Skip to main content
Top
Published in: Current Infectious Disease Reports 11/2016

Open Access 01-11-2016 | Sepsis and ICU (JL Vincent, Section Editor)

Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges

Authors: Manu Shankar-Hari, Gordon D. Rubenfeld

Published in: Current Infectious Disease Reports | Issue 11/2016

Login to get access

Abstract

Sepsis is life-threating organ dysfunction due to infection. Incidence of sepsis is increasing and the short-term mortality is improving, generating more sepsis survivors. These sepsis survivors suffer from additional morbidities such as higher risk of readmissions, cardiovascular disease, cognitive impairment and of death, for years following index sepsis episode. In the first year following index sepsis episode, approximately 60 % of sepsis survivors have at least one rehospitalisation episode, which is most often due to infection and one in six sepsis survivors die. Sepsis survivors also have a higher risk of cognitive impairment and cardiovascular disease contributing to the reduced life expectancy seen in this population, when assessed with life table comparisons. For optimal design of interventional trials to reduce these bad outcomes in sepsis survivors, in-depth understanding of major risk factors for these morbid events, their modifiability and a causal relationship to the pathobiology of sepsis is essential. This review highlights the recent advances, clinical and methodological challenges in our understanding of these morbid events in sepsis survivors.
Literature
3.
go back to reference Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis - Current Estimates and Limitations. Am J Respir Crit Care Med. 2015. doi:10.1164/rccm.201504-0781OC. Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis - Current Estimates and Limitations. Am J Respir Crit Care Med. 2015. doi:10.​1164/​rccm.​201504-0781OC.
4.
go back to reference Churpek MM, Zadravecz FJ, Winslow C, Howell M, Edelson DP. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients. Am J Respir Crit Care Med. 2015. doi:10.1164/rccm.201502-0275OC. Churpek MM, Zadravecz FJ, Winslow C, Howell M, Edelson DP. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients. Am J Respir Crit Care Med. 2015. doi:10.​1164/​rccm.​201502-0275OC.
6.
go back to reference Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311(13):1308–16. doi:10.1001/jama.2014.2637.PubMedCrossRef Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311(13):1308–16. doi:10.​1001/​jama.​2014.​2637.PubMedCrossRef
11.
12.
go back to reference 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(7):1303–10.PubMedCrossRef 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(7):1303–10.PubMedCrossRef
18.
go back to reference Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016. doi:10.1016/s2213-2600(16)00046-1. Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016. doi:10.​1016/​s2213-2600(16)00046-1.
25.••
go back to reference Shankar-Hari M, Ambler M, Mahalingasivam V, Jones A, Rowan K, Rubenfeld G. Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies. Critical Care. 2016;20(1):101. This systematic review challenges the causal relationship between sepsis and long-term mortality. Highlights methodological issues in the literatures.PubMedPubMedCentralCrossRef Shankar-Hari M, Ambler M, Mahalingasivam V, Jones A, Rowan K, Rubenfeld G. Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies. Critical Care. 2016;20(1):101. This systematic review challenges the causal relationship between sepsis and long-term mortality. Highlights methodological issues in the literatures.PubMedPubMedCentralCrossRef
26.••
go back to reference 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. doi:10.1164/rccm.201307-1321OC. Landmark paper on cadiovascular events in sepsis survivors and value of control arms in determining attributable risk to sepsis.PubMedPubMedCentralCrossRef 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. doi:10.​1164/​rccm.​201307-1321OC. Landmark paper on cadiovascular events in sepsis survivors and value of control arms in determining attributable risk to sepsis.PubMedPubMedCentralCrossRef
