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INHALATIONAL ANAESTHETICS Dr. Shaik Nawaz Ahmed, Assistant professor, Dept. of anaesthesia, RIMS, KADAPA

Inhalational Anaesthetics : 

Inhalational Anaesthetics Inhalational anesthesia refers to the delivery of gases or vapors to the respiratory system to produce anesthesia

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Ether trilene Methoxyflurane Cyclopropane chloroform Nitrous oxide Xenon Halothane Enflurane Isoflurane Sevoflurane Desflurane

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WORLD ANAESTHESIA DAY 16TH OCT 1846 W.T.G.MORTON John collin warren Gilbert Abortt

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Structural activity-relationship 2-chloro,bromo 1-trifluro ethane. Methyl –isopropyl ether. 2-fluro,1-trifluro methyl ethyl ether. 2-chloro 1-trifluro methyl-ethyl ether. 1-chloro ,fluro 2-difluro methyl-ethyl ether.

Match the following : 

Match the following d c a b Halothane Sevoflurane Isoflurane Desflurane

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The main target of inhalation anesthetics is the brain.

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Uptake and distribution of inhalational agents Alveolar ventilation Cardiac output MAC Blood-gas partition co-efficient Concentration effect Second gas effect Diffusion hypoxia

MAC : 

Minimum Alveolar Concentration = MAC. 1 MAC is the Minimum Alveolar Concentration at which 50% of humans have no response (movement) to surgical stimulus (skin incision). MACawake is the alveolar concentration when 50% of persons will awake to vocal stimulus. Anesthetic potency is measured in MAC MAC is consistent within a species and between species. MAC is different for each inhaled agent. MAC

Which of following is correct sequence of potency? : 

Which of following is correct sequence of potency? A)methoxy-flurane > enflurane > halothane > sevoflurane B)sevoflurane >methoxy-flurane > halothane > enlurane C)methoxy-flurane > halothane > enflurane > sevoflurane D)halothane > enlurane > sevolurane > methoxy-flurane.

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Factors that do not effect MAC are --- Sex-male or female Thyroid disease.

MAC is altered by all except : 

MAC is altered by all except A)hypernatrimia. B)anemia. C)alcoholism. D)male sex. MAC is altered by all except A)pregnancy. B)thyroid disease C)hypomagnesimia. D)old male

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Two important characteristics of Inhalational anesthetics which govern the anesthesia are : Solubility in the fat (oil : gas partition co-efficient) Solubility in the blood (blood : gas partition co-efficient)

oil : gas partition co-efficient : 

oil : gas partition co-efficient It indicates the amount of gas that is soluble in oil phase. It a measure of lipid solubility of anaesthetic. It a measure of anaesthetic potency.

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Meyer – Overton Rule Anesthetic potency correlates with lipid solubility Holds true across species Lipid solubility is measured by oil/gas partition coefficient.

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0.8 1.4 220

Blood – gas partition co-efficient : 

It is a measure of solubility in the blood. It determines the rate of induction and recovery of Inhalational anesthetics. Lower the blood : gas co-efficient faster the induction and recovery – Nitrous oxide. Higher the blood : gas co-efficient slower induction and recovery – Halothane. Blood – gas partition co-efficient

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Second Gas Effect Second Gas Effect – addition of a second more soluble gas (usually N2O) increases the rate of uptake Korman B, Mapleson WW, BJA 1997; 78:618 Concentrating effect Second gas effect

Diffusion hypoxia : 

Diffusion hypoxia Also called as fink effect. N2O N2- 79% O2-21% O2-21% N2- 79% N2O O2-16% N2-70% N2O-14% ALVEOLI PULMONARY CAPILLARY

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PULMONARY CAPILLARY ALVEOLI O2-100% O2-100% N2O O2-86% O2-86% N2O-14% N2O

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Nitrous oxide N2O discovered by joseph pristley. Anaesthetic property was demonstrated by sir humphry davy and coined the term laughing gas. 1st public demonstration of anaesthesia – john quincy culton with N20 N2O is a liquid gas . Colour coding = french blue. Other liquid gas is cyclopropane – comes in orange cylinder. Gas cylinders are made of molybdenum steel. Blood gas partition coeficient is 0.47. MAC is 104% Pin index is 3;5

Entonox : 

Entonox 50% N2O + 50% O2 Colour coding = blue body with blue &white quarters. Pin index = 7 Poyinting effect: normally N2O is liquid at 2400 psig. But If N2O is mixed with O2 it remains in gaseous state called poyinting efect. Use: 1)labour analgesia. 2)field analgesia(wars)

Contra-indications to N2O : 

35 times more soluble in blood than nitrogen, N2 so fills and expands any air-containing cavities: air embolism pneumothorax intracranial air lung cysts intraocular air bubbles tympanoplasty endotracheal tube cuff (monitor and reduce pressure periodically) may exacerbate pulmonary hypertension Contra-indications to N2O

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Toxicities – Nitrous Oxide Hematologic: N2O antagonizes B12 metabolism inhibition of methionine-synthetase Decreased DNA production RBC production depressed post a 2 h N2O exposure ca. 12 later Leukocyte production depressed if > 12 h exposure Megoloblastic anemia. Aplasia in bone marrow Neurologic Long term exposure to N2O (vets, dentists and assistants) is hypothesized to result in neurologic disease similar to B12 deficiency

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Toxicities – Nitrous Oxide Reproduction Increased miscarriage rate in pregnant patients given GA Related to underlying medical condition responsible for need for surgery Low birth rate Getting and staying pregnant (veterinary and dental workers less for OR personnel) Teratogenicity No evidence that the halogenated agents N2O is suspect risk but not proven in human studies Carcinogenicity OR, dental and vet personnel have increased rates of cancer (1.3-1.9 increase in rate in dental workers) But studies have been negative for AA as cause

Halothane : 

Halothane Amber colored bottled – red colour coding Thymol preservative. Pleasant smell , non-irritant, bronco-dilatation, potent to induce in single puff make it best for paediatric induction. Agent of choice for asthamatics. MAC is 0.74%, B:G p co-ef.- 2.4. 2-chloro,bromo 1-trifluro ethane.

