Efficacy and safety of dantrolene in toxic hyperthermia: a systematic review

What is it about?

Objective: Assess the efficacy and safety of dantrolene treatment for hyperthermia with a focus on toxin-induced hyperthermia. Methods: Multiple publication databases were systematically searched from inception to 31 December 2017 to identify human studies in English, French and Spanish. Randomized control trials (RCT), observational studies and case reports were included. Article selection followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system using predefined criteria for the use of dantrolene in the acute treat- ment of hyperthermia. Results: Of 757 full-text articles, 157 met our study criteria. No randomised controlled trial (RCT) on toxin-induced hyperthermia but two on heatstroke were found. One reported a 19.5 minutes difference in cooling time for patients treated with dantrolene 2.5mg/kg. None reported improved neurological outcomes, sur- vival or length of stay in patients treated with a single dose of dantrolene 2-4mg/kg compared to conventional cooling meas- ures. One observational study on malignant hyperthermia (MH) reported an average 2.4 °C decrease, normalization of heart rate and rigidity after one dose of dantrolene 2.5mg/kg. Another observational study reported a vague significant improvement in temperature and rigidity with dantrolene 2.5mg/kg in patients with neuroleptic malignant syndrome compared to treatment with other medications. Table 1 presents aggregate data on 153 case reports. Precise chronology and magnitude of reported improvements is lacking. The overall evidence is very low with only one RCT achieving moderate Grading of Recommendations Assessment, Development and Evaluation (GRADE). No major adverse reactions were identified. Conclusion: The use of dantrolene outside of MH is not sup- ported by high quality evidence. While dantrolene seems effica- cious to treat toxin-induced rigidity and hyperthermia or heatstroke, its use is mainly anecdotal with very poor reporting of essential data. Standardized reporting of essential criteria to assess dantrolene treatment for toxin-induced hyperthermia would improve evaluation of its potential efficacy.

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