VOLATILE ANESTHETICS Nurcan Kızılcık YTUH Anesthesiology Dept.

Learning objectives Pharmacokinetics and systemic effects of volatile anesthetic agents Definition of MAC (minimal alveolar concentration) and the factors that can modify MAC Side effects of volatile anesthetic

Anesthetics are divided into two classes: Inhalation Anesthetics Gases or Vapors Usually Halogenated Intravenous Anesthetics Injections Anesthetics or induction of agents

Pathway for General Anesthetics

Rate of Entry into the Brain: Influence of Blood and Lipid Solubility

MAC (minimal alveolar concentration) A measure of potency 1 MAC; Defined as the alveoler concentration of an inhalational anesthetic at which 50% of patients do not move in response to surgical stimulation.

FACTORS THAT INFLUENCE MAC MAC INCREASED (anesthetic potency decreases) Drugs that increase catecholamines (MAOI, acute amphetamine, cocaine, ephedrine ) hyperthermia Chronic alcoholism hypernatremia

MAC DECREASED ( anesthetic potency increases) Elderly age Metabolic acidosis Hypoxia Hypercarbia Induced hypotension Hypoosmolality Hypothermia Hyponatremia Pregnancy Anemia Acute ethanol intake (intox.) Chronic amphetamines

Local anesthetics Ketamine Opioids Barbiturates Benzodiazepines Lithium Clonidine Cholinesterase inhibitors Hydroxyzine Verapamil

MAC unchanged Duration of anesthesia Gender Hyper-or hypotyroidism

Blood/Gas Partition coeff. MAC Agent [agent] 1 MAC Blood/Gas Partition coeff. Halothane 0.75 % 2.4 Isoflurane 1.46 % 1.4 Sevoflurane 1.80% 0.65 Desflurane 6.60 % 0.42 Nitrous Oxide 104% 0.47

Shared Properties Increase in cerebral blood flow (CBF) and intracranial pressure (ICP) Depression of myocardial activity Rapid shallow breathing pattern Pulmonary bronchodilation Decrease in renal blood flow and GFR Relaxation of skeletal muscle

Nitrous Oxide Prepared by Priestly in 1776 Anesthetic properties described by Davy in 1799 Colorless, odorless, tasteless

Nitrous Oxide Low blood solubility (quick recovery) MAC value is 105% (low potency) Weak anesthetic, powerful analgesic Needs other agents for surgical anesthesia (Most often administered as an adjuvant in combination with other volatile anesthetics or opioid)

Nitrous Oxide Systemic Effects Minimal effects on heart rate and blood pressure May cause myocardial depression in sick patients Little effect on respiration

Nitrous Oxide Side Effects N2O is 35 times more soluble then nitrogen in blood. Its adverse effect is related to its absorption into air- filled cavities and bubbles. Inhalation of 75% nitrous oxide can expand a pneumothorax to double its size in 10 minutes. Accumulation of N2O in the middle ear can diminish hearing postoperatively.

Contraindications Pneumothorax Pulmonary embolus Pneumocephalus Bowel obstruction

End of the case: Diffusion hypoxia

DIFFUSION HYPOXIA This effect is seen in first 5-10 minutes of recovery when large volumes of nitrous oxide is released into the lung. The blood gas solubility of N2O is 0.42 which is less than that of any other inhaled agents. But N2O is more soluble than Nitrogen in blood. Hence blood and body fluids are rich in N2O. At the end of anesthesia, N2O diffuses back into alveoli from blood down to a concentration gradient and this diffusion back is rapid than uptake of Nitrogen from the alveoli by blood. This leads to replacement of all alveoli gases by N2O and subsequent hypoxia.

Nitrous Oxide Side Effects Inhibits methionine synthetase (precursor to DNA synthesis) & vitamin B12 metabolism Dentists, OR personnel, abusers are at risk

Halothane Synthesized in 1956 by Suckling Most potent inhalational anesthetic MAC of 0.75% Efficacious in depressing consciousness Very soluble in blood and adipose tissue

Halothane Systemic Effects Inhibits sympathetic response to painful stimuli Sensitizes myocardium to effects of exogenous catecholamines-- ventricular arrhythmias Depresses myocardium-- lowers BP and slows conduction, mild peripheral vasodilation Decreases respiratory drive-- central response to CO2 and peripheral to O2 Respirations shallow-- atelectasis Depresses protective airway reflexes

Halothane Side Effects “Halothane Hepatitis” -- 1/10,000 cases fever, jaundice, hepatic necrosis, death metabolic breakdown products are hapten-protein conjugates immunologically mediated assault exposure dependent Malignant Hyperthermia- 1/60.000 with succinylcholine to 1/260,000.

Enflurane Developed in 1963 by Terrell, released for use in 1972 Stable, nonflammable liquid MAC 1.68% Metabolism releases fluoride ion-- renal toxicity Epileptiform EEG pattern

Isoflurane İsoflurane is halogenated methyl ethyl ether Cardio-protective It is not suitable for gas induction Coronary vasodilation is a characteristic of isoflurane and in patients with coronary artery disease there has been concern that coronary steal could occur –rare occurence-

Desflurane The fastest of the current anesthetics Low solubility in blood and tissues Causes very rapid induction of and emergence from anesthesia Low residual at the end of the case High cost CNS stimulation (minor) Pollution of environment (minor) It is not suitable for gas induction It has the highest vapor pressure

Sevoflurane Suitable for mask induction Potent bronchodilator Less CNS activation Mildly depresses myocardial contractility SVR and ABP decline, Slightly low solubility

Sevoflurane & Compound A Sevoflurane reacts with CO2 absorbant soda-lime to form “compound A” Compound A is renal toxin Large amounts are produced at low gas flow rates Recommended ≥2 L/min flow rate Little evidence of harm unless Low flows Long exposure Some evidence for changes in markers of damage but not clinically significant

Xenon An inert gas, nonexplosive, NMDA antagonist No metabolism Minimal cardiovascular effects Low blood solubility Rapid induction & recovery Doesn’t trigger malign hyperthermia EXPENSIVE NOT AVAILABLE FOR THE CLINICAL USE YET

Toxicity - Hepatitis First described with Halothane use.

Fluoride Nephrotoxicty F- is a nephrotoxic by product of metabolism in liver and kidney Fluoride nephrotoxicity F- opposes ADH leading to polyuria methoxyflurane 2.5 MAC-hours (no longer used) enflurane 9.6 MAC-hours

Anesthetics and CO All anesthetic agents react with sodalime to produce CO CO is toxic and binds to Hgb in preference to oxygen Desflurane > enflurane >>> isoflurane > sevoflurane >halothane Risk Factors Dryness & Temperature of soda lime Barylime produces more CO than soda lime & removed from the market In general, not clinically significant No deaths reported