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Published in: Critical Care 3/2013

Open Access 01-06-2013 | Research

One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response

Authors: Petch Wacharasint, John H Boyd, James A Russell, Keith R Walley

Published in: Critical Care | Issue 3/2013

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Abstract

Introduction

Obesity is an increasingly common comorbidity in critically ill patients. Whether obesity alters sepsis outcome, susceptibility, treatment, and response is not completely understood.

Methods

We conducted a retrospective analysis comparing three group of septic shock patients based on the intervals of actual body mass index (BMI) in patients enrolled in the VASST (Vasopressin and Septic Shock Trial) cohort. Primary outcome measurement was 28-day mortality. We tested for differences in patterns of infection by comparing the primary site of infection and organism. We also compared the treatments (fluids and vasopressors) and inflammatory response, measuring adipose tissue-related cytokine concentrations (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1, tumor necrosis factor [TNF]-α, and resistin) in plasma in a subset of 382 patients. Of the 778 patients in VASST, 730 patients who had body weight and height measurements were analyzed. Patients with BMI <25 kg/m2 (n = 276) were grouped as a reference and compared to 'overweight' (25< BMI <30 kg/m2, n = 209) and 'obese' (BMI > 30 kg/m2,n = 245) patients.

Results

Obese patients had the lowest 28-day mortality followed by overweight patients while patients with BMI <25 kg/m2 had the highest mortality (p = 0.02). Compared to the patients with BMI <25 kg/m2, obese and overweight patients also had a different pattern of infection with less lung (obese 35%, overweight 45%, BMI<25 kg/m2 50%, p = 0.003) and fungal infection (obese 8.2%, overweight 11%, and BMI<25 kg/m2 15.6%, p = 0.03). Per kilogram, obese and overweight patients received less fluid during the first four days (p<0.05) and received less norepinephrine (obese 0.14, overweight 0.21, BMI <25 kg/m2 0.26 µg/kg/min, p<0.0001) and vasopressin (obese 0.28, overweight 0.36, BMI <25 kg/m2 0.43 µU/kg/min, p<0.0001) on day 1 compared to patients with BMI <25 kg/m2. Obese and overweight patients also had a lower plasma IL-6 concentration at baseline (obese 106 [IQR 34-686], overweight 190 [IQR 44-2339], BMI <25 kg/m2 235 [IQR 44-1793] pg/mL, p = 0.046).

