What is the maximum dose of propofol (2,6-diisopropylphenol) for induction and maintenance of sedation or anesthesia?

Maximum Dose of Propofol

For ICU sedation in adults, propofol maintenance rates should not exceed 70 mcg/kg/min (4.2 mg/kg/h) to avoid propofol infusion syndrome (PRIS), with most patients requiring 5-50 mcg/kg/min (0.3-3 mg/kg/h) for adequate sedation. 1, 2

Critical Safety Threshold

Propofol doses exceeding 4-5 mg/kg/h (approximately 67-83 mcg/kg/min) for prolonged periods (>48 hours) must be avoided due to the risk of fatal propofol infusion syndrome. 2, 3 This syndrome is characterized by:

• Severe metabolic acidosis
• Rhabdomyolysis of cardiac and skeletal muscle
• Cardiac arrhythmias (bradycardia, bundle branch block, asystole)
• Myocardial failure and circulatory collapse
• Renal failure and death 2, 3

PRIS has been reported even at lower infusion rates (1.9-2.6 mg/kg/h), indicating that the traditional "safe" threshold may need re-evaluation. 2

Context-Specific Maximum Doses

Induction of Anesthesia

Healthy adults (<55 years, ASA I-II):

• Standard dose: 2-2.5 mg/kg administered as approximately 40 mg every 10 seconds 4, 5

Elderly, debilitated, or ASA III-IV patients:

• Reduced dose: 1-1.5 mg/kg administered as approximately 20 mg every 10 seconds 4
• Rapid bolus administration must be avoided in these populations as it significantly increases risk of hypotension, apnea, airway obstruction, and oxygen desaturation 4

Pediatric patients (3-16 years, ASA I-II):

• 2.5-3.5 mg/kg, with younger children requiring higher doses than older children 4

Maintenance of Anesthesia

Adults:

• Continuous infusion: 100-200 mcg/kg/min (6-12 mg/kg/h) with nitrous oxide 4
• Higher rates (150-200 mcg/kg/min) typically required for first 10-15 minutes, then decrease by 30-50% 4
• Optimal maintenance rates of 50-100 mcg/kg/min should be targeted to optimize recovery times 4

Pediatric patients:

• Initial maintenance: 200-300 mcg/kg/min (12-18 mg/kg/h) 4
• After first 30 minutes: 125-150 mcg/kg/min (7.5-9 mg/kg/h) 4
• Younger children require higher maintenance rates than older children 4

Monitored Anesthesia Care (MAC) Sedation

Adults:

• Typical range: 25-75 mcg/kg/min (1.5-4.5 mg/kg/h) 4
• Initiation: 100-150 mcg/kg/min for 3-5 minutes, then titrate 4
• Rapid bolus administration is contraindicated for MAC sedation, especially in elderly, debilitated, or ASA III-IV patients 4

Procedural Sedation

Pediatric emergency department procedures:

• Initial bolus: 1-2 mg/kg 6
• Supplemental boluses: 0.5-1 mg/kg as needed 6
• Mean effective doses ranged from 2.9-3.9 mg/kg across multiple studies 6
• Maximum single bolus documented: 7.5 mg/kg (pentobarbital comparison study) 6

Endoscopic sedation (NAPS protocols):

• Mean doses for EGD: 107-245 mg total 6
• Mean doses for colonoscopy: 144-287 mg total 6
• When targeting moderate sedation: 72 mg (EGD) and 94 mg (colonoscopy) 6

Combination propofol (with opioids/benzodiazepines):

• Significantly lower doses: 35-70 mg for EGD, 65-100 mg for colonoscopy 6
• Initial bolus reduced to 10-20 mg when combined with other sedatives 1

Cardiac Anesthesia Considerations

When propofol is the primary agent:

• Maintenance rates should not be less than 100 mcg/kg/min 4
• Must be supplemented with analgesic levels of continuous opioid 4

When opioid is the primary agent:

• Propofol maintenance rates should not be less than 50 mcg/kg/min 4
• Propofol should NOT be administered with high-dose opioid technique as this increases likelihood of hypotension 4

Pharmacokinetic Rationale for Dosing Limits

Propofol follows a three-compartment model with half-lives of 2-4 minutes, 30-45 minutes, and 3-63 hours. 7 The drug is highly lipophilic with:

• Rapid distribution into small central compartment (V1)
• Slower redistribution from larger peripheral compartments (V2 and V3) 8
• A descending dosing strategy is necessary to maintain constant central compartment concentration while preventing excessive accumulation 8

Target blood concentration for sedation is approximately 1 mg/L, with recovery occurring at concentrations ≤1 mg/L in most patients. 8 Hypnosis is maintained by blood concentrations of 1.5-6 mcg/mL with nitrous oxide supplementation. 7

Common Pitfalls to Avoid

Never administer loading doses in hemodynamically unstable patients - propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and arterial pressure. 9, 1

Never use doses >70 mcg/kg/min or prolonged infusions without monitoring for PRIS - monitor for metabolic acidosis, elevated creatine kinase, myoglobinuria, and cardiac arrhythmias. 1, 2

Never forget propofol has no analgesic properties - painful procedures require additional analgesics; propofol alone is insufficient. 1

Never ignore propofol's caloric contribution - the lipid emulsion provides 1.1 kcal/mL, which must be factored into nutritional calculations. 1

Never use rapid bolus technique in elderly or ASA III-IV patients - this dramatically increases risk of cardiovascular collapse and respiratory depression. 4

Monitoring Requirements

Continuous monitoring is mandatory and includes: 6, 9, 1

• Heart rate
• Blood pressure
• Pulse oximetry
• Supplemental oxygen administration (recommended in most protocols) 6, 1
• Consider capnography for deeper sedation 6

Approximately 5-10% of patients experience transient oxygen desaturation <90%, typically responding to simple airway maneuvers. 6, 1