Hypothermia After In-Hospital Cardiac Arrest - HACA-IHCA

Contribution To Literature:

Among patients presenting with coma after in-hospital cardiac arrest in the HACA-IHCA trial, hypothermic temperature control did not improve survival nor functional outcomes at day 180 as compared with normothermia.


The goal of the trial was to compare the effect of hypothermic temperature control versus normothermia after in-hospital cardiac arrest on mortality and functional outcomes.

Study Design

The HACA-IHCA trial was a multicenter, open-label, blinded outcome-assessed randomized controlled trial among patients with coma after in-hospital cardiac arrest. Patients were randomized in 1:1 fashion to hypothermic temperature control (n = 126) with a target temperature of 32° to 34°C or normothermia (n = 123).  The analyzing team and physicians assessing trial endpoints were unaware of the group assignment. Mild therapeutic hypothermia was induced and maintained for 24 hours followed by slow rewarming at a rate of 0.25°C/h to achieve a targeted temperature of 37.5°C. Centers were asked to maintain temperatures under 37.5°C until functional recovery was achieved with use of fever-control measures at the discretion of participating centers. Hypothermia was initiated with cold fluids (61.4%) or cool packs (54%) with further cooling by intravascular cooling catheter (43%) or closed-loop surface device (28.3%). After 50% of the intended accrual was reached, the study was prematurely terminated for futility.

  • Total screened: 1,055
  • Total randomized participants: 249
  • Total included in primary endpoint analysis: 238
  • Duration of follow-up: 180 days
  • Mean patient age: 73 years
  • Percentage female: 36%

Inclusion criteria:

  • Age >18 years
  • Cardiac arrest defined as in-hospital with indication for chest compression and/or cardiac defibrillation within hospital premises irrespective of initial rhythm or etiology of arrest.
  • Feasibility of hypothermic temperature control within 4 hours of return of spontaneous circulation (ROSC)
  • Glasgow Coma Scale score ≤8 for >45 minutes after in-hospital cardiac arrest

Exclusion criteria:

  • Initial out-of-hospital cardiac arrest and rearrest within the hospital

Other salient features/characteristics:

  • 73% witnessed cardiac arrest
  • 94% with time to CPR 0-5 minutes
  • Mean time to ROSC 16 minutes
  • Defibrillation: 28%
  • Initial rhythm: 38% asystole, 32% pulseless electrical activity, 20% ventricular fibrillation
  • Average temperature within 12 hours after randomization: hypothermia 34.0°C vs. normothermia 36.6°C

Principal Findings:

The primary outcome, all-cause mortality after 180 days, for hypothermic temperature control vs. normothermia, was: 73% vs. 71% (p = 0.822).

Key secondary endpoints for hypothermic temperature control vs. normothermia:

  • In-hospital death: 63% vs. 58% (p = 0.443)
  • Cerebral Performance Category score of 1 or 2 by 180 days: 23% vs. 24% (p = 0.822)
  • Length of intensive care unit stay: 7.0 days vs. 8.0 days (p = 0.584)
  • Length of hospital stay: 11.0 days vs. 13.0 days (p = 0.164)


The results of this trial show that, among patients with coma successfully resuscitated from in-hospital cardiac arrest, hypothermic temperature control with a targeted temperature of 32° to 34°C compared with normothermia did not lead to differences in all-cause mortality or functional outcomes at 180 days. The current study is limited, as it was stopped early for futility and thus was underpowered to detect a small and potentially clinically significant mortality reduction.

Currently, hypothermic temperature control is recommended for post-resuscitation care irrespective of initial rhythm or location of arrest, with the seminal HACA (Hypothermia After Cardiac Arrest) trial in 2002 illustrating targeted hypothermia associated with improved survival and neurologic outcomes among patients with a shockable rhythm. However, more recent evidence reveals ambiguity around the benefits of hypothermia, with the hypothesis that strict avoidance of fever may be the main measure for better outcomes with hypothermia after cardiac arrest. The HYPERION (Therapeutic Hypothermia After Cardiac Arrest in Nonshockable Rhythm) trial, published in 2019, demonstrated improved survival with favorable neurologic outcomes with hypothermia for patients with nonshockable rhythm. More recently, the TTM2 (Targeted Hypothermia Versus Targeted Normothermia After Out-of-Hospital Cardiac Arrest) study, published in 2021, did not support hypothermia to improve survival and performance outcomes for patients of out-of-hospital cardiac arrest as compared to strict normothermia.

It is within the context of these previous studies that the HACA-IHCA trial should be interpreted. The present study illustrates that a well-managed normothermia group (mean temperature 37.0°C) with avoidance of fever may be as sufficient as compared to targeting lower temperatures and has similar findings to the 2021 TTM2 trial among patients with in-hospital arrest as compared to the out-of-hospital arrest from TTM2.


Wolfrum S, Roedl K, Hanebutte A, et al., on behalf of the Hypothermia After In-Hospital Cardiac Arrest Study Group. Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. Circulation 2022;146:1357-66.

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Arrhythmias, Cardiac, Cardiopulmonary Resuscitation, Coma, Critical Care, Defibrillators, Heart Arrest, Hypothermia, Hypothermia, Induced, Out-of-Hospital Cardiac Arrest, Rewarming, Ventricular Fibrillation

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