28.
go back to reference Zhang JX, Iwashyna TJ, Christakis NA. The performance of different lookback periods and sources of information for charlson comorbidity adjustment in Medicare claims. Med Care. 1999;37(11):1128–39.PubMedCrossRef Zhang JX, Iwashyna TJ, Christakis NA. The performance of different lookback periods and sources of information for charlson comorbidity adjustment in Medicare claims. Med Care. 1999;37(11):1128–39.PubMedCrossRef
30.
go back to reference Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11(5):550–60.PubMedCrossRef Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11(5):550–60.PubMedCrossRef
32.•
go back to reference Prescott HC, Osterholzer JJ, Langa KM, Angus DC, Iwashyna TJ. Late mortality after sepsis: propensity matched cohort study. BMJ. 2016;353. doi:10.1136/bmj.i2375. Highlights post-acute mortality in sepsis survivors using novel statistical methods. Prescott HC, Osterholzer JJ, Langa KM, Angus DC, Iwashyna TJ. Late mortality after sepsis: propensity matched cohort study. BMJ. 2016;353. doi:10.​1136/​bmj.​i2375. Highlights post-acute mortality in sepsis survivors using novel statistical methods.
33.•
go back to reference Ou SM, Chu H, Chao PW, Lee YJ, Kuo SC, Chen TJ, et al. Long-term mortality and major adverse cardiovascular events in sepsis survivors. A nationwide population-based study. Am J Respir Crit Care Med. 2016;194(2):209–17. doi:10.1164/rccm.201510-2023OC. Highlights post acute mortality in sepsis survivors.PubMedCrossRef Ou SM, Chu H, Chao PW, Lee YJ, Kuo SC, Chen TJ, et al. Long-term mortality and major adverse cardiovascular events in sepsis survivors. A nationwide population-based study. Am J Respir Crit Care Med. 2016;194(2):209–17. doi:10.​1164/​rccm.​201510-2023OC. Highlights post acute mortality in sepsis survivors.PubMedCrossRef
35.
go back to reference Linder A, Guh D, Boyd JH, Walley KR, Anis AH, Russell JA. Long-term (10-year) mortality of younger previously healthy patients with severe sepsis/septic shock is worse than that of patients with nonseptic critical illness and of the general population. Crit Care Med. 2014;42(10):2211–8. doi:10.1097/CCM.0000000000000503.PubMedCrossRef Linder A, Guh D, Boyd JH, Walley KR, Anis AH, Russell JA. Long-term (10-year) mortality of younger previously healthy patients with severe sepsis/septic shock is worse than that of patients with nonseptic critical illness and of the general population. Crit Care Med. 2014;42(10):2211–8. doi:10.​1097/​CCM.​0000000000000503​.PubMedCrossRef
43.
go back to reference Zilberberg MD, Shorr AF, Micek ST, Kollef MH. Risk factors for 30-day readmission among patients with culture-positive severe sepsis and septic shock: a retrospective cohort study. J Hosp Med. 2015;10(10):678–85. doi:10.1002/jhm.2420.PubMedCrossRef Zilberberg MD, Shorr AF, Micek ST, Kollef MH. Risk factors for 30-day readmission among patients with culture-positive severe sepsis and septic shock: a retrospective cohort study. J Hosp Med. 2015;10(10):678–85. doi:10.​1002/​jhm.​2420.PubMedCrossRef
44.
go back to reference Borzecki AM, Chen Q, Restuccia J, Mull HJ, Shwartz M, Gupta K et al. Do pneumonia readmissions flagged as potentially preventable by the 3M PPR software have more process of care problems? A cross-sectional observational study. BMJ Qual Saf. 2015. doi:10.1136/bmjqs-2014-003911. Borzecki AM, Chen Q, Restuccia J, Mull HJ, Shwartz M, Gupta K et al. Do pneumonia readmissions flagged as potentially preventable by the 3M PPR software have more process of care problems? A cross-sectional observational study. BMJ Qual Saf. 2015. doi:10.​1136/​bmjqs-2014-003911.
45.••
