How should methotrexate therapy be managed during the peri‑operative period for a patient undergoing anesthesia?

Methotrexate and Anesthesia

Methotrexate can be safely continued through the perioperative period for patients with rheumatoid arthritis and other rheumatic diseases undergoing elective orthopedic surgery, and this approach is generally recommended for dermatologic indications as well.

Primary Recommendation for Rheumatoid Arthritis

Continue methotrexate at the current dose through surgery 1, 2. This recommendation is based on:

• Level 1b evidence showing methotrexate continuation does not increase postoperative complications 1
• Two randomized controlled trials demonstrating no difference in infection rates between patients who continued versus stopped methotrexate (mean dose 10 mg/week) 1
• Significantly fewer RA flares in patients who continued methotrexate compared to those who stopped 1
• The 2017 ACR/AAHKS guideline explicitly recommends continuing methotrexate for patients with RA, spondyloarthropathies, juvenile idiopathic arthritis, and SLE undergoing total hip or knee arthroplasty 2

Evidence Quality and Nuances

The evidence base shows some heterogeneity that warrants discussion:

• One prospective cohort study reported 30% postoperative infections in patients continuing methotrexate versus 0% in those who stopped 1. However, this finding was contradicted by a larger multivariate analysis showing perioperative methotrexate use was not associated with wound morbidity (p=0.84) and significantly reduced RA flares 1

• The systematic review supporting the ACR/AAHKS guideline found that continuing DMARDs actually decreased infection risk (RR 0.39,95% CI 0.17-0.91) 2

• Most studies evaluated doses of 10-15 mg/week in elective orthopedic surgery settings 1

Dermatologic Indications

For patients taking methotrexate for skin disease, continuation during the perioperative period is assumed safe 3. The British Association of Dermatologists guidelines note:

• No studies specifically evaluated peri/postoperative complications in dermatology patients receiving low-dose methotrexate
• The recommendation extrapolates from rheumatology literature showing safety in elective orthopedic surgery
• When methotrexate is controlling skin disease, it can be continued perioperatively 3

Important Caveats and Risk Stratification

High-Risk Scenarios Requiring Individualized Assessment

For major surgery with additional risk factors, case-by-case decisions are necessary 3:

• Patients with diabetes or other comorbidities that increase infection risk
• Major non-orthopedic surgical procedures (limited evidence available)
• Emergency/non-elective surgery

Dose Considerations

• High methotrexate doses (>15 mg/week) may warrant reduction to ≤15 mg/week if there is high infection risk 4
• Doses >20 mg/week in adults show significantly increased incidence of serious toxic reactions, particularly bone marrow suppression 5

Severe SLE Exception

For patients with severe SLE (organ-threatening disease), methotrexate should be continued through surgery due to the risk of serious flares 6, 2. For not-severe SLE, withholding methotrexate 1 week prior to surgery may be considered 6.

Practical Implementation

Timing

• No specific washout period required for standard cases
• Surgery can proceed on the patient's regular methotrexate schedule
• Resume immediately postoperatively once wound healing is adequate

Monitoring

• Ensure recent laboratory monitoring is current (CBC, creatinine, liver enzymes) 1
• Assess for active infection or poor disease control preoperatively
• Monitor wound healing and infection signs postoperatively

Common Pitfalls to Avoid

1. Do not routinely discontinue methotrexate "to be safe" - this increases flare risk without clear infection benefit in most cases
2. Do not confuse chronic methotrexate use with high-dose chemotherapy protocols - perioperative recommendations apply to low-dose weekly regimens (typically 7.5-25 mg/week)
3. Do not use preserved methotrexate formulations for intrathecal or high-dose therapy 5
4. Do not forget folic acid supplementation - at least 5 mg/week should continue perioperatively 1

Evidence Limitations

The available evidence has important gaps:

• Most studies evaluated elective orthopedic surgery specifically
• Limited data on non-orthopedic, emergency, or high-risk surgical procedures
• Evidence quality is predominantly observational with some RCT support
• Dermatologic surgery data extrapolated from rheumatology literature

The balance of evidence favors continuation in standard elective surgery, with the understanding that infection risk must be weighed against disease flare risk in higher-risk scenarios.