Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial
Carandang, Raphael A.
Hall, Wiley R.
van der Bom, Imramsjah M. J.
Flood, Thomas F.
Gounis, Matthew J.
Weaver, John P.
Barton, Bruce A.
Wakhloo, Ajay K.
Student AuthorsThomas Flood
UMass Chan AffiliationsDepartment of Radiology
Department of Quantitative Health Sciences
Department of Neurology
Document TypeJournal Article
MetadataShow full item record
AbstractBACKGROUND: 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.
SourceJ Neurol Neurosurg Psychiatry. 2014 Oct 24. pii: jnnp-2014-308778. doi: 10.1136/jnnp-2014-308778. [Epub ahead of print]. Link to article on publisher's website
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48029
Related ResourcesLink to article in PubMed