| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
© 1999 International Anesthesia Research Society
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
We studied the effects of subanesthetic concentrations of sevoflurane and nitrous oxide, alone and in combination, on analgesia, mood, and psychomotor performance in human volunteers. We hypothesized that nitrous oxide and sevoflurane would produce both opposing and potentiating effects within the same study. Over the course of three sessions, 20 subjects inhaled 0%, 0.2%, or 0.4% end-tidal sevoflurane for a 68-min period that was divided into four 17-min blocks. During either the second or fourth block, 30% end-tidal nitrous oxide was added to the concentration of sevoflurane being inhaled. Pain response, psychomotor performance, and mood were evaluated during the second and fourth blocks. Pain ratings were higher when sevoflurane and nitrous oxide were administered together than when nitrous oxide was administered alone, which indicates that sevoflurane attenuated the analgesic effects of nitrous oxide. Sevoflurane increased self-reported ratings of sleepiness, and the addition of nitrous oxide decreased these ratings. Nitrous oxide potentiated psychomotor impairment that was induced by sevoflurane. The combination of sevoflurane and nitrous oxide produced both opposing and potentiating effects within the same study. The results suggest that nitrous oxide and sevoflurane may act through different neurochemical mechanisms on some end points, such as analgesia and sleepiness.
Implications: Healthy volunteers inhaled subanesthetic concentrations of sevoflurane and nitrous oxide. Sevoflurane made nitrous oxide less effective as an analgesic, and nitrous oxide made sevoflurane less effective as a sedative. The two drugs may work at cross purposes on different end points of anesthesia.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Several studies examining a number of different outcome measures have investigated the interaction of nitrous oxide and volatile anesthetics. Depending on the particular end point being measured, the interaction can result in a potentiated effect (defined as a larger effect from the drug combination than either drug alone with no implications as to whether the larger effect is additive or greater or lesser than additive) or an antagonist-like effect. A number of animal and human studies have examined the combined effect of volatile anesthetics and nitrous oxide on electroencephalogram (EEG) activity and have determined that nitrous oxide reverses, or attenuates, the EEG waves indicative of central nervous system (CNS) depression (1–5). For example, in several animal and human studies, volatile anesthetic-induced EEG burst suppression was reversed by the addition of nitrous oxide (1–4). In this respect, nitrous oxide opposes, or antagonizes, the effects of a volatile anesthetic. Similarly, nitrous oxide presentation has been found to antagonize the ability of volatile anesthetics to suppress responses to verbal commands and the recall of material in humans (6,7). Likewise, in rats, nitrous oxide-induced analgesia was attenuated by the addition of volatile anesthetics (8). In contrast to these examples of antagonism, somatosensory evoked potentials that were depressed by volatile anesthetics were depressed further (i.e., a potentiated effect) by nitrous oxide (4,5). In addition, the psychomotor-impairing effects of a volatile anesthetic were potentiated by nitrous oxide in human volunteers (9).
In the present study, we investigated the hypothesis that nitrous oxide and a volatile anesthetic, sevoflurane, would have both opposing effects and potentiating effects within the same study. The behavioral end points measured were analgesia, sleepiness and other mood variables, and psychomotor performance. Based on the previously published results summarized above, we predicted that sevoflurane would oppose the analgesic effects of nitrous oxide, that nitrous oxide would oppose the soporific effects of sevoflurane, and that nitrous oxide would potentiate the psychomotor-impairing effects of sevoflurane.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study was approved by the local institutional review board. Informed, written consent was obtained from each subject before initiating the study. Before the first session, subjects attended a screening interview in which their psychiatric and medical status was assessed to determine whether there were any contraindications to their study participation (10,11). Twelve men and eight women completed the study (mean ± SD age 26.3 ± 3.9 yr).
The experiment consisted of three sessions, each separated by at least 3 days. A randomized, cross-over design was used. Subjects inhaled either 100% oxygen (placebo), 0.2% end-tidal sevoflurane in oxygen, or 0.4% end-tidal sevoflurane in oxygen for a 68-min period that was divided into four 17-min blocks. During either the second or fourth block, 30% end-tidal nitrous oxide was added to the concentration of sevoflurane (0%, 0.2%, or 0.4%) being inhaled. This design yielded six conditions in which mood, psychomotor performance, and analgesia were assessed: placebo (100% oxygen), 30% nitrous oxide alone, 0.2% sevoflurane alone, 0.2% sevoflurane combined with 30% nitrous oxide, 0.4% sevoflurane alone, and 0.4% sevoflurane combined with 30% nitrous oxide. The study was double-blinded: the research technician administering the tests and the subjects were unaware of the drug or dose being inhaled. The anesthesiologist administering the drugs had minimal verbal contact with the subjects during the experimental sessions.
