Sepsis cost-effectiveness of therapy

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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

Cost-Effectiveness of Therapy

Economic burden of sepsis

  • Sepsis is the most expensive condition treated in U.S. hospitals, estimated at approximately $24 billion in 2013 among all payers. Estimates that incorporate indirect and long-term costs are substantially higher, at approximately $67 billion annually. Medicare fee-for-service inpatient sepsis spending alone reached approximately $23 billion by 2019. These figures derive from differing case definitions and costing methods and should not be treated as interchangeable.[1][2][3]
  • Per-case costs and mortality rise steeply with severity and are markedly higher when sepsis is not present on admission: $16,324 for sepsis without organ dysfunction, $24,638 for severe sepsis, and $38,298 for septic shock, with corresponding inpatient mortality of 5.6%, 14.9%, and 34.2%; cost is $18,023 when sepsis is present on admission versus $51,022 when it develops after admission. These findings identify early recognition and treatment as an important potential cost lever.[4]

Cost-effectiveness of protocolized and quality-improvement care

  • Early economic evaluations of integrated sepsis protocols reported favorable cost-effectiveness. Talmor et al. estimated approximately $16,309 per quality-adjusted life-year (QALY) for an integrated sepsis treatment protocol.[5]
  • In a prospective nationwide Spanish study, implementation of the Surviving Sepsis Campaign protocol was associated with an estimated cost of approximately €4,435 per life-year gained.[6]
  • Not all protocolized-care economic analyses are favorable, and the early positive studies evaluated early goal-directed therapy (EGDT)-based bundles that included components since abandoned, including drotrecogin alfa and intensive insulin therapy. In the ProMISe randomized trial, EGDT was not cost-effective versus usual resuscitation, with an incremental net benefit of -£725 at 1 year and a probability of cost-effectiveness of <30%. Contemporary cost-effectiveness therefore rests more on usual sepsis care delivered through effective performance-improvement programs than on EGDT itself.[7][8]
  • Sepsis quality-improvement programs may reduce resource use and costs. Afshar et al. reported improved outcomes with a health-system sepsis quality-improvement program that was cost-saving.[9]
  • The economic literature on sepsis care bundles is heterogeneous. A 2025 systematic review found variable cost impacts across bundle studies, with most evidence observational and therefore vulnerable to confounding by indication and differences in implementation and costing methods.[10]
  • The 2026 Surviving Sepsis Campaign recommends sepsis quality-improvement strategies as part of a performance improvement program (strong recommendation, moderate certainty evidence for quality improvement strategies), recognizing that such programs likely improve care processes and may have a small effect on mortality. This recommendation is supported by the SCREEN stepped-wedge cluster randomized trial (60,055 patients), in which an electronic alert, education, and feedback intervention was associated with lower 90-day in-hospital mortality (adjusted risk ratio 0.85; 95% CI, 0.77-0.93).[11]
  • Observational evidence also suggests an association between compliance with the CMS SEP-1 early management bundle and lower mortality. In a propensity-matched Medicare cohort, SEP-1 compliance was associated with an approximately 5.7% absolute reduction in mortality; however, causal inference is limited by the observational design.[12]
  • A 2025 systematic review of SEP-1 implementation found no randomized trials directly evaluating SEP-1-like bundles, and a French/Spanish cluster randomized trial did not demonstrate a survival benefit. Thus, economic and outcome claims for mandatory bundles should be interpreted separately from the stronger evidence supporting effective performance-improvement strategies.[13]

