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
|
Parameter |
Effect |
|
Sedation |
Dose-dependent hypnosis |
|
Amnesia |
Moderate |
|
Analgesia |
None |
|
Anticonvulsant |
Yes |
|
Antiemetic |
Strong |
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
|
System |
Findings |
|
CVS |
Bradycardia → cardiac failure |
|
Metabolic |
Severe metabolic acidosis |
|
Muscle |
Rhabdomyolysis |
|
Renal |
AKI |
|
Labs |
↑ CK, ↑ lactate, hyperkalemia |
Management
- Immediate stop propofol
- Supportive care (vasopressors, CRRT)
- Consider ECMO in refractory shock
COMPARISON WITH OTHER ICU SEDATIVES
|
Feature |
Propofol |
Midazolam |
Dexmedetomidine |
|
Onset |
Rapid |
Moderate |
Slow |
|
Offset |
Rapid |
Prolonged |
Moderate |
|
Delirium |
↓ |
↑ |
↓ |
|
Analgesia |
No |
No |
Mild |
|
Hemodynamics |
↓ BP |
Stable |
Bradycardia |
CONTRAINDICATIONS
- Egg/soy allergy (relative, controversial)
- Hemodynamic instability
- Severe hypertriglyceridemia
- Suspected PRIS