Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Protracted immune disorders at one year after ICU discharge in patients with septic shock

Authors: Florence Riché, Benjamin G. Chousterman, Patrice Valleur, Alexandre Mebazaa, Jean-Marie Launay, Etienne Gayat

Published in: Critical Care | Issue 1/2018

Login to get access

Abstract

Background

Sepsis is a leading cause of mortality and critical illness worldwide and is associated with an increased mortality rate in the months following hospital discharge. The occurrence of persistent or new organ dysfunction(s) after septic shock raises questions about the mechanisms involved in the post-sepsis status. The present study aimed to explore the immune profiles of patients one year after being discharged from the intensive care unit (ICU) following treatment for abdominal septic shock.

Methods

We conducted a prospective, single-center, observational study in the surgical ICU of a university hospital. Eighty-six consecutive patients admitted for septic shock of abdominal origin were included in this study. Fifteen different plasma biomarkers were measured at ICU admission, at ICU discharge and at one year after ICU discharge. Three different clusters of biomarkers were distinguished according to their functions, namely: (1) inflammatory response, (2) cell damage and apoptosis, (3) immunosuppression and resolution of inflammation. The primary objective was to characterize variations in the immune status of septic shock patients admitted to ICU up to one year after ICU discharge. The secondary objective was to evaluate the relationship between these biomarker variations and patient outcomes.

Results

At the onset of septic shock, we observed a cohesive pro-inflammatory profile and low levels of inflammation resolution markers. At ICU discharge, the immune status demonstrated decreased but persistent inflammation and increased immunosuppression, with elevated programmed cell death protein-1 (PD-1) levels, and a counterbalanced resolution process, with elevated levels of interleukin-10 (IL-10), resolvin D5 (RvD5), and IL-7. One year after hospital discharge, homeostasis was not completely restored with several markers of inflammation remaining elevated. Remarkably, IL-7 was persistently elevated, with levels comparable to those observed after ICU discharge, and PD-1, while lower, remained in the elevated abnormal range.

