What propofol dosing (initial bolus and continuous infusion) is recommended for an adult patient with cirrhosis requiring procedural or intensive‑care sedation, including adjustments for hepatic impairment (Child‑Pugh B‑C) and elderly patients?

Propofol Dosing for Procedural and ICU Sedation in Adults with Cirrhosis

Initial Bolus Dosing

For cirrhotic patients undergoing procedural sedation, initiate propofol with slow boluses of 10–20 mg every 20–30 seconds, using lower total doses than in non-cirrhotic patients. 1

• Age-adjusted protocol for cirrhotic patients: Start with 30–40 mg for patients <70 years and 20–30 mg for patients ≥70 years, with additional 10–20 mg boluses as needed (maximum 120 mg total). 2
• The mean effective dose in Child-Pugh A and B cirrhotic patients during upper endoscopy is approximately 46 mg (range 30–120 mg), significantly lower than the 203 mg average used in some non-cirrhotic populations. 2, 3
• Clinical effect begins within 30–45 seconds, reaches maximal sedation in 1–2 minutes, and a single bolus lasts approximately 4–8 minutes. 1, 4

Continuous Infusion Dosing

For ICU sedation in cirrhotic patients, target-controlled infusion (TCI) with BIS monitoring demonstrates that cirrhotic patients require lower target plasma concentrations (2.7 μg/mL) compared to non-cirrhotic patients (3.3 μg/mL) at 30 minutes. 5

• Standard maintenance infusion for non-cirrhotic adults: 50–100 mcg/kg/min (or 5–50 μg/kg/min for lighter sedation). 6, 7, 4
• In cirrhotic patients, reduce the infusion rate by approximately 20–30% from standard dosing based on evidence showing lower propofol consumption (270 mg vs. 391 mg) and lower target plasma concentrations needed for equivalent sedation depth. 5
• Sedation maximum is achieved within 1 hour after starting continuous infusion. 4

Hepatic Impairment Adjustments

Propofol pharmacokinetics are NOT significantly altered by cirrhosis or renal insufficiency, but pharmacodynamic sensitivity is increased, requiring dose reduction. 1, 4

• Child-Pugh A and B cirrhosis: Use the reduced bolus protocol above (30–40 mg initial dose with 10–20 mg increments). 2
• Child-Pugh C cirrhosis: Although not specifically studied in the provided evidence, extrapolate from Child-Pugh B data and reduce initial boluses to 20–30 mg with 10 mg increments, monitoring closely for cumulative effects.
• Critical consideration: Cirrhotic patients demonstrate a significant decline in required target plasma concentration over time (from 3.3 μg/mL at 5 minutes to 2.7 μg/mL at 30 minutes), indicating cumulative drug effect despite normal clearance. 5
• Recovery time is prolonged in cirrhotic patients (8.5 minutes vs. 6.2 minutes) despite lower total propofol doses. 5

Elderly Patient Adjustments

Reduce initial bolus to 20–30 mg in patients ≥70 years, regardless of hepatic function. 2

• Additional boluses should be 10–20 mg with minimum 20–30 second intervals between doses. 2
• Elderly patients with cirrhosis require the most conservative approach: start with 20 mg boluses and titrate slowly.

Critical Safety Monitoring

Have vasopressors (ephedrine or metaraminol) immediately available, as propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and arterial blood pressure. 7, 4

• Provide supplemental oxygen to all patients prior to propofol administration. 1
• Monitor heart rate, blood pressure, and pulse oximetry continuously. 7
• Hypotension responds quickly to propofol reduction or discontinuation due to rapid hepatic metabolism. 1
• Bolus administration can cause transient but clinically significant hypotensive episodes, particularly in cirrhotic patients with baseline hemodynamic compromise. 1, 4

Analgesic Considerations

Propofol possesses NO intrinsic analgesic properties—always combine with analgesics for painful procedures. 1, 4

• For painful procedures (e.g., cardioversion, ERCP): Add fentanyl 25–50 μg or local anesthetic before propofol. 1, 4
• Co-administration of opioids potentiates propofol's sedative effect, allowing lower propofol doses. 4
• Typical combination for endoscopy: fentanyl 50–100 μg + propofol titrated to effect. 4

Propofol Infusion Syndrome (PRIS) Risk

PRIS typically occurs with doses >70 μg/kg/min for >48 hours but has been reported at doses as low as 1.9–2.6 mg/kg/hr. 6, 4

• Mortality from PRIS is up to 33%. 6
• Immediately discontinue propofol if PRIS is suspected: worsening metabolic acidosis, hypertriglyceridemia, hypotension with increasing vasopressor requirements, arrhythmias, rhabdomyolysis. 6, 4
• Monitor serum triglycerides during prolonged infusions (>3 days). 8

Contraindications and Precautions

Avoid propofol in patients with known allergy to egg, soy, or sulfites (the emulsion contains soybean oil and egg phosphatide). 1, 4

• Sulfonamide allergy is NOT a contraindication to propofol. 1, 4
• Up to 30% of patients experience injection-site pain; use larger-bore peripheral veins to minimize discomfort. 1, 4

Hepatic Encephalopathy Considerations

Propofol does not exacerbate subclinical hepatic encephalopathy in compensated cirrhotic patients (Child-Pugh A-B) and provides faster recovery than midazolam. 9

• Time to recovery: 4.1 minutes with propofol vs. 11.5 minutes with midazolam in cirrhotic patients. 9
• Time to discharge: 38 minutes with propofol vs. 110 minutes with midazolam. 9
• Number connection test scores improved slightly after propofol sedation (87.5 seconds before to 74.2 seconds after) compared to midazolam (72.8 seconds before to 85.6 seconds after). 9

Practical Algorithm Summary

1. Pre-procedure: Provide supplemental oxygen, ensure vasopressors available, establish IV access in large-bore vein. 1, 7
2. Initial bolus:
   • Non-cirrhotic, <70 years: 40 mg
   • Non-cirrhotic, ≥70 years: 30 mg
   • Cirrhotic (Child-Pugh A-B), <70 years: 30–40 mg
   • Cirrhotic (Child-Pugh A-B), ≥70 years: 20–30 mg
   • Cirrhotic (Child-Pugh C): 20–30 mg 2
3. Titration: Add 10–20 mg every 20–30 seconds until adequate sedation. 1, 2
4. Continuous infusion (if needed): Start at 50 mcg/kg/min in non-cirrhotic patients; reduce by 20–30% in cirrhotic patients. 7, 5
5. Analgesia: Add fentanyl 25–100 μg for painful procedures. 1, 4
6. Monitoring: Continuous pulse oximetry, blood pressure, heart rate; consider BIS monitoring for prolonged sedation. 7, 5