CHAPTER 2 Historical Milestones in Anesthesia


On October 16, 1846 (considered as the era of the beginning of anesthesia), William TG Morton gave the first successful public demonstration of anesthesia using ether at the Massachusetts General Hospital, and that is why October 16 is celebrated as world anesthesia day. This chapter covers the historical evolution of various anesthetic agents, be it inhalational, intravenous (IV), and muscle relaxants.

Inhaled Anesthetic Agents

The muddle experienced by the surgeon during surgery played a pivotal role in the development of “inhalational agents.” Active physical resistance, crying, and screaming by the patients were distracting during the surgery and, overall, increased the mortality and morbidity.

In the 15th century, Paracelsus was aware of the soporific action of ether, a compound synthesized from sulfuric acid and alcohol by the chemist Valerius Cordus (called as volatile liquid “sweet vitriol”). Paracelsus observed the effect of ether on chickens and stated that “it quiets all suffering without harm and relieves all pain.” Various inhalational anesthetic agents are briefly explained below.


The propensity to explode in ether prompted the search of alternative inhaled agents, including chloroform (CHCl3). David Waldie suggested CHCl3 (prepared in 1931) to James Young Simpson. Simpson and his friends at a dinner party on November 4, 1847 inhaled it and promptly felt unconscious and within 2 weeks submitted his discovery to The Lancet.

The entity of CHCl3 had gained popularity when John Snow used it for the pain-free delivery of Queen Victoria.

Nitrous Oxide

The annals of nitrous oxide (N2O) backdated with its isolation in 1772 by Joseph Priestly. Over the decade, Humphry Davy accidentally noted its analgesic property. The idea of using N2O with oxygen was credited to Edmund Andrews (1824–1904) and provided analgesia without cyanosis. He also advocated the use of liquid N2O in iron flasks. Paul Bert (1833–1886) demonstrated the effect of surgical anesthesia without hypoxia when delivered at a pressure greater than 1 atmosphere.

Frederick Hewitt (1857–1916) devised an anesthesia machine to deliver N2O and oxygen at variable proportions.

Diethyl Ether

William TG Morton gave a successful public demonstration of ether at the Massachusetts General Hospital. It is an excellent muscle relaxant.

Inhaled Fluorinated Anesthetics

A survey on 166 gases concluded that fluorine substitution for halogens increased stability and reduced the boiling point and toxicity. The first fluorinated anesthetic (1954), namely, fluroxene or trifluoromethyl vinyl ether, was discovered and later on withdrawn (1974) due to toxic metabolite found in animals.

In 1954, Charles Suckling synthesized halothane. James Raventos (1905–1983) studied the pharmacological properties of halothane, which later on was widely accepted clinically across the world in 1956 by Michael Johnstone. Some of the flourinated inhalational anesthetic agents are as follows:

  • Methoxyflurane: In 1960, methoxyflurane followed halothane and remained popular for a decade. However, due to its high fluoride content, nephrotoxicity (high-output renal failure), and risk of oxalate stone, the search for the ideal volatile agent started.

  • Enflurane and isoflurane: Ohio Medical products developed enflurane and isoflurane about 40 years ago. Enflurane utilization was limited due to its cardiodepressant, fluorine nephrotoxicity, and its epileptiform activities, while isoflurane has been widely used since that time.

  • Desflurane and sevoflurane: Desflurane was one of the last volatile anesthetics to be manufactured and had high vapor pressure (fast induction, recovery, and pungent smell). Furthermore, the Travenol laboratories synthesized sevoflurane more than 40 years ago with rapid recovery and form an unstable component in soda lime.

Although William Ramsay in the 1940s (noble gas) isolated xenon and considered very close to ideal gas, it is still not used widely due to scarcity in availability and is also very expensive.

Intravenous Anesthetics

The discovery of IV anesthetic agents began with barbiturates, and later on, phencyclindine derivatives, benzodiazepines and etomidate joined the series. These are commonly used agents for induction as well as maintenance of anesthesia with unique physicochemical properties and pharmacodynamics. The historical track of these agents is discussed in this chapter.


IV anesthesia dates back from the introduction of thiopentone in 1934, preceded by hexobarbital in 1932.

Sodium thiopental (sodium pentothal) was discovered by Ernest H. Volwiler and Donalee L. Tabern, working in collaboration with Abbott Laboratories. On March 8, 1934, Dr Ralph M. Water used it for the first time in human beings. Although Water was the first to clinically use thiopentone, Dr John S. Lundy (June 18, 1934) was the first to press and responsible for the large popularity of the drug.

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Dec 11, 2022 | Posted by in ANESTHESIA | Comments Off on CHAPTER 2 Historical Milestones in Anesthesia

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