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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

Risk factors, host response and outcome of hypothermic sepsis

Authors: Maryse A. Wiewel, Matthew B. Harmon, Lonneke A. van Vught, Brendon P. Scicluna, Arie J. Hoogendijk, Janneke Horn, Aeilko H. Zwinderman, Olaf L. Cremer, Marc J. Bonten, Marcus J. Schultz, Tom van der Poll, Nicole P. Juffermans, W. Joost Wiersinga

Published in: Critical Care | Issue 1/2016

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Abstract

Background

Hypothermia is associated with adverse outcome in patients with sepsis. The objective of this study was to characterize the host immune response in patients with hypothermic sepsis in order to determine if an excessive anti-inflammatory response could explain immunosuppression and adverse outcome. Markers of endothelial activation and integrity were also measured to explore potential alternative mechanisms of hypothermia. Finally we studied risk factors for hypothermia in an attempt to find new clues to the etiology of hypothermia in sepsis.

Methods

Consecutive patients diagnosed with sepsis within 24 hours after admission to ICUs in two tertiary hospitals in the Netherlands were included in the study (n = 525). Hypothermia was defined as body temperature below 36 °C in the first 24 h of ICU admission.

Results

Hypothermia was identified in 186 patients and was independently associated with mortality. Levels of proinflammatory and anti-inflammatory cytokines were not different between groups. Hypothermia was also not associated with an altered response to ex vivo stimulation with lipopolysaccharide in a subset of 15 patients. Risk factors for hypothermia included low body mass index, hypertension and chronic cardiovascular insufficiency. Levels of the endothelial activation marker fractalkine were increased during the first 4 days of ICU stay.

