Propofol, marketed as Diprivan, amongst different names, is a short-acting remedy that ends in a decreased degree of consciousness and an absence of reminiscence for occasions.[4] Its makes use of embody the beginning and upkeep of basic anesthesia, sedation for mechanically ventilated adults, and procedural sedation.[4] It is usually used for standing epilepticus if different drugs haven’t labored.[4] It’s given by injection right into a vein, and the utmost impact takes about two minutes to happen and usually lasts 5 to 10 minutes.[4] Propofol can also be used for medical help in dying in Canada.[5]

The remedy seems to be secure to be used throughout being pregnant however has not been properly studied to be used on this case.[4] It’s not really helpful to be used throughout a cesarean part.[4] It’s not a ache remedy, so opioids equivalent to morphine might also be used;[6] nevertheless, whether or not or not they’re at all times wanted just isn’t clear.[7] Propofol is believed to work at the least partly by way of a receptor for GABA.[4]

Propofol was found in 1977 and accepted to be used in the US in 1989.[4][8] It’s on the World Well being Group’s Listing of Important Medicines.[9] It’s accessible as a generic remedy.[4] It has been known as milk of amnesia (a play on “milk of magnesia”), due to the milk-like look of the intravenous preparation, and due to its tendency to suppress reminiscence recall.[10][11] Propofol can also be utilized in veterinary medication for anesthesia.[12][13]

Medical makes use of


To induce basic anesthesia, propofol is the drug used nearly at all times, having largely changed sodium thiopental.[14][6] It can be administered as a part of an anesthesia upkeep method known as complete intravenous anesthesia, utilizing both manually programmed infusion pumps or computer-controlled infusion pumps in a course of known as goal managed infusion (TCI). Propofol can also be used to sedate people who’re receiving mechanical air flow however not present process surgical procedure, equivalent to sufferers within the intensive care unit.[15][16] In critically in poor health sufferers, propofol is superior to lorazepam each in effectiveness and total value.[17] Propofol is comparatively cheap in comparison with drugs of comparable use resulting from shorter ICU keep size.[17] One of many causes propofol is considered simpler (though it has an extended half-life than lorazepam) is as a result of research have discovered that benzodiazepines like midazolam and lorazepam are inclined to accumulate in critically in poor health sufferers, prolonging sedation.[17] Propofol has additionally been prompt as a sleep help in critically in poor health adults within the ICU; nevertheless, the effectiveness of this medication at replicating the psychological and bodily points of sleep for folks within the ICU aren’t clear.[16]

Propofol is usually used as an alternative of sodium thiopental for beginning anesthesia as a result of restoration from propofol is extra speedy and “clear”.[citation needed]

Propofol could be run via a peripheral IV or central line. Propofol is incessantly paired with fentanyl (for ache aid) in intubated and sedated folks.[18] Each are appropriate in IV type.[18]

Procedural sedation

Propofol is secure and efficient for gastrointestinal endoscopy procedures. Its use in these settings ends in a sooner restoration in comparison with midazolam.[19] It can be mixed with opioids or benzodiazepines.[20][21][22] Due to its speedy induction and restoration time, propofol can also be extensively used for sedation of infants and youngsters present process MRI.[23] It is usually usually utilized in mixture with ketamine with minimal unwanted side effects.[24]

Assisted Demise in Canada

A deadly dose of propofol is used for medical help in dying in Canada to rapidly induce deep coma and demise, however Rocuronium is at all times given—even when affected person dies because of propofol injection. Supply order of IV remedy is as follows:[5]

Step 1: Midazolam 10-20mg given as 2−4ml of 5mg/ml preparation for pre-anesthesia, induces sleep in 1−2 minutes.

Step 2: Lidocaine 40mg given as 4ml of 1{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} preparation to scale back potential burning in peripheral vein attributable to Propofol. Pause to permit impact.

Step 3: Propofol 1000mg given as 100ml of 10mg/ml preparation. Lack of consciousness happens inside 10 seconds and coma happens in 1-2 minutes. Demise could end result from the propofol however rocuronium continues to be given.

Step 4: Rocuronium 200mg given as 20ml of 10mg/ml preparation to induce cardiac arrest, which normally happens inside 5 minutes of injection.


