index date, 1.10; 95% confidence interval, 0.67-1.78; p = .72). No differences in survival were found between those who received prone positioning vs. inhaled vasodilators (propensity score-adjusted hazard ratio for prone 0.87; 95% confidence interval, 0.86-2.10; p = .76). ####CONCLUSIONS: Rescue therapies are utilized in younger patients with more severe oxygenation deficits. Patterns of rescue therapy utilization appear to be changing over time. Within the limits of an observational study design, we did not find evidence of a survival benefit with use of rescue therapies in acute lung injury. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148145/ %0 Journal Article %A Wang, W %A Scharfstein, D %A Wang, C %A Daniels, C %A Needham, D %A Brower, R %A NHLBI ARDS Clinical Network, the %D 2011 %T Estimating the Causal Effect of Low Tidal Volume Ventilation on Survival in Patients with Acute Lung Injury %B J R Stat Soc Ser C Appl Stat %V 1 %N 60 %P 475-496 %8 08/2011 %! Estimating the Causal Effect of Low Tidal Volume Ventilation on Survival in Patients with Acute Lung Injury %2 PMC3197806 %X Acute lung injury (ALI) is a condition characterized by acute onset of severe hypoxemia and bilateral pulmonary infiltrates. ALI patients typically require mechanical ventilation in an intensive care unit. Low tidal volume ventilation (LTVV), a time-varying dynamic treatment regime, has been recommended as an effective ventilation strategy. This recommendation was based on the results of the ARMA study, a randomized clinical trial designed to compare low vs. high tidal volume strategies (The Acute Respiratory Distress Syndrome Network, 2000) . After publication of the trial, some critics focused on the high non-adherence rates in the LTVV arm suggesting that non-adherence occurred because treating physicians felt that deviating from the prescribed regime would improve patient outcomes. In this paper, we seek to address this controversy by estimating the survival distribution in the counterfactual setting where all patients assigned to LTVV followed the regime. Inference is based on a fully Bayesian implementation of Robins' (1986) G-computation formula. In addition to re-analyzing data from the ARMA trial, we also apply our methodology to data from a subsequent trial (ALVEOLI), which implemented the LTVV regime in both of its study arms and also suffered from non-adherence. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197806/ %0 Journal Article %A Agrawal, A %A Zhuo, H %A Brady, S %A Levitt, J %A Steingrub, J %A Siegel, MD %A Soto, G %A Peterson, MW %A Chesnutt, MS %A Matthay, MA %A Liu, KD %D 2012 %T Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials %B Am J Physiol Lung Cell Mol Physiol %V 303 %N 8 %P 634-9 %! Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials %2 PMC3469636 %X Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469636/ %0 Journal Article %A Calfee, CS %A Gallagher, D %A Abbott, J %A Thompson, BT %A Matthay, MA %A NHLBI ARDS Network, the %D 2012 %T Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance %B Crit Care Med %V 40 %N 6 %P 1731-7 %8 06/2012 %! Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance %2 PMC3601049 %X ####BACKGROUND: Angiopoietin-2 is a proinflammatory mediator of endothelial injury in animal models, and increased plasma angiopoietin-2 levels are associated with poor outcomes in patients with sepsis-associated acute lung injury. Whether angiopoietin-2 levels are modified by treatment strategies in patients with acute lung injury is unknown. ####OBJECTIVES: To determine whether plasma angiopoietin-2 levels are associated with clinical outcomes and affected by fluid management strategy in a broad cohort of patients with acute lung injury. ####DESIGN, SETTING, AND PARTICIPANTS: Plasma levels of angiopoietin-2 and von Willebrand factor (a traditional marker of endothelial injury) were measured in 931 subjects with acute lung injury enrolled in a randomized trial of fluid liberal vs. fluid conservative management. ####MEASUREMENTS AND MAIN RESULTS: The presence of infection (sepsis or pneumonia) as the primary acute lung injury risk factor significantly modified the relationship between baseline angiopoietin-2 levels and mortality (p = .01 for interaction). In noninfection-related acute lung injury, higher baseline angiopoietin-2 levels were strongly associated with increased mortality (odds ratio, 2.43 per 1-log increase in angiopoietin-2; 95% confidence interval, 1.57-3.75; p < .001). In infection-related acute lung injury, baseline angiopoietin-2 levels were similarly elevated in survivors and nonsurvivors; however, patients whose plasma angiopoietin-2 levels increased from day 0 to day 3 had more than double the odds of death compared with patients whose angiopoietin-2 levels declined over the same period of time (odds ratio, 2.29; 95% confidence interval, 1.54-3.43; p < .001). Fluid-conservative therapy led to a 15% greater decline in angiopoietin-2 levels from day 0 to day 3 (95% confidence interval, 4.6-24.8%; p = .006) compared with fluid-liberal therapy in patients with infection-related acute lung injury. In contrast, plasma levels of von Willebrand factor were significantly associated with mortality in both infection-related and noninfection-related acute lung injury and were not affected by fluid therapy. ####CONCLUSIONS: Unlike von Willebrand factor, plasma angiopoietin-2 has differential prognostic value for mortality depending on the presence or absence of infection as an acute lung injury risk factor. Fluid conservative therapy preferentially lowers plasma angiopoietin-2 levels over time and thus may be beneficial in part by decreasing endothelial inflammation. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601049/ http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv024/00003246/00003246-201206000-00006.pdf %> internal-pdf://2886162590/Calfee-2012-Plasma angiopoietin-2 in clinical.pdf %0 Journal Article %A Engoren, M %D 2012 %T The Effect of Red Blood Cell Transfusion on 90-day Mortality in Patients With Acute Lung Injury %B J Intensive Care Med %V 27 %N 2 %P 112-8 %! The Effect of Red Blood Cell Transfusion on 90-day Mortality in Patients With Acute Lung Injury %X ####BACKGROUND: Erythrocyte blood transfusions are commonly given to intensive care unit (ICU) patients. Recent studies have suggested that transfusions may increase, have no effect on, or decrease short-term mortality. These disparate results may reflect different patient populations, diseases, and characteristics; different transfusion triggers and thresholds; or differences in controlling for confounding variables. The aim of this study was to determine the association of transfusion and 90-day mortality in patients with acute lung injury. ####METHODS: Retrospective analysis using binary logistic regression and then propensity analysis to control for variables on the day of the transfusion decision. One thousand patients initially enrolled in ARDSNET 05 Fluid and Catheter Treatment Trial. ####RESULTS: A total of 361 patients (36%) received transfusions during the 8-day course of the study and by univariable analysis were more likely to be dead by 90 days (131 of 361, 36%, vs. 153 of 639, 24%, P < .001). After multivariable correction using propensity analysis to control for factors present on the day the transfusion was given, transfusion was not associated with mortality. Instead, factors such as hypotension and laboratory values as measured by propensity scores that predicted transfusion on days 1, 2, and 5 were associated with increased mortality, and not transfusion itself. ####CONCLUSION: In patients suffering with acute lung injury, transfusion of erythrocytes in the ICU was not associated with 90-day mortality. %U http://jic.sagepub.com/content/27/2/112.long %0 Journal Article %A Kangelaris, KN %A Sapru, A %A Calfee, CS %A Liu, KD %A Pawlikowska, L %A Witte, JS %A Vittinghoff, E %A Zhou, H %A Auerbach, AD %A Ziv, E %A Matthay, MA %A NHLBI ARDS Network, the %D 2012 %T The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury %B Chest %V 141 %N 5 %P 1160-9 %8 05/2012 %! The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury %2 PMC3342784 %X ####BACKGROUND: Acute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an increase in circulating Duffy-binding, proinflammatory chemokines like IL-8. We sought to determine the effect of the functional rs2814778 polymorphism, C/C genotype (Duffy null state), on clinical outcomes in African Americans with acute lung injury. ####METHODS: Clinical data and biologic specimens from African American patients with ALI who enrolled in three randomized controlled trials were analyzed. Multivariate analysis accounted for proportion of African ancestry, sex, cirrhosis, and severity of illness on presentation. ####RESULTS: Among 132 subjects, 88 (67%) were Duffy null (C/C genotype). The Duffy null state was associated with a 17% absolute risk increase (95% CI, 1.4%-33%) in mortality at 60 days, a median of 8 fewer ventilator-free days (95% CI, 1-18.5), and 4.5 fewer organ failure-free days (95% CI, 0-18) compared with individuals with the C/T or T/T genotypes (all P values < .05). Estimates were similar on multivariate analysis. In African Americans without the null variant, clinical outcomes were similar to those in patients of European descent. A subgroup analysis suggested that plasma IL-8 levels are increased in Duffy null individuals. ####CONCLUSIONS: Our results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342784/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342784/pdf/111766.pdf %> internal-pdf://4060702526/Kangelaris-2012-The association between a Darc.pdf %0 Journal Article %A NHLBI ARDS Clinical Trials Network, the %A Rice, TW %A Wheeler, AP %A Thompson, BT %A Steingrub, J %A Hite, RD %A Moss, M %A Morris, A %A Dong, N %A Rock, P %D 2012 %T Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial %B JAMA %V 307 %N 8 %P 795-803 %8 02/2012 %! Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial %2 PMC3743415 %X ####CONTEXT: The amount of enteral nutrition patients with acute lung injury need is unknown. ####OBJECTIVE: To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding. ####DESIGN, SETTING, AND PARTICIPANTS: The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. ####INTERVENTIONS: Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol. ####MAIN OUTCOME MEASURES: Ventilator-free days to study day 28. ####RESULTS: Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days. ####CONCLUSION: In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743415/ %0 Journal Article %A Noto, MJ %A Wheeler, AP %D 2012 %T Macrolides for acute lung injury %B Chest %V 141 %N 5 %P 1131-2 %8 05/2012 %9 Comment on Macrolide antibiotics and survival in patients with acute lung injury %! Macrolides for acute lung injury %2 PMC3342786 %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342786/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342786/pdf/113245.pdf %> internal-pdf://1511877443/Noto-2012-Macrolides for acute lung injury.pdf %0 Journal Article %A Rice, TW %A Rubinson, L %A Uyeki, TM %A Vaughn, FL %A John, BB %A Miller 3rd, RR %A Higgs, E %A Randolph, AG %A Smoot, BE %A Thompson, BT %A NHLBI ARDS Network, the %D 2012 %T Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States %B Crit Care Med %V 40 %N 5 %P 1487-98 %8 05/2012 %! Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States %2 PMC3653183 %X ####OBJECTIVES: The contribution of bacterial coinfection to critical illness associated with 2009 influenza A virus infection remains uncertain. The objective of this study was to determine whether bacterial coinfection increased the morbidity and mortality of 2009 influenza A. ####DESIGN: Retrospective and prospective cohort study. ####SETTING: Thirty-five adult U.S. intensive care units over the course of 1 yr. ####PATIENTS: Six hundred eighty-three critically ill adults with confirmed or probable 2009 influenza A. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: A confirmed or probable case was defined as a positive 2009 influenza A test result or positive test for influenza A that was otherwise not subtyped. Bacterial coinfection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hrs of intensive care unit admission. The mean age was 45±16 yrs, mean body mass index was 32.5±11.1 kg/m, and mean Acute Physiology and Chronic Health Examination II score was 21±9, with 76% having at least one comorbidity. Of 207 (30.3%) patients with bacterial coinfection on intensive care unit admission, 154 had positive cultures with Staphylococcus aureus (n=57) and Streptococcus pneumoniae (n=19), the most commonly identified pathogens. Bacterial coinfected patients were more likely to present with shock (21% vs. 10%; p=.0001), require mechanical ventilation at the time of intensive care unit admission (63% vs. 52%; p=.005), and have longer duration of intensive care unit care (median, 7 vs. 6 days; p=.05). Hospital mortality was 23%; 31% in bacterial coinfected patients and 21% in patients without coinfection (p=.002). Immunosuppression (relative risk 1.57; 95% confidence interval 1.20 -2.06; p=.0009) and Staphylococcus aureus at admission (relative risk 2.82; 95% confidence interval 1.76-4.51; p<.0001) were independently associated with increased mortality. ####CONCLUSIONS: Among intensive care unit patients with 2009 influenza A, bacterial coinfection diagnosed within 72 hrs of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653183/ http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv024/00003246/00003246-201205000-00013.pdf %> internal-pdf://3237772262/Rice-2012-Critical illness from 2009 pandemic.pdf %0 Journal Article %A Schoenfeld, DA %A Hayden, D %A Oldmixon, C %A Ringwood, N %A Thompson, BT %D 2012 %T Statistical design and analysis issues for the ARDS Clinical Trials Network: the Coordinating Center perspective %B Clin Invest %V 2 %N 3 %P 275-289 %8 03/2012 %! Statistical design and analysis issues for the ARDS Clinical Trials Network: the Coordinating Center perspective %X We describe the statistical design principals for clinical trials conducted by the Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network that is funded by the National Heart Lung and Blood Institute. These include the definition of ARDS used by the network, the choice of measures of treatment efficacy, the choice of sample size, eligibility criteria, the choice of data to collect, stratification and randomization, the use of factorial trials and coenrollment of patients on more than one trial, early stopping for futility and efficacy, the choice of control group, the control of cointerventions, treatment administration and covariate adjustment. %U http://www.future-science.com/doi/abs/10.4155/cli.12.14 %0 Journal Article %A Valentine, SL %A Sapru, A %A Higgerson, RA %A Spinella, PC %A Flori, HR %A Graham, DA %A Brett, M %A Convery, M %A Christie, LM %A Karamessinis, L %A Randolph, AG %D 2012 %T Fluid balance in critically ill children with acute lung injury %B Critical Care Medicine %V 40 %N 10 %P 2883-9 %8 10/2012 %! Fluid balance in critically ill children with acute lung injury %2 PMC3455114 %X ####OBJECTIVES: In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms. ####DESIGN: Multicentered retrospective cohort study. ####SETTING: Five pediatric intensive care units. ####PATIENTS: Mechanically ventilated children (age≥1 month to <18 yrs) with acute lung injury admitted in 2007-2010. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p<.001, each day) and was similar to adults in the liberal arm. ####CONCLUSIONS: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455114/ http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv031/00003246/00003246-201210000-00019.pdf %> internal-pdf://1756206556/Valentine-2012-Fluid balance in critically ill.pdf %0 Journal Article %A Walkey, AJ %A Weiner, RS %D 2012 %T Macrolide antibiotics and survival in patients with acute lung injury %B Chest %V 141 %N 5 %P 1153-9 %8 05/2012 %! Macrolide antibiotics and survival in patients with acute lung injury %2 PMC3342785 %X ####BACKGROUND: Animal models suggest that immunomodulatory properties of macrolide antibiotics have therapeutic value for patients with acute lung injury (ALI). We investigated the association between receipt of macrolide antibiotics and clinical outcomes in patients with ALI. ####METHODS: Secondary analysis of multicenter, randomized controlled trial data from the Acute Respiratory Distress Syndrome Network Lisofylline and Respiratory Management of Acute Lung Injury Trial, which collected detailed data regarding antibiotic use among participants with ALI. ####RESULTS: Forty-seven of 235 participants (20%) received a macrolide antibiotic within 24 h of trial enrollment. Among patients who received a macrolide, erythromycin was the most common (57%), followed by azithromycin (40%). The median duration of macrolide use after study enrollment was 4 days (interquartile range, 2-8 days). Eleven of the 47 (23%) patients who received macrolides died, compared with 67 of the 188 (36%) who did not receive a macrolide (P = .11). Participants administered macrolides were more likely to have pneumonia as an ALI risk factor, were less likely to have nonpulmonary sepsis or to be randomized to low tidal volume ventilation, and had a shorter length of stay prior to trial enrollment. After adjusting for potentially confounding covariates, use of macrolide was associated with lower 180-day mortality (hazard ratio [HR], 0.46; 95% CI, 0.23-0.92; P = .028) and shorter time to successful discontinuation of mechanical ventilation (HR, 1.93; 95% CI, 1.18-3.17; P = .009). In contrast, fluoroquinolone (n = 90) and cephalosporin antibiotics (n = 93) were not associated with improved outcomes. ####CONCLUSIONS: Receipt of macrolide antibiotics was associated with improved outcomes in patients with ALI. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342785/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342785/pdf/111908.pdf %> internal-pdf://0315402369/Walkey-2012-Macrolide antibiotics and survival.pdf %0 Journal Article %A Bajwa, EK %A Volk, JA %A Christiani, DC %A Harris, RS %A Matthay, MA %A Thompson, BT %A Januzzi, JL %A ARDS Network, NHLBI %D 2013 %T Prognostic and Diagnostic Value of Plasma Soluble Suppression of Tumorigenicity-2 Concentrations in Acute Respiratory distress Syndrome %B Crit Care Med %V 41 %N 11 %P 2521-2531 %8 11/2013 %! Prognostic and Diagnostic Value of Plasma Soluble Suppression of Tumorigenicity-2 Concentrations in Acute Respiratory distress Syndrome %2 PMC3812317 %X ####OBJECTIVES: Soluble suppression of tumorigenicity-2 is a biomarker of myocardial strain and inflammation. The characteristics of acute respiratory distress syndrome include inflammation and cardiovascular dysfunction. We sought to determine whether plasma soluble suppression of tumorigenicity-2 concentration is associated with outcome and response to conservative fluid management and whether soluble suppression of tumorigenicity-2 concentration discriminates acute respiratory distress syndrome from decompensated heart failure. ####DESIGN: A retrospective analysis of the Fluid and Catheter Treatment Trial, a multi-center randomized controlled trial of conservative fluid management in the acute respiratory distress syndrome, as well as of a cohort of patients with decompensated heart failure. ####SETTING: Twenty acute care hospitals. ####PATIENTS: Eight hundred twenty-six patients with acute respiratory distress syndrome and 209 patients with acutely decompensated heart failure. ####MEASUREMENTS AND MAIN RESULTS: Nonsurvivors had higher day 0 (p < 0.0001) and day 3 (p < 0.0001) soluble suppression of tumorigenicity-2 concentrations. After adjustment for severity of illness, higher soluble suppression of tumorigenicity-2 concentration was associated with mortality, with odds ratioadj 1.47 (95% CI, 0.99-2.20; p = 0.06) at day 0, 2.94 (95% CI, 2.00-4.33; p < 0.0001) at day 3, and 3.63 (95% CI, 2.38-5.53; p < 0.0001) if soluble suppression of tumorigenicity-2 increased between days. Cumulative fluid balance was more positive among patients with higher day 0 (median, 5,212 mL [interquartile range, 200-12,284 mL] vs median, 2,020 mL [interquartile range, -2,034 to 7,091 mL]; p < 0.0001) and day 3 soluble suppression of tumorigenicity-2 (median, 7,678 mL [interquartile range, 2,217-14,278 mL] vs median, 1,492 mL [interquartile range, -2,384 to 6,239 mL]; p < 0.0001). Soluble suppression of tumorigenicity-2 showed excellent discriminative ability between the Fluid and Catheter Treatment Trial and heart failure populations (area under receiver-operating characteristic curve = 0.98; p < 0.0001). ####CONCLUSIONS: Higher soluble suppression of tumorigenicity-2 concentrations are associated with worse outcome in acute respiratory distress syndrome and may have value for discriminating acute respiratory distress syndrome from heart failure. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=TynQYbHJLLtjGhhyCGd2fnThRzSGy3QwwZm3jbs9w94jvQr5Lgxh!-423127214!181195628!8091!-1?issn=0090-3493&volume=41&issue=11&spage=2521 http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv031/00003246/00003246-201311000-00007.pdf %> internal-pdf://2049579996/Bajwa-2013-Prognostic and Diagnostic Value of.pdf %0 Journal Article %A Bauer, SR %A Lam, S %A Reddy, AJ %A NIH/NHLBI/ARDSNetwork %D 2013 %T Continuation or discontinuation of statin therapy did not influence patient outcomes after the development of acute lung injury and acute respiratory distress syndrome %B ISRN Critical Care %V 2013 %P 1-8 %! Continuation or discontinuation of statin therapy did not influence patient outcomes after the development of acute lung injury and acute respiratory distress syndrome %X ####Background The anti-inflammatory effects of statin therapy may be beneficial in the treatment and prevention of acute respiratory distress syndrome (ARDS). ####Objectives Determine if continuation or discontinuation of prior statin therapy is associated with ventilator-free days (VFDs) at day 28 in patients with ARDS. ####Methods Patients with ARDS admitted to the intensive care units of a tertiary care medical center were evaluated in this retrospective cohort study. Included patients were allocated to three groups: patients in whom statin therapy was given before and continued after ARDS diagnosis (Group 1), patients with statin therapy only before ARDS diagnosis (Group 2), and patients never exposed to statins (Group 3). ####Results Of 244 patients evaluated, 187 were included; 17 (9.1%) patients in Group 1, 20 (10.7%) in Group 2, and 150 in Group 3. There were no differences among groups in APACHE II or SOFA scores. VFDs were not significantly different among groups (median 0 versus 4.5 versus 13.5 days, ). After adjustment for baseline characteristics, including propensity for statin administration, statin therapy was not associated with increased VFDs on linear regression. ####Conclusions Exposure to statins before or after ARDS diagnosis was not associated with improved VFDs in this cohort of patients with ARDS. %U http://www.hindawi.com/journals/isrn/2013/382015/ %0 Journal Article %A Brown, LM %A Calfee, CS %A Howard, JP %A Craig, TR %A Matthay, MA %A McAuley, DF %D 2013 %T Comparison of thermodilution measured extravascular lung water with chest radiographic assessment of pulmonary oedema in patients with acute lung injury %B Ann Intensive Care %V 3 %N 1 %8 08/2013 %! Comparison of thermodilution measured extravascular lung water with chest radiographic assessment of pulmonary oedema in patients with acute lung injury %2 PMC3846630 %X ####BACKGROUND: Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are characterized by pulmonary oedema, measured as extravascular lung water (EVLW). The chest radiograph (CXR) can potentially estimate the quantity of lung oedema while the transpulmonary thermodilution method measures the amount of EVLW. This study was designed to determine whether