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dc.contributor.authorMuehlschlegel, Susanne
dc.contributor.authorCarandang, Raphael A.
dc.contributor.authorHall, Wiley R.
dc.contributor.authorKini, Nisha
dc.contributor.authorIzzy, Saef
dc.contributor.authorGarland, Bridget
dc.contributor.authorOuillette, Cynthia
dc.contributor.authorvan der Bom, Imramsjah M. J.
dc.contributor.authorFlood, Thomas F.
dc.contributor.authorGounis, Matthew J.
dc.contributor.authorWeaver, John P.
dc.contributor.authorBarton, Bruce A.
dc.contributor.authorWakhloo, Ajay K.
dc.date2022-08-11T08:10:46.000
dc.date.accessioned2022-08-23T17:19:15Z
dc.date.available2022-08-23T17:19:15Z
dc.date.issued2014-10-24
dc.date.submitted2015-05-27
dc.identifier.citationJ Neurol Neurosurg Psychiatry. 2014 Oct 24. pii: jnnp-2014-308778. doi: 10.1136/jnnp-2014-308778. [Epub ahead of print]. <a href="http://dx.doi.org/10.1136/jnnp-2014-308778">Link to article on publisher's website</a>
dc.identifier.issn1468-330X
dc.identifier.doi10.1136/jnnp-2014-308778
dc.identifier.pmid25344064
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48029
dc.description.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.
dc.language.isoen_US
dc.publisherBMJ Publishing Group
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25344064&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1136/jnnp-2014-308778
dc.subjectNeurology
dc.subjectRadiology
dc.titleDantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial
dc.typeJournal Article
dc.source.journaltitleJournal of neurology, neurosurgery, and psychiatry
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiology_pubs/136
dc.identifier.contextkey7147764
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p> <p>CONCLUSIONS: In this small trial, IV-D after aSAH was feasible, tolerable and safe.</p> <p>TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov NCT01024972.</p>
dc.identifier.submissionpathradiology_pubs/136
dc.contributor.departmentDepartment of Radiology
dc.contributor.departmentDepartment of Quantitative Health Sciences
dc.contributor.departmentDepartment of Neurology
dc.contributor.studentThomas Flood
dc.description.thesisprogramMD/PhD


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