Significant Developments in the 1990s

  • Edmond I EgerII
  • Rod N. Westhorpe
  • Lawrence J. Saidman


The 1990s advanced safety, control and understanding of clinical anesthesia. Two new, poorly soluble inhaled anesthetics, sevoflurane and desflurane allowed a more precise control over the anesthetic state. Sevoflurane did so without cardiorespiratory stimulation. Both protected the heart from hypoxia. An older anesthetic, isoflurane, could reverse mental depression. We learned that all these anesthetics acted on central pattern generators in the ventral spinal cord to make patients immobile despite ongoing surgery. We also learned that the Meyer-Overton theory correlating lipophilicity and anesthetic potency didn’t always work, indirectly suggesting that inhaled anesthetics operated on proteins. Two new muscle relaxants, recuronium and cis-atracurium added to safety by acting more rapidly and for shorter times.


History of anesthesia Anesthesia history Anesthesia in the 1990s Sevoflurane history Desflurane history Anesthesia society history 


  1. 1.
    Muir AW, Houston J, Green KL, Marshall RJ, Bowman WC, Marshall IG. Effects of a new neuromuscular blocking agent (Org 9426) in anaesthetized cats and pigs and in isolated nerve-muscle preparations. Br J Anaesth. 1989;63:400–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Wierda JM, de Wit AP, Kuizenga K, Agoston S. Clinical observations on the neuromuscular blocking action of Org 9426, a new steroidal non-depolarizing agent. Br J Anaesth. 1990;64:521–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Prielipp RC, Coursin DB, Scuderi PE, Bowton DL, Ford SR, Cardenas VJ Jr., Vender J, Howard D, Casale EJ, Murray MJ. Comparison of the infusion requirements and recovery profiles of vecuronium and cisatracurium 51W89 in intensive care unit patients. Anesth Analg. 1995;81:3–12.PubMedGoogle Scholar
  4. 4.
    Fleming NW, Chung F, Glass PS, Kitts JB, Kirkegaard-Nielsen H, Gronert GA, Chan V, Gan TJ, Cicutti N, Caldwell JE. Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol. Anesthesiology. 1999;91:1311–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Rajchert DM, Pasquariello CA, Watcha MF, Schreiner MS. Rapacuronium and the risk of bronchospasm in pediatric patients. Anesth Analg. 2002;94:488–93.PubMedCrossRefGoogle Scholar
  6. 6.
    Jones RM, Cashman JN, Mant TGK. Clinical impressions and cardiorespiratory effects of a new fluorinated inhalation anaesthetic, desflurane (I-653), in volunteers. Br J Anaesth. 1990;64:11–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Wallin RF, Napoli MD, Regan BM. Laboratory investigation of a new series of inhalational anesthetic agents: the halomethyl polyfluoroisopropyl ethers. In: Fink BR, editor. Cellular Biology and Toxicity of Anesthetics. Baltimore: Williams & Wilkins Co; 1972. pp. 286–95.Google Scholar
  8. 8.
    Wallin RF, Regan BM, Napoli MD, Stern IJ. Sevoflurane: a new inhalational anesthetic agent. Anesth Analg. 1975;54:758–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Holaday DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers. Anesthesiology. 1981;54:100–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Cook TL, Beppu WJ, Hitt BA, Kosek JC, Mazze RI. A comparison of renal effects and metabolism of sevoflurane and methoxyflurane in enzyme-induced rats. Anesth Analg. 1975;54:829–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Hitt BA, Mazze RI, Cook TL, Beppu WJ, Kosek JC. Thermoregulatory defect in rats during anesthesia. Anesth Analg. 1977;56:9–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Brown BR Jr. Sevoflurane: introduction and overview. Anesth Analg. 1995;81:S. 1–3.CrossRefGoogle Scholar
  13. 13.
    Yasuda N, Lockhart SH, Eger EI II, Weiskopf RB, Johnson BH, Freire BA, Fassoulaki A. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology. 1991;74:489–98.PubMedCrossRefGoogle Scholar
  14. 14.
    Yasuda N, Lockhart SH, Eger EI II, Weiskopf RB, Liu J, Laster M, Taheri S, Peterson NA. Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth Analg. 1991;72:316–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Weiskopf RB, Eger EI II, Ionescu P, Yasuda N, Cahalan MK, Freire B, Peterson N, Lockhart SH, Rampil IJ, Laster M. Desflurane does not produce hepatic or renal injury in human volunteers. Anesth Analg. 1992;74:570–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Eger EI II, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, Gong D, Sonner J, Weiskopf RB. Nephrotoxicity of sevoflurane vs. desflurane anesthesia in volunteers. Anesth Analg. 1997;84:160–8.PubMedGoogle Scholar
  17. 17.
