Inhaled anesthetics By: Israa Omar

Classification / pharmacokinetics The agents currently used in clinical practice are nitrous oxide and several easily vaporized liquid halogenated hydrocarbons, including Halothane, Desflurane, Enflurane, Isoflurane and Methoxyflurane They administered as gases; their partial pressure in the inhaled air or in blood or in tissue is the measure of their concentration.

Classification / pharmacokinetics Because the standard pressure of total inhaled mixture is atmospheric pressure(760 mm Hg at sea level), the partial pressure may also expressed in percentage. Thus 50% nitrous oxide in the inhaled air would have 380 mm Hg.

Theories for Mechanism of Action Theory #1 Gas movement into lipid membrane disrupting ion channels and action potential propagation Theory #2 Binding theory = anesthetics bind to hydrophobic portion of the ion channel Theory #3 Neuromodulator theory = anesthetics bind to cell-surface receptors. increased Cl- flux (possible GABA mediation

Factors affect the speed of induction of inhaled anesthetics Solubility: the more the drug equilibrates with the blood, the more quickly the drug passes in to the brain to produce effect. This means the induction will be slower with more lipid soluble gases and faster with less soluble ones.

Factors affect the speed of induction of inhaled anesthetics For a given concentration of 2 gases in inspired air, it will take much longer time with halothane than nitrous oxide for the blood partial pressure to rise to the same partial pressure as in the alveoli. Because the concentration in the brain can rise no faster than the blood, the onset will be slower with halothane than with nitrous oxide.

Factors affect the speed of induction of inhaled anesthetics Inspired gas partial pressure: A high partial pressure of the gas in the lungs results in more rapid achievement of anesthetic levels in the blood. Ventilation rate: The greater the ventilation, the more rapid is the rise in the alveolar and blood partial pressure of the agent and the onset of anesthesia

Factors affect the speed of induction of inhaled anesthetics Pulmonary blood flow: At high pulmonary blood flows, the gas partial pressure rises at slower rate; thus, the speed of onset of anesthesia is reduced. At low flow rates, onset is faster. In case of circulatory shock

Elimination Anesthesia is terminated by redistribution of the drug from the brain to the blood and elimination of the drug through the lung. The rate of recovery from anesthesia using agent with low blood: gas is faster than that with high blood solubility Desflurane and sevoflurane are characterized by recovery times that are considerably shorter than is the case with older agent.

Elimination Halothane and Methoxyflurane are metabolized by liver to significant extent This could play a role in potential toxicity of these anesthetics in case of liver disease

Minimum alveolar concentration MAC of anesthetic measures potency of anesthetic vapour. High MAC means low potency Defined as the concentration of anesthetic that prevents movement induced by a painful stimulus in 50 % of subjects. Each agent has a defined MAC but this value may vary among patients depending on age, cardiovascular status, and use of adjuvant drugs

Minimum alveolar concentration Estimation of MAC value suggest a relativly “steep” dose-response relationship for inhaled anesthetics MAC for infant and elderly are lower than that for young adults When several anesthetics are used simultaneously, their MAC values are additive

Effects of inhaled anesthetics CNS effects: Reduction of metabolic rate in the brain Increase cerebral blood flow Increase in ICP (intracranial pressure) High concentration of Enflurane may cause changes on EEG and muscle twitching, but this effect is unique to this drug. Although nitrous oxide has low anesthetic potency (high MAC), it exerts marked analgesic and amnesic effect

Effects of inhaled anesthetics Cardiovascular effects: Most of inhaled agents decrease arterial blood pressure moderately. Enflurane and halothane are myocardial depressant that decrease cardiac out put Isoflurane, Desflurane and sevoflurane cause peripheral vasodilatation Nitrous oxide is less likely to lower blood pressure than are other inhaled anesthetics

Effects of inhaled anesthetics Blood flow to the liver and kidney is decreased by most inhaled agents. Inhaled anesthetics depress myocardial function –nitrous oxide least Halothane and to lesser extent Isoflurane, may sensitize the myocardium to the arrhythmogenic effects of catecholeamines.

Effects of inhaled anesthetics Respiratory effects: Increase the rate of respiration They all can cause dose- dependent reduction of tidal volume and minute ventilation; leading to an increase in arterial CO2 tension They can cause reduction of the ventilatory response to hypoxia even at sub-anesthetic concentration

Effects of inhaled anesthetics Nitrous oxide has the smallest effect on respiration Most of inhaled anesthetics are bronchodilators, but Desflurane is a pulmonary irritant and may cause bronchospasm.

Toxicity of inhaled anesthetics Post-operative hepatitis may occur rarely after halothane anesthesia in patients experiencing hypovolemic shock or other severe stress(may be immune mediated or due to formation of reactive metabolite). Fluoride released by metabolism of Methoxyflurane(and possibly Enflurane and sevoflurane) may cause renal insufficiency after prolong anesthesia

Toxicity of inhaled anesthetics Prolonged exposure to nitrous oxide decreases methionine synthase activity and lead to megaloblastic anemia Susceptible patient may develop malignant hyperthermia when anesthetics are used together with neuromuscular blockers(especially succinylcholine).

Focus Points Induction of anesthesia is through use of any of the IV agents (Barbiturates: Thiopental, Opiate: Fentanyl, Benzodiazepines: Midazolam, Dissociative: Ketamine, Others: Propofol, Etomidate and Droperidol) Maintenance of anesthesia is through use of any of the inhalation agents -N2O (70% in oxygen) is not suitable alone - N2O is usually combined with another inhalation agent or with opioids e.g. fentanyl