Observational Study

. 2025 Apr 1;53(4):e928-e940.

doi: 10.1097/CCM.0000000000006621. Epub 2025 Feb 24.

Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis

Keibun Liu¹, Takaya Nakashima^{2

3}, Tadahiro Goto², Kensuke Nakamura^{4

5}, Hidehiko Nakano⁵, Maiko Motoki⁵, Hiroshi Kamijo⁶, Matsuoka Ayaka⁷, Kenzo Ishii⁸, Yasunari Morita⁹, Takashi Hongo^{10

11}, Nobutake Shimojo¹², Yukiko Tanaka¹³, Manabu Hanazawa¹⁴, Tomohiro Hamagami¹⁵, Kenji Oike¹⁶, Daisuke Kasugai¹⁷, Yutaka Sakuda¹⁸, Yuhei Irie¹⁹, Masakazu Nitta²⁰, Kazuki Akieda²¹, Daigo Shimakura²², Hajime Katsukawa²³, Toru Kotani²⁴, Peter Nydahl^{25

26}, Stefan J Schaller²⁷, Takayuki Ogura²⁸; Investigating Long term Outcomes of ICU patients with Sepsis or Septic shock (ILOSS) Study Group

Affiliations

¹ Non-Profit Organization ICU Collaboration Network (ICON), Tokyo, Japan.
² TXP Medical Co. Ltd., Tokyo, Japan.
³ Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁴ Department of Critical Care Medicine, Yokohama City University Hospital 3-9, Yokohama, Kanagawa, Japan.
⁵ Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Hitachi, Ibaraki, Japan.
⁶ Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, Nagano, Japan.
⁷ Department of Emergency and Critical Care Medicine Faculty, Saga University Hospital, Saga, Japan.
⁸ Department of Anesthesiology, ICU, Fukuyama City Hospital, Fukuyama, Hiroshima, Japan.
⁹ Department of Emergency and Intensive Care Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
¹⁰ Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
¹¹ Department of Emergency, Okayama Saiseikai General Hospital, Okayama, Japan.
¹² Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
¹³ Department of Emergency, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki, Japan.
¹⁴ Department of Rehabilitation, Japan Red Cross Narita Hospital, Narita, Chiba, Japan.
¹⁵ Tajima Emergency and Critical Care Medical Center, Toyooka Public Hospital, Toyooka, Hyogo, Japan.
¹⁶ Department of Rehabilitation, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan.
¹⁷ Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
¹⁸ Department of Intensive Care Medicine, Okinawa Kyodo Hospital, Naha, Okinawa, Japan.
¹⁹ Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Fukuoka, Japan.
²⁰ Department of ICU, Niigata University Medical and Dental Hospital, Niigata, Japan.
²¹ Department of Emergency Medicine, SUBARU Health Insurance Society Ota Memorial Hospital, Ota, Gunma, Japan.
²² Graduate School of Data Science, Shiga University, Japan.
²³ Japanese Society for Early Mobilization, Tokyo, Japan.
²⁴ Department of Intensive Care Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
²⁵ Nursing Research, University Hospital Schleswig-Holstein, Kiel, Germany.
²⁶ Institute of Nursing Science and Development, Paracelsus Medical University, Salzburg, Austria.
²⁷ Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria.
²⁸ Department of Emergency Medicine and Critical Care Medicine, Tochigi Prefectural Emergency and Critical Care Center, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.

PMID: 39992173
DOI: 10.1097/CCM.0000000000006621

Observational Study

Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis

Keibun Liu et al. Crit Care Med. 2025.

. 2025 Apr 1;53(4):e928-e940.

doi: 10.1097/CCM.0000000000006621. Epub 2025 Feb 24.

Authors

Affiliations

¹ Non-Profit Organization ICU Collaboration Network (ICON), Tokyo, Japan.
² TXP Medical Co. Ltd., Tokyo, Japan.
³ Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁴ Department of Critical Care Medicine, Yokohama City University Hospital 3-9, Yokohama, Kanagawa, Japan.
⁵ Department of Emergency and Critical Care Medicine, Hitachi General Hospital, Hitachi, Ibaraki, Japan.
⁶ Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine, Nagano, Japan.
⁷ Department of Emergency and Critical Care Medicine Faculty, Saga University Hospital, Saga, Japan.
⁸ Department of Anesthesiology, ICU, Fukuyama City Hospital, Fukuyama, Hiroshima, Japan.
⁹ Department of Emergency and Intensive Care Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
¹⁰ Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
¹¹ Department of Emergency, Okayama Saiseikai General Hospital, Okayama, Japan.
¹² Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
¹³ Department of Emergency, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki, Japan.
¹⁴ Department of Rehabilitation, Japan Red Cross Narita Hospital, Narita, Chiba, Japan.
¹⁵ Tajima Emergency and Critical Care Medical Center, Toyooka Public Hospital, Toyooka, Hyogo, Japan.
¹⁶ Department of Rehabilitation, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan.
¹⁷ Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
¹⁸ Department of Intensive Care Medicine, Okinawa Kyodo Hospital, Naha, Okinawa, Japan.
¹⁹ Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Fukuoka, Japan.
²⁰ Department of ICU, Niigata University Medical and Dental Hospital, Niigata, Japan.
²¹ Department of Emergency Medicine, SUBARU Health Insurance Society Ota Memorial Hospital, Ota, Gunma, Japan.
²² Graduate School of Data Science, Shiga University, Japan.
²³ Japanese Society for Early Mobilization, Tokyo, Japan.
²⁴ Department of Intensive Care Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
²⁵ Nursing Research, University Hospital Schleswig-Holstein, Kiel, Germany.
²⁶ Institute of Nursing Science and Development, Paracelsus Medical University, Salzburg, Austria.
²⁷ Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria.
²⁸ Department of Emergency Medicine and Critical Care Medicine, Tochigi Prefectural Emergency and Critical Care Center, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.

