Dantrolene (Dantrium) | Medication Reference

Bedside Snapshot

Core Use: Life-saving antidote for malignant hyperthermia (MH) triggered by volatile anesthetics or succinylcholine; also used adjunctively for neuroleptic malignant syndrome (NMS)
Mechanism: Blocks calcium release from sarcoplasmic reticulum in skeletal muscle by antagonizing RyR1, reducing muscle contraction and heat production
Typical Dosing: MH crisis: 2.5 mg/kg IV push, repeat every 5–10 minutes up to at least 10 mg/kg total until rigidity resolves and ETCO₂/temperature improve
Maintenance: Post-crisis: 1 mg/kg IV q4–6h or 0.25 mg/kg/h infusion for 24–48 hours to prevent recrudescence
Key Dangers: Muscle weakness (including respiratory muscles), extravasation tissue injury (high pH solution), rare cardiovascular collapse with calcium channel blockers

Brand & Generic Names

Generic Name: Dantrolene sodium
Brand Names: Dantrium, Revonto, Ryanodex (formulations vary by region)

Medication Class

Skeletal muscle relaxant; ryanodine receptor (RyR1) antagonist; antidote for malignant hyperthermia

Pharmacology

Mechanism of Action:

Acts directly on skeletal muscle by inhibiting ryanodine receptor type 1 (RyR1) calcium channels in the sarcoplasmic reticulum
In susceptible patients exposed to MH-triggering agents, RyR1 becomes abnormally activated, causing uncontrolled calcium release, sustained muscle contraction, hypermetabolism, heat production, and rhabdomyolysis
By reducing calcium release, dantrolene decreases excitation–contraction coupling, leading to reduced muscle tone, heat production, and metabolic demand
Cardiac and smooth muscle are relatively spared because they predominantly use different ryanodine receptor isoforms (RyR2, RyR3) and calcium-handling mechanisms, making dantrolene somewhat selective for skeletal muscle

Pharmacokinetics:

Onset: Clinical improvement in ETCO₂, rigidity, and heart rate is often seen within minutes of IV administration in malignant hyperthermia
Distribution: Widely distributed; highly protein bound; crosses the placenta but is generally considered acceptable in emergent MH treatment
Metabolism: Primarily hepatic via oxidative pathways to active and inactive metabolites
Elimination: Mainly renal excretion of metabolites; terminal half-life ~8–12 hours (varies with age and organ function)
Special Note: In hepatic dysfunction or repeated dosing, accumulation and prolonged muscle weakness may occur; however, under-treatment of MH is more dangerous than short-term toxicity from appropriate dosing

Indications

Emergency treatment of malignant hyperthermia crisis associated with exposure to volatile inhalational anesthetics or succinylcholine
Adjunctive treatment for neuroleptic malignant syndrome (NMS) when severe rigidity and hyperthermia are present, usually in combination with dopaminergic agents (e.g., bromocriptine, amantadine) and supportive care
Occasional off-label use for severe spasticity in chronic neurologic conditions (usually oral, outpatient), but this is outside typical ED/ICU practice

Dosing & Administration

Available Forms:

Conventional IV dantrolene (e.g., Dantrium, Revonto): vials containing 20 mg dantrolene plus mannitol; reconstituted with 60 mL sterile water (no bacteriostatic agent) to a concentration of ~0.33 mg/mL
Ryanodex (where available): each vial contains 250 mg dantrolene; reconstituted with 5 mL sterile water to a concentration of 50 mg/mL, allowing rapid administration through smaller volumes
Oral capsules (e.g., 25 mg, 50 mg, 100 mg) are used for chronic spasticity and for prophylaxis or maintenance dosing after MH, but acute ED/ICU management is predominantly IV

Dosing – Dantrolene (Adult IV):

Indication / Scenario	Dose	Frequency / Duration	Notes
Acute malignant hyperthermia – initial dose (conventional vials)	2.5 mg/kg IV bolus	Give rapidly; may repeat q5–10 min	Continue until signs (rigidity, ETCO₂, HR, temp) improve; many patients need 5–10 mg/kg total
Acute MH – Ryanodex (if available)	2.5 mg/kg IV (50 mg/mL)	Single bolus; may repeat as needed up to 10 mg/kg	Smaller volume, faster reconstitution; useful in peri-op/ED crises
Maximum cumulative dose during acute MH	At least 10 mg/kg; higher doses sometimes required	Titrate to clinical effect	Do not withhold further doses if MH not controlled; underdosing is hazardous
Post-crisis maintenance (IV)	1 mg/kg IV q4–6h or 0.25 mg/kg/h infusion	Typically continued for 24–48 hours	Prevents recrudescence; adjust for organ function and weakness
Neuroleptic malignant syndrome (adjunct)	0.25–2 mg/kg IV q6–12h (varies by source)	Titrate to improvement in rigidity and hyperthermia	Use with dopaminergic agents and aggressive supportive care; off-label but common in severe cases
Oral transition / chronic use (for reference)	25–100 mg PO three or four times daily	Titrated to effect and tolerability	Used more in spasticity management and MH prophylaxis than in acute ED setting

Contraindications

Absolute Contraindications:

