Nurcan Kızılcık Sancar YTUH Anesthesiology Dept. VOLATILE ANESTHETICS Nurcan Kızılcık Sancar YTUH Anesthesiology Dept.

Anesthetics are divided into two classes: Inhalation Anesthetics Gasses 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 volatile potency 1 MAC is the concentration necessary to prevent movement in response to painful stimulus in 50% of the patients.

FACTORS THAT INFLUENCE MAC Increased central neurotransmitter levels (MOI, acute amphetamine intake, cocain, ephedrine, levodopa) Hyperthermia Chronic ethanol abuse Hypernatremia INCREASE the Volatile MAC VALUE

DECREASE the Volatile MAC Value OLD age Metabolic acidosis Hypoxia Induced hypotension Decreased central neurotransmitter levels (α-methyldopa, reserpine) α-2 agonists Hypothermia Hyponatremia Lithium Hypoosmolality DECREASE the Volatile MAC Value

DECREASE the Volatile MAC Pregnancy Acute ethanol intake Ketamine Lidocaine Opioids, agonist-antagonist analgesics Barbiturates, Diazepam Hydroxyzin Verapamil Anemia DECREASE the Volatile MAC

MAC Agent [agent] 1 MAC Halothane 0.75 % Isoflurane 1.46 % Sevoflurane 1.80% Desflurane 6.60 % Nitrous Oxide 104%

General Actions of Inhaled Anesthetics Respiration Depressed respiratory depth, increased RR Kidney Decreased renal blood flow, GFR & urine output Hepatic: Decreased blood flow Neuromuscular High concentrations will relax skeletal muscle Prolong the effect of non-depolarizing neuromuscular blockade

Cardiovascular System Decreased arterial blood pressure. Variable effects on heart rate & cardiac output Central Nervous System Increased cerebral blood flow, increased ICP & decreased cerebral metabolic rate (except N2O)

METABOLISM RATE OF THE VOLATILES N2O Halothane Isoflurane Desflurane Sevoflurane 0.004% 15-20% 0.2% <0.1% 5% Least metabolized most metabolized

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

Nitrous Oxide Major difference is low potency MAC value is 105% Weak anesthetic, powerful analgesic Combination with other agents for surgical anesthesia is required Low blood solubility (quick recovery)

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

Nitrous Oxide Side Effects Generally combined with other volatile anesthetics or opioids It tends to diffuse into air containing cavities and air buubles in the blood rapidly For example: If a patient with a 100 ml pneumothorax inhales 50% N2O, the gas content of the pneumothorax expands until it contains 100 mL of air and 100 ml of N2O. N2O diffused into the middle ear can lead to hearing loss postoperatively.

Beginning of the case: Second gas effect When two volatile agents are delivered to the patient simultaneously (N2O & a potent volatile) the uptake, therefore, the alveolar concentration of the volatile anesthetic will be increased due to the high N2O uptake.

At the end of the case: diffusion hypoxia

DIFFUSION HYPOXIA Observed within first 5-10 mins of recovery, when large volumes of N2O is released into the lungs. The blood gas solubility of N2O is very low. It is even more soluble than Nitrogen in blood. At the end of the anesthesia, N2O diffuses back into alveoli from blood down to a concentration gradient and this is even more rapid than the uptake of Nitrogen. Result of the rapid diffuse of pure N2O into the alveoli is 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 Halogen substituted ethane Volatile liquid easily vaporized, stable, and nonflammable

Halothane 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 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 Pungent odor MAC 1.68%

Enflurane Systemic Effects Sensitizes myocardium to effects of exogenous catecholamines– arrhythmias Metabolism 1/10 that of halothane-- does not release hepatotoxic metabolites Metabolism releases fluoride ion-- renal toxicity Epileptiform EEG patterns

Isoflurane İsoflurane is a halogenated methyl ethyl ether Cheap Very soluble – slow emergence Cardio-protective Risk of awareness It is not suitable for volatile anesthesia induction

Coronary vasodilation is a characteristic of isoflurane and in patients with coronary artery disease there has been concerns about the coronary steal ? –experimental-

Desflurane Insoluble Fast on-off Easy to use Loss of potency Faster turnover of OR & PACU Low residual at end of case High cost CNS stimulation (minor) Pollution of environment (minor) Can’t be used for gas induction CO production (not relevant)

Sevoflurane It is suitable for volatile anesthesia induction Potent bronchodilator Less CNS activation Cardio-protective High-cost Solubility Compound A

Toxicity - Hepatitis First described with Halothane use.

complications of surgery. The estimated rate is: 1: 1 000 000 Hepatitis and Pancreatitis are known complications of surgery. The estimated rate is: 1: 1 000 000

Fluoride Nephrotoxicty F- is a nephrotoxic byproduct 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

Potency of renal injury Methoxy > enflur > sevoflur > isoflur >desflur Lead to potentially permanent renal injury

Toxins – Sevoflurane and Compound A Sevoflurane reacts with CO2 absorbant of the anesthetic circuit “soda lime” to form “compound A” fluoromethyl-2-2-difluoro-1-(trifluoromethyl) vinyl ether There are some reports of fire & explosions Compound A is renal toxin Large amounts are produced at low gas flow rates ≥2 L/min flow rate is recommended Little evidence of harm unless Low flows Long exposure

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