Propofol

Usage

Propofol is a short-acting, intravenous anesthetic and sedative agent used for:

• Induction and maintenance of general anesthesia: For both adult and pediatric patients undergoing surgical, diagnostic, or other medical procedures requiring general anesthesia.
• Monitored Anesthesia Care (MAC) sedation: Provides conscious sedation for procedures where the patient needs to be relaxed and comfortable but responsive.
• Sedation of intubated, mechanically ventilated patients in the Intensive Care Unit (ICU): For short-term sedation and control of anxiety and agitation.

Pharmacological Classification: Short-acting hypnotic, general anesthetic, sedative-hypnotic.

Mechanism of Action: Propofol is believed to act primarily through positive modulation of the inhibitory function of the gamma-aminobutyric acid (GABA) type A receptors in the central nervous system. It enhances the effects of GABA, the primary inhibitory neurotransmitter in the brain, leading to sedation and loss of consciousness.

Alternate Names

Propofol is the generic name.

Brand Names: Diprivan, Fresofol, Propofol-Lipuro.

How It Works

Pharmacodynamics: Propofol produces dose-dependent effects ranging from mild sedation to deep unconsciousness and anesthesia. It has rapid onset of action (within 1 minute) and a short duration of effect due to its rapid redistribution and metabolism. Propofol decreases cerebral blood flow and metabolic rate, resulting in decreased intracranial pressure. It also has antiemetic properties.

Pharmacokinetics:

• Absorption: Administered intravenously, resulting in 100% bioavailability.
• Distribution: Rapidly distributes to highly perfused tissues (brain, heart, liver, kidneys) followed by redistribution to less perfused tissues (muscle, fat).
• Metabolism: Primarily metabolized in the liver by conjugation with glucuronide and sulfate, forming inactive metabolites. CYP450 enzymes play a minor role in its metabolism.
• Elimination: Excreted mainly through the kidneys, with a small fraction excreted in bile.

Mode of Action: Propofol enhances the activity of GABA_A receptors by increasing the duration of chloride channel opening, leading to hyperpolarization of neurons and decreased neuronal excitability.

Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Positive allosteric modulator of GABA_A receptors. Weak inhibitor of CYP3A4 but unlikely to be clinically significant.

Elimination Pathways: Primarily hepatic metabolism via conjugation, followed by renal excretion.

Dosage

Propofol dosage is highly individualized and titrated to the desired clinical effect based on patient age, physical status, concomitant medications, and the procedure being performed. Please refer to the full prescribing information for detailed dosing instructions and guidelines.

Standard Dosage

Adults:

• Induction of general anesthesia: 1-2.5 mg/kg IV titrated to effect.
• Maintenance of general anesthesia: 100-200 mcg/kg/min IV infusion or intermittent bolus injections.
• MAC sedation: Initial bolus of 0.5-1 mg/kg IV followed by infusion of 25-75 mcg/kg/min or intermittent bolus injections.
• ICU sedation: 5-50 mcg/kg/min IV infusion.

Children:

• Induction of general anesthesia (3-16 years): 2.5-3.5 mg/kg IV. Not recommended for children under 3 years of age for induction of anesthesia.
• Maintenance of general anesthesia (2 months-16 years): 125-300 mcg/kg/min IV infusion.

Special Cases:

• Elderly Patients: Lower doses are generally required due to decreased clearance and reduced volume of distribution. Titrate cautiously.
• Patients with Renal Impairment: Dosage adjustment is usually not necessary but monitor closely.
• Patients with Hepatic Dysfunction: Reduce dosage and administer cautiously due to reduced metabolic capacity.
• Patients with Comorbid Conditions: Consider adjusting dose based on the specific comorbidity and its impact on drug clearance and patient response.

Clinical Use Cases

• Intubation: Facilitates endotracheal intubation by providing sedation and muscle relaxation.
• Surgical Procedures: Induction and maintenance of general anesthesia for various surgical procedures.
• Mechanical Ventilation: Sedation of mechanically ventilated patients in the ICU.
• Intensive Care Unit (ICU) Use: Short-term sedation of critically ill patients.
• Emergency Situations: May be used for rapid sequence intubation in certain emergency situations.

Dosage Adjustments

Adjust dosage based on patient response, age, organ function, and concomitant medications.