Conclusions

Overall obesity was associated with improved survival in septic shock and differences in pattern of infection, fluids, and vasopressors. Importantly, the magnitude of inflammatory IL-6 response is muted in the obese.
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Literature
1.
go back to reference Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ, Comparative Risk Assessment Collaborating Group: Selected major risk factors and global and regional burden of disease. Lancet 2002, 360: 1347-1360. 10.1016/S0140-6736(02)11403-6CrossRefPubMed Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ, Comparative Risk Assessment Collaborating Group: Selected major risk factors and global and regional burden of disease. Lancet 2002, 360: 1347-1360. 10.1016/S0140-6736(02)11403-6CrossRefPubMed
2.
go back to reference Huttunen R, Syrjanen J: Obesity and the outcome of infection. Lancet Infect Dis 2010, 10: 442-443. 10.1016/S1473-3099(10)70103-1CrossRefPubMed Huttunen R, Syrjanen J: Obesity and the outcome of infection. Lancet Infect Dis 2010, 10: 442-443. 10.1016/S1473-3099(10)70103-1CrossRefPubMed
3.
go back to reference Milner JJ, Beck MA: The impact of obesity on the immune response to infection. Proc Nutr Soc 2012, 71: 298-306. 10.1017/S0029665112000158CrossRefPubMed Milner JJ, Beck MA: The impact of obesity on the immune response to infection. Proc Nutr Soc 2012, 71: 298-306. 10.1017/S0029665112000158CrossRefPubMed
4.
go back to reference Huttunen R, Syrjanen J: Obesity and the risk and outcome of infection. Int J Obes (Lond) 2013, 37: 333-340. 10.1038/ijo.2012.62CrossRef Huttunen R, Syrjanen J: Obesity and the risk and outcome of infection. Int J Obes (Lond) 2013, 37: 333-340. 10.1038/ijo.2012.62CrossRef
5.
go back to reference Harrington G, Russo P, Spelman D, Borrell S, Watson K, Barr W, Martin R, Edmonds D, Cocks J, Greenbough J, Lowe J, Randle L, Castell J, Browne E, Bellis K, Aberline M: Surgical-site infection rates and risk factor analysis in coronary artery bypass graft surgery. Infect Control Hosp Epidemiol 2004, 25: 472-476. 10.1086/502424CrossRefPubMed Harrington G, Russo P, Spelman D, Borrell S, Watson K, Barr W, Martin R, Edmonds D, Cocks J, Greenbough J, Lowe J, Randle L, Castell J, Browne E, Bellis K, Aberline M: Surgical-site infection rates and risk factor analysis in coronary artery bypass graft surgery. Infect Control Hosp Epidemiol 2004, 25: 472-476. 10.1086/502424CrossRefPubMed
6.
go back to reference Wisse BE: The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004, 15: 2792-2800. 10.1097/01.ASN.0000141966.69934.21CrossRefPubMed Wisse BE: The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004, 15: 2792-2800. 10.1097/01.ASN.0000141966.69934.21CrossRefPubMed
7.
go back to reference Benson S, Arck PC, Tan S, Mann K, Hahn S, Janssen OE, Schedlowski M, Elsenbruch S: Effects of obesity on neuroendocrine, cardiovascular, and immune cell responses to acute psychosocial stress in premenopausal women. Psychoneuroendocrinology 2009, 34: 181-189. 10.1016/j.psyneuen.2008.08.019CrossRefPubMed Benson S, Arck PC, Tan S, Mann K, Hahn S, Janssen OE, Schedlowski M, Elsenbruch S: Effects of obesity on neuroendocrine, cardiovascular, and immune cell responses to acute psychosocial stress in premenopausal women. Psychoneuroendocrinology 2009, 34: 181-189. 10.1016/j.psyneuen.2008.08.019CrossRefPubMed
8.
go back to reference Habbu A, Lakkis NM, Dokainish H: The obesity paradox: Fact or fiction? Am J Cardiol 2006, 98: 944-948. 10.1016/j.amjcard.2006.04.039CrossRefPubMed Habbu A, Lakkis NM, Dokainish H: The obesity paradox: Fact or fiction? Am J Cardiol 2006, 98: 944-948. 10.1016/j.amjcard.2006.04.039CrossRefPubMed
9.
go back to reference Kalantar-Zadeh K, Horwich TB, Oreopoulos A, Kovesdy CP, Younessi H, Anker SD, Morley JE: Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 2007, 10: 433-442. 10.1097/MCO.0b013e3281a30594CrossRefPubMed Kalantar-Zadeh K, Horwich TB, Oreopoulos A, Kovesdy CP, Younessi H, Anker SD, Morley JE: Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 2007, 10: 433-442. 10.1097/MCO.0b013e3281a30594CrossRefPubMed
10.
go back to reference Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M, ADHERE Scientific Advisory Committee and Investigators: An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Herat Failure National Registry. Am Heart J 2007, 153: 74-81.CrossRefPubMed Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M, ADHERE Scientific Advisory Committee and Investigators: An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Herat Failure National Registry. Am Heart J 2007, 153: 74-81.CrossRefPubMed
11.
go back to reference 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. 10.1097/01.CCM.0000297885.60037.6ECrossRefPubMed 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. 10.1097/01.CCM.0000297885.60037.6ECrossRefPubMed
12.
go back to reference Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneil JJ, Ayers D, VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008, 358: 877-887. 10.1056/NEJMoa067373CrossRefPubMed Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneil JJ, Ayers D, VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008, 358: 877-887. 10.1056/NEJMoa067373CrossRefPubMed
13.
go back to reference Roytblat L, Rachinsky M, Fisher A, Greemberg L, Shapira Y, Douvdevani A, Gelman S: Raised interleukin-6 levels in obese patients. Obese Res 2000, 8: 673-675. 10.1038/oby.2000.86CrossRef Roytblat L, Rachinsky M, Fisher A, Greemberg L, Shapira Y, Douvdevani A, Gelman S: Raised interleukin-6 levels in obese patients. Obese Res 2000, 8: 673-675. 10.1038/oby.2000.86CrossRef
14.
go back to reference Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD: Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001, 175: 81-92. 10.1016/S0303-7207(01)00394-XCrossRefPubMed Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD: Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001, 175: 81-92. 10.1016/S0303-7207(01)00394-XCrossRefPubMed
15.
