What is the typical dosage and administration regimen for propofol (a general anesthetic) in a patient with a history of respiratory or cardiovascular disease requiring sedation or anesthesia?

Propofol: Essential Clinical Information

Mechanism of Action and Pharmacokinetics

Propofol is a potent hypnotic agent that works by enhancing GABA-A receptor activity, prolonging chloride channel opening and causing neuronal hyperpolarization, resulting in rapid sedation with onset in 30-45 seconds but providing minimal analgesic effect. 1

• Highly lipophilic, allowing rapid blood-brain barrier penetration and quick onset of action 1
• Rapid hepatic metabolism via glucuronide and sulfate conjugation, with renal excretion of water-soluble metabolites 1
• Duration of effect: 4-8 minutes after single bolus dose 1
• Terminal half-life: 1-3 days after prolonged infusion 1
• Pharmacokinetics remain stable in cirrhosis or renal insufficiency 1

Dosing Regimens by Clinical Context

General Anesthesia Induction

For healthy adults under 55 years (ASA I-II):

• Standard dose: 2-2.5 mg/kg IV, titrated as 40 mg every 10 seconds until loss of consciousness 2
• Premedication with benzodiazepines or opioids reduces requirements 2

For elderly, debilitated, or ASA III-IV patients:

• Reduced dose: 1-1.5 mg/kg IV (approximately 20 mg every 10 seconds) 2
• Avoid rapid bolus - increases risk of severe hypotension, apnea, and oxygen desaturation 2
• Reduce dose by 20-80% when combined with sedatives or analgesics 3

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

• Dose: 2.5-3.5 mg/kg IV, with younger children requiring higher doses 2
• Lower doses for ASA III-IV patients 2

Maintenance of General Anesthesia

Adult maintenance:

• Initial rate: 100-200 mcg/kg/min for first 10-15 minutes 4, 2
• Reduce by 30-50% after first half-hour 2
• Target maintenance: 50-100 mcg/kg/min to optimize recovery 4, 2
• Incremental boluses of 25-50 mg for breakthrough responses to surgical stimulation 2

Pediatric maintenance:

• Initial rate: 200-300 mcg/kg/min immediately following induction 2
• Reduce to 125-150 mcg/kg/min after first half-hour 2
• Younger children require higher rates than older children 2

Monitored Anesthesia Care (MAC) Sedation

Initiation (healthy adults):

• Infusion method: 100-150 mcg/kg/min for 3-5 minutes, then titrate 2
• Slow injection method: 0.5 mg/kg over 3-5 minutes 2

Maintenance:

• Variable rate infusion: 25-75 mcg/kg/min (preferred over boluses) 2
• Initial 10-15 minutes: 25-75 mcg/kg/min, then decrease to 25-50 mcg/kg/min 2
• If using intermittent boluses: 10-20 mg increments (increases respiratory depression risk) 2

For elderly/debilitated/ASA III-IV:

• Reduce all doses to 80% of standard adult dosing 2
• Never use rapid bolus - administer over 3-5 minutes minimum 2

Procedural Sedation (Endoscopy/ED Procedures)

Nurse-Administered Propofol Sedation (NAPS):

• Initial bolus: 10-60 mg 4, 1
• Additional boluses: 10-20 mg with minimum 20-30 seconds between doses 4, 1
• Average total dose for colonoscopy: 144-287 mg 4
• Average total dose for EGD: 107-245 mg 4

Combination propofol (with opioid + benzodiazepine):

• EGD: 35-70 mg total 4
• Colonoscopy: 65-100 mg total 4
• Allows moderate sedation instead of deep sedation, reducing cardiopulmonary complications 4

Pediatric ED procedures:

• Initial bolus: 1 mg/kg, then 0.5 mg/kg increments 4
• Mean effective dose: 2.9-3.9 mg/kg total 4
• Always combine with fentanyl for painful procedures 4

Critical Safety Considerations

Cardiovascular and Respiratory Effects

Propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and blood pressure without compensatory tachycardia. 4, 1, 5

