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Therapeutic Hypothermia Following Cardiac Arrest.

Citation/s: The hypothermia After Cardiac Arrest Study Group (2002). Mild Therapeutic Hypothermia To Improve Neurologic Outcome After Cardiac Arrest. NEJM 346;8:549-56
 

Lead author's name and fax: Dr Fritz Sterz, Universitatsklinik fur Notfallmedizin, Allgemeines Krankenhaus der Stadt Wien, Wahringer Gurtel 18-20/6D, 1090 Vienna, Austria. fritz.sterz@akh-wien.ac.at

Three-part Clinical Question: Does the use of therapeutic mild hypothermia improve mortality or neurological outcome after resuscitation from cardiac arrest due to ventricular fibrillation or VT?

The Study: Single-blinded concealed randomised controlled trial with intention-to-treat.

The Study Patients: All patients admitted to hospital following a cardiac arrest were assessed for inclusion into this multicentre study. March 1996- January 2001.

Inclusion criteria: Witnessed cardiac arrest, ventricular fibrillation or pulseless VT, a presumed cardiac origin of the arrest, age 18-75yrs, an estimated interval of 5 to 15 minutes from the patient's collapse to the first attempt at resuscitation by emergency personnel, an interval of no more than 60 mins from the collapse to the restoration of a spontaneous circulation.

Exclusion criteria: Tympanic temperature <30C on admission, a comatosed state before the cardiac arrest due to the administration of drugs that depress the central nervous system, pregnancy, response to verbal commands after the return of spontaneous circulation and before randomization, evidence of hypotension (MAP<60mmHg) for more than 30 mins after the return of spontaneous circulation and before randomization, evidence of hypoxaemia (SpO2<85%) for more than 15 mins after the return of spontaneous circulation and before randomization, a terminal illness that preceded the arrest, factors that made the participation in follow-up unlikely, enrolment in another study, the occurrence of cardiac arrest after the arrival of emergency medical personnel, or a known pre-existing coagulopathy.

All patients received standard intensive care according to a detailed protocol. Sedation was induced with IV midazolam and fentanyl, the doses adjusted to facilitate mechanical ventilation. To prevent shivering pancuronium was given every 2 hours for a total of 32 hours.

Control group (N = 138; 137 analysed): Patients randomly assigned to the normothermia group were place on a conventional bed and normothermia was maintained. Temperature on admission was measure by an infrared tympanic monitor. Subsequent temperatures were from a bladder temperature probe. Conventional care as above.
 

Experimental group (N = 137; 136 analysed): Patients randomly assigned to the hypothermic group were cooled to the target temperature of 32-34C within four hours after the return of spontaneous circulation. This was attempted with an external cooling device (TheraKool). If this target was not achieved then ice packs were applied. The temperature was maintained at 32-34C for 24 hours from the start of cooling, followed by passive rewarming to normothermia over approximately 8 hours. Temperature measurement was as in the control group. Otherwise conventional care.

The Evidence:

EBM Comments:

1. Do the methods allow accurate testing of the hypothesis? Yes, although hypothermia was discontinued early in 14 patients due to; death (6), arrhythmia and haemodynamic instability (3), technical problems with the cooling device (2), liver rupture (1), previous random assignment to the hypothermia group (1), an error in the duration of cooling. All randomised patients were included in the analysis of mortality. It is unclear whether they were included in the 'favourable outcome' analysis.

2. Do the statistical tests correctly test the results to allow differentiation of statistically significant results? Yes

3. Are conclusions valid in light of the results? Yes. The use of therapeutic hypothermia following OOHCA is associated with a clear improvement in outcome. Note of caution: When compared with the Bernard study; The major benefit in this HACA was in reduced mortality. The proportion of good outcomes in survivors at 6 months was similar in both groups. Therefore HACA reduced death – may have been due to poor neurology and withdrawal of support – but the caregivers were not blinded!!!

4. Did results get omitted, and why? Yes. One patient in each group was lost to follow-up for neurologic status.

5. Did they suggest areas of further research? Yes. To determine whether these findings apply to patients at less risk of brain damage and to those with cardiac arrest due to causes other that ventricular fibrillation.

6. Did they make any recommendations based on the results and were they appropriate? Yes. That therapeutic hypothermia should be used routinely in these patients. This is appropriate. It is very important to highlight the fact that almost 3,500 patients were screened and <10% enrolled. This is very important when it comes to assessing generalisability of data.

7. Is the study relevant to my clinical practice? Yes, In Europe approximately 375,000 people have a cardiac arrest each year, 30,000 of whom would fulfil the study inclusion criteria. Adopting this technique may result in the prevention of 1200 to 7500 unfavourable neurological outcomes per year.

8. What level of evidence does this study represent? 1⁺ (in patients who would have

9. What grade of recommendation can I make on this result alone? B

10. What grade of recommendation can I make when this study is considered along with other available evidence? A

11. Should I change my practice because of these results? Yes. Patients fulfilling trial entry requirements should be managed with therapeutic hypothermia.

12. Should I audit my current practice because of these results? Yes

Appraised by: Dr Chris Cairns, Department of Anaesthesia and Intensive Care, Stirling Royal Infirmary, Livilands, Stirling, FK8 2UA.Wednesday, September 22nd, 2004

Email: Chris.Cairns@btinternet.com

Kill or Update By: Sept 2009

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