Pharmacokinetics
Propofol is highly protein-bound in vivo and is metabolised by conjugation in the liver. The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter, because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol typically wears off within minutes. Propofol is versatile; the drug can be given for short or prolonged sedation, as well as for general anesthesia. Its use is not associated with nausea as is often seen with opioid medications. These characteristics of rapid onset and recovery along with its amnestic effects have led to its widespread use for sedation and anesthesia. History
John B. Glen, a veterinarian and researcher at Imperial Chemical Industries (ICI) spent 13 years developing propofol, an effort which led to the awarding to him of the prestigious 2018 Lasker Award for clinical research. Propofol was originally developed as ICI 35868. It was chosen for development after extensive evaluation and structure–activity relationship studies of the anesthetic potencies and pharmacokinetic profiles of a series of ortho-alkylated phenols.First identified as a drug candidate in 1973, clinical trials followed in 1977, using a form solubilised in cremophor EL. However, due to anaphylactic reactions to cremophor, this formulation was withdrawn from the market and subsequently reformulated as an emulsion of a soya oil/propofol mixture in water. The emulsified formulation was relaunched in 1986 by ICI (now AstraZeneca) under the brand name Diprivan.
It is also often used in combination with ketamine with minimal side effects. Assisted death in Canada
A lethal dose of propofol is used for medical assistance in dying in Canada to quickly induce deep coma and death, but rocuronium is always given—even when patient dies as a result of propofol injection. Delivery order of IV medication is as follows:Step 1: Midazolam 10–20 mg given as 2−4ml of 5 mg/ml preparation for pre-anesthesia, induces sleep in 1−2 minutes. Step 2: Lidocaine 40 mg given as 4ml of 1% preparation to reduce possible burning in peripheral vein caused by propofol. Pause to allow effect. Step 3: Propofol 1000 mg given as 100ml of 10 mg/ml preparation. Loss of consciousness occurs within 10 seconds and coma occurs in 1–2 minutes. Death may result from the propofol but rocuronium is still given. Step 4: Rocuronium 200 mg given as 20ml of 10 mg/ml preparation to induce respiratory arrest. Cardiac arrest subsequently follows about 5 minutes later due to hypoxia. COVID-19
In March 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for Propofol‐Lipuro 1% to maintain sedation via continuous infusion in people older than sixteen with suspected or confirmed COVID-19 who require mechanical ventilation in an intensive care unit ICU setting.