Cited by 1,059Sepsis Diagnosis and TreatmentIntensive Care Unit Cognitive DisordersVitamin C and Antioxidants Research

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Enhancing Recovery From Sepsis: A Review

Open access

Prescott, Hallie C., Angus, Derek C.·2018·JAMA

DOI 10.1001/jama.2017.17687PMC PMC5839473

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Abstract

Importance: Survival from sepsis has improved in recent years, resulting in an increasing number of patients who have survived sepsis treatment. Current sepsis guidelines do not provide guidance on posthospital care or recovery. Observations: Each year, more than 19 million individuals develop sepsis, defined as a life-threatening acute organ dysfunction secondary to infection. Approximately 14 million survive to hospital discharge and their prognosis varies. Half of patients recover, one-third die during the following year, and one-sixth have severe persistent impairments. Impairments include development of an average of 1 to 2 new functional limitations (eg, inability to bathe or dress independently), a 3-fold increase in prevalence of moderate to severe cognitive impairment (from 6.1% before hospitalization to 16.7% after hospitalization), and a high prevalence of mental health problems, including anxiety (32% of patients who survive), depression (29%), or posttraumatic stress disorder (44%). About 40% of patients are rehospitalized within 90 days of discharge, often for conditions that are potentially treatable in the outpatient setting, such as infection (11.9%) and exacerbation of heart failure (5.5%). Compared with patients hospitalized for other diagnoses, those who survive sepsis (11.9%) are at increased risk of recurrent infection than matched patients (8.0%) matched patients (P < .001), acute renal failure (3.3% vs 1.2%, P < .001), and new cardiovascular events (adjusted hazard ratio [HR] range, 1.1-1.4). Reasons for deterioration of health after sepsis are multifactorial and include accelerated progression of preexisting chronic conditions, residual organ damage, and impaired immune function. Characteristics associated with complications after hospital discharge for sepsis treatment are not fully understood but include both poorer presepsis health status, characteristics of the acute septic episode (eg, severity of infection, host response to infection), and quality of hospital treatment (eg, timeliness of initial sepsis care, avoidance of treatment-related harms). Although there is a paucity of clinical trial evidence to support specific postdischarge rehabilitation treatment, experts recommend referral to physical therapy to improve exercise capacity, strength, and independent completion of activities of daily living. This recommendation is supported by an observational study involving 30 000 sepsis survivors that found that referral to rehabilitation within 90 days was associated with lower risk of 10-year mortality compared with propensity-matched controls (adjusted HR, 0.94; 95% CI, 0.92-0.97, P < .001). Conclusions and Relevance: In the months after hospital discharge for sepsis, management should focus on (1) identifying new physical, mental, and cognitive problems and referring for appropriate treatment, (2) reviewing and adjusting long-term medications, and (3) evaluating for treatable conditions that commonly result in hospitalization, such as infection, heart failure, renal failure, and aspiration. For patients with poor or declining health prior to sepsis who experience further deterioration after sepsis, it may be appropriate to focus on palliation of symptoms.