EVLW as estimated by a CXR score predicts EVLW measured by the thermodilution method and whether changes in EVLW by either approach predict mortality in ALI/ARDS. ####METHODS: Clinical data were collected within 48 hours of ALI/ARDS diagnosis and daily up to 14 days on 59 patients with ALI/ARDS. Two clinicians scored each CXR for the degree of pulmonary oedema, using a validated method. EVLW indexed to body weight was measured using the single indicator transpulmonary thermodilution technique. ####RESULTS: The CXR score had a modest, positive correlation with the EVLWI measurements (r = 0.35, p < 0.001). There was a 1.6 ml/kg increase in EVLWI per 10-point increase in the CXR score (p < 0.001, 95% confidence interval 0.92-2.35). The sensitivity of a high CXR score for predicting a high EVLWI was 93%; similarly the negative predictive value was high at 94%; the specificity (51%) and positive predictive value (50%) were lower. The CXR scores did not predict mortality but the EVLW thermodilution did predict mortality. ####CONCLUSION: EVLW measured by CXR was modestly correlated with thermodilution measured EVLW. Unlike CXR findings, transpulmonary thermodilution EVLWI measurements over time predicted mortality in patients with ALI/ARDS. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846630/ %0 Journal Article %A Clark, B %A Bull, TM %A Benson, AB %A Stream, AR %A Macht, M %A Gaydos, J %A Meadows, C %A Burnham, EL %A Moss, M %A Investigators, Acute Respiratory Distress Syndrome Network %D 2013 %T Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study %B Crit Care %V 17 %N 3 %8 05/2013 %! Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study %2 PMC3706804 %X ####INTRODUCTION: We sought to determine whether higher levels of the novel biomarker growth differentiation factor-15 (GDF-15) are associated with poor outcomes and the presence of pulmonary vascular dysfunction (PVD) in patients with acute respiratory distress syndrome (ARDS). ####METHODS: We conducted a retrospective cohort study in patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment (FACT) Trial. Patients enrolled in the FACT Trial who received a pulmonary artery catheter (PAC), had plasma available from the same study day and sufficient hemodynamic data to determine the presence of PVD were included. Logistic regression was used to determine the association between GDF-15 level and 60-day mortality. ####RESULTS: Of the 513 patients enrolled in the FACT Trial assigned to receive a PAC, 400 were included in this analysis. Mortality at 60 days was significantly higher in patients whose GDF-15 levels were in the third (28%) or fourth (49%) quartile when compared to patients with GDF-15 levels in the first quartile (12%) (P <0.001). Adjusting for severity of illness measured by APACHE III score, the odds of death for patients with GDF-15 levels in the fourth quartile when compared to the first quartile was 4.26 (95% CI 2.18, 10.92, P <0.001). When added to APACHE III alone for prediction of 60-day mortality, GDF-15 levels increased the area under the receiver operating characteristic curve from 0.72 to 0.77. At an optimal cutoff of 8,103 pg/mL, the sensitivity and specificity of GDF-15 for predicting 60-day mortality were 62% (95% CI 53%, 71%) and 76% (95% CI 71%, 81%), respectively. Levels of GDF-15 were not useful in identifying the presence of PVD, as defined by hemodynamic measurements obtained by a PAC. ####CONCLUSIONS: In patients with ARDS, higher levels of GDF-15 are significantly associated with poor outcome but not PVD. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706804/ %0 Journal Article %A Clark BJ %A Williams A %A LM, Feemster %A KA, Bradley %A M, Macht %A Moss M %A EL, Burnham %A ARDS Network, the NHLBI %D 2013 %T Alcohol screening scores and 90-day outcomes in patients with acute lung injury %B Critical Care Medicine %V 41 %N 6 %P 1518-25 %8 06/2013 %! Alcohol screening scores and 90-day outcomes in patients with acute lung injury %X ####OBJECTIVES: The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test that correspond to past-year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with acute lung injury. ####DESIGN: Secondary analysis. ####SETTING: The Acute Respiratory Distress Syndrome Network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in patients with acute lung injury. ####SUBJECTS: Patients meeting consensus criteria for acute lung injury enrolled in one of three recent Acute Respiratory Distress Syndrome Network clinical trials. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Of 1,133 patients enrolled in one of three Acute Respiratory Distress Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders Identification Test score available for analysis. Alcohol misuse was common with 70 (7%) of patients having Alcohol Use Disorders Identification Test scores in zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between validated Alcohol Use Disorders Identification Test zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients having Alcohol Use Disorders Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio 1.70; 95% confidence interval 1.00, 2.87; p = 0.048). ####CONCLUSIONS: Severe but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in acute lung injury patients. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=Tv2MbfY1ryQ7vd9PzJyKjr6QnLCfLsLRlWKTQ2W4zWGftk8cM4q0!-813027467!181195628!8091!