    Higuchi H, Sumita S, Wada H, Ura T, Ikemoto T, Nakai T, Kanno M, Satoh T. Effects of sevoflurane and isoflurane on renal function and on possible markers of nephrotoxicity. Anesthesiology. 1998;89:307–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Gonsowski CT, Laster MJ, Eger EI II, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of a 3-hour administration. Anesthesiology. 1994;80:556–65.PubMedCrossRefGoogle Scholar
  19. 19.
    Gonsowski CT, Laster MJ, Eger EI II, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of increasing duration of administration. Anesthesiology. 1994;80:566–73.PubMedCrossRefGoogle Scholar
  20. 20.
    Ebert TJ, Muzi M, Lopatka CW. Neurocirculatory responses to sevoflurane in humans. A comparison to desflurane. Anesthesiology. 1995;83:88–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Weiskopf RB, Eger EI II, Noorani M, Daniel M. Repetitive rapid increases in desflurane concentration blunt transient cardiovascular stimulation in humans. Anesthesiology. 1994;81:843–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Ter Riet MF, De Souza GJA, Jacobs JS, Young D, Lewis MC, Herrington C, Gold MI. Which is most pungent: isoflurane, sevoflurane or desflurane? Br J Anaesth. 2000;85:305–7.CrossRefGoogle Scholar
  23. 23.
    Rampil IJ, Lockhart SH, Zwass MS, Peterson N, Yasuda N, Eger EI 2nd, Weiskopf RB, Damask MC. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration. Anesthesiology. 1991;74:429–33.PubMedCrossRefGoogle Scholar
  24. 24.
    Weiskopf RB, Eger EI 2nd, Noorani M, Daniel M. Fentanyl, esmolol, and clonidine blunt the transient cardiovascular stimulation induced by desflurane in humans. Anesthesiology. 1994;81:1350–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Vickery RG, Sheridan BC, Segal IS, Maze M. Anesthetic and hemodynamic effects of the stereoisomers of medetomidine, an alpha 2-adrenergic agonist, in halothane-anesthetized dogs. Anesth Analg. 1988;67:611–5.PubMedGoogle Scholar
  26. 26.
    Oliver MF, Goldman L, Julian DG, Holme I. Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT). Anesthesiology. 1999;91:951–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, Mangano DT. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology. 1995;82:620–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, Bohner D. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg. 1991;72:275–81.PubMedCrossRefGoogle Scholar
  29. 29.
    Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A, Hampl K, von Hochstetter A. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5 % lidocaine. Anesth Analg. 1993;76:1154–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Pollock JE, Neal JM, Stephenson CA, Wiley CE. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology. 1996;84:1361–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Adverse Reactions with Bupivacaine. FDA Drug Bull. 1983;13:23.Google Scholar
  32. 32.
    Valenzuela C, Snyders DJ, Bennett PB, Tamargo J, Hondeghem LM. Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation. 1995;92:3014–24.PubMedCrossRefGoogle Scholar
  33. 33.
    Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Kapral S, Krafft P, Eibenberger K, Fitzgerald R, Gosch M, Weinstabl C. Ultrasound-guided supraclavicular approach for regional anesthesia of the brachial plexus. Anesth Analg. 1994;78:507–13.PubMedCrossRefGoogle Scholar
  35. 35.
    Slogoff S, Keats AS. Does perioperative myocardial ischemia lead to postoperative myocardial infarction? Anesthesiology. 1985;62:107–14.PubMedCrossRefGoogle Scholar
  36. 36.
    Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996;335:1713–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Wallace AW, Galindez D, Salahieh A, Layug EL, Lazo EA, Haratonik KA, Boisvert DM, Kardatzke D. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology. 2004;101:284–93.PubMedCrossRefGoogle Scholar
  38. 38.
    Cason BA, Gamperl AK, Slocum RE, Hickey RF. Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology. 1997;87:1182–90.PubMedCrossRefGoogle Scholar
  39. 39.
    Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial KATP channels via multiple signaling pathway. Anesthesiology. 2002;97:4–14.PubMedCrossRefGoogle Scholar
  40. 40.
    De Hert SG, Cromheecke S, ten Broecke PW, Mertens E, De Blier IG, Stockman BA, Rodrigus IE, Van der Linden PJ. Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high risk patients. Anesthesiology. 2003;99:314–23.PubMedCrossRefGoogle Scholar
  41. 41.
    Parke TJ, Stevens JE, Rice AS, Greenaway CL, Bray RJ, Smith PJ, Waldmann CS, Verghese C. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. BMJ. 1992;305:613–6.PubMedCrossRefGoogle Scholar
  42. 42.
    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
  43. 43.
    Hopf HW, Hunt TK, West JM, Blomquist P, Goodson WH 3rd, Jensen JA, Jonsson K, Paty PB, Rabkin JM, Upton RA, von Smitten K, Whitney JD. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg. 1997;132:997–1004. (discussion 1005)Google Scholar
