From the Guidelines
Dantrolene should not be used as a primary treatment for refractory heat stroke with hyperthermia despite active cooling measures, due to limited and conflicting evidence of its effectiveness in this context. The use of dantrolene in heat stroke is based on its mechanism of action, which involves inhibiting calcium release from the sarcoplasmic reticulum in muscle cells, thereby reducing heat production from muscle activity and potentially helping to lower core temperature in severe cases 1. However, the evidence for its use in heat stroke is limited to a few small studies with conflicting results. For example, one study found that dantrolene reduced cooling time in patients with classic heatstroke, but this study had a small sample size and methodological flaws 1. In contrast, a larger and more rigorous study found no significant difference in cooling time, organ dysfunction, length of hospital stay, or mortality between patients treated with dantrolene and those treated with placebo 1.
Key Considerations
- The most recent and highest quality study on the use of dantrolene in heat stroke, published in 1991, found no benefit of dantrolene in reducing cooling time, organ dysfunction, length of hospital stay, or mortality 1.
- The use of dantrolene in heat stroke is not supported by strong evidence, and its use remains controversial.
- Standard cooling measures such as ice packs, cooling blankets, cold IV fluids, and evaporative cooling should be used as the primary treatment for heat stroke.
- Dantrolene may be considered as an adjunct to standard cooling measures in severe cases of heat stroke, but its use should be carefully weighed against the potential risks and benefits.
Dosing and Administration
If dantrolene is considered for use in heat stroke, the recommended dose is typically 1-2.5 mg/kg IV initially, which can be repeated up to a maximum total dose of 10 mg/kg 1. However, the dosing schedule for dantrolene in heat stroke is not well established, and the use of dantrolene in this context is not supported by strong evidence.
Monitoring and Safety
Treatment with dantrolene should occur in an intensive care setting with close monitoring of vital signs, electrolytes, and organ function, as heat stroke is a medical emergency with significant mortality risk if not promptly and effectively managed. Potential side effects of dantrolene include muscle weakness, respiratory depression, and hepatotoxicity 1.
From the FDA Drug Label
In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. It is hypothesized that addition of dantrolene sodium to the "triggered" malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. The efficacy of intravenous dantrolene in the treatment of human and porcine malignant hyperthermia crisis, when considered along with prophylactic experiments in malignant hyperthermia susceptible swine, lends support to prophylactic use of oral or intravenous dantrolene in malignant hyperthermia susceptible humans
Dantrolene can be used to treat malignant hyperthermia, which is a condition that may share some similarities with refractory heat stroke with hyperthermia. However, the FDA drug label does not directly address the use of dantrolene for refractory heat stroke with hyperthermia despite active cooling measures.
- The label discusses the use of dantrolene in malignant hyperthermia, which is a specific condition.
- There is no direct information on the use of dantrolene for refractory heat stroke with hyperthermia. 2
From the Research
Dantrolene in Refractory Heat Stroke with Hyperthermia
- Dantrolene has been studied as a potential treatment for heat stroke, with some evidence suggesting its effectiveness in accelerating cooling rates 3, 4, 5.
- A study published in 1990 found that dantrolene administration decreased cooling time by approximately 19.5 minutes compared to a control group 3.
- Another study in 1999 found that dantrolene improved cooling in an animal model of heat stroke, with a proposed mechanism of action involving attenuation of heat production and peripheral vascular relaxation 4.
- A review of cooling methods in heat stroke published in 2005 suggested that dantrolene may be considered as a supportive cooling method in severe cases or when no improvement is observed with other treatments 5.
- However, the routine use of dantrolene as an adjuvant cooling technique in heat stroke is not supported by accumulated data, and further trials are needed to assess its true effectiveness 5.
- Other cooling methods, such as ice-water immersion or evaporative plus convective cooling, are generally recommended as primary treatments for heat stroke 6, 7.