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AS4.1 | Pharmacology of Drugs Used in General Anaesthesia — SDL Guide (Part 3)
Malignant Hyperthermia: Recognition and Emergency Management
Malignant hyperthermia (MH) deserves dedicated emphasis because it is triggered by pharmacological agents discussed in this SDL — specifically suxamethonium and all potent volatile inhalational agents (halothane, sevoflurane, isoflurane, desflurane). MH is a hypermetabolic crisis of skeletal muscle and represents one of the most rapidly fatal intraoperative emergencies if not recognised immediately.
The pathophysiology centres on defective regulation of ryanodine receptor type 1 (RYR1) — an autosomal dominant mutation. When an MH-susceptible patient is exposed to a triggering agent, massive uncontrolled release of calcium from the sarcoplasmic reticulum occurs, causing continuous muscle contracture, explosive ATP consumption, and heat generation. The clinical presentation includes: tachycardia (often first sign), masseter spasm on suxamethonium, rapidly rising end-tidal CO₂ (the most sensitive early indicator — far outstrips the thermometer), skeletal muscle rigidity, hyperthermia (temperature rise exceeding 1°C every 5 minutes), severe metabolic and respiratory acidosis, hyperkalaemia, myoglobinuria from rhabdomyolysis, and eventually coagulopathy (DIC) and multiorgan failure if untreated.
Emergency management (MH crisis protocol):
1. Immediately discontinue triggering agents — switch to TIVA with propofol; change anaesthetic machine (use one pre-flushed with high-flow oxygen)
2. Dantrolene 2.5 mg/kg IV bolus, repeated every 5–10 minutes to a maximum of 10 mg/kg (or until crisis abates); dantrolene inhibits ryanodine receptor calcium release and is the specific antidote
3. Surface cooling and cold IV saline; ice packs to axillae and groin
4. Treat hyperkalaemia with insulin/dextrose, calcium gluconate
5. Treat acidosis with sodium bicarbonate
6. Monitor urine output (target >2 mL/kg/h); bladder irrigation if required for myoglobinuria
7. ICU admission; dantrolene continuation for 24–48 hours to prevent recrudescence
Patients with confirmed or suspected MH susceptibility must be preoperatively identified (personal/family history; or prior masseter spasm under anaesthesia). They require anaesthesia using a TIVA technique with propofol and NMBAs (non-triggering), and all volatile agents must be avoided. Every operating theatre must stock dantrolene.
Self-Assessment: Putting the Pharmacology Together
Having worked through the pharmacology of all major drug classes used in general anaesthesia, it is worth pausing to consolidate your understanding through active self-testing. The ability to reason across drug classes — not merely recite individual facts — is what distinguishes a clinically capable practitioner from one who has simply memorised a formulary. Consider the following self-check questions and attempt to answer them before reading the explanations.
First, can you construct a complete balanced anaesthetic plan for a 60-year-old hypertensive patient with moderate aortic stenosis presenting for elective hip arthroplasty? Justify each agent chosen: why propofol (or etomidate) for induction, why rocuronium over suxamethonium for intubation, why sevoflurane for maintenance, and why fentanyl plus paracetamol for multimodal analgesia. What reversal agent would you use and why?
Second, for each of the following contraindications, identify the drug and the mechanism: (a) raised end-tidal CO₂ + rising temperature under isoflurane/suxamethonium anaesthesia — which drug triggered this and what is the antidote? (b) A burn patient needing urgent surgery — which NMBA is contraindicated and which do you use instead? (c) An asthmatic patient requiring emergency intubation — which induction agent is preferred and why?
Third, test your reversal pharmacology: if you give neostigmine alone without an anticholinergic, what will happen and why? If you have used 1.2 mg/kg rocuronium for RSI in a cannot-intubate scenario and the patient is now desaturating, what single agent can rapidly reverse the block?
Finally, recite the key doses (mg/kg) for: propofol induction, thiopentone induction, ketamine induction (IV), suxamethonium, and neostigmine maximum dose. If you can answer all of these accurately from memory — including the mechanistic rationale — you have achieved the depth of understanding that AS4.1 requires.
CLINICAL PEARL
Drug dosing in anaesthesia — always state mg/kg, not fixed volumes: Because body weight varies enormously, anaesthetic drug doses must be calculated per kilogram. Giving a fixed 20 mL of propofol to every patient is dangerous — a 50 kg elderly woman receives 400 mg (overdose) while a 100 kg young man receives 200 mg (potentially inadequate). Always calculate: propofol 1.5–2.5 mg/kg, suxamethonium 1–1.5 mg/kg, ketamine 1–2 mg/kg. Similarly, never give neostigmine without an anticholinergic — the first landmark of reversal pharmacology that every clinical student must internalise.