-1?issn=0090-3493&volume=41&issue=6&spage=1518 %0 Journal Article %A Fares, WH %A Carson, S %A NIH NHLBI ARDS Network, the %D 2013 %T The Relationship Between Positive End-Expiratory Pressure and Cardiac Index in Patient with Acute Respiratory Distress Syndrome %B J Crit Care %V 28 %N 6 %P 992-7 %8 12/2013 %! The Relationship Between Positive End-Expiratory Pressure and Cardiac Index in Patient with Acute Respiratory Distress Syndrome %2 PMC3830652 %X ####PURPOSE: The purpose of the study is to evaluate the association between positive end-expiratory pressure (PEEP) and cardiac index in patients with acute respiratory distress syndrome (ARDS). ####METHODS: This is a secondary cross-sectional analysis of the multicenter randomized controlled Fluid and Catheter Treatment Trial enrolling adult patients within 48 hours of ARDS onset. Patients randomized to the pulmonary artery catheter arm, who had PEEP and cardiac index measurements performed within a short period of each other during the first 3 days of the FACTT study enrollment, were included in this study. Because FACTT had a 2 × 2 factorial design, half of the patients were in a "liberal fluids" study arm, and the other half were in a "conservative fluids" study arm. ####RESULTS: The final study population (833 measurements or observations, in 367 patients) was comparable with the original overall FACTT study population. The mean PEEP level used was 8.2 ± 3.4 cm H2O, and the mean cardiac index was 4.2 ± 1.2 L/min per square meter. There was no association between PEEP and cardiac index in patients with ARDS, even when adjusted for Acute Physiology and Chronic Health Evaluation score, age, fluid study arm in FACTT, and sepsis. ####CONCLUSION: In patients with ARDS who are managed with liberal or conservative fluid management protocols, PEEP is not associated with lower cardiac index. %U http://www.mdconsult.com/das/article/body/445799692-2/jorg=journal&source=&sp=27188006&sid=0/N/1194123/1.html?issn=08839441&_returnURL=http%3A//linkinghub.elsevier.com/retrieve/pii/S0883944113001962%3Fshowall%3Dtrue http://www.mdconsult.com/das/article/body/476410716-2/jorg=journal%26source=%26sp=27188006%26sid=0/N/1194123/s0883944113001962.pdf?issn=0883-9441 %> internal-pdf://3590107589/Fares-2013-The Relationship Between Positive E.pdf %0 Journal Article %A Mealer, M %A Kittelson, J %A Thompson, BT %A Wheeler, AP %A Magee, JC %A Sokol, RJ %A Moss, M %A Kahn, MG %D 2013 %T Remote source document verification in two national clinical trials networks: A Pilot Study %B PLoS ONE %V 8 %N 12 %P e81890 %8 12/2013 %! Remote source document verification in two national clinical trials networks: A Pilot Study %2 PMC3857788 %X ####OBJECTIVE: Barriers to executing large-scale randomized controlled trials include costs, complexity, and regulatory requirements. We hypothesized that source document verification (SDV) via remote electronic monitoring is feasible. ####METHODS: Five hospitals from two NIH sponsored networks provided remote electronic access to study monitors. We evaluated pre-visit remote SDV compared to traditional on-site SDV using a randomized convenience sample of all study subjects due for a monitoring visit. The number of data values verified and the time to perform remote and on-site SDV was collected. ####RESULTS: Thirty-two study subjects were randomized to either remote SDV (N=16) or traditional on-site SDV (N=16). Technical capabilities, remote access policies and regulatory requirements varied widely across sites. In the adult network, only 14 of 2965 data values (0.47%) could not be located remotely. In the traditional on-site SDV arm, 3 of 2608 data values (0.12%) required coordinator help. In the pediatric network, all 198 data values in the remote SDV arm and all 183 data values in the on-site SDV arm were located. Although not statistically significant there was a consistent trend for more time consumed per data value (minutes +/- SD): Adult 0.50 +/- 0.17 min vs. 0.39 +/- 0.10 min (two-tailed t-test p=0.11); Pediatric 0.99 +/- 1.07 min vs. 0.56 +/- 0.61 min (p=0.37) and time per case report form: Adult: 4.60 +/- 1.42 min vs. 3.60 +/- 0.96 min (p=0.10); Pediatric: 11.64 +/- 7.54 min vs. 6.07 +/- 3.18 min (p=0.10) using remote SDV. ####CONCLUSIONS: Because each site had different policies, requirements, and technologies, a common approach to assimilating monitors into the access management system could not be implemented. Despite substantial technology differences, more than 99% of data values were successfully monitored remotely. This pilot study demonstrates the feasibility of remote monitoring and the need to develop consistent access policies for remote study monitoring. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857788/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857788/pdf/pone.0081890.pdf %> internal-pdf://1294049851/Mealer-2013-Remote source document verificatio.pdf %0 Journal Article %A Mendez-Tellez, PA %A Jackson, JC %A Hough, CL %A DM, Needham %A Dinglas, VD %A Morris, PE %A Wozniak, AW %A Colantuoni, E %A Ely, EW %A Rice, TW %A Hopkins, RO %A NIH NHLBI ARDS Network %D 2013 %T Physical and cognitive performance of acute lung injury patients one year after initial trophic vs full enteral feeding: EDEN trial follow-Up %B American Journal of Respiratory and Critical Care Medicine. %V 188 %N 5 %P 567-76 %8 09/2013 %! Physical and cognitive performance of acute lung injury patients one year after initial trophic vs full enteral feeding: EDEN trial follow-Up %2 PMC3827703 %X ####RATIONALE: We hypothesized that providing patients with acute lung injury two different protein/calorie nutritional strategies in the intensive care unit may affect longer-term physical and cognitive performance. ####OBJECTIVES: To assess physical and cognitive performance 6 and 12 months after acute lung injury, and to evaluate the effect of trophic versus full enteral feeding, provided for the first 6 days of mechanical ventilation, on 6-minute-walk distance, cognitive impairment, and secondary outcomes. ####METHODS: A prospective, longitudinal ancillary study of the ARDS Network EDEN trial evaluating 174 consecutive survivors from 5 of 12 centers. Blinded assessments of patients' arm anthropometrics, strength, pulmonary function, 6-minute-walk distance, and cognitive status (executive function, language, memory, verbal reasoning/concept formation, and attention) were performed. ####MEASUREMENTS AND MAIN RESULTS: At 6 and 12 months, respectively, the mean (SD) percent predicted for 6-minute-walk distance was 64% (22%) and 66% (25%) (P = 0.011 for difference between assessments), and 36 