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

Yaseen M Arabi, Saqib I Dara, Hani M Tamim, Asgar H Rishu, Abderrezak Bouchama, Mohammad K Khedr, Daniel Feinstein, Joseph E Parrillo, Kenneth E Wood, Sean P Keenan, Sergio Zanotti, Greg Martinka, Aseem Kumar, Anand Kumar, Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group, Phillip Dellinger, Sandra Dial, Peter Dodek, Paul Ellis, Dave Gurka, Jose Guzman, Andreas Kramer, Stephen Lapinsky, Denny Laporta, Kevin Laupland, Bruce Light, Dennis Maki, John Marshall, Ziad Al Memish, Yazdan Mirzanejad, Gourang Patel, Charles Penner, Dan Roberts, John Ronald, Dave Simon, Sat Sharma, Nehad Al Shirawi, Yoanna Skrobik, Gordon Wood, Muhammed Wali Ahsan, Mozdeh Bahrainian, Rob Bohmeier, Lindsey Carter, Harris Chou, Sofia Delgra, Collins Egbujuo, Winnie Fu, Catherine Gonzales, Harleena Gulati, Erica Halmarson, John Hansen, Ziaul Haque, Johanne Harvey, Farah Khan, Laura Kolesar, Laura Kravetsky, Runjun Kumar, Nasreen Merali, Sheri Muggaberg, Heidi Paulin, Cheryl Peters, Jody Richards, Christa Schorr, Norrie Serrano, Mustafa Suleman, Amrinder Singh, Katherine Sullivan, Robert Suppes, Leo Taiberg, Ronny Tchokonte, Omid Ahmadi Torshizi, Kym Wiebe, Yaseen M Arabi, Saqib I Dara, Hani M Tamim, Asgar H Rishu, Abderrezak Bouchama, Mohammad K Khedr, Daniel Feinstein, Joseph E Parrillo, Kenneth E Wood, Sean P Keenan, Sergio Zanotti, Greg Martinka, Aseem Kumar, Anand Kumar, Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group, Phillip Dellinger, Sandra Dial, Peter Dodek, Paul Ellis, Dave Gurka, Jose Guzman, Andreas Kramer, Stephen Lapinsky, Denny Laporta, Kevin Laupland, Bruce Light, Dennis Maki, John Marshall, Ziad Al Memish, Yazdan Mirzanejad, Gourang Patel, Charles Penner, Dan Roberts, John Ronald, Dave Simon, Sat Sharma, Nehad Al Shirawi, Yoanna Skrobik, Gordon Wood, Muhammed Wali Ahsan, Mozdeh Bahrainian, Rob Bohmeier, Lindsey Carter, Harris Chou, Sofia Delgra, Collins Egbujuo, Winnie Fu, Catherine Gonzales, Harleena Gulati, Erica Halmarson, John Hansen, Ziaul Haque, Johanne Harvey, Farah Khan, Laura Kolesar, Laura Kravetsky, Runjun Kumar, Nasreen Merali, Sheri Muggaberg, Heidi Paulin, Cheryl Peters, Jody Richards, Christa Schorr, Norrie Serrano, Mustafa Suleman, Amrinder Singh, Katherine Sullivan, Robert Suppes, Leo Taiberg, Ronny Tchokonte, Omid Ahmadi Torshizi, Kym Wiebe

Abstract

Introduction: Data 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.

Methods: We 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.

Results: Of 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).

Conclusions: The 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.

Figures

Figure 1
Figure 1
Odds ratios and confidence intervals of hospital mortality among different BMI groups in multivariate logistic regression analysis. Panel A: Crude analysis. Panel B: Adjusted analysis to baseline characteristics (model 1). Panel C: Adjusted analysis to baseline characteristics and sepsis interventions (model 2). BMI, body mass index.

