Should azathioprine be stopped prior to surgery?

Perioperative Management of Azathioprine for Surgery

For patients with non-severe SLE, azathioprine should be withheld 1 week prior to surgery and restarted 3-5 days after surgery if there are no wound healing complications or infection. 1

Disease-Specific Recommendations

For Systemic Lupus Erythematosus (SLE):

• Severe SLE: Continue azathioprine through the surgical period without interruption 1

  • This recommendation is based on indirect evidence from organ transplant patients who continue anti-rejection therapy during surgery 1
  • The risk of SLE flare after withholding immunosuppression may outweigh infection risk in severe disease 1

• Non-severe SLE: Withhold azathioprine 1 week prior to surgery 1

  • Restart 3-5 days after surgery if no wound healing complications or infection 1
  • This allows some return of normal immune function while minimizing flare risk 1
  • The morbidity of infection may outweigh the risk of flare in non-severe SLE 1

For Inflammatory Bowel Disease (IBD):

• Azathioprine can be continued during the perioperative period 1
  • Evidence suggests that purine analogues (azathioprine and mercaptopurine) do not adversely affect postoperative outcomes 1
  • Thiopurines take up to 3 months to reach therapeutic levels and 3 months to fully wash out, making immediate pre-surgical discontinuation unlikely to impact complication risk 1
  • The elimination half-life of these agents is only 1-2 hours 1

Timing of Medication Restart

• For patients who had azathioprine withheld, restart when:

  • 3-5 days after surgery if no wound healing complications or infection 1
  • Once oral intake is resumed in IBD patients 1

• For biologic therapies (different from azathioprine but often used in combination):

  • Restart once the wound shows evidence of healing (typically ~14 days) 1
  • All sutures/staples are out 1
  • No significant swelling, erythema, or drainage 1
  • No clinical evidence of non-surgical site infections 1

Evidence Quality and Considerations

• The recommendations for perioperative azathioprine management are based on low-level evidence 1
• Studies specifically examining azathioprine in surgical settings show:
  • No increased rate of postoperative complications with azathioprine use before colectomy for ulcerative colitis 2
  • No association between thiopurine use and postoperative complications in Crohn's disease 3

Important Caveats

• Decisions regarding elective surgery in patients with severe SLE should involve the patient's rheumatologist 1
• Multiple mechanisms are postulated for immunosuppression with azathioprine, including leukopenia, interference with T cell signaling, and blocking the de novo pathway of purine synthesis 1
• Unlike azathioprine, high-dose corticosteroids are associated with increased risk of postoperative infectious complications (RR 1.55; 95% CI 1.23-1.95) 3
• For IBD patients, the risk of disease flare from stopping azathioprine likely outweighs any theoretical benefit of discontinuation 1

Algorithm for Decision-Making

1. Identify the underlying condition requiring azathioprine:

   • Severe SLE → Continue azathioprine through surgery 1
   • Non-severe SLE → Withhold 1 week before surgery 1
   • IBD → Continue azathioprine through surgery 1

2. Monitor for complications after surgery:

   • Wound healing issues
   • Signs of infection
   • Disease flare symptoms

3. Restart medication:

   • For non-severe SLE: 3-5 days after surgery if no complications 1
   • For IBD: Continue throughout or restart with oral intake 1