Targeted Temperature Management for 24 vs. 48 Hours After OHCA
Does targeted temperature management at 33° C for 48 hours improve neurologic outcomes compared with 24-hour targeted temperature management in unconscious patients following out-of-hospital cardiac arrest (OHCA)?
Following admission to an intensive care unit (at any of 10 European centers) after OHCA presumed secondary to cardiac etiology, 355 patients ages 18-79 were randomized to receive targeted temperature management at 33° C (±1° C) for either 24 or 48 hours using surface and/or invasive cooling methods. Primary outcome was neurologic status 6 months after cardiac arrest, and secondary outcomes were 6-month mortality and time to death. Neurologic assessors and statisticians were blinded to the study group assignment, but medical personnel, research staff, and relatives were not.
Favorable neurologic outcome at 6 months following OHCA was achieved in 69% of patients in the 48-hour group compared with 64% in the 24-hour group; however, the difference did not reach statistical significance. The 6-month mortality was lower in the 48-hour group at 27% versus 34% in the 24-hour group but did not reach statistical significance. Time to death overall showed no significant difference between the 2 groups.
Neurologic outcome was defined by the Cerebral Performance Categories score. A score of 1 or 2 was deemed a favorable neurologic outcome:
- Alert and able to work and lead a normal life
- Moderate cerebral disability and sufficient cerebral function for part-time work
- Severe cerebral disability, dependent on others, and impaired brain function
- Coma and vegetative state
- Dead or certified brain dead
The rate of adverse events in the 48-hour group was higher (97 vs. 91%) than for the 24-hour group; this was statistically significant at p = 0.04. There were more incidents of hypotension in the 48-hour group (62 vs. 49%, p = 0.013). There was no significant difference for rates of pneumonia or any bleeding. However, there were fewer episodes of severe bleeding in the 48-hour group (1 vs. 4%, p = 0.03) compared with the 24-hour group.
Median length of stay in the intensive care unit was longer for the 48-hour group (median 151 vs. 117 hours, p < 0.001), but overall hospital length of stay was not significantly different. Four patients in the 48-hour group had coronary artery bypass surgery compared with none in the 24-hour group.
The trial was completed by 351 patients. Baseline characteristics were comparable between the 2 groups; however, time from return of spontaneous circulation to achievement of target temperature was shorter in the 48-hour group (281 vs. 320 minutes, p = 0.01) than in the 24-hour group.
There were no statistically significant differences between the 2 groups in the other pre-specified primary and secondary outcomes (i.e., Cerebral Performance Categories score at hospital discharge, 3 months, and 6 months, or in the level of consciousness at 3 days following cardiac arrest. Causes of death were comparable between the 2 groups. There was no significant difference in the number of patients for whom life-support therapy was withdrawn due to neurologic causes.
Favorable neurologic outcome occurred in 69% of patients treated with targeted temperature management for 48 hours vs. 64% treated for 24 hours, but the difference did not reach statistical significance. The 6-month mortality was lower in the 48-hour group at 27% versus 34% for the 24-hour group, but this also was not statistically significant. Adverse events including hypotension occurred in 97% of the 48-hour group versus 91% in the 24-hour group, but most adverse events were mild.
This study did not demonstrate a statistically significant difference in favorable neurologic outcome or mortality at 6 months following OHCA in patients treated with targeted temperature management for 48 hours versus 24 hours. The researchers concluded the results not statistically significant due to sample size, and thus further research is needed.
Keywords: Out-of-Hospital Cardiac Arrest, Acute Coronary Syndrome, Temperature, Body Temperature, Coma, Persistent Vegetative State, Brain Death, Consciousness, Length of Stay, Unconsciousness, Death, Intensive Care Units, Brain
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