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Ketamine

Ketamine is a well established useful drug in anaesthesia. In this article, we outline its role as an adjunct to TIVA.,
Structure of ketamine. It is a stereoisomer: A.  S(+)-ketamine;  B.  R(-)-ketamine.

Ketamine

Ketamine is a phencyclidine derivative that produces a state of dissociative anaesthesia. It has strong amnesic and analgesic properties and can have an important role in preventive analgesia and improving patient mood after surgery.

It acts at multiple receptor systems (such as the µ-opioid receptor and the HCN1 pacemaker cell), but its main powerful analgesic effects are as a non-competitive antagonist of the NMDA receptor. This is an excitatory ionotropic glutamate receptor present in the spinal cord and the brain. The addition of ketamine to TIVA will reduce propofol requirements by 20-40%. For longer procedures, we recommended discontinuing the infusion or repeat doses 60 minutes prior to completion of surgery to avoid delays in recovery. We strongly recommend this adjunct for major surgery.

Uses:

Sedation, premedication, analgesia and anaesthesia. Produces dose-dependent sedation, anxiolysis and analgesia with no respiratory depression and good cardiovascular stability. Recently the US FDA has approved its use as an antidepressant.

Preparations:

Usually presented as a racemic mixture of R(-) and S (+). Clear, colourless solution 10, 50 or 100 mg/ml. S-ketamine is available in some countries and has supposedly fewer psychomimetic effects.

Actions:

  • Sympathetic nervous system stimulation: slight increase in circulating levels of catecholamines
    • Increases HR, BP, CO
  • NMDA antagonist
  • Agonist effects on mu-opioid, cholinergic, HCN-1 and adenosine receptors
  • Can induce hallucinations / vivid dreams

Benefits:

  • Analgesic and anaesthetic sparing effect
  • Decreased risk of hyperalgesia, allodynia and tolerance
  • Does not cause respiratory depression and laryngeal reflexes preserved
  • Possible neuroprotection

Dose:

  • Low dose as an adjunct to anaesthesia for it’s analgesic effect
  • IV loading doses of 0.1 – 1 mg/kg have been recommended / used
  • +/- infusion 0.1-0.2mg/kg/hr or repeat doses 0.1 – 0.2 mg/kg at one hour intervals

Onset:

45-60 seconds IV with a peak effect at 1-5 minutes

Route:

  • Intravenous bolus and infusion
  • Subcutaneous and intramuscular
  • Oral
  • Intranasal
  • Sublingual and Rectal
  • Epidural (again, this is not recommended by use but has been used)

Kinetics:

  • Half-life ~ 2.5-3 hours
  • Bi-exponential reduction in plasma concentration
    • Distribution across lipid membranes
    • Hepatic metabolism
  • Low plasma protein binding ~ 25%
  • Metabolized by the liver to an active metabolite (norketamine).
  • Excreted in the urine

Caution:

  • Increases myocardial oxygen demand slightly but this is seldom a problem
  • Increased postoperative delirium, +/- PONV (opioid-sparing can reduce PONV)
  • Increased salivation
  • Processed EEG readings (e.g. BIS number) will increase and become unreliable

Neuropsychiatric adverse events may occur but this is uncommon at the low adjunct doses. Patients may appear a bit “spaced out” in recovery but don’t seem to be bothered by this on follow up. Nystagmus is commonly observed after acute administration.

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Introduction to Using Total Intravenous Anaesthesia (TIVA)

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