What are the considerations for anesthesia in patients taking methotrexate (MTX)?

Methotrexate and Anesthesia: Considerations and Management

Methotrexate can generally be safely continued during the perioperative period for most patients undergoing surgery and anesthesia, as evidence suggests no increased risk of infection or surgical complications when maintained. 1

Perioperative Management of Methotrexate

General Recommendations

• For elective orthopedic surgery, evidence from prospective randomized studies indicates that methotrexate (MTX) can be safely continued without increased risk of infection or postoperative complications 1
• For patients with well-controlled skin disease, it is generally safe to continue MTX during the perioperative period 1
• Maintaining MTX therapy helps prevent disease flares that could complicate recovery 2

Special Considerations for Discontinuation

• For major surgery in patients with significant comorbidities (especially diabetes), temporary discontinuation of MTX may be warranted due to theoretical increased infection risk 1, 3
• In patients with acute illness, infection, or receiving medications that may interact with MTX, temporary discontinuation during hospitalization should be considered 3
• If MTX is discontinued, it should be resumed upon discharge when the acute illness has resolved 3

Risk Assessment Before Anesthesia

Renal Function Evaluation

• Assess renal function with eGFR before anesthesia, as MTX is primarily excreted by the kidneys 1, 4
• For patients with creatinine clearance <20 mL/min, MTX should be avoided 1
• For patients with creatinine clearance between 20-50 mL/min, the MTX dose should be reduced by half 1
• Impaired renal function significantly increases the risk of myelosuppression, which is the most important cause of MTX-associated death 1

Medication Interactions with Anesthetics

• Avoid concomitant use of nitrous oxide anesthesia in patients receiving MTX, as it potentiates MTX's effect on folate-dependent metabolic pathways, increasing the risk of toxicity (stomatitis, myelosuppression, neurotoxicity) 5
• Be cautious with medications commonly used during anesthesia that may interact with MTX, including NSAIDs and certain antibiotics 1, 5

Monitoring During Perioperative Period

Laboratory Monitoring

• Complete blood count should be checked before surgery to assess for bone marrow suppression 3
• Liver function tests should be evaluated, as MTX can cause hepatotoxicity 3
• If MTX was administered shortly before surgery, monitor renal function closely 3

Signs of Toxicity

• Monitor for signs of MTX toxicity including mucositis, fever, diarrhea, erythema, and ulceration 3
• Watch for myelosuppression, which can manifest as increased susceptibility to infection 1

Post-Anesthesia Considerations

Medication Management

• If antibiotics are required postoperatively for severe infection, consider temporarily stopping MTX until the patient recovers and completes the antibiotic course 1
• Be aware of potential drug interactions that may increase MTX toxicity, including many NSAIDs, salicylates, penicillin, proton pump inhibitors, and tetracyclines 1, 5

Fluid Management

• Maintain adequate hydration to improve renal elimination of MTX, especially if the patient received MTX shortly before surgery 3, 6
• Consider urine alkalinization with sodium bicarbonate if there are concerns about MTX toxicity 1

Common Pitfalls and Caveats

• Abrupt discontinuation of MTX may lead to disease flares, which could complicate recovery 3
• When restarting MTX after prolonged discontinuation, consider resuming at a lower dose with gradual escalation while monitoring for toxicity 3
• The presence of interstitial lung disease is not an absolute contraindication for MTX use but requires careful monitoring, especially in the perioperative period 1
• For patients with diabetes or other comorbidities that increase infection risk, the decision to continue MTX must be made on a case-by-case basis, weighing the risk of disease flare against the potential for increased complications 1

By following these guidelines, anesthesiologists and surgeons can safely manage patients on methotrexate therapy during the perioperative period while minimizing the risk of complications and disease flares.