go back to reference Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM: Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995, 95: 2409-2415. 10.1172/JCI117936PubMedCentralCrossRefPubMed Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM: Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995, 95: 2409-2415. 10.1172/JCI117936PubMedCentralCrossRefPubMed
16.
go back to reference Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001, 409: 307-312. 10.1038/35053000CrossRefPubMed Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001, 409: 307-312. 10.1038/35053000CrossRefPubMed
17.
go back to reference American College of Chest Physicians/Society of Critical care medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Crit Care Med 1992, 20: 864-874. 10.1097/00003246-199206000-00025 American College of Chest Physicians/Society of Critical care medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Crit Care Med 1992, 20: 864-874. 10.1097/00003246-199206000-00025
18.
go back to reference Sibbald WJ, Vincent JL: Roundtable conference on clinical trials for the treatment of sepsis. Brussels, march 12-14, 1994. Chest 1995, 107: 522-527. 10.1378/chest.107.2.522CrossRefPubMed Sibbald WJ, Vincent JL: Roundtable conference on clinical trials for the treatment of sepsis. Brussels, march 12-14, 1994. Chest 1995, 107: 522-527. 10.1378/chest.107.2.522CrossRefPubMed
20.
go back to reference Sutherland AM, Walley KR, Manocha S, Russell JA: The association of interleukin 6 haplotype clades with mortality in critically ill adults. Arch Intern Med 2005, 165: 75-82. 10.1001/archinte.165.1.75CrossRefPubMed Sutherland AM, Walley KR, Manocha S, Russell JA: The association of interleukin 6 haplotype clades with mortality in critically ill adults. Arch Intern Med 2005, 165: 75-82. 10.1001/archinte.165.1.75CrossRefPubMed
21.
go back to reference National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, 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.CrossRef National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, 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.CrossRef
22.
go back to reference Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA: Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011, 39: 259-265. 10.1097/CCM.0b013e3181feeb15CrossRefPubMed Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA: Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011, 39: 259-265. 10.1097/CCM.0b013e3181feeb15CrossRefPubMed
23.
go back to reference Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308.
24.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent J-L, Moreno R, and the Surviving Sepsis Campaign Guidelines Committee including the Pediatric subgroup: Surviving sepsis campaign: international guidelines for the management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83afCrossRefPubMed Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent J-L, Moreno R, and the Surviving Sepsis Campaign Guidelines Committee including the Pediatric subgroup: Surviving sepsis campaign: international guidelines for the management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83afCrossRefPubMed
25.
go back to reference Miller JT, Welage LS, Kraft MD, Alaniz C: Does body weight impact the efficacy of vasopressin therapy in the management of septic shock? J Crit Care 2012, 27: 289-293. 10.1016/j.jcrc.2011.06.018CrossRefPubMed Miller JT, Welage LS, Kraft MD, Alaniz C: Does body weight impact the efficacy of vasopressin therapy in the management of septic shock? J Crit Care 2012, 27: 289-293. 10.1016/j.jcrc.2011.06.018CrossRefPubMed
26.
go back to reference Abhyankar S, Leishear K, Callaghan FM, Demner-Fushman D, McDonald CJ: Lower short- and long-term mortality associated with overweight and obesity in a large cohort study of adult intensive care unit patients. Crit Care 2012, 16: R235. 10.1186/cc11903PubMedCentralCrossRefPubMed Abhyankar S, Leishear K, Callaghan FM, Demner-Fushman D, McDonald CJ: Lower short- and long-term mortality associated with overweight and obesity in a large cohort study of adult intensive care unit patients. Crit Care 2012, 16: R235. 10.1186/cc11903PubMedCentralCrossRefPubMed
27.
go back to reference Winfield RD, Delano MJ, Cuenca AG, Cendan JC, Lottenberg L, Efron PA, Maier RV, Remick DG, Moldawer LL, Cuschieri J: Obese patients show a depressed cytokine profile following severe blunt injury. Shock 2012, 37: 253-256. 10.1097/SHK.0b013e3182449c0ePubMedCentralCrossRefPubMed Winfield RD, Delano MJ, Cuenca AG, Cendan JC, Lottenberg L, Efron PA, Maier RV, Remick DG, Moldawer LL, Cuschieri J: Obese patients show a depressed cytokine profile following severe blunt injury. Shock 2012, 37: 253-256. 10.1097/SHK.0b013e3182449c0ePubMedCentralCrossRefPubMed
28.
go back to reference Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ: Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med 2007, 35: 1536-1542. 10.1097/01.CCM.0000266536.14736.03CrossRefPubMed Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ: Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med 2007, 35: 1536-1542. 10.1097/01.CCM.0000266536.14736.03CrossRefPubMed
29.
go back to reference Gibson JG, Evans WA: Clinical studies of blood volume. I. Clinical application of a method employing the azo dye 'evans blue' and the spectrophotometer. J Clin Invest 1937, 16: 301-316. 10.1172/JCI100859PubMedCentralCrossRefPubMed Gibson JG, Evans WA: Clinical studies of blood volume. I. Clinical application of a method employing the azo dye 'evans blue' and the spectrophotometer. J Clin Invest 1937, 16: 301-316. 10.1172/JCI100859PubMedCentralCrossRefPubMed
30.
go back to reference Gregersen MI, Nickerson JL: Relation of blood volume and cardiac output to body type. J Appl Physiol 1950, 3: 329-341.PubMed Gregersen MI, Nickerson JL: Relation of blood volume and cardiac output to body type. J Appl Physiol 1950, 3: 329-341.PubMed
Metadata
Title
One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response
Authors
Petch Wacharasint
John H Boyd
James A Russell
Keith R Walley
Publication date
01-06-2013
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2013
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc12794

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