Use of Potent Inhalational Anesthetic Agents During Mechanical Ventilation

  • Joseph D. TobiasEmail author


The clinical practice of inhalational anesthesia began in the 1840s with the demonstration of the efficacy of diethyl ether by Crawford Long and WTG Morton and nitrous oxide (N2O) by Horace Wells. In 1946, Robbins reported the development of various fluorinated hydrocarbons (Robbins 1946). This work led to the synthesis in 1951 of fluroxene (2,2,2-trifluoroethyl vinyl ether), a fluorinated hydrocarbon, which was the first of this class of agents to be widely used in clinical practice (Krantz et al. 1953; Tucker et al. 1973; Johnston et al. 1973; Harris and Cromwell 1972). Halothane, a halogenated alkane, was introduced into clinical practice in 1956 (Raventos 1956). When compared with its predecessors, halothane offered several favorable properties including nonflammability, a favorable blood-gas partition coefficient, a favorable profile for inhalation induction including a rapid onset and limited pungency, bronchodilatation, relative cardiovascular stability, and a decreased incidence of nausea and vomiting. However, halothane’s potential to elicit an immune-mediated hepatotoxicity especially in the adult population favored the development of additional agents with less hepatotoxicity.


Mean Arterial Pressure Status Epilepticus Status Asthmaticus Procedural Sedation Ventilator Circuit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adams RW, Cucchiara RF, Gronert GA, Messick JM, Michenfelder JD (1981) Isoflurane and cerebrospinal fluid pressure in neurosurgical patients. Anesthesiology 54:97–99PubMedCrossRefGoogle Scholar
  2. Arnold JH, Truog RD, Rice SA (1993a) Prolonged administration of isoflurane to pediatric patients during mechanical ventilation. Anesth Analg 76:520–526PubMedCrossRefGoogle Scholar
  3. Arnold JH, Truog RD, Molengraft JA (1993b) Tolerance to isoflurane during prolonged administration. Anesthesiology 78:985–988PubMedCrossRefGoogle Scholar
  4. Atkinson JB, Hamid R, Steward DJ (1994) General anesthesia with isoflurane for diaphragmatic hernia repair during ECMO. ASAIO J 40:986–989PubMedCrossRefGoogle Scholar
  5. Babl FE, Jamison SR, Spicer M et al (2006) Inhaled methoxyflurane as a prehospital analgesic in children. Emerg Med Australas 18:404–410PubMedCrossRefGoogle Scholar
  6. Babl F, Barnett P, Palmer G et al (2007) A pilot study of inhaled methoxyflurane for procedural analgesia in children. Paediatr Anaesth 17(2):148–153PubMedCrossRefGoogle Scholar
  7. Baum J, Sachs G, Driesch C et al (1995) Carbon monoxide generation in carbon dioxide absorbents. Anesth Analg 81:144–146PubMedGoogle Scholar
  8. Benumof JL, Augustine SD, Gibbons JA (1987) Halothane and isoflurane only slightly impair arterial oxygenation during one lung ventilation in patients undergoing thoracotomy. Anesthesiology 67:910–915PubMedCrossRefGoogle Scholar
  9. Berton J, Sargntini C, Nguyen JL et al (2007) AnaConDa® reflection filter : bench and patient evaluation of safety and volatile anesthetic conservation. Anesth Analg 104:130–134PubMedCrossRefGoogle Scholar
  10. Bierman MI, Brown M, Muren O et al (1986) Prolonged isoflurane anesthesia in status asthmaticus. Crit Care Med 14:832–833PubMedCrossRefGoogle Scholar
  11. Breheny FX, Kendall PA (1992) Use of isoflurane for sedation in the intensive care. Crit Care Med 20:1062–1064PubMedCrossRefGoogle Scholar
  12. Brown BR Jr, Gandolfi AJ (1987) Adverse effects of volatile anesthetics. Br J Anaesth 59:14–23PubMedCrossRefGoogle Scholar
