Physiology · Year 1 · from Physiology
Case 3: Malignant Hyperthermia - Positive Feedback Catastrophe
Clinical Image
Source: Clinical illustration of calcium dysregulation in skeletal muscle - Educational use
Patient Presentation
A 24-year-old man is undergoing general anesthesia for elective knee arthroscopy. Twenty minutes after induction with sevoflurane and succinylcholine, the anesthesiologist notices the patient's jaw is unusually rigid. Over the next 10 minutes, the patient develops rapidly rising end-tidal CO2, tachycardia to 140 bpm, and a core temperature increase from 37.0°C to 39.5°C.
Demographics
- Age: 24 years
- Sex: Male
- Past Medical History: No prior surgeries or anesthetic exposures
- Family History: Cousin died unexpectedly during surgery (details unknown)
Chief Complaint
Intraoperative findings: jaw rigidity, rising CO2, tachycardia, and hyperthermia
Physical Examination (Intraoperative)
- Temperature: Rising rapidly (39.5°C to 41.0°C over 15 minutes)
- Heart rate: 150 bpm
- Blood pressure: Initially hypertensive, then becoming hypotensive
- End-tidal CO2: 85 mmHg (markedly elevated despite increased minute ventilation)
- Muscle rigidity: Generalized, especially jaw (masseter spasm)
- Skin: Mottled, hot
Workup
- Arterial blood gas: pH 7.12, PaCO2 72 mmHg, PaO2 85 mmHg (combined acidosis)
- Potassium: 6.8 mEq/L (severe hyperkalemia)
- CK: 45,000 U/L (severe rhabdomyolysis)
- Lactate: 12 mmol/L
- Myoglobin: Markedly elevated
- Later: Genetic testing for RYR1 mutation (positive)
Diagnosis
Malignant Hyperthermia
Treatment
- STOP all triggering agents immediately (volatile anesthetics, succinylcholine)
- Hyperventilate with 100% oxygen using clean anesthesia circuit
- Dantrolene sodium 2.5 mg/kg IV bolus, repeat every 5-10 minutes until symptoms resolve
- Aggressive cooling measures
- Treat hyperkalemia (calcium, insulin/glucose, bicarbonate)
- Maintain high urine output for myoglobin clearance
- Continue dantrolene for 24-48 hours
- Genetic counseling and testing for family members
Physiological Principles Demonstrated
- Positive feedback in disease: Malignant hyperthermia demonstrates catastrophic positive feedback. Triggering agents cause uncontrolled calcium release from the sarcoplasmic reticulum, causing sustained muscle contraction, which generates heat, which further destabilizes calcium handling.
- Normal termination of positive feedback: Unlike physiological positive feedback (e.g., childbirth), MH has no natural termination point. Without intervention, the cycle continues until cell death occurs.
- Calcium homeostasis: The RYR1 mutation affects the ryanodine receptor, which normally controls calcium release from the sarcoplasmic reticulum. Dantrolene works by inhibiting calcium release, breaking the positive feedback cycle.
- Metabolic consequences of sustained contraction: Continuous muscle contraction depletes ATP, causes rhabdomyolysis (releasing potassium and myoglobin), generates CO2 and lactate, and produces heat faster than it can be dissipated.