Each session was approximately 150 min in duration and took place in either the morning or the afternoon. Participants had been instructed not to eat food for 4 h and not to drink any liquids for 2 h before sessions. All subjects were given breath alcohol tests, and female subjects were given pregnancy tests before the start of each session. Anesthetics and oxygen were delivered via a semiclosed circuit from an anesthetic machine. Subjects were seated in a chair and breathed through a clear anesthesia face mask that was held tightly in place with rubber straps. Oil of peppermint was placed in the circuit to mask any differential odors between the two study drugs. Noninvasive measurements of heart rate, peripheral oxygen saturation, and blood pressure were initiated at the beginning of the session and were continuously monitored throughout the inhalation. Inhaled and exhaled levels of oxygen, carbon dioxide, sevoflurane, and nitrous oxide were measured continuously with a gas analyzer (Capnomac®; Datex, Helsinki, Finland) and were recorded at periodic intervals during inhalation.
At the beginning of the inhalation, subjects were told that they would be inhaling air that may or may not contain drugs for the next 68 min. The anesthesiologist alerted the technician to begin timing the session and began administering the assigned concentration of sevoflurane (0%, 0.2%, or 0.4% end-tidal). Inspired gas concentrations were not to exceed 1.0% sevoflurane or 40% nitrous oxide. Using these maximal concentrations as limits, the anesthesiologist applied overpressure to equilibrate the exhaled gas concentration with the target concentration as rapidly as possible, which usually (>90% of the sessions) occurred within 5 min of drug administration. Total fresh open flow was maintained at 5 L/min. During either the second or the fourth inhalation block, 30% end-tidal nitrous oxide was added to the concentration of sevoflurane being inhaled. Subjects completed mood forms and psychomotor tests 10 min into the second inhalation block (i.e., at 27 min) and 10 min into the fourth inhalation block (i.e., at 61 min). A 2-min test in which the subject's nondominant forearm was immersed in 2°C water was initiated 15 min into the second block (i.e., at 32 min) and 15 min into the fourth block (i.e., 66 min) to test the analgesic effects of the inhaled anesthetics (12).
To assess the subjects' experience of pain, we used both verbal ratings and a written questionnaire. Subjects were instructed to verbally rate the pain and its bothersomeness on a scale of 0–10 during the immersion of the arm in 2°C water (0 = not painful/bothersome at all to 10 = extremely painful/bothersome). The questions "How painful is it?" and "How much does it bother you?" were asked 10, 30, 50, 80, and 110 s into the immersion. One minute into the cold water immersion, subjects completed a questionnaire containing seven adjectives (throbbing, shooting, stabbing, gnawing, aching, tender, and splitting) taken from the short form of the McGill Pain Questionnaire (SF-MPQ) (13). Each descriptor is ranked on an intensity scale of 0–3 (0 = none, 1 = mild, 2 = moderate, 3 = severe).
To assess subjective effects, we used three measures: a visual analog scale (VAS), a drug effects/liking questionnaire, and an odor detection/liking questionnaire. The subjective effects battery took subjects approximately 2–4 min to complete. The VAS consisted of 21 100-mm lines, each labeled with an adjective (e.g., anxious, high, lightheaded, sedated [calm, tranquil], sleepy [drowsy, tired]). Subjects were instructed to place a mark on each line indicating how they felt at the moment, ranging from 0 ("not at all") to 100 ("extremely"). The drug effects/liking questionnaire consisted of two items and assessed on an integer scale of 1–5 (1 = "I feel no effect from it at all" to 5 = "I feel a very strong effect") the extent to which subjects currently felt a drug effect, and, on a 100-mm line (0 = dislike a lot, 50 = neutral, 100 = like a lot) the extent to which subjects liked the drug effect. The odor detection/liking questionnaire consisted of two items and assessed on an integer scale of 1–5 (1 = "I do not smell an odor at all" to 5 = "I smell a very strong odor") the extent to which subjects currently detected an odor in the air that they were inhaling, and, on a 100-mm line (0 = dislike a lot, 50 = neutral, 100 = like a lot) the extent to which subjects liked/disliked the odor.