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Severe inflammation in C57/BL6 mice leads to prolonged cognitive impairment by initiating the IL-1β/TRPM2 pathway
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Outcomes of Surgical Sepsis
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“Among initial survivors, one-half recover fully, one-third die within one year, and one-sixth have severe, persistent impairments [11] that may be functional, cognitive, or behavioral (e.g., anxiety, depression, post-traumatic stress disorder).”
Resveratrol glycoside mediates microglial endoplasmic reticulum stress to mitigate LPS-induced sepsis-associated cognitive dysfunction
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An Interpretable Early Dynamic Sequential Predictor for Sepsis-Induced Coagulopathy Progression in the Real-World Using Machine Learning
Cui, R., Hua, W., Qu, K., Yang, H., Tong, Y., Li, Q., Wang, H., Ma, Y., Liu, S., Lin, T. Y., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.775047 · Cited by 9
“Septic-induced organ dysfunction is a major cause of sepsis high mortality (2).”
Background
Effects of evidence-based ICU care on long-term outcomes of patients with sepsis or septic shock (ILOSS): protocol for a multicentre prospective observational cohort study in Japan
Liu, K., Kotani, T., Nakamura, K., Takai, C., Morita, Y., Ishii, K., Fujizuka, K., Yasumura, D., Taniguchi, D., Hamagami, T., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-054478 · Cited by 9
Pediatric Sepsis Requiring Intensive Care Admission: Potential Structured Follow-Up Protocols to Identify and Manage New or Exacerbated Medical Conditions
Reddy, A. R., Stinson, H. R., Alcamo, A. M., Pinto, N. P., & Fitzgerald, J. C. (2023) · Risk Management and Healthcare Policy · doi:10.2147/rmhp.s394458 · Cited by 9
Single-cell transcriptional gene signature analysis identifies IL-17 signaling pathway as the key pathway in sepsis
Zhao, H., Li, Y., Sun, G., Cheng, M., Ding, X., & Wang, K. (2023) · Immunobiology · doi:10.1016/j.imbio.2023.152763 · Cited by 9
Changes in Early T-Cell Subsets and Their Impact on Prognosis in Patients with Sepsis: A Single-Center Retrospective Study
Li, Y., Wang, Y., Chen, B., Guo, J., & Zhang, D. (2023) · International Journal of Clinical Practice · doi:10.1155/2023/1688385 · Cited by 9
“Research has shown that 50% of sepsis survivors experience recovery upon discharge, while one-third of patients die in the second year, and one-sixth sufer from severe and persistent impairments, with mortality of 40%– 80% in the subsequent three years [7, 8].”
Background
Identification of key genes as potential diagnostic biomarkers in sepsis by bioinformatics analysis
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“Incorrect distinction and diagnosis can cause inappropriate patient management, overuse of antibiotics and result in death in severe cases ( Prescott & Angus, 2018 ).”
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Impact of negative emotions and insomnia on sepsis: A mediation Mendelian randomization study
Ni, F., Liu, X., & Wang, S. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.108858 · Cited by 9
COVID‐19 and Mental Health: A “Pandemic Within a Pandemic”
Fisicaro, F., Lanza, G., Concerto, C., Rodolico, A., Napoli, M. D., Mansueto, G., Cortese, K., Mogavero, M. P., Ferri, R., Bella, R., et al. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-61943-4_1 · Cited by 10
Predicting early diagnosis of intensive care unit-acquired weakness in septic patients using critical ultrasound and biological markers
Lei, L., He, L., Zou, T., Qiu, J., Li, Y. W., Zhou, R., Qin, Y., & Yin, W. (2025) · BMC Anesthesiology · doi:10.1186/s12871-025-02911-8 · Cited by 9
Analysis of the inflammatory storm response and heparin binding protein levels for the diagnosis and prognosis of sepsis-associated encephalopathy
Yu, D., Liu, J., Song, X., Ao, Y., Li, X., & Han, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-02369-x · Cited by 12
CD177 neutrophils exacerbate septic lung injury via the NETs/AIM2 pathway: An experimental and bioinformatics study
Wang, F., Zhang, Y., Sun, M., Xia, H., Jiang, W., Zhang, D., & Yao, S. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114292 · Cited by 9
α‑ketoglutarate protects against septic cardiomyopathy by improving mitochondrial mitophagy and fission
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“Septic cardiomyopathy, characterized by reduced left ventricular systolic and diastolic functions (3,4), is a considerable and fatal complication of sepsis, with mortality rates ranging between 40 and 50% (5,6). despite extensive research identifying apop‑ tosis, oxidative stress, inflammation and…”