In March 2021, the U.S. Meals and Drug Administration (FDA) issued an emergency use authorization (EUA) for Propofol‐Lipuro 1{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} to keep up sedation by way of steady infusion in folks better than age sixteen with suspected or confirmed COVID‑19 who require mechanical air flow in an intensive care unit ICU setting.[25][26][27][28] Within the circumstances of this public well being emergency, it might not be possible to require healthcare suppliers to hunt to restrict Fresenius Propoven 2{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} Emulsion or Propofol-Lipuro 1{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} solely for use for sufferers with suspected or confirmed COVID‑19; subsequently, this authorization doesn’t restrict use to such sufferers.[28]

Different makes use of


The US state of Missouri added propofol to its execution protocol in April 2012. Nonetheless, Governor Jay Nixon halted the primary execution by the administration of a deadly dose of propofol in October 2013 following threats from the European Union to restrict the drug’s export if it had been used for that function.[29][30] The UK had already banned the export of medicines or veterinary medicines containing propofol to the US.[31]

Leisure use

Leisure use of the drug by way of self-administration has been reported[32][33] however is comparatively uncommon resulting from its efficiency and the extent of monitoring required for secure use.[citation needed] Critically, a steep dose-response curve makes leisure use of propofol very harmful, and deaths from self-administration proceed to be reported.[34][35] The short-term results sought by way of leisure use embody delicate euphoria, hallucinations, and disinhibition.[36][37]

Leisure use of the drug has been described amongst medical workers, equivalent to anesthetists who’ve entry to the drug.[38][39] It’s reportedly extra widespread amongst anesthetists on rotations with quick relaxation intervals, as utilization usually produces a well-rested feeling.[40] Lengthy-term use has been reported to end in habit.[38][41]

Consideration to the dangers of off-label use of propofol elevated in August 2009 because of the Los Angeles County coroner’s conclusion that music icon Michael Jackson died from a combination of propofol and the benzodiazepine medication lorazepam, midazolam, and diazepam on June 25, 2009.[42][43][44][45] In accordance with a July 22, 2009 search warrant affidavit unsealed by the district court docket of Harris County, Texas, Jackson’s doctor, Conrad Murray, administered 25 milligrams of propofol diluted with lidocaine shortly earlier than Jackson’s demise.[43][44][46] Even so, as of 2016, propofol was not on a US Drug Enforcement Administration schedule.[40][47]

Uncomfortable side effects

Certainly one of propofol’s commonest unwanted side effects is ache on injection, particularly in smaller veins. This ache arises from activation of the ache receptor, TRPA1,[48] discovered on sensory nerves and could be mitigated by pretreatment with lidocaine.[49] Much less ache is skilled when infused at a slower fee in a big vein (antecubital fossa). Sufferers present appreciable variability of their response to propofol, at instances displaying profound sedation with small doses[1].

Extra unwanted side effects embody low blood strain associated to vasodilation, transient apnea following induction doses, and cerebrovascular results. Propofol has extra pronounced hemodynamic results relative to many intravenous anesthetic brokers.[50] Studies of blood strain drops of 30{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} or extra are considered at the least partially resulting from inhibition of sympathetic nerve exercise.[51] This impact is expounded to the dose and fee of propofol administration. It could even be potentiated by opioid analgesics.[52]

Propofol may trigger decreased systemic vascular resistance, myocardial blood stream, and oxygen consumption, presumably via direct vasodilation.[53] There are additionally experiences that it could trigger inexperienced discolouration of the urine.[54]

Though propofol is closely used within the grownup ICU setting, the unwanted side effects related to propofol appear to be of better concern in youngsters. Within the Nineties, a number of reported deaths of youngsters in ICUs related to propofol sedation prompted the FDA to situation a warning.[55]

As a respiratory depressant, propofol incessantly produces apnea. The persistence of apnea can rely on components equivalent to premedication, dose administered, and fee of administration, and should generally persist for longer than 60 seconds.[56] Presumably as the results of despair of the central inspiratory drive, propofol could produce vital decreases in respiratory fee, minute quantity, tidal quantity, imply inspiratory stream fee, and purposeful residual capability.[50]

Diminishing cerebral blood stream, cerebral metabolic oxygen consumption, and intracranial strain are additionally traits of propofol administration.[57] As well as, propofol could lower intraocular strain by as a lot as 50{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} in sufferers with regular intraocular strain.[58]

A extra severe however uncommon aspect impact is dystonia.[59] Delicate myoclonic actions are widespread, as with different intravenous hypnotic brokers. Propofol seems to be secure to be used in porphyria, and has not been recognized to set off malignant hyperpyrexia.[citation needed]

Propofol can also be reported to induce priapism in some people,[60][61] and has been noticed to suppress REM sleep stage and to worsen the poor sleep high quality in some sufferers.[62]

Uncommon [63]

  • Anxiousness.
  • adjustments in imaginative and prescient.
  • cloudy urine.
  • coughing up blood.
  • delirium or hallucinations.
  • tough urination.
  • issue swallowing.
  • dry eyes, mouth, nostril, or throat.

As with all different basic anesthetic agent, propofol ought to be administered solely the place appropriately educated workers and amenities for monitoring can be found, in addition to correct airway administration, a provide of supplemental oxygen, synthetic air flow, and cardiovascular resuscitation.[64]

Due to its lipid base, some hospital amenities require the IV tubing (of steady propofol infusions) to be modified after 12 hours. It is a safety measure towards microbial development and an infection.[65]

Propofol infusion syndrome

A uncommon, however severe, aspect impact is propofol infusion syndrome. This doubtlessly deadly metabolic derangement has been reported in critically in poor health sufferers after a chronic infusion of high-dose propofol, generally together with catecholamines and/or corticosteroids.[66]


The respiratory results of propofol are elevated if given with different respiratory depressants, together with benzodiazepines.[67]



Propofol has been proposed to have a number of mechanisms of motion,[68][69][70] each via potentiation of GABAA receptor exercise and subsequently performing as a GABAA receptor constructive allosteric modulator, thereby slowing the channel-closing time. At excessive doses, propofol could possibly activate GABAA receptors within the absence of GABA, behaving as a GABAA receptor agonist as properly.[71][72][73] Propofol analogs have been proven to additionally act as sodium channel blockers.[74][75] Some analysis has additionally prompt that the endocannabinoid system could contribute considerably to propofol’s anesthetic motion and to its distinctive properties.[76] EEG analysis upon these present process basic anesthesia with propofol finds that it causes a distinguished discount within the mind’s info integration capability.[77]


Large vial filled with milky white fluid

A 20 ml ampoule of 1{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} propofol emulsion, as offered in Australia by Sandoz

Propofol is very protein-bound in vivo and is metabolised by conjugation within the liver.[78]
The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. Nonetheless, its length of scientific impact is far shorter, as a result of propofol is quickly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol usually wears off inside minutes. Propofol is flexible; the drug could be given for brief or extended sedation, in addition to for basic anesthesia. Its use just isn’t related to nausea as is usually seen with opioid drugs. These traits of speedy onset and restoration together with its amnestic results[79] have led to its widespread use for sedation and anesthesia.

Historical past

John B. Glen, a veterinarian and researcher at Imperial Chemical Industries (ICI) spent 13 years growing propofol, an effort which led to the awarding to him of the distinguished 2018 Lasker Award for scientific analysis. Propofol was initially developed as ICI 35868. It was chosen for improvement after intensive analysis and construction–exercise relationship research of the anesthetic potencies and pharmacokinetic profiles of a collection of ortho-alkylated phenols.[80]

First recognized as a drug candidate in 1973, scientific trials adopted in 1977, utilizing a type solubilised in cremophor EL.[81] Nonetheless, resulting from anaphylactic reactions to cremophor, this formulation was withdrawn from the market and subsequently reformulated as an emulsion of a soya oil/propofol combination in water. The emulsified formulation was relaunched in 1986 by ICI (now AstraZeneca) beneath the model identify Diprivan. The presently accessible preparation is 1{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} propofol, 10{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} soybean oil, and 1.2{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} purified egg phospholipid as an emulsifier, with 2.25{ae90547d17d4d74b17007ee836a04674fd006933c139011dc78eb03c100070a7} glycerol as a tonicity-adjusting agent, and sodium hydroxide to regulate the pH. Diprivan incorporates EDTA, a standard chelation agent, that additionally acts alone (bacteriostatically towards some micro organism) and synergistically with another antimicrobial brokers. Newer generic formulations comprise sodium metabisulfite or benzyl alcohol as antimicrobial brokers. Propofol emulsion is a extremely opaque white fluid because of the scattering of sunshine from the tiny (about 150-nm) oil droplets it incorporates: Tyndall Impact.


A water-soluble prodrug type, fospropofol, has been developed and examined with constructive outcomes. Fospropofol is quickly damaged down by the enzyme alkaline phosphatase to type propofol. Marketed as Lusedra, this formulation could not produce the ache at injection web site that always happens with the traditional type of the drug. The U.S. Meals and Drug Administration (FDA) accepted the product in 2008.[82]
Nonetheless fospropofol is a Schedule IV managed substance with the DEA ACSCN of 2138 in the US in contrast to propofol.[83]

By incorporation of an azobenzene unit, a photoswitchable model of propofol (AP2) was developed in 2012, that permits for optical management of GABAA receptors with gentle.[84] In 2013, a propofol binding web site on mammalian GABAA receptors has been recognized by photolabeling utilizing a diazirine by-product.[85] Moreover, it was proven that the hyaluronan polymer current within the synovia could be protected against free-radical depolymerization by propofol.[86]

  • “Propofol”. Drug Data Portal. U.S. Nationwide Library of Medication.
  • GB patent 1472793, John B Glen & Roger James, “Pharmaceutical Compositions”, printed 1977-05-04, assigned to Imperial Chemical Industries Ltd 

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