In an adult patient receiving standard RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) therapy, should the anti‑tubercular drugs be continued or withheld before anesthesia, especially if hepatic dysfunction or elevated liver enzymes are present?

Management of Anti-Tubercular Drugs Before Anesthesia

Continue anti-tubercular drugs through the perioperative period without interruption, as there is no evidence-based indication to withhold RIPE therapy before anesthesia in patients with normal or mildly elevated liver function. 1

Key Decision Algorithm

For Patients with Normal Baseline Liver Function (AST/ALT <2× Normal)

• Continue all anti-tubercular drugs without interruption through the perioperative period 1, 2
• No routine liver function monitoring is required before anesthesia unless symptoms develop (fever, malaise, vomiting, jaundice, unexplained deterioration) 1
• The risk of treatment interruption (drug resistance, disease progression) far outweighs theoretical perioperative concerns 3

For Patients with Moderately Elevated Transaminases (AST/ALT 2-5× Normal)

• Continue anti-tubercular drugs but obtain liver function tests immediately before anesthesia 1
• Monitor liver function weekly for two weeks, then biweekly until normalized 1
• If transaminase levels are stable or falling, proceed with surgery while continuing all TB medications 1
• Only hold medications if AST/ALT rises to ≥5× normal or bilirubin increases 1, 4

For Patients with Severe Hepatotoxicity (AST/ALT ≥5× Normal or Any Bilirubin Elevation)

• Stop rifampicin, isoniazid, and pyrazinamide immediately 1, 5
• If the patient has infectious TB (smear-positive) or is clinically unwell, substitute with streptomycin and ethambutol until liver function normalizes 1
• If the patient has non-infectious TB and is clinically stable, no treatment is needed until liver function returns to normal 1
• Never ignore bilirubin elevation—any rise mandates immediate cessation of hepatotoxic drugs regardless of transaminase levels 5, 4

Critical Perioperative Considerations

Hepatotoxicity Monitoring

• Baseline liver function tests (AST, ALT, bilirubin) are mandatory before initiating TB therapy, but routine preoperative repeat testing is only needed if symptoms develop or baseline was abnormal 1, 5, 4
• The FDA warns that severe and sometimes fatal hepatitis can occur even after many months of treatment, with risk increasing with age and daily alcohol consumption 4
• Rifampicin can cause hepatotoxicity ranging from asymptomatic enzyme elevations to fulminant liver failure, particularly when combined with other hepatotoxic agents 6

Drug Interaction Concerns

• Rifampicin is a powerful enzyme inducer that may affect anesthetic drug metabolism, but this is not an indication to withhold therapy 6, 7
• Avoid concomitant high-dose cefazolin with rifampicin in the perioperative period, as this combination can prolong prothrombin time and cause life-threatening coagulation disorders 6
• Monitor coagulation tests (prothrombin time) in patients at risk of vitamin K deficiency, as rifampicin may cause vitamin K-dependent coagulation disorders 6

Timing Patterns of Hepatotoxicity

• Early hepatotoxicity (within first 15 days) is typically rifampicin-enhanced isoniazid toxicity with generally good prognosis 7
• Late hepatotoxicity (>1 month) is often pyrazinamide-related with poorer prognosis 7
• This distinction is irrelevant for perioperative decision-making—the key is current liver function status, not timing 1

Common Pitfalls to Avoid

Do Not Stop Treatment for Asymptomatic Mild Elevations

• Never discontinue TB drugs for asymptomatic transaminase elevations <5× normal, as this risks treatment failure and drug resistance 5, 3
• Modest elevations of hepatic transaminases are common in pretreatment liver function tests of TB patients and do not contraindicate therapy 1

Do Not Delay Surgery for Stable TB Treatment

• There is no evidence that elective surgery should be postponed in patients on stable anti-tubercular therapy with normal liver function 1, 2
• The standard 6-month regimen (2 months RIPE, then 4 months isoniazid/rifampicin) should continue uninterrupted through the perioperative period 2

Do Not Use Combined Drug Preparations if Hepatotoxicity Develops

• If hepatotoxicity occurs and sequential drug reintroduction is needed, never use fixed-dose combinations (Rifinah, Rimactazid, Rifater) during the reintroduction phase, as this prevents identification of the offending agent 8
• Sequential reintroduction should follow the order: isoniazid first (50 mg/day increasing to 300 mg/day), then rifampicin (75 mg/day increasing to full dose), then pyrazinamide (250 mg/day increasing to full dose) 1, 8

Special Populations Requiring Enhanced Vigilance

• Women, particularly Black and Hispanic women, and those in the postpartum period have increased risk of fatal hepatitis and require more careful monitoring 4
• Patients with daily alcohol consumption, chronic liver disease, or injection drug use have significantly increased hepatotoxicity risk 4, 7
• For patients over 35 years, monthly hepatic enzyme monitoring (AST, ALT) should be performed throughout treatment in addition to symptom reviews 4