Sepsis secondary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2] Jason Le, B.S.[3]
Synonyms and keywords: sepsis syndrome; septic shock; septicemia
Sepsis secondary prevention
Secondary prevention of sepsis comprises interventions applied after survival from an episode of sepsis or septic shock to reduce recurrence, recurrent infection, readmission, late organ complications, and long-term functional, cognitive, and psychological impairment. Approximately 40% of sepsis survivors are rehospitalized within 90 days, most often because of recurrent infection or exacerbation of chronic conditions. Sepsis was also the condition most commonly associated with 30-day all-cause readmission, accounting for 8.3% of readmissions in the 2018 National Readmissions Database. Approximately half of post-sepsis readmissions are infection-related.[1][2][3] Adult data also suggest that approximately 1 in 21 sepsis survivors is readmitted with a new sepsis diagnosis within 30 days, with cumulative recurrent-sepsis readmission reaching approximately 8.1% by 90 days.[3]
Survivors also carry an excess long-term hazard of cardiovascular events and death that persists for years.[4][5]
Post-sepsis syndrome and the burden it targets
Post-sepsis syndrome (PSS) encompasses new physical, cognitive, and psychological deficits after sepsis. In longitudinal data, 91.2% of survivors had at least one new physical impairment, 57.9% new cognitive symptoms, and 40.9% new psychological symptoms up to 3 years after the acute illness.[6]
Among older adults, moderate-to-severe cognitive impairment increased from 6.1% before to 16.7% after a sepsis hospitalization, accompanied by new functional limitations.[7][5]
Persistent inflammatory and immunosuppressive marker activation in approximately two-thirds of survivors is associated with increased all-cause mortality and may contribute to recurrent infection.[5]
Late organ complications to anticipate
Sepsis survivorship is associated with increased long-term risk of myocardial infarction (adjusted hazard ratio [aHR] 1.77, 95% CI 1.26-2.48), stroke (aHR 1.67, 95% CI 1.37-2.05), and heart failure (aHR 1.65, 95% CI 1.46-1.86), with excess hazard persisting for at least 5 years.[4] Survivors are also at increased risk of recurrent infection and acute kidney injury compared with non-sepsis hospitalized controls.[1]
Structured post-discharge care
The Surviving Sepsis Campaign 2021 long-term outcomes recommendations provide the core framework for secondary prevention:[1]
- Use shared decision-making in post-ICU and discharge planning.
- Consider a critical-care transition program rather than usual care upon transfer to the hospital ward.
- Perform medication reconciliation at both ICU and hospital discharge.
- Provide a discharge summary that includes the ICU course, sepsis diagnosis, treatments, and common post-sepsis impairments.
- Ensure follow-up with clinicians able to manage new or persistent sequelae when new impairments are present.
- Assess and provide follow-up for physical, cognitive, and emotional problems after discharge.
- Refer to a post-critical-illness follow-up program if available.
- Refer survivors who received mechanical ventilation for more than 48 hours or had an ICU stay longer than 72 hours to a post-hospital rehabilitation program when appropriate.
The Surviving Sepsis Campaign 2026 likewise suggests offering sepsis- and critical-illness follow-up services, citing probable small improvements in physical quality of life, anxiety, and post-traumatic stress and a potential reduction in readmissions (RR 0.88, 95% CI 0.73-1.07), while noting low certainty of evidence and possible resource and equity barriers.[8]
Early post-discharge medical follow-up should focus on medication reconciliation, identification of treatable relapse drivers such as recurrent infection, heart failure, renal dysfunction, and dysphagia, rehabilitation planning, and referral to appropriate post-critical-illness support programs.[9]
Care coordination and transition programs
In the IMPACTS randomized clinical trial (691 patients, 3 metropolitan hospitals), a nurse navigator-led sepsis transition and recovery program reduced the composite of 30-day mortality or readmission (28.7% vs 33.3%; adjusted OR 0.80, 95% CI 0.64-0.98), corresponding to an absolute reduction of about 5% at 30 days and 7.2% at 12 months.[10]
A subsequent larger multicenter stepped-wedge randomized trial (ENCOMPASS, 7 hospitals, 3548 patients) delivering proactive telehealth-based transition and recovery support through 90 days did not reduce the primary composite of 90-day all-cause readmission or death (48.2% vs 48.0%; adjusted OR 1.05, 95% CI 0.90-1.24; P=0.53). Ninety-day mortality was lower as a secondary outcome (17.3% vs 20.5%; adjusted OR 0.88, 95% CI 0.77-0.99), while readmission was numerically higher (35.9% vs 33.5%; adjusted OR 1.13).[2]
These findings support structured post-sepsis follow-up as a reasonable care model when resources permit, but the neutral primary endpoint of the larger multicenter trial indicates that benefit should not be assumed for all transition-program models or settings.
