Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial

Abstract

Purpose: To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest. Methods:A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystanderwitnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1-2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes.Results: In total, 300 patients were analyzed and the proportion with CPC 1-2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95-3.85, p = .07. In patients with shockable rhythm, CPC 1-2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06-9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12-4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55-18.3, p = .008. Conclusions:In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.

European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care

“…Both trials reported no significant benefits on patient outcomes, although in the latter trial a post hoc analysis of the subgroup of patients with an initial shockable rhythm and in whom cooling was initiated < 20 min from collapse showed improved neurological outcome at 90 days. 226,227 [ 2 4 _ T D $ D I F F ] Optimal target temperature during hypothermia [ 2 0 _ T D $ D I F F ] The Targeted Temperature Management after Cardiac Arrest trial (TTM-trial) randomised 950 OHCA patients with both initial shockable and non-shockable rhythms to a strategy including 36 h of temperature control (i.e. 28 h at target temperature followed by slow rewarming) and fever control up to 72 h after randomisation; the two target temperatures during the intervention phase were 33 C or 36 C. 27 Strict protocols were followed for assessing prognosis and for withdrawal of life-sustaining treatment (WLST).…”

Individualized management objectives for hypoxic-ischemic brain injury after cardiac arrest

“…A recent large multicenter RCT confirmed that prehospital transnasal evaporative intra-arrest cooling did not improve the 90-day survival rate and neurologic outcomes of patients with OHCA compared with routine cooling after admission [60,61]. Although evidence supporting the benefit of starting prehospital TH before ROSC is lacking, this method is safe and facilitates the application of TTM in hospitals [62].…”

Therapeutic hypothermia for stroke: Unique challenges at the bedside

“…Another approach is that of intranasal cooling, which leads to heat exchange by direct heat loss to air and evaporation of water, which can reach up to a 10% rate of total body heat loss in normal conditions ( 107 ). Transnasal evaporative cooling has been shown to improve neurological outcomes in patients who received cardiopulmonary resuscitation after cardiac arrest with acceptable feasibility and safety ( 112 , 113 ). However, non-invasive cooling using surface cooling and nasopharyngeal cooling is relatively less effective in lowering temperature of the brain parenchyma ( 20 ).…”