go back to reference Krumholz HM, Lin Z, Keenan PS, Chen J, Ross JS, Drye EE, et al. Relationship between hospital readmission and mortality rates for patients hospitalized with acute myocardial infarction, heart failure, or pneumonia. JAMA. 2013;309(6):587–93. doi:10.1001/jama.2013.333. Landmark paper on readmissions literature.PubMedPubMedCentralCrossRef Krumholz HM, Lin Z, Keenan PS, Chen J, Ross JS, Drye EE, et al. Relationship between hospital readmission and mortality rates for patients hospitalized with acute myocardial infarction, heart failure, or pneumonia. JAMA. 2013;309(6):587–93. doi:10.​1001/​jama.​2013.​333. Landmark paper on readmissions literature.PubMedPubMedCentralCrossRef
50.••
go back to reference Shah FA, Pike F, Alvarez K, Angus D, Newman AB, Lopez O, et al. Bidirectional relationship between cognitive function and pneumonia. Am J Respir Crit Care Med. 2013;188(5):586–92. doi:10.1164/rccm.201212-2154OC. Important paper that addresses challenges with pre-illness cognitive decline and pneumonia.PubMedPubMedCentralCrossRef Shah FA, Pike F, Alvarez K, Angus D, Newman AB, Lopez O, et al. Bidirectional relationship between cognitive function and pneumonia. Am J Respir Crit Care Med. 2013;188(5):586–92. doi:10.​1164/​rccm.​201212-2154OC. Important paper that addresses challenges with pre-illness cognitive decline and pneumonia.PubMedPubMedCentralCrossRef
52.
go back to reference Davydow DS, Hough CL, Langa KM, Iwashyna TJ. Symptoms of depression in survivors of severe sepsis: a prospective cohort study of older Americans. Am J Geriatr Psychiatry. 2013;21(9):887-97. doi:10.1016/j.jagp.2013.01.017. 10.1097/JGP.0b013e31825c0aed. Davydow DS, Hough CL, Langa KM, Iwashyna TJ. Symptoms of depression in survivors of severe sepsis: a prospective cohort study of older Americans. Am J Geriatr Psychiatry. 2013;21(9):887-97. doi:10.1016/j.jagp.2013.01.017. 10.1097/JGP.0b013e31825c0aed.
53.•
go back to reference Klein Klouwenberg PM, Zaal IJ, Spitoni C, Ong DS, van der Kooi AW, Bonten MJ, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652. doi:10.1136/bmj.g6652. Conceptual paper exploring acute delerium and attributable mortality.PubMedPubMedCentralCrossRef Klein Klouwenberg PM, Zaal IJ, Spitoni C, Ong DS, van der Kooi AW, Bonten MJ, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652. doi:10.​1136/​bmj.​g6652. Conceptual paper exploring acute delerium and attributable mortality.PubMedPubMedCentralCrossRef
54.
go back to reference Wolters AE, van Dijk D, Pasma W, Cremer OL, Looije MF, de Lange DW, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care. 2014;18(3):R125. doi:10.1186/cc13929.PubMedPubMedCentralCrossRef Wolters AE, van Dijk D, Pasma W, Cremer OL, Looije MF, de Lange DW, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care. 2014;18(3):R125. doi:10.​1186/​cc13929.PubMedPubMedCentralCrossRef
63.
64.
go back to reference Uthbertson BH, Elders A, Hall S, Taylor J, MacLennan G, Mackirdy F, et al. Mortality and quality of life in the five years after severe sepsis. Crit Care. 2013;17(2):R70. doi:10.1186/cc12616.CrossRef Uthbertson BH, Elders A, Hall S, Taylor J, MacLennan G, Mackirdy F, et al. Mortality and quality of life in the five years after severe sepsis. Crit Care. 2013;17(2):R70. doi:10.​1186/​cc12616.CrossRef
65.
go back to reference Yende S, Austin S, Rhodes A, Finfer S, Opal S, Thompson T et al. Long-Term Quality of Life Among Survivors of Severe Sepsis: Analyses of Two International Trials. Crit Care Med. 2016. doi:10.1097/CCM.0000000000001658. Yende S, Austin S, Rhodes A, Finfer S, Opal S, Thompson T et al. Long-Term Quality of Life Among Survivors of Severe Sepsis: Analyses of Two International Trials. Crit Care Med. 2016. doi:10.​1097/​CCM.​0000000000001658​.
66.
go back to reference Heyland DK, Hopman W, Coo H, Tranmer J, McColl MA. Long-term health-related quality of life in survivors of sepsis. Short Form 36: a valid and reliable measure of health-related quality of life. Crit Care Med. 2000;28(11):3599–605.PubMedCrossRef Heyland DK, Hopman W, Coo H, Tranmer J, McColl MA. Long-term health-related quality of life in survivors of sepsis. Short Form 36: a valid and reliable measure of health-related quality of life. Crit Care Med. 2000;28(11):3599–605.PubMedCrossRef