Vaccination and infection prevention in survivors
Updating age- and risk-appropriate vaccinations, including pneumococcal, influenza, COVID-19, and other indicated vaccines, is an appropriate component of post-sepsis review to reduce preventable infection risk.[9][11] Detailed vaccination schedules belong in the Sepsis primary prevention microchapter; the secondary-prevention action is to verify and complete indicated vaccinations during recovery.
Infection is a major driver of post-sepsis readmission. Adult studies identify infectious etiologies as the most common causes of early readmission, supporting attention to vaccination, source-specific prevention, antimicrobial stewardship, and evaluation for recurrent infection.[12][13]
Antimicrobial stewardship
Limit antimicrobial exposure to the shortest effective course supported by the infectious source, source control, microbiologic data, and clinical response. De-escalation and infectious-disease consultation when appropriate can reduce unnecessary antimicrobial exposure and resistance pressure.[14][15]
Hospital program infrastructure
The Centers for Disease Control and Prevention Hospital Sepsis Program Core Elements frame sepsis survivorship and outcome monitoring as an ongoing quality-improvement process across the continuum of care, complementing bedside sepsis-management guidance.[16]
Clinically actionable recommendations
- Reconcile medications at ICU and hospital discharge, accounting for changes in renal function, body weight, and other physiologic changes after critical illness.[1][9]
- Screen survivors for new physical, cognitive, and emotional problems during post-discharge follow-up.[1]
- Arrange early clinician follow-up and refer to post-critical-illness and rehabilitation programs when appropriate.[1][8]
- Update indicated vaccinations during recovery.[9]
- Evaluate for treatable relapse drivers, including recurrent infection, heart failure, acute kidney injury, and dysphagia.[9]
- Consider structured care-coordination programs, such as nurse-navigator or STAR-type models, when available; recognize that evidence is mixed and the larger ENCOMPASS trial had a neutral primary endpoint.[10][2]
- Optimize modifiable cardiovascular risk factors in survivors given the persistent excess risk of myocardial infarction, stroke, and heart failure.[4]
Areas of uncertainty
- Evidence is insufficient to establish an optimal timing for post-discharge follow-up or to recommend for or against early cognitive therapy after sepsis.[1]
- Post-critical-illness clinic efficacy remains uncertain; meta-analytic evidence has not established clear mortality, quality-of-life, or functional benefit, although small psychological benefits may occur and SSC 2026 suggests offering follow-up services with low certainty of evidence.[1][8]
- No targeted pharmacologic therapy has been established to enhance recovery after sepsis.[5]
- The positive IMPACTS trial and neutral ENCOMPASS trial indicate that the effectiveness of structured transition programs may depend on program design, implementation, patient selection, and care setting.[10][2]
- The Surviving Sepsis Campaign 2026 addresses post-sepsis and post-critical-illness recovery but does not establish a specific universal transition-program model.[8]
High-yield clinical pearls
- Approximately 40% of sepsis survivors are rehospitalized within 90 days; proactive discharge planning and follow-up should therefore begin before hospital discharge.[1]
- Recurrent infection is a major contributor to early post-sepsis readmission, and approximately 1 in 21 adult survivors is readmitted with a new sepsis diagnosis within 30 days.[3]
- Cognitive impairment can persist after physical and psychological deficits improve; screening should not be limited to mobility or mood.[7]
- Long-term myocardial infarction, stroke, and heart-failure risk remains elevated for at least 5 years after sepsis.[4]
- Structured transition programs should be viewed as potentially useful care models rather than universally effective interventions; the largest multicenter trial to date had a neutral primary endpoint.[2]
Common pitfalls
- Treating secondary prevention as equivalent to primary prevention.