Known hypersensitivity to dantrolene or formulation components
Pre-existing significant hepatic impairment is a contraindication for chronic oral use due to hepatotoxicity risk; in true MH crisis, life-saving benefits outweigh this concern, but close monitoring is essential

Major Precautions:

Hepatic dysfunction: risk of hepatotoxicity increases with chronic high-dose oral therapy; for acute MH, use full recommended dosing but monitor LFTs during and after treatment
Baseline muscle weakness, respiratory insufficiency, or neuromuscular disease: dantrolene-induced weakness may worsen ventilatory failure; be prepared for mechanical ventilation (which is already indicated in MH/NMS crises)
Concurrent calcium channel blocker use (especially verapamil): case reports of hyperkalemia and myocardial depression when combined with IV dantrolene; avoid this combination if possible, or use with extreme caution and close monitoring
Extravasation risk: high-pH solution can cause local irritation and tissue damage; ensure secure IV access, preferably a large-bore peripheral or central line
Mannitol content of conventional vials contributes to osmotic load; may assist with urine output but can be an issue in volume-sensitive patients

Critical Warning: Dantrolene does NOT replace core MH management (stop trigger agents, hyperventilate with 100% O₂, active cooling, treat acidosis and hyperkalemia, manage dysrhythmias). It is one pillar in a bundle of interventions. Give as soon as MH is suspected—do not wait for confirmatory testing.

Adverse Effects

Common (acute IV use):

Muscle weakness, including neck and respiratory muscles
Drowsiness, dizziness
Nausea, vomiting, diarrhea
Flushing, sweating
Pain, phlebitis, or irritation at injection site

Serious:

Hepatotoxicity (primarily with chronic oral therapy; rare with short-term MH treatment but monitor liver function)
Profound muscle weakness leading to respiratory failure, particularly in patients with pre-existing neuromuscular compromise or high cumulative doses
Cardiovascular collapse or hyperkalemia when combined with certain calcium channel blockers (e.g., verapamil) in case reports
Severe local tissue injury with extravasation of IV solution

Special Populations

Hepatic Impairment:

Risk of hepatotoxicity with chronic oral therapy
In acute MH crisis, life-saving benefits outweigh hepatotoxicity concerns
Monitor LFTs during and after treatment

Renal Impairment:

Metabolites excreted renally; accumulation possible with repeated dosing
Do not withhold treatment in MH crisis due to renal concerns
Monitor for prolonged muscle weakness

Neuromuscular Disease:

Baseline weakness may be exacerbated by dantrolene
Be prepared for mechanical ventilation (already indicated in MH crisis)
Monitor respiratory function closely

Pregnancy & Lactation:

Crosses placenta; use is acceptable in emergent MH treatment despite pregnancy
Life-threatening nature of MH makes treatment imperative
Benefits far outweigh theoretical risks to fetus

Monitoring

Clinical Monitoring:

Core temperature, end-tidal CO₂ (ETCO₂), heart rate, blood pressure, and arrhythmias as primary MH endpoints
Neuromuscular status and ventilatory function; anticipate need for prolonged mechanical ventilation with repeated dantrolene dosing
Urine output and color (myoglobinuria) as part of rhabdomyolysis management; consider mannitol contribution from dantrolene vials

Laboratory Monitoring:

Serial CK, electrolytes (especially K⁺, Ca²⁺), lactate, and renal function as markers of rhabdomyolysis and end-organ damage
Liver function tests (AST, ALT, bilirubin) during and after therapy, especially with prolonged courses or in patients with known hepatic disease

Clinical Pearls

Immediate Treatment: In malignant hyperthermia, dantrolene should be given as soon as MH is suspected—do not wait for confirmatory testing; treat the clinical picture (rapid rise in ETCO₂, rigidity, hyperthermia, acidosis, tachycardia).

Mixing Team: Conventional dantrolene requires reconstituting many vials (each 20 mg with 60 mL sterile water); assigning a dedicated mixing team during MH crisis can speed delivery.

Ryanodex Advantage: Ryanodex dramatically simplifies dosing and volume if available (250 mg in 5 mL), but centers must still maintain conventional dantrolene stocks unless protocols specify otherwise.

Recrudescence Risk: MH often recrudesces after initial control; continued dantrolene (1 mg/kg q4–6h or infusion) and close ICU monitoring for at least 24–48 hours are standard practice.

NMS Treatment: In NMS, dantrolene is adjunctive: stopping the offending agent, aggressive supportive care, and dopaminergic therapy are the foundation; dantrolene can help with rigidity and heat but is not a standalone cure.

References

1. Lexicomp. (2025). Dantrolene: Drug information. Wolters Kluwer.
2. Rosenberg, H., Pollock, N., Schiemann, A., Bulger, T., & Stowell, K. (2015). Malignant hyperthermia: A review. Orphanet Journal of Rare Diseases, 10, 93.
3. Malignant Hyperthermia Association of the United States (MHAUS). (2023). MH treatment protocol and dantrolene dosing guidelines.
4. Tobias, J. D., & Schleien, C. L. (2016). Dantrolene: A review of its pharmacology and applications in pediatric anesthesia. Paediatric Anaesthesia, 26(10), 1001–1010.
5. Adnet, P., & Krivosic-Horber, R. (2019). Neuroleptic malignant syndrome. In Neurologic Critical Care (2nd ed.).