What is the interval between doses of Dantrolene (Dantrium) for malignant hyperthermia?

Dantrolene Dosing Interval for Malignant Hyperthermia

After the initial dose of 2-3 mg/kg, additional boluses of 1 mg/kg dantrolene should be administered every 5 minutes in children, or as rapidly as possible in adults (ideally every 10 minutes), until treatment goals are achieved. 1

Initial Dosing Strategy

• Start with 2-3 mg/kg IV based on actual body weight (not ideal body weight), administered as rapidly as possible 1
• In adults, administer each syringe immediately as it is prepared rather than waiting for the complete dose to be reconstituted, since preparation is time-consuming 1, 2
• The FDA label specifies a minimum starting dose of 1 mg/kg, though current guidelines recommend the higher 2-3 mg/kg range for optimal efficacy 3

Repeat Dosing Intervals

For Children

• Give 1 mg/kg boluses every 5 minutes until treatment goals are met 1

For Adults

• Give additional doses every 10 minutes (or as often as possible if reconstitution takes longer than 10 minutes) until signs of MH regress 1, 2
• Each repeat dose should be 1 mg/kg 1

Treatment Goals to Guide Dosing

Continue repeat doses until ALL of the following are achieved:

• End-tidal CO₂ < 6 kPa (45 mmHg) with normal minute ventilation 1
• Core temperature < 38.5°C 1, 2
• Resolution of muscle rigidity and metabolic abnormalities 1

Maximum Dosing Considerations

• The traditional maximum cumulative dose is 10 mg/kg 1, 3
• However, this maximum may need to be exceeded in fulminant MH cases if symptoms persist 1, 2
• When 10 mg/kg cumulative dose is reached, perform a formal diagnostic reappraisal, but continue dantrolene if MH remains the likely diagnosis 1

Management of Recrudescence

If MH signs recur after initial control:

• Within 6 hours of initial reaction: Give 1 mg/kg boluses 1
• More than 6 hours after initial reaction: Give 2-3 mg/kg boluses 1
• Repeat every 10 minutes until signs regress again 1, 2

Critical Timing Considerations

Rapid administration is directly associated with survival. Research demonstrates that:

• Mortality increases 1.6 times for every 30-minute delay in dantrolene administration 4
• The interval from first MH sign to dantrolene start was significantly longer in deceased patients (100 min) versus survivors (45 min) 5
• Starting treatment at lower body temperatures prevents critical elevations associated with worse prognosis 5

Important Caveats

Do NOT Use Continuous Infusion

• Routine continuous infusion or scheduled intermittent boluses are NOT recommended after the initial loading dose 1, 2
• Continuous infusion causes high rates of thrombophlebitis due to solution osmolarity 1
• Therapeutic plasma levels persist for approximately 6 hours after loading dose 1, 2
• Prophylactic post-crisis dosing causes unnecessary muscle weakness and nausea 1

Preparation Time

• Traditional formulation (20 mg vials) requires vigorous shaking for up to 5 minutes per vial with 60 mL sterile water 1, 2
• Newer formulation (Ryanodex 250 mg) dissolves rapidly in 5 mL water, though not available in all countries 1, 2
• This preparation delay is why each dose should be given immediately upon reconstitution rather than waiting 1, 2