Intravenous anaesthetic agents

• Intravenous anaesthetic agents


  Drugs that, when given intravenously in an appropriate dose, cause a rapid loss of consciousness in one arm-brain circulation
• Uses of intravenous anaesthetic agents

  • Induction of anaesthesia
  • Maintenance of anaesthesia
  • Sedation (Regional Anaesthesia, ICU, Short procedure)
  • Treatment of some medical conditions (status epilepticus)
• The concept of intravenous anaesthesia was born


  1932
• Hexobarbitone


  The first rapidly acting intravenous drug
• Sodium thiopentone


  Marked the advent of modern intravenous anesthesia
• Chlordiazepoxide (Librium)


  First clinically useful benzodiazepine, introduced in 1960
• Diazepam


  Introduced in 1963
• Midazolam


  Introduced in 1978
• Ketamine


  Introduced in 1966
• Etomidate


  Introduced in 1973
• Propofol


  Introduced clinically in 1977
• Pharmacology of IV induction drugs

  1. Drug binds to plasma proteins

  2. Unbound drug passes to cerebral circulation

  3. Drug passes from blood into brain

  4. Secondary tissue uptake causes plasma concentration to fall
• Ideal IV induction drug

  • Water soluble & stable in solution
  • Stable on exposure to light
  • Long shelf life
  • No pain on intravenous injection
  • Painful when injected into an artery
  • Non-irritant when injected subcutaneously
  • Low incidence of thrombophlebitis
  • Cheap
  • Rapid onset in one arm-brain circulation time
  • Rapid redistribution to vessel rich tissue
  • Rapid clearance and metabolism
  • No active metabolites
  • High therapeutic ratio
  • Minimal cardiovascular and respiratory effects
  • No histamine release/hypersensitivity reactions
  • No emetic effects
  • No involuntary movements
  • No emergence nightmares
  • No hang over effect
  • No adrenocortical suppression
  • Safe to use in porphyria
• Classification of intravenous anaesthetic agents

  • Barbiturates (Sodium thiopentone, methohexitone, pentobarbital)
  • Phenols (Propofol)
  • Imidazoles (Etomidate)
  • Phencyclidines (Ketamine)
  • Benzodiazepines (Diazepam, midazolam, flunitrazepam)
• Sodium thiopental


  A barbiturate, supplied as a hygroscopic pale yellow powder
• Reconstitution of sodium thiopental

  1. Ampoules contain 500mg of sodium thiopental with 6% sodium carbonate

  2. Reconstituted with 20ml of water yields a 2.5% solution (25mg/ml) with a pH of 10.8
• Dose of sodium thiopental

  1. 5mg/kg produces a smooth onset of hypnosis with good definitive endpoints within 30 seconds of intravenous injection
• Sodium thiopental


  • 65-85% protein bound in plasma
  • Metabolism is slow and occurs in the liver
  • Excretion of metabolites occurs mainly in the urine
  • Metabolism follows zero order kinetics with repeated doses or infusions
• Methohexitone


  An oxybarbiturate, a white crystalline powder mixed with anhydrous sodium carbonate
• Methohexitone


  • 70-80% bound to plasma protein
  • Less lipid soluble than thiopentone, smaller volume of distribution
  • Fast elimination half life of 1-2 hrs (thiopentone 3.5-21 hrs)
• Propofol


  A short-acting general anaesthetic drug, presented as a 1 or 2% aqueous emulsion
• No ideal intravenous anaesthetic agent is available
• Propofol


  2,6 di-isopropylphenol
• Propofol


  • Usually presented as a 1 or 2% aqueous emulsion containing soya oil, egg phosphatide and glycerol
  • Isotonic to plasma and has a pH of 7.0 - 8.5
  • Can cause pain on injection into small veins
• Propofol


  Short-acting general anaesthetic drug, with an onset of action of approximately 30 seconds
• Propofol administration


  1. Titrate against patient response until onset of anaesthesia

  2. Best endpoint is loss of verbal contact with patient
• Propofol

  • Causes the most marked fall in blood pressure of all the induction drugs
  • Acts on the respiratory centre to cause respiratory depression, usually resulting in a period of apnoea
  • Markedly reduces airway and pharyngeal reflexes, making it ideal for use with the laryngeal mask
• Propofol has been associated with epileptiform movements, but is anticonvulsant in normal doses
• Propofol has been shown to reduce cerebral blood flow, metabolic rate and intra-cranial pressure
• Propofol infusion

  • Used commonly to provide sedation for adult patients undergoing minor procedures and on the intensive care unit
  • The most commonly used drug to provide total intravenous anaesthesia, TIVA
• Propofol infusion is contraindicated for sedation in children due to concerns regarding its safety
• Propofol infusion syndrome

  Affected children developing metabolic acidosis, lipidaemia, cardiac arrhythmias and an increased mortality
• Etomidate

  An imidazole ester, usually presented as a lipid emulsion or as a clear solution containing propylene glycol
• Etomidate

  • Pain on injection is common and there is a high rate of thrombophlebitis in the post operative period
  • Induction of anaesthesia can be accompanied by involuntary movements which may be mistaken for generalized seizure activity
  • Recovery is frequently unpleasant and accompanied by nausea and vomiting
• Etomidate


  • Rapidly metabolized by hepatic and plasma esterases to yield inactive metabolites
  • Causes the least cardiovascular depression of the IV anaesthetic drugs, with only a small reduction in the cardiac output and blood pressure
• Etomidate causes transient apnoea, though less so than other drugs, and can cause cough or hiccups
• Etomidate inhibits 11-β-hydroxylase, an enzyme important in adrenal steroid production, blocking the normal stress-induced increase in adrenal cortisol production for 4-8 hours, and up to 24 hours in elderly and debilitated patients
• Ketamine


  A derivative of phencyclidine, a dissociative drug formerly used as an anaesthetic agent, which exhibited hallucinogenic and neurotoxic effects
• Dissociative drug


  Reduces signals to the conscious mind from other parts of the brain, typically the senses
• Ketamine


  • Has hypnotic, analgesic and local anaesthetic properties
  • Its effects are mediated primarily by noncompetitive antagonism at the N-methyl-D-aspartate (NMDA) receptor in the brain and spinal cord