Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

See related commentary by Dickerson, http://ccforum.com/content/17/3/154IntroductionData are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.MethodsWe performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.ResultsOf the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).ConclusionsThe obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

[1]  F. Dekker,et al.  Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[2]  D. Annane,et al.  Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial , 2007, The Lancet.

[3]  K. Wood,et al.  Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* , 2006, Critical care medicine.

[4]  A. E. El Solh,et al.  Effect of obesity on intensive care morbidity and mortality: A meta-analysis* , 2008, Critical care medicine.

[5]  I. L. Cohen.  Guidelines for the use of innovative therapies in sepsis. , 1993, Critical care medicine.

[6]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. , 2009, Chest.

[7]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[8]  J. Timsit,et al.  Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. , 2005, Journal of critical care.

[9]  A. Anzueto,et al.  Influence of body mass index on outcome of the mechanically ventilated patients , 2010, Thorax.

[10]  Gordon R Bernard,et al.  Comparison of two fluid-management strategies in acute lung injury. , 2006, The New England journal of medicine.

[11]  N. Lakkis,et al.  The obesity paradox: fact or fiction? , 2006, The American journal of cardiology.

[12]  J. Sunderram,et al.  Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003* , 2007, Critical care medicine.

[13]  S. Lemeshow,et al.  The association between body mass index, processes of care, and outcomes from mechanical ventilation: A prospective cohort study* , 2012, Critical care medicine.

[14]  P. Pronovost,et al.  The impact of obesity on outcomes after critical illness: a meta-analysis , 2009, Intensive Care Medicine.

[15]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[16]  O. Fourcade,et al.  Predictive value of abdominal obesity vs. body mass index for determining risk of intensive care unit mortality , 2010, Critical care medicine.

[17]  S. Yusuf,et al.  Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study , 2005, The Lancet.

[18]  K. Reinhart,et al.  The obesity paradox in surgical intensive care unit patients , 2011, Intensive Care Medicine.

[19]  Parvez Hossain,et al.  Obesity and diabetes in the developing world--a growing challenge. , 2007, The New England journal of medicine.

[20]  D. Christiani,et al.  Body mass index is associated with the development of acute respiratory distress syndrome , 2009, Thorax.

[21]  Nadira A Al-Baghli,et al.  Overweight and obesity in the eastern province of Saudi Arabia. , 2008, Saudi medical journal.

[22]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[23]  J. Vincent,et al.  Obesity is associated with increased morbidity but not mortality in critically ill patients , 2008, Intensive Care Medicine.

[24]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[25]  E. Villamor,et al.  Obesity and Mortality in Critically Ill Adults: A Systematic Review and Meta‐analysis , 2008, Obesity.

[26]  K. Rodvold,et al.  Antimicrobial dosing in obese patients. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  M. Mathru.  Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock , 2010 .

[28]  A. Kramer,et al.  Excess Body Weight Is Not Independently Associated with Outcome in Mechanically Ventilated Patients with Acute Lung Injury , 2004, Annals of Internal Medicine.

[29]  P. Parsons,et al.  The association between BMI and plasma cytokine levels in patients with acute lung injury. , 2010, Chest.

[30]  S. Lapinsky,et al.  Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: A propensity-matched analysis* , 2010, Critical care medicine.

[31]  Brian L. Erstad,et al.  Dosing of medications in morbidly obese patients in the intensive care unit setting , 2004, Intensive Care Medicine.

[32]  S. Lemeshow,et al.  Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury* , 2006, Critical Care Medicine.

[33]  P. Katzmarzyk,et al.  Body Mass Index and Risk of Cardiovascular Disease, Cancer and All-cause Mortality , 2012, Canadian Journal of Public Health.

[34]  D. Mannino,et al.  The epidemiology of sepsis in the United States from 1979 through 2000. , 2003, The New England journal of medicine.

[35]  D. Heyland,et al.  Extreme obesity and outcomes in critically ill patients. , 2010, Chest.

[36]  D. Granger,et al.  Obesity Exacerbates Sepsis‐Induced Inflammation and Microvascular Dysfunction in Mouse Brain , 2005, Microcirculation.

[37]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[38]  W. Grander,et al.  The association between body-mass index and patient outcome in septic shock: a retrospective cohort study , 2009, Wiener klinische Wochenschrift.

[39]  K. Maitland,et al.  Mortality after fluid bolus in African children with severe infection. , 2011, The New England journal of medicine.

[40]  Sangeeta Mehta,et al.  Vasopressin versus norepinephrine infusion in patients with septic shock. , 2008, The New England journal of medicine.

[41]  A. El‐Solh,et al.  Clinical approach to the critically ill, morbidly obese patient. , 2004, American journal of respiratory and critical care medicine.