Clinical Applications of Ketamine and Anesthesia Flow

Ketamine

• Clinical applications include induction before gaseous anesthesia, rarely used as a sole agent, usually given with xylazine or diazepam
• Ketamine does not produce a true anesthetic state, but induces dissociation from the environment, amnesia, and peripheral analgesia.
• Increases muscle tone
• Provides greater analgesia for somatic or peripheral pain
• Mechanism of action: Acts as an NMDA (N-methyl-D-aspartate) receptor antagonist and sigma agonist. NMDA is an excitatory amino acid mimicking the action of glutamate in the CNS.
• Adverse effects: CNS: raises intracranial pressure alone, but not when combined with benzodiazepine; can cause hallucinatory behavior, delirium, excitement, and purposeless muscle activity.

Sequence of Flow of Anesthetics

• Gas is inhaled and diluted with residual air in the lungs
• Gas is distributed into the alveoli where alveolar gas equilibrates almost immediately with pulmonary blood
• Gas dissolved in the blood is distributed throughout the body: into the interstitial fluid and into the brain

Halothane

• Primarily used to maintain anesthesia following induction with an injectable anesthetic.
• 75% to 80% of inspired halothane is exhaled unchanged, metabolized by cytochrome P450 in the hepatocytes
• Adverse effects:
  • CNS: dose-dependent depression of CNS without significant relaxation, complete paralysis of the thoracic muscles, only the diaphragm functions.
  • Respiratory: jerky diaphragmatic movement, respiration gasping in nature, wide papillary dilatation.
  • Mental blocking: loss of awareness (unconsciousness) and no recall of events at the conscious level (amnesia).
  • Ataraxia: Phenothiazine derivatives; Ketamine
  • Light sleep: Fentanyl-droperidol
  • Delirium: all that produces deep sleep
  • Reflex blocking: minimize autonomic nervous system response to noxious stimuli
  • Blocking undesirable reflexes: Atropine
  • Respiratory, circulatory, and digestive reflexes: Persistent pharyngeal reflex which becomes progressively depressed.

Stages of Anesthesia

• Best recognized when anesthesia is induced by relatively slow-acting drugs such as diethyl ether.
• Ketamine, nitrous oxide, and enflurane do not induce stage III.
• Either they induce stage II only or advance to an increased level of CNS excitation, rather than depression, resulting in myoclonic jerking followed by convulsive seizures.
• Irregular respiration; sometimes breath holding.

Pre-Anesthetic Agents

• Tranquilizers: acepromazine, promazine
• Analgesics: morphine, meperidine
• Anesthetics: Xylazine, ketamine
• Anticholinergic: atropine

Injectable Anesthetics

• Examples: thiopental, alphaxolone, propofol, etomidate, ketamine, tiletamine-zolazepam, methohexital, pentobarbital.
• Thiopental, methohexital, and pentobarbital belong to the barbituric acid group, classified according to either duration of action or chemical substitution on the parent molecule.

Pentobarbital

• Infrequently used for induction.
• Used as a sole agent for procedures.
• Struggling may be seen in the early stages of anesthesia.
• Inadequate dose may cause hyperesthesia.
• Respiratory: transient dose-dependent respiratory depression.

Etomidate

• Clincial applications: sole agent for non-painful procedures, induction prior to gaseous anesthesia, poor fetal transfer.
• Mechanism of action: Produces dose-dependent cortical depression, activates GABA receptors to open chloride channels, analgesia.
• Adverse effects:
  • Cardiovascular: direct depressant effect and indirect stimulatory effect.
  • Respiratory: respiratory depression.
  • Liver: no effect on hepatic function.
  • Renal: no effect on renal function.
  • Skeletal muscle: extreme muscle tone and spontaneous movements.
  • Other: hypersalivation, increased bronchial secretion, increased intraocular pressure.
• Potentiates the action of non-depolarizing neuromuscular drugs.

Tiletamine-Zolazepam

• Clincial applications: administered as the sole agent for short to moderate duration sedation or for induction before gaseous anesthesia.
• Separately, they do not have ideal sedative or anesthetic properties.
• Together, they produce dissociative anesthesia, muscle relaxation, and some analgesia.

Isoflurane

• Clincial applications: most prevalent inhalation anesthetics, agent of choice in critically ill patients.
• It enhances GABA-mediated inhibition of synaptic transmission by opening membrane chloride channels, causing cellular hyperpolarization.
• Adverse effects:
  • CNS: dose-dependent CNS depression.
  • Cardiovascular: increased heart rate, decrease stroke volume, transient fall in cardiac output and arterial blood pressure.
  • Respiratory: respiratory depression.
  • Other: As anesthesia deepens, the pupil constricts rather than dilates.

Tension of Anesthetic Agent

• The tension of an agent dissolved in a liquid refers to the pressure of the agent in gas.
• At any given temperature the mass of gas dissolved in a solution varies directly with its tension.
• The ratio of gas dissolved in solution to its tension is called its solubility coefficient.
• The solubility of anesthetics varies widely, and the quantities of different anesthetics in the solvent are not equal.
• The tension of the anesthetic agent in the brain is maintained when its concentration in the alveoli is kept constant.
• When concentration in the alveoli decreases, the tension in the brain also decreases.
• Minimum alveolar concentration (MAC) of the anesthetic must be maintained.

Drug Interactions

• Potentiates the action of non-depolarizing neuromuscular drugs.