• 
• 

Three Part Question

In [adult patients with classical heat-stroke] does [treatment with Dantrolene] [improve outcome]?

Clinical Scenario

A 53 year old male is brought in by ambulance from a nearby building site after a collapse, on an uncharacteristically hot day. In the resuscitation room he has a GCS of 3. He is found to be warm and dry and to have a temperature of 42.3°C. You diagnose heat stroke and wonder if Dantrolene would be useful in this scenario.

Search Strategy

Medline 1966 to 2008 week 9 using the Ovid interface. Embase 1980 to 2008 Week 9 using the Ovid interface
The Cochrane Library Issue 1 2008
Medline: [(*heatstroke OR classical heatstroke) and (dantrolene.mp OR dantrolene sodium)]. Limit to human and English.

Embase: [(*heatstroke OR classical heatstroke) and (dantrolene OR dantrolene sodium)] and (emergency department.mp OR emergency medicine). Limit to human and English

Cochrane: Dantrolene [*Therapeutic use] [MeSH] and heatstroke [*Therapy] [MeSH]

The bibliographies of relevant papers were cross-referenced.

Search Outcome

A total of 43 papers was found, of which two randomised controlled trials comparing dantrolene with conventional cooling were also felt to be of sufficient quality to be included. Two clinical reviews were also found that referenced these two trials.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Channa AB, Seraj MA, Saddique AA, Kadiwal GH, Shaikh MH, Samarkandi AH 1990 Saudi Arabia	20 heatstroke patients, Tre>41.9°C. Randomised to receive dantrolene 2–4 mg/kg.In both the placebo and treatment arms cooling by "conventional methods" or using a body cooling unit was initiated	RCT	Mean cooling time to T(rectal)<39.0°C	49.7 ± 4.4 vs 69.2 ± 4.8 minutes (p<0.01)	Small study method of randomisation unclear. Inclusion and exclusion criteria not clearly stated Not blinded Possible bias from different cooling
			neurological outcome	No difference
			mortality	No difference
Bouchama A, Cafege A, Devol EB, Labdi O, El-Assil K, Seraj M 1991 Saudi Arabia	52 adult patients with classical heatstroke. Tre>40.1° Patients were assigned to receive either Dantrolene sodium (2 mg/kg body weight iv) or placebo. Cooling therapy using a body cooling unit was initiated in all.	RCT	Mean cooling time to Tre <39.4°C	No significant difference 67.9 vs 69 minutes.	Patients randomized in groups of 10. Not stated whether outcomes were blinded.
			Complication rate	Complications seen in 6 (23%) patients receiving dantrolene sodium and 7 (27%) patients receiving placebo; the difference was not statistically significant
			mean length of stay in hospital	4.7 ± 2.0 vs 2.9 ± 0.9 days in the control (not statistically significant)
			Mortality	No significant difference (1 patient in control group died)

Comment(s)

Heat stroke is characterised by a failure of the body’s thermoregulatory system in the presence of high core body temperature. The core temperature necessary for the condition to be classified as heat stroke is most often quoted as a rectal temperature exceeding 40.6°C. Heat stroke may be divided into exertional and non-exertional (classic) heat stroke. Classic heat stroke occurs during extreme heat waves, the elderly being particularly vulnerable. Although dantrolene has been shown to be useful in the treatment of other heat illness, it has not clearly been shown to be useful in the treatment of classic heat stroke. In the first study although the mean cooling time was significantly slower in the untreated group there was no difference in clinical outcome. There were a number of methodological flaws in the study making confident interpretation of the results difficult.

Clinical Bottom Line

There is insufficient evidence to recommend using Dantrolene in patients with classical heat-stroke.

References

1. Eran Hadad, Yoav Cohen-Sivan, Yuval Heled, and Yoram Epstein. Clinical review: Treatment of heat stroke: should dantrolene be considered? Crit Care. 2005; 9(1): 86–91.
2. Channa AB, Seraj MA, Saddique AA, Kadiwal GH, Shaikh MH, Samarkandi AH: Is dantrolene effective in heat stroke patients? Critical Care Medicine 1990 18:290-292
3. Bouchama A, Cafege A, Devol EB, Labdi O, El-Assil K, Seraj M Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Critical Care Medicine 1991, 19:176-180