Propofol

Propofol is chemically described as 2, 6-diisopropylphenol and has a molecular weight of 178.27.

The structural and molecular formulas are:

.

Available emulsion contains 10 mg/mL of propofol.

Propofol is slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion of pKa 11 that contains

· Soybean oil (100 mg/ml),

· Glycerol (22.5 mg/ml),

· Egg lecithin (12 mg/ml);

· Disodium edetate (0.005%); with sodium hydroxide to adjust pH to 7-8.5. or sodium metabisulphite 0.25%

Once opened it should be used within 6 hours - Available preparation contains either no preservative or some newer preparation contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, for up to 12 hours but as it is not an antimicrobially preserved product under USP standards and can still support the growth of microorganisms. Microbial contamination can lead to fever, infection/sepsis, other life-threatening illness, and/or death. Strict aseptic technique must always be maintained during handling.

Propofol can be used in patients allergic to eggs. (Egg allergies are due to protein, propofol does not contain egg protein it contains egg lecithin.) Propofol infusion may cause hyperlipidemia.

I.V. Injection of propofol is painful (less common in elderly patients).Pain can be decreased by prior injection of lidocaine or by mixing lidocaine with propofol prior to injection (2 mL of 1% lidocaine in 18 mL propofol).

Doses of Intravenous Propofol

Induction of GA	1-2.5 mg/kg IV dose reduced with increasing age
Maintenance of GA	50-150 µg/kg/min IV combined with N2O or an opiate
Sedation	25-75 µg/kg/min IV
Antiemetic	10-20 mg IV, can repeat every 5-10 min or infusion of 10 µg/kg/min

Mechanisms of Action- Facilitation of inhibitory neurotransmission mediated by beta subunit of GABA

· Produces sedation/hypnosis rapidly (within 40 sec) and smoothly with minimal excitation; termination of action is due to redistribution.

· It has anti pruritic and anti emetic property.

· Decreases IOP and systemic vascular resistance;

· Rarely is associated with malignant hyperthermia and histamine release;

· Suppresses cardiac output and respiratory drive.

· During induction there may be muscle twitching, spontaneous movement, opisthotonus, or hiccupping due to subcortical glycine antagonism. This may mimic tonic-clonic seizure although propofol is predominantly anticonvulsant.

Pharmacokinetics

· Rapid rate of distribution - The drug is highly lipophilic and rapidly and extensively distributed. Crosses blood brain barrier and placenta; distributes into breast milk. Protein binding is 95% to 99%. T _½ of rapid distribution is 2 to 4 min. T _½ of slower distribution is 30 to 64 min.

· Metabolism - Liver conjugation to inactive metabolites.

· Elimination - 50% of dose is excreted in the kidney (metabolites). Clearance is 23 to 50 mL/kg/min.

· Onset - Rapid onset, usually within 40 sec from start of injection.

· Duration - 3 to 5 min (single bolus).

· In elderly the dose requirement decreases because of occurrence of higher peak plasma concentrations.

Effects on body Systems

Cardiovascular

1. Propofol decreases arterial blood pressure due to a reduction in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), cardiac contractility, and preload.

2. Hypotension is more than with thiopentone but is usually reversed by the stimulation due to laryngoscopy and intubation.

3. Factors exacerbating the hypotension include large doses, rapid injection, and old age.

4. Aarterial baroreflex response to hypotension is impaired, particularly in conditions of normocarbia or hypocarbia.

5. Might cause vegally mediated bradycardia(less common)

Changes in heart rate and cardiac output are usually transient and insignificant in healthy patients but may be severe enough to lead to asystole, particularly in patients at the extremes of age and patients with impaired ventricular function.

Respiratory

1. Propofol causes profound respiratory depression resulting in apnea following an induction dose.

2. Propofol inhibits hypoxic ventilatory drive and depresses the normal response to hypercarbia.

3. Depression of upper airway reflexes is more than thiopentone.

4. Propofol is better than thiopentone for induction in asthmatics. It causes lower incidence of wheezing in asthmatic and nonasthmatic patients compared with barbiturates or etomidate.

Cerebral

1. Cerebral blood flow and intracranial pressure is reduced by propofol. In patients with raised ICP, propofol can cause a critical reduction in Cerebral Perfusion Pressure (< style="mso-bidi-font-weight:normal">protects brain from focal ischemia.

2. Propofol have anticonvulsant properties (i.e. burst suppression), has been successfully used to terminate status epilepticus, and safely used in epileptic patients.

3. Propofol has antipruritic and antiemetic (at blood propofol concentration 200 ng/mL) properties.

On eye

· Propofol decreases intraocular pressure. Tolerance does not develop after long-term propofol infusions.

Indications and Usage

1. Induction and maintenance of anaesthesia in adults

2. Induction agent of choice for day care surgery (Outpatient anaesthesia).

3. Induction anaesthesia in children at least 3 yr of age; maintenance anaesthesia in children at least 2 mo of age

4. Initiation and maintenance of monitored anaesthesia care sedation in adults

5. Sedation in intubated or respiratory-controlled adult ICU patients.

Adverse Reactions

· Cardiovascular: hypotension, bradycardia, decreased cardiac output; hypertension (especially in children), Myocardial ischemia.

· CNS: Amorous behavior; movement hypotonia; hallucinations; neuropathy; opisthotonus.

· Respiratory - Apnea; respiratory acidosis during weaning.

· Metabolic- Hyperlipidemia.

· Dermatologic: Rash.

· Eye: Conjunctival hyperemia; nystagmus.

· Miscellaneous - Asthenia; burning, stinging, or pain at injection site; fever.

Propofol infusion syndrome is a rare Complication with Potentially Fatal Results

1. It is associated with high doses and long-term use of propofol.(>4mg/kg/hr for more than 24 hours or infusion more than 48 hours)

2. More common in children. Critically ill patients receiving catecholamines, glucocorticoids are at high risk.

3. Severe metabolic acidosis, rhabdomyolysis, hyperkalemia, hypertriglyceridemia, renal failure, hepatomegaly and cardiovascular collapse are key features.

4. Treatment – Supportive. Early recognition of the syndrome and discontinuation of the propofol infusion reduces morbidity and mortality.