
Everything You Need To Know About Propofol
Propofol is one of those names you might not hear in everyday conversation, but it’s a critical player in the medical world, particularly in anesthesia. If you’ve ever undergone surgery, you’ve likely witnessed propofol in action. Although its name may not be as widely recognized as other medications, it excels in both the induction and maintenance of anesthesia.
So, what exactly is propofol, and why is it so widely used? Let’s explore its journey, what makes it unique, and why it’s crucial in modern medicine.
What is Propofol?
Propofol is an intravenous anesthetic that is frequently used as an induction drug for general anesthesia, during monitored anesthesia treatment, or for procedural sedation. It can be delivered as a bolus, continuous infusion, or a combination of both methods. Propofol is formulated as a lipid emulsion, resulting in its distinctive milky white appearance, which has led to its informal name as “milk of amnesia.”
The formula includes soybean oil, glycerol, egg lecithin, and a minimal quantity of the preservative EDTA. Due to the emulsion’s ability to support microbial growth, it is essential to employ strict aseptic techniques when handling and drawing up the drug.
There are various clinical uses of propofol, including:
- Induction of general anesthesia for patients aged 3 years and older, though it can also be used in children under 3 if IV access is available.
- Maintenance of anesthesia for patients over 2 months old.
- Sedation in supervised anesthetic care for patients undergoing procedures.
- Sedation in ICU patients on mechanical ventilation and intubation.
Mechanism of Action of Propofol
The propofol’s mechanism, like many other general anesthetic agents, is not fully understood but is thought to involve its effects on GABA-mediated chloride channels in the brain. Propofol may work by reducing the dissociation of GABA from its receptors, thereby enhancing the inhibitory effects of the neurotransmitter. This leads to prolonged activation of the GABA receptor, increasing chloride conductance across the neuron. The result is hyperpolarization of the cell membrane, which makes it more difficult for a successful action potential to occur, contributing to its anesthetic and sedative properties.
Administration, Pharmacodynamics, and Pharmacokinetics
- Route of Administration: Intravenous.
- Onset of Action: Propofol has a rapid onset of action that is dose-dependent, typically occurring in less than a minute.
- Duration of Action: An induction dose of propofol produces a clinical effect lasting about 10 minutes. Prolonged or repeated administration can result in accumulation in peripheral tissues, leading to an increased duration of action.
- Distribution: Propofol has a large volume of distribution.
- Protein Binding: Highly bound to plasma proteins, approximately 97% to 99%.
- Metabolism: Primarily metabolized in the liver through hepatic oxidation and conjugation to sulfate and glucuronide conjugates.
- Clearance: Around 60% of propofol is cleared via the liver, with the remaining 40% through extrahepatic clearance, mostly by the kidneys.
- Half-life: Propofol exhibits a bi-phasic pharmacokinetic profile, characterized by an initial half-life of approximately 40 minutes, followed by a terminal half-life that typically ranges from 4 to 7 hours. After prolonged infusions, the context-sensitive half-time may extend to 1 to 3 days following a 10-day infusion, although the clinical effect is much shorter.
- Excretion: Primarily through renal excretion.
After a single bolus or short-term infusion, the termination of action is mostly due to redistribution because of the drug’s lipophilicity. Metabolism and excretion play smaller roles in ending the effects of a single bolus. However, after prolonged infusions, there may be a slower emergence from anesthesia, as the tissues and blood reach a steady-state concentration.
Unfavorable Findings
Adverse Reactions
The most common adverse reaction associated with propofol is transient local pain at the injection site. Administering IV lidocaine prior to the propofol bolus may help reduce this discomfort. Other possible reactions include:
- Hypotension
- Myoclonus
- In some cases, propofol can cause EKG changes, such as QT interval prolongation, although this is rarely clinically significant.
- An exceedingly rare adverse event is discolored urine, often presenting as a green tint.
Pregnancy
Propofol is generally regarded safe for usage during pregnancy, however it does cross the placenta and may cause newborn CNS and respiratory depression. Out of all the induction drugs now in use, it is the drug of choice for inducing general anesthesia in stable obstetric patients and belongs to the lowest-risk class.
Before, propofol was classified as a Category B medication for usage during pregnancy. However, the FDA abandoned the lettering system in late 2014 to replace it with a more descriptive system that focused on the specific effects of pharmaceutical drugs during pregnancy and breastfeeding.
