Propofol (Diprivan)
Anesthesia Implications
Classification: Hypnotic
Therapeutic Effects: Sedation, Anxiolysis, Analgesia
Time to Onset: 40 seconds from the start of injection
Duration: Distribution half-life is 2-8 min. Context Sensitive half-life for infusions is < 40 min (for infusions less than 8 hours).
Primary Considerations
Expiration – Expires 6 hours after drawn into a syringe, and 12 hours after being used as an infusion all remaining drug and tubing should be discarded and replaced.
Pain – pain on injection can range from moderate to intense. The smaller the vein the higher the risk/intensity of pain. Some mix lidocaine with propofol, which tends to decrease pain on injection. However, the propofol label recommends against this – lidocaine additive greater than 20 mg in 200 mg of propofol results in instability, increased globule sizes over time, and a reduced anesthetic potency. Therefore, it is recommended to either give lidocaine prior to propofol, or if mixed, the mixture should happen just prior to administration and should not exceed 20 mg per 200 mg of propofol.
Cardiovascular Affects – All of the following are reduced: Contractility, preload, SVR, and MAP. Heart rate minimally affected.
Respiratory Affects – Profound respiratory depression, decreased upper airway reflexes.
Cerebral Affects – reduces the following: cerebral blood flow, CMRO2 (for this reason it is also considered a cerebral vasoconstrictor), IOP, and ICP. Some studies suggest that propofol might be protective against ischemic brain injury for BRIEF ischemic events.
PONV – propofol, in small doses, is useful for PONV prophylaxis/treatment.
Epilepsy – Propofol causes burst suppression on the EEG and has been used successfully in stopping status epilepticus. HOWEVER, propofol administration to epilepsy patients increases the risks of a seizure in the recovery phase.
Pregnancy – Propofol crosses the placenta and may be associated with neonatal depression. Propofol also crosses into breast milk. Affects of oral ingestion of propofol is unknown.
Soy and Egg Allergies – Patients with soy allergy or egg allergy CAN receive propofol without any special precautions.
Use – lower induction doses and slower maintenance rates should be used in the elderly, debilitated, and/or ASA III or IV patients. If high ICP is suspected, hyperventilation and hypocarbia should accompany a slower propofol administration to avoid significant decreases in cerebral perfusion pressure. Pediatric patients can get severe bradycardia when propofol is administered concomitantly with fentanyl.
IV push dose
Adult Induction of anesthesia – Adults: 2.0-2.5 mg/kg. Geriatric patients may require a smaller dose (generally 1.0-1.5 mg/kg). Use LEAN body weight in the obese.
Pediatric Induction of anesthesia: 2.5mg/kg – 3.5 mg/kg
PONV Prophylaxis – 0.5-1.0 mg/kg 15 minutes before the end of surgery. As little as 30 mg has been reported to be as effective as 10 mg of metoclopromide.
Anxiolysis – 0.4 mg/kg
IV infusion dose
Adult Maintenance Infusion: 25-200 mcg/kg/min (typically the maintenance dose is > 100 mcg/kg/min). Obese – use TOTAL body weight
Pediatric Maintenance Infusion: 80-360 mcg/kg/min (typically the maintenance dose is > 140 mcg/kg/min). The younger the patient, the higher the MEDIAN maintenance dose.
Antiemetic Infusion: 16.7 mcg/kg/min.
Method of Action
Positive modulation of the inhibitory function of the
neurotransmitter GABA through the ligand-gated GABAA receptors. Binding of these receptors in the hippocampus and prefrontal cortex reduces acetylcholine release which appears to contribute to the sedative effects. Propofol also inhibits NMDA receptors which contributes to the central effects.
Metabolism
Rapidly metabolized in the liver. Byproducts are glucuronide and sulphate. Clearance is faster than hepatic blood flow, which suggests additional metabolism elsewhere (lungs)
Elimination
Excreted through the kidneys. Elimination half-life is 4-7 hours.
Additional Notes
Propofol is a water-soluble, lipophillic weak acid (pKa of 11) and contains soybean oil, glycerol, and egg lecithin. Disodium edetate is added to reduce bacterial and fungal growth.
Anesthesia Patient Safety Foundation. The Propofol Safety Review. 2007. web link
Khan. Pharmacology of anaesthetic agents I: intravenous anaesthetic agents. 2014 web link
Kotani. The Experimental and Clinical Pharmacology of Propofol, an Anesthetic Agent with Neuroprotective Properties. 2008 web link
DIPRIVAN (propofol) injectable emulsion, USP. 2017 web link
Kim. Antiemetic effect of propofol administered at the end of surgery in laparoscopic assisted vaginal hysterectomy. 2014 web link
Hsiao. The analgesic effect of propofol associated with the inhibition of hypoxia inducible factor and inflammasome in complex regional pain syndrome. Journal of Biomedical Science. 2019. web link
Fassoulaki. Is propofol an analgesic? European Journal of Anaesthesiology. 2011. web link
Wender. Efficacy of Propofol or Midazolam compare to placebo for preoperative medication. 2015. web link
Mossa-Basha. What is the appropriate subhynotic propofol infusion dose for the prevention of post-operative nausea and vomiting: A meta-analysis of six randomized-controlled trials. 2019.
Naghibi. Prevention of postoperative nausea and vomiting with a subhypnotic dose of Propofol in patients undergoing lower abdominal surgery: A prospective, randomized, double-blind study. 2015.
American Academy of Allergy Asthma and Immunology. Soy-allergic and Egg-allergic Patients Can Safely Receive Anesthesia. 2023. web link
