Propofol

Aka: Propofol, Diprivan

1. See Also
   1. Procedural Sedation and Analgesia (PSAA)
   2. Rapid Sequence Intubation
2. Mechanism
   1. Sedative hypnotic
      1. Potentiates gamma-aminobutyric acid receptors
   2. No Analgesic effect
      1. Administer concurrent Analgesics (typically given 20-30 minutes prior to Propofol start)
   3. Drug Abuse potential (especially among anesthesiologists, nurse anesthetists, emergency medicine staff, dentists)
      1. Increases Dopamine levels which may reinforce addiction
      2. Increases Serotonin levels which may be Hallucinogenic
      3. References
         1. Majoewsky (2012) EM:RAP 12(1): 3
3. Precautions
   1. See Procedural Sedation and Analgesia (PSAA)
   2. Propofol has no Analgesic effect, and therefore Opioid Analgesics are often used before Propofol
   3. Propofol (esp. with concurrent Opioids) increases the risk of cardiopulmonary depression (Hypoxia, Hypotension)
      1. Close monitoring is critical (second provider skilled in airway management is preferred)
      2. Consider pre-procedure crystalloid bolus of 500 ml (or 10-20 ml/kg)
      3. Consider oxygen via nasal canula at 2 L/min
      4. Suction, Bag-valve mask, Nasopharyngeal Airway, and intubation equipment should be ready for use
      5. Consider Capnography
4. Pharmacokinetics
   1. Rapid onset and short half-life
   2. Lipid-soluble and crosses blood-brain barrier
   3. Onset: 30-45 seconds (<1 minute)
   4. Duration: 6 minutes on average (5 to 15 minutes, prolonged with repeated dosing)
   5. Lipid emulsion bottle is at risk of Bacterial contamination and growth once accessed
      1. Discard any open bottles after 12 hours
5. Preparation
   1. See Procedural Sedation
   2. Second provider skilled in airway management (preferred)
   3. Preventive measures
      1. Pre-procedure crystalloid bolus of 500 ml (or 10-20 ml/kg)
      2. Oxygen via nasal canula at 2 L/min
      3. Opioid Analgesics given at least 20 minutes before procedure
   4. Monitoring Equipment
      1. Pulse Oximetry (Oxygen Saturation and Heart Rate)
      2. Blood Pressure cuff, manual or automatic cycled every few minutes
      3. Consider Capnography
   5. Emergency Equipment
      1. Wall Suction (typically with yanker catheter tip)
      2. Bag-valve mask
      3. Nasopharyngeal Airway
      4. Intubation equipment (see Advanced Airway)
6. Dosing: Adults
   1. Conscious Sedation (not FDA approved)
      1. Adult (preferred procedural Sedative)
         1. Initial: 0.5 to 1 mg/kg IV over 20-30 seconds (typically given as smaller increments)
            1. Obese patients: Consider 0.7 to 0.8 mg/kg for starting dose
            2. Thin young patients: Consider 1.5 mg/kg for starting dose (risk of respiratory depression)
            3. Frail elderly patients: Consider 20-30 mg IV for starting dose
         2. Next: 0.25 to 0.5 mg/kg IV every 1 to 3 minutes
         3. Decrease dose in older patients (cummulative required total dose decreases with age)
            1. Age 18-40 years old: 2 mg/kg total dose
            2. Age 41-64 years old: 1.7 mg/kg total dose
            3. Age >64 years old: 1.2 mg/kg total dose
            4. Patanwala (2013) J Emerg Med 44(4): 823-8 +PMID:23333181 [PubMed]
      2. Typically no respiratory depression at 1 mg/kg dose
         1. Amnesia occurs at this dose
      3. Perform painful procedures immediately following infusion
         1. Amnestic effect wears off prior to sedation
   2. Propofol Infusion for Procedural Sedation
      1. Infusion: 100 to 150 mcg/kg/min (6 to 9 mg/kg/h)
   3. Intubation Sedation (not FDA approved)
