What are the recommended induction and maintenance doses of propofol for adults and children, and what precautions, contraindications, and alternative agents should be considered?

Propofol Dosing and Clinical Considerations

Induction Dosing

For healthy adults under 55 years (ASA I-II), administer 2-2.5 mg/kg IV for induction, titrated as approximately 40 mg every 10 seconds until loss of consciousness. 1

Adult Populations

• Healthy adults (<55 years, ASA I-II): 2-2.5 mg/kg IV, administered as 40 mg boluses every 10 seconds 1
• Elderly, debilitated, or ASA III-IV patients: Reduce to 1-1.5 mg/kg (approximately 20 mg every 10 seconds), avoiding rapid bolus to prevent severe hypotension, apnea, and oxygen desaturation 1
• Neurosurgical patients: 1-2 mg/kg using slower boluses of 20 mg every 10 seconds 1
• Cardiac patients: Similar dose reduction as elderly patients, avoiding high-dose opioid combinations that increase hypotension risk 1

Pediatric Populations

• Children 3-16 years (ASA I-II): 2.5-3.5 mg/kg IV for induction, with younger children requiring higher doses than older children 1
• Pediatric ASA III-IV: Lower dosage required, titrated to clinical response 1
• Pain on injection: Occurs in 45% when small hand veins used without lidocaine pretreatment; reduced to <10% with lidocaine pretreatment or antecubital vein use 2, 1

Maintenance Dosing

For maintenance anesthesia in adults, initiate continuous infusion at 150-200 mcg/kg/min for the first 10-15 minutes, then decrease 30-50% to achieve optimal rates of 50-100 mcg/kg/min. 1

Adult Maintenance

• Initial maintenance rate: 150-200 mcg/kg/min for first 10-15 minutes 1
• Subsequent maintenance: Decrease to 50-100 mcg/kg/min to optimize recovery 1
• With nitrous oxide (60-70%): 100-200 mcg/kg/min provides adequate anesthesia for general surgery 1
• Intermittent bolus alternative: 25-50 mg increments when vital signs indicate light anesthesia 1

Pediatric Maintenance

• Initial rate: 200-300 mcg/kg/min immediately following induction 1
• After first 30 minutes: Reduce to 125-150 mcg/kg/min 1
• Age consideration: Younger children require higher maintenance rates than older children 1

Monitored Anesthesia Care (MAC) Sedation

• Initiation: 100-150 mcg/kg/min for 3-5 minutes, OR 0.5 mg/kg administered slowly over 3-5 minutes 1
• Maintenance: 25-75 mcg/kg/min, with most patients requiring 25-50 mcg/kg/min after initial 10-15 minutes 1
• Elderly/debilitated patients: Reduce to 80% of usual adult dosage, administered over 3-5 minutes 1
• Critical warning: Never use rapid bolus dosing for MAC sedation in elderly, debilitated, or ASA III-IV patients due to severe cardiorespiratory depression risk 1

Pharmacokinetics and Mechanism

Propofol acts through GABA-A receptor potentiation, reducing GABA dissociation rate and prolonging chloride channel opening, resulting in neuronal hyperpolarization and sedation with onset in 30-45 seconds. 3

• Onset: 30-45 seconds (arm-brain circulation time) 3, 4
• Duration: 4-8 minutes after single bolus 3
• Terminal half-life: 1-3 days after prolonged infusion 3
• Metabolism: Hepatic conjugation to glucuronide/sulfate with renal excretion 3
• Pharmacokinetic stability: Not significantly affected by cirrhosis or renal insufficiency 3, 5

Critical Precautions and Contraindications

Absolute Contraindications

• Egg allergy: Propofol contains 1.2% purified egg phosphatide 3, 5, 4
• Soy allergy: Contains 10% soybean oil 3, 5, 4
• Sulfite allergy: Metabisulfite-containing formulations contraindicated 3, 4
• Note: NOT contraindicated in sulfonamide allergy 3, 5

Cardiovascular Effects

Propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and blood pressure through peripheral vasodilation and negative inotropy. 3, 6

• Hypotension mechanism: Peripheral vasodilation, decreased myocardial contractility, baroreflex resetting, sympathetic inhibition 6
• Clinical impact: Transient hypotension common but rarely requires intervention in healthy patients 2
• High-risk patients: Profound hypotension possible in hypovolemic or limited cardiac reserve patients 7
• Monitoring requirement: Continuous blood pressure, heart rate, and ECG monitoring mandatory 4
• Vasopressor availability: Have ephedrine or metaraminol immediately available 5, 4

Respiratory Effects

Propofol causes dose-dependent respiratory depression with frequent apnea during induction, often lasting >60 seconds and requiring ventilatory support. 1

• Desaturation incidence: 5-11.6% experience oxygen saturation <90-93% 2, 4
• Airway obstruction: 3-4% require jaw thrust maneuver 2
• Bag-valve-mask ventilation: Required in 0.8-2.5% of cases 2, 4
• Monitoring: Continuous pulse oximetry mandatory; capnography strongly recommended 4
• Equipment: Bag-valve-mask must be immediately available 4

Propofol Infusion Syndrome (PRIS)

PRIS is a potentially fatal complication characterized by severe metabolic acidosis, rhabdomyolysis, cardiac failure, and up to 33% mortality, typically occurring with doses >70 mcg/kg/min for >48 hours. 3, 8

• Classic presentation: Metabolic acidosis, rhabdomyolysis, arrhythmias, myocardial failure, renal failure 3, 8
• Dose threshold: Typically >70 mcg/kg/min (4-5 mg/kg/h) for >48 hours, but reported at doses as low as 1.9-2.6 mg/kg/h 3, 8
• Warning signs: Worsening metabolic acidosis, hypertriglyceridemia, hypotension with increasing vasopressor requirements, arrhythmias 3
• Management: Immediately discontinue propofol if PRIS suspected 3, 8

CYP2B6 Poor Metabolizers

In confirmed CYP2B6 poor metabolizers, reduce propofol infusion dose by 50% to 25 mcg/kg/min to avoid excessive drug exposure and prolonged sedation. 3

Analgesic Considerations

Propofol is a pure sedative with NO analgesic properties—it must be combined with opioids or local anesthetics for painful procedures. 2, 3

For Painful Procedures

• Level B recommendation: Propofol combined with opiates is effective for painful procedures 2
• Typical combination: Fentanyl 1-2 mcg/kg (or 50-75 mcg) administered prior to propofol induction 2, 4
• Alternative opioids: Remifentanil (1-3 ng/ml effect-site concentration), alfentanil (5 mcg/kg bolus) 5
• Benefit of combination: Allows lower propofol doses, reducing cardiorespiratory depression 4

For Painless Procedures

• Level C recommendation: Propofol alone is effective for painless diagnostic studies (MRI, CT) 2

Balanced Anesthesia Approach

Combining small doses of multiple agents (propofol + benzodiazepine + opioid) maximizes therapeutic effects while minimizing dose-related adverse reactions. 3

• Example regimen: Midazolam 0.5-1 mg + fentanyl 50-100 mcg + propofol 35-100 mg for colonoscopy 3
• Amnesia enhancement: Add midazolam 0.5-1 mg when amnesia is desired, as propofol's amnestic effects at light sedation are less reliable than benzodiazepines 3, 4

Drug Interactions

• CNS depressants: Opioids, benzodiazepines, and other sedatives potentiate propofol's effects, requiring dose reduction 3, 1
• Morphine premedication: Decreases required propofol maintenance infusion rate compared to lorazepam premedication 1
• Sodium nitroprusside: NEVER administer through same Y-site due to severe additive hypotensive effects; use separate dedicated IV lines 4
• Lidocaine combination: Do not exceed 20 mg lidocaine per 200 mg propofol to prevent emulsion instability 1

Administration Technique

• Pain reduction: Use larger forearm or antecubital veins; consider lidocaine 1 mL of 1% solution prior to injection 1
• Pediatric pain management: Pretreat with lidocaine or use antecubital/larger veins (reduces pain from 45% to <10%) 2, 1
• Infusion equipment: Use syringe or volumetric pumps for controlled infusion rates 1
• Titration interval: Allow 3-5 minutes between dose adjustments to assess clinical effects 1
• Emulsion stability: Shake well before use; do not use if excessive creaming, large droplets, or phase separation visible 1

Common Pitfalls

• Rapid bolus in elderly: Causes severe hypotension, apnea, and oxygen desaturation—always use slow titration (20 mg every 10 seconds) 1
• Inadequate monitoring: Continuous cardiorespiratory monitoring is non-negotiable 4
• Using propofol alone for painful procedures: Results in need for deep sedation with higher adverse event risk—always combine with analgesics 3
• Prolonged high-dose infusions: Avoid >70 mcg/kg/min for >48 hours due to PRIS risk 3, 8
• Ignoring lipid load: Monitor triglycerides in prolonged infusions; propofol provides 1.1 kcal/mL from lipid content 9