Malignant Hyperthermia Triggering: Ether vs. Nitrous Oxide
Ether (diethyl ether) triggers malignant hyperthermia in susceptible patients, while nitrous oxide does NOT trigger malignant hyperthermia and is safe to use.
Understanding MH Triggering Agents
The European Malignant Hyperthermia Group clearly defines that triggering agents include all potent inhalation anesthetic agents (desflurane, sevoflurane, isoflurane, halothane, and methoxyflurane) and succinylcholine 1. Ether, as a potent volatile anesthetic, falls into this category of triggering agents 1.
In direct contrast, nitrous oxide is explicitly identified as a non-triggering agent that is safe for MH-susceptible patients 2, 3, 4. The American Society of Anesthesiologists specifically states that malignant hyperthermia is triggered by potent inhalational anesthetics and succinylcholine, but NOT by nitrous oxide 2.
Safe Anesthetic Agents for MH-Susceptible Patients
Non-Triggering Agents (Safe to Use)
- Nitrous oxide 2, 3, 4
- Intravenous induction agents (propofol, etomidate, ketamine) 3, 5
- Benzodiazepines 3
- Opioids 3
- Non-depolarizing muscle relaxants 3, 4
- Local anesthetics 4
- Xenon 4
Triggering Agents (Must Avoid)
- All potent volatile anesthetics including ether, halothane, isoflurane, sevoflurane, desflurane, methoxyflurane 1
- Succinylcholine (depolarizing muscle relaxant) 1, 3
Clinical Implications
MH-susceptible patients must NEVER be exposed to ether or any other volatile anesthetic agent 1. The pathophysiology involves dysregulation of calcium control in skeletal muscle, leading to sustained muscle contraction, hypermetabolism, and potentially fatal hyperthermia 2.
The mortality rate for MH remains approximately 4% even with dantrolene availability, making absolute avoidance of triggering agents the cornerstone of prevention 6. Previous uneventful anesthetics do NOT exclude MH susceptibility, as patients can have multiple exposures before developing a reaction 6.
Critical Management Points
- Use total intravenous anesthesia (TIVA) with propofol or other non-triggering agents for MH-susceptible patients 7
- Nitrous oxide can be safely incorporated into the anesthetic plan 2, 4
- Regional anesthesia should be prioritized when appropriate to avoid general anesthesia entirely 7
- Dantrolene must be immediately available (initial dose 2-3 mg/kg) 7, 6
- Continuous monitoring of end-tidal CO₂ is essential, as increased ETCO₂ is the cardinal early sign of MH 7, 2, 6
Common Pitfall
The most dangerous error is assuming that because nitrous oxide is an inhalational agent, it shares the same MH risk as volatile anesthetics like ether. This is categorically false—nitrous oxide has a completely different mechanism of action and does not trigger MH 2, 3, 4.