Antimicrobial stewardship and economic considerations

  • Antimicrobial stewardship can reduce avoidable antibiotic exposure and associated costs while maintaining appropriate treatment of infection. The 2021 and 2026 Surviving Sepsis Campaign guidelines support antimicrobial reassessment, de-escalation when appropriate, and discontinuation when infection is not supported by the clinical course.[14][15]
  • Biomarker-guided antimicrobial discontinuation may reduce antibiotic exposure without worsening outcomes in selected critically ill adults with sepsis. A 2024 systematic review and network meta-analysis found benefits and harms varied by biomarker strategy and outcome, supporting use as an adjunct to clinical assessment rather than as a stand-alone economic intervention.[16]
  • A 2025 economic analysis found procalcitonin-guided antibiotic duration to be potentially cost-effective in hospitalized patients with sepsis, although results depend on assumptions regarding antibiotic costs, test costs, treatment duration, and health outcomes.[17]

Long-term costs after sepsis

  • The economic burden of sepsis extends beyond the index hospitalization. Sepsis survivors may require substantial post-discharge healthcare because of persistent physical, cognitive, and functional morbidity; the cost consequence, rather than the underlying mechanisms of these sequelae, is the relevant consideration in this microchapter.[18]
  • A 2025 systematic review reported median healthcare costs after sepsis exceeding $28,000 during the first year after discharge, exceeding $22,000 during the second year, and exceeding $20,000 per readmission, expressed in 2022 U.S. dollars. Estimates varied substantially across studies and healthcare systems.[19]
  • Sepsis-associated resource use and healthcare costs remain elevated after discharge and contribute substantially to the overall economic burden. Propensity-matched cohort data also demonstrate increased healthcare utilization and costs among patients with sepsis compared with matched controls.[20]

Economic interpretation and limitations

  • Cost-effectiveness estimates for sepsis interventions are highly sensitive to the intervention definition, comparator, healthcare system, costing method, and analytic time horizon. Results from older EGDT-era protocols should not be extrapolated directly to contemporary sepsis care.
  • Most bundle and quality-improvement economic evaluations are observational or model-based. Confounding by indication, secular changes in sepsis recognition and treatment, differences in implementation, and heterogeneous cost accounting limit direct comparison across studies and countries.[21][22]
  • The most defensible contemporary economic conclusion is that timely, evidence-based sepsis care and effective performance-improvement systems can be economically favorable, but individual bundle components should not be assumed to be cost-effective solely because the overall sepsis program is associated with improved outcomes.