Time-series deep learning and conformal prediction for improved sepsis diagnosis in primarily Non-ICU hospitalized patients
Dalal, S., Ardabili, A. K., & Bonavia, A. S. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110497 · Cited by 9
Fluid balance and mortality in adult ICU patients with sepsis or septic shock: a systematic review and meta-analysis of observational studies
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Damage-associated Molecular Patterns, Immunothrombosis, and Intravascular Inflammation in Sepsis: A Narrative Integrative Review
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Door-to-antibiotic Time and In-hospital Mortality of Elder Patients Presenting to Emergency Department with Sepsis; a Cross-Sectional Study.
Tantarattanapong, S., & Hemwej, T. (2021) · Archives of Academic Emergency Medicine · doi:10.22037/aaem.v9i1.1266 · Cited by 9
“Sepsis remains as a public health problem worldwide and is one of the leading causes of death (1).”
Background
Thyroid function and risk of bloodstream infections: Results from the Norwegian prospective population‐based HUNT Study
Thorkildsen, M. S., Mohus, R. M., Åsvold, B. O., Skei, N. V., Nilsen, T. I. L., Solligård, E., Damås, J. K., & Gustad, L. T. (2021) · Clinical Endocrinology · doi:10.1111/cen.14658 · Cited by 9
The 6-Minute Walk Test predicts long-term physical improvement among intensive care unit survivors: a prospective cohort study
Rosa, R. G., Dietrich, C., do Valle, E. L. T., de Souza, D., Tagliari, L., Mattioni, M. F., Tonietto, T. F., da Rosa, R., Barbosa, M. G., Lovatel, G. A., et al. (2021) · Revista Brasileira de Terapia Intensiva · doi:10.5935/0103-507x.20210056 · Cited by 11
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“Approximately 40% die within 2 years, 80% within 5 years (Annane & Sharshar, 2015; Prescott & Angus, 2018; ShankarHari & Rubenfeld, 2016).”
Background
Recent advances in the study of sepsis-induced depression
Wang, Y., Zhu, Y., Tian, M., Wang, Y., Pei, X., Jiang, J., He, Y., & Gong, Y. (2023) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2022.12.002 · Cited by 12
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Schlapbach, L. J., Zimmermann, E., Meylan, S., Stocker, M., Suter, P. M., Jakob, S. M., & on behalf of the Swiss Sepsis National Action Plan Working Group (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1114546 · Cited by 9
Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis
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Background
Metabolic syndrome improves cardiovascular dysfunction and survival during cecal ligation and puncture-induced mild sepsis in mice
Nakama, R. P., Malvezi, A. D., Lovo‐Martins, M. I., dos Santos, L. F., Cardoso, A. P. C., Scacco, G., Dionísio, A. D. F. M., Martins‐Pinge, M. C., & Pinge‐Filho, P. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120033 · Cited by 9
Long-Term Functional Outcomes After Sepsis for Adult and Pediatric Critical Care Patients—Protocol for a Systematic Review
Simpson, A., Long, D. A., Fleischmann-Struzek, C., Minogue, J., Venkatesh, B., Hammond, N. E., Tian, D. H., & Schlapbach, L. J. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.734205 · Cited by 9
Parecoxib ameliorates renal toxicity and injury in sepsis‐induced mouse model and LPS ‐induced HK ‐2 cells
Guo, Y., Wu, B., Chen, Q., & Min, S. (2021) · Drug Development Research · doi:10.1002/ddr.21897 · Cited by 9
“It is estimated that sepsis affects more than 19 million people worldwide every year, and the in- hospital mortality rate of sepsis patients is about 15% 25% (Cecconi et al., 2018; Prescott & Angus, 2018).”
Background
Post COVID‐19 condition: critical need for a clear definition and detailed pathophysiology
Kerkhoff, T. J., Charlton, B. T., Appelman, B., van Vugt, M., & Wüst, R. C. I. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13108 · Cited by 9
“Importantly, recovery from a viral infection or hospitalization is complicated by the observation of a slow recovery, or a blunted response to rehabilitation in older people and in patients with chronic diseases.(16,17) Older people and those with inflammation often do not fully recover within 3 months after hospitali…”
Background
The role of place-based factors and other social determinants of health on adverse post-sepsis outcomes: a review of the literature
Ehrman, R. R., Malik, A., Haber, B. D., Glassman, S. R., Bowen, C. A., Korzeniewski, S. J., Bauer, S., & Sherwin, R. L. (2024) · Frontiers in Disaster and Emergency Medicine · doi:10.3389/femer.2024.1357806 · Cited by 8