Side Effects

Common Side Effects:

• Hypotension
• Apnea
• Bradycardia
• Pain at injection site
• Nausea and vomiting

Rare but Serious Side Effects:

• Anaphylaxis
• Propofol Infusion Syndrome (PRIS): Characterized by metabolic acidosis, rhabdomyolysis, hyperkalemia, and cardiac dysfunction.

Long-Term Effects:

• Potential for abuse and dependence with prolonged use.

Adverse Drug Reactions (ADR):

• Severe hypotension
• Respiratory arrest
• Cardiac arrhythmias

Contraindications

• Hypersensitivity to propofol or any component of the formulation (egg, soy).
• History of anaphylaxis to eggs, egg products, soybeans, or soy products.

Drug Interactions

• CNS depressants: (opioids, benzodiazepines, barbiturates, alcohol) - additive effects leading to increased sedation and respiratory depression.
• CYP450 inhibitors: May increase propofol concentrations.
• Valproate: Increased blood levels of propofol.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Formerly Category B, now removed. Propofol crosses the placenta and can cause neonatal depression. Use only if clearly needed and weigh risks versus benefits. Not recommended for obstetric anesthesia, including Cesarean section.
• Breastfeeding: Propofol is excreted in breast milk in small amounts. While generally considered safe, some recommend interrupting breastfeeding for a short period after administration. Consult current guidelines for specific recommendations.

Drug Profile Summary

• Mechanism of Action: Potentiates GABA_A receptor activity.
• Side Effects: Hypotension, apnea, bradycardia, injection site pain, nausea/vomiting. Rarely: anaphylaxis, PRIS.
• Contraindications: Hypersensitivity, allergy to egg/soy.
• Drug Interactions: CNS depressants, CYP450 inhibitors, valproate.
• Pregnancy & Breastfeeding: Crosses placenta, excreted in breast milk. Use with caution.
• Dosage: Titrate to effect based on indication and patient characteristics.
• Monitoring Parameters: Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness.

Popular Combinations

• Opioids (fentanyl, morphine): For analgesia during general anesthesia.
• Neuromuscular blocking agents: For muscle relaxation during intubation and surgery.

Precautions

• General Precautions: Monitor vital signs continuously. Use cautiously in patients with cardiovascular, respiratory, or hepatic impairment.
• Specific Populations: Use cautiously in elderly patients and those with renal/hepatic dysfunction.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Propofol?

A: Propofol dosing is highly individualized and dependent on indication, patient age, and comorbidities. Refer to the detailed dosage guidelines above and consult the full prescribing information.

Q2: How is Propofol administered?

A: Propofol is administered intravenously, either as a bolus injection or continuous infusion.

Q3: What are the common side effects of Propofol?

A: Common side effects include hypotension, apnea, bradycardia, injection site pain, nausea, and vomiting.

Q4: What is Propofol Infusion Syndrome (PRIS)?

A: PRIS is a rare but serious complication associated with prolonged high-dose propofol infusions, particularly in critically ill patients. It is characterized by metabolic acidosis, rhabdomyolysis, hyperkalemia, and cardiac dysfunction.

Q5: Can Propofol be used in pregnant or breastfeeding women?

A: Propofol should be used cautiously during pregnancy and breastfeeding. It crosses the placenta and is excreted in breast milk. Weigh the risks and benefits carefully and consult current guidelines.

Q6: What drugs interact with Propofol?

A: Drugs that interact with propofol include other CNS depressants (opioids, benzodiazepines), CYP450 inhibitors, and valproate.

Q7: What precautions should be taken when administering Propofol?

A: Continuously monitor vital signs, use cautiously in patients with cardiovascular, respiratory, or hepatic impairment, and avoid rapid bolus injections in elderly or debilitated patients.

Q8: How long does it take for Propofol to take effect?

A: Propofol has a rapid onset of action, typically within one minute of intravenous administration.

Q9: What are the contraindications to using Propofol?

A: Contraindications include hypersensitivity to propofol or any component of the formulation, and a history of anaphylaxis to egg or soy products.

It’s important to remember that this information is current as of today’s date, February 17, 2025, and may change with future research and clinical experience. Always consult the most up-to-date prescribing information and relevant guidelines before making any clinical decisions.