Conclusions

Hypothermia during sepsis is independently associated with mortality, which cannot be attributed to alterations in the host immune responses that were measured in this study. Given that risk factors for hypothermic sepsis are mainly cardiovascular and that the endothelial activation marker fractalkine increased in hypothermia, these findings may suggest that vascular dysfunction plays a role in hypothermic sepsis.
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Literature
1.
2.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29(4):530–8.CrossRefPubMed
3.
Clemmer TP, Fisher Jr CJ, Bone RC, Slotman GJ, Metz CA, Thomas FO. Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 1992;20(10):1395–401.CrossRefPubMed
4.
Kushimoto S, Gando S, Saitoh D, Mayumi T, Ogura H, Fujishima S, Araki T, Ikeda H, Kotani J, Miki Y, et al. The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis. Crit Care. 2013;17(6):R271.CrossRefPubMedPubMedCentral
5.
Marik PE, Zaloga GP. Hypothermia and cytokines in septic shock. Norasept II Study Investigators. North American study of the safety and efficacy of murine monoclonal antibody to tumor necrosis factor for the treatment of septic shock. Intensive Care Med. 2000;26(6):716–21.CrossRefPubMed
6.
Arons MM, Wheeler AP, Bernard GR, Christman BW, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson W, Wright P, et al. Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med. 1999;27(4):699–707.CrossRefPubMed
7.
Pajkrt D, Camoglio L, Tiel-van Buul MC, de Bruin K, Cutler DL, Affrime MB, Rikken G, van der Poll T, ten Cate JW, van Deventer SJ. Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration. J Immunol. 1997;158(8):3971–7.PubMed
8.
Leon LR, Kozak W, Rudolph K, Kluger MJ. An antipyretic role for interleukin-10 in LPS fever in mice. Am J Physiol. 1999;276(1 Pt 2):R81–9.PubMed
9.
10.
Drewry AM, Fuller BM, Skrupky LP, Hotchkiss RS. The presence of hypothermia within 24 hours of sepsis diagnosis predicts persistent lymphopenia. Crit Care Med. 2015.
11.
12.
Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T. Endotoxin shock: thermoregulatory mechanisms. Am J Physiol. 1996;270(4 Pt 2):R693–703.PubMed
13.
Scicluna BP, Klein Klouwenberg PM, van Vught LA, Wiewel MA, Ong DS, Zwinderman AH, Franitza M, Toliat MR, Nurnberg P, Hoogendijk AJ, et al. A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission. Am J Respir Crit Care Med. 2015;192(7):826–35.CrossRefPubMed
14.
Klein Klouwenberg PM, Ong DS, Bos LD, de Beer FM, van Hooijdonk RT, Huson MA, Straat M, van Vught LA, Wieske L, Horn J, et al. Interobserver agreement of Centers for Disease Control and Prevention criteria for classifying infections in critically ill patients. Crit Care Med. 2013;41(10):2373–8.CrossRefPubMed
15.
Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16(3):128–40.CrossRefPubMed
16.
Calandra T, Cohen J. International Sepsis Forum definition of infection in the ICUCC. The International Sepsis Forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med. 2005;33(7):1538–48.CrossRefPubMed
17.
Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526–33.
18.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204–12.CrossRefPubMedPubMedCentral
19.
Peres Bota D, Lopes Ferreira F, Melot C, Vincent JL. Body temperature alterations in the critically ill. Intensive Care Med. 2004;30(5):811–6.CrossRefPubMed
20.
van Vught LA, Wiewel MA, Hoogendijk AJ, Scicluna BP, Belkasim-Bohoudi H, Horn J, Schultz MJ, van der Poll T. Reduced responsiveness of blood leukocytes to lipopolysaccharide does not predict nosocomial infections in critically ill patients. Shock. 2015;44(2):110–4.CrossRefPubMed
21.
Tiruvoipati R, Ong K, Gangopadhyay H, Arora S, Carney I, Botha J. Hypothermia predicts mortality in critically ill elderly patients with sepsis. BMC Geriatr. 2010;10:70.CrossRefPubMedPubMedCentral
22.
Wiersinga WJ, van't Veer C, van den Pangaart PS, Dondorp AM, Day NP, Peacock SJ, van der Poll T. Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation predicts mortality in Gram-negative sepsis (melioidosis). Crit Care Med. 2009;37(2):569–76.CrossRefPubMed
23.
Laupland KB, Zahar JR, Adrie C, Minet C, Vesin A, Goldgran-Toledano D, Azoulay E, Garrouste-Orgeas M, Cohen Y, Schwebel C, et al. Severe hypothermia increases the risk for intensive care unit-acquired infection. Clin Infect Dis. 2012;54(8):1064–70.CrossRefPubMed
24.
Nerad JL, Griffiths JK, Van der Meer JW, Endres S, Poutsiaka DD, Keusch GT, Bennish M, Salam MA, Dinarello CA, Cannon JG. Interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist, and TNF alpha production in whole blood. J Leukoc Biol. 1992;52(6):687–92.PubMed
25.
Sakr Y, Alhussami I, Nanchal R, Wunderink RG, Pellis T, Wittebole X, Martin-Loeches I, Francois B, Leone M, Vincent JL, et al. being overweight is associated with greater survival in ICU patients: results from the Intensive Care Over Nations Audit. Crit Care Med. 2015;43(12):2623–32.CrossRefPubMed
26.
Steiner AA, Romanovsky AA. Leptin: at the crossroads of energy balance and systemic inflammation. Prog Lipid Res. 2007;46(2):89–107.CrossRefPubMed
27.
28.
Hoogendijk AJ, Wiewel MA, van Vught LA, Scicluna BP, Belkasim-Bohoudi H, Horn J, Zwinderman AH, Klein Klouwenberg PM, Cremer OL, Bonten MJ, et al. Plasma fractalkine is a sustained marker of disease severity and outcome in sepsis patients. Crit Care. 2015;19(1):412.CrossRefPubMedPubMedCentral
29.
Sung MJ, Kim W, Ahn SY, Cho CH, Koh GY, Moon SO, Kim DH, Lee S, Kang KP, Jang KY, et al. Protective effect of alpha-lipoic acid in lipopolysaccharide-induced endothelial fractalkine expression. Circ Res. 2005;97(9):880–90.CrossRefPubMed
Metadata
Title
Risk factors, host response and outcome of hypothermic sepsis
Authors
Maryse A. Wiewel
Matthew B. Harmon
Lonneke A. van Vught
Brendon P. Scicluna
Arie J. Hoogendijk
Janneke Horn
Aeilko H. Zwinderman
Olaf L. Cremer
Marc J. Bonten
Marcus J. Schultz
Tom van der Poll
Nicole P. Juffermans
W. Joost Wiersinga
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1510-3

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