What are the risks of using Metaxolone (a muscle relaxant) in the postoperative period?

Metaxalone Postoperative Risks

Metaxalone should be held on the day of surgery due to risks of excessive central nervous system depression when combined with anesthetic agents, potential interactions with sedatives, and concerns in patients with hepatic or renal dysfunction. 1

Primary Perioperative Concerns

Central Nervous System Depression and Anesthetic Interactions

• Metaxalone potentiates the sedative effects of anesthetic agents and other CNS depressants, creating risk for excessive sedation, respiratory depression, and prolonged recovery from anesthesia 1, 2

• The FDA label explicitly warns that "the sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive" 3

• The mechanism involves central nervous system depression, though the precise pathway remains unclear 1

Specific Adverse Effects in the Perioperative Setting

• CNS effects include drowsiness, dizziness, and irritability, which can complicate postoperative monitoring and recovery 1

• Enhanced CNS depression occurs when metaxalone is taken with food, with elderly patients being especially susceptible 3

• Mental and physical impairment may affect patient cooperation with postoperative care, ambulation, and physical therapy 3

High-Risk Patient Populations

Hepatic and Renal Dysfunction

• Metaxalone is absolutely contraindicated in patients with significant hepatic or renal dysfunction 1, 4

• The drug should be administered with great care to patients with pre-existing liver damage, with serial liver function studies recommended 3

• Impaired elimination in hepatic or renal disease increases risk of drug accumulation and toxicity 2, 4

Hematologic Risks

• Metaxalone has been associated with drug-induced, hemolytic, or other anemias 1, 4

• This risk is particularly concerning in the perioperative period when patients may already have compromised hematologic status from surgical blood loss 4

Dangerous Drug Interactions in the Postoperative Period

Serotonergic Medications

• At supratherapeutic concentrations, metaxalone demonstrates monoamine oxidase A (MAO-A) inhibition, creating risk for serotonin syndrome when combined with SSRIs or other serotonergic drugs 5, 6

• Case reports document severe serotonin toxicity with hyperthermia (up to 41.6°C), rigidity, myoclonus, hyperreflexia, and altered mental status in patients taking metaxalone with SSRIs 5

• Toxic metaxalone concentrations (31-61 mcg/mL) show significant MAO-A inhibition compared to therapeutic levels (0.9 mcg/mL) 5, 6

Opioid Combinations

• The combination of metaxalone with postoperative opioids significantly increases sedation risk 4

• This interaction is particularly problematic given that opioids are standard postoperative analgesics 4

Clinical Management Algorithm

Preoperative Planning

1. Hold metaxalone on the day of surgery per Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus 1, 2

2. Document all concurrent medications, particularly SSRIs, other serotonergic agents, and CNS depressants 5, 6

3. Assess hepatic and renal function preoperatively in chronic metaxalone users 3

Intraoperative Considerations

• Anticipate increased sensitivity to anesthetic agents and adjust dosing accordingly 1

• Monitor for prolonged effects of sedatives and muscle relaxants 2

• Maintain vigilance for signs of excessive CNS depression 3

Postoperative Monitoring

• Enhanced monitoring is required if metaxalone was not held preoperatively or in cases of chronic use 1

• Watch for signs of serotonin syndrome if patient is on SSRIs: hyperthermia, rigidity, myoclonus, hyperreflexia, altered mental status 5, 6

• Elderly patients require particular attention due to increased susceptibility to CNS effects 3

Important Caveats and Pitfalls

Withdrawal Considerations

• Unlike some muscle relaxants (carisoprodol, cyclobenzaprine, tizanidine), the literature does not document significant withdrawal symptoms with metaxalone discontinuation 1

• This makes holding the medication on the day of surgery safer compared to agents requiring tapering 1

Overdose Risk

• Metaxalone has documented toxicity in overdose, with one fatal case reporting femoral vein blood concentration of 39 mg/L (compared to therapeutic peak of 0.9 mcg/mL) 7

• Polydrug fatalities have been reported, particularly when combined with alcohol and other CNS depressants 7

False Laboratory Results

• Metaxalone can cause false-positive Benedict's tests due to an unknown reducing substance; glucose-specific tests should be used to differentiate findings 3

Comparative Safety Profile

• Among commonly prescribed skeletal muscle relaxants, metaxalone has the fewest reports of side effects and no reports of major safety issues in therapeutic use 8

• However, this favorable profile does not eliminate perioperative risks from CNS depression and drug interactions 8

• The lack of direct skeletal muscle relaxation means metaxalone works purely through sedative properties, making CNS effects unavoidable 3