PMID: 39992173
DOI: 10.1097/CCM.0000000000006621

Abstract

Objective: Sepsis often leads to heterogeneous symptoms of post-intensive care syndrome (PICS) composing physical, cognitive, and psychiatric disabilities, resulting in deteriorated quality of life (QoL), with limited interventions. This study aimed to identify phenotypes of sepsis-associated PICS by physical, cognitive, and psychiatric function and QoL at hospital discharge.

Design: A prospective observational study.

Setting: Twenty-one mixed ICUs.

Patients: All consecutive adult patients between November 2020 and April 2022, diagnosed with sepsis at ICU admissions and survived discharge, were enrolled.

Interventions: None.

Measurements and main results: Phenotyping with clusters determined by three approaches was performed with following variables at hospital discharge: Barthel Index (≤ 90 defined physical PICS), Short Memory Questionnaire (< 40 defined cognitive PICS), Hospital Anxiety and Depression Scale (≥ 8 defined psychiatric PICS), Impact of Event Scale-Revised (≥ 25 defined psychiatric PICS), EuroQoL 5-dimension 5-level, Clinical Frailty Scale hand-grip strength, and Medical Research Council. Each disability, employment, destination, and survival, were followed over the first year of hospital discharge. In total, 220 ICU patients were included (median age: 72.5 yr, 129 males (59%), 166 septic shocks (75%), and median Sequential Organ Failure Assessment Score: 8). Four phenotypes were identified: group 1 ( n = 62) with no PICS, group 2 ( n = 55) with mild PICS (physical and cognitive), group 3 ( n = 53) with moderate PICS (all domains), and group 4 ( n = 50) with severe PICS (all domains). Functional decline and recovery significantly varied among the phenotypes. Physical and cognitive PICS in group 2 improved by the 3-month follow-up, whereas the disabilities in groups 3 and 4 remained over the year. Psychiatric PICS in groups 3 and 4 ameliorated, whereas depression symptoms in group 4 were still evident at the 12-month follow-up. All groups showed persistent moderate to severe reduced QoL and low employment (0-50%). The survival in group 4 continuously decreased.

Conclusions: Four clinical phenotypes of ICU sepsis survivors might contribute to a deeper understanding of post-sepsis trajectories and an individualized treatment approach.

Keywords: follow-up studies; intensive care units; phenotype; post-intensive care syndrome; sepsis.

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Conflict of interest statement

Dr. Liu is performing a preclinical study with funding from MERA completely outside the submitted work. Dr. Katsukawa receives a salary from the Japanese Society for Early Mobilization (non-profit society) as a chair (full-time) outside the submitted work. Drs. Liu and Tanaka received support for article research from the Japanese Association for Acute Medicine. Dr. Schaller’s institution received funding from Fresenius Kabi GmbH, ASP GmbH, and Reactive Robotics GmbH; he received funding from Reactive Robotics GmbH, ASP GmbH, STIMIT AG, ESICM, Fresenius Kabi Deutschland GmbH, the Innovationsfond of The Federal Joint Committee (G-BA), Springer Verlag GmbH, and Advanz Pharma GmbH; he disclosed he holds stocks in Alphabet Inc., Bayer AG, and Siemens AG. Dr. Schaller holds stocks in small amounts from Alphabet Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. Dr. Irie received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

1. Kaukonen K-M, Bailey M, Suzuki S, et al.: Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014; 311:1308–1316
1. Mostel Z, Perl A, Marck M, et al.: Post-sepsis syndrome—an evolving entity that afflicts survivors of sepsis. Mol Med. 2019; 26:6
1. Kurematsu K, Ikematsu Y: Quality of life of sepsis survivors. Crit Care Med. 2023; 51:1339–1349
1. Inoue S, Nakanishi N, Amaya F, et al.: Post-intensive care syndrome: Recent advances and future directions. Acute Med Surg. 2024; 11:e929
1. Harvey MA, Davidson JE: Postintensive care syndrome: Right care, right now…and later. Crit Care Med. 2016; 44:381–385

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Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis

Affiliations

Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous