Does perioperative exposure to immunosuppressants (e.g. azathioprine, tacrolimus), corticosteroids (e.g. prednisone), or other medications that impair tissue integrity and wound healing increase the risk of anastomotic leak or surgical site infection in adults undergoing colorectal surgery, particularly those with a history of autoimmune diseases or transplant recipients?

Perioperative Immunosuppressants and Surgical Complications in Colorectal Surgery

Corticosteroids significantly increase the risk of anastomotic leak and surgical site infection in colorectal surgery, with an odds ratio of 1.68-1.7, while biologic agents (anti-TNF therapy) and thiopurines (azathioprine, mercaptopurine) do NOT increase perioperative complications and should be continued. 1

Corticosteroid Risk Profile

Corticosteroids are uniquely problematic among immunosuppressants and carry substantial surgical risk:

• Anastomotic leak risk increases with an adjusted pooled OR of 1.7 (95% CI 1.38-2.09) in steroid-exposed patients 1
• All postoperative complications increase with an OR of 1.41 (95% CI 1.07-1.87) 1
• Patients on long-term corticosteroids (≥20 mg prednisone daily or equivalent for >6 weeks) face up to a doubling of surgical site infections 1
• Research confirms anastomotic leakage rates of 6.77% in corticosteroid-treated patients versus 3.26% in non-steroid patients 2
• Patients on chronic steroids have a 7-fold increased risk of anastomotic leak in colorectal surgery 3

Dose-Dependent Risk Thresholds

The risk is dose-dependent with specific cut-offs:

• Significant risk begins at ≥15-20 mg/day prednisone equivalent 4
• Cut-offs for increased surgical complications range between 10-40 mg prednisolone daily for more than 3-6 weeks 1
• Lower doses (≤10-16 mg/day) carry lower but still present infection risk 4

Preoperative Steroid Management Algorithm

For elective colorectal surgery, follow this stepwise approach:

1. Taper steroids to the lowest possible dose before surgery, ideally to <20 mg/day prednisone equivalent or complete cessation when medically feasible 1, 4

2. If unable to taper adequately, consider a staged procedure with temporary diverting stoma, especially in emergency surgery or when other risk factors coexist 1

3. For high-risk anastomoses (especially inflammatory bowel disease patients on high-dose steroids), strongly consider diverting stoma 3

Intraoperative Steroid Management

Continue the patient's usual daily steroid dose perioperatively via IV route when oral intake is not possible:

• Convert oral to IV equivalent: prednisolone 5 mg = hydrocortisone 20 mg = methylprednisolone 4 mg 3
• Do NOT routinely administer high-dose "stress steroids" (200-300 mg hydrocortisone) as this increases infection risk without hemodynamic benefit 3, 4
• Reserve rescue dosing (100 mg hydrocortisone IV) only for unexplained hypotension unresponsive to fluids and vasopressors 3

Biologic Agents: Safe to Continue

Anti-TNF therapy (infliximab, adalimumab), vedolizumab, and ustekinumab do NOT increase perioperative complications and should be continued without interruption:

• Meta-analysis of 1,407 patients on infliximab versus 4,589 controls showed no differences in major complications, minor complications, infectious complications, or anastomotic leak 1
• Continue perioperatively without interruption 1
• Research confirms no difference in postoperative infection rates (pneumonia, wound infection, abscess, or anastomotic leakage) in patients pretreated with infliximab 5

Thiopurines: Safe to Continue

Azathioprine and mercaptopurine do NOT adversely affect postoperative outcomes:

• Systematic reviews of 11 studies found no increase in risk of postoperative complications 1
• Continue perioperatively and restart immediately when oral intake resumes 1
• Research in 484 consecutive operations showed no differences in complication rates between patients with and without thiopurine immunosuppression 6

Critical Clinical Algorithm for All Patients

Apply this decision tree for every patient undergoing elective colorectal surgery:

Step 1: Identify Current Immunosuppression

• If on corticosteroids ≥20 mg/day: Attempt to taper to <20 mg/day or discontinue if medically feasible 1, 4
• If unable to taper: Consider diverting stoma or staged procedure 1

Step 2: Manage Biologic Agents

• If on anti-TNF therapy, vedolizumab, or ustekinumab: Continue perioperatively without interruption 1

Step 3: Manage Thiopurines

• If on azathioprine or mercaptopurine: Continue perioperatively and restart immediately when oral intake resumes 1

Step 4: Risk Stratification

Additional risk factors that compound steroid risk include:

• Low preoperative serum albumin (<3.5 g/dL) 7
• Male sex 7
• Increased duration of surgery 7
• Blood transfusion requirement 8

Common Pitfalls to Avoid

Do not unnecessarily discontinue biologic agents or thiopurines before surgery, as this provides no benefit and may worsen underlying disease control 1

Do not underestimate the risk of corticosteroids, even at moderate doses (10-20 mg/day), which can increase complication rates 1

Do not assume all immunosuppressants carry equal risk—corticosteroids are uniquely problematic while biologics and thiopurines are safe 1

Do not administer unnecessary stress-dose steroids to patients on chronic low-dose therapy, as this increases infection risk without hemodynamic benefit 3, 4

Do not delay necessary surgery due to thiopurine or biologic use, as perioperative immunosuppression with these agents does not significantly alter surgical complication rates 6