Two new studies may cast some doubt upon the now widely held belief that core cooling improves outcomes in unconscious cardiac arrest patients.
The studies, presented at the American Heart Association scientific sessions, found that neither cooling to hypothermic levels, compared with normothermic, nor prehospital, compared with in-hospital, significantly improved mortality or neurologic outcomes in more 2,000 patients. The papers were simultaneously published – one in the New England Journal of Medicine, and the other in JAMA.
Induced hypothermia is now standard of care for unconscious survivors of out-of-hospital cardiac arrests. But some animal models suggest that the earlier cooling begins, the better outcomes result. Dr. Francis Kim and his colleagues, however, found almost identical outcomes in a group of 1,359 patients, whatever the timing of hypothermia induction (JAMA 2013 Nov. 17 [doi:10.1001/jama.2013.282173]).
Dr. Kim of the University of Washington, Seattle, and his coauthors randomized patients to induction in the field and during transport, or upon hospital arrival. The intervention group received an infusion of up to 2L of ice-cold normal saline, 7-10 mg pancuronium, and 1-2 mg diazepam, with a target temperature goal of 34°C.
In the control group, hypothermia induction occurred in the hospital, according to each site’s protocol, with either surface or intravascular regimens.
Dr. Niklas Nielsen
Patients were divided into two groups: those with ventricular fibrillation and those without. Patients without VF were older (68 vs. 62 years). Other baseline characteristics – including time from the call to the return of spontaneous circulation, heart rate, and blood pressure – were similar.
The in-field intervention decreased mean core temperature by about 1.2°C in patients with VF and 1.3°C in those without VF. These patients achieved the target core temperature of 34°C more than 1 hour sooner than patients cooled in the hospital.
Survival to discharge was not significantly different between the intervention and control groups (63% vs. 64% of those with VF; 19% vs. 16% of those without VF).
Nor were there significant differences in the neurologic status of full recovery or mild impairment at discharge, the investigators said. Among those with VF, good neurologic status occurred in 57% of the intervention group and 62% of the control group. For those patients without VF, good neurologic outcomes occurred in 14% of the intervention group and 13% of the control group.
There were no significant differences in the proportion of patients who awakened from coma or died without awakening in any of the groups. The median length of stay was within the VF group (9 days for both treatment groups), and among those without VF (about 11 days for each treatment group).
The intervention carried some evidence of increased harm, the authors noted. Significantly more of the intervention patients rearrested during transport (26% vs. 21% of the controls). They also had significantly lower oxygenation, increased pulmonary edema on the first chest x-ray, and greater use of diuretics in the first 12 hours of hospitalization.
"Importantly, the method of pre-hospital hypothermia may have been associated with early harm that could have masked subsequent improvement," the investigators noted. "Rearrest possibly worsened brain ischemia that did not affect early mortality, but manifested as increased risk of death later during the hospitalization."
The second study released at the AHA meeting questioned whether induced hypothermia confers significant benefit over maintaining a near-normothermic temperature. Patients cooled to 33°C had no better outcomes than those whose core temperatures were held at 36°C, Dr. Niklas Nielsen and colleagues reported Nov. 18 (N. Engl. J. Med. 2013 Nov. 17 [doi:10.1056/NEJMoa1310519]).
"Our trial does not provide evidence that targeting a body temperature of 33° C confers any benefit for unconscious patients admitted to the hospital after out-of-hospital cardiac arrest, as compared with targeting a body temperature of 36°C," wrote Dr. Nielsen of Helsingborg Hospital, Sweden, and his colleagues.
The team analyzed outcomes for 939 patients who had been randomized to the two cooling regimens. The study’s primary outcome was all-cause mortality by 180 days after enrollment. The secondary outcomes included a composite of death or poor neurologic outcome at 180 days as evaluated with the Cerebral Performance Category (CPC) and modified Rankin scales.
The intervention consisted of 36 hours of cooling and gradual rewarming. Treatment teams were allowed to use ice packs, ice-cold fluid, and intravascular or surface temperature management. Gradual rewarming to 37°C commenced after 28 hours; this was discontinued or tapered at 36 hours. After this, patients in both groups were treated with fever-control measures to prevent a rebound temperature of above 37.5°C.
The patients were a mean of 64 years old; most of them (about 75%) had VF as the first shocked rhythm. Spontaneous circulation returned a median of 25 minutes after the arrest. All were unconscious when they arrived at the hospital. The mean follow-up was 256 days.