Dantrolene for Rigors and Fever
Dantrolene is the definitive life-saving treatment for malignant hyperthermia and should be administered immediately at 2 mg/kg IV when this diagnosis is suspected, with repeated doses until cardiorespiratory stabilization occurs, potentially exceeding the traditional maximum of 10 mg/kg. 1
Malignant Hyperthermia: Primary Indication
When to suspect and treat:
- Rigors (generalized muscle rigidity) and fever developing during or within 12 hours after exposure to volatile anesthetic agents (sevoflurane, desflurane, isoflurane) or succinylcholine 2, 3
- Masseter spasm if succinylcholine was used 1
- Associated signs include tachycardia, hypercarbia, metabolic acidosis, hyperthermia, and dysrhythmias 4
Immediate management algorithm:
- Stop all trigger agents immediately and disconnect vaporizers 1, 3
- Hyperventilate with 100% oxygen at 2-3 times normal minute volume 1, 3
- Administer dantrolene 2 mg/kg IV (mix 20 mg vials with 60 ml sterile water) 1
- Repeat dantrolene boluses until cardiac and respiratory systems stabilize—do not hesitate to exceed 10 mg/kg if needed 1
- Secure 36-50 ampoules from pharmacy/nearby hospitals for adult patients 1, 3
Critical pitfall: The FDA label emphasizes that dantrolene is not a substitute for supportive measures—you must simultaneously manage oxygen requirements, metabolic acidosis, cooling, and electrolyte imbalances. 5
Neuroleptic Malignant Syndrome: Secondary Indication
When to suspect:
- Rigors (lead-pipe rigidity) and fever developing over 1-7 days after exposure to dopamine antagonists (antipsychotics, metoclopramide, domperidone) or withdrawal of dopaminergic drugs 2, 6
- Gradual onset distinguishes this from malignant hyperthermia's acute presentation 2
Dantrolene use in NMS:
- Dantrolene has been used successfully in NMS cases, particularly when combined with bromocriptine and supportive care 2, 4, 7
- Important caveat: Evidence suggests dantrolene monotherapy in NMS may be associated with higher mortality and should be combined with dopaminergic agents (bromocriptine) rather than used alone 8
- The exception is when premedication was neuroleptic monotherapy—here dantrolene monotherapy shows significantly shorter recovery time 8
Management approach for NMS:
- Discontinue all dopamine antagonists immediately 2
- Administer dantrolene 2 mg/kg IV 7, 6
- Add bromocriptine (dopamine agonist) unless contraindicated 2
- Provide aggressive supportive care with benzodiazepines for agitation 2
Monitoring and Supportive Care
All patients receiving dantrolene require:
- ICU monitoring for minimum 24 hours 1, 2, 3
- Core temperature monitoring with active cooling (chilled saline 2000-3000 ml at 4°C IV, surface cooling with ice packs to axillae/groin) until temperature <38.5°C 1
- Serial measurements of potassium, creatine kinase, arterial blood gases, myoglobin, and glucose 1
- Monitoring for hyperkalemia (treat with dextrose 50 ml + 50 IU insulin, calcium chloride 0.1 mmol/kg IV) 1
- Monitoring for acidosis (hyperventilate to normocapnia, give sodium bicarbonate if pH <7.2) 1
- Monitoring for arrhythmias (treat with amiodarone 300 mg or beta-blockers) 1
- Maintaining urine output >2 ml/kg/h with furosemide 0.5-1 mg/kg or mannitol 1 g/kg 1
Mechanism and Efficacy
Dantrolene inhibits calcium release from the sarcoplasmic reticulum by acting on the ryanodine receptor, directly addressing the pathophysiology of both malignant hyperthermia and NMS 4, 9. In malignant hyperthermia, early treatment with dantrolene has increased survival from 20% in the 1960s to >90% today, with rapid resolution of hyperthermia, rigidity, dysrhythmias, and metabolic derangements 4, 9.
Key clinical pearl: Dantrolene's poor water solubility requires preparation time—each 20 mg vial needs 60 ml sterile water, and multiple personnel should prepare multiple vials simultaneously during a crisis. 1, 9