HACA-IHCA

What is the research question

• What is the impact of hypothermic temperature management after an in-hospital cardiac arrest on mortality and functional recovery as compared with normothermia?

How did they do it?

• This is an open-label, investigator-initiated study that was conducted in 11 hospitals across Germany comparing normothermic control with a temperature of 32-34°C for 24 hours after IHCA.

• The primary endpoint was all-cause mortality 180 days post-injury, and the secondary endpoint included favorable functional outcome as defined by the Cerebral Performance Category scale after 180 days. A score of 1 or 2 on the Cerebral Performance Category scale indicated a favorable functional outcome.

What did the study show?

• A total of 249 patients were assigned to hypothermic temperature control (126) or normothermia (123).

• The overall mean age of the group was 72.6 years old, with 64 percent male participants, 73 percent witnessed cardiac arrests, 25%  had an initial shockable rhythm, and the time to return spontaneous circulation was 16.4 minutes.

• The target temperature was reached within 4.1 hours after IHCA and the temperature was maintained for 48 hours at 37°Celsius in the normothermia group.

• Mortality was 72.5%  in the hypothermic temperature control arm by day 180, compared with 71.2% in the normothermia group (relative risk, 1.03 [95% CI, 0.79–1.40]; P=0.822). In-hospital mortality did not significantly differ between the two groups (62.5%  vs 57.6%, relative risk, 1 .11 [9 5 % CI , 0 .86 –1 .46 ]; P =0 443 ).

• 22.5% of the 120 individuals in the hypothermic temperature group had a favorable functional outcome by day 180, compared with 23.7% of those in the normothermia group (relative risk, 1.04 [95% CI, 0.78–1.44]; P=0.822).

Are there any limitations?

• The study ended earlier than planned due to an unplanned interim analysis that showed very little chance of achieving the primary endpoint; however, because of early termination, the utility only had a power of 80% to detect an 18% difference in mortality. Consequently, detecting smaller yet still clinically relevant reductions in mortality is underpowered.

• There is a possibility of bias against a protective effect of hypothermic temperature control as the rate of shockable rhythm in the hypothermic group was lower. Also, a selection bias cannot be excluded as the cause of in-hospital death was not monitored and formal neuro-prognostication guidelines in the study were performed without standardized withdrawal of life-sustaining therapy.

What does it mean?

• In individuals who had been in a coma following IHCA, hypothermic temperature control compared with normothermia did not improve survival or functional outcome at day 180. The trial was underpowered, and significant differences between hypothermia and normothermia may have gone undetected.

• This study supports avoiding fever and controlling temperature between 36-37.5 °C in patients with coma after in-hospital cardiac arrest.