Perioperative Management of Rheumatologic Conditions: A Critical Care Perspective

A Comprehensive Review for Critical Care Trainees

Dr Neeraj Manikath , claude.ai

Introduction

The perioperative management of patients with rheumatologic conditions represents a delicate balance between minimizing disease flare risk and reducing perioperative complications. With the expanding arsenal of biologic disease-modifying antirheumatic drugs (DMARDs) and the complex interplay of immunosuppression, infection risk, and surgical stress, intensivists must navigate multiple competing priorities. This review addresses three critical domains essential for optimizing outcomes in this vulnerable population.

Timing of Biologic DMARDs and Immunosuppressants

The Pharmacokinetic Approach

The modern paradigm for timing biologic DMARD withdrawal centers on achieving drug washout equivalent to one half-life before surgery, thereby minimizing circulating drug levels while avoiding prolonged discontinuation that precipitates disease flare.

TNF-α Inhibitors:

Infliximab (half-life 7-12 days): Discontinue 4-6 weeks preoperatively[1]
Adalimumab (half-life 10-20 days): Discontinue 2-4 weeks preoperatively[2]
Etanercept (half-life 3-5 days): Discontinue 1-2 weeks preoperatively[1]
Certolizumab pegol (half-life 14 days): Discontinue 2-4 weeks preoperatively
Golimumab (half-life 14 days): Discontinue 2-4 weeks preoperatively

Pearl: Certolizumab, lacking an Fc region, does not cross the placenta and may be preferred in pregnant patients requiring perioperative management.

IL-6 Inhibitors:

Tocilizumab IV (half-life 11-13 days): Discontinue 4 weeks preoperatively[3]
Tocilizumab SC (half-life similar): Discontinue 3-4 weeks preoperatively
Sarilumab (half-life 8-22 days): Discontinue 3-4 weeks preoperatively

B-Cell Depleting Agents:

Rituximab (half-life 18-32 days): Ideally schedule surgery when B-cell reconstitution begins (typically 6-9 months post-infusion)[4]
Effect persists far beyond drug clearance due to sustained B-cell depletion

Oyster: The 2017 ACR/AAHKS guidelines recommend continuing rituximab and abatacept through elective arthroplasty, challenging conventional wisdom. However, this applies specifically to elective orthopedic procedures in carefully selected patients[5].

T-Cell Costimulation Inhibitor:

Abatacept IV (half-life 8-25 days): Discontinue 4 weeks preoperatively
Abatacept SC (half-life 14 days): Discontinue 1-2 weeks preoperatively[2]

IL-17 and IL-23 Inhibitors:

Secukinumab (half-life 27 days): Discontinue 3-4 weeks preoperatively
Ixekizumab (half-life 13 days): Discontinue 2-3 weeks preoperatively
Ustekinumab (half-life 19-28 days): Discontinue 4-6 weeks preoperatively
Guselkumab (half-life 15-18 days): Discontinue 3-4 weeks preoperatively

JAK Inhibitors: The Unique Challenge

JAK inhibitors (tofacitinib, baricitinib, upadacitinib) present distinct perioperative considerations:

Short half-lives (3-12 hours) allow rapid washout
Discontinue 3-7 days preoperatively[6]
Black box warnings for thrombosis and infection necessitate careful risk stratification
Emerging data suggest increased venous thromboembolism risk in elderly patients with cardiovascular risk factors

Hack: For urgent surgery, JAK inhibitors' rapid clearance is advantageous—a 24-48 hour delay may suffice for adequate washout in emergency settings.

Conventional Synthetic DMARDs

Methotrexate: Controversy resolved: Continue methotrexate perioperatively[5,7]. The landmark PEXIVAS and multiple cohort studies demonstrate no increased infection risk and reduced flare rates with continuation.

