PT  - JOURNAL ARTICLE
AU  - Susanne Muehlschlegel
AU  - Raphael Carandang
AU  - Wiley Hall
AU  - Nisha Kini
AU  - Saef Izzy
AU  - Bridget Garland
AU  - Cynthia Ouillette
AU  - Imramsjah M J van der Bom
AU  - Thomas F Flood
AU  - Matthew J Gounis
AU  - John P Weaver
AU  - Bruce Barton
AU  - Ajay K Wakhloo
TI  - Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial
AID  - 10.1136/jnnp-2014-308778
DP  - 2015 Sep 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 1029--1035
VI  - 86
IP  - 9
4099  - http://jnnp.bmj.com/content/86/9/1029.short
4100  - http://jnnp.bmj.com/content/86/9/1029.full
SO  - J Neurol Neurosurg Psychiatry2015 Sep 01; 86
AB  - Background Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH.Methods In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed.Results Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy.Conclusions In this small trial, IV-D after aSAH was feasible, tolerable and safe.Trial registration number http://clinicaltrials.gov NCT01024972.