Abstract
A prospective, crossover, double-blind trial was conducted in nine healthy volunteers in which the subjective, psychomotor and memory effects of isoflurane (0.0, 0.3 and 0.6%) and nitrous oxide (N2O) (0, 20 and 40%) were examined. Dependent measures included visual analog scales and a standardized drug effects inventory (subjective effects), reaction time and eye-hand coordination (e.g., psychomotor performance), and immediate and delayed free recall (memory). There were some similarities in subjective effects between the two inhaled drugs (e.g., increased ratings of “drunk” and “spaced out”), but isoflurane had effects which N2O did not have. Isoflurane but not N2O increased visual analog scale ratings of “confused,” “sedated,” and “carefree,” and decreased ratings of “in control of thoughts” and “in control of body.” An odor was detected with isoflurane and it was disliked. Psychomotor performance was more grossly impaired during isoflurane inhalation than during N2O inhalation. Psychomotor recovery from both agents was rapid and complete so that 5 min after the inhalation period had ceased, performance had returned to baseline levels. Both isoflurane and nitrous oxide impaired immediate and delayed free recall. The feasibility of using isoflurane in conscious sedation procedures is discussed.
Similar content being viewed by others
References
Adam N (1973) Effects of general anesthetics on memory functions in man. J Comp Physiol Psychol 83:294–305
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC
Atkinson RM, Morozumi P, Green JD, Kramer JC (1977) Nitrous oxide intoxication: subjective effects in healthy young men. J Psychedelic Drugs 9:317–328
Block RI, Ghoneim MM, Kumar V, Pathak D (1990) Psychedelic effects of a subanesthetic concentration of nitrous oxide. Anesth Prog 37:271–276
Cohen EN, Gift HC, Brown BW (1980) Occupational disease in dentistry and chronic exposure to trace anesthetic gases. J Am Dent Assoc 101:21–31
Cromwell TH, Eger EI, Stevens WC, Dolan MW (1971) Forane uptake, excretion, and blood solubility in man. Anesthesiology 35:401–408
Davy H (1800) Researches, chemical and philosophical: chiefly concerning nitrous oxide, or dephlogisticated nitrous air, and its respiration. J Johnson, London
Derogatis LR, Lipman RS, Cozi L (1973) HSCL-90: an outpatient psychiatric rating scale — preliminary report. Psychopharmacol Bull 9:13–17
Dohrn C, Lichtor JL, Finn RS, Uitvlugt A, Coalson DW, Rupani G, de Wit H, Zacny JP (1992) Subjective and psychomotor effects of nitrous oxide in healthy volunteers. Behav Pharmacol 3:19–30
Doi M, Ikeda K (1993) Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. Can J Anaesth 40:122–126
Dwyer R, Bennett HL, Eger EI, Heilbron D (1992) Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. Anesthesiology 77:888–898
File SE, Balakrishnan J, Murray A, Harris A, Skelly AM (1992) Effects of nitrous oxide on memory for instructions in dental patients. Hum Psychopharmacol 7:37–44
Finck AD (1985) Nitrous oxide analgesia. In: Eger EI (ed) Nitrous oxide/N2O. Edward Arnold, London
Flemming DC, Johnstone RE (1977) Recognition thresholds for diethyl ether and halothane. Anesthesiology 46:68–69
Gambill AF, McCallum RN, Henrichs TF (1979) Psychomotor performance following exposure to trace concentrations of inhalation anesthetics. Anesth Analg 58:475–482
Garfield JM, Garfield FB, Sampson J (1975) Effects of nitrous oxide on decision-strategy and sustained attention. Psychopharmacology 42:5–10
GasMan (1990) Understanding anesthesia uptake and distribution (JE Philip). Harvard Medical School, Boston
Haertzen CA (1966) Development of scales based on patterns of drug effects, using the Addiction Research Center Inventory (ARCI). Psychol Rep 18:163–194
Henrie JR, Parkhouse J, Bickford RG (1961) Alteration of human consciousness by nitrous oxide as assessed by electroencephalography and psychological tests. Anesthesiology 22:247–259
Ho ET, Parbrook GD, Still DM, Parbrook EO (1990) Memory function after i.v. midazolam or inhalation of isoflurane for sedation during dental surgery. Br J Anaesth 64:337–340
Jarvis MJ, Lader MH (1970) The effect of nitrous oxide on reaction time and cerebral evoked potential. Br J Pharmacol 39:254–255
Korttila K, Ghoneim MM, Jacobs L, Mewaldt SP, Petersen RC (1981) Time course of mental and psychomotor effects of 30 percent nitrous oxide during inhalation and recovery. Anesthesiology 54:220–226
Layzer RB (1978) Myeloneuropathy after prolonged exposure to nitrous oxide. Lancet 2:1227–1230
Marshall BE, Longnecker DE (1990) General anesthetics. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilman's the pharmacological basis of therapeutics. Pergamon, New York, pp 285–310
Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258
McMenemin IM, Parbrook GD (1988) Comparison of the effects of subanesthetic concentrations of isoflurane or nitrous oxide in volunteers. Br J Anaesth 60:56–63
Nathan JE, Venham LL, West MS, Werboff J (1988) The effects of nitrous oxide on anxious young pediatric patients across sequential visits: a double-blind study. J Dent Child May/June:220–230
Newton DE, Thornton C, Konieczko K, Frith CD, Dore CJ, Webster NR, Luff N (1992) Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane. Br J Anaesth 65:609–615
Nuotto EJ, Korttila K (1991) Evaluation of a new computerized psychomotor test battery: effects of alcohol. Pharmacol Toxicol 68:360–365
Paivio A, Yuille JC, Madigan SA (1968) Concreteness, imagery, and meaningfulness values for 925 nouns. J Exp Psychol 76:1–25
Parbrook GD, James J, Braid DOP (1987) Inhalational sedation with isoflurane: an alternative to nitrous oxide sedation in dentistry. Br Dent J 163:88–92
Parbrook GB, Still DM, Parbrook EO (1989) Comparison of i.v. sedation with midazolam and inhalation sedation with isoflurane in dental outpatients. Br J Anaesth 63:81–86
Rodrigo MRC, Rosenquist JB (1988) Isoflurane for conscious sedation. Anaesthesia 43:369–375
Rosenberg P (1974) The effect of N2O-oxygen inhalation on subjective experiences of healthy young adults. Ann Chir Gynaecol Fenn 63:500–504
Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ (1992) Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. N Engl J Med 327:993–997
Steinberg H (1956) “Abnormal behaviour” induced by nitrous oxide. Br J Psychol 47:183–194
Sweeney B, Bingham RM, Amos RJ, Petty AC, Cole PV (1985) Toxicity of bone marrow in dentists exposed to nitrous oxide. BMJ 291:567–569
Thorndike EL, Lorge L (1944) The teacher's word book of 30,000 words. Columbia University Press, New York
Timsit-Berthier M, de Thier D, Timsit M (1987) Electrophysiological and psychological aspects of the derealization state induced by nitrous oxide in nine control subjects. Adv Biol Psychiatry 16:90–101
Tiplady B, Sinclair WA, Morrison LM (1992) Effects of nitrous oxide on psychological performance. Psychopharmacology Bull 28:207–211
Trieger N, Loskota WJ, Jacobs AW, Newman MG (1971) Nitrous oxide-a study of physiological and psychomotor effects. J Am Dent Assoc 82:142–150
Wechsler D (1958) The measurement and appraisal of adult intelligence. Williams and Wilkins, Baltimore
Yurino M, Kimura H (1993) Vital capacity rapid inhalation induction technique: comparison of sevolurane and halothane. Can J Anaesth 40:440–443
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zacny, J.P., Sparacino, G., Hoffmann, P.M. et al. The subjective, behavioral and cognitive effects of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers. Psychopharmacology 114, 409–416 (1994). https://doi.org/10.1007/BF02249330
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02249330