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Toxicity Heart :- most arrythmogenic agent. Sensitises heart to catacolamines. maximum decrease in B.P,S.V.R,C.O.bradycardia. Uterus:- Atony of uterus-disadv-postpartum hemorage. adv- manual removal retained placenta. Halothane shakes- post op shivering. Malignant hyperthermia:- massater spasm-rabdomyolysis-ARF-death. calcium-rynodyne receptors. Rx dantrolene sodium.

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Halothane - Hepatic Toxicity All inhaled AA can cause hepatic injury in animal studies All inhaled AA have immunohistochemical evidence of binding to hepatocytes Thought that Trifluoroacetic acid metabolites are root cause Njoku, Anest Analg 1997; 84:173. Exception : sevolurane – it is metabolised to he So no hepatitis

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Normal liver Halothane hepatitis Avoid halothane repeat exposure with in 3 months.

Contraindications/Precautions : 

Contraindications/Precautions Malignant hyperthermia. susceptibility unexplained liver dysfunction after previous halothane exposure intracranial mass lesion hypovolemia aortic stenosis pheochromocytoma with aminophylline has been associated with severe ventricular dysrhythmias

Enflurane : 

Enflurane 1-chloro ,fluro 2-difluro methyl-ethyl ether. Epileptogenic inhalational agent is enlurane. contraindications/Precautions malignant hyperthermia susceptibility preexisting kidney disease seizure disorder intracranial hypertension isoniazid enhances enflurane defluorination

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Isoflurane 2-chloro 1-trifluro methyl-ethyl ether. MAC is 1.17 % & B:G p co-ef is 1.17. Only agent that preserves baroreceptor reflex –isof. So that relex tachycardia occurs in response to decrease B.P mantaining cardiac output. Agent of choice for cardiac anaesthesia is isof.

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Agent that cause coroanary steal – isof. Agent of choice for controlled hypotension. Agent that causes minimal increase in intracranial tension is isof. Agent of choice for nueroanaesthesia.

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Desflurane 2-fluro,1-trifluro methyl ethyl ether. Agent that boils at room temperature(22.8*c)-DF. Agent of choice for day care (fastest induction)- DF. Agent of choice for geriatric (old) patients – DF. Agent of choice for hepatic failure Agent of choice for renal failure

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Carbonmonoxide toxicity All anesthetic agents react with soda lime to produce CO CO is toxic and binds to Hgb in preference to oxygen Des > enfl >>> iso > sevo >halo Risk Factors Dryness of soda lime Temperature of soda lime Fi(agent) Barylime produces more than soda lime.

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Sevoflurane Methyl –isopropyl ether. Pleasant smell , non irritant and bronchodilatation makes it agent of choice for paediaric anaesthesia. 2nd agent of choice for Neuro anaesthesia. Cardiac anaesthesia . asthamatics

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Sevoflurane and Compound A Sevoflurane reacts with soda lime used in anesthetic circuit to form “compound A” compound A is renal toxin. Agents that should not be given with sodalime. 1)trielene.(trichlor ethylene) 2)sevolurane. 3)desflurane

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Fluoride Nephrotoxicty F- is nephrotoxic F- is a byproduct of metabolism in liver and kidney Fluoride nephrotoxicity [F-] = 50 mol/l F- opposes ADH leading to polyuria methoxyflurane 2.5 MAC-hours (no longer used) enflurane 9.6 MAC-hours Methoxy > sevo >>> iso >des Results in potentially permanent renal injury Less of a problem with modern anesthetics


XENON Most ideal inhalational agent. Blood gas partition co-efficient is 0.14. least of all .least soluble. so fastest induction and fastest recovery. MAC is 70% so can be given with 30%O2. Most cardiostable. No metabolism in body –least side effects non tertogenic. Non inflamble,do not deplete ozone layer. Disadvantages = costly, needs special equipment for delivary, bronchospasm.

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Which of the following is not true about xenon anaesthesia ? a. non explosive b. minimal cardiovascular side effects c. slow induction and slow recovery d. low blood gas solubility

Review : 


Ether : 

Ether 1st public demonstration – 16th oct 1986 – w.t.g.morton. Complete anaesthetic agent - ether. Agent with max.muscle relaxation- ether. Safest anaeshtetic in untrained hands – ether. Only inhalational agent that stimulates respiration –ehter. Only inhalational agent that preserves cilliary funtion – ehter. Agent with highest incidence of nausea &vomiting – ether.

Methoxy-flurane : 

Methoxy-flurane Most potent inhalational agent is M-F(mac-0.16%). Slowest induction and recovery is M-F(b:g – 15). Most nephro-toxic agent – M-F (high output renal failure,highest fluride toxicity). Cyclopropane Most inflamable & explosive agent – Cp. Liquid gas-Orange cylinder. Cyclopropane shock.

Trichloroethylene (trielene) : 

Trichloroethylene (trielene) Most potent analgesic agent - tcl. 2-xenon 3-N2O. Reaction with sodalime :- dichloroacetylene – neurotoxic- V, VII. phosgene - pulmonary toxicity(ARDS) CHLOROFORM 1st agent used for lobour analgesia. Cardiotoxic- death due to ventricular fibrillation. Hepatotoxic. Profound hyperglycemia.

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That’s all. Thanks for listening

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