67.
68.
go back to reference Orwelius L, Lobo C, Teixeira Pinto A, Carneiro A, Costa-Pereira A, Granja C. Sepsis patients do not differ in health-related quality of life compared with other ICU patients. Acta Anaesthesiol Scand. 2013;57(9):1201–5. doi:10.1111/aas.12164.PubMedCrossRef Orwelius L, Lobo C, Teixeira Pinto A, Carneiro A, Costa-Pereira A, Granja C. Sepsis patients do not differ in health-related quality of life compared with other ICU patients. Acta Anaesthesiol Scand. 2013;57(9):1201–5. doi:10.​1111/​aas.​12164.PubMedCrossRef
69.
go back to reference Feemster LC, Cooke CR, Rubenfeld GD, Hough CL, Ehlenbach WJ, Au DH et al. The Influence of Hospitalization or ICU Admission on Declines in Health-Related Quality of Life. Ann Am Thorac Soc. 2014. doi:10.1513/AnnalsATS.201404-172OC. Feemster LC, Cooke CR, Rubenfeld GD, Hough CL, Ehlenbach WJ, Au DH et al. The Influence of Hospitalization or ICU Admission on Declines in Health-Related Quality of Life. Ann Am Thorac Soc. 2014. doi:10.​1513/​AnnalsATS.​201404-172OC.
73.
78.
go back to reference Dal-Pizzol F, Pasquali M, Quevedo J, Gelain DP, Moreira JC. Is there a role for high mobility group box 1 and the receptor for advanced glycation end products in the genesis of long-term cognitive impairment in sepsis survivors? Mol Med. 2012;18:1357-8; author reply 9. doi:10.2119/molmed.2012.00317. Dal-Pizzol F, Pasquali M, Quevedo J, Gelain DP, Moreira JC. Is there a role for high mobility group box 1 and the receptor for advanced glycation end products in the genesis of long-term cognitive impairment in sepsis survivors? Mol Med. 2012;18:1357-8; author reply 9. doi:10.​2119/​molmed.​2012.​00317.
79.
go back to reference Kaynar A, Yende S, Zhu L, Frederick D, Chambers R, Burton C, et al. Effects of intra-abdominal sepsis on atherosclerosis in mice. Crit Care. 2014;18(5):469.PubMedPubMedCentralCrossRef Kaynar A, Yende S, Zhu L, Frederick D, Chambers R, Burton C, et al. Effects of intra-abdominal sepsis on atherosclerosis in mice. Crit Care. 2014;18(5):469.PubMedPubMedCentralCrossRef
80.
go back to reference Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015;7(287):287ra71. doi:10.1126/scitranslmed.aaa5993. Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015;7(287):287ra71. doi:10.​1126/​scitranslmed.​aaa5993.
82.
go back to reference van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA. 2016;315(14):1469–79. doi:10.1001/jama.2016.2691.PubMedCrossRef van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA. 2016;315(14):1469–79. doi:10.​1001/​jama.​2016.​2691.PubMedCrossRef
89.
go back to reference Zaborin A, Smith D, Garfield K, Quensen J, Shakhsheer B, Kade M et al. Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness. mBio. 2014;5(5). doi:10.1128/mBio.01361-14. Zaborin A, Smith D, Garfield K, Quensen J, Shakhsheer B, Kade M et al. Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness. mBio. 2014;5(5). doi:10.​1128/​mBio.​01361-14.
Metadata
Title
Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges
Authors
Manu Shankar-Hari
Gordon D. Rubenfeld
Publication date
01-11-2016
Publisher
Springer US
Published in
Current Infectious Disease Reports / Issue 11/2016
Print ISSN: 1523-3847
Electronic ISSN: 1534-3146
DOI
https://doi.org/10.1007/s11908-016-0544-7

Other articles of this Issue 11/2016

Current Infectious Disease Reports 11/2016 Go to the issue

Central Nervous System Infections (K Bloch, Section Editor)

Ocular Syphilis: a Clinical Review

Central Nervous System Infections (K Bloch, Section Editor)

Human Rabies: a 2016 Update

Central Nervous System Infections (K Bloch, Section Editor)

Central Nervous System Device Infections

Central Nervous System Infections (K Bloch, Section Editor)

Laboratory Diagnosis of Central Nervous System Infection

Central Nervous System Infections (K Bloch, Section Editor)

Progressive Multifocal Leukoencephalopathy in HIV-Uninfected Individuals

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.