Methotrexate Should Generally Be Continued Through Surgery
For most patients undergoing elective surgery, methotrexate should be continued at the usual dose throughout the perioperative period, as this approach reduces infection risk and prevents disease flares without increasing surgical complications. 1, 2
Evidence-Based Recommendation
The 2022 American College of Rheumatology conditionally recommends continuing methotrexate through surgery for patients undergoing elective orthopedic procedures, based on moderate-quality evidence showing a decreased infection risk (relative risk 0.39,95% CI 0.17-0.91) when methotrexate is continued compared to discontinuation. 1, 2
Supporting Evidence from Multiple Sources:
Prospective randomized trials in 388 patients with rheumatoid arthritis undergoing elective orthopedic surgery demonstrated that continuing methotrexate resulted in only 2% infection/complication rates versus 15% in those who discontinued the medication. 3
A meta-analysis of IBD and rheumatoid arthritis patients found no increased risk of postoperative complications with pre-operative methotrexate use. 4
Long-term follow-up studies (10 years) showed no evidence of late deep infections in patients who continued methotrexate perioperatively. 5
Disease-Specific Considerations
For Rheumatoid Arthritis Patients:
- Continue methotrexate at the usual dose for total hip/knee arthroplasty and other orthopedic procedures. 2
- Patients who continue methotrexate experience significantly fewer disease flares postoperatively (0% flares) compared to those who discontinue (8% flares at 6 weeks). 3
- The medication can be safely continued for minor surgery without interruption. 2
For IBD Patients:
- Immunomodulators including methotrexate can be continued during the perioperative period without adversely affecting postoperative outcomes. 4
- The elimination half-life is only 1-2 hours, so stopping immediately before surgery provides no measurable benefit. 4
Specific Exceptions Requiring Discontinuation
Stop methotrexate temporarily in these situations:
- Active infection requiring antibiotics: Discontinue until infection resolves and antibiotic course is completed. 1
- Abnormal liver function: Stop if transaminases exceed twice the upper limit of normal. 1
- Bone marrow suppression: Withhold if total white cells <3.5×10^9/L or neutrophils <2×10^9/L until counts normalize. 1
- Severe renal impairment: Avoid if creatinine clearance <20 mL/min; reduce dose by half if creatinine clearance 20-50 mL/min. 1
- Major surgery with significant comorbidities (diabetes, immunocompromise): Consider case-by-case discontinuation weighing infection risk against disease flare risk. 1, 6
Practical Perioperative Management Algorithm
Pre-operative Assessment:
- Check renal function (eGFR) before anesthesia, as methotrexate is primarily renally excreted. 1
- Review for interacting medications (NSAIDs, antibiotics, proton pump inhibitors) that increase toxicity risk. 1
- Ensure adequate folic acid supplementation (at least 5 mg weekly) is maintained. 2
Intra-operative:
- Continue methotrexate on the regular dosing schedule without interruption. 2
Post-operative:
- Resume methotrexate immediately when oral intake recommences. 4
- If severe postoperative infection develops requiring antibiotics, temporarily stop methotrexate until recovery. 1
- Monitor complete blood count, liver function, and renal function if methotrexate was recently administered before admission. 1
Common Pitfalls to Avoid
Do not routinely discontinue methotrexate "to be safe" - this outdated practice from the 1990s actually increases complication rates and causes disease flares. 5, 3
Do not confuse methotrexate management with biologic agents - while biologics should be withheld according to their dosing cycle, methotrexate follows different perioperative guidelines. 2
Do not restart at lower doses after brief perioperative continuation - since the medication was never stopped, continue at the same therapeutic dose. 1