Conclusions

In this study, protracted immune disturbances were observed one year after ICU discharge. The study results suggested the presence of long-lasting immune illness disorders following a long-term septic insult, indicating the need for long-term patient follow up after ICU discharge and questioning the use of immune intervention to restore immune homeostasis after abdominal septic shock.
Appendix
Available only for authorised users
Literature
1.
2.
Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, Osborn T, Lemeshow S, Chiche JD, Artigas A, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43(1):3–12.CrossRefPubMed
3.
Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J, Reinhart K, Antonelli M, Pickkers P, Njimi H, et al. Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. Lancet Respir Med. 2014;2(5):380–6.CrossRefPubMed
4.
Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE. Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med. 2010;38(5):1276–83.CrossRefPubMed
5.
Laupland KB, Zygun DA, Doig CJ, Bagshaw SM, Svenson LW, Fick GH. One-year mortality of bloodstream infection-associated sepsis and septic shock among patients presenting to a regional critical care system. Intensive Care Med. 2005;31(2):213–9.CrossRefPubMed
6.
Yende S, Linde-Zwirble W, Mayr F, Weissfeld LA, Reis S, Angus DC. Risk of cardiovascular events in survivors of severe sepsis. Am J Respir Crit Care Med. 2014;189(9):1065–74.CrossRefPubMedPubMedCentral
7.
Wang HE, Moore JX, Donnelly JP, Levitan EB, Safford MM. Risk of acute coronary heart disease after sepsis hospitalization in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort. Clin Infect Dis. 2017;65(1):29–36.CrossRefPubMed
8.
Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611–8.CrossRefPubMed
9.
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683–93.CrossRefPubMed
10.
Morgera S, Schneider M, Neumayer HH. Long-term outcomes after acute kidney injury. Crit Care Med. 2008;36(4 Suppl):S193–7.CrossRefPubMed
11.
Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787–94.CrossRefPubMedPubMedCentral
12.
Yende S, D'Angelo G, Kellum JA, Weissfeld L, Fine J, Welch RD, Kong L, Carter M, Angus DC, Gen IMSI. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008;177(11):1242–7.CrossRefPubMedPubMedCentral
13.
Rydingsward JE, Horkan CM, Mogensen KM, Quraishi SA, Amrein K, Christopher KB. Functional status in ICU survivors and out of hospital outcomes: a cohort study. Crit Care Med. 2016;44(5):869–79.CrossRefPubMedPubMedCentral
14.
Kale S, Yende S, Kong L, Perkins A, Kellum JA, Newman AB, Vallejo AN, Angus DC, Gen IMSI. The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia. PLoS One. 2010;5(11):e13852.CrossRefPubMedPubMedCentral
15.
Reade MC, Yende S, D'Angelo G, Kong L, Kellum JA, Barnato AE, Milbrandt EB, Dooley C, Mayr FB, Weissfeld L, et al. Differences in immune response may explain lower survival among older men with pneumonia. Crit Care Med. 2009;37(5):1655–62.CrossRefPubMedPubMedCentral
16.
Yende S, Alvarez K, Loehr L, Folsom AR, Newman AB, Weissfeld LA, Wunderink RG, Kritchevsky SB, Mukamal KJ, London SJ, et al. Epidemiology and long-term clinical and biologic risk factors for pneumonia in community-dwelling older Americans: analysis of three cohorts. Chest. 2013;144(3):1008–17.CrossRefPubMedPubMedCentral
17.
Condotta SA, Rai D, James BR, Griffith TS, Badovinac VP. Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection. J Immunol. 2013;190(5):1991–2000.CrossRefPubMedPubMedCentral
18.
Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol. 2003;81(4):247–65.CrossRefPubMed
19.
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
20.
Riche F, Gayat E, Barthelemy R, Le Dorze M, Mateo J, Payen D. Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock. Crit Care. 2015;19:439.CrossRefPubMedPubMedCentral
21.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMed
22.
Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957–63.CrossRefPubMed
23.
Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23(10):1638–52.CrossRefPubMed
24.
Kema IP, Schellings AM, Hoppenbrouwers CJ, Rutgers HM, de Vries EG, Muskiet FA. High performance liquid chromatographic profiling of tryptophan and related indoles in body fluids and tissues of carcinoid patients. Clin Chim Acta. 1993;221(1-2):143–58.CrossRefPubMed
25.
Fujigaki S, Saito K, Takemura M, Fujii H, Wada H, Noma A, Seishima M. Species differences in L-tryptophan-kynurenine pathway metabolism: quantification of anthranilic acid and its related enzymes. Arch Biochem Biophys. 1998;358(2):329–35.CrossRefPubMed
26.
Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol. 2014;307(1):C39–54.CrossRefPubMedPubMedCentral
27.
Hotchkiss RS, Moldawer LL. Parallels between cancer and infectious disease. N Engl J Med. 2014;371(4):380–3.CrossRefPubMed
28.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95.CrossRefPubMed
29.
Pellegrin K, Neurauter G, Wirleitner B, Fleming AW, Peterson VM, Fuchs D. Enhanced enzymatic degradation of tryptophan by indoleamine 2,3-dioxygenase contributes to the tryptophan-deficient state seen after major trauma. Shock. 2005;23(3):209–15.PubMed
30.
Mbongue JC, Nicholas DA, Torrez TW, Kim NS, Firek AF, Langridge WH. The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines (Basel). 2015;3(3):703–29.CrossRef
31.
Logters TT, Laryea MD, Altrichter J, Sokolowski J, Cinatl J, Reipen J, Linhart W, Windolf J, Scholz M, Wild M. Increased plasma kynurenine values and kynurenine-tryptophan ratios after major trauma are early indicators for the development of sepsis. Shock. 2009;32(1):29–34.CrossRefPubMed
32.
Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR, et al. Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat Med. 2010;16(3):279–85.CrossRefPubMedPubMedCentral
33.
Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012;72(21):5435–40.CrossRefPubMed
34.
Murr C, Grammer TB, Kleber ME, Meinitzer A, Marz W, Fuchs D. Low serum tryptophan predicts higher mortality in cardiovascular disease. Eur J Clin Invest. 2015;45(3):247–54.CrossRefPubMed
35.
36.
Mickiewicz B, Tam P, Jenne CN, Leger C, Wong J, Winston BW, Doig C, Kubes P, Vogel HJ, Alberta Sepsis N. Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit. Crit Care. 2015;19:11.CrossRefPubMedPubMedCentral
37.
Mickiewicz B, Duggan GE, Winston BW, Doig C, Kubes P, Vogel HJ, Alberta Sepsis N. Metabolic profiling of serum samples by 1H nuclear magnetic resonance spectroscopy as a potential diagnostic approach for septic shock. Crit Care Med. 2014;42(5):1140–9.CrossRefPubMed
38.
39.
Ruan S, Samuelson DR, Assouline B, Morre M, Shellito JE. Treatment with interleukin-7 restores host defense against pneumocystis in CD4+ T-lymphocyte-depleted mice. Infect Immun. 2015;84(1):108–19.CrossRefPubMedPubMedCentral
Metadata
Title
Protracted immune disorders at one year after ICU discharge in patients with septic shock
Authors
Florence Riché
Benjamin G. Chousterman
Patrice Valleur
Alexandre Mebazaa
Jean-Marie Launay
Etienne Gayat
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1934-4

Other articles of this Issue 1/2018

Critical Care 1/2018 Go to the issue

Research

Intravenous ivabradine versus placebo in patients with low cardiac output syndrome treated by dobutamine after elective coronary artery bypass surgery: a phase 2 exploratory randomized controlled trial

Research

In vivo quantification of rolling and adhered leukocytes in human sepsis

Letter

Loop diuretic use in patients with AKI: different severity, different response

Letter

Clinical benefit of high-volume hemofiltration in severe burn injury: is it removing bad humors or actually avoiding hypervolemia?

Research

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Letter

A brief comment on the predictive value of myeloperoxidase-conjugated DNA level in patients with septic shock