1. Inhaled anesthetics
By: Israa Omar

2. 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.

3. 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.

4. 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

5. 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.

6. 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.

7. 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

8. 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

9. 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.

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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.

16. 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

17. 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.

18. 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

19. 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).

20. 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