Propofol

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Propofol

• Physical Chemical properties
• Propofol consists of phenol ring is chemically
  described as 2, 6-di-isopropylphenol.

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• The colour of solution is Milky white and is
  available in 1 and 2 concentration.
• The formulation also contains soybean oil, Egg,
  Lecithin glycerol. So injection is painful.
• The propofol injectable emulsion is isotonic and
  has a pH of 4.5-6.4.
• It is preservative free so should be used within
  6hrs after opening the vial because there have
  been death reports following the use of
  contaminated solution of propofol ( as egg
  lecithin is a good media for bacterial growth ).
• To prevent this formulations have disodium
  edetate or sodium metabisulfite as
  antimicrobials.

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• Mechanism of Action
• Specific mechanism is unknown. But it is mainly
  due to GABA medaited.
• Anaesthetic properties
• It is a sedative hypnotic used in the induction
  and maintenance of anesthesia.
• Induction is achieved in one brain arm
  circulation time i.e. 15 seconds. Consciousness
  is regained after 2-8 minutes due to
  redistribution.
• Elimination half life is 2-4 hrs, recovery is
  rapid associated with less hangover than
  thiopentone.
• It has no analgesic property.
• It is not a muscle relaxant.
• Dose 2 mg /kg.

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• Metabolism
• It is chiefly eliminated by hepatic conjugation
  to inactive metabolites which are excreted by the
  kidney.
• Elimination half life is 2-4 hrs ,recovery is
  rapid.
• All metabolic products of propofol are inactive.

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Systemic Effects

• Cardiovascular
• Hypotension produced is significant it also
  impairs baroreceptor response to hypotension.
• Respiratory
• The first respiratory disturbance after a bolus
  dose of propofol is a profound fall in tidal
  volume leading to apnea in many patients. There
  has been no accompanying cough or hiccup and
  otherwise anesthesia is smooth.
• Induces broncho dilatation.
• During sedation, attention must be given to the
  cardiorespiratory effects of propofol.
  Hypotension, apnea, airway obstruction, and/or
  oxygen desaturation can occur, especially with a
  rapid bolus injection.

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• Cerebral
• It also has cerebral protection effect by
  decreasing cerebral oxygen consumption, cerebral
  metabolic rate and intracranial pressure.
• It is also a reliable amnestic agent.
• It can sometimes produce muscle twitching
  myoclonic activity.
• Eye
• Reduces intraocular pressure.
• GIT
• It is anti-emetic
• Immunologic
• It is antipruritic.

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DOSAGE AND ADMINISTRATION

• Healthy Adults Less Than 55 Years of Age 40 mg
  every 10 seconds until induction onset (2 to 2.5
  mg/kg). 
• Elderly, Debilitated, or ASA III/IV Patients 20
  mg every 10 seconds until induction onset (1 to
  1.5 mg/kg). 
• Cardiac Anesthesia 20 mg every 10 seconds until
  induction onset (0.5 to 1.5 mg/kg).  
• Neurosurgical Patients 20 mg every 10 seconds
  until induction onset (1 to 2 mg/kg).  
• Pediatric - healthy, 3 years of age or older 2.5
  to 3.5 mg/kg administered over 20-30 seconds.

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Indications

• Because of its early induction, early smooth
  recovery, inactive metabolites anti emetic
  effects it is,the IV agent of choice for day care
  surgery.
• Along with opioids (alfentanil or remifentanil )
  it is the agent of choice for total intravenous
  anaesthesia (TIVA).
• Propofol injection can be used to produce
  sedation in ICU patients.
• Agent of choice for induction in susceptible
  individuals for malignant hyperthermia.

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Contraindications

• Hypersensitivity to propofol which contains
  soybean oil and egg phoshpolipid
• Obstetrical procedures( Propofol crosses the
  placenta and may be associated with neonatal
  depression )
• Propofol is not recommended for use in nursing
  mothers because propofol has been reported to be
  excreted in human milk, and the effects of oral
  absorption of small amounts of propofol are still
  not known.
• Propofol is not recommended for anesthesia in
  children below the age of 3 years because safety
  and effectiveness have not been established yet.

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Advantages of propofol over thiopentone

• Rapid and smooth recovery.
• Completely eliminated from body in 4 hours so
  patient is ambulatory early.
• Anti-emetic.
• Anti-pruritic.
• Bronchodilator.

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Disadvantages

• Apnea is more profound and longer.
• Hypotension is more severe.
• Injection is painful.
• Solution is less stable (6 hrs).
• Chances of sepsis with contaminated solution is
  high.
• Myoclonic activity.
• Sexual fantasies and hallucination.
• Expensive than thiopentone.
• Allergic reactions in individuals who are
  allergic to egg lecitin.
• Propofol addiction has also been reported.
• Propofol infusion syndrome It is very rare but
  is a lethal complication. Usually seen if
  infusion is continued for more than 48 hrs is
  much more common in children.

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OVERDOSAGE

• If accidental overdosage occurs, propofol
  administration should be discontinued
  immediately.
• Overdosage is likely to cause cardio-respiratory
  depression.
• Respiratory depression should be treated by
  artificial ventilation with oxygen.
  Cardiovascular depression may require
  repositioning of the patient by raising the
  patient's legs, increasing the flow rate of i.v.
  fluids.

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Special Risk Patients

• Use lower induction and maintenance doses in
  elderly, debilitated, and severely ill patients,
  and monitor continuously for sign of hypotension
  or bradycardia.

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Etomidate

• Etomidate is a carboxylated imidazole derivative.
  Etomidate has anesthetic and amnetic properties,
  but has no analgesic properties

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Uses

• Etomidate is commonly used in the emergency
  setting as part of a rapid sequence induction to
  induce anesthesia or for conscious sedation. It
  is often used in this setting since it has a
  rapid onset of action and a low cardiovascular
  risk profile, and therefore is less likely to
  cause a significant drop in blood pressure than
  other induction agents
• It is the agent IV anesthetic agent of choice for
  aneurysm surgery patients with cardiac disease.

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Dosage

• The anaesthetic induction dose for adult humans
  is 0.3 mg/kg intravenously, with a typical dose
  being 20 mg. In common with all induction agents,
  etomidate causes loss of consciousness after one
  arm-brain circulation time.
• At the typical dose, anesthesia is induced for
  about 510 minutes even though the half-life of
  drug metabolism is approximately 75 minutes. This
  is because etomidate is redistributed from the
  plasma to other tissues.

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Metabolism

• Etomidate is highly protein bound in blood plasma
  and is metabolised by hepatic and plasma
  esterases to inactive products with a
  redistribution half-life of 25 minutes and an
  elimination half-life of 6875 minutes.

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Actions and effects

• Etomidate does not cause significant
  cardiovascular or respiratory depression, but may
  cause a brief period of apnea.
• The decrease in cerebral blood flow produced by
  etomidate is approximately the same as that
  produced by thiopental
• Etomidate slightly lowers intracranial pressure
  and it usually causes a moderate decrease in
  intraocular pressure

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Side effects ( disadvantages)

• Adrenocortical suppressioin on long term
  infusion.
• Nausea vomiting. ( 40 )
• Has very high incidence of myoclonus.
• High incidence of thrombophlebitis.
• It can cause vitamin C deficiency platelet
  dysfunction.
• May produce pain on injection
• No analgesia.
• Hiccups are common.

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Contraindications and precautions

• Use of etomidate is not recommended since data
  are insufficient to support its use in
  obstetrics, including cesarean section deliveries
  
• It is not known whether etomidate is distributed
  into breast milk. However, problems in humans
  have not been documented

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• Appropriate studies with etomidate have not been
  performed in children up to 10 years of age .
  Safety and efficacy have not been established.
• Elderly patients are more sensitive to the
  effects of etomidate than are younger patients.
  In addition, geriatric patients are more likely
  to have age-related hepatic function impairment,
  which may require reduction of dosage in patients
  receiving etomidate