Association Between Targeted Temperature Management and New-Onset Brain Disability in in-Hospital Cardiac Arrest Survivors: A Nationwide Cohort Study

Abstract

Objectives

Targeted temperature management (TTM) is the standard of care for comatose cardiac arrest survivors. However, evidence regarding its long-term neurological impact specifically on in-hospital cardiac arrest (IHCA) survivors remains limited. This study investigated the association between TTM and the risk of new-onset brain disability in adult IHCA survivors using a “hard” endpoint derived from a national registry.

Design

This nationwide retrospective cohort study utilized the South Korean National Health Insurance Service database (2013-2022). Adult IHCA survivors were categorized into TTM and non-TTM groups. The primary endpoint was newly diagnosed brain disability registered in the Korea National Disability Registration System. This endpoint requires stringent certification by board-certified specialists after at least six months of active treatment to confirm irreversibility. We performed 1:5 propensity score matching and used stratified Cox proportional hazards models to estimate hazard ratios (HR).

Results

Among 95 337 eligible survivors, 31 592 patients were included in the matched cohort (5633 TTM vs 25 959 non-TTM). The TTM group showed a significantly lower incidence of new-onset brain disability compared with the non-TTM group (5.0% vs 5.2%). In the PS-matched analysis, TTM was independently associated with a reduced risk of new-onset brain disability (HR, 0.85; 95% confidence interval [CI], 0.75-0.96; P = .012). Multivariable sensitivity analysis in the entire cohort confirmed this protective association (adjusted HR, 0.80; 95% CI, 0.70-0.90; P < .001).

Conclusion

In this large-scale nationwide cohort of IHCA survivors, TTM implementation was associated with a decreased risk of legally certified, permanent brain disability. These findings provide real-world evidence supporting the continued use of TTM as a neuroprotective strategy to improve long-term quality of survivorship in the IHCA population.

Keywords

in-hospital cardiac arrest targeted temperature management brain disability prognosis cohort studies

Get full access to this article

View all access options for this article.

References

Andersson

Arctaedius

Cronberg

, et al. In-hospital versus out-of-hospital cardiac arrest: Characteristics and outcomes in patients admitted to intensive care after return of spontaneous circulation. Resuscitation. 2022;176:1‐8. doi:10.1016/j.resuscitation.2022.04.023

Andersen

Holmberg

Berg

Donnino

Granfeldt

. In-Hospital cardiac arrest: A review. JAMA. 2019;321(12):1200‐1210. doi:10.1001/jama.2019.1696

Nolan

Neumar

Adrie

, et al. Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A scientific statement from the international liaison committee on resuscitation; the American Heart Association emergency cardiovascular care committee; the council on cardiovascular surgery and anesthesia; the council on cardiopulmonary, perioperative, and critical care; the council on clinical cardiology; the council on stroke. Resuscitation. 2008;79(3):350‐379. doi:10.1016/j.resuscitation.2008.09.017

Girotra

Nallamothu

Spertus

, et al. Trends in survival after in-hospital cardiac arrest. N Engl J Med. 2012;367(20):1912‐1920. doi:10.1056/NEJMoa1109148

Panchal

Bartos

Wyckoff

, et al. Part 2: Evidence evaluation and guidelines development: 2025 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2025;152(16_suppl_2):S313‐S322.

Nolan

Sandroni

Bottiger

, et al. European resuscitation council and European society of intensive care medicine guidelines 2021: Post-resuscitation care. Intensive Care Med. 2021;47(4):369‐421. doi:10.1007/s00134-021-06368-4

Dankiewicz

Cronberg

Lilja

, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021;384(24):2283‐2294. doi:10.1056/NEJMoa2100591

Lascarrou

Merdji

Le Gouge

, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019;381(24):2327‐2337. doi:10.1056/NEJMoa1906661

Yin

Xie

, et al. Survival to hospital discharge and neurological outcomes with targeted temperature management after in-hospital cardiac arrest: A systematic review and meta-analysis. Ann Palliat Med. 2022;11(1):68‐76. doi:10.21037/apm-21-3403

10.

Geocadin

Callaway

Fink

, et al. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: A scientific statement from the American Heart Association. Circulation. 2019;140(9):e517‐e542. doi:10.1161/CIR.0000000000000702

11.

Becker

Aufderheide

Geocadin

, et al. Primary outcomes for resuscitation science studies: A consensus statement from the American Heart Association. Circulation. 2011;124(19):2158‐2177. doi:10.1161/CIR.0b013e3182340239

12.

Von Elm

Altman

Egger

Pocock

Gøtzsche

Vandenbroucke

. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. Lancet. 2007;370(9596):1453‐1457.

13.

Lee

Park

S-H

Shin

Kim

. Cohort profile: The national health insurance service–national sample cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15‐e15.

14.

Kim

Jung

Kim

Park

Shin

. The Korea national disability registration system. Epidemiol Health. 2023;45:e2023053. doi:10.4178/epih.e2023053

15.

Ohura

Hase

Nakajima

Nakayama

. Validity and reliability of a performance evaluation tool based on the modified barthel Index for stroke patients. BMC Med Res Methodol. 2017;17(1):131.

16.

Rhee

Jentzsch

Kadri

, et al. Variation in identifying sepsis and organ dysfunction using administrative versus electronic clinical data and impact on hospital outcome comparisons. Crit Care Med. 2019;47(4):493‐500. doi:10.1097/CCM.0000000000003554

17.

Day

Edelsbrunner

. Efficient algorithms for agglomerative hierarchical clustering methods. J Classif. 1984;1(1):7‐24.

18.

Rosenbaum

Rubin

. Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc. 1984;79(387):516‐524.

19.

Albinali

Alumran

Alrayes

. Impact of cardiopulmonary resuscitation duration on the neurological outcomes of out-of-hospital cardiac arrest. Int J Emerg Med. 2022;15(1):12. doi:10.1186/s12245-022-00418-4

20.

Haywood

Whitehead

Nadkarni

, et al. COSCA (Core outcome set for cardiac arrest) in adults: An advisory statement from the international liaison committee on resuscitation. Circulation. 2018;137(22):e783‐e801. doi:10.1161/CIR.0000000000000562

21.

Lilja

Nielsen

Friberg

, et al. Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33 degrees C versus 36 degrees C. Circulation. 2015;131(15):1340‐1349. doi:10.1161/CIRCULATIONAHA.114.014414

22.

Choi

. Legal and ethical issues regarding end-of-life care in Korea. Development and Society. 2016;45(1):151‐164.

23.

Teixeira

FJP

Ahmad

Gibatova

, et al. Do neuroprognostic studies account for self-fulfilling prophecy bias in their methodology? The SPIN protocol for a systematic review. Crit Care Explor. 2023;5(7):e0943. doi:10.1097/CCE.0000000000000943

24.

Saxena

Young

Pilcher

, et al. Early temperature and mortality in critically ill patients with acute neurological diseases: Trauma and stroke differ from infection. Intensive Care Med. 2015;41(5):823‐832. doi:10.1007/s00134-015-3676-6

25.

Taccone

Lascarrou

Skrifvars

. Targeted temperature management and cardiac arrest after the TTM-2 study. Crit Care. 2021;25(1):275. doi:10.1186/s13054-021-03718-y