  13. Coleman MA, Coles S, Lytle T (1994) Prevention of atmospheric contamination during isoflurane sedation. Clin Intensive Care 5:217–220PubMedGoogle Scholar
  14. Delgado-Escueta AV, Waterlain C, Treiman DM, Porter RJ (1982) Management of status epilepticus. N Engl J Med 306:1337–1340PubMedCrossRefGoogle Scholar
  15. Drummond JC, Todd MM, Scheller MS, Shapiro HM (1986) A comparison of the direct cerebral vasodilating potencies of halothane and isoflurane in the New Zealand white rabbit. Anesthesiology 65:462–467PubMedCrossRefGoogle Scholar
  16. Echeverria M, Gelb AW, Wexler HR et al (1986) Enflurane and halothane in status asthmaticus. Chest 89:152–154PubMedCrossRefGoogle Scholar
  17. Eckenhoff RG (1998) Do specific or nonspecific interactions with proteins underlie inhalational anesthetic action? Mol Pharmacol 54:610–615PubMedGoogle Scholar
  18. Eckenhoff R, Constant I, Seeman R, Murat I (2005) Sevoflurane and epileptiform EEG changes. Paediatr Anaesth 15:266–274CrossRefGoogle Scholar
  19. Eger EI II, Bahlman S (1971) Is end-tidal anesthetic partial pressure an accurate measure of the arterial anesthetic partial pressure? Anesthesiology 35:301–303PubMedCrossRefGoogle Scholar
  20. Enluynd M, Lambert H, Wiklund L (2002) The sevoflurane saving capacity of a new anaesthetic agent conserving device compared with a low flow circle system. Acta Anaesthesiol Scand 46:506–511CrossRefGoogle Scholar
  21. Fang ZX, Eger EI II, Laster MJ et al (1995) Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and baralyme. Anesth Analg 80:1187–1192PubMedGoogle Scholar
  22. Frink EJ Jr, Malan TP, Morgan SE et al (1992) Quantification of the degradation products of sevoflurane in two CO2 absorbents during low-flow anesthesia in surgical patients. Anesthesiology 77:1064–1069PubMedCrossRefGoogle Scholar
  23. Fuchs AM (1937) Interruption of asthmatic crisis by tribomethanol (Avertin). J Allergy 8:340–346CrossRefGoogle Scholar
  24. Fukuda H, Hirabayashi Y, Shimizu R et al (1996) Sevoflurane is equivalent to isoflurane for attenuating bupivacaine-induced arrhythmias and seizures in rats. Anesth Analg 83:570–573PubMedGoogle Scholar
  25. Gregory G, Eger EI 2nd, Munson ES (1969) The relationship between age and halothane requirement in man. Anesthesiology 30:488–491PubMedCrossRefGoogle Scholar
  26. Haafiz A, Kissoon N (1999) Status epilepticus: current concepts. Pediatr Emerg Care 15:119–129PubMedCrossRefGoogle Scholar
  27. Harris JA, Cromwell TH (1972) Jaundice following fluroxene anesthesia. Anesthesiology 37:462–463PubMedCrossRefGoogle Scholar
  28. Hilz MJ, Bauer K, Claus D et al (1992) Isoflurane anaesthesia in the treatment of convulsive status epilepticus. J Neurol 239:135–137PubMedCrossRefGoogle Scholar
  29. Hirshman CA, Edelstein G, Peetz S et al (1982) Mechanism of action of inhalational anesthesia on airways. Anesthesiology 56:107–111PubMedCrossRefGoogle Scholar
  30. Hoerauf K, Koller C, Vescia F et al (1995) Exposition des intensivpersonals durch isofluran bei langzeitsedierung. Anasthesiol Intensivmed Notfallmed Schmerzther 30:483–487PubMedCrossRefGoogle Scholar
  31. Howie AF, Spencer EM, Beckett GJ (1992) Aspartate aminotransferase, alanine aminotransferase and glutathione transferase in plasma during and after sedation by low-dose isoflurane or midazolam. Clin Chem 38:476–479PubMedGoogle Scholar
  32. Hughes DR, Sharpe MD, McLachlan RS (1992) Control of epilepsia partialis continua and secondarily generalized status epilepticus with isoflurane. J Neurol Neurosurg Psychiatry 55:739–740PubMedCentralPubMedCrossRefGoogle Scholar
  33. Huhges J, Leach HJ, Choonara I (1993) Hallucinations on withdrawal of isoflurane used as sedation. Acta Paediatr 82:885–886CrossRefGoogle Scholar
  34. Johnston RR, Cromwell TH, Eger EI 2nd et al (1973) The toxicity of fluroxene in animals and man. Anesthesiology 38:313–319PubMedCrossRefGoogle Scholar
  35. Johnston RG, Noseworthy TW, Friesen EG et al (1990) Isoflurane therapy for status asthmaticus in children and adults. Chest 97:698–701PubMedCrossRefGoogle Scholar
  36. Katoh T, Ikeda K (1994) A comparison of sevoflurane with halothane, enflurane, and isoflurane on bronchoconstriction caused by histamine. Can J Anaesth 41:1214–1219PubMedCrossRefGoogle Scholar
  37. Kelsall AWR, Ross-Russell R, Herrick MJ et al (1994) Reversible neurologic dysfunction following isoflurane sedation in pediatric intensive care. Crit Care Med 22:1032–1034PubMedCrossRefGoogle Scholar
  38. Kenna JG, Jones RM (1995) The organ toxicity of inhaled anesthetics. Anesth Analg 81(suppl):S51–S66PubMedCrossRefGoogle Scholar
  39. Kenna JG, Neuberger J, Williams R (1988) Evidence for expression in human liver of halothane-induced neoantigens recognized by antibodies in sera from patients with halothane hepatitis. Hepatology 8:1635–1641PubMedCrossRefGoogle Scholar
  40. Kofke WA, Snider MT, Young RS, Ramer JC (1985) Prolonged low flow isoflurane anesthesia for status epilepticus. Anesthesiology 62:653–656PubMedCrossRefGoogle Scholar
  41. Kofke WA, Young RSK, Davis P et al (1989) Isoflurane for refractory status epilepticus: a clinical series. Anesthesiology 71:653–659PubMedCrossRefGoogle Scholar
  42. Kong KL, Willatts SM, Prys-Roberts C (1989) Isoflurane compared with midazolam for sedation in the intensive care unit. Br Med J 298:1277–1280CrossRefGoogle Scholar
  43. Krantz JC Jr, Carr J, Lu G et al (1953) Anesthesia: anesthetic action of trifluoroethyl vinyl ether. J Pharmacol Exp Ther 108:488–492PubMedGoogle Scholar
  44. Le Dez K, Lerman J (1987) The minimum alveolar concentration (MAC) of isoflurane in preterm neonates. Anesthesiology 67:301–307CrossRefGoogle Scholar
  45. Marshall MA, Ozorio HPL (1972) Analgesia for burns dressing using methoxyflurane. Br J Anaesth 44:80–82PubMedCrossRefGoogle Scholar
  46. Mazze RI (1992) The safety of sevoflurane in humans. Anesthesiology 77:1062–1066PubMedCrossRefGoogle Scholar
  47. Mazze RI (2006) Methoxyflurane revisited: tale of an anesthetic from cradle to grave. Anesthesiology 105:843–846PubMedCrossRefGoogle Scholar
  48. Mazze RI, Calverley RK, Smith NT (1977) Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers. Anesthesiology 46:265–271PubMedCrossRefGoogle Scholar
  49. McIndoe AK, Steward P, Wilson IH (1997) Drawover vaporizers for sedation in intensive care. Intensive Care Med 23:704–707PubMedCrossRefGoogle Scholar
  50. Meeke RI, Soifer BE, Gelb AW (1989) Isoflurane for the management of status epilepticus. DICP 23:579–581PubMedGoogle Scholar
  51. Meiser A, Sirtl C, Bellgardt M et al (2003) Desflurane compared with propofol for postoperative sedation in the intensive care unit. Br J Anaesth 90:273–280PubMedCrossRefGoogle Scholar
  52. Meyer NE, Schotz S (1939) Relief of severe intractable bronchial asthma with cyclopropane anesthesia: report of case. J Allergy 10:239–240CrossRefGoogle Scholar
  53. Millane TA, Bennett ED, Grounds RM (1992) Isoflurane and propofol for long-term sedation in the intensive care unit. Anaesthesia 47:468–774CrossRefGoogle Scholar
  54. Mirsattari SM, Sharpe MD, Young GB (2004) Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol 61:1254–1259PubMedCrossRefGoogle Scholar
  55. Mori N, Nagata H, Ohta S et al (1996) Prolonged sevoflurane inhalation was not nephrotoxic in two patients with refractory status asthmaticus. Anesth Analg 83:189–191PubMedGoogle Scholar
  56. Morio M, Fujii K, Satoh N et al (1992) Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts. Anesthesiology 77:1155–1164PubMedCrossRefGoogle Scholar
  57. Morray JP, Geiduschek JM, Ramamoorthy C et al (2000) Anesthesia-related cardiac arrest in children: initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry. Anesthesiology 93:6–14PubMedCrossRefGoogle Scholar
  58. O’Rourke PP, Crone RK (1982) Halothane in status asthmaticus. Crit Care Med 10:341–343PubMedCrossRefGoogle Scholar
  59. Opitz A, Marschall M, Degen R, Koch D (1982) General anesthesia in patients with epilepsy and status epilepticus. Adv Neurol 34:531–535Google Scholar
  60. Parnass SM, Feld JM, Chamberlin WH et al (1986) Status asthmaticus treated with isoflurane and enflurane. Anesth Analg 66:193–195CrossRefGoogle Scholar
  61. Pohl LR, Satoh H, Christ DD et al (1988) The immunologic and metabolic basis of drug hypersensitivities. Annu Rev Pharmacol 28:367–387CrossRefGoogle Scholar
  62. Prys-Roberts C, Corbett JL, Kerr JH et al (1969) Treatment of sympathetic overactivity in tetanus. Lancet 294:542–545CrossRefGoogle Scholar
  63. Raventos J (1956) Action of fluothane – new volatile anesthetic. Br J Pharmacol 11:394–397Google Scholar
  64. Reilly CS, Wood AJJ, Koshakji RP, Wood M (1985) The effect of halothane on drug disposition: contribution of changes in intrinsic drug metabolizing capacity and hepatic blood flow. Anesthesiology 63:70–76PubMedCrossRefGoogle Scholar
  65. Revell S, Greenhalgh D, Absalom SR et al (1988) Isoflurane in the treatment of asthma. Anaesthesia 43:477–479PubMedCrossRefGoogle Scholar
  66. Robbins J (1946) Preliminary studies of the activity of fluorinated hydrocarbons. J Pharmacol Exp Ther 86:197–200PubMedGoogle Scholar
  67. Robertson CE, Steedman D, Sinclair CJ et al (1985) Use of ether in life-threatening acute severe asthma. Lancet 336:187–188CrossRefGoogle Scholar
  68. Ropper AH, Kofke WA, Bromfield EB et al (1986) Comparison of isoflurane, halothane, and nitrous oxide in status epilepticus. Ann Neurol 19:98–99PubMedCrossRefGoogle Scholar
  69. Rosseel P, Lauwers LF, Baute L (1985) Halothane treatment in life-threatening asthma. Intensive Care Med 11:241–246PubMedCrossRefGoogle Scholar
  70. Sackey PV, Martling CR, Granath F, Radell PJ (2004) Prolonged isoflurane sedation of intensive care unit patients with the Anesthetic Conserving Device. Crit Care Med 32:2241–2246PubMedGoogle Scholar
  71. Sackey PV, Martling CR, Nise G, Radell PJ (2005a) Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device. Crit Care Med 33:585–590PubMedCrossRefGoogle Scholar
  72. Sackey PV, Martling CR, Radell PJ (2005b) Three cases of PICU sedation with isoflurane delivered the “AnaConDa®”. Paediatr Anaesth 15:879–885PubMedCrossRefGoogle Scholar
  73. Sakaki T, Abe K, Hoshida T et al (1992) Isoflurane in the management of status epilepticus after surgery for lesion around the motor area. Acta Neurochir 116:38–43PubMedCrossRefGoogle Scholar
  74. Satoh H, Gillette JR, Takemura T et al (1986) Investigation of the immunological basis of halothane-induced hepatotoxicity. Adv Exp Med Biol 197:657–773PubMedCrossRefGoogle Scholar