and 25% of survivors had cognitive impairment (P = 0.001). Patients performed below predicted values for secondary physical tests with small improvement from 6 to 12 months. There was no significant effect of initial trophic versus full feeding for the first 6 days after randomization on survivors' percent predicted for 6-minute-walk distance, cognitive impairment status, and all secondary outcomes. ####CONCLUSIONS: EDEN trial survivors performed below predicted values for physical and cognitive performance at 6 and 12 months, with some improvement over time. Initial trophic versus full enteral feeding for the first 6 days after randomization did not affect physical and cognitive performance. %U http://www.atsjournals.org/doi/abs/10.1164/rccm.201304-0651OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U2LAHoFdWsI %0 Journal Article %A Needham, DM %A Dinglas, VD %A Bienvenu, OJ %A Colantuoni, E %A Wozniak, AW %A Rice, TW %A Hopkins, RO %D 2013 %T One year outcomes in patients with acute lung injury randomized to initial trophic or full enteral feeding: prospective follow-up of EDEN randomized trial %B British Medical Journal %V 346 %P f1532 %8 03/2013 %! One year outcomes in patients with acute lung injury randomized to initial trophic or full enteral feeding: prospective follow-up of EDEN randomized trial %2 PMC3601941 %X ####OBJECTIVE: To evaluate the effect of initial low energy permissive underfeeding ("trophic feeding") versus full energy enteral feeding ("full feeding") on physical function and secondary outcomes in patients with acute lung injury. ####DESIGN: Prospective longitudinal follow-up evaluation of the NHLBI ARDS Clinical Trials Network's EDEN trial ####SETTING: 41hospitals in the United States. ####PARTICIPANTS: 525 patients with acute lung injury. ####INTERVENTIONS: Randomised assignment to trophic or full feeding for up to six days; thereafter, all patients still receiving mechanical ventilation received full feeding. ####MEASUREMENTS: Blinded assessment of the age and sex adjusted physical function domain of the SF-36 instrument at 12 months after acute lung injury. Secondary outcome measures included survival; physical, psychological, and cognitive functioning; quality of life; and employment status at six and 12 months. ####RESULTS: After acute lung injury, patients had substantial physical, psychological, and cognitive impairments, reduced quality of life, and impaired return to work. Initial trophic versus full feeding did not affect mean SF-36 physical function at 12 months (55 (SD 33) v 55 (31), P=0.54), survival to 12 months (65% v 63%, P=0.63), or nearly all of the secondary outcomes. ####CONCLUSION: In survivors of acute lung injury, there was no difference in physical function, survival, or multiple secondary outcomes at 6 and 12 month follow-up after initial trophic or full enteral feeding. %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601941/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601941/pdf/bmj.f1532.pdf %> internal-pdf://0017625599/Needham-2013-One year outcomes in patients wit.pdf %0 Journal Article %A Prescott, HC %A Brower, RG %A Cooke, CR %A Phillips, G %A O'Brien, JM %A Investigators, The Acute Respiratory Distress Syndrome Network %D 2013 %T Factors associated with elevated plateau pressure in patients with acute lung injury receiving lower tidal volume ventilation %B Critical Care Medicine %V 41 %N 3 %P 756-64 %8 03/2013 %! Factors associated with elevated plateau pressure in patients with acute lung injury receiving lower tidal volume ventilation %X ####OBJECTIVES: Lung-protective ventilation with lower tidal volume and lower plateau pressure improves mortality in patients with acute lung injury and acute respiratory distress syndrome. We sought to determine the incidence of elevated plateau pressure in acute lung injury /acute respiratory distress syndrome patients receiving lower tidal volume ventilation and to determine the factors that predict elevated plateau pressure in these patients. ####PATIENTS: We used data from 1398 participants in Acute Respiratory Distress Syndrome Network trials, who received lower tidal volume ventilation (≤ 6.5mL/kg predicted body weight). ####DESIGN: We considered patients with a plateau pressure greater than 30cm H2O and/or a tidal volume less than 5.5mL/kg predicted body weight on study day 1 to have "elevated plateau pressure." We used logistic regression to identify baseline clinical variables associated with elevated plateau pressure and to develop a model to predict elevated plateau pressure using a subset of 1,188 patients. We validated the model in the 210 patients not used for model development. ####SETTING: Medical centers participating in Acute Respiratory Distress Syndrome Network clinical trials. ####INTERVENTIONS: None. ####MEASUREMENTS AND MAIN RESULTS: Of the 1,398 patients in our study, 288 (20.6%) had elevated plateau pressure on day 1. Severity of illness indices and demographic factors (younger age, greater body mass index, and non-white race) were independently associated with elevated plateau pressure. The multivariable logistic regression model for predicting elevated plateau pressure had an area under the receiving operator characteristic curve of 0.71 for both the developmental and the validation subsets. ####CONCLUSIONS: acute lung injury patients receiving lower tidal volume ventilation often have a plateau pressure that exceeds Acute Respiratory Distress Syndrome Network goals. Race, body mass index, and severity of lung injury are each independently associated with elevated plateau pressure. Selecting a smaller initial tidal volume for non-white patients and patients with higher severity of illness may decrease the incidence of elevated plateau pressure. Prospective studies are needed to evaluate this approach. %U http://pt.wkhealth.com/pt/re/lwwgateway/landingpage.htm;jsessionid=Tv8drFvbhh2B0spYbpgypLqgmCzC6lsqwhYdnM1vk9sxt6LTZ20n!-867019713!181195629!8091!