Dantrolene sodium is used orally in the management of spasticity resulting from upper motor neuron disorders such as multiple sclerosis, cerebral palsy, spinal cord injury, and stroke syndrome. Dantrolene is not indicated for the treatment of muscle spasms resulting from rheumatic disorders or musculoskeletal trauma and is ineffective in the management of amyotrophic lateral sclerosis.
In the management of spasticity, dantrolene is particularly useful in patients whose functional rehabilitation has been slowed by the sequelae of spasticity. For the drug to be beneficial, such patients must have presumably reversible spasticity where relief of spasticity will aid in restoring residual function. Although effective doses of dantrolene frequently cause muscle weakness, the patient may feel more confident in the use of his residual strength because of a parallel decrease in involuntary muscle activity. The desirability of long-term dantrolene therapy in ambulatory patients depends on the balance between the weakness and other adverse effects caused by the drug and the benefits obtained from its use. Adverse effects such as weakness may not be as important a consideration in paraplegic patients as in ambulatory patients.
There is presently no method of predicting which patients will benefit from dantrolene therapy; therefore, a therapeutic trial of the drug is necessary to determine the benefits to a specific individual. Many patients with chronic spasticity may not benefit from long-term (several months or longer) dantrolene therapy; however, the benefits may be considerable in some patients. Tolerance to the therapeutic effects of dantrolene apparently does not occur. Although the safety and efficacy of long-term therapy have not been established, long-term administration of dantrolene is considered justifiable if the drug produces a substantial reduction in painful and/or disabling spasticity or a reduction in the intensity of nursing care needed, or if annoying manifestations of spasticity are eliminated as judged by the patient. Subjective impressions of improvement noted by the physician, patient, or persons in close contact with the patient may sometimes be confirmed by withdrawal of the drug for 2-4 days. Observation of the patient for exacerbations of the condition during this time may demonstrate improvements which are otherwise difficult to document. Because of dantrolene's potential for causing liver damage, therapy with the drug should be continued only if it is clearly beneficial.
There are no well-controlled clinical studies comparing the efficacy of baclofen and dantrolene; baclofen may cause less severe adverse effects than does dantrolene. Dantrolene and diazepam are about equally effective in spasticity caused by various upper motor neuron disorders; however, diazepam causes drowsiness more frequently than does dantrolene and dantrolene causes more muscle weakness than does diazepam. Therefore, dantrolene may be preferred in patients who are easily sedated and have marginal cerebral function whereas diazepam may be preferred in those with borderline muscle strength. Concomitant administration of dantrolene and diazepam has produced better control of spasticity in some patients than either drug alone and enabled a decrease in the dosage of either or both drugs. It should be kept in mind that concomitant therapy with dantrolene and diazepam may cause an additive sedative effect.
(See Cautions: Precautions and Contraindications.)
Malignant Hyperthermia Crisis
IV dantrolene sodium is used with appropriate supportive measures in the management of fulminant hypermetabolism of skeletal muscle that is characteristic of malignant hyperthermia crisis. As soon as malignant hyperthermia crisis is recognized (i.e., tachycardia, tachypnea, central venous desaturation, hypercarbia, metabolic acidosis, skeletal muscle rigidity, increased utilization of anesthesia circuit carbon dioxide absorber, cyanosis and mottling of the skin, and, in many cases, fever), all anesthetic agents should be discontinued immediately and IV dantrolene therapy initiated. IV dantrolene is used in conjunction with supportive measures which include administering oxygen, treating metabolic acidosis, and instituting cooling procedures if necessary; urinary output should be maintained and serum electrolytes should be monitored. The use of IV dantrolene in the management of malignant hyperthermia crisis is not a substitute for these supportive measures. Since the combination of IV dantrolene and a calcium-channel blocking agent (e.g., diltiazem, verapamil) in anesthetized animals resulted in myocardial depression, in ventricular fibrillation, and cardiovascular collapse in association with marked hyperkalemia, it is recommended that the combination of IV dantrolene and a calcium-channel blocking agent not be used during the management of malignant hyperthermia crisis.
(See Drug Interactions: Calcium-Channel Blocking Agents.)If mannitol is used for the prevention or treatment of late renal complications of malignant hyperthermia, the amount of mannitol administered as part of the IV dantrolene formulation should be considered.
Following a malignant hyperthermia crisis, oral dantrolene is used for up to 3 days to prevent recurrence of manifestations of the condition; IV dantrolene may be used postoperatively for this purpose when oral therapy is not practical or feasible. Dantrolene may also be administered orally and/or IV preoperatively to prevent or attenuate the manifestations of malignant hyperthermia crisis in individuals thought to be at risk; when administered IV preoperatively, additional IV doses may be necessary intraoperatively if early signs of malignant hyperthermia develop or if surgery is prolonged. Vital signs should be monitored in patients receiving dantrolene preoperatively, and the usual precautions associated with surgery in susceptible patients must still be employed since malignant hyperthermia may only be attenuated rather than prevented.
Neuroleptic Malignant Syndrome
Although the manufacturer states that dantrolene currently is not indicated for the management of neuroleptic malignant syndrome, the drug has been used successfully in a limited number of patients with this syndrome. The manufacturer states that fatalities have occurred in patients with neuroleptic malignant syndrome despite therapy with the drug. Further study is needed to determine the efficacy and optimum dosage and route of administration of the drug in this condition.
Dantrolene was also reportedly successful for the management of a fulminant hypermetabolic reaction induced by an acute overdosage of phenelzine.
In one study, preoperative administration of dantrolene sodium substantially reduced the strength of succinylcholine-induced muscle fasciculations intraoperatively and decreased the incidence of postoperative muscle pain.