  75. Saulnier FF, Durocher AV, Deturck RA et al (1990) Respiratory and hemodynamic effects of halothane in status asthmaticus. Intensive Care Med 16:104–107PubMedCrossRefGoogle Scholar
  76. Schwartz SH (1984) Treatment of status asthmaticus with halothane. JAMA 251:2688–2689PubMedCrossRefGoogle Scholar
  77. Spencer EM, Willatts SM, PRys-Roberts C (1991) Plasma inorganic fluoride concentrations during and after prolonged (>24 h) isoflurane sedation: effect on renal function. Anesth Analg 73:731–737PubMedCrossRefGoogle Scholar
  78. Sponheim S, Skraastad O, Helseth E et al (2003) Effects of 0.5 and 1.0 MAC isoflurane, sevoflurane and desflurane on intracranial and cerebral perfusion pressures in children. Acta Anaesthesiol Scand 47:932–938PubMedCrossRefGoogle Scholar
  79. Subcommittee on the National Halothane Study of the Committee on Anesthesia (1966) Possible association between halothane anesthesia and postoperative hepatic necrosis. JAMA 197:775–788CrossRefGoogle Scholar
  80. Sury MRJ, Harker H, Thomas ML (2005) Sevoflurane sedation in infants undergoing MRI: a preliminary report. Paediatr Anaesth 15:16–22PubMedCrossRefGoogle Scholar
  81. Tempia A, Olivei MC, Calza E et al (2003) The anesthetic conserving device compared with conventional circle system used under different flow conditions for inhaled anesthesia. Anesth Analg 96:1056–1061PubMedCrossRefGoogle Scholar
  82. Tobias JD, Garrett JS (1997) Therapeutic options for severe, refractory status asthmaticus: inhalational anaesthetic agents, extracorporeal membrane oxygenation, and helium/oxygen ventilation. Paediatr Anaesth 7:47–57PubMedCrossRefGoogle Scholar
  83. Tobias JD, Miltenberg L (2009) Changes in delivered tidal volume with the addition of carbon dioxide to mechanical ventilation. Paediatr Anaesth 19:240–243PubMedCrossRefGoogle Scholar
  84. Truog RA, Rice SA (1989) Inorganic fluoride and prolonged isoflurane anesthesia in the intensive care unit. Anesth Analg 69:843–845PubMedCrossRefGoogle Scholar
  85. Tucker WK, Munson ES, Holaday DA et al (1973) Hepatorenal toxicity following fluroxene anesthesia. Anesthesiology 39:104–107PubMedCrossRefGoogle Scholar
  86. Vaughan RS, Mapleson WW, Mushin WW (1973) Prevention of pollution of operating theatres with halothane vapour by adsorption with activated charcoal. Br Med J 1:727–729PubMedCentralPubMedCrossRefGoogle Scholar
  87. Wark HJ (1983) Postoperative jaundice in children – the influence of halothane. Anaesthesia 38:237–242PubMedGoogle Scholar
  88. Warner LO, Beach TP, Garvin JP et al (1984) Halothane and children: the first quarter century. Anesth Analg 63:838–840PubMedGoogle Scholar
  89. Warner DO, Vettermann J, Brichant JF et al (1990) Direct and neurally mediated effects of halothane on pulmonary resistance in vivo. Anesthesiology 72:1057–1063PubMedCrossRefGoogle Scholar
  90. Watanabe K, Mizutani T, Yamashita S et al (2008) Prolonged sevoflurane inhalation therapy for status asthmaticus in an infant. Paediatr Anaesth 18:543–545PubMedCrossRefGoogle Scholar
  91. Wheeler DS, Clapp CR, Ponaman ML, McEachren HM, Poss B (2000) Isoflurane therapy for status asthmaticus in children: a case series and protocol. Pediatr Crit Care Med 1:55–59PubMedCrossRefGoogle Scholar
  92. Woehlck HJ (1999) Severe intraoperative CO poisoning. Should apathy prevail? Anesthesiology 90:353–355PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Anesthesiology and Pain MedicineNationwide Children’s HospitalColumbusUSA
  2. 2.Department of Anesthesiology and PediatricsThe Ohio State UniversityColumbusUSA

Personalised recommendations