History of anaesthesia

timeline of anaesthesia from antiquity to present in brief

1. HISTORY OF ANAESTHESIA Presenter- Dr Chimi Handique PGT Dept of Pharmacology

2. Anaesthesia : A clinical and philosophical concept It is in the Hippocratic Corpus , that the word ‘ anaesthesia ’ was used for the first time in a medical context as reversible loss of sensation and unconsciousness, when Hippocrates writes: “ For when they [breaths] pass through the flesh and puff it up, the parts of body affected lose the power of feeling [‘ anaestheta ’]”.

3. What was done to a patient before an operation ? It was the custom then, as for centuries afterward, to bind the patient to the table with ropes or straps. His screams were disregarded, but if he struggled too Violently, assistants grasped his arms and legs.

4. Pain had not prevented surgery in the past, but it had made it almost an unbearable, excruciating agony. In January 1843, George Wilson, a medical student who underwent surgery to amputate an infected leg, described his experience of surgery without anaesthesia and analgesia. “ Of the agony it occasioned, I will say nothing. Suffering so great as I underwent cannot be expressed in words. ... The particular pangs are now forgotten;but the black whirlwind of emotion, the horror of great darkness, and the sense of desertion by God and man, bordering close upon despair, which swept through my mind and overwhelmed my heart, I can never forget ...”

5. By the early 1840s successive cultural and medical changes based on newer humanistic standards had resulted in the view that physical pain is purposeless. This new concept regarding pain prevention and its relief is the social scenery for the discovery of modern ‘ anaesthesia ’ during the middle of the 19th century.

6. The word “ Anaesthesia “ was coined by Oliver Wendell Holmes in 1846. It originates from the Greek   an - "without” and “ aisthēsis ” refers to the inhibition of sensation. Oliver Wendell Holmes (1809–1894)

7. In a letter to William T. G. Morton, the first practitioner to publicly demonstrate the use of ether during surgery, he wrote: "Everybody wants to have a hand in a great discovery. All I will do is to give a hint or two as to names—or the name—to be applied to the state produced and the agent. The state should, I think, be called ' Anaesthesia .' This signifies insensibility—more particularly ... to objects of touch.“

8. A Brief Overview

9. Attempts at producing a state of general anaesthesia can be traced throughout recorded history. The   Renaissance  saw significant advances in anatomy and surgical technique. However, despite all this progress, surgery remained a treatment of last resort. An appreciation of the  germ theory of disease  led rapidly to the development of antiseptic techniques in surgery reducing the overall morbidity and mortality of surgery to a far more acceptable rate.

10. Concurrent with these developments were the significant advances in  pharmacology and physiology  which led to the development of general anesthesia and the control of pain. In the 20th century , the safety and efficacy of general anesthesia was improved by the routine use of tracheal intubation and other advanced airway management techniques . Significant advances in monitoring and new anesthetic agents  with improved  pharmacokinetic and   pharmacodynamic characteristics also contributed to this trend.

11. TIMELINE OF ANESTHESIA Antiquity Middle ages and Renaissance 18 th Century 19 th Century 20 th Century 21 st Century

12. Antiquity Antiquity saw the dawn of anesthesia. This era saw the uses of poppy, mandrake, Indian hemp, cocaine and carotid compression.

13. Origin of Opium

14. Opium , is a very popular ancient pain relieving and euphoria inducing remedy. It is first said to have been cultivated in lower mesopotamia (Southwest Asia) in 3400 BC. Sumerians referred it as “ hul-gil ” which means “ joy plant ” Sumerians passed this “miracle drug” to the Assyrians who in turn passed opium to the Babylonians and then to the Egyptians. 3400 BC

15. The knowledge and use of opium passed on from Egypt across Mediterranean Sea trade routes to various civilizations including the Phoenicians and the Greeks. Later, around 330 BC,  Alexander the Great  and his armies introduced opium to the people of India, Persia and other eastern and Middle Eastern kingdoms.

16. Prior to the introduction of opium to ancient India  and China, these civilizations pioneered the use of cannabis incense and aconitum. By the 8th century AD, Arab traders had brought opium to India and China.

