Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest
This review may be edited
Posted By: Anthony Delaney
Posted Date: 13/3/02
Title: Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest
Authors: The Hypothermia after Cardiac Arrest Study Group
Reference: N Engl J Med 2002;346:549-556
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: Background: Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation.
Methods: In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32C to 34C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days.
Results: Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral-performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups.
Conclusions: In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
Treatment allocation was randomly generated by a computer, stratified according to centre and sealed envelopes were used to assign patients.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
Only one patient in each group was lost to follow-up for neurological status.
2b. Were patients analyzed in the groups to which they were randomized?
Yes. "Analysis was carried out according to the intention-to-treat principle".
3. Were patients, health workers, and study personnel blind to treatment?
The treating medical and nursing staff were not blinded to the treatment allocation, but the physicians responsible for assessing neurological outcome were blinded.
4. Were the groups similar at the start of the trial?
No. There were more patients in the normothermia group with a history of diabetes mellitus and coronary heart disease, and more patients in the normothermia group received bystander CPR. These imbalances were controlled for in a multivariate analysis and did not appear to influence outcome.
5. Aside from the experimental intervention, were the groups treated equally?
The groups were treated according to a detailed (unspecified) intensive care protocol.There is no reporting of major treatment differences between the two groups.
What are the Results?
1. How large was the treatment effect?
Neurological outcome
The primary outcome measured was favourable neurological outcome at 6 months, defined as a Pittsburgh cerebral-performance category of 1 (good recovery) or 2 (moderate recovery).
55% of patients in the hypothermia group reported a favourable neurological outcome as compared to 39% in the normothermia group (p=0.009). The absolute risk reduction for favourable neurological outcome was a 16% improvement. The relative risk was 1.40% and the NNT was 6. The authors report that the risk ratio was unchanged after adjustment for the baseline imbalance.
The authors also reported a significant improvement in the secondary outcome of mortality. The overall mortality rate in the normothermia group was 55%, compared to 41% in the hypothermia group (p=0.02)
2. How precise was the estimate of the treatment effect?
The authors report the 95% confidence interval for the relative risk of improved neurological outcome in the hypothermia group as 1.40 (1.08 to 1.81).
The 95% confidence interval for the relative risk of reduced mortality in the hypothermia group was 0.74(0.58 to 0.95).
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
Most likely. The equipment and monitoring used to perform the therapy is readily available, and seems simple to use. The inclusion criteria for the study did select out a group of patients with a high probability of survival(91% of patients were ineligible), so it will need to be remembered that favourable neurological outcome won't occur in 55% of all patients with out of hospital cardiac arrest. There was not a lot coronary intervention performed in these patients which is an increasing consideration in the management of patients with ischaemic coronary events.
2. Were all clinically important outcomes considered?
The primary end point of neurological outcome at 6 months seems quite reasonable. Complications that might be expected from hypothermia were examined and although there was an increase in bleeding and sepsis in the patients treated with hypothermia this was not statistically significent. THere was no analysis of the costs of the treatment or of ICU or hospital length of stay.
3. Are the likely treatment benefits worth the potential harms and costs?
Poor neurological outcome in survivors of sudden out of hospital cardaic arrest is a major problem for the patient, their family and carers, and places a large burden on the health care system. Mild therapeutic hypothermia, as presented in this paper, is a promising therapy for improving neurological outcome in people likely to survive the initial event.
An evidence-based recommendation, which is the building block for an evidence-based guideline, that summarizes this topic can be found in the EBR section.

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