      1. Dose 2 to 2.5 mg/kg IV over 20 to 30 seconds
   4. Ventilator sedation in ICU
      1. Infusion: 5-50 mcg/kg/min
   5. Anesthesia
      1. Age under 55 years old
         1. Titration: 40 mg IV every 10 seconds until induction achieved
         2. Typical cummulative total dose: 2 to 2.5 mg/kg
         3. Maintenance infusion: 100-200 mcg/kg/min
      2. Age 55 years old or older
         1. Decrease dose from that list above for younger patients
7. Dosing: Children
   1. Avoid for prolonged ICU use
   2. Conscious Sedation (not FDA approved)
      1. Initial: 1 mg/kg IV (up to 40 mg) over 20-30 seconds (typically given as smaller increments)
         1. Dose per kilogram typically higher in children than adults for adequate sedation
         2. Age <3 years: 2 mg/kg
         3. Older children and teens: 1.5 mg/kg
      2. May repeat 0.5 to 1 mg/kg IV (up to 20 mg maximum) every 1 to 3 minutes as needed
   3. Propofol Infusion for Procedural Sedation
      1. Infusion: 100 to 250 mcg/kg/min (6 to 15 mg/kg/h)
   4. Anesthesia (age 3 years and older)
      1. Typical cummulative total dose: 2.5 to 3.5 mg/kg over 20-30 seconds
      2. Maintenance infusion: 125-300 mcg/kg/min
8. Indications
   1. Procedural Sedation and Analgesia (PSAA)
      1. Indicated for ASA Physical Status Score 2 (non-hypotensive, stable)
   2. Rapid Sequence Intubation
      1. Other agents (e.g. Etomidate, Ketamine) are preferred for emergency department induction (Hypotension risk)
9. Contraindications: Relative
   1. See Procedural Sedation and Analgesia (PSAA)
   2. Age <6 months or weight <5 kg
   3. Age >75 years old
   4. ASA Physical Status Class 3 and above
   5. Soy allergy (soybean allergy) is no longer considered a contraindication
   6. Egg allergy (egg Lecithin allergy) is no longer considered a contraindication
10. Adverse Effects
    1. Propofol Infusion Syndrome
       1. Seen with prolonged use (not associated with short-term Procedural Sedation and Analgesia)
    2. Hypertriglyceridemia (with prolonged infusion)
       1. Propofol is a lipid-based infusion that contains 1 kcal/ml
       2. Risk of Acute Pancreatitis
          1. Devlin (2005) Pharmacotherapy 25(10):1348-52 +PMID:16185179 [PubMed]
    3. Cardiopulmonary adverse effects (reduced by administering with lower dose and slower titration)
       1. Respiratory depression
          1. More common in older adults
          2. Close monitoring by a second provider skilled in airway management is preferred
          3. Consider oxygen via nasal canula at 2 L/min
          4. Suction, Bag-valve mask, Nasopharyngeal Airway, and intubation equipment should be ready for use
          5. Consider Capnography
       2. Transient Hypotension and myocardial depression
          1. Systolic Blood Pressure drops 10-18 mmHg, Diastolic Blood Pressure drops 10-16 mmHg
          2. Consider pre-procedure crystalloid bolus of 500 ml (or 10-20 ml/kg)
          3. Increase time (>20 minutes) between IV Opioids and Propofol
          4. Consider alternative Sedatives (e.g. Etomidate or Ketamine) in hypotensive patients
          5. Phenylephrine may be used to counter the hypotensive effects of Propofol
    4. Overdose
       1. No antidote
       2. Manage with ABC Management and supportive care
11. Safety
    1. No delay in Lactation
    2. Pregnancy category B
       1. However, minimal data available
       2. Not Teratogenic based on limited data
12. References
    1. Acker, Koval and Leeper (2017) Crit Dec Emerg Med 31(4): 3-13
    2. Miller (2019) Ann Emerg Med 73(5): 470-80 [PubMed]