The First Use of Divinyl Ether The First Use of Divinyl Ether in Humans in HumansBT Finucane MB FRCPCBT Finucane MB FRCPC

Professor EmeritusProfessor EmeritusDepartment of Department of

Anesthesiology and Pain Anesthesiology and Pain MedicineMedicine

University of AlbertaUniversity of Alberta

Horace Wells (1815-Horace Wells (1815-1848)1848)

The First Operation with Ether

(Painting by Robert C Hinckley.Oil on Canvas 8’ x 10’. Boston Medical Library 1893

James Young Simpson-James Young Simpson-ChloroformChloroform

Ethyl ChlorideEthyl Chloride

EthyleneEthylene

Nitrous Oxide N20

Ethylene C2H4

Cyclopropane C3H6

Xenon Xe

Di-Ethyl Ether C2H5-O-C2H5

Di-Vinyl Ether C2H4-O-C2H4

Ethyl-n-Propyl Ether

Chloroform CHCl3

Ethyl Chloride C2H5Cl

Trichlorethylene CCl2CHCl

Halothane CF3CHClBr

The Evolution of Inhalation Anesthesia

Ethyl-Methyl Ether C2H5-O-CH3

Methoxyflurane CHCl2CF2-O-CH3

Enflurane CHFClCF2-O-CH3

Isoflurane CF3CHCl-O-CHF2Desflurane CF3CHF-O-CHF2

Sevoflurane C3HF6-O-CH2F

Chauncey D. LeakeChauncey D. LeakePharmacologistPharmacologist

Pharmacological ManipulationPharmacological Manipulation

CH2 = CH2

CH3 – CH2 – O – CH2 – CH3

CH2 = CH – O – CH = CH2

Ethylene

Diethyl Ether

Divinyl Ether

Leake CD and Chen MY Proc Soc Exper Biol Med 1930 ; 28: 151

“ “ Further study of this Further study of this interesting series of interesting series of agents is justified and agents is justified and cordially invited.”cordially invited.”

Leake CD and Chen MY Proc Soc Exper Biol Med 1930 ; 28: 151

Physicochemical Properties Physicochemical Properties of Inhalation Anestheticsof Inhalation Anesthetics

Property Diethyl Ether Divinyl Ether Halothane Desflurane

Boiling point 34 28 50 24

Vapour pressure 442 553 241 669at 20ºC (mmHg)

Molecular 74 70 198 168weight

Blood/Gassolubility 12.1 2.8 2.4 1.3coefficient

From Leake’s essay in The History of Surgical Anesthesia by Thomas

E Keys

“ “ On the basis of the experiments On the basis of the experiments performed by Leake and his performed by Leake and his associates and our tests of the associates and our tests of the anesthetic in the human, we feel anesthetic in the human, we feel that divinyl oxide is worthy of that divinyl oxide is worthy of clinical trial and evaluation.”clinical trial and evaluation.”

- - Gelfan and BellGelfan and Bell J Pharmacol Exp TherapJ Pharmacol Exp Therap 1933 ; 47: 11933 ; 47: 1

Divinyl EtherDivinyl Ether Merck and Co – Vinethine 1935Merck and Co – Vinethine 1935 Rapid induction and recoveryRapid induction and recovery Very volatileVery volatile Low incidence of Nausea & Low incidence of Nausea &

VomitingVomiting Very useful for short proceduresVery useful for short procedures Expensive- 60 cents for 25 ml in Expensive- 60 cents for 25 ml in

19351935 25 ml of Sevoflurane costs $30 in 25 ml of Sevoflurane costs $30 in

20082008

1930s Advertisements1930s Advertisements

Connection between Connection between Gelfan and LeakeGelfan and Leake

Dr.Irving BellDr.Irving Bell

CommemorationCommemoration

AcknowledgementsAcknowledgements Dr.Roy Humble (Retired Dr.Roy Humble (Retired

Anesthetist at U of A)Anesthetist at U of A) The Board and Staff of the WLMThe Board and Staff of the WLM Archives, Merck & Co., Inc.Archives, Merck & Co., Inc.