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Three Part Question

In [adults who have sustained an out-of-hospital cardiac arrest] does [therapeutic hypothermia] [improve outcome]?

Clinical Scenario

A 46 year old father of three collapses in the street with a cardio-respiratory arrest. He receives five minutes of bystander CPR. When the ambulance crew arrives he is in VF. Return of spontaneous circulation is achieved after defibrillation. On arrival in the emergency department he is still in coma. You wonder if his chances of survival or of a good neurological outcome would be improved by therapeutic hypothermia?

Search Strategy

Medline 1966-05/04 using the Ovid interface, The Cochrane Library, Issue 2, 2004 and Bandolier to 05/04.
Medline: [exp Hypothermia, Induced/ OR hypothermia, therapeutic.mp.] AND [exp Heart Arrest/ OR cardiac arrest.mp.] LIMIT to human AND English language.
Cochrane Library: 'hypothermia'

Search Outcome

Altogether 176 papers were found in Medline, only four described any sort of comparative study. Four papers were found in Cochrane, none of which were relevant to the three-part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bernard, SA 1997 Australia	22 adults who remained unconscious after return of spontaneous circulation after out-of-hospital cardiac arrest Hypothermia group cooled to 33C for 12h and rewarmed over 6h to 36C	Prospective study with historical control group.	Good neurological recovery (Glasgow Outcome Scale 1 or 2)	Hypothermia gp 11/22 v Normothermia gp 3/22 P<0.05	Prospective study with 22 historical controls rather than a randomised control trial
			Survival	Hypothermia gp 12/22 v Normothermia gp 5/22 P<0.05
Yanagawa Y et al, 1998, Japan	13 adults with out-of-hospital cardiac arrest and return of spontaneous circulation Core temperature 33-34C for 48h. Rewarmed to 37C at 1C/day. Control group 15 patients treated before the hypothermia protocol was started	Prospective study	Good neurological recovery (GOS 1)	Hypothermia gp 3/13 v Normothermia gp 1/15	Historical controls rather than randomised study
			Survival	Hypothermia gp 7/13 v Normothermia gp 5/15 P=0.27
The Hypothermia after Cardiac Arrest Study Group 2002 Europe	275 adults with out-of-hospital cardiac arrest and return of spontaneous circulation Hypothermia to 32-34C for 24h then passive rewarming over 8h v normothermia	Randomised controlled trial with blinded assessment of outcome.	Good neurological outcome at 6 months (GOS 1 or 2)	Hypothermia gp 75/136 v Normothermia gp 54/137, p=0.009	Enrollment rate slower than expected Study ended when funds ran out
			Survival at 6 months	80/136 v Normothermia gp 61/137, p=0.02
Bernard, SA 2002 Australia	77 adults who remained unconscious after resuscitation from out-of-hospital cardiac arrest hypothermia to 33C for 12h v normothermia	Randomised control trial	Good neurological recovery (GOS 1-2)	Hypothermia gp 21/43 v Normothermia gp 9/34, p=0.046	Odd and even day pre-hospital randomisation
			Survival	Hypothermia gp 21/43 v Normothermia 11/34, p=0.145

Comment(s)

There are only four trials of mild hypothermia after cardiac arrest, and only two are randomised controlled trials. Treatment could not be blinded. All show a neurological benefit from mild hypothermia. Only two showed a survival benefit. The main inclusion criterion for these two trials was that patients had been in ventricular fibrillation. In study number 5 patients with a nonperfusing ventricular tachycardia were also included. There is no uniform protocol for how long hypothermia should be maintained, or the rate of rewarming.

Clinical Bottom Line

Patients remaining unconscious after out-of-hospital cardiac arrest, from ventricular fibrillation or nonperfusing ventricular tachycardia, should be cooled to 32-34C for at least 12h as part of their post-arrest intensive care to optimise neurological recovery. This therapeutic strategy has been endorsed by the International Liaison Committee on Resuscitation (1,2).

References

1. Bernard SA, Jones BM, Horne MK. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 1997;30(2):146-153.
2. Yanagawa Y, Ishihara S, Norio H, et al. Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resuscitation 1998;39(1-2):61-66.
3. The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346(22):549-556.
4. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346(8):557-563.
5. Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation 2003;57:231-235.
6. Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 2003;108:118-121.