We read with enthusiasm the Society of Ambulatory Anesthesia’s position statement for the care of malignant hyperthermia (MH)–susceptible patients in the August issue.1 Dantrolene was first described for the treatment of MH in humans in 1979,2 and still remains the definitive therapy for this disorder.1,3,4 Until recently, all available dantrolene formulations including dantrolene sodium (Dantrium; Par Pharmaceuticals, Chestnut Ridge, NY) have been poorly soluble in water and required significant time and labor to prepare as a suspension for injection. In 2015, the Food and Drug Administration (FDA) approved dantrolene nanosuspension (Ryanodex; Eagle Pharmaceuticals, Woodcliff Lake, NJ). Dantrolene nanosuspension can be rapidly prepared for administration, and an entire adult therapeutic dose is contained in a single vial. On average, 9 vials of dantrolene sodium are needed for an equivalent dose. We describe a small study that was used to pass the newer formulation, dantrolene nanosuspension, through our institution’s pharmacy and therapeutics committee. This formulary change had failed to pass twice prior.
The time actually needed to prepare dantrolene nanosuspension has not been documented for a 70 kg dose. We performed a crossover study with anesthesiology residents, faculty, and registered nurses following package recommendations. At one station, a 20 mg vial of Dantrium was reconstituted into 60 mL sterile water, while, at a second station, a 250 mg vial of Ryanodex was mixed in a 5 mL syringe of sterile water. Time from when the practitioner began to fill the syringe with water to reconstitute each preparation until the drug was injected into the side port of an intravenous (IV) tubing set was recorded.
Twenty trials with Ryanodex and 21 with Dantrium were performed; the 20 paired trials were included in the analysis. The mean time to reconstitute and administer a single vial of Dantrium was 189 seconds (95% confidence interval [CI], 163–215 seconds) compared to a mean of 53.9 seconds
(95% CI, 43.3–64.4 seconds) for a single vial of Ryanodex (P < .01), a mean difference of 135.1 seconds. The estimated time that would be required to prepare and administer the therapeutic dose of Dantrium to treat a 70-kg adult (2.5 mg/kg or 175 mg = 9 vials) is 1701 seconds (28.4 minutes) if a single practitioner reconstituted all 9 vials in series. Even if several people were available, dantrolene sodium would still require significantly more time to prepare than Ryanodex and would prevent those physicians and nurses from performing other important management tasks.
During an MH crisis, any delay in the administration of dantrolene is associated with increased morbidity and mortality.3,4 We used the data generated in this small study to justify a hospital formulary switchover from dantrolene sodium to dantrolene nanosuspension, a win for patient safety at Stanford University. Anesthesiologists, pharmacists, and hospital administrators should be aware of the significant time and potential resource advantages of dantrolene nanosuspension in the management of MH events, with particular attention to the benefits of its use in ambulatory surgical settings where available personnel may be few.
James C. McAvoy, MD
Jay B. Brodsky, MD
John Brock-Utne, MD, PhD
Department of Anesthesiology,
Perioperative and Pain Medicine
Stanford University School of Medicine
Stanford, California
jcmcavoy@stanford.edu