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Impact of frailty on mortality, functional outcome, and health status after out-of-hospital cardiac arrest : insights from the TTM2-trial

Göbel Andertun, Sara LU orcid ; Wissendorff-Ekdahl, Anne LU orcid ; Ullén, Susann LU ; Cronberg, Tobias LU ; Friberg, Hans LU ; Jakobsen, Janus Christian ; Blennow Nordström, Erik LU orcid ; Heimburg, Katarina LU orcid ; Cariou, Alain and Grejs, Anders Morten , et al. (2025) In Intensive Care Medicine 51(12). p.2367-2377
Abstract

Purpose: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.

Methods: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6... (More)

Purpose: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.

Methods: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6 month Glasgow Outcome Scale Extended score), health status (EQ-5D-5L, EQ-VAS), and life satisfaction at 6 and 24 months.

Results: Of 1861 participants, 240 (13%) were prefrail, and 188 (10%) were frail or severely frail. Mortality and poor functional outcome increased significantly with greater frailty. Compared to fit participants, adjusted ORs (95% CI) for 6 month mortality were: prefrail 2.7 (1.8–3.8), frail 3.7 (1.9–7.1), and severely frail 8.9 (4.2–18.7); and poor functional outcome: prefrail 2.9 (1.9–4.2), frail 3.9 (1.9–8.1), and severely frail 35.4 (8.4–148.8). Severely frail participants underwent neuroprognostication less often (p < 0.001), while WLST was more common in the prefrail, frail and severely frail (p < 0.001). Prefrail and frail survivors tended to report more frequent functional decline and lower health status, though with individual variation.

Conclusion: Frailty was associated with a significantly increased risk of mortality and poor functional outcome after out-of-hospital cardiac arrest. Findings suggest more frequent functional decline and lower overall health status in frail survivors.

Trial registration: NCT02908308.

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Abstract (Swedish)
Purpose: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.

Methods: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6... (More)
Purpose: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.

Methods: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6 month Glasgow Outcome Scale Extended score), health status (EQ-5D-5L, EQ-VAS), and life satisfaction at 6 and 24 months.

Results: Of 1861 participants, 240 (13%) were prefrail, and 188 (10%) were frail or severely frail. Mortality and poor functional outcome increased significantly with greater frailty. Compared to fit participants, adjusted ORs (95% CI) for 6 month mortality were: prefrail 2.7 (1.8–3.8), frail 3.7 (1.9–7.1), and severely frail 8.9 (4.2–18.7); and poor functional outcome: prefrail 2.9 (1.9–4.2), frail 3.9 (1.9–8.1), and severely frail 35.4 (8.4–148.8). Severely frail participants underwent neuroprognostication less often (p < 0.001), while WLST was more common in the prefrail, frail and severely frail (p < 0.001). Prefrail and frail survivors tended to report more frequent functional decline and lower health status, though with individual variation.

Conclusion: Frailty was associated with a significantly increased risk of mortality and poor functional outcome after out-of-hospital cardiac arrest. Findings suggest more frequent functional decline and lower overall health status in frail survivors.

Trial registration: NCT02908308. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Frailty, Functional outcome, Mortality, Out-of-hospital cardiac arrest, Patient-reported outcomes, Frailty, Out‑of‑hospital cardiac arrest, Mortality, Functional outcome, Patient‑reported outcomes
in
Intensive Care Medicine
volume
51
issue
12
pages
2367 - 2377
publisher
Springer Science and Business Media B.V.
external identifiers
  • pmid:41212202
  • scopus:105021576313
ISSN
0342-4642
DOI
10.1007/s00134-025-08185-5
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
f3a3d7c4-6e7d-4b11-84ed-c3517bc6c79d
date added to LUP
2026-01-14 11:11:21
date last changed
2026-01-14 13:41:19
@article{f3a3d7c4-6e7d-4b11-84ed-c3517bc6c79d,
  abstract     = {{<p>Purpose: To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.</p><p>Methods: This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6 month Glasgow Outcome Scale Extended score), health status (EQ-5D-5L, EQ-VAS), and life satisfaction at 6 and 24 months.</p><p>Results: Of 1861 participants, 240 (13%) were prefrail, and 188 (10%) were frail or severely frail. Mortality and poor functional outcome increased significantly with greater frailty. Compared to fit participants, adjusted ORs (95% CI) for 6 month mortality were: prefrail 2.7 (1.8–3.8), frail 3.7 (1.9–7.1), and severely frail 8.9 (4.2–18.7); and poor functional outcome: prefrail 2.9 (1.9–4.2), frail 3.9 (1.9–8.1), and severely frail 35.4 (8.4–148.8). Severely frail participants underwent neuroprognostication less often (p &lt; 0.001), while WLST was more common in the prefrail, frail and severely frail (p &lt; 0.001). Prefrail and frail survivors tended to report more frequent functional decline and lower health status, though with individual variation.</p><p>Conclusion: Frailty was associated with a significantly increased risk of mortality and poor functional outcome after out-of-hospital cardiac arrest. Findings suggest more frequent functional decline and lower overall health status in frail survivors.</p><p>Trial registration: NCT02908308.</p>}},
  author       = {{Göbel Andertun, Sara and Wissendorff-Ekdahl, Anne and Ullén, Susann and Cronberg, Tobias and Friberg, Hans and Jakobsen, Janus Christian and Blennow Nordström, Erik and Heimburg, Katarina and Cariou, Alain and Grejs, Anders Morten and Haenggi, Matthias and Hovdenes, Jan and Robba, Chiara and Rylander, Christian and Taccone, Fabio Silvio and Wise, Matt P. and Young, Paul J. and Nielsen, Niklas and Lilja, Gisela}},
  issn         = {{0342-4642}},
  keywords     = {{Frailty; Functional outcome; Mortality; Out-of-hospital cardiac arrest; Patient-reported outcomes; Frailty; Out‑of‑hospital cardiac arrest; Mortality; Functional outcome; Patient‑reported outcomes}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2367--2377}},
  publisher    = {{Springer Science and Business Media B.V.}},
  series       = {{Intensive Care Medicine}},
  title        = {{Impact of frailty on mortality, functional outcome, and health status after out-of-hospital cardiac arrest : insights from the TTM2-trial}},
  url          = {{http://dx.doi.org/10.1007/s00134-025-08185-5}},
  doi          = {{10.1007/s00134-025-08185-5}},
  volume       = {{51}},
  year         = {{2025}},
}