17. Pictographs showing practice of Acupuncture in China on bone and Tortoise shells with inscriptions dating from the time of Shang dynasty have been found, and it is thought that these were used for divination in the art of healing.   1600 BC

18. Sushruta in Sushruta Samhita advocated the use of wine with incense of cannabis  for anaesthesia . The use of henbane and of  Sammohini  and  Sanjivani  are reported at a later period 600 BC

19. Assyrians and Egyptians used carotid compression to produce brief unconsciousness before circumcision or cataract surgery . In a passage in History of Animals, Aristotle says of the jugular veins: “If these veins are pressed externally, men, though not actually choked, become insensible, shut their eyes, and fall flat on the ground." 400 BC

20. Pedanius Dioscorides , a Greek surgeon in the Roman army of Emperor Nero, recommended mandrake boiled in wine to "cause the insensibility of those who are to be cut or cauterized .” in his writings in De Materia Medica   C. 64 BC

21. Hua Tuo of China used to perform surgery under anesthesia using a formula he had developed and called   mafeisan . The word  mafeisan probably means something like " cannabis boil powder ". The exact composition of mafeisan , similar to all of Hua Tuo's clinical knowledge, was lost when he burned his manuscripts, just before his death. ca 160

22. &

23. History of Ether

24. Origin The compound may have been created by Jābir ibn Hayyān  in the 8th century . Alchemist Ramon Llull  has also been credited with discovering diethyl ether in 1275, although there is no contemporary evidence of this.

25. Paracelsus (1493–1541) isolated substances that resulted from interaction of alcohol and vitriol and demonstrated its action in chickens. He noted chickens enjoy sweet vitriol [ether] - after which they "undergo prolonged sleep, awake unharmed". However, he did not extend this discovery from farm animals to people.  1525

26. German physician Valerius Cordus (1515–1544), is widely credited with developing a method for synthesizing ether. He synthesized diethyl ether by distilling ethanol and sulphuric acid into what he called by the poetic Latin name  oleum dulci vitrioli , or "sweet oil of vitriol” 1540

27. The name  ether   was given to the substance in 1729 by August Sigmund Frobenius . William T. G. Morton was First in the world to publicly and successfully demonstrate the use of ether anesthesia for surgery.

28. Developments in 18 th century

29. History of Nitrous oxide

30. Joseph Priestley  (1733–1804) was an English chemist who discovered  nitrous oxide (1772), nitric oxide, ammonia,  hydrogen chloride and   oxygen (1774). He originally named nitrous oxide as " nitrous air, diminished ”, on account of his preparative method of allowing NO to standing in contact with moist iron filing . 1771-1786

31. Priestley’s apparatus Priestley’s Experiment

32. Priestley was clearly perplexed as to the nature of his diminished nitrous air. A candle burnt with an increased brightness in the gas. When mice were placed in a bell-jar of N 2 O their liveliness was reduced and they soon died. In contrast they seemed livelier if they respired oxygen, which Priestley subsequently discovered.(1774). But general anaesthesia by the inhalation of nitrous oxide wasn't demonstrated for over 40 years till December 1844 by US dentist Horace Wells .

33. Developments in 19 th Century

34. July, 1800 Even though N 2 O was discovered by Joseph Priestley it Humphry Davy who spotted its medical potential  In 1798, Humphry Davy was appointed laboratory superintendent of the Pneumatic Institute in Bristol, UK. This was an establishment founded on the belief that the recently discovered gases might have curative applications  

35. Curiously, the use of this gas in therapy is barely mentioned: a couple of accounts of its use on paralysed patients, and that's about the extent. It is at the end of this book “the history, chemistry, physiology and recreational use of nitrous oxide” that he makes his off-repeated statement about the possible use of nitrous oxide in surgery: " As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place."

36. Henry Hill Hickman  (1800–1830) experimented with the use of carbon dioxide as an anesthetic in the 1820s. He would make the animal insensible, effectively via almost suffocating it with carbon dioxide, then determine the effects of the gas by amputating one of its limbs. . 1824

37. In 1824, Hickman submitted the results of his research to the Royal Society in a short treatise entitled  Letter on suspended animation: with the view of ascertaining its probable utility in surgical operations on human subjects . The response was an 1826 article in The Lancet titled 'Surgical Humbug' that ruthlessly criticized his work. Hickman died four years later at age 30. Though he was unappreciated at the time of his death, his work has since been positively reappraised and he is now recognized as one of the fathers of anesthesia

38. Crawford W. Long had observed in the ether frolics gatherings, that some participants experienced bumps and bruises, but afterward had no recall of what had happened. He postulated that that diethyl ether produced pharmacologic effects similar to those of nitrous oxide. On 30 March 1842, he administered diethyl ether by inhalation to a man named James Venable, in order to remove a cysts from the man's neck.  1842

39. Dr . Horace Wells ( 1815-1848) volunteered to inhale nitrous oxide for his own dental extraction back in December of 1844. Wells then began to administer nitrous oxide to his patients, successfully performing several dental extractions over the next couple of weeks. 1845

40. In spite of these convincing results being reported by Wells to the medical society in Boston already in December 1844, this new method was not immediately adopted by other dentists. The reason for this was most likely that Wells, in January 1845 at his first public demonstration to the medical faculty in Boston, had been partly unsuccessful, leaving his colleagues doubtful regarding its efficacy and safety the partial anesthetic was judged as a " humbug. "

41. History of ether dome

42. On October 16,1846 William T. G. Morton ( 1819-1868) became first in the world to publicly and successfully demonstrate the use of ether anesthesia for surgery. This occurred at what came to be called " The Ether Dome ," at Massachusetts General Hospital. 1846

43. The  Ether Dome  is a surgical operating amphitheater in the  Bulfinch Building  at Massachusetts General Hospital in  Boston. It was the site of the first public demonstration of the use of inhaled ether as a surgical anesthetic on 16 October 1846. 

44. Crawford Long , had previously administered ether in 1842, but this went unpublished until 1849. The Ether Dome event occurred when  William T. G. Morton, used ether to anesthetize Edward Gilbert Abbott.  John Collins Warren , the first dean of Harvard Medical School, then painlessly removed part of a tumor from Abbott's neck. After Warren had finished, and Abbott regained consciousness, Warren asked the patient how he felt.

45. Reportedly, Abbott said, " Feels as if my neck's been scratched" . Warren then turned to his medical audience and uttered "Gentlemen, this is no Humbug".  This was presumably a reference to the unsuccessful demonstration of nitrous oxide anesthesia by Horace Wells in the same theater the previous year, which was ended by cries of " Humbug! " after the patient groaned with pain..

46. History of Chloroform

47. Chloroform was discovered independently in 1831 by the USA's Samuel Guthrie, France's Eugène Soubeiran , and Germany's Justus von Liebig. Prof . James Y. Simpson (1811-1870)-Scottish obstetrician begins administering chloroform to women for pain during childbirth . Chloroform quickly became a popular anesthetic for surgery and dental procedures as well. 1847

48. Dr . John Snow ( 1813-1858) who was a fulltime anesthetist since 1847, popularized obstetric anesthesia by chloroforming Queen Victoria for the birth of Prince Leopold (1853) and Princess Beatrice (1857). 1853 & 1857

49. Knowledge of the narcotic effect of chloroform spread rapidly, but very soon reports of sudden deaths mounted. The first fatality was a 15-year-old girl called Hannah Greener, who died on January 28, 1848. Between 1864 and 1910 numerous commissions in UK studied chloroform, but failed to come to any clear conclusions. The reservations about chloroform could not halt its soaring popularity. Between about 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in UK and German-speaking countries.

50. History of Cocaine

51. Dr . Karl Koller (1857-1944)-Viennese ophthalmologist and colleague of Sigmund Freud, introduced cocaine as an anesthetic for eye surgery . Koller recognized its tissue-numbing capabilities, and in 1884 demonstrated its potential as a local anaesthetic to the medical community. 1884

52. Koller's findings were a medical breakthrough. Prior to his discovery, performing eye surgery was difficult because the involuntary reflex motions of the eye to respond to the slightest stimuli. Later, cocaine was also used as a local anaesthetic in other medical fields such as dentistry

53. Dr . August Bier ( 1861-1949) was a German surgeon. On 16 August 1898, Bier performed the first operation under spinal anesthesia at the Royal Surgical Hospital of the University of Kiel. The subject was scheduled to undergo segmental resection of his left ankle, which was severely infected with tuberculosis. 1898

54. But Bier dreaded the prospect of general anesthesia because he had suffered severe adverse side effects during multiple previous operations. Therefore, Bier suggested "cocainization" of the spinal cord as an alternative to general anesthesia. Bier injected 15 mg of cocaine intrathecally , which was sufficient to allow him to perform the operation. The subject was fully conscious during the operation, but felt no pain.  

55. Two hours after the operation, the subject complained of nausea, vomiting, severe headache, and pain in his back and ankle. The vomiting, back and leg pain improved by the following day, but the headache was still present. Bier performed spinal anesthetics on five more subjects for lower extremity surgery, using a similar technique and achieving similar results

56. 20 th C E N T U R y

57. The 20th century saw the transformation of the practices of tracheotomy, endoscopy and non-surgical tracheal intubation from rarely employed procedures to essential components of the practices of anesthesia, critical care medicine, emergency medicine, gastroenterology, pulmonology and surgery.

58. In 1902, Hermann Emil Fischer (1852–1919) and Joseph von Mering  (1849–1908) discovered that diethylbarbituric acid was an effective hypnotic  agent.

59. Also called barbital or  Veronal , the trade name assigned to it by Bayer Pharmaceuticals, this new drug became the first commercially marketed barbiturate. It was used as a treatment for insomnia from 1903 until the mid-1950s.

