PROPOFOL

PRESENTED BY OKECH MICHAEL

MODULATOR: Sr. ELLEN
KIU FORT PORTAL SITE
18/08/25
CLASS
• Type: Short-acting intravenous general anaesthetic
(hypnotic agent)
• Chemical class: Alkylphenol derivative
• Supplied as a sterile, oil-in-water emulsion
containing soybean oil, glycerol, egg lecithin
• Highly lipophilic and insoluble in water.
• A history story of egg allergy does not necessarily
contraindicate the use of propofol because most
egg allergies involve a reaction to egg white (egg
albumin), whereas egg lecithin is extracted from
egg yolk.
• Pain during injection can be decreased by prior
injection of lidocaine
• Propofol formulations can support the growth of
bacteria, so sterile technique must be observed in
preparation and handling.
• Propofol should be administered within 6 hours of
opening the [Link] and death have been
linked to contaminated propofol preparations.
• Current formulations of propofol contain 0.005%
disodium edetate or 0.025% sodium metabisulfite
to help retard the rate of growth of microorganisms
• However, these additives do not render the
product “antimicrobially preserved”
• Appears as a white liquid (“milk of anaesthesia”)
• Onset: ~30–60 seconds
• Duration (single bolus): ~3–10 minutes due to rapid
redistribution
Mechanism of Action
• Propofol induction of general anesthesia involves
facilitation of inhibitory neurotransmission
mediated by GABA A receptor binding.
• Propofol allosterically increases binding affinity of
GABA for the GABA A receptor.
• This receptor is coupled to a chloride channel, and
activation of the receptor leads to
hyperpolarization of the nerve membrane.
• Propofol (like most general anesthetics) binds
multiple ion channels and receptors.
• Propofol actions are not reversed by the specific
benzodiazepine antagonist flumazenil
Metabolism
• Primarily in the liver via conjugation to inactive
metabolites
• The clearance of propofol exceeds hepatic blood
flow, implying the existence of extrahepatic
metabolism.
• This exceptionally high clearance rate contributes
to relatively rapid recovery after continuous
infusions.
• Excretion: Mainly via the kidneys as metabolites
(chronic kidney failure does not aff ect clearance of
the parent drug)
PRIS
• Prolonged propofol
infusion has been
associated with
sporadic cases of
lipemia, metabolic
acidosis, and death, the
so-termed propofol
infusion syndrome.
Dose
• Adults:
• Induction: 1.5–2.5 mg/kg IV bolus
• Maintenance: 4–12 mg/kg/h infusion
• Sedation:
• 0.3–4 mg/kg/h
• Paediatrics:
• Induction: 2.5–3.5 mg/kg IV bolus
• Maintenance dosing varies; titrate to effect. Adjust
dose for elderly, debilitated, or hypovolemic
patients to low doses to avoid cardiovascular
Indications

• Rapid induction of GA
• Maintenance of GA
• Neuro monitoring
• Sedation in mechanically ventilated patients where
rapid onset/offset is desired
Absolute Contraindications

• Hypersensitivity to propofol or any component

(soybean oil, egg lecithin, glycerol)
• Severe haemodynamic instability or shock
• Severe cardiac failure
• Disorders of fat metabolism
• Infants under 1 month of age
• History of Propofol Infusion Syndrome (PRIS)
Effects on CVS
• Propofol causes a decrease in arterial blood pressure
due to a drop in systemic vascular resistance
(inhibition of sympathetic vasoconstrictor activity),
preload, and cardiac contractility.
• Hypotension following induction is usually reversed
by the stimulation accompanying laryngoscopy and
intubation.
• Factors associated with propofol-induced
hypotension include large doses, rapid injection,
and old age.
Effect on RS.
• Propofol is a profound respiratory depressant that
usually causes apnea following an induction dose.
• Even when used for conscious sedation in
subanesthetic doses, propofol inhibits hypoxic
ventilatory drive and depresses the normal
response to hypercarbia.
• Although propofol can cause histamine release,
induction with propofol is accompanied by a lower
incidence of wheezing in asthmatic and
nonasthmatic patients compared with
barbiturates or etomidate.
Effect on CNS
• Propofol decreases cerebral blood fl ow and
intracranial pressure.
• In patients with elevated intracranial pressure,
propofol can cause a critical reduction in CPP (<50
mm Hg) unless steps are taken to support mean
arterial blood pressure.
• Propofol and thiopental probably provide a similar
degree of cerebral protection during experimental
focal ischemia.
• Propofol has antipruritic properties and anti-emetic
effects.
• Induction is occasionally accompanied by excitatory
phenomena such as muscle twitching, spontaneous
movement, opisthotonus, or hiccupping.
• Propofol has anticonvulsant properties.
• Propofol may be safely administered to epileptic
patients
• Propofol decreases intraocular pressure.
• Tolerance does not develop after long-term
propofol infusions.
• Propofol is an uncommon agent of physical
dependence or addiction.
• Death may result due to inappropriate use of
propofol by medically untrained individuals to
induce sleep in nonsurgical settings
Drug Reactions
• Metabolised mainly by CYP2B6; also affects CYP3A4
• High protein binding — interactions with other
highly protein-bound drugs (warfarin, phenytoin,
diazepam)
• Potentiates sedative effects of opioids,
benzodiazepines
• May reduce clearance of midazolam when co-
administered
• Dose adjustment may be needed with enzyme
inducers/inhibitors
Drug interactions
• Fentanyl and alfentanil concentrations may be
increased with concomitant administration of
propofol.
• Many clinicians administer a small amount of
midazolam (eg, 30 mcg/kg) prior to induction with
propofol as midazolam can reduce the required
propofol dose by more than 10%.
Side Effects

• Hypotension
• Bradycardia
• Apnoea
• Pain at injection site
• Hypertriglyceridaemia with prolonged infusion
causing pancreatitis.
• Rare: green urine, involuntary movements
Propofol Toxicity
• Signs and Symptoms: • Renal failure (reduced urine
• Unexplained metabolic output)
acidosis • Lactic acidosis with elevated
lactate levels
• Bradyarrhythmias or
asystole • ECG changes (e.g., ST
segment elevation)
• Hypotension unresponsive
• Propofol Infusion Syndrome
to standard treatment
(PRIS):
• Rhabdomyolysis (muscle • Severe metabolic acidosis
weakness, dark urine)
• Cardiac failure or
• Hyperkalaemia arrhythmias
• Hepatomegaly • Rhabdomyolysis
Toxicity Reversal

• No specific antidote
• Stop propofol immediately
• Supportive management:
• Correct acidosis
• Inotropes/vasopressors for cardiovascular collapse
• Renal replacement therapy if needed
References.
• Sahinovic, M. M., Struys, M. M., & Absalom, A. R.
(2018). Clinical pharmacokinetics and
pharmacodynamics of propofol. Clinical
Pharmacokinetics, 57(12), 1539–1558.
• Luo, Y., Zhang, X., Zhou, W., Xu, W., & Yan, M. (2022).
Effects of different injection methods of propofol
anesthesia on the behavior and memory of rats.
iBrain, 8(2), 137–146
• Morgan, G. E., Mikhail, M. S., & Murray, M. J. (2013).
Clinical anesthesiology (5th ed.). McGraw-Hill
Education.