PROPOFOL 

• Formulation: Lipid emulsion (10% soybean oil, egg lecithin, glycerol)
• Appearance: Milky white
• pH: ~7–8.5

High risk of bacterial growth → strict asepsis

 MECHANISM OF ACTION

• Potentiates GABA-A receptor
• ↑ Chloride influx → neuronal hyperpolarization
• ↓ Excitatory neurotransmission

 Also:

• NMDA inhibition (minor)
• ↓ sympathetic tone

 PHARMACOKINETICS

1. Distribution

• Highly lipophilic
• Rapid CNS penetration → onset 30–45 sec
• Redistribution → early recovery

2. Metabolism

• Hepatic conjugation
• Extrahepatic metabolism (lungs, kidneys)

3. Elimination

• Context-sensitive half-time:
• Short infusions: short recovery
• Prolonged infusions: still relatively short vs benzodiazepines

 PHARMACODYNAMICS

DOSING IN ICU 

 Sedation (Ventilated patients)

• Initial: 5–10 mcg/kg/min
• Maintenance: 5–50 mcg/kg/min
• Typical ICU: 10–30 mcg/kg/min

 According to Society of Critical Care Medicine:

• Prefer light sedation (RASS -2 to 0)

SYSTEMIC EFFECTS

 Cardiovascular

• ↓ SVR (vasodilation)
• ↓ preload + afterload
• Mild myocardial depression

 Result: Hypotension (dose-dependent)

 Respiratory

• Respiratory depression → apnea (bolus)
• ↓ ventilatory response to CO₂
• Bronchodilation (useful in asthma)

 CNS EFFECTS

• ↓ CMRO₂
• ↓ CBF → ↓ ICP
• Maintains autoregulation

Drug of choice in neurocritical care

 Metabolic Effects

• ↓ cortisol (mild adrenal suppression possible)
• Lipid load → ↑ triglycerides

MONITORING

• RASS / SAS scale
• Hemodynamics (BP, HR)
• Triglycerides (if >48 hrs infusion)
• CK, lactate (PRIS suspicion)

 ADVERSE EFFECTS

1. Common

• Hypotension
• Bradycardia
• Injection pain

2. Hypertriglyceridemia

• Due to lipid emulsion
• Risk of pancreatitis

3.  PROPOFOL INFUSION SYNDROME (PRIS)

 Definition

Life-threatening syndrome due to mitochondrial dysfunction

 Risk Factors

• Dose >4 mg/kg/hr (>67 mcg/kg/min)
• Duration >48 hrs
• Sepsis
• Catecholamines + steroids
• Critical illness (esp. children)

 Pathophysiology

• Impaired fatty acid oxidation
• Mitochondrial failure

 Clinical Features

 Management

• Immediate stop propofol
• Supportive care (vasopressors, CRRT)
• Consider ECMO in refractory shock

 COMPARISON WITH OTHER ICU SEDATIVES

CONTRAINDICATIONS

• Egg/soy allergy (relative, controversial)
• Hemodynamic instability
• Severe hypertriglyceridemia
• Suspected PRIS