60. Barbitone was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide , and then by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.

61. Alfred Einhorn (1857-1917)-German chemist develops procaine and names the substance "Novocain .“ from the Latin  nov -  (meaning  new ) and  - caine , a common ending for alkaloids used as anesthetics. It was introduced into medical use by surgeon  Heinrich Braun . 1905

62. Arthur Guedel publishes his eye signs of Ether anesthesia in the  American Journal of Surgery . He also described 4 stages of ether anaesthesia dividing the stage III into 4 planes His Guedel (oral) airway is still used today. He has been memorialized by the Arthur E. Guedel Memorial Anesthesia Center, San Francisco. 1920

63. HISTORY OF SODIUM THIOPENTAL

64. Sodium thiopental , the 1 st  IV anesthetic, was synthesized in 1934 by  Ernest H. Volwiler & Donalee L. Tabern  , working for Abbott Laboratories. In the mid 1930s, Volwiler and Tabern spent three years screening over 200 candidate compounds in search of a substance which could be injected directly into the blood stream to produce unconsciousness

65. It was first used in humans on 8 March 1934 by Ralph M. Waters  in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, John Silas Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott Laboratories.

66. Volwiler and Tabern were awarded U.S. Patent No. 2,153,729 in 1939 for the discovery of thiopental, and they were inducted into the National Inventors Hall of Fame in 1986. The popularity of thiopental-as a swift-onset intravenous agent for inducing general anesthesia- paved the way for other totally unrelated intravenous induction agents, such as ketamine , etomidate , and propofol .

67. On 23 January 1942 Griffith and his resident Enid Johnson administered curare to a young man undergoing appendicectomy .. Dr. Harold Griffith (1894-1985) & Enid Johnson (1909-2001) 1942

68. The credit for introducing curare to anaesthetics belongs to Griffith. Griffith and Johnson reported their use of curare in July 1942, and the introduction to their report is memorable: ‘ Every anaesthetist has wished at times that he might be able to produce rapid and complete muscular relaxation in resistant patients under general anaesthesia ”

69. Many new intravenous and inhalational anesthetics were developed and brought into clinical use during the second half of the 20th century. Paul Janssen (1926–2003), the founder of Janssen Pharmaceutica , is credited with the development of over 80 pharmaceutical compounds. Janssen synthesized nearly all of the  butyrophenone  class of antipsychotic agents, beginning with haloperidol (1958) and  droperidol  (1961).

70. These agents were rapidly integrated into the practice of anesthesia.  In 1960, Janssen's team synthesized  fentanyl , the first of the  piperidinone -derived opioids . Fentanyl was followed by  sufentanil  (1974),  alfentanil (1976),  carfentanil (1976), and lofentanil (1980). Janssen and his team also developed  etomidate  (1964),a potent intravenous anesthetic induction agent.

71. 1956 - UK's Dr. Michael Johnstone clinically introduces halothane, the first modern-day brominated general anesthetic. 1963 - Dr. Edmond I. Eger, II described minimum alveolar concentration (MAC) , later characterized as "the concentration of inhaled anesthetic producing immobility in 50% of patients subjected to a noxious stimulus."

72. 1964- Dr . Günter Corssen   et al.  begin human trials of the dissociative intravenous anesthetic ketamine . 1966- Dr . Robert Virtue  et al.  begin human trials of the inhalational anesthetic enflurane . 1972 - Isoflurane is clinically introduced as an inhalational anesthetic . 1992- Desflurane is clinically introduced as an inhalational anesthetic. 1994- Sevoflurane is clinically introduced as an inhalational anesthetic.

73. 21 st CENTURY 21 st Century: Age of Digital Revolution

74. Among the most widely used drugs are Propofol , Etomidate , Barbiturates such as  methohexital and  thiopentone , Benzodiazepines such as  midazolam and Ketamine . The "digital revolution“ of the 21st century has brought newer technology to the art and science of tracheal intubation. Several manufacturers have developed video laryngoscopes

75. Xenon has been used as a general anesthetic. Although it is expensive, anesthesia machines that can deliver xenon are about to appear on the European market, because advances in recovery and recycling of xenon have made it economically viable. New agents based on benzodiazepine, etomidate , and propofol structures are being developed.

76. Conclusion Surgery learned many lessons through the ages, but never was it able to banish Pain. More than a century ago, a vapor in the operating-room of the Massachusetts General Hospital blotted out sufferrings from surgery. It was the most beneficent change in the history of surgery, and has since been one of the greatest gift to mankind. However, the history of anaesthetics will remain an unfinished work, until some one is able to synthesize a drug that will have all of the desirable properties of the ideal anaesthetic .

77. THANK YOU