  44. 44.
    Kohn LT, Corrigan JM, Donaldson MS. To err is human: building a safer health system. Washingon, DC: National Academy Press (Institute of Medicine); 2000.Google Scholar
  45. 45.
    Pronovost P, Jenckes M, Dorman T, Garrett E, Breslow MJ, Rosenfeld BA, Lipsett PA, Bass E. Organizational characteristics of intensive care units related to outcomes of abdominal aortic surgery. J Amer Med Assoc. 1999;281:1310–7.CrossRefGoogle Scholar
  46. 46.
    Lagasse RS. Anesthesia safety: model or myth? A review of the published literature and analysis of current original data. Anesthesiology. 2002;97:1609–17.PubMedCrossRefGoogle Scholar
  47. 47.
    Langer G, Neumark J, Koinig G, Graf M, Schoenbeck G. Rapid psychotherapeutic effects of anesthesia with isoflurane (ED narcotherapy) in treatment-refractory depressed patients. NeuropsychoBiology. 1985;14:118–20.PubMedCrossRefGoogle Scholar
  48. 48.
    Langer G, Karazman R, Neumark J, Saletu B, Schoenbeck G, Gruenberger J, Dittrich R, Petricek W, hoffmann P, Linzmayer L, Anderer P, Steinberger K. Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment. NeuropsychoBiology. 1995;31:182–94.PubMedCrossRefGoogle Scholar
  49. 49.
    Engelhardt W, Carl G, Hartung E. Intra-individual open comparison of burst-suppression-isoflurane-anaesthesia versus electroconvulsive therapy in the treatment of severe depression. Eur J Anaesthesiol. 1993;10:113–8.PubMedGoogle Scholar
  50. 50.
    Schwilden H. A general method for calculating the dosage scheme in linear pharmacokinetics. Eur J Clin Pharmacol. 1981;20:379–86.PubMedCrossRefGoogle Scholar
  51. 51.
    Raemer DB, Buschman A, Varvel JR, Philip BK, Johnson MD, Stein DA, Shafer SL. The prospective use of population pharmacokinetics in a computer-driven infusion system for alfentanil. Anesthesiology. 1990;73:66–72.PubMedCrossRefGoogle Scholar
  52. 52.
    Shafer SL, Varvel JR, Aziz N, Scott JC. Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Anesthesiology. 1990;73:1091–102.PubMedCrossRefGoogle Scholar
  53. 53.
    Glen JB. The development of ‘Diprifusor’: a TCI system for propofol. Anaesthesia. 1998;53 Suppl 1:13–21.PubMedCrossRefGoogle Scholar
  54. 54.
    Denson JS, Abrahamson S. A computer-controlled patient simulator. JAMA. 1969;208:504–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Gaba DM, DeAnda A. A comprehensive anesthesia simulation environment: re-creating the operating room for research and training. Anesthesiology. 1988;69:387–94.PubMedCrossRefGoogle Scholar
  56. 56.
    Cooper JB, Taqueti VR. A brief history of the development of mannequin simulators for clinical education and training. Qual Saf Health Care. 2004;13 Suppl 1:i11–8.CrossRefGoogle Scholar
  57. 57.
    Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology. 1993;79:1244–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology. 1993;78:707–12.PubMedCrossRefGoogle Scholar
  59. 59.
    Koblin DD, Chortkoff BS, Laster MJ, Eger EI II, Halsey MJ, Ionescu P. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg. 1994;79:1043–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature. 1994;367:607–14.PubMedCrossRefGoogle Scholar
  61. 61.
    Lysko GS, Robinson JL, Casto R, Ferrone RA. The stereospecific effects of isoflurane isomers in vivo. Eur J Pharmacol. 1994;263:25–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Franks NP, Lieb WR. Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels. Science. 1991;254:427–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Saidman LJ. The 33rd Rovenstine Lecture. What I have learned from 9 years and 9,000 papers. Anesthesiology. 1995;83:191–7.CrossRefGoogle Scholar
  64. 64.
    Fischer SP. Development and effectiveness of an anesthesia preoperative evaluation clinic in a teaching hospital. Anesthesiology. 1996;85:196–206.PubMedCrossRefGoogle Scholar
  65. 65.
    Gualtieri AC, Cosentino JP, Becker JS: The California experience with the diversion program for impaired physicians. JAMA. 1983;249:226–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Pelton C, Ikeda RM. The California Physicians Diversion Program’s experience with recovering anesthesiologists. J Psychoactive Drugs. 1991;23:427–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Paris RT, Canavan DI. Physician substance abuse impairment: anesthesiologists vs. other specialties. J Addict Dis. 1999;18:1–7.PubMedCrossRefGoogle Scholar

Copyright information

© Edmond I Eger, MD 2014

Authors and Affiliations

  • Edmond I EgerII
    • 1
  • Rod N. Westhorpe
    • 2
  • Lawrence J. Saidman
    • 3
  1. 1.Department of Anesthesia and Perioperative CareUniversity of CaliforniaSan FranciscoUSA
  2. 2.MelbourneAustralia
  3. 3.Departments of AnesthesiaStanford UniversityStanfordUSA

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