Malignant Hyperthermia

Question 1

What is malignant hyperthermia?

Answer 1

• Autosomal dominant condition
• More common in males & pediatric population
• hypermetabolic state of skeletal muscle
• thought to involve ryanodine receptor, ion channel responsible for Ca²⁺ in sarcoplasmic reticulum (SR)
• increase in Ca²⁺ in (SR) induced by inhalational regimen

Question 2

Clinical signs of malignant hyperthermia during anesthesia:

Answer 2

1. muscle rigidity
2. tachycardia
3. sudden rise in End tidal CO₂
4. hypercarbia
5. hyperthermia may be a late sign, rising 1^o C every 5 mins
6. dark colored urine, reflecting myoglobinuria

Question 3

Laboratory findings malignant hyperthermia

Answer 3

1. mixed metabolic and respiratory acidosis
2. hyperkalemia
3. reduced mixed venous oxygen saturation
4. myoglobinemia

Question 4

Treatment of malignant hyperthermia:

Answer 4

1. stop operation immediately
2. stop all halogenated inhalational agents
3. stop succinylcholine
4. Administer dantrolene (2.5 mg/kg) IV every 5 minutes until episode is terminated
5. After initial control of symptoms, 1 mg/kg of dantrolene given every 6 hours for 24-48 hrs to prevent relapse

Question 5

Mechanism of action of dantrolene?

Answer 5

• directly interferes with muscle contraction by binding Ryr1 receptor and inhibiting Ca²⁺ release from sarcoplasmic reticulum

Question 6

Secondary therapy of malignant hyperthermia (MH)?

Answer 6

1. Cooling measures: cooling blanket, cold lavages
2. hyperkalemia aggressively treated with:
   
   • insulin
   • Ca²⁺
   • bicarbonate
3. metabolic acidosis managed with sodium bicarbonate
4. diuresis should be established with furosemide (lasix) to prevent acute renal failure secondary to myoglobinuria