1. VOLATILE ANESTHETICS
Nurcan Kızılcık
YTUH Anesthesiology Dept.

2. 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

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

4. Pathway for General Anesthetics

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

6. 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.

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

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

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

10. MAC unchanged
Duration of anesthesia
Gender
Hyper-or hypotyroidism

11. 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

12. 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

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

14. 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)

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

16. 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.

17. Contraindications Pneumothorax Pulmonary embolus Pneumocephalus
Bowel obstruction

18. End of the case: Diffusion hypoxia

19. 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.

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

21. 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

22. 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

23. 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/ with succinylcholine to 1/260,000.

24. 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

25. 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-

26. 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

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

28. 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

29. 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

30. Toxicity - Hepatitis
First described with Halothane use.

31. 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

32. 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