• Respiratory depression is dose-dependent and potentiated by opioids 4
• Apnea on induction occurs more frequently than with other anesthetics 6
• Hypotension risk increases with rapid bolus administration 2
• Bradycardia may occur due to reduced sympathetic activity 2

High-Risk Populations Requiring Extreme Caution

Patients with pulmonary hypertension:

• Use with extreme caution - propofol's vasodilation and negative inotropy can precipitate right ventricular failure 5
• Administer in small incremental doses with continuous hemodynamic monitoring 5
• Be prepared for immediate intervention including discontinuation, IV fluids, and vasopressors 5

Patients with cardiovascular disease:

• Reduce induction dose to 1-1.5 mg/kg administered slowly 2
• Avoid rapid bolus in any patient with limited cardiac reserve 3
• Even small doses (0.75-1.5 mg/kg) can cause profound hypotension in hypovolemic patients 3

Patients with respiratory insufficiency:

• Cardiopulmonary instability more likely with baseline respiratory compromise 5
• Combine with opioids cautiously - synergistic respiratory depression 4

Propofol Infusion Syndrome (PRIS)

PRIS is a rare but frequently fatal complication characterized by metabolic acidosis, rhabdomyolysis, cardiac arrhythmias, myocardial failure, renal failure, and death. 7

• Classic risk factors: doses >70 mcg/kg/min (4 mg/kg/h) for >48 hours 7
• Fatal cases reported at doses as low as 1.9-2.6 mg/kg/h 1, 7
• Mortality rate: up to 33% 1
• Immediate discontinuation required if PRIS suspected (worsening acidosis, hypertriglyceridemia, hypotension with increasing vasopressor needs, arrhythmias) 1

CYP2B6 Poor Metabolizers

Reduce propofol infusion dose by approximately 50% (to 25 mcg/kg/min) in confirmed CYP2B6 poor metabolizers to avoid excessive drug exposure and prolonged sedation. 1

Additional Important Considerations

Analgesia Requirements

Propofol has NO analgesic properties - always combine with short-acting opioids (fentanyl, remifentanil) for painful procedures. 4, 1

• Morphine premedication (0.15 mg/kg) decreases propofol maintenance requirements 4, 2
• Opioid co-administration potentiates sedative effects 1

Monitoring Requirements

Continuous monitoring of heart rate, blood pressure, and pulse oximetry is mandatory during all propofol administration. 4, 5

• Supplemental oxygen should be administered 4
• Capnography is optional but recommended for deeper sedation 4

Contraindications and Allergies

Avoid in patients with allergies to eggs, soy, or sulfites (formulation contains 10% soybean oil and 1.2% egg phosphatide) 1

• NOT contraindicated in sulfonamide allergy 1

Recovery Profile

Propofol provides significantly faster recovery than benzodiazepines (midazolam), even after prolonged infusions >72 hours. 8, 9

• Time to arousal: 5 minutes average 4
• Time to discharge: 12.5 minutes average 4
• Recovery is rapid due to fast redistribution and metabolic clearance 8
• Lower incidence of nausea and vomiting compared to other anesthetics 6

Amnesia Considerations

Propofol's amnestic effects at light sedation are LESS reliable than benzodiazepines. 1

• For guaranteed amnesia, combine with low-dose midazolam (0.5-1 mg) 1
• At deep sedation doses, amnesia is more consistent 1
• Benzodiazepines remain superior when amnesia is the primary goal 1

Administration Technique

Administer via slow infusion or incremental boluses - never rapid bolus in high-risk patients. 2

• Pain on injection occurs in up to 30% when given peripherally 1
• Pretreat peripheral veins with lidocaine in pediatric patients 2
• Use antecubital or larger veins when possible 2
• Allow 2 minutes between doses to assess peak effect 2

ICU Sedation Specific

Avoid abrupt discontinuation - taper gradually to prevent anxiety, agitation, and ventilator resistance. 2

• Target light sedation (patient arousable) rather than deep sedation 4
• Deep sedation associated with prolonged mechanical ventilation and worse outcomes 4
• Monitor serum triglycerides during prolonged infusions (>3 days) 8