What are the classification, mechanism of action, effects on the heart and other body systems, indication, route and dosage, titration parameters, contraindications, hold parameters, adverse reactions, interactions, and assessment parameters for propofol (a sedative-hypnotic medication) in patients?

Propofol: Comprehensive Medication Profile

Classification

Propofol is a sedative-hypnotic agent, chemically classified as a phenolic derivative (2,6-diisopropilphenol) that is structurally unrelated to other anesthetic agents. 1, 2

Mechanism of Action

• Propofol potentiates GABA-A receptors (ligand-gated chloride channels) by reducing the rate of dissociation of GABA from its receptor, prolonging chloride influx into neurons, causing neuronal hyperpolarization and subsequent sedation. 1, 3
• The drug produces sedation, hypnosis, anxiolysis, amnesia, antiemetic effects, and anticonvulsant properties, but has no analgesic effect—requiring combination with opioids for painful procedures. 1, 4
• Onset of action occurs within 30-45 seconds (equivalent to arm-brain circulation time), with effect duration of 4-8 minutes after a single bolus dose. 1

Effects on the Heart

Propofol causes significant cardiovascular depression through multiple mechanisms:

• Decreases cardiac output, systemic vascular resistance, and blood pressure through peripheral vasodilation and negative inotropic effects. 1, 5
• Reduces myocardial oxygen consumption and may lower heart rate by reducing sympathetic activity and/or resetting baroreceptor reflexes. 3, 5
• The magnitude of cardiovascular depression is proportional to blood concentration, which depends on dose and speed of administration. 3
• Use with extreme caution in patients with pulmonary hypertension due to potential hemodynamic instability. 1

Critical Cardiac Precaution:

• Rapid bolus administration significantly increases risk of severe hypotension, particularly in elderly, debilitated, or ASA-PS III-IV patients. 3

Effects on Other Body Systems

Respiratory System:

• Dose-dependent respiratory depression is the primary concern, with apnea occurring more frequently than with other intravenous anesthetics. 1, 6
• Risk increases with rapid bolus administration and when combined with opioids or benzodiazepines. 3

Central Nervous System:

• Provides amnesia at subhypnotic doses, though less reliably than benzodiazepines at light sedation levels. 1
• For procedures requiring guaranteed amnesia, combine with low-dose benzodiazepines (midazolam 0.5-1 mg). 1

Metabolic/Hepatorenal:

• Rapidly metabolized in the liver by conjugation to glucuronide and sulfate, producing water-soluble compounds excreted by kidneys. 1
• Cirrhosis or chronic renal failure does not significantly alter pharmacokinetics. 1, 7
• Terminal half-life extends to 1-3 days after prolonged infusion due to tissue accumulation. 1

Local Effects:

• Pain at injection site occurs in up to 30% of patients; pretreat with lidocaine or use larger veins. 1, 3

Immunologic:

• Contains 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide. 1

Indications

• Induction and maintenance of general anesthesia 3
• Monitored Anesthesia Care (MAC) sedation 3
• ICU sedation for mechanically ventilated patients 3
• Procedural sedation (including endoscopy) 1

Route and Dosage

Induction of General Anesthesia:

Adult Patients (Healthy, ASA-PS I-II):

• 2-2.5 mg/kg IV, administered as 40 mg every 10 seconds until loss of consciousness. 3

Elderly, Debilitated, or ASA-PS III-IV:

• 1-1.5 mg/kg IV, administered as 20 mg every 10 seconds. 3
• Reduce dose to approximately 80% of usual adult dosage. 3
• Never use rapid bolus in these patients. 3

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

• 2.5-3.5 mg/kg IV for induction when unpremedicated. 3
• Younger children require higher doses than older children. 3

Cardiac Anesthesia:

• 0.5-1.5 mg/kg administered as 20 mg every 10 seconds until induction. 3

Maintenance of General Anesthesia:

Adult Patients:

• Continuous infusion: 100-200 mcg/kg/min initially, then decrease by 30-50% during first 30 minutes. 3
• Maintenance range: 50-100 mcg/kg/min to optimize recovery. 3
• Intermittent bolus: 25-50 mg increments when vital signs indicate light anesthesia. 3

Pediatric Patients:

• 200-300 mcg/kg/min immediately following induction, then 125-150 mcg/kg/min after first 30 minutes. 3

MAC Sedation:

Initiation:

• Infusion method: 100-150 mcg/kg/min for 3-5 minutes, titrated to effect. 3
• Slow injection method: 0.5 mg/kg over 3-5 minutes. 3
• For elderly/debilitated: Reduce to 80% of usual dose, administered over 3-5 minutes. 3

Maintenance:

• 25-75 mcg/kg/min via variable rate infusion (preferred method). 3
• During first 10-15 minutes: 25-75 mcg/kg/min, then decrease to 25-50 mcg/kg/min. 3
• Intermittent bolus (less preferred): 10-20 mg increments, but increases risk of respiratory depression. 3

