What is the administration protocol for Dantrolene (Dantrolene) in a patient suspected of having malignant hyperthermia?

Dantrolene Administration for Malignant Hyperthermia

Administer dantrolene immediately at an initial dose of 2-3 mg/kg IV based on actual body weight, and give each syringe as soon as it is prepared rather than waiting for the complete dose—continue with 1 mg/kg boluses every 5-10 minutes until end-tidal CO2 falls below 6 kPa with normal minute ventilation and core temperature drops below 38.5°C. 1

Immediate Dosing Protocol

Initial Dose

• Start with 2-3 mg/kg IV push based on actual body weight (not ideal body weight, even in obese patients) 1, 2
• The FDA label specifies a minimum starting dose of 1 mg/kg, but current expert guidelines recommend the higher 2-3 mg/kg range for more effective initial treatment 3, 1
• In adults: administer each syringe immediately as it is prepared—do not wait for the complete initial dose to be ready, as reconstitution takes time 1
• In children: give 2-3 mg/kg initially, then 1 mg/kg boluses every 5 minutes until treatment goals are met 1, 2

Repeat Dosing

• Continue giving 1 mg/kg boluses every 5-10 minutes until clinical signs resolve 1, 2
• The Association of Anaesthetists emphasizes titrating to effect rather than adhering to rigid time intervals 1

Treatment Goals (When to Stop)

Pause dantrolene administration when ALL three criteria are met: 1, 2

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

Critical timing consideration: Delayed dantrolene treatment increases complications every 10 minutes, reaching 100% complication rate with a 50-minute delay 4. Japanese registry data shows that starting dantrolene at lower body temperatures (39.1°C vs 41.6°C) significantly improves survival 5.

Maximum Dosing and Reappraisal

• The traditional maximum is 10 mg/kg cumulative dose 1, 3
• At 10 mg/kg cumulative dose, formally reassess the diagnosis 1
• If MH remains the likely diagnosis, continue dantrolene beyond 10 mg/kg despite product labeling—this is explicitly recommended by the Association of Anaesthetists 1
• Case reports document successful treatment with doses up to 42 mg/kg in severe cases 6
• When exceeding 10 mg/kg, intensify aggressive body cooling measures 1

Preparation and Reconstitution

Traditional Formulation (20 mg vials)

• Reconstitute each 20 mg vial with 60 mL sterile water for injection (without bacteriostatic agent) 1, 3
• Requires vigorous shaking for up to 5 minutes until solution is clear 1
• Do NOT use 5% dextrose, 0.9% saline, or other acidic solutions—these are incompatible 3
• Use within 6 hours of reconstitution 3
• Store reconstituted solution at 15-30°C (59-86°F) 3

Newer Formulation (Ryanodex®)

• Contains 250 mg per vial, rapidly dissolves in 5 mL water 1
• Not licensed in UK/Europe but available in USA 1

Management of Recrudescence

Recrudescence occurs in up to 20% of cases and can happen up to 14 hours after initial control 1, 2

Dosing for Recurrence

• If recurrence within 6 hours: start with 1 mg/kg boluses 1
• If recurrence after 6 hours: restart with 2-3 mg/kg (full initial dose) 1
• Continue until treatment goals are re-achieved 1

Prophylaxis After Crisis

• Do NOT give prophylactic continuous infusion—it is not required in most cases and causes muscle weakness and nausea 1, 2
• Continuous infusion also causes high rates of thrombophlebitis due to solution osmolarity 1, 2
• Therapeutic plasma levels persist for approximately 6 hours after loading dose 2

Common Pitfalls and Complications

Dantrolene-Related Complications

• Muscle weakness (14.6-21.7% of cases)—most common complication, may compromise ventilator weaning 7, 2
• Phlebitis (9-9.2%)—due to high osmolarity, avoid continuous infusion 7, 2
• Gastrointestinal upset (4.1-4.3%)—nausea and vomiting 7, 2
• Risk increases 25-29% for every doubling of total dantrolene dose, but complications are rarely life-threatening 7

Critical Errors to Avoid

• Do not delay treatment waiting for diagnostic certainty—mortality increases dramatically with each 10-minute delay 4, 5
• Do not use ideal body weight for dosing—always use actual body weight 1, 2
• Do not stop at 10 mg/kg if MH signs persist—continue treatment and reassess diagnosis 1
• Do not give continuous infusion routinely—bolus dosing is preferred 1, 2
• Do not use dantrolene as sole treatment—must be combined with discontinuation of triggering agents, hyperventilation with 100% oxygen, active cooling, and treatment of complications 1

Stock Requirements

Facilities using volatile anesthetics or succinylcholine must stock adequate dantrolene: 1

• 36 vials minimum if additional 24 vials available within 30 minutes
• 48 vials if additional 12 vials available within 60 minutes
• 60 vials if no additional supply available within 60 minutes
• Each vial contains 20 mg dantrolene 1