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

Direct Answer

Corticosteroids significantly increase the risk of both anastomotic leak and surgical site infection in colorectal surgery, with an odds ratio of 1.68-1.7 for infectious complications and should be tapered to <20 mg/day prednisone equivalent or discontinued before elective surgery when medically feasible, while biologic agents (anti-TNF therapy) and thiopurines (azathioprine) do not increase perioperative complications and can be safely continued. 1

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Risk Stratification by Medication Class

Corticosteroids: HIGH RISK - Requires Intervention

Corticosteroids are uniquely problematic among immunosuppressants and carry substantial surgical risk 1:

• Anastomotic leak risk: Increased with OR 1.68 (95% CI 1.24-2.28) and adjusted pooled OR 1.7 (95% CI 1.38-2.09) 1
• All postoperative complications: Increased with OR 1.41 (95% CI 1.07-1.87) 1
• Surgical site infections: Up to doubling of risk in patients on ≥20 mg prednisone daily for >6 weeks 1
• Anastomotic leakage rate: 6.77% in corticosteroid-exposed patients vs 3.26% in non-exposed patients 2
• Seven-fold increased risk of anastomotic leak specifically in colorectal surgery 3

The risk threshold begins at 10-40 mg prednisolone daily for 3-6 weeks, with highest risk at ≥20 mg/day 1, 4. Even moderate doses carry significant complication rates 1.

Biologic Agents (Anti-TNF Therapy): SAFE - Continue Perioperatively

Biologic immunosuppressants do not increase perioperative complications and represent a critical distinction from corticosteroids 1:

• Meta-analysis of 1,407 patients on infliximab vs 4,589 controls showed no differences in major complications, minor complications, infectious complications, or anastomotic leak 1
• Recent meta-analyses confirm no increased risk of postoperative complications with biological treatment 1
• Continue anti-TNF therapy, vedolizumab, and ustekinumab perioperatively without interruption 1

Thiopurines (Azathioprine/Mercaptopurine): SAFE - Continue Perioperatively

Thiopurines do not adversely affect postoperative outcomes 1:

• Systematic reviews of 11 studies found no increase in risk of postoperative complications 1
• Can be safely continued perioperatively and restarted immediately when oral intake resumes 1
• Study of 484 consecutive CD operations showed no difference in complication rates with thiopurine use 5

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Preoperative Optimization Algorithm

For Elective Colorectal Surgery:

Step 1: Assess Current Medications

• Identify all immunosuppressants, dose, and duration 1
• Calculate prednisone-equivalent dose (prednisolone 5 mg = hydrocortisone 20 mg = methylprednisolone 4 mg) 3

Step 2: Corticosteroid Management (if applicable)

• Goal: Taper to <20 mg/day prednisone equivalent or complete cessation when medically feasible 1, 4
• Timeline: Allow adequate time for tapering before elective surgery 1
• If unable to taper: Consider diverting stoma or staged procedure, especially with other risk factors present 1

Step 3: Biologic and Thiopurine Management

• Continue without interruption - discontinuation provides no benefit and may worsen disease control 1
• Plan to restart thiopurines immediately when oral intake resumes postoperatively 1

Step 4: Risk Assessment for Protective Stoma

• Consider temporary diverting stoma when high-dose steroids cannot be weaned, particularly in emergency surgery or when multiple risk factors coexist 1

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Perioperative Steroid Continuation (When Cessation Not Possible)

For Patients on Chronic Steroids (≥20 mg/day for ≥3 weeks):

Intraoperative management 3:

• Convert oral dose to IV equivalent when NPO (prednisolone 5 mg = hydrocortisone 20 mg) 3
• Continue usual daily dose - do NOT routinely administer high-dose "stress steroids" (200-300 mg hydrocortisone) 3
• Current evidence does not support routine stress dosing; patients maintain adequate endogenous production with usual dose continuation 3

Rescue dosing only for unexplained hypotension 3:

• If fluid-unresponsive hypotension occurs: 100 mg IV hydrocortisone immediately 3
• Follow with 50 mg IV hydrocortisone every 6 hours 3

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Additional Risk Factors to Consider

Beyond immunosuppressants, other definitive risk factors for anastomotic leak include 6:

• Low preoperative albumin (<3.5 g/dL): OR 2.56 6
• Male sex: OR 3.12 6
• Increased operative duration: OR 1.53 per 60-minute increment 6
• Blood transfusion: OR 2.43 7

These factors compound with corticosteroid use and should inform decisions about protective stomas 1, 6.

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Critical Pitfalls to Avoid

Do not discontinue biologics or thiopurines unnecessarily - this provides no surgical benefit and risks worsening underlying disease control 1. This is a common error that increases patient harm.

Do not underestimate moderate-dose corticosteroids - even doses below 20 mg/day carry increased risk, though lower than higher doses 1, 4.

Do not assume all immunosuppressants carry equal risk - corticosteroids are uniquely problematic while biologics and thiopurines are safe 1. This distinction is critical for surgical planning.

Do not administer routine high-dose stress steroids - continue usual equivalent dose only, reserving rescue dosing for hemodynamic instability 3.

Do not delay necessary surgery due to immunosuppression alone - nearly 50% of CD patients undergo surgery while on immunosuppressants, and with appropriate management (particularly corticosteroid optimization), surgery should proceed when indicated 5.