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Ideal Postdischarge Follow-Up After Severe Pneumonia or Acute Respiratory Failure
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Lung-brain crosstalk: Behavioral disorders and neuroinflammation in septic survivor mice
Bonorino, K. C., Kraus, S. I., Martins, G. H. C., Probst, J. J., Moecke, D. P., Sumar, A. H. D. S., Casal, Y. R., Oliveira, F. R. M. B., Sordi, R., Assreuy, J., et al. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100823 · Cited by 9
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Background
Multifunctional endogenous small molecule-derived polymer composite nanoparticles for the treatment of acute sepsis therapy
Gao, J., Li, H., Yue, P., Xie, D., Li, H., Hao, K., Li, Y., & Tian, H. (2024) · Science China Materials · doi:10.1007/s40843-024-3051-y · Cited by 8
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Older Adult Sepsis Survivors Discharged to Skilled Nursing Facilities: Age‐Adjusted Charlson Comorbidity Index as a Predictor of 6‐Month Mortality
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Xuebijing Injection Alleviates Sepsis-Induced Acute Lung Injury by Inhibition of Cell Apoptosis and Inflammation Through the Hippo Pathway
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Does postoperative plasma IL-6 improve early prediction of infection after pulmonary cancer surgery? A two-centre prospective study
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Single-nucleus transcriptomics reveals sepsis-related neurovascular dysfunction in the human hippocampus
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VIP alleviates sepsis-induced cognitive dysfunction as the TLR-4/NF-κB signaling pathway is inhibited in the hippocampus of rats
Yang, Y., Yun, D., Dong, B., Geng, Y., & Wan, Y. (2022) · Journal of Molecular Histology · doi:10.1007/s10735-022-10068-8 · Cited by 8
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Background
Exploring the Muscle Metabolomics in the Mouse Model of Sepsis-Induced Acquired Weakness
Jiang, Y., Wei, Q., Liu, W., Chen, Q., Chen, X., Yuan, Z., Luo, N., Chen, X., & Wang, C. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/6908488 · Cited by 8
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Clinical Impact of a Sepsis Alert System Plus Electronic Sepsis Navigator Using the Epic Sepsis Prediction Model in the Emergency Department
Schertz, A. R., Smith, S. A., Lenoir, K. M., & Thomas, K. W. (2023) · Journal of Emergency Medicine · doi:10.1016/j.jemermed.2023.02.025 · Cited by 8
Influence of Sepsis on the Middle-Term Outcomes for Urinary Tract Infections in Elderly People
Artero, A., Lopez, I. F. H., Alberola, J., Bouza, J. M. E., Ruiz, E. R., Piles, L., & Madrazo, M. (2023) · Microorganisms · doi:10.3390/microorganisms11081959 · Cited by 8
The predictive values of admission characteristics for 28-day all-cause mortality in septic patients with diabetes mellitus: a study from the MIMIC database
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Circ_0006944 aggravates LPS-induced HK2 cell injury via modulating miR-205-5p/UBL4A pathway
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Causal Association Between Sepsis and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization Study
Zeng, Y., Cao, S., Pang, K., Tang, J., & Lin, G. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-230954 · Cited by 8
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Authors: Prescott, H. C., & Angus, D. C.
Affiliations: University of Michigan (US)
University of Pittsburgh (US)
ORCID: Prescott, Hallie C.
Angus, Derek C.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2018-01-02
Volume: 319
Issue: 1
Pages: 62
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.2017.17687
PMC: PMC5839473
OpenAlex: W2782135811
Semantic Scholar: 98cad261fafa6b5df5332a165d01f11de1afd48e
Cited by: 1,059
References: 93
Citations by year: 2026: 143 · 2025: 149 · 2024: 161 · 2023: 142 · 2022: 124 · 2021: 135 · 2020: 103 · 2019: 67 · 2018: 32
FWCI: 65.73
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM097471, K08GM115859)
Topics: Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords: sepsis survivors, post-hospital care, post-discharge rehabilitation, physiotherapy referral, functional recovery, cognitive impairment, post-traumatic stress disorder, depression, anxiety, hospital readmission, recurrent infections, acute kidney injury, cardiovascular events, activities of daily living, sepsis severity, immune dysfunction, hospital quality of care, sepsis management guidelines
MeSH terms: Activities of Daily Living, Adult, Mental Disorders, Cognition Disorders, Hospitalization, Humans, Sepsis

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