Exception: Major surgery with anticipated prolonged NPO status or severe renal impairment

Leflunomide:

Extremely long half-life (14-18 days for active metabolite)
Discontinue 4-6 weeks preoperatively for major surgery[8]
Consider cholestyramine washout for urgent cases (8g TID for 11 days reduces levels by 40%)

Hydroxychloroquine:

Continue perioperatively—no immunosuppressive effect at therapeutic doses[5]
Provides disease control without infection risk

Sulfasalazine:

Continue perioperatively for most procedures
Consider holding for bowel surgery due to potential anastomotic healing concerns (limited evidence)

Glucocorticoids

Never discontinue abruptly—continue at maintenance dose
Address adrenal insufficiency risk (see next section)
Doses >10mg/day prednisone equivalent: consider wound healing and infection implications

Pearl: The infection risk from glucocorticoids is dose-dependent and duration-dependent. Current prednisone >20mg/day or cumulative exposure matters more than biologic use for infection risk[9].

Postoperative Resumption

General Principle: Resume therapy when:

Adequate wound healing established
No signs of infection
Patient tolerating oral intake (if applicable)
Typically 14 days for major surgery, 7 days for minor procedures[2]

Hack: For patients at high flare risk (active lupus nephritis, vasculitis), consider bridging with low-dose prednisone rather than prolonged DMARD discontinuation.

Managing Adrenal Insufficiency in Chronic Steroid Users

Understanding HPA Axis Suppression

Hypothalamic-pituitary-adrenal (HPA) axis suppression risk correlates with:

Dose: >5mg prednisone daily for >3 weeks
Duration: Risk increases substantially after 3 months
Timing: Evening doses suppress more than morning doses
Formulation: Systemic > inhaled/topical (though high-dose inhaled steroids can suppress)

Oyster: Not all patients on chronic steroids are adrenally insufficient. Studies show only 50-60% of patients on chronic prednisone ≥5mg have HPA suppression[10]. However, testing is impractical perioperatively—empiric coverage is standard.

Risk Stratification Framework

High Risk for Perioperative Adrenal Crisis:

Prednisone ≥20mg daily for >3 weeks
Any dose of systemic glucocorticoids for >3 months with Cushingoid features
Previous adrenal insufficiency diagnosis
Major surgery with significant physiologic stress

Moderate Risk:

Prednisone 5-20mg daily for >3 weeks
Intermediate-risk surgery (orthopedic, vascular)

Low Risk:

Prednisone <5mg daily
Minor surgery (cataract, dental)
Topical/inhaled steroids only (unless very high dose)

Perioperative Steroid Supplementation Protocols

The traditional "stress dose steroid" teaching has evolved toward more conservative approaches based on physiologic cortisol response to surgical stress[11].

For Minor Surgery (local anesthesia, minimal stress):

Continue home dose
No supplementation needed
Examples: cataract surgery, dental procedures, skin biopsies

For Moderate Surgery (peripheral orthopedic, open cholecystectomy):

Classic approach: Hydrocortisone 50mg IV at induction, then 25mg IV q8h × 24-48 hours
Modern conservative approach: Continue home dose + hydrocortisone 25-50mg IV at induction, then resume home dose[12]

For Major Surgery (cardiothoracic, major abdominal, vascular):

Hydrocortisone 100mg IV at induction
Followed by 50mg IV q8h or continuous infusion at 200mg/24h
Taper over 2-3 days as patient stabilizes
Resume home dose once tolerating oral intake

Pearl: Hydrocortisone provides both glucocorticoid and mineralocorticoid activity, making it ideal for acute stress coverage. If unavailable, methylprednisolone 40mg IV = hydrocortisone 100mg, but add fludrocortisone 0.1mg daily for mineralocorticoid support.

The Septic Shock Conundrum

Patients with baseline adrenal insufficiency risk presenting differently in septic shock:

May have relative adrenal insufficiency superimposed on chronic suppression
Consider hydrocortisone 50mg IV q6h or 200mg/24h infusion per Surviving Sepsis guidelines[13]
This dose provides both stress coverage and septic shock management
Critical: Don't delay recognition—unexplained hypotension refractory to fluids and vasopressors despite adequate resuscitation suggests adrenal crisis

Hack: Random cortisol <10 μg/dL during shock suggests insufficiency, but never delay treatment for testing. In known chronic steroid users with refractory shock, empiric stress-dose steroids are lifesaving.

