Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study

Abstract

Purpose: To examine the use of intravenous dantrolene in hospitalized patients. Materials and Methods: Medical Records of patients treated with intravenous dantrolene between 2007 and 2012 at 6 teaching hospitals were reviewed. Temperature, muscle rigidity, creatine kinase levels, and mortality were assessed in association with dantrolene use. Results: Twenty-five patients received intravenous dantrolene, 9 patients with neuroleptic malignant syndrome (NMS), 8 with hyperthermia due to sepsis, 4 with NMS and sepsis, 2 for malignant hyperthermia (MH), and 2 with hypermetabolic syndrome associated with juvenile diabetic ketoacidosis. Dantrolene was administered as a bolus of 1 -3 mg/kg. Core temperature decreased after dantrolene administration in all groups but significant only for MH, NMS cases (Pre 102.3 ± 0.9˚F vs. Post 99.5 ± 0.9˚F; p < 0.001), in Sepsis cases (Pre 104.3 ± 1.5˚F vs. Post 100.6 ± 1.0˚F; p < 0.001). Mean rigidity scores decreased in all groups but significant only for NMS cases, and mean CK did not change significantly in any group. Conclusion: Dantrolene was associated with reductions in temperature and rigidity in hyperthermia of diverse origins in patients admitted to Intensive care settings.

Intravenous dantrolene in hypermetabolic syndromes: a survey of the U.S. Veterans Health Administration database

“…In the sample, NMS was diagnosed in 35.55% of the patients who received dantrolene, similar to two previous samples [ 42 , 47 ]. Although previous reports documented improved survival of NMS following dantrolene treatment [ 34 – 37 , 42 , 47 ], not all have been favorable [ 39 , 41 , 48 ].…”

“…In the sample, NMS was diagnosed in 35.55% of the patients who received dantrolene, similar to two previous samples [ 42 , 47 ]. Although previous reports documented improved survival of NMS following dantrolene treatment [ 34 – 37 , 42 , 47 ], not all have been favorable [ 39 , 41 , 48 ]. Recent guidelines recommend specific treatments based on character, duration and severity NMS symptoms, with dantrolene reserved for patients showing extreme temperature elevations and severe symptoms [ 49 ].…”

“…Dantrolene was likely used as a last resort in a minority of patients with poor prognoses and significant co-morbidities or severe symptoms. Although the fact that treated patients showed higher mortality compared with NMS cases not receiving dantrolene suggests it may be ineffective or worse, the effectiveness of dantrolene in NMS cannot be addressed by our data because groups were neither randomized, controlled, blinded, nor matched [ 42 ]. For example, concurrent sepsis or other comorbidities and symptom severity have been identified as significant predictors of mortality and response in NMS in previous studies [ 38 , 42 , 48 , 50 , 51 ].…”

“…Although the fact that treated patients showed higher mortality compared with NMS cases not receiving dantrolene suggests it may be ineffective or worse, the effectiveness of dantrolene in NMS cannot be addressed by our data because groups were neither randomized, controlled, blinded, nor matched [ 42 ]. For example, concurrent sepsis or other comorbidities and symptom severity have been identified as significant predictors of mortality and response in NMS in previous studies [ 38 , 42 , 48 , 50 , 51 ]. Evidence on the efficacy of dantrolene for NMS is inconclusive pending studies using standardized diagnostic criteria that also control for co-morbidities and severity of symptoms [ 52 – 54 ].…”

“…Alternative phenotypic manifestations of RYR1 variants have been speculated as predisposing to neuroleptic malignant syndrome (NMS) [23,24], serotonin syndrome [25], stimulant abuse [26,27], parkinsonism-hyperpyrexia syndrome [28], sepsis [29], toxicity of uncoupling agents dinitrophenol and aspirin [30], and others [31][32][33]. Because of the clinical parallels with MH, dantrolene has been used "off-label" (i.e., for disorders other than the officially approved indication) for these syndromes with some positive results [26,27,32,[34][35][36][37][38][39][40][41][42].…”