Propofol: An Overview

Administration of propofol, an IV anesthetic, can result in dose-dependent effects, ranging from sedation to general anesthesia.

Formulations

Two formulations of propofol are available for veterinary use in the United States. Both are isotonic 1% (10 mg/mL) macroemulsions with 10% soybean oil, 2.25% glycerol, and 1.2% egg-lecithin. The pH is adjusted to approximately 7.5 with sodium hydroxide.

The original formulation has no preservative and, given the medium used to solubilize propofol, the label recommends discarding the container within 6 hours of first use to minimize microbial or fungal contamination. Refrigeration is not recommended so as to prevent separation of active drug from the emulsion.

To reduce potential waste from incomplete use of an opened container of preservative-free propofol, 2% benzyl alcohol has been included in the new formulation, with a 28-day shelf life after initial use. This formulation is only approved for use in dogs; safety and efficacy studies in cats are ongoing. Because the 2 formulation labels differ only slightly, users must be aware of which propofol formulation has been selected.

Additional nonlipid-based formulations of propofol have been evaluated to a limited extent for use in several species and are available in Europe and Australia; macroemulsion products with varying preservatives are also available for use in humans in the United States.

Administration

Either veterinary propofol formulation may be administered over 30 to 90 seconds IV for induction of anesthesia. A titrated dose of 6 to 10 mg/kg is recommended in healthy, unsedated animals. Dose reduction is suggested for compromised patients.

Both sedation (premedication) and the addition of benzodiazepines to anesthetic induction protocol often reduce the dose requirement (by 1–4 mg/kg) and have the potential to reduce costs associated with propofol administration. Slow administration (versus rapid bolus) of propofol is recommended to allow blood and brain concentrations of drug to equilibrate and minimize the likelihood of a relative overdose. Slow administration is not usually associated with excitement as with historic drugs; cardiovascular and respiratory effects are also minimized.

Indications & Duration of Action

Propofol is primarily indicated as an IV sedative to facilitate a short period of restraint for nonpainful or minor procedures (eg, ultrasound evaluation, bandage change, upper airway examination) or as an anesthetic induction agent to facilitate intubation before maintenance with inhaled anesthetics. However, because of its unique pharmacokinetic profile (including a short context-sensitive half-time in dogs), it may be given by repeated injection or continuous infusion to maintain total IV anesthesia without significantly prolonging recovery.

Propofol has also been used concurrently with inhaled anesthetic agents (partial IV anesthesia). Analgesic drugs (eg, opioids, α₂ agents) are recommended to reduce dose and/or provide analgesia when use is extended to painful procedures.

Propofol is metabolized and redistributed by the liver and  extrahepatic sites, resulting in an ultrashort duration of action. The effective clinical duration of action during which a patient can be manipulated is typically <10 minutes. Complete recovery to ambulation occurs within 20 minutes (dogs) or 30 minutes (cats) after an anesthesia induction dose and is rapid, smooth, and excitement free. These properties also make propofol a good choice in patients with underdeveloped (eg, kittens, puppies) or impaired (eg, geriatric patients, those with a portacaval shunt) liver function. Puppy viability after cesarean section is reportedly better following the dam’s anesthesia induction with propofol than with other injectable induction agents.

Propofol is considered appropriate for patients with CNS disease, including refractory seizures and raised intracranial pressure, as long as rises in CO₂ tension are minimized. The effects on intraocular pressure are more variable and potentially influenced by other drugs and changes in CO₂ tension. Propofol mediates CNS actions by facilitating inhibitory transmission through postsynaptic activation of the GABA-a receptor chloride complex. It also inhibits NMDA subtype of glutamate receptor, slow calcium channels, and voltage-gated sodium channels.

Disadvantages & Adverse Effects

Some animals (7.5% of unpremedicated dogs) may withdraw their limb in response to propofol administration (presumably from a burning or painful sensation), but peri-vascular injection does not cause a local inflammatory reaction. An animal may show focal twitches or muscle fasciculations, which do not appear harmful but can be disruptive, especially if localized to the surgical site.

Cardiovascular depression may be observed when propofol is administered as an IV bolus. This is more likely in volume-depleted patients and those with underlying cardiovascular disease. Arterial hypotension, the most common cardiovascular effect reported, primarily results from a decrease in systemic vascular resistance, although negative inotropic effects have also been reported. Slow administration of the drug and prior administration of IV fluids (5–10 mL/kg balanced electrolyte solution over ≤5–10 minutes) can help reduce these effects. However, in certain patients (eg, those with significant mitral regurgitation or heart failure), fluid administration at this rate may be inappropriate and could preclude propofol use. Respiratory depression to the point of the apnea is the most common effect reported after administration and may be minimized by slow administration.

While propofol may be used repeatedly or by infusion in dogs, cats respond less predictably, presumably from hepatic enzyme saturation (limited ability to glucuronidate). Prolonged recoveries following propofol infusion, Heinz body anemia, general malaise, anorexia, and diarrhea have been reported with sequential daily administration in cats. Recent reports suggest that the magnitude of some of these changes may be dose related. Other considerations with the macroemulsion formulation include the potential to exacerbate hyperlipidemia (increase triglycerides) in certain disease states. In addition to life-threatening sepsis possibly resulting from microbial contamination of propofol, an increase in the incidence of wound infections has been reported with propofol use in dogs. These findings may have been confounded by the methodology for administration and storage of the preservative-free intralipid compound.

Drug Interactions

As mentioned, propofol is commonly used with IV fluids and adjunct drugs (eg, α2 agonists, benzodiazepines, opioids). Combinations of ketamine and propofol are also used for anesthesia induction. While concurrent use of these drugs may reduce the dose requirement of propofol, combinations may increase the incidence of adverse effects. Cardiovascular effects tend to vary and should be weighed in patients with cardiovascular disease; bradycardia with concurrent use of opioids is a possible effect but easily mitigated by administration of an anticholinergic.

Advantages

Propofol offers bronchodilation, which may be useful in asthmatic patients and has no detrimental effects on mucociliary function. Its effects on splenic size are either better or no worse than other contemporary induction agents. It may be used to maintain anesthesia in patients with malignant hyperthermia as it doesn’t trigger this syndrome. It may also be considered the anesthetic-induction agent of choice in healthy greyhounds. Propofol is reported to have antiemetic benefits in recovery in humans.

Economic Impact

Although the cost of propofol is more than the most common alternative (ketamine–diazepam), it is likely that the drug costs are somewhat offset by improved recovery time and quality. Because of the advantages and generally manageable disadvantages, propofol is rapidly becoming the anesthetic induction agent of choice for healthy dogs and cats.

Consider This

Propofol is not considered an analgesic drug; it does, however, have the potential to cause adverse reactions in animals that are allergic to components of the emulsion (eg, soy, peanuts, egg protein). The volume of drug necessary for anesthesia induction is larger than required for other common anesthetic drug combinations (eg, ketamine–diazepam), which may be of practical consideration if an IV catheter has not been placed. While generally not considered cost prohibitive, an equivalent dose of propofol is more expensive than a combination of ketamine and diazepam. Recently, propofol has come under scrutiny for its potential as a drug of diversion and abuse with reports of both accidental overdose and intentional suicide in humans. This has led the US Drug Enforcement Agency to consider whether to assign it a scheduled drug designation.