MD. DA. DNB., Dip.diab. MD(acu) , DCA, Dip. Software-statistics. Ether to sevoflurane Dr . S. Parthasarathy MD. DA. DNB., Dip.diab. MD(acu) , DCA, Dip. Software-statistics. Ph D ( physiology) Mahatma Gandhi medical college and research institute , puducherry – India

19th century to 21st century

Why this ether to sevo In search of the almighty Or the ideal anaesthetic

The topic in one slide

What is ideal anaesthetic ? Physical Boiling point above ambient temperature Simple apparatus Chemically stable Long shelf-life, compatible with soda-lime, metals and plastics Not inflammable Cheap

What is ideal anaesthetic ? Pharmacodynamic High potency Allows high FiO2 High therapeutic index Analgesic

What is ideal anaesthetic ? Pharmacokinetic Low solubility Rapid onset, rapid offset, adjustable depth Minimal metabolism Predictable in all age groups

What is ideal anaesthetic ? Adverse actions Minimal toxicity Minimal unwanted effects Nausea, vomiting, cardiac arrhythmogenicity No toxicity with chronic low-level exposure of staff

We – rare doctors to use drugs through lungs completely painless induction No IV (intravenous) access needed. Most rapid entry and exit Most efficient choice in patient with difficult IV access. So easily and safely administered by modern anesthesia machines

Ether CH3– O – CH3 Dimethyl ether C2H5 – O -- C2H5 Diethyl ether

WTG morton and his demo

ETHER Blood gas PC – 12 MW = 74.1 Boiling point = 34.6 SVP = 440 MAC = 1.92 Simple safe - used for centuries

Problems with ether It attacks plastic and rubber Vomiting is quite common Inflammable Dense than air Flames along the floor B/G = 12 ??

Simpson and snow Chloroform Snow gave analgesic doses of chloroform on a folded handkerchief. This technique was soon termed chloroform à la reine. Victoria enjoyed the relief from labour pain She wrote in her journal, “Dr. Snow gave that blessed chloroform and the effect was soothing, quieting, and delightful beyond measure.”

Chloroform was OK but Liver and Cardiac toxicity

Ethyl chloride and ethylene Spray Freeze and painless Ethylene – high doses needed – explosive Propylene in steel cylinder produced toxic substances – one was cyclopropane It anaesthetized WHOM ??

Explosion

TRILENE Oh This does not explode But phosgene was produced in sodalime Cannot use

Halogens and alkanes convulsant properties complete halogenation, or complete end-methyl halogenation on alkanes & ethers results in decreased anaesthetic potency and the appearance of convulsant activity the "cutoff effect" increasing homologues of alkane series display cutoff point, beyond which anaesthetic potency sharply decreases

Fluorine No explosion No flammability Resist separation by thermal and chemical means Less toxic The answer was

Fluroxene First flourinated anaesthetic But a metabolite is toxic to animals Suckling created halothane in 1953 Halogenated ethane

Halothane

Advantages least expensive volatile anesthetic agent SVP - 240 B/G = 2.1 O/G = 224 MAC = 0.75

Halothane No flammability Fast induction Sweet smell Thymol needed BUT Thymol needed Uv rays instability Arrhythmia Hepatotoxic Metabolism 20 %

So the search was on and on Methoxyflurane BP = 104 and SVP of 22 B/G = 11 O/G = 950 and hence MAC = 0.16 But metabolism and flouride induced nephro toxicity - dangerous

So came enflurane and isoflurane

Enflurane a nonflammable fluorinated ethyl methyl ether BP = 56 B/G = 1.9 O/G = 97 MAC = 1.6 Scientists came back to ethers to avoid arrythmogenicity

Enflurane Negative inotropy seizures

Isoflurane vapor pressure = 240 mmHg at 20 deg C pungent ethereal odor chemical isomer of enflurane minimal cardiac depression carotid baroreflexes relatively intact heart rate increases 10-20% mild beta-adrenergic stimulation

Isoflurane BP = 48.5 SVP = 240 B/G = 1.4 O/G = 91 MAC = 1.1 Metabolism – 2% , no hepatotoxic, no nephrotoxic fears

Then came sevo and des

En, iso Vs sevo, des - only fluorine

Sevoflurane Seven fluorine atoms and hence the name Sweet smell to allow smooth induction Fast induction and recovery Green house effect global warming potential of 345.

Sevoflurane BP= 58.5 B/G = 0.6 O/G = 55 MAC = 2 Degradation with soda lime – compound A and compound B Numerous evidence showed its safety of prolong ed use in hypothermic patients with low flows

DESFLURANE BP = 22 SVP = 660 B/G = 0.42 O/G = 18.7 MAC = 6

DESFLURANE Irritant to airways No to inh. Induction Paediatric emergence delirium Cost excessive Carbonmonoxide formation risk -as with all present- but insignificant

Des Vs Sevo switching from isoflurane to desflurane toward the end of anesthesia does not significantly accelerate recovery nor does faster emergence Desflurane emergence has been associated with delirium in some pediatric patients. Rapid increases in desflurane concentration lead to transient but sometimes worrisome elevations in heart rate, blood pressure, and catecholamine levels

Sevo and des- cardiac output – ok even in 2 MAC

UV light stability Enf Iso Sevo Des OK

Actions of all anaesthetics general anesthesia, slightly increases CBF and ICP decreases CMRO2 Increases nondepolarizers depresses respiration bronchodilator Hypoxic response, ventilatory response to CO2 Negative inotropy and vasodilation Uterine relaxant

Relative Contraindications of all inhaled anaesthetics Malignant hyperthermia Increased ICT Severe hypovolumia

We don’t know when he will come XENON

Xenon Greek for stranger First used in 1951 by Cullen on an 81yr old man having an orchidectomy B/G = 0.115 O/G = 20 MAC = 60 – 70 %

XENON Fast in and fast out No metabolism inert gas that is nonexplosive, nonpungent odorless, chemically inert, some analgesia Cardiac safety No fink hypoxia not to trigger malignant hyperthermia Stability – good But

The cost Use of semiclosed systems cost £1200/hr. Rs. 90,000/ hour Very low flow e.g. 0,3 l/min will cost £160-180/hr. Rs. 15,000 / hour

Anaesthetic Agent Blood:Gas coefficient at 37°C Ether 12.1 Methoxyflurane 15 Halothane 2.4 Enflurane 1.8 Isoflurane 1.4 Sevoflurane 0.69 Desflurane 0.42 Nitrous Oxide 0.47

This is what the blood gas PC means

Oil gas and MAC Ether = O/G = 65 MAC = 1.92 Halothane O/G = 220 MAC = 0.75 Methoxy flu. O/G = 950 MAC = 0.16 Isoflurane O/G = 91 MAC = 1.1 Sevoflurane O/G = 55 MAC =2.6 Desflurane O/G = 18 MAC = 6

Molecular weight Non ionized and low molecular weight enables inhalational agents to go to tissues without Processes like Active transport Facilitated diffusion MW = VAPOUR PRESSURE ETHER = 74 440 HALOTHANE = 197 240 NOT UNIVERSAL

BRAIN BLOOD COEFFICIENT Halo = 1.9 Iso = 1.6 Sevo = 1.7 Des = 1.3

METABOLISM Halothane: 20% Enflurane: 2.5% Isoflurane: 0.2% Desflurane: 0.01-0.02% Sevoflurane:5%

SUMMARY Ether , fire Halo – rhythm disturbance Go back to ethers Flourine – stability Metabolism Safety

CARRY HOME MESSAGE

Letter from my 5 year old daughter on my birthday

Enjoy life’s precious moments thank you all