see also:

• historic perspectives of medicine
• anaesthetics

• 1860: Niemann purifies cocaine, an alkaloid contained in the leaves of Erythroxylon coca, a shrub growing in the Andes.
• 1880: Von Anrep observed the local anaesthetic effects of cocaine when given subcutaneously.
• 1884: Sigmund Freud studied the physiologic effects of cocaine & used it to wean a colleague off morphine but produced one of the 1st-known cocaine addicts of modern times!
• Koller introduced cocaine as a LA in ophthalmology & Hall in dentistry.
• 1885: Halsted lays foundation for nerve block anaesthesia surgery by demonstrating that cocaine could stop the transmission in nerve trunks.
• Corning produced spinal anaesthesia in dogs.
• 1905: After 13 yrs research, a cocaine substitute was found - procaine - which became the prototype for local anaesthetic agents for nearly 50 yrs.
• 1948: lignocaine introduced.
• 2005: articaine introduced in Australia as LA for dental use.

• Surgical procedures uncommon.
• Understanding of the pathophysiology of disease & the rationale for surgery was rudimentary.
• Aseptic technique & the prevention of wound infection were almost unknown.
• Lack of a satisfactory anaesthetic was a major deterrent.
• Mortality was high & surgery mainly for emergencies only - eg. limb amputation;
• Analgesics available included alcohol, hashish, opium derivatives, while physical methods such as packing a limb in ice or making it ischaemic with a tourniquet were occasionally used.
• Despite nitrous oxide being discovered in 1776 by Priestley, & its anaesthetic properties being noted in 1796 it was not used in medicine.
• Faraday noted in ~1816 that inhalation of diethyl ether produced similar effects to nitrous oxide. But despite its use at carnivals & at “ether frolics” it was not used in medicine.
• Partly this was due to general lack of concern for the well-being of one's fellows & at a time when burning witches at the stake was commonplace. The gradual change in attitudes along with advances in medicine & chemistry in mid-19th century paved the way for development of anaesthetics.

• 1846: Morton's classic public demonstration of ether as a surgical anaesthetic.
  • Ether - the ideal “first” anaesthetic:
    • readily made in pure form; liquid at room temp.; readily vaporised;
    • potent (unlike nitrous oxide) - a few volumes percent adequate
    • supported respiration & circulation - important at a time when known physiology was inadequate for assisted ventilation & circulation.
    • not toxic to vital organs
• 1847: Scottish obstetrician James Simpson introduced chloroform as anaesthetic.
  • Chloroform became popular anaesthetic esp. in UK for nearly 100yrs as it had a more pleasant odour & non-inflammable, despite it being hepatotoxic & a severe cardiovascular depressant with a relatively high incidence of post-op death!
• 1863: Nitrous oxide re-introduced largely through efforts of Colton.
• 1868: Combined use of oxygen & nitrous oxide described by Andrews.
  • soon thereafter, the 2 gases became available in steel cylinders.
• 1929: Anaesthetic properties of cyclopropane accidentally discovered.
  • After extensive clinical trials, cyclopropane became the most widely used GA for next 30yrs.
  • However, the increasing risk of explosions by the increasing use of electrical equipment meant a safer agent was needed.
• 1935: Lundy demonstrates usefulness of IV thiopentone, originally as sole agent, but doses required caused serious depression of CVS, Resp & CNS depression. It did however, become enthusiastically accepted for rapid induction of GA.
• 1940's: Anaesthetists use curare to provide muscle relaxation, permitting adequate conditions for surgery with light levels of anaesthesia, minimising cardiovascular depression & post-op sedation. Several synthetic substitutes used over next 6 yrs.
• 1956: ICI introduce halothane - a non-flammable anaesthetic which became the basis for most of the newer agents.
• 1960: methoxyflurane introduced but its use as a GA limited due to nephrotoxicity.
• 1973: Enflurane introduced into general clinical use, initially to avoid rpt use of halothane.
  • Lower incidence of arrhythmias, post-op nausea & vomiting than halothane
  • Potentiates muscle relaxants, reducing doses needed of those.
  • Problems:
    • seizures may occur in predisposed pts
    • uterine relaxation at deep levels a problem in labor
• 1981: Isoflurane introduced:
  • Depth of anaesthesia more rapidly adjusted than with enflurane or halothane.
  • Causes systemic vasodilation (incl. coronary vessels), but maintains cardiac output.
  • Arrhythmias uncommon allowing higher doses of adrenaline for hemostasis.
  • Potentiates muscle relaxants, reducing doses needed of those.
  • Allows control of cerebral blood flow & intracranial pressure.
  • Minimal metabolism & no reported hepato/nephrotoxicity.
  • Problems:
    • more pungent odor than halothane
    • progressive resp. depression & hypotension
    • uterine relaxation can be undesirable
• 1990's propofol introduced as an IV induction agent
  • Rapid induction & recovery from GA - good for brief anaesthesia in day stay pts
  • Minimal post-op confusion cf thiopentone but similar nausea, vomiting & headache.
  • Injection is more painful but rarely followed by phlebitis or thrombosis.
  • Can be used as continuous infusion with opioids/nitrous oxide.
• 1990's: Sevoflurane introduced