Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation

Background Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS. Objective To estimate the attributable mortality, if any, of ARDS. Design First, we performed a systematic review and meta-analysis of observational studies reporting mortality of critically ill patients with and without ARDS matched for underlying risk factor. Next, we conducted a survival analysis of prospectively collected patient-level data from subjects enrolled in three intensive care unit (ICU) cohorts to estimate the attributable mortality of critically ill septic patients with and without ARDS using a novel causal inference method. Results In the meta-analysis, 44 studies (47 cohorts) involving 56 081 critically ill patients were included. Mortality was higher in patients with versus without ARDS (risk ratio 2.48, 95% CI 1.86 to 3.30; p<0.001) with a numerically stronger association between ARDS and mortality in trauma than sepsis. In the survival analysis of three ICU cohorts enrolling 1203 critically ill patients, 658 septic patients were included. After controlling for confounders, ARDS was found to increase the mortality rate by 15% (95% CI 3% to 26%; p=0.015). Significant increases in mortality were seen for severe (23%, 95% CI 3% to 44%; p=0.028) and moderate (16%, 95% CI 2% to 31%; p=0.031), but not for mild ARDS. Conclusions ARDS has a direct causal link with mortality. Our findings provide information about the extent to which continued funding of ARDS prevention trials has potential to impart survival benefit. PROSPERO Registration Number CRD42017078313

[1]  Mary E. Choi,et al.  Effect of Neutropenic Critical Illness on Development and Prognosis of Acute Respiratory Distress Syndrome. , 2020, American journal of respiratory and critical care medicine.

[2]  P. Meybohm,et al.  Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study , 2020, Annals of Intensive Care.

[3]  E. Schenck,et al.  Attributable Mortality of Acute Respiratory Distress Syndrome in Critically Ill Septic Patients: Estimation Using a Novel Causal Inference Method , 2020 .

[4]  D. Berlin,et al.  Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials , 2019, Chest.

[5]  J. Crapo,et al.  Control of Confounding and Reporting of Results in Causal Inference Studies. Guidance for Authors from Editors of Respiratory, Sleep, and Critical Care Journals , 2019, Annals of the American Thoracic Society.

[6]  E. Schenck,et al.  Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials , 2018, Journal of critical care.

[7]  J. Laffey,et al.  Immunocompromised patients with acute respiratory distress syndrome: secondary analysis of the LUNG SAFE database , 2018, Critical Care.

[8]  S. Ryter,et al.  RIPK3 mediates pathogenesis of experimental ventilator-induced lung injury. , 2018, JCI insight.

[9]  Marco Carone,et al.  Improved estimation of the cumulative incidence of rare outcomes , 2018, Statistics in medicine.

[10]  B. Souweine,et al.  Effect of Transfusion on Mortality and Other Adverse Events Among Critically Ill Septic Patients: An Observational Study Using a Marginal Structural Cox Model* , 2017, Critical care medicine.

[11]  J. Laffey,et al.  Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study , 2017, Annals of Intensive Care.

[12]  E. Finkelsztein,et al.  Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit , 2017, Critical Care.

[13]  Tool to Assess Risk of Bias in Cohort Studies , 2017 .

[14]  R. Cartotto,et al.  The Acute Respiratory Distress Syndrome (ARDS) in mechanically ventilated burn patients: An analysis of risk factors, clinical features, and outcomes using the Berlin ARDS definition. , 2016, Burns : journal of the International Society for Burn Injuries.

[15]  Jeremy W. Cannon,et al.  Incidence, risk factors, and mortality associated with acute respiratory distress syndrome in combat casualty care , 2016, The journal of trauma and acute care surgery.

[16]  Liang-wan Chen,et al.  Analysis of risk factors for and the prognosis of postoperative acute respiratory distress syndrome in patients with Stanford type A aortic dissection. , 2016, Journal of thoracic disease.

[17]  G. Perkins,et al.  The impact of the acute respiratory distress syndrome on outcome after oesophagectomy. , 2016, British journal of anaesthesia.

[18]  Gordon S. Smith,et al.  Trauma indices for prediction of acute respiratory distress syndrome. , 2016, The Journal of surgical research.

[19]  J. Palakshappa,et al.  Low Plasma Levels of Adiponectin Do Not Explain Acute Respiratory Distress Syndrome Risk: a Prospective Cohort Study of Patients with Severe Sepsis , 2016, Critical Care.

[20]  Anders Larsson,et al.  Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. , 2016, JAMA.

[21]  R. Bellomo,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[22]  S. Bailly,et al.  What’s new in the quantification of causal effects from longitudinal cohort studies: a brief introduction to marginal structural models for intensivists , 2016, Intensive Care Medicine.

[23]  M. Elhoseny,et al.  Severe pneumonia requiring ICU admission: Revisited , 2015 .

[24]  M. Cohen,et al.  Differences in degree, differences in kind: Characterizing lung injury in trauma , 2015, The journal of trauma and acute care surgery.

[25]  K. Inaba,et al.  Adult respiratory distress syndrome risk factors for injured patients undergoing damage-control laparotomy: AAST multicenter post hoc analysis , 2014, The journal of trauma and acute care surgery.

[26]  Xi Zhu,et al.  [Risk factors of the occurence and death of acute respiratory distress syndrome: a prospective multicenter cohort study]. , 2014, Zhonghua wei zhong bing ji jiu yi xue.

[27]  L. Bai,et al.  Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome , 2014, BMC Infectious Diseases.

[28]  Nehemiah T. Liu,et al.  Acute respiratory distress syndrome in wartime military burns: Application of the Berlin criteria , 2014, The journal of trauma and acute care surgery.

[29]  G. Bernard,et al.  Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: a case-control study , 2014, Annals of Intensive Care.

[30]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[31]  Ching‐Chih Hu,et al.  Predictors of Acute Respiratory Distress Syndrome in Patients with Paraquat Intoxication , 2013, PloS one.

[32]  S. Bellamy,et al.  The Epidemiology of Acute Respiratory Distress Syndrome in Patients Presenting to the Emergency Department With Severe Sepsis , 2013, Shock.

[33]  N. Mohr,et al.  Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study. , 2013, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[34]  T. Fabian,et al.  Does plasma transfusion portend pulmonary dysfunction? A tale of two ratios , 2013, The journal of trauma and acute care surgery.

[35]  A. Torres,et al.  Predictive factors of mortality in severe community-acquired pneumonia: a model with data on the first 24h of ICU admission. , 2013, Medicina intensiva.

[36]  A. Ferruelo,et al.  Genetic Predisposition to Acute Respiratory Distress Syndrome in Patients With Severe Sepsis , 2013, Shock.

[37]  H. Lei,et al.  Acute lung injury in patients with severe acute pancreatitis. , 2013, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[38]  Joel D. Stitzel,et al.  An innovative approach to predict the development of adult respiratory distress syndrome in patients with blunt trauma , 2012, The journal of trauma and acute care surgery.

[39]  Arthur S Slutsky,et al.  Acute Respiratory Distress Syndrome The Berlin Definition , 2012 .

[40]  Stijn Vansteelandt,et al.  Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. , 2011, American journal of respiratory and critical care medicine.

[41]  Lesly A. Dossett,et al.  Gender and acute respiratory distress syndrome in critically injured adults: a prospective study. , 2011, The Journal of trauma.

[42]  Ognjen Gajic,et al.  Derivation and Diagnostic Accuracy of the Surgical Lung Injury Prediction Model , 2011, Anesthesiology.

[43]  F. Granath,et al.  Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit , 2010, Acta anaesthesiologica Scandinavica.

[44]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[45]  Michael Rosenblum,et al.  Targeted Maximum Likelihood Estimation of the Parameter of a Marginal Structural Model , 2010, The international journal of biostatistics.

[46]  A. Salim,et al.  Acute respiratory distress syndrome in nontrauma surgical patients: a 6-year study. , 2009, The Journal of trauma.

[47]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[48]  Paul N. Lanken,et al.  The impact of development of acute lung injury on hospital mortality in critically ill trauma patients , 2008, Critical care medicine.

[49]  A. Leaver,et al.  Acute lung injury after ruptured abdominal aortic aneurysm repair: The effect of excluding donations from females from the production of fresh frozen plasma* , 2008, Critical care medicine.

[50]  O. Gajic,et al.  Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study , 2008 .

[51]  Arthur S Slutsky,et al.  Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome , 2008, Intensive Care Medicine.

[52]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2007, Preventive medicine.

[53]  M. Malinchoc,et al.  Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. , 2007, American journal of respiratory and critical care medicine.

[54]  M. J. van der Laan,et al.  Statistical Applications in Genetics and Molecular Biology Super Learner , 2010 .

[55]  M. J. van der Laan,et al.  The International Journal of Biostatistics Targeted Maximum Likelihood Learning , 2011 .

[56]  H. Belzberg,et al.  Acute respiratory distress syndrome in the trauma intensive care unit: Morbid but not mortal. , 2006, Archives of surgery.

[57]  J. Robins,et al.  Doubly Robust Estimation in Missing Data and Causal Inference Models , 2005, Biometrics.

[58]  P. Rhee,et al.  The decreasing incidence and mortality of acute respiratory distress syndrome after injury: a 5-year observational study. , 2005, The Journal of trauma.

[59]  G. Martin,et al.  The role of acute blood transfusion in the development of acute respiratory distress syndrome in patients with severe trauma. , 2005, The Journal of trauma.

[60]  I. Hozo,et al.  Estimating the mean and variance from the median, range, and the size of a sample , 2005, BMC medical research methodology.

[61]  J. Vincent,et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure , 1996, Intensive Care Medicine.

[62]  O. Gajic,et al.  Acute lung injury after blood transfusion in mechanically ventilated patients , 2004, Transfusion.

[63]  Diane P. Martin,et al.  Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients* , 2004, Critical care medicine.

[64]  D. Morabito,et al.  The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. , 2003, The Journal of trauma.

[65]  S. Hugonnet,et al.  Acute respiratory distress syndrome after bacteremic sepsis does not increase mortality. , 2003, American journal of respiratory and critical care medicine.

[66]  P. Parsons,et al.  Chronic alcohol abuse is associated with an increased incidence of acute respiratory distress syndrome and severity of multiple organ dysfunction in patients with septic shock , 2003, Critical care medicine.

[67]  Timothy C Fabian,et al.  Acute Respiratory Distress Syndrome in Blunt Trauma: Identification of Independent Risk Factors , 2002, The American surgeon.

[68]  J. Vincent,et al.  Serial evaluation of the SOFA score to predict outcome in critically ill patients. , 2001, JAMA.

[69]  R. Wachter,et al.  Assessment of prognosis in patients with community-acquired pneumonia who require mechanical ventilation. , 2000, Chest.

[70]  D. Morabito,et al.  Initial severity of metabolic acidosis predicts the development of acute lung injury in severely traumatized patients , 2000, Critical care medicine.

[71]  G. Rubenfeld,et al.  The effect of acute respiratory distress syndrome on long-term survival. , 1999, American journal of respiratory and critical care medicine.

[72]  Arthur S Slutsky,et al.  ARDS in patients with thermal injury , 1999, Intensive Care Medicine.

[73]  C. Steiner,et al.  Comorbidity measures for use with administrative data. , 1998, Medical care.

[74]  J. Vincent,et al.  Is outcome from ARDS related to the severity of respiratory failure? , 1997, The European respiratory journal.

[75]  R. Maunder,et al.  Clinical risks for development of the acute respiratory distress syndrome. , 1995, American journal of respiratory and critical care medicine.

[76]  M. Lamy,et al.  The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. , 1994, American journal of respiratory and critical care medicine.

[77]  in mechanically ventilated patients , 2022 .