Sedative and anesthetic medications are one of the basic tools in many operating rooms and intensive care spaces.

Sedation and induction of anesthesia are necessary in many medical acts and surgical interventions, as they block the tactile and painful sensitivity of patients, and facilitate the work of professionals. In this sense, one of the most widely used drugs is propofol, a powerful fast-acting sedative used as an anaesthetic.

In this article we explain what propofol is, its clinical uses, its mechanism of action, as well as the most common side effects caused by this drug.

Propofol: characteristics and clinical uses

Propofol is a drug from the group of fast-acting sedative hypnotics that is usually given intravenously . It was discovered in 1977 and approved for marketing in 1989, and is now considered an effective and safe drug. In some countries it is known as “milk of amnesia” because of the rapid induction of sleep and anaesthesia it produces.

This drug is used to initiate and maintain sedation in monitored anesthesia care, in combined sedation and local anesthesia, in induction of general anesthesia, and in intensive care when intubated or mechanically ventilated patients are to be sedated. Propofol works quickly; its peak effect takes approximately two minutes to occur and usually lasts five to ten minutes.

However, there have been reports of the abuse of propofol for recreational and other inappropriate purposes , resulting in deaths and other injuries. Cases of self-administration of propofol by health professionals have also been reported, with similar episodes. Propofol was also used in executions of prisoners on death row, although its use for this purpose was banned in 2013.

Effects and mechanism of action

The mechanism of action of propofol, as with the vast majority of anaesthetic drugs, is unknown; however, it has been suggested that this drug produces its sedative and anaesthetic effects by positively modulating the inhibitory function of the neurotransmitter GABA, through ligand activated GABAa receptors.

The pharmacodynamic properties of propofol depend on the concentrations of the drug in the blood. In patients who maintain spontaneous ventilation, the main cardiovascular effect of propofol is high blood pressure, with little or no change in heart rate , and without an appreciable decrease in cardiac output; however, if ventilation is assisted, there is an increase in the incidence and degree of depression of cardiac output.

Studies have shown that the effects of propofol on induction of anaesthesia are generally more pronounced than those of other intravenous induction drugs. Induction of anaesthesia with propofol is frequently associated with apnoea , both in adults and in paediatric patients. During maintenance of anaesthesia, propofol causes a decrease in spontaneous ventilation per minute, usually associated with an increase in carbon dioxide pressure.

Hypotension, oxyhemoglobin desaturation, apnea and airway obstruction may occur during sedation with monitored anesthesia care. Special caution should be taken with elderly and debilitated patients, as bolus dosing (single dose given over a short period of time) is not recommended for sedation in monitored anesthesia care.

Side effects

The clinical use of propofol may entail a number of risks and possible adverse effects that are worth considering . One of the most common side effects of propofol is pain at the site of injection, especially when it is performed in the smaller veins; this pain arises from activation of the TRPA1 pain receptor, located in the sensory nerves.

When propofol is used in anesthesia or monitored anesthesia care, the most common side effects include bradycardia, tachycardia, arrhythmia, hypertension, burning or stinging on movement, pain at the injection site, apnea , rash, and itching.

In cases where propofol is used for sedation in intensive care units, the most common symptoms are bradycardia, decreased cardiac output, hypotension, hyperlipidemia (presence of elevated blood lipid levels), and respiratory acidosis (increased concentration of carbon dioxide in blood plasma and decreased blood pH).

Although propofol is frequently used in the adult intensive care setting, special emphasis has been placed on the side effects affecting paediatric patients , as several deaths of children related to the sedation of this sedative and hypnotic drug were reported in the 1990s. Finally, it should be noted that the respiratory effects of propofol are increased if it is administered in conjunction with other depressant drugs (including benzodiazepines).

Propofol Infusion Syndrome

Propofol Infusion Syndrome is a rare disorder that affects some patients undergoing long-term treatment with high doses of this anesthetic and sedative drug . This syndrome usually occurs in children, and critically ill patients receiving catecholamines and glucocorticoids are at increased risk.

This disorder can lead to heart failure, rhabdomyolysis (a disease caused by muscle necrosis), metabolic acidosis, and kidney failure, and is often fatal. It can also cause hyperkalaemia, increased blood triglycerides and enlargement of the liver, which may be due to direct inhibition of the mitochondrial respiratory chain or impaired mitochondrial fatty acid metabolism.

Early recognition of the syndrome and interruption of propofol infusion is critical , as it significantly reduces morbidity and mortality. Treatment consists of providing cardiopulmonary support by means of inotropes (drugs that increase heart contraction), vasopressors and mechanical ventilation. Bradycardia usually does not respond to catecholamine infusion and external pacemaker.

To eliminate propofol and its metabolites, hemodialysis and hemofiltration are recommended. Some patients may need assistance with extracorporeal membrane oxygenation. Treatment for rhabdomyolysis includes maintaining intravascular volume and supporting renal function. And in the event of lactic acidosis, aggressive hemodialysis treatment is recommended.

Bibliographic references:

  • Kang, T. M. (2002). Propofol infusion syndrome in critically ill patients. Annals of Pharmacotherapy, 36(9), 1453-1456.
  • Mackenzie, N., & Grant, I. S. (1987). Propofol for intravenous sedation. Anaesthesia, 42(1), 3-6.
  • Tan, C. H., & Onsiong, M. K. (1998). Pain on injection of propofol. Anaesthesia, 53(5), 468-476.