Monitoring and Complications

Clinical Monitoring:

Vital signs, especially blood pressure
Electrolytes (hyponatremia, hyperkalemia suggest insufficiency)
Blood glucose (stress steroids cause hyperglycemia)
Signs of infection (steroids mask fever and inflammatory response)

Red Flags for Adrenal Crisis:

Hypotension unresponsive to fluid resuscitation
Altered mental status
Fever, nausea, vomiting, abdominal pain
Hyponatremia, hyperkalemia, hypoglycemia

Weaning Strategy

For patients requiring stress-dose coverage:

Rapid taper once hemodynamically stable and tolerating oral intake
Day 1 post-stability: Reduce to 50mg q8h (or equivalent)
Day 2: Reduce to 25mg q8h or switch to oral prednisone 20-30mg
Day 3: Transition to home dose

Oyster: HPA axis recovery is unpredictable. Some patients require months to recover function after stopping chronic steroids. This doesn't affect acute perioperative management but matters for long-term planning.

Assessing Infection Risk in Immunocompromised Rheumatology Patients

The Multifactorial Nature of Infection Risk

Infection risk in rheumatology patients results from:

Underlying disease activity (lupus, vasculitis themselves impair immunity)
Immunosuppressive medications
Structural damage (bronchiectasis, skin ulcers)
Comorbidities (diabetes, chronic kidney disease, lung disease)
Surgical factors (procedure type, duration, implanted devices)

Risk Stratification by Medication Class

Highest Risk (Relative Risk 2-5× baseline):

Rituximab: Profound hypogammaglobulinemia, encapsulated bacterial infections, PJP risk[14]
Cyclophosphamide: Severe leukopenia, PJP, fungal infections
High-dose glucocorticoids (>20mg/day): Bacterial, fungal, opportunistic infections[9]
JAK inhibitors: Herpes zoster (10-15% annually), tuberculosis reactivation[15]

Moderate Risk (Relative Risk 1.5-2× baseline):

TNF-α inhibitors: Tuberculosis reactivation, fungal infections (especially histoplasmosis, coccidioidomycosis)[16]
Tocilizumab: Bacterial infections, GI perforation risk
Mycophenolate mofetil: Herpes virus infections, PJP
Azathioprine: Modest immunosuppression

Lower Risk (Relative Risk <1.5× baseline):

Methotrexate (monotherapy): Minimal infection risk at standard doses[7]
Hydroxychloroquine: No immunosuppression
Sulfasalazine: Minimal risk
Abatacept, IL-17/IL-23 inhibitors: Relatively safer profiles

Pearl: Combination therapy dramatically increases risk. Prednisone + biologic + conventional DMARD creates additive/synergistic infection susceptibility.

Specific Pathogen Considerations

Tuberculosis Screening:

Mandatory before TNF-α inhibitors, JAK inhibitors, rituximab[17]
Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
Chest radiograph
Consider IGRA over TST in BCG-vaccinated patients
Treat latent TB before immunosuppression (isoniazid 300mg daily × 9 months or rifampin 600mg daily × 4 months)

Hack: In urgent surgical situations where TB screening was never completed, obtain baseline testing and start prophylaxis empirically if high-risk epidemiology or chest X-ray abnormalities exist. Don't delay necessary surgery for TB workup completion.

Pneumocystis jirovecii Pneumonia (PJP):

Prophylaxis indicated when: Prednisone ≥20mg × >1 month + another immunosuppressant, or cyclophosphamide, or rituximab[18]
Trimethoprim-sulfamethoxazole: Single-strength daily or double-strength TIW
Alternatives: Dapsone 100mg daily (check G6PD), atovaquone 1500mg daily, or inhaled pentamidine

Oyster: PJP risk persists 3-6 months after stopping high-risk medications. Continue prophylaxis during this window.

