Propofol

Approved Indications:

• Induction of General Anesthesia
• For adults and children >3 years undergoing surgical procedures.
• Maintenance of General Anesthesia
• In both adults and children >3 years during surgeries requiring continuous sedation.
• Sedation for Mechanically Ventilated Adults in Intensive Care Units (ICU)
• For patients requiring continuous sedation while intubated.
• Monitored Anesthesia Care (MAC) Sedation
• For diagnostic and minor surgical procedures in adults (e.g., colonoscopy, endoscopy).

Clinically Accepted Off-Label Uses:

• Refractory Status Epilepticus
• Used as an adjunct in controlling seizures when standard anticonvulsants fail.
• Procedural Sedation in Children
• Sedation for imaging or minor procedures under close monitoring (e.g., MRI, CT scan).
• Sedation in Palliative Care
• For terminal restlessness or intractable distress in end-of-life care.

Route: Intravenous (IV) only
Formulation: Lipid emulsion (1% = 10 mg/mL)

Adults:

• Induction of Anesthesia:
• 1.5–2.5 mg/kg IV bolus over 20–30 seconds
• Reduce dose in ASA Class III/IV: 1.0–1.5 mg/kg
• Maintenance of Anesthesia:
• Continuous infusion: 100–200 mcg/kg/min (6–12 mg/kg/hr)
• Adjust based on depth of anesthesia and patient response
• MAC Sedation:
• Initial bolus: 0.5–1 mg/kg IV slowly
• Maintenance infusion: 25–75 mcg/kg/min
• ICU Sedation (Ventilated Adults):
• Initial infusion: 5 mcg/kg/min
• Titrate up to 50 mcg/kg/min
• Limit duration to <7 days due to risk of Propofol Infusion Syndrome (PRIS)

Pediatric Patients (>3 years):

• Induction of Anesthesia:
• 2.5–3.5 mg/kg IV bolus
• Maintenance of Anesthesia:
• 125–300 mcg/kg/min (7.5–18 mg/kg/hr) infusion

Note: Use in children <3 years is not approved. Use with extreme caution and expert monitoring.

Elderly:

• Reduce induction dose to 1.0–1.5 mg/kg
• Titrate maintenance infusion slowly due to increased sensitivity

Renal/Hepatic Impairment:

• No routine dose adjustment required, but monitor for delayed recovery or accumulation

Propofol is a short-acting intravenous anesthetic that enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor complex. This increases chloride ion influx into neurons, causing hyperpolarization of the cell membrane and reducing neuronal excitability. The result is rapid onset of hypnosis, sedation, and amnesia. It lacks analgesic properties. The drug’s rapid redistribution and metabolism result in a brief duration of action, ideal for anesthesia induction and procedural sedation.

• Absorption: Not applicable (IV only)
• Distribution:
• Rapid distribution phase: brain, heart, liver, kidneys
• Volume of distribution: 2–10 L/kg
• Metabolism:
• Primarily hepatic via glucuronidation and sulfate conjugation
• Involves CYP2B6, CYP2C9 enzymes
• Metabolites: Inactive
• Elimination:
• 88% renal excretion (mostly as metabolites)
• 2% fecal
• Onset of Action: 30–60 seconds
• Duration: 5–10 minutes after a bolus
• Half-life:
• Initial distribution half-life: 2–4 minutes
• Terminal elimination half-life: 4–7 hours
• Context-sensitive half-time increases with prolonged infusion

• Pregnancy:
• Not assigned under new FDA system (formerly Category B)
• Crosses placenta; may cause neonatal respiratory depression
• Use only if clearly necessary; not typically used for obstetric anesthesia
• Lactation:
• Propofol is excreted in breast milk in small amounts
• Considered safe for breastfeeding after single-dose use
• For high-dose or prolonged use, wait 6–12 hours before resuming breastfeeding
• Observe infant for sedation or feeding difficulty

• Primary Class: General Anesthetic
• Subclass: Sedative-Hypnotic Agent (Non-barbiturate)

• Known hypersensitivity to propofol or any of its ingredients (e.g., soybean oil, egg lecithin)
• Allergy to egg or soy products (use caution, especially in children)
• Severe hemodynamic instability or hypovolemia
• Disorders of fat metabolism (e.g., hyperlipidemia, pancreatitis)
• Pediatric ICU sedation (due to risk of Propofol Infusion Syndrome)

• Propofol Infusion Syndrome (PRIS):
• Rare but potentially fatal; characterized by metabolic acidosis, cardiac failure, rhabdomyolysis
• Risk increases with high-dose or prolonged infusions, especially in children
• Cardiovascular Depression:
• Hypotension, bradycardia, and potential cardiac arrest in high-risk patients
• Respiratory Depression:
• Apnea or hypoventilation requires continuous airway and oxygenation monitoring
• Strict Aseptic Technique:
• Risk of microbial contamination and fatal sepsis; use single-dose vials and discard after 6 hours
• Abuse and Dependence:
• Reports of abuse, especially in healthcare professionals, due to euphoric effects
• Monitor Elderly and Frail Patients:
• Slower recovery and greater sensitivity to sedative effects

Common (by System):

• CNS: Sedation, dizziness, euphoria
• CVS: Hypotension, bradycardia
• Respiratory: Apnea, hypoventilation
• GI: Nausea, vomiting
• Injection Site: Burning or pain

Serious/Rare:

• Propofol Infusion Syndrome (PRIS)
• Cardiac arrest
• Metabolic acidosis
• Rhabdomyolysis
• Anaphylaxis
• Pancreatitis

Timing: Common effects occur immediately after bolus or within a few minutes. PRIS risk increases after >48 hours of infusion.

• Other CNS Depressants (opioids, benzodiazepines, barbiturates):
• Increased sedation and respiratory depression
• Alcohol:
• Enhances CNS depressant effect; avoid during and after treatment
• CYP450 Enzyme Modulators:
• CYP inducers (e.g., rifampin, carbamazepine): May decrease effect
• CYP inhibitors (e.g., fluconazole): May increase plasma concentration
• Analgesics and Inhalational Agents:
• Additive anesthetic effect; dose reduction of Propofol may be required

• FDA and EMA Safety Alerts:
  Reinforced warning against prolonged infusions (>48 hrs) due to PRIS risk, especially in children and critically ill adults.
• EU Pediatric Guidelines:
  Pediatric sedation in ICU is contraindicated due to PRIS risk; recommended only under anesthesiologist supervision for short-term surgical use.
• Aseptic Technique Guidelines Updated:
  Emphasis on using within 6 hours once vial is opened; discard any unused emulsion.

• Temperature: Store at 2°C to 25°C (36°F to 77°F)
• Light Protection: Keep in original packaging; protect from light
• Freezing: Do not freeze
• Handling Instructions:
• Shake gently before use
• Inspect for separation or discoloration before use
• Discard vial 6 hours after opening (use aseptically)
• Do not reuse partially used vials