To assess arousal level of the volunteer, the blinded technician used the Modified Observer's Assessment of Alertness/Sedation scale (14). The ratings are as follows: 1 = asleep, not readily arousable; 2 = asleep, slowly responds to verbal commands and/or gentle stimulation; 3 = drowsy, readily responds to verbal commands and/or gentle stimulation; 4 = awake, calm, and quiet; 5 = awake and active. Observer ratings were recorded for 16 of the 20 subjects.
To assess psychomotor functioning, we used the Digit Symbol Substitution Test (DSST), a simple written test in which the subject is instructed to replace digits with corresponding symbols for a 60-s period (15). The score is the correct number of symbols drawn by the subject.
Data were analyzed using repeated-measures analyses of variance (ANOVA). The factors were sevoflurane concentration (0%, 0.2%, and 0.4%) and nitrous oxide concentration (0% and 30%). For ratings of pain intensity and pain bothersomeness, the additional factor of time (10, 30, 50, 80, and 110 s into the immersion) was included. F values were considered significant for P 
0.05, with adjustments of within-factors degrees of freedom (16) to protect against violations of sphericity. Tukey's post hoc comparison tests were conducted when appropriate. For main effects and interactions that were statistically significant, an ANOVA was performed at each sevoflurane concentration to determine whether nitrous oxide produced differential effects between subjects who received nitrous oxide during the second inhalation block and those who received nitrous oxide during the fourth inhalation block. The factors for these ANOVAs were nitrous oxide concentration (0% and 30%) and the order of nitrous oxide administration (second or fourth block).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Ratings of pain intensity (F[1,19] = 41.2, P < 0.0001) and pain bothersomeness (F[1,19] = 26.9, P < 0.0001) were significantly decreased by nitrous oxide. A significant sevoflurane nitrous oxide interaction (F[2,38] = 3.3, P < 0.05) was obtained on ratings of pain intensity. Post hoc tests revealed that pain intensity ratings were significantly higher with 0.2% sevoflurane/30% nitrous oxide and 0.4% sevoflurane/30% nitrous oxide than with 0% sevoflurane/30% nitrous oxide. Neither 0.2% sevoflurane/0% nitrous oxide nor 0.4% sevoflurane/0% nitrous oxide produced pain intensity ratings that differed significantly from placebo (0% sevoflurane/0% nitrous oxide), which indicates that sevoflurane did not produce a hyperalgesic effect (Fig. 1). The order of nitrous oxide administration (i.e., whether subjects received nitrous oxide during the second or the fourth inhalation block) did not affect pain intensity or pain bothersomeness ratings.
|
The ratings of aching, gnawing, and shooting from the SF-MPQ were significantly decreased by nitrous oxide (P < 0.05). For the terms "splitting" and "stabbing," there were main effects of both sevoflurane and nitrous oxide (P < 0.05), with nitrous oxide decreasing ratings on these terms and sevoflurane increasing ratings on these terms. There was one order effect on the SF-MPQ: in the 0% sevoflurane sessions, subjects who received nitrous oxide 27 min into the inhalation reported higher ratings for the term "aching" (mean 1.8) than did subjects who received nitrous oxide 51 min into the inhalation (mean 1.2) (F[1,18] = 10.5, P < 0.005).
VAS
Three ratings were affected by nitrous oxide but not by sevoflurane. Nitrous oxide decreased ratings of "sedated" (calm, tranquil) (P < 0.001) and increased ratings of "confused" (P < 0.005) and of "having pleasant bodily sensations" (P < 0.05). Sevoflurane, but not nitrous oxide, increased ratings of "down" (P < 0.05). "Sleepy" (drowsy, tired) ratings were increased by sevoflurane (P < 0.001) and decreased by nitrous oxide (P < 0.001) with a marginal sevoflurane x nitrous oxide interaction (P < 0.10). Figure 2 shows that sevoflurane increased "sleepy" ratings and that, when nitrous oxide was added to the volatile anesthetic, the ratings were decreased to a level that did not differ statistically from placebo ratings. There were another six sevoflurane x nitrous oxide interactions: "tingling" (P < 0.05), "coasting" (P < 0.005), "floating" (P < 0.001), "lightheaded" (P < 0.05), "high" (P < 0.001), and "feel good" (P < 0.05). "Tingling" ratings were significantly increased by nitrous oxide (relative to placebo) when the drug was given alone, but not when it was given in combination with sevoflurane. When given alone, both drugs increased ratings of "coasting," "floating," "lightheaded," and "high." However, for each of these mood adjectives, the combination of the two drugs together did not produce ratings that differed significantly from the ratings achieved with either drug alone (Figure 2). "Feel good" ratings were significantly lower when 30% nitrous oxide was combined with 0.4% sevoflurane, compared with nitrous oxide alone; neither drug condition differed significantly from placebo. Finally, "drunk" ratings were increased by both sevoflurane and nitrous oxide without a significant interaction between the two drugs.
|
Drug Effects/Liking
A significant sevoflurane x nitrous oxide interaction (F[2,34] = 11.9, P < 0.0001) was obtained on drug effects ratings. Post hoc tests indicated that ratings from all five active drug conditions were significantly greater than placebo ratings. With both 0% sevoflurane and 0.2% sevoflurane, the addition of nitrous oxide increased drug effects ratings. However, with 0.4% sevoflurane, the addition of nitrous oxide did not result in an increase in drug effects ratings, perhaps due to a ceiling effect (i.e., ratings were close to maximal with 0.4% sevoflurane). Nitrous oxide significantly increased ratings of drug liking (F[1,17] = 8.3, P < 0.01), but there was an order effect with 0.2% sevoflurane (nitrous oxide x order interaction: F[1,18] = 8.9, P < 0.01); liking ratings were significantly increased by the addition of nitrous oxide to 0.2% sevoflurane when the two were presented during the second inhalation block, but not during the fourth block.
Odor Detection/Liking
Sevoflurane dose-dependently increased odor detection ratings (F[2,32] = 13.2, P < 0.0001). In addition, there was a marginally significant main effect of nitrous oxide (F[1,16] = 4.2, P < 0.06), with nitrous oxide increasing odor detection ratings. Nitrous oxide increased odor liking ratings (F[1,17] = 8.3, P < 0.01).
Observer Ratings of Sedation
Sevoflurane dose-dependently decreased observer ratings (F[2,30] = 23.9, P < 0.0001), which indicates increased sedation with sevoflurane. The addition of nitrous oxide did not alter the ratings.
Psychomotor Performance
There were main effects of both sevoflurane (F[2,36] = 111.8, P < 0.0001) and nitrous oxide (F[1,18] = 158.2, P < 0.0001) on the number of DSST symbols drawn correctly, with both drugs producing psychomotor impairment (Fig. 3). There was a significant order effect with 0.4% sevoflurane (F[1,17] = 6.7, P < 0.05): subjects who received nitrous oxide during the 27-min block drew significantly fewer symbols than did subjects who received nitrous oxide during the 51-min block (11.4 and 21.2, respectively).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
We hypothesized that subanesthetic concentrations of nitrous oxide and sevoflurane would produce both opposing and potentiating effects within the same study. Specifically, we predicted that sevoflurane would oppose the analgesic effects of nitrous oxide, that nitrous oxide would oppose the soporific effects of sevoflurane, and that both anesthetics would impair psychomotor performance. In the present study, pain intensity ratings were higher when sevoflurane and nitrous oxide were administered together than when nitrous oxide was administered alone, which indicates that sevoflurane attenuated the analgesic effects of nitrous oxide. Although not statistically significant, a similar pattern occurred with pain bothersomeness ratings. Sevoflurane increased VAS ratings of "sleepy," nitrous oxide decreased these ratings, and the addition of nitrous oxide to sevoflurane resulted in ratings not significantly different from that of placebo. Both sevoflurane and nitrous oxide induced psychomotor impairment.
The results from the present study, along with those from other studies examining the interaction of nitrous oxide and volatile anesthetics, suggest that the two anesthetics may act through different mechanisms on some end points, such as pain and sleepiness (or drowsiness). For example, sevoflurane attenuated nitrous oxide-induced reductions in pain intensity in the present study. This result is concordant with an animal study in which volatile anesthetics antagonized the analgesic effect of nitrous oxide (8). Although the exact mechanism of this antagonistic effect is not fully understood, it has been postulated that volatile anesthetics decrease cerebral metabolic rate (17), resulting in the interference of nitrous oxide-activating descending pain inhibitory pathways (18). Sevoflurane alone did not increase pain ratings compared with those of placebo; lack of such a hyperalgesic effect has been found in two other human studies (19,20). At the concentrations tested, the two drugs may also have opposing actions when it comes to producing drowsiness. Based on past studies in which subjects reported feeling sedated while inhaling sevoflurane (20) and isoflurane (21) and feeling stimulated while inhaling nitrous oxide (22,23), we predicted less somnolent effects of sevoflurane when the volatile anesthetic was inhaled with nitrous oxide than when it was inhaled alone. In the present study, sevoflurane increased self-reports of sleepiness, and the addition of nitrous oxide seemed to make subjects less sleepy. This result coincides with findings from previous studies in which nitrous oxide reduced the ability of sevoflurane (6) and isoflurane (7) to suppress response to verbal commands. Although nitrous oxide has some properties of a CNS depressant in that it decreases minimum alveolar anesthetic concentration of volatile anesthetics in an additive fashion (24), the drug also has some characteristics of a CNS stimulant in that it enhances dopaminergic (25), noradrenergic (26), and cholinergic activity (27); increases sympathetic nervous system activity (28); and induces EEG waves that are associated with an increase in spontaneous firing of reticular neurons (29).
One finding from the present study merits mention. Sevoflurane increased self-reported ratings of sleepiness, and the addition of nitrous oxide decreased these ratings. However, a similar effect was not found on the observer ratings of sedation: sedation ratings were not significantly decreased by the addition of nitrous oxide. It is not clear why there was a discrepancy between the self-report ratings and the observer ratings. At the concentrations of drugs used in the present study, the subjects' behavioral changes, if any such changes occurred, may have been too subtle for the observer to detect. In fact, most observer ratings (83%) with 0.2% and 0.4% sevoflurane, alone or in combination with nitrous oxide, were in the limited range of 3–5.
Subjects in this study were always challenged with nitrous oxide while inhaling sevoflurane. It is unclear whether identical results would have been obtained had the reverse been true; that is, if subjects had been challenged with sevoflurane while inhaling nitrous oxide.
The present study provides further evidence that nitrous oxide and the volatile anesthetics differ in some respects. Studies that have examined the interaction of the two anesthetics indicate that they oppose each other on some end points. Most important, perhaps, to the clinical use of this anesthetic combination is the finding that the two anesthetics seem to oppose each other on a measure of drowsiness. Data from the present study, along with results from other investigations in which nitrous oxide has opposed the sedative/hypnotic effects of volatile anesthetics, suggest that nitrous oxide may work at cross purposes with the volatile anesthetics on this component of anesthesia.
|
Acknowledgments |
|---|
Supported in part by the National Institute on Drug Abuse Grant DA08391.
We thank Aisling Conran, MD, Jerome Klafta, MD, Matthew Black, MD, Christine Bialek, CRNA, Mary Maurer, CRNA, Robert Shaughnessy, CRNA, and Nada Williamson, CRNA, for their assistance in administering the drugs and monitoring the physiological status of the subjects; and Karin Kirulis, BA, for performing the volunteer interviews.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Rampil IJ, Lockhart SH, Eger EI II, et al. The electroencephalographic effects of desflurane in humans. Anesthesiology 1991;74:434–9.[Web of Science][Medline]
-
Roald OK, Forsman M, Heier MS, Steen PA. Cerebral effects of nitrous oxide when added to low and high concentrations of isoflurane in the dog. Anesth Analg 1991;72:75–9.
[Abstract/Free Full Text] -
Yli-Hankala A, Lindgren L, Porkkala T, Jantti V. Nitrous oxide-mediated activation of the EEG during isoflurane anaesthesia in patients. Br J Anaesth 1993;70:54–7.
[Abstract/Free Full Text] - Porkkala T, Jantti V, Kaukinen S, Hakkinen V. Nitrous oxide has different effects on the EEG and somatosensory evoked potentials during isoflurane anesthesia in patients. Anaesthesiol Scand 1997;41:497–501.
-
Utsumi J, Adachi T, Kurata J, et al. Effect of xenon on central nervous system electrical activity during sevoflurane anaesthesia in cats : comparison with nitrous oxide. Br J Anaesth 1998;80:628–33.
[Abstract/Free Full Text] - Katoh T, Ikeda K, Bito H. Does nitrous oxide antagonize sevoflurane-induced hypnosis? Anaesth 1997;79:465–8.
- Chortkoff BS, Bennett HL, Eger EI II. Does nitrous oxide antagonize isoflurane-induced suppression of learning? Anesthesiology 1993;79:724–32.[Web of Science][Medline]
-
Goto T, Marota JJ, Crosby G. Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat. Br J Anaesth 1996;76:702–6.
[Abstract/Free Full Text] - Zacny JP, Yajnik S, Lichtor JL, et al. The acute and residual effects of subanesthetic concentrations of isoflurane/nitrous oxide combinations on cognitive and psychomotor performance in healthy volunteers. Anesth Analg 1996;82:153–7.[Abstract]
- Derogatis LR, Lipman RS, Covi L. SCL-90. An outpatient psychiatric rating scale-preliminary report. Psychopharmacol Bull 1973;9:13–7.[Medline]
- American Psychiatric Association.Diagnostic and statistical manual of mental disorders. Washington, DC:American Psychiatric Association, 1987.
- Chen ACN, Dworkin SF, Huag J. Human pain responsivity in a tonic pain model : physiological determinants. Pain 1989;37:143–60.[Web of Science][Medline]
- Melzak R. The short-form McGill Pain Questionnaire. Pain 1987;30:191–7.[Web of Science][Medline]
- Glass PS, Bloom M, Kearse L, et al. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997;86:836–47.[Web of Science][Medline]
- Wechsler D. The measurement and appraisal of adult intelligence. Baltimore:Williams & Wilkins, 1958.
- Wilcox RR. Statistics for the social sciences. San Diego:Academic, 1996:246–8.
- Goto T, Marota JA, Crosby G. Nitrous oxide induces preemptive analgesia in the rat that is antagonized by halothane. Anesthesiology 1994;80:409–16.[Web of Science][Medline]
- Komatsu T, Shingu K, Tomemori N, et al. Nitrous oxide activates the supraspinal pain inhibition system. Acta Anaesthesiol Scand 1981;25:519–22.[Web of Science][Medline]
-
Tomi K, Mashimo T, Tashiro C, et al. Alterations in pain threshold and psychomotor response associated with subanaesthetic concentrations of inhalation anaesthetics in humans. Br J Anaesth 1993;70:684–6.
[Abstract/Free Full Text] - Galinkin JL, Janiszewski DJ, Young CJ, et al. Subjective, psychomotor, cognitive, and analgesic effects of subanesthetic concentrations of sevoflurane and nitrous oxide. Anesthesiology 1997;87:1082–8.[Web of Science][Medline]
- Zacny JP, Sparacino G, Hoffmann PM, et al. The subjective, behavioral and cognitive effects of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers. Psychopharmacology (Berl) 1994;114:409–16.[Medline]
- Dohrn CS, Lichtor JL, Coalson DW, et al. Reinforcing effects of extended inhalation of nitrous oxide in humans. Drug Alcohol Depend 1993;31:265–80.[Web of Science][Medline]
- Zacny JP, Lichtor JL, Coalson DW, et al. Examining the subjective, psychomotor-impairing, and reinforcing effects of nitrous oxide in healthy volunteers : a dose-response analysis. Behav Pharmacol 1996;7:194–9.[Web of Science][Medline]
- 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.[Web of Science][Medline]
- Murakawa M, Adachi T, Nakao S, et al. Activation of the cortical and medullary dopaminergic systems by nitrous oxide in rats : a possible neurochemical basis for psychotropic drug effects and postanesthetic nausea and vomiting. Anesth Analg 1994;78:376–81.[Web of Science][Medline]
- Karuri AR, Kugel G, Engelking LR, Kumar MSA. Alterations in catecholamine turnover in specific regions of the rat brain following acute exposure to nitrous oxide. Brain Res Bull 1998;45:557–61.[Web of Science][Medline]
-
Shichino T, Murakawa M, Adachi T, et al. Effects of inhalation anaesthetics on the release of acetylcholine in the rat cerebral cortex in vivo. Br J Anaesth 1998;80:365–70.
[Abstract/Free Full Text] -
Ebert TJ, Kampine JP. Nitrous oxide augments sympathetic outflow : direct evidence from human peroneal nerve endings. Anesth Analg 1989;69:444–9.
[Abstract/Free Full Text] - Mori K, Winters WD. Neural background of sleep and anesthesia. Int Anesthesiol Clin 1975;13:67–108.[Medline]
This article has been cited by other articles:
|
|
 |
|
  S. T. Yeo, A. Holdcroft, S. M. Yentis, A. Stewart, and P. Bassett Analgesia with sevoflurane during labour: II. Sevoflurane compared with Entonox for labour analgesia Br. J. Anaesth., January 1, 2007; 98(1): 110 - 115. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