- Failing to reconcile medications after major changes in renal function, body weight, or clinical status.[1][9]
- Omitting the sepsis diagnosis, ICU course, major treatments, and expected sequelae from the discharge summary.[1]
- Overlooking vaccination updates and treatable relapse drivers at the first post-discharge assessment.[9]
- Assuming recovery is linear; functional, cognitive, psychological, or medical deterioration may emerge weeks to months after discharge.[5]
- Assuming that a successful single-system transition program will necessarily reproduce the same benefit in other health systems or populations.[10][2]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Evans L, Rhodes A, Alhazzani W; et al. (2021). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021". Critical Care Medicine. 49 (11): e1063–e1143. doi:10.1097/CCM.0000000000005337.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Taylor SP, Eaton T, Rios A; et al. (2025). "Proactive Telehealth-Based Sepsis Transition and Recovery Support, Hospital Readmission, and Mortality: A Randomized Clinical Trial". JAMA Internal Medicine. 185 (10): 1238–1246. doi:10.1001/jamainternmed.2025.3699.
- ↑ 3.0 3.1 3.2 Ackermann K, Lynch I, Aryal N, Westbrook J, Li L. (2025). "Hospital Readmission After Surviving Sepsis: A Systematic Review of Readmission Reasons and Meta-Analysis of Readmission Rates". Journal of Critical Care. 85: 154925. doi:10.1016/j.jcrc.2024.154925. PMID 39393165 Check
|pmid=value (help). - ↑ 4.0 4.1 4.2 4.3 Kosyakovsky LB, Angriman F, Katz E; et al. (2021). "Association Between Sepsis Survivorship and Long-Term Cardiovascular Outcomes in Adults: A Systematic Review and Meta-Analysis". Intensive Care Medicine. 47 (9): 931–942. doi:10.1007/s00134-021-06479-y. PMID 34373953 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 5.3 5.4 Meyer NJ, Prescott HC. (2024). "Sepsis and Septic Shock". The New England Journal of Medicine. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213.
- ↑ Bircak-Kuchtova B, Rose N, Geis C; et al. (2025). "Effectiveness of targeted post-acute interventions and follow-up services for sepsis survivors: a systematic review". Critical Care. 29 (1): 351. doi:10.1186/s13054-025-05585-3.
- ↑ 7.0 7.1 Iwashyna TJ, Ely EW, Smith DM, Langa KM. (2010). "Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis". JAMA. 304 (16): 1787–1794. doi:10.1001/jama.2010.1553.
- ↑ 8.0 8.1 8.2 8.3 Prescott HC, Antonelli M, Alhazzani W; et al. (2026). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026". Critical Care Medicine. 54 (4): 725–812. doi:10.1097/CCM.0000000000007075.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Prescott HC, Angus DC. (2018). "Enhancing Recovery From Sepsis: A Review". JAMA. 319 (1): 62–75. doi:10.1001/jama.2017.17687.
- ↑ 10.0 10.1 10.2 10.3 Taylor SP, Murphy S, Rios A; et al. (2022). "Effect of a Multicomponent Sepsis Transition and Recovery Program on Mortality and Readmissions After Sepsis: The Improving Morbidity During Post-Acute Care Transitions for Sepsis Randomized Clinical Trial". Critical Care Medicine. 50 (3): 469–479. doi:10.1097/CCM.0000000000005300.
- ↑ Rahmel T, Siegler BH, Weigand MA; et al. (2026). "The evolution of sepsis care: from protocol-driven management to personalized intensive care". Infection. doi:10.1007/s15010-026-02852-5.
- ↑ Sun A, Netzer G, Small DS; et al. (2016). "Association Between Index Hospitalization and Hospital Readmission in Sepsis Survivors". Critical Care Medicine. 44 (3): 478–487. doi:10.1097/CCM.0000000000001464.
- ↑ Gadre SK, Shah M, Mireles-Cabodevila E, Patel B, Duggal A. (2019). "Epidemiology and Predictors of 30-Day Readmission in Patients With Sepsis". Chest. 155 (3): 483–490. doi:10.1016/j.chest.2018.12.008.
- ↑ Lanckohr C, Bracht H. (2022). "Antimicrobial Stewardship". Current Opinion in Critical Care. 28 (5): 551–556. doi:10.1097/MCC.0000000000000967.
- ↑ Rhee C, Masur H, Klompas M; et al. (2026). "IDSA/ACEP/ASM/PIDS/SCCM/SHEA/SHM/SIDP Multisociety Position Paper: Hospital Strategies to Improve Sepsis Outcomes". Clinical Infectious Diseases. doi:10.1093/cid/ciag438. PMID 42640090 Check
|pmid=value (help). - ↑ Prescott HC, Posa PJ, Dantes R. (2023). "The Centers for Disease Control and Prevention's Hospital Sepsis Program Core Elements". JAMA. 330 (17): 1617–1618. doi:10.1001/jama.2023.16693.