References

  1. ↑ Rudd KE, Delaney A, Finfer S (2017). "Counting Sepsis, an Imprecise but Improving Science". JAMA. 318 (13): 1228–1229. doi:10.1001/jama.2017.13697. PMID 28903154.
  2. ↑ Vincent JL, Jones G, David S, Olariu E, Cadwell KK (2019). "Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis". Critical Care. 23 (1): 196. doi:10.1186/s13054-019-2478-6. PMID 31151462.
  3. ↑ Frank CE, Buchman TG, Simpson SQ; et al. (2021). "Sepsis Among Medicare Beneficiaries: 4. Precoronavirus Disease 2019 Update January 2012-February 2020". Critical Care Medicine. 49 (12): 2058–2069. doi:10.1097/CCM.0000000000005332. PMID 34582410 Check |pmid= value (help).
  4. ↑ Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E (2018). "Epidemiology and Costs of Sepsis in the United States-an Analysis Based on Timing of Diagnosis and Severity Level". Critical Care Medicine. 46 (12): 1889–1897. doi:10.1097/CCM.0000000000003342. PMID 30048332.
  5. ↑ Talmor D, Greenberg D, Howell MD; et al. (2008). "The Costs and Cost-Effectiveness of an Integrated Sepsis Treatment Protocol". Critical Care Medicine. 36 (4): 1168–1174. doi:10.1097/CCM.0b013e318168f649. PMID 18379243.
  6. ↑ Suarez D, Ferrer R, Artigas A; et al. (2011). "Cost-Effectiveness of the Surviving Sepsis Campaign Protocol for Severe Sepsis: A Prospective Nation-Wide Study in Spain". Intensive Care Medicine. 37 (3): 444–452. doi:10.1007/s00134-010-2102-3. PMID 21152895.
  7. ↑ Mouncey PR, Osborn TM, Power GS; et al. (2015). "Protocolised Management in Sepsis (ProMISe): A Multicentre Randomised Controlled Trial of the Clinical Effectiveness and Cost-Effectiveness of Early, Goal-Directed, Protocolised Resuscitation for Emerging Septic Shock". Health Technology Assessment. 19 (97): i–xxv, 1–150. doi:10.3310/hta19970. PMID 26597979.
  8. ↑ 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. PMID 34605781 Check |pmid= value (help).
  9. ↑ Afshar M, Arain E, Ye C; et al. (2019). "Patient Outcomes and Cost-Effectiveness of a Sepsis Care Quality Improvement Program in a Health System". Critical Care Medicine. 47 (10): 1371–1379. doi:10.1097/CCM.0000000000003919. PMID 31306176.
  10. ↑ Ladbrook E, Bouchoucha S, McDonall J, Hutchinson AF (2025). "A Systematic Review of the Cost-Impact of Sepsis Care Bundles". Journal of Hospital Infection. doi:10.1016/j.jhin.2025.08.006. PMID 40962143 Check |pmid= value (help).
  11. ↑ 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.
  12. ↑ Townsend SR, Phillips GS, Duseja R; et al. (2022). "Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study". Chest. 161 (2): 392–406. doi:10.1016/j.chest.2021.07.2167. PMID 34364867 Check |pmid= value (help).
  13. ↑ Ford JS, Morrison JC, Kyaw M; et al. (2025). "The Effect of Severe Sepsis and Septic Shock Management Bundle (SEP-1) Compliance and Implementation on Mortality Among Patients With Sepsis". Annals of Internal Medicine. 178 (4): 543–557. doi:10.7326/ANNALS-24-02426.
  14. ↑ 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. PMID 34605781 Check |pmid= value (help).
  15. ↑ 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.
  16. ↑ Kubo K, Sakuraya M, Sugimoto H; et al. (2024). "Benefits and Harms of Procalcitonin- Or C-Reactive Protein-Guided Antimicrobial Discontinuation in Critically Ill Adults With Sepsis: A Systematic Review and Network Meta-Analysis". Critical Care Medicine. 52 (10): e522–e534. doi:10.1097/CCM.0000000000006366. PMID 38949476 Check |pmid= value (help).
  17. ↑ Stevenson M, Forsyth JE, Hossain A; et al. (2025). "Cost-effectiveness of procalcitonin-guided antibiotic duration for hospitalized patients with sepsis". Critical Care. 29 (1): 508. doi:10.1186/s13054-025-05732-w.
  18. ↑ Meyer NJ, Prescott HC (2024). "Sepsis and Septic Shock". The New England Journal of Medicine. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213. PMID 39620920 Check |pmid= value (help).
  19. ↑ Chechulina V, Sheikh F, Lóser M; et al. (2025). "Healthcare costs after sepsis: a systematic review". Critical Care. 29 (1): 381. doi:10.1186/s13054-025-05600-7.
  20. ↑ Farrah K, McIntyre L, Doig CJ; et al. (2021). "Sepsis-Associated Mortality, Resource Use, and Healthcare Costs: A Propensity-Matched Cohort Study". Critical Care Medicine. 49 (2): 215–227. doi:10.1097/CCM.0000000000004777. PMID 33372748 Check |pmid= value (help).
  21. ↑ Ladbrook E, Bouchoucha S, McDonall J, Hutchinson AF (2025). "A Systematic Review of the Cost-Impact of Sepsis Care Bundles". Journal of Hospital Infection. doi:10.1016/j.jhin.2025.08.006. PMID 40962143 Check |pmid= value (help).
  22. ↑ Chechulina V, Sheikh F, Lóser M; et al. (2025). "Healthcare costs after sepsis: a systematic review". Critical Care. 29 (1): 381. doi:10.1186/s13054-025-05600-7.

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