References

    1. Katzmarzyk PT, Reeder BA, Elliott S, Joffres MR, Pahwa P, Raine KD, Kirkland SA, Paradis G. Body mass index and risk of cardiovascular disease, cancer and all-cause mortality. Can J Public Health. 2012;103:147–151.
    1. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai P Jr, Razak F, Sharma AM, Anand SS. INTERHEART Study Investigators. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet. 2005;366:1640–1649. doi: 10.1016/S0140-6736(05)67663-5.
    1. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world--a growing challenge. N Engl J Med. 2007;356:213–215. doi: 10.1056/NEJMp068177.
    1. Al-Baghli NA, Al-Ghamdi AJ, Al-Turki KA, El-Zubaier AG, Al-Ameer MM, Al-Baghli FA. Overweight and obesity in the eastern province of Saudi Arabia. Saudi Med J. 2008;29:1319–1325.
    1. Institute of Medicine of the National Academics Recommendation on Obseity Prevention. [ ] Accessed on 14 May 2009.
    1. El-Solh AA. Clinical approach to the critically ill, morbidly obese patient. Am J Respir Crit Care Med. 2004;169:557–561. doi: 10.1164/rccm.200309-1256CC.
    1. Sakr Y, Madl C, Filipescu D, Moreno R, Groeneveld J, Artigas A, Reinhart K, Vincent JL. Obesity is associated with increased morbidity but not mortality in critically ill patients. Intensive Care Med. 2008;34:1999–2009. doi: 10.1007/s00134-008-1243-0.
    1. Martino JL, Stapleton RD, Wang M, Day AG, Cahill NE, Dixon AE, Suratt BT, Heyland DK. Extreme obesity and outcomes in critically ill patients. Chest. 2011;140:1198–1206. doi: 10.1378/chest.10-3023.
    1. Hutagalung R, Marques J, Kobylka K, Zeidan M, Kabisch B, Brunkhorst F, Reinhart K, Sakr Y. The obesity paradox in surgical intensive care unit patients. Intensive Care Med. 2011;37:1793–1799. doi: 10.1007/s00134-011-2321-2.
    1. Habbu A, Lakkis NM, Dokainish H. The obesity paradox: fact or fiction? Am J Cardiol. 2006;98:944–948. doi: 10.1016/j.amjcard.2006.04.039.
    1. Oliveros H, Villamor E. Obesity and mortality in critically ill adults: a systematic review and meta-analysis. Obesity (Silver Spring) 2008;16:515–521. doi: 10.1038/oby.2007.102.
    1. Akinnusi ME, Pineda LA, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta-analysis. Crit Care Med. 2008;36:151–158. doi: 10.1097/01.CCM.0000297885.60037.6E.
    1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310. doi: 10.1097/00003246-200107000-00002.
    1. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med. 2007;35:1244–1250. doi: 10.1097/01.CCM.0000261890.41311.E9.
    1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554. doi: 10.1056/NEJMoa022139.
    1. Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, Meshaka P, Cheval C, Thuong M, Troche G, Garrouste-Orgeas M, Timsit JF. 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. J Crit Care. 2005;20:46–58. doi: 10.1016/j.jcrc.2004.10.005.
    1. Vachharajani V, Russell JM, Scott KL, Conrad S, Stokes KY, Tallam L, Hall J, Granger DN. Obesity exacerbates sepsis-induced inflammation and microvascular dysfunction in mouse brain. Microcirculation. 2005;12:183–194.
    1. Wurzinger B, Dunser MW, Wohlmuth C, Deutinger MC, Ulmer H, Torgersen C, Schmittinger CA, Grander W, Hasibeder WR. The association between body-mass index and patient outcome in septic shock: a retrospective cohort study. Wien Klin Wochenschr. 2010;122:31–36.
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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. Chest. 1992;101:1644–1655. doi: 10.1378/chest.101.6.1644.
    1. Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Simon D, Peters C, Ahsan M, Chateau D. Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136:1237–1248. doi: 10.1378/chest.09-0087.
    1. Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G, Keenan S, Wood G, Arabi Y, Feinstein D, Kumar A, Dodek P, Kravetsky L, Doucette S. Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med. 2010;38:1773–1785. doi: 10.1097/CCM.0b013e3181eb3ccd.
    1. WHO classification of body mass index (BMI) [ ] Accessed on 9 April 2012.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–829. doi: 10.1097/00003246-198510000-00009.
    1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–470. doi: 10.7326/0003-4819-130-6-199903160-00002.
    1. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41. doi: 10.1159/000180580.
    1. Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT. Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol. 2010;5:1003–1009. doi: 10.2215/CJN.06870909.
    1. Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis. 1997;25:112–118. doi: 10.1086/514505.
    1. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–1596. doi: 10.1097/01.CCM.0000217961.75225.E9.
    1. Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004;30:18–32. doi: 10.1007/s00134-003-2059-6.
    1. Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E. CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007;370:676–684. doi: 10.1016/S0140-6736(07)61344-0.
    1. Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D. VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–887. doi: 10.1056/NEJMoa067373.
    1. O'Brien JM Jr, Welsh CH, Fish RH, Ancukiewicz M, Kramer AM. Excess body weight is not independently associated with outcome in mechanically ventilated patients with acute lung injury. Ann Intern Med. 2004;140:338–345. doi: 10.7326/0003-4819-140-5-200403020-00009.
    1. Hogue CW Jr, Stearns JD, Colantuoni E, Robinson KA, Stierer T, Mitter N, Pronovost PJ, Needham DM. The impact of obesity on outcomes after critical illness: a meta-analysis. Intensive Care Med. 2009;35:1152–1170. doi: 10.1007/s00134-009-1424-5.
    1. O'Brien JM Jr, Philips GS, Ali NA, Aberegg SK, Marsh CB, Lemeshow S. The association between body mass index, processes of care, and outcomes from mechanical ventilation: a prospective cohort study. Crit Care Med. 2012;40:1456–1463. doi: 10.1097/CCM.0b013e31823e9a80.
    1. O'Brien JM Jr, Phillips GS, Ali NA, Lucarelli M, Marsh CB, Lemeshow S. Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury. Crit Care Med. 2006;34:738–744.
    1. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564–2575.
    1. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM. FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364:2483–2495. doi: 10.1056/NEJMoa1101549.
    1. Anzueto A, Frutos-Vivar F, Esteban A, Bensalami N, Marks D, Raymondos K, Apezteguia C, Arabi Y, Hurtado J, Gonzalez M, Tomicic V, Abroug F, Elizalde J, Cakar N, Pelosi P, Ferguson ND. Ventila group. Influence of body mass index on outcome of the mechanically ventilated patients. Thorax. 2011;66:66–73. doi: 10.1136/thx.2010.145086.
    1. Gong MN, Bajwa EK, Thompson BT, Christiani DC. Body mass index is associated with the development of acute respiratory distress syndrome. Thorax. 2010;65:44–50. doi: 10.1136/thx.2009.117572.
    1. Stapleton RD, Dixon AE, Parsons PE, Ware LB, Suratt BT. The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest. 2010;138:568–577. doi: 10.1378/chest.10-0014.
    1. Paolini JB, Mancini J, Genestal M, Gonzalez H, McKay RE, Samii K, Fourcade OA. Predictive value of abdominal obesity vs. body mass index for determining risk of intensive care unit mortality. Crit Care Med. 2010;38:1308–1314.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться