A History of Research in Anesthesia

  • Edmond I Eger II


Research in anesthesia has taken several forms. Other essays in this book supply detailed histories of those specific researches, including the discovery of new anesthetics and anesthetic adjuvant drugs, advances in anesthetic delivery and monitoring, measurement and codification of anesthetic pharmacodynamics and kinetics, and the development of vehicles for the exchange of information on research (societies, books and journals). We refer the reader to these chapters for details of the histories of specific researches. The present chapter supplies an overview, a summary of the progress in anesthesia research.


History of anesthesia research Anesthesia research history Drug research in anesthesia Pharmacokinetic research history 



I thank Dr. John W. Severinghaus for his several suggestions.


  1. 1.
    Adriani J. The pharmacology of anesthetic drugs. Springfield: Charles C Thomas; 1952Google Scholar
  2. 2.
    Weese H, Scharpff W. Evipan, cin neuartiges Einschlafmittel. Deut Med Wochenschr. 1932;58:1205–7.CrossRefGoogle Scholar
  3. 3.
    Bernard C. Etudes phsiologiques sue quelques poisons americains. Revue des Deux Mondes 1864;53:164–90.Google Scholar
  4. 4.
    Griffith HR, Johnson E. The use of curare in general anesthesia. Anesthesiology. 1942;3:418–20.CrossRefGoogle Scholar
  5. 5.
    Holmdahl MH. Xylocain (lidocaine, lignocaine), its discovery and Gordh’s contribution to its clinical use. Acta Anaesthesiol Scand Suppl. 1998;113:8–12Google Scholar
  6. 6.
    Johnstone M. Halothane: the first five years. Anesthesiology. 1961;22:591–614.PubMedCrossRefGoogle Scholar
  7. 7.
    Vitcha JF. A history of Forane®. Anesthesiology. 1971;35:4–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Terrell RC. The invention and development of enflurane, isoflurane, sevoflurane, and desflurane. Anesthesiology. 2008;108:531–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Wallin RF, Regan BM, Napoli MD, Stern IJ. Sevoflurane: A new inhalational anesthetic agent. Anesth Analg. 1975;54:758–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Snow J. On the inhalation of the vapour of ether in surgical operations: containing a description of the various stages of etherization, and a statement of the result of nearly eighty operations in which ether has been employed in St. George’s and University College Hospitals. London: John Churchill; 1847. pp 1–88.Google Scholar
  11. 11.
    Snow J. On chloroform and other anaesthetics: their action and administration. John Churchill, New Burlington Street. London 1858. pp 1–443.Google Scholar
  12. 12.
    Guedel AE. Inhalation anesthesia: a fundamental guide. New York, Macmillan; 1937. pp 1–172Google Scholar
  13. 13.
    Cushing HW. Anaesthesia charts of 1895. Letter to F.A. Washburn. Treadwell Library, Massachusetts General Hospital, Boston, MAGoogle Scholar
  14. 14.
    Haggard AW. The absorption, distribution and elimination of ethyl ether. II. Analysis of the mechanism of absorption and elimination of such a gas or vapor as ethyl ether. J Biol Chem. 1924;59:753–96.Google Scholar
  15. 15.
    Haggard AW. The absorption, distribution and elimination of ethyl ether. III. The relation of the concentration of ether, or any similar volatile substance in the central nervous system to the concentration in the arterial blood and the buffer action of the body. J Biol Chem. 1924;59:797–832.Google Scholar
  16. 16.
    Kety SS. Theory and application of exchange of inert gas at the lungs and tissues. Pharmacol Rev. 1951;3:1–41.PubMedGoogle Scholar
  17. 17.
    Severinghaus JW. The rate of uptake of nitrous oxide in man. J Clin Invest. 1954;33:1183–9.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Lowe HJ, Ernst EA. The quantitative practice of anesthesia. Use of closed circuit. Baltimore, Williams & Wilkins; 1981. pp 1–234Google Scholar
  19. 19.
    Price HL. A dynamic concept of the distribution of thiopental in the human body. Anesthesiology. 1960;21:40–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Eger EI II. Anesthetic uptake and action. Baltimore, Williams & Wilkins; 1974. pp 1–371.Google Scholar
  21. 21.
    Eger EI II. A mathematical model of uptake and distribution. In: Papper EM, Kitz RJ, Editors. Uptake and distribution of anesthetic agents. New York, McGraw-Hill; 1963, pp 72–87.Google Scholar
  22. 22.
    Severinghaus JW. Role of lung factors. In: Papper EM, Kitz RJ, Editors. Uptake and distribution of anesthetic agents. New York, McGraw-Hill; 1963Google Scholar
  23. 23.
    Mapleson WW. Quantitative prediction of anesthetic concentrations. In: Papper EM, Kitz RJ, Editors. Uptake and distribution of anesthetic agents. New York, McGraw-Hill; 1963, pp 104–19.Google Scholar
  24. 24.
    Merkel G, Eger EI II. A comparative study of halothane and halopropane anesthesia. Including a method for determining equipotency. Anesthesiology. 1963;24:346–57.PubMedCrossRefGoogle Scholar
  25. 25.
    Saidman LJ, Eger EI II. Effect of nitrous oxide and of narcotic premedication on the alveolar concentration of halothane required for anesthesia. Anesthesiology. 1964;25:302–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Andrews DT, Leslie K, Sessler DI, Bjorksten AR. The arterial blood propofol concentration preventing movement in 50% of healthy women after skin incision. Anesth Analg. 1997;85:414–9.PubMedGoogle Scholar
  27. 27.
    Eger EI II, Eisenkraft JB, Weiskopf RB. The pharmacology of inhaled anesthetics. Chicago: Healthcare Press; 2002. pp 1–327.Google Scholar
  28. 28.
    Lawrie E. The Hyderbad chloroform commission. Lancet. 1889;1:952–3.Google Scholar
  29. 29.
    Embley EH. The causation of death during the administration of chloroform. Br Med J. 1902;2(2153):817–21.CrossRefGoogle Scholar
  30. 30.
    Embley EH. The causation of death during the administration of chloroform. Br Med J. 1902;2(2154):885–93.CrossRefGoogle Scholar
  31. 31.
    Embley EH. The causation of death during the administration of chloroform. Br Med J. 1902;1(2155):951–61.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Beecher HK, Todd DP. A study of the deaths associated with anesthesia and surgery: based on a study of 599, 548 anesthesias in ten institutions 1948–1952, inclusive. Ann Surg. 1954;140:2–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Prescott F, Organe G, Rowbotham S. Tubocurarine as an adjunct to anaesthesia. Lancet. 1946;2:80–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Arbous MS, Meursing AE, Kleef JW van, Lange JJ de, Spoormans HH, Touw P, Werner FM, Grobbee DE. Impact of anesthesia management characteristics on severe morbidity and mortality. Anesthesiology. 2005;102:257–68.PubMedCrossRefGoogle Scholar
  35. 35.
    Summary of the National Halothane Study. Possible association between halothane anesthesia and postoperative hepatic necrosis. Report by Subcommittee on the National Halothane Study of the Committee on Anesthesia, National Academy of Science. JAMA. 1966;197:775–88.CrossRefGoogle Scholar
  36. 36.
    Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334:1209–15.PubMedCrossRefGoogle Scholar
  37. 37.
    Hopf HW, Hunt TK, West JM, Blomquist P, Goodson WH 3rd, Jensen JA, Jonsson K, Paty PB, Rabkin JM, Upton RA, Smitten K von, Whitney JD. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg. 1997;132:997–1004. (discussion 1005).PubMedCrossRefGoogle Scholar
  38. 38.
    Wallace A, Layug B, Tateo I, Li J, Hollenberg M, Browner W, Miller D, Mangano D. Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology. 1998;88:7–17.PubMedCrossRefGoogle Scholar
  39. 39.
    Lassen HCA, Henriksen E, Neukirch F, Kristensen HS. Treatment of tetanus. Severe bone-marrow depression after prolonged nitrous-oxide anaesthesia. Lancet. 1956;1:527–30.CrossRefGoogle Scholar
  40. 40.
    Eger EI II, Editor. Nitrous Oxide/N2O. New York: Elsevier; 1985. pp 1–357.Google Scholar
  41. 41.
    Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007;107:221–31.PubMedCrossRefGoogle Scholar
  42. 42.
    Myles PS, Chan MT, Leslie K, Peyton P, Paech M, Forbes A. Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery. Br J Anaesth. 2008;100:780–6.PubMedCrossRefGoogle Scholar
  43. 43.
    McGregor DG, Lanier WL, Pasternak JJ, Rusy DA, Hogan K, Samra S, Hindman B, Todd MM, Schroeder DR, Bayman EO, Clarke W, Torner J, Weeks J. Effect of nitrous oxide on neurologic and neuropsychological function after intracranial aneurysm surgery. Anesthesiology. 2008;108:568–79.PubMedCrossRefGoogle Scholar
  44. 44.
    Meyer HH. Theorie der Alkoholnarkose. Arch Exptl Pathol Pharmakol. 1899;42:109–18.CrossRefGoogle Scholar
  45. 45.
    Overton E. Ueber die allgemeinen osmotischen Eigenschaften der Zelle, ihre vermutliche Ursachen und ihre Bedeutung fur die Physiologie. Vierteljahrschr Naturforsch Ges Zurich. 1899;44:88–114.Google Scholar
  46. 46.
    Franks NP, Lieb WR. Do general anaesthetics act by competitive binding to specific receptors? Nature. 1984;310:599–601.PubMedCrossRefGoogle Scholar
  47. 47.
    Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, Crestani F, Zaugg M, Vogt KE, Ledermann B, Antkowiak B, Rudolph U. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J. 2003;17:250–2.PubMedGoogle Scholar
  48. 48.
    Eger EI, II, Raines DE, Shafer SL, Hemmings HC Jr, Sonner JM. Is a new paradigm needed to explain how inhaled anesthetics produce immobility? Anesth Analg. 2008;107:832–48.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Zhang Y, Sonner JM, Eger EI II, Stabernack CR, Laster MJ, Raines DE, Harris RA. GABAA receptors do not mediate the immobility produced by inhaled anesthetics. Anesth Analg. 2004;99:85–90.PubMedCrossRefGoogle Scholar
  50. 50.
    Sonner JM, Werner DF, Elsen FP, Xing Y, Liao M, Harris RA, Harrison NL, Fanselow MS, Eger EI, 2nd, Homanics GE. Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane. Anesthesiology. 2007;106:107–13.PubMedCrossRefGoogle Scholar
  51. 51.
    Lichtenstein ME, Method H. Edmund Andrews, M.D., a biographical sketch with historical notes concerning nitrous oxide anesthesia. Q Bull Northwest Univ Med Sch. 1953;27(4):337–52.Google Scholar
  52. 52.
    Morris LE. A new vaporizer for liquid anesthetic agents. Anesthesiology. 1952;13:587–93.PubMedCrossRefGoogle Scholar
  53. 53.
    Severinghaus JW, Bradley AF. Electrodes for blood pO2 and pCO2 determination. J Appl Physiol. 1958;13:515–20.PubMedGoogle Scholar
  54. 54.
    Luft K. Über eine neue Methode der registrierenden Gasanalyse mit Hilfe der Absorption ultraroter Strahlen ohne spektrale Zerlegung. Ztschrf Techn Phys. 1943;24:97–104.Google Scholar
  55. 55.
    Severinghaus JW. Ozanne G: Multioperating room monitoring with one mass spectrometer. Acta Anaesthesiol Scand Suppl. 1978;70:186–7.PubMedGoogle Scholar
  56. 56.
    Ozanne GM, Young WG, Mazzei WJ, Severinghaus JW. Multipatient anesthetic mass spectrometry: rapid analysis of data stored in long catheters. Anesthesiology. 1981;55:62–70.PubMedCrossRefGoogle Scholar
  57. 57.
    Severinghaus JW. Gadgeteering for health care: the John W. Severinghaus lecture on translational science. Anesthesiology. 2009;110:721–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Spears RS Jr, Yeh A, Fisher DM, Zwass MS. The “educated hand”. Can anesthesiologists assess changes in neonatal pulmonary compliance manually? Anesthesiology. 1991;75:693–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Egbert LD, Bisno D. The educated hand of the anesthesiologist. A study of professional skill. Anesth Analg. 1967;46:195–200.PubMedCrossRefGoogle Scholar
  60. 60.
    Oka Y. The evolution of intraoperative transesophageal echocardiography. Mt Sinai J Med. 2002;69:18–20.PubMedGoogle Scholar
  61. 61.
    Millikan GA. The oximeter: an instrument for measuring continuously oxygen saturation of arterial blood in man. Rev Sci Instr. 1942;13:434–44.CrossRefGoogle Scholar
  62. 62.
    Wood EH, Geraci JE. Photoelectric determination of arterial oxygen saturation in man. J Lab Clin Med. 1949;34:387–401.PubMedGoogle Scholar
  63. 63.
    Nakajima S, Hirai Y, Takase H. Performances of new pulse wave earpiece oximeter. Respir Circ. 1975;23:41–5.Google Scholar
  64. 64.
    Moller JT, Pedersen T, Rasmussen LS, Jensen PF, Pedersen BD, Ravlo O, Rasmussen NH, Espersen K, Johannessen NW, Cooper JB, et al. Randomized evaluation of pulse oximetry in 20,802 patients: I. Design, demography, pulse oximetry failure rate, and overall complication rate. Anesthesiology. 1993;78:436–44.PubMedCrossRefGoogle Scholar
  65. 65.
    Eger EI II, Hamilton WK. Positive-negative pressure ventilation with a modified Ayre’s T-piece. Anesthesiology. 1958;19:611–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Schwinn DA, Balser JR. Anesthesiology physician scientists in academic medicine: a wake-up call. Anesthesiology. 2006;104:170–8.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Edmond I Eger, MD 2014

Authors and Affiliations

  1. 1.Department of Anesthesia and Perioperative CareUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations