Chemistry - Propofol is an alkylphenol derivative (2,6 - diisopropylphenol). The commercially available injection is an emulsion containing 100 mg/ml of soybean oil, 22.5 mg/ml of glycerol, and 12 mg/ml of egg lecithin. The emulsion has a pH of 7-8.5. Propofol may also be known as disoprofol .
Storage/Stability/Compatibility - Store propofol injection below 22°C (72°F), but not below 4°C (40°F.); do not refrigerate or freeze. Protect from light. Shake well before using. Do not use if the emulsion has separated. The manufacturer recommends discarding any unused portion at the end of the anesthetic procedure or after 6 hours, whichever occurs sooner.
Compatibility with other agents has not been well established. Propofol is compatible with the commonly used IV solutions (e.g., LRS, D5W) when injected into a running IV line.
Pharmacology - Propofol is a short acting hypnotic unrelated to other general anesthetic agents. Its mechanism of action is not well understood.
In dogs, propofol produces rapid, yet smooth and excitement-free anesthesia induction (in 30-60 seconds) when given slowly IV. Sub-anesthetic dosages will produce sedation, restraint and an unawareness of surroundings. Anesthetic dosages produces unconsciousness.
Propofol’s cardiovascular effects include arterial hypotension, bradycardia, (especially in combination with opiate premedicants) and negative inotropism. It causes significant respiratory depression, particularly with rapid administration or very high dosages. Propofol also decreases intraocular pressure, increases appetite and has antiemetic properties. It does not appear to precipitate malignant hyperthermia and it has little or no analgesic properties.
Uses/Indications - In appropriate patients, propofol may be useful as an induction agent (especially before endotracheal intubation or an inhalant anesthetic); as an anesthetic for outpatient diagnostic or minor procedures (e.g., laceration repair, radiologic procedures, minor dentistry, minor biopsies, endoscopy, etc.). Propofol may be of particular usefulness for use in Greyhounds and in patients with preexisting cardiac dysrhythmias.
In dogs, propofol’s labeled indications are: 1) for induction of anesthesia; 2) for maintenance of anesthesia for up to 20 minutes; 3) for induction of general anesthesia where maintenance is provided inhalant anesthetics.
Pharmacokinetics - After IV administration, propofol rapidly crosses the blood brain barrier and has an onset of action usually within one minute. Duration of action after a single bolus lasts about 2-5 minutes. It is highly bound to plasma proteins (95-99%), crosses the placenta, is highly lipophilic and reportedly enters maternal milk.
Propofol’s short duration of action is principally due to its rapid redistribution from the CNS to other tissues. It is rapidly biotransformed in the liver via glucuronide conjugation to inactive metabolites which are then excreted primarily by the kidneys. Because cat’s do not glucuronidate as well as dogs or humans, this may help explain their problems with consecutive day administration (see Adverse Effects below).
There are limited data available on propofol’s pharmacokinetic parameters in dogs. The steady state volume of distribution is >3L/kg, elimination half life is about 1.4 hours and clearance is about 50 ml/kg/min.
Contraindications/Precautions/Reproductive Safety - Propofol is contraindicated in patients hypersensitive to it or any of component of the product. It should not be used in patients where general anesthesia or sedation are contraindicated. Propofol should only be used in facilities where sufficient monitoring and patient-support capabilities are available.
Because patients who are in shock, under severe stress or have undergone trauma may be overly sensitive to the cardiovascular and respiratory depressant effects of propofol, it should be used with caution in these patients. Adequate perfusion should be maintained before and during propofol anesthesia and dosage adjustments may be necessary.
Because propofol is so highly bound to plasma proteins, patients with hypoproteinemia may be susceptible to untoward effects. Other general anesthetic agents may be a safer choice in these patients.
The benefits of propofol should be weighed against its risks in patients with a history of hyperlipidemia, seizures or anaphylactic reactions. Cat’s with preexisting liver disease may be susceptible to longer recovery times.
Propofol crosses the placenta and its safe use during pregnancy has not been established. High dosages (6 times those recommended) in laboratory animals caused increased maternal death and decreased offspring survival rates after birth.
Adverse Effects/Warnings - Because there is a high incidence of apnea with resultant cyanosis if propofol is given too rapidly, it should be given slowly (25% of the calculated dose every 30 seconds until desired effect).
Propofol has been documented to cause histamine release in some patients and anaphylactoid reactions (rare) have been noted in humans. Propofol has direct myocardial depressant properties and resultant arterial hypotension has been reported.
Occasionally, dogs may exhibit seizure-like symptoms (paddling, opisthotonus, myoclonic twitching) during induction, which if persist, may be treated with intravenous diazepam. Propofol may have both anticonvulsant and seizure-causing properties. It should be used with caution in patients with a history of, or active seizure disorders. However, some clinicians believe that propofol is actually better suited to use in seizure patients or in high seizure-risk procedures (e.g., myelography) than is thiopental.
While propofol is not inexpensive, it should be used in a single-use fashion as it is a good growth medium (contains no preservative) for bacteria.
When used repeatedly (once daily) in cats, increased Heinz body production, slowed recoveries, anorexia, lethargy, malaise, and diarrhea have been noted. Heinz body formation is due to oxidative injury to RBC’s and has been documented in cats with other phenolic compounds as well. Consecutive use in dogs appears to be safe.
Pain upon injection has been reported in humans, but does not appear to be of major significance for dogs or cats. Extravasation of injection is not irritating nor does it cause tissue sloughing.
Overdosage/Acute Toxicity - Overdosages are likely to cause significant respiratory depression and potentially cardiovascular depression. Treatment should consist of propofol discontinuation, artificial ventilation with oxygen, and if necessary, symptomatic and supportive treatment for cardiovascular depression (e.g., intravenous fluids, pressors, anticholinergics, etc.).
Drug Interactions - Propofol used in conjunction with preanesthetic agents (e.g., acepromazine, opiates) may cause increased vasodilation and negative cardiac inotropy. This may be of particular concern in animals with preexisting cardiopulmonary disease, in shock, or suffering from trauma. Propofol-induced bradycardia may be exacerbated in animals receiving opiate premedicants, particularly when anticholinergic agents (e.g., atropine) are not given concurrently. As would be logically expected, increased CNS depressant effects and recovery times may be noted in patients receiving other CNS depressant medications with propofol. Drugs that inhibit the hepatic P-450 enzyme system (e.g., chloramphenicol, cimetidine) or other basic lipophilic drugs (e.g., fentanyl, halothane) may potentially increase the recovery times associated with propofol. Clinical significance is unclear, but in cats it may be of significance.
Dogs & Cats:
a) As a single injection (25% of the calculated dose every 30 seconds until desired effect):
For healthy, unpremedicated animal: 6 mg/kg IV
For healthy, premedicated animal: After tranquilizer (e.g., acepromazine) = 4 mg/kg IV; After sedative (e.g., xylazine, opioids) = 3 mg/kg IV
As a constant infusion:
For sedation only: 0.1 mg/kg/minute
For minor surgery: 0.6 mg/kg/min, or 1 ml (10 mg) per minute per 12-25 kg of body weight (Robinson, Sanderson et al. 1993)
b) 4 - 8 mg/kg IV (Hubbell 1994)
c) 6 mg/kg IV; in healthy animals 25% of the calculated dose is administered every 30 seconds until intubation is possible. After induction, duration of anesthesia is only 2.5 - 9.4 minutes. Maintenance anesthesia obtained using either inhalational agents or a continuous infusion of propofol at approximately 0.4 mg/kg/minute. If anesthesia appears inadequate, a small bolus of 1 mg/kg followed by an increase in the infusion rate by 25%. If infusion is too deep, discontinue infusion until suitable anesthesia level is achieved. An infusion dose of 0.1 mg/kg/min appears to be suitable dose for sedation in the dog. (Ilkiw 1992)
d) As an induction agent for halothane or isoflurane anesthesia: 6.6 mg/kg IV given over 60 seconds to unpredmedicated dogs. Best achieved by early intubation and administration of the inhalant following propofol induction. (Bufalari, Miller et al. 1998)
Monitoring Parameters - 1) Level of anesthesia/CNS effects; 2) Respiratory depression;
3) Cardiovascular status (cardiac rate/rhythm; blood pressure)
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Propofol Injectable 10 mg/ml in 20 ml (single use) amps & vials; Rapinovet® (Schering); PropoFlo ® (Abbott) (Rx). Approved for use in dogs.
Propofol Injection 10 mg/ml in 20 ml ampules and 50 & 100 ml vials for infusion; Diprivan® (Zeneca); (Rx)
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