Is there a risk of Malignant Hyperthermia (MH) in a patient with GNE (Glycogenosis Nonaka Episodica) myopathy undergoing surgical procedures with anesthesia?

Risk of Malignant Hyperthermia in GNE Myopathy

Patients with GNE myopathy do not have an established increased risk for malignant hyperthermia, as GNE myopathy is not caused by mutations in the genes specifically implicated in MH susceptibility (RYR1, CACNA1S, STAC3). However, given the lack of specific evidence and the general principle that patients with clinical myopathies warrant cautious anesthetic management, a trigger-free anesthetic approach is the safest strategy.

Understanding the MH Risk Framework

The 2021 Association of Anaesthetists guidelines clearly define which patients are at increased risk for MH 1:

• Patients with clinical myopathy who have a genetic etiology involving genes implicated in MH susceptibility (RYR1, CACNA1S, STAC3) are at increased risk 1
• GNE myopathy is caused by mutations in the GNE gene (encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase), not the MH-associated genes
• The genetic basis of GNE myopathy is distinct from the calcium channel dysregulation that causes true MH 2

Critical Distinction: True MH vs. Myopathy-Related Complications

While GNE myopathy patients are not at increased risk for true MH, they may still experience anesthesia-related complications:

• True MH susceptibility requires mutations in RYR1, CACNA1S, or STAC3 genes 2
• Patients with various myopathies can develop anesthesia-induced rhabdomyolysis (AIR), which clinically mimics MH but has different pathophysiology 3
• The clinical presentations of MH and AIR overlap significantly: hypermetabolic state, hyperpyrexia, hypercarbia, acute renal failure, and hyperkalemia 3

Recommended Anesthetic Management Approach

Despite the lack of established MH risk, a cautious trigger-free approach is warranted:

Preoperative Planning

• Contact an MH Unit for specialized advice when managing patients with any clinical myopathy, even if not specifically MH-associated 1
• Consider deferring non-urgent surgery if the unclear MH status would compromise usual anesthetic management 1
• Obtain baseline creatine kinase levels, as patients with myopathies may have baseline elevations 1

Anesthetic Technique Selection

• Prioritize regional anesthesia techniques when appropriate to avoid general anesthesia entirely 1
• If general anesthesia is required, use total intravenous anesthesia (TIVA) with non-triggering agents 1, 4
• Absolutely avoid succinylcholine, as depolarizing muscle relaxants can cause severe rhabdomyolysis in patients with underlying muscle disease 5, 6, 3
• Avoid all volatile inhalational anesthetics (sevoflurane, isoflurane, desflurane, halothane) 1

Machine Preparation

• If using an anesthesia machine previously exposed to volatile agents, flush with 100% oxygen to achieve <5 ppm residual volatile anesthetic 1
• Consider using activated charcoal filters for more rapid elimination of trace volatiles 1
• Alternatively, use a dedicated trigger-free anesthesia machine 7

Intraoperative Monitoring

• Continuously monitor end-tidal CO₂ (ETCO₂), as increased ETCO₂ is the cardinal early sign of MH 2, 8
• Monitor core temperature continuously 2, 8
• Monitor for tachycardia, which accompanies increased CO₂ production 2
• Have dantrolene immediately available (initial dose 2-3 mg/kg, then 1 mg/kg every 5 minutes until treatment goals reached) 2, 4, 5

Safe Anesthetic Agents for GNE Myopathy

• Propofol, etomidate, ketamine (intravenous induction agents) 6, 7
• Nitrous oxide 6, 9, 7
• Benzodiazepines 6, 7
• Opioids 6, 9, 7
• Non-depolarizing muscle relaxants (rocuronium, vecuronium, cisatracurium) 6, 9, 7
• Local anesthetics 7

Common Pitfalls to Avoid

• Do not assume safety based on previous uneventful anesthetics—MH susceptibility can manifest after multiple exposures 2
• Do not delay treatment if signs of hypermetabolism develop—mortality increases with delayed dantrolene administration 2
• Do not confuse the absence of specific MH gene mutations with complete safety—myopathy patients can still develop life-threatening complications 3
• Do not use succinylcholine in any patient with known myopathy, regardless of MH risk 5, 3

Postoperative Management

• Monitor in a recovery area with continuous pulse oximetry and capnography for at least 2 hours 7
• Observe for delayed rhabdomyolysis by monitoring urine output, color, and creatine kinase levels 3
• Day case surgery can be considered if all safety measures are implemented and the patient remains stable 7