ICU Sedation:

• Initiate slowly with continuous infusion at 5-50 mcg/kg/min to minimize hypotension. 1, 3
• Sedation maximum achieved within 1 hour of starting infusion. 1

Endoscopy (NAPS - Nurse-Administered Propofol Sedation):

• Initial bolus: 10-60 mg 1
• Additional boluses: 10-20 mg with minimum 20-30 seconds between doses 1
• Average total dose for colonoscopy: 107-287 mg; for EGD: 67-190 mg. 1

Titration Parameters

Dosing Adjustments:

• Allow approximately 2 minutes for onset of peak drug effect when titrating. 3
• Reduce infusion rates by 30-50% during first 30 minutes of maintenance to prevent tissue accumulation. 3
• Infusion rates should be reduced by up to 50% during prolonged infusions to maintain constant plasma levels. 7

Special Populations:

CYP2B6 Poor Metabolizers:

• Reduce infusion dose by 50% (to 25 mcg/kg/min) to avoid excessive drug exposure and prolonged sedation. 1

Elderly Patients:

• Use lower doses due to decreased volume of distribution and intercompartmental clearance, resulting in higher peak plasma concentrations. 7

Cardiac Patients:

• When propofol is primary agent: maintenance rates should not be less than 100 mcg/kg/min with analgesic opioid levels. 3
• When opioid is primary agent: propofol rates should not be less than 50 mcg/kg/min. 3

Contraindications and Precautions

Absolute Contraindications:

• Allergy to eggs, soy, or sulfites (due to formulation components). 1
• NOT contraindicated in sulfonamide allergy. 1

Critical Precautions:

• Never use rapid bolus administration in elderly, debilitated, or ASA-PS III-IV patients for MAC sedation—causes severe cardiorespiratory depression. 3
• Use with extreme caution in pulmonary hypertension. 1
• Should only be administered by practitioners trained and experienced in providing general anesthesia due to narrow therapeutic margin. 2

Drug Interactions:

• Co-administration with opioids, benzodiazepines, or other CNS depressants potentiates sedative and respiratory effects, requiring dose reduction. 1, 3
• Combination with opioids produces highly synergistic pharmacodynamic interactions. 2

Hold Parameters

Immediate Discontinuation Required:

• Suspected Propofol Infusion Syndrome (PRIS): worsening metabolic acidosis, hypertriglyceridemia, hypotension with increasing vasopressor requirements, arrhythmias. 1
  • PRIS typically occurs with doses >70 mcg/kg/min for >48 hours but reported as low as 1.9-2.6 mg/kg/hr. 1
  • Mortality rate up to 33%. 1

Weaning Considerations:

• Avoid abrupt discontinuation prior to weaning or daily sedation assessment—causes rapid awakening with anxiety, agitation, and ventilator resistance. 3
• Maintain minimal sedation level throughout weaning process. 3

Clinical Hold Criteria:

• Severe hypotension unresponsive to fluid resuscitation
• Apnea or severe respiratory depression
• Oxygen desaturation despite intervention
• Airway obstruction

Adverse Reactions and Side Effects

Common:

• Hypotension (most common cardiovascular effect) 1, 5
• Respiratory depression and transient apnea 1, 6
• Pain at injection site (up to 30%) 1
• Bradycardia 3, 5

Serious:

• Propofol Infusion Syndrome: metabolic acidosis, rhabdomyolysis, cardiac arrhythmias, myocardial failure, renal failure 1
• Severe hypotension and cardiovascular collapse (especially with rapid bolus) 3
• Prolonged apnea 6
• Airway obstruction 3

Other:

• Hypertriglyceridemia (with prolonged use) 4
• Development of tolerance to sedative effects (long-term use) 4
• Lower incidence of postoperative nausea and vomiting compared to other agents 8

Assessment, Monitoring, and Desired Outcomes

Continuous Monitoring Required:

• Cardiorespiratory function (blood pressure, heart rate, respiratory rate, oxygen saturation) 3
• Airway patency and adequacy of ventilation 3
• Level of sedation using validated scales 3

Periodic Monitoring:

• Triglyceride levels during prolonged infusions (>48 hours) 4
• Metabolic acidosis markers if PRIS suspected 1
• Renal function and creatine kinase if prolonged use 1

Desired Outcomes:

• Rapid, smooth induction of anesthesia within 30-45 seconds 1
• Adequate sedation depth appropriate to procedure 3
• Hemodynamic stability with blood pressure maintained within 20% of baseline 3
• Rapid, clear emergence with minimal residual sedation 4, 8
• Absence of awareness or recall (when combined with appropriate adjuncts) 1
• Minimal postoperative nausea and vomiting 8
• Quick recovery allowing early extubation and ICU discharge 4

Recovery Advantages:

• Propofol provides faster recovery and more precise sedation control compared to midazolam, particularly beneficial for short-term sedation and day case surgery. 5, 4