Beneficial Effects of Dantrolene in the Treatment of Rhabdomyolysis as a Potential Late Complication Associated With COVID-19: A Case Report (preprint)

ABSTRACT

Background: Patients with severe COVID-19 have disorders of the respiratory, cardiovascular, coagulation, skeletal muscle and central nervous systems. These system failures may be associated with cytokine release syndrome, characterized by hyperpyrexia, thrombocytopenia, hyperferritinemia, and the elevation of other inflammatory markers. Rhabdomyolysis with high fever is a complication that is rarely found in COVID-19. The exact relations of these clinical conditions in patients with COVID-19 are still unknown. Case presentation We present the case of a 36-year-old man with severe COVID-19 complicated by rhabdomyolysis and high fever. After admission, his condition continued to deteriorate, with a high body temperature. After 9 days, in his laboratory examination, creatine kinase and myoglobin levels were noted to increase (to 26046 U/L, 3668 ng/mL). In addition to viral therapy, he was immediately treated with hydration. However, high fever and levels of rhabdomyolysis continued. The patient had been diagnosed with malignant hyperthermia associated with a late complication of COVID-19, although he had no hereditary predisposition to malignant hyperthermia or neuroleptic malignant syndrome. The administration of dantrolene with muscle relaxation and anti-inflammatory function showed potential efficacy for rhabdomyolysis, high fever and increased plasma inflammatory markers. Conclusions: Malignant hyperthermia is triggered by not only anesthetic agents but also viral infections. A possible mechanism of malignant hyperthermia is a hypersensitivity of calcium release from the sarcoplasmic reticulum. These include mutations in or the activation of the skeletal muscle ryanodine receptor calcium release channel. Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent. The administration of dantrolene showed potential efficacy for rhabdomyolysis, high body temperature due to inflammation, and increased inflammatory markers. The underlying mechanism of the association of rhabdomyolysis and high fever in COVID-19 might be a similar pathogenesis in malignant hyperthermia.