Hepatitis B Reactivation:

Screen all patients before rituximab, TNF-α inhibitors, JAK inhibitors[19]
Test: HBsAg, anti-HBc, anti-HBs
HBsAg positive: Entecavir or tenofovir prophylaxis throughout therapy + 12 months post-cessation
HBsAg negative/anti-HBc positive (past infection): Monitor HBV DNA or consider prophylaxis for high-risk drugs (rituximab)

Fungal Infections:

Endemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis): Consider geographic risk with TNF-α inhibitors
Invasive aspergillosis: Rare but reported with high-dose steroids + other immunosuppressants
Candida: Increased risk with prolonged antibiotics and glucocorticoids

Viral Infections:

Herpes zoster: Dramatically increased with JAK inhibitors (consider vaccination pre-treatment with Shingrix)[15]
CMV reactivation: Rare except with high-dose steroids + rituximab or cyclophosphamide
COVID-19: Higher severity in rituximab, JAK inhibitor, mycophenolate users—vaccination critical[20]

Perioperative Infection Prevention Strategies

Preoperative Optimization:

Achieve disease remission when possible before elective surgery
Minimize glucocorticoid dose (target <10mg prednisone equivalent)
Complete vaccination (pneumococcal, influenza, herpes zoster) ≥4 weeks before biologics
Address modifiable risk factors: glucose control, smoking cessation, nutritional status
Antibiotic prophylaxis: Standard surgical prophylaxis protocols apply; no modifications needed for immunosuppression

Pearl: Live vaccines are contraindicated during biologic therapy and high-dose immunosuppression. Plan vaccinations during disease quiescent periods before intensifying therapy.

Intraoperative Considerations:

Standard surgical aseptic technique
Maintain normothermia
Judicious use of implanted materials (consider infection risk vs. benefit)

Postoperative Surveillance:

High index of suspicion for infection—fever may be blunted by steroids
Low threshold for imaging and cultures
Consider atypical pathogens in deteriorating patients
Daily wound assessment in high-risk patients

The ICU Patient with Suspected Infection

Diagnostic Approach:

Broad initial workup: Blood cultures (2 sets), respiratory cultures, urine culture, wound cultures
Consider opportunistic pathogens: PJP (bronchoscopy with BAL if hypoxemic), fungal cultures/antigens (galactomannan, β-D-glucan)
CT imaging earlier than standard patients (subtle findings significant)
Serum biomarkers: Procalcitonin less reliable (may be blunted), CRP trends useful

Empiric Antibiotic Principles:

Broad-spectrum coverage including MRSA, Pseudomonas
Add PJP coverage (TMP-SMX high-dose) if respiratory failure + ground-glass opacities + CD4 <200 or recent rituximab/cyclophosphamide
Consider antifungal coverage (voriconazole or echinocandin) in high-risk patients with persistent fever despite antibiotics
Lower threshold for empiric antivirals (acyclovir for HSV/VZV if vesicular lesions or unclear encephalopathy)

Hack: In rituximab-treated patients with hypoxemic respiratory failure, PJP and CMV can coexist. Consider both empirically while awaiting BAL results. CMV PCR from BAL fluid aids diagnosis.

Balancing Immunosuppression in Acute Illness

Continue or Stop DMARDs?

Serious infection: Hold biologics, JAK inhibitors, and conventional DMARDs (except hydroxychloroquine) until infection resolving
Maintain maintenance steroids (adrenal insufficiency risk)
Resume therapy after clinical improvement and appropriate antimicrobial therapy duration

Oyster: Paradoxically, abrupt DMARD cessation can precipitate disease flare, which itself increases infection risk and complicates management. Case-by-case assessment with rheumatology consultation is ideal.

Conclusion: The Critical Care Synthesis

Managing rheumatology patients perioperatively demands integration of pharmacokinetic principles, physiologic stress response understanding, and infection risk stratification. Key tenets include:

Individualize biologic DMARD timing based on half-lives while balancing flare risk
Assume HPA axis suppression in chronic steroid users and provide appropriate stress coverage
Maintain high suspicion for opportunistic infections and employ risk-stratified prophylaxis
Multidisciplinary collaboration with rheumatology, surgery, and infectious disease optimizes outcomes

The perioperative period represents both vulnerability and opportunity—vulnerability to infection and disease flare, but opportunity for optimization through evidence-based management. As our therapeutic armamentarium expands, so must our sophistication in navigating these complex clinical scenarios.

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Conflict of Interest: None declared

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Sunday, November 9, 2025