Drug Interactions
Propofol may increase the effects of other drugs that lower blood pressure and induce respiratory or CNS depression. When using additional agents that could cause the QT interval to lengthen, caution is advised. Despite its modest CYP3A4 inhibitory actions, propofol is not expected to pose a significant clinical risk.
Hazardousness
Propofol Infusion Syndrome (PRIS) is a rare but serious adverse effect associated with prolonged infusions of propofol, typically at doses exceeding 4 mg/kg/hour for more than 24 hours. This syndrome can manifest with metabolic acidosis, hyperkalemia, hyperlipidemia, and rhabdomyolysis, potentially leading to renal and cardiac failure, and ultimately resulting in death.
The onset of PRIS generally occurs within four days of starting propofol treatment. It is believed to arise from disruptions in mitochondrial metabolism and the function of the electron transport chain, although the exact mechanism remains unknown. PRIS has been observed primarily in pediatric and young adult patients, particularly those requiring prolonged sedation, such as mechanically ventilated individuals with head trauma.
Diagnosis of PRIS is made by exclusion. The primary management strategy involves discontinuing the propofol infusion and providing supportive care. The estimated mortality rate associated with PRIS is around 33%, which can increase significantly if the diagnosis is delayed.
Observed Contraindications
Propofol is contraindicated in patients with any known hypersensitivity to the drug. Caution is advised for individuals with abnormally low blood pressure.
Some medication package inserts recommend against administering propofol to patients with reported allergies to eggs, egg products, soy, or soy products. Allergic reactions may arise from exposure to specific proteins found in both egg and soy sources, rather than from the fats (lecithin and oil) that constitute the emulsion. The oils used in the production of propofol are unlikely to contain sufficient protein quantities to trigger an allergic cross-reaction.
Nonetheless, research has demonstrated that atopy patients are more likely to experience allergic reactions to different drugs, and some case studies suggest that atopic people may also be cross-sensitive to propofol. As a result, clinical judgment ought to be used on an individual basis.
Propofol’s Therapeutic Effects
Propofol, when given as a bolus, offers a rapid and smooth onset of action with a highly predictable duration of effect. It has minimal organ toxicity and demonstrates excellent compatibility with a variety of commonly used drugs in anesthesia settings.
Effects on the Central Nervous System
Propofol induces a dose-dependent decrease in consciousness, making it suitable for sedation to general anesthesia. It can suppress protective airway reflexes, so patients must follow proper fasting guidelines.
Propofol reduces cerebral blood flow, intracranial pressure, and cerebral oxygen consumption, and at higher doses, it may cause burst suppression or an isoelectric EEG. In rat studies, it has shown neuroprotective effects, reducing oxidative damage and apoptosis.
Transient excitatory movements like choreiform movements or opisthotonus can occur after injection. Propofol also suppresses seizures and may be used off-label for refractory status epilepticus. Its antiemetic effects reduce postoperative nausea and vomiting, likely by depressing the chemoreceptor trigger zone and vagal nuclei.
Effects on the Cardiovascular System
Propofol induces vasodilation by inhibiting sympathetic vasoconstriction and mildly depressing myocardial contractility, often leading to hypotension, especially when given as a bolus. This can significantly lower mean arterial pressure, so caution is advised in hypovolemic or catecholamine-depleted patients.
Effects on the Respiratory System
Propofol causes dose-dependent respiratory depression by inhibiting the hypercapnic ventilatory drive, which is worsened when combined with other sedatives like benzodiazepines, opioids, or anesthetics. An induction dose typically results in apnea. It may also cause a low incidence of bronchospasm in asthmatic patients.
Improving Outcomes of Healthcare Team
Propofol is a commonly used induction agent in anesthesia, utilized by anesthesiologists, nurse anesthetists, and intensivists. All healthcare providers should be aware of its adverse effects, including PRIS. During induction, a dedicated member of the anesthesia team should monitor the patient, ensuring they are connected to cardiac monitors and an additional IV line is available to manage potential hypotension.
A coordinated effort among clinicians, nurses, and surgical staff is essential for achieving optimal patient outcomes when using propofol.
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Conclusion
Propofol is an essential anesthetic agent with wide-ranging applications in modern medicine, known for its rapid onset, smooth action, and minimal organ toxicity. However, its use requires careful monitoring to manage potential adverse effects such as PRIS.
Armein Pharmaceuticals Pvt. Ltd. ensures the highest quality in producing propofol injectables, trusted by healthcare professionals nationwide for safety and reliability. Choose Armein Pharmaceuticals for dependable anesthetic solutions.