-1?issn=0090-3493&volume=41&issue=3&spage=756 http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv024/00003246/00003246-201303000-00007.pdf %> internal-pdf://3446258721/Prescott-2013-Factors associated with elevated.pdf %0 Journal Article %A Sinha, P %A Sanders, RD %A Soni, N %A Vukoja, MK %A Gajic, O %D 2013 %T Acute respiratory distress syndrome: the prognostic value of ventilatory ratio -a simple bedside tool to monitor ventilatory efficiency %B American Journal of Respiratory and Critical Care Medicine %V 187 %N 10 %P 1150-3 %8 05/2013 %! Acute respiratory distress syndrome: the prognostic value of ventilatory ratio -a simple bedside tool to monitor ventilatory efficiency %U http://www.atsjournals.org/doi/abs/10.1164/rccm.201211-2037LE?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U2K9s4FdWsI http://www.atsjournals.org/doi/pdf/10.1164/rccm.201211-2037LE %> internal-pdf://3843280816/Sinha-2013-Acute respiratory distress syndrome.pdf %0 Journal Article %A Smart A %A BT, Thompson %A DM, Needham %A RO, Hopkins %A Williams A %A EL, Burnham %A Moss M %A ARDS Network, the NHLBI %D 2013 %T Surrogate consent for genetic testing, the reconsent process, and consent for long-term outcomes in acute respiratory distress syndrome trials %B American Journal of Respiratory and Critical Care Medicine %V 118 %N 11 %P 1370-3 %8 12/2013 %! Surrogate consent for genetic testing, the reconsent process, and consent for long-term outcomes in acute respiratory distress syndrome trials %2 PMC3919075 %U http://www.atsjournals.org/doi/abs/10.1164/rccm.201307-1235LE?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U2kUW4FdWsI %0 Journal Article %A Hsieh, SJ %A Zhuo, H %A Benowitz, NL %A Thompson, BT %A Liu, KD %A Matthay, MA %A Calfee, CS %A Network, the NHLBI Acute Respiratory Distress Syndrome Clinical Trials %D 2014 %T Prevalence and impact of active and passive cigarette smoking in acute respiratory distress syndrome %B Crit Care Med. %V 42 %N 9 %P 2058-68 %8 09/2014 %! Prevalence and impact of active and passive cigarette smoking in acute respiratory distress syndrome %R 10.1097/ccm.0000000000000418 %2 PMC4134734 %U http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCJDHEPC00/fs047/ovft/live/gv024/00003246/00003246-201409000-00012.pdf %> internal-pdf://2791037296/Hsieh-2014-Prevalence and impact of active and.pdf %0 Journal Article %A Kallet, RH %A Zhou, H %A Liu, KD %A Calfee, CS %A Matthay, MA %A Investigators, NHBLI ARDSNet %D 2014 %T The Association Between Physiologic Dead-Space Fraction and Mortality in Subjects With ARDS Enrolled in a Prospective Multi-Center Clinical Trial %B Respiratory Care %V 59 %N 11 %P 1611-1618 %8 11/2014 %! The Association Between Physiologic Dead-Space Fraction and Mortality in Subjects With ARDS Enrolled in a Prospective Multi-Center Clinical Trial %2 PMC4077995 %X **BACKGROUND:** We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [VD/VT]) and mortality in subjects with ARDS (Berlin definition, PaO2/FIO2 ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. **METHODS:** We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. VD/VT and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. **RESULTS:** At baseline, non-survivors had a trend toward higher VD/VT compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in VD/VT between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in VD/VT [95% CI]: 6.84 [1.62–28.84] P = .01; and study day 2: 4.90 [1.28–18.73] P = .02) after adjusting for VD/VT, PaO2/FIO2, oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, VD/VT was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99–19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12–3.35] P = .04). **CONCLUSIONS:** Markedly elevated VD/VT (≥ 0.60) in early ARDS is associated with higher mortality. Measuring VD/VT may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial.c trial. %U http://rc.rcjournal.com/content/59/11/1611.full http://rc.rcjournal.com/content/59/11/1611.full.pdf %> internal-pdf://4200966632/Kallet-2014-The Association Between Physiologi.pdf %0 Journal Article %A Needham, DM %A Wozniak, AW %A Hough, CL %A Morris, PE %A Dinglas, VD %A Jackson, JC %A Mendez-Tellez, PA %A Shanholtz, C %A Ely, EW %A Colantuoni, E %A Hopkins, RO %A The Acute Respiratory Distress Syndrome Network %D 2014 %T Risk Factors for Physical Impairment after Acute Lung Injury in a National Multi-Center Study %B American Journal of Respiratory and Critical Care Medicine %8 In Press %! Risk Factors for Physical Impairment after Acute Lung Injury in a National Multi-Center Study %X ####Rationale: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. ####Objectives: To evaluate risk factors for 3 measures of physical impairments commonly experienced by ALI survivors in the first year after hospitalization. ####Methods: A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute walk distance, and SF-36 Physical Function score) for 203 ALI survivors enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. ####Measurements and Main Results: At 6- and 12-months, respectively, mean (±SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (±8%) and 93% (±9%), 6-minute walk distance (as percent-predicted) was 64% (±22%) and 67% (±26%), and SF-36 Physical Function score (as percent-predicted) was 61% (±36%) and 67% (±37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and ICU length of stay with impairments in physical outcomes. ####Conclusions: Patients had substantial impairments, from predicted values, for 6-minute walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of ICU stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes. %U http://www.atsjournals.org/doi/abs/10.1164/rccm.201401-0158OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U2kXqIFdWsI %0 Journal Article %A NHLBI, ARDSNet %D 2014 %T A Randomized Trial of Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome %B New Engl J Med %9 Letter %! A Randomized Trial of Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome ]]>

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