Acta Anaesthesiol Scand 1992: 36: 592-594
Oxygen consumption after flumazenil reversal P. DUVALDESTIN', C. LEBRAULT~, H. COSTES", N. BARRAL*and E. RAIMBAULT, Departments of Anesthesiology, 'Hospital Henri Mondor, Creteil and 'Hospital Ambroise ParC, Boulogne, France
The eKect of flumazenil reversal of midazolam-induced anesthesia on whole body oxygen uptake (Vo,) was investigated in a double-blind trial in 48 patients (ASA, 1 or 2) undergoing elective surgery under gcneral anesthesia. Vo, was measured in spontaneously breathing patients during recovery from anaesthesia induced with midazolam 0.25 mg. kg-' and maintained with nitrous oxide 60% in oxygen and halothane. The level of sedation was evaluated by a subjective score. To reverse midazolam-induced anesthesia, patients were randomly allocated to receive placebo or flumazenil (6 p g ' k g - ' ) . No significant changes in Vo, (160 t 53 vs 150 k 39 ml.min-l.m-2 or sedation score (2.5 k 1.0 vs 2.1 f 0 . 9 ) were observed in the placebo group. After flumazenil administration, the sedation score significantly ( P c 0 . 0 5 ) improved (2.9 f I .O vs I .3 f 0.8) whereas no significant change in Vo, was observed (158k 67 vs 157 f 6 1 ml O,.min " I T - ' ) . These data show that reversal of benzodiazepine effects with flumazenil resulted in no significant change in oxygen uptake. Received 24 August 1991, accepted for publication 12 February 1992
Key words: Anesthesiology: postop. care; benzodiazepinr antagonists: flumazenil; henzodiazepines: midazolam. care; metabolism; oxygen consumption.
Recovery from anaesthesia is usually associated with excitatory phenomena, shivering, pain and increased autonomic nervous system discharge, all of which contribute to a sudden increase in oxygen uptake (Vo,). Rapid emergence from anesthesia induced by benzodiazepines can be achieved with flumazenil ( 1, 2). Abrupt awakening and anxiety reactions have been observed in some patients after flumazenil (3). Such a situation may cause a sudden increase in oxygen consumption, which is potentially harmful in patients with coronary artery disease or cardiac insufficiency. This study was designed to examine in a doubleblind, randomized controlled trial, the effect of flumazenil reversal of midazolam sedation on oxygen uptake in patients without pre-existing cardiovascular disease.
PATIENTS AND METHODS The protocol was approved by the Institution's Ethics Committee and written informed consent was obtained from all subjects. Fortyeight ASA physical status I or I1 patients scheduled for elective surgery including inguinal hernia repair, stripping of varices, thyroid or orthopedic surgery participated in the study. The expected duration of surgery was 1-3 h. Patients between 18 and 65 years old whose body weight did not exceed 20% of the ideal value were selected for the study. The patients were premedicated with lorazepam 2.5 mg orally 2 h before induction of anesthesia. Anesthesia was induced with midazolam 0.25 mg. kg-' and fentanyl 2 pg. kg-' intravenously. When tracheal intubation was judged necessary, vecuronium 0.1
L
mg. kg-' was given. Ventilation was maintained by controlled or assisted ventilation to keep end-tidal CO, (Capnomac Datex", Helsinki, Finland) between 4 and 5%. Anesthesia was maintained with nitrous oxide 60% in oxygen and halothane 0.5% end-tidal delivered in a semi-closed circuit with a fresh gas flow of 1.5 1.min-l and repeated doses of 1 pg .kg- of fentanyl. During recovery from anesthesia, the patients were treated in a double-blind manner. Placebo (saline) was given 15 min after the start of the study in the recovery room (see below) to 24 patients, or flumazenil 6 pg. kg-' bolus was given at the same time to 24 patients. No patient received any sedative or central analgesics during recovery. The study started in the recovery room in spontaneously breathing patients 30-50 min after halothane and nitrous oxide were discontinued and 120-150 min after midazolam administration. Two sets of measures each lasting 15 min were performed before and after the administration of flumazenil or placebo. Central body temperature was estimated by measuring the tympanic temperature. Sedation, pain, and shivering were assessed by an independent observer unaware of the drug administerrd. The degree of sedation was scored from 1 to 4 with the following scale: awake and tense = 1, drowsy = 2, asleep but arousable = 3, asleep and not arousable= 4. The intensity of pain was scored subjectively as follows: pain recall absent = 1, transient and provoked recall= 2, spontaneous recall = 3, intense requiring immediate relief= 4.Shivering was scored as: absent = I, mild but discernible as artifacts on the baseline of the electrocardioscope = 2, present and discernible by simple observation = 3, intense and generalized = 4.The incidence of vomiting was also recorded. Vo, was measured with a Deltatrac" (Datex, Helsinki, Finland) monitor (4, 5) using the canopy mode (6). This instrument allowed the simultaneous measurement of Vo,, of carbon dioxide production (Vco,) and of the respiratory quotient (RQJ. The measurement of R Q during the combustion of methanol (RQ=0.67) was used to calibrate the monitor (4).Results are expressed as mean & s.d. Data (for these groups) were analyzed using one-way analysis or varianre. The paired and unpaired t-test were used for comparison of mean intra-group and inter-group values, respectively. Values of P < 0.05 were defined as significant.
'
593
OXYGEN CONSUMPTION AFTER FLUMAZENIL REVERSAL Table I Demographic data in the flumazenil and the placebo groups
Age (Yr) Weight (kg) Sex (M/F) Total fentanyl dose (pg) during anesthesia Duration of anesthesia (min)
Placebo rn = 24)
Flumazenil ( n = 24)
4 5 f 14 6 5 f 10 10/14
43f 13 67f 12 15/9
215 f 90 95 f 37
225 f 85 98f37
Mean f s.d.
Table 3 Oxygen uptake (Vo,), carbon dioxide production (Vco,) and respiratory quotient (R) before and after placebo or flumazenil. Placebo (n = 24)
vo,
(ml.rnin-'.m-') vco, (rnl.min-'.m-') QR
Flumazenil (n = 24)
Before
After
Before
After
160f53
1.50539
158f67
157f61
130k48 126532 132f63 133+45 0.82+0.100.85+0.05 0.83f0.100.88f0.07
Mean s.d. No significant intra- and inter-group changes were found.
RESULTS There were no significant differences between the treatment groups with respect to age, body weight, sex distribution, duration of anesthesia and fentanyl dose (Table 1 ) . At the time of the pretreatment evaluation, there were no differences in the sedation score, pain score, shivering score, or body temperature (Table 2). The Vos values were similar between the two groups before treatment (Table 3). After administration of flumazenil, there was a significant reduction of the sedation score from 2.9 f 1.0 to 1.3 f 1.8, whereas it remained unchanged after placebo. The pain score and shivering score were unaffected by the administration of flumazenil or placebo. Tympanic temperatures increased progressively in the two groups throughout the time of the study, although the change was not significant. There was no increase in Vo2 after either flumazenil or placebo. Vomiting was observed in 4 out of 24 patients after flumazenil compared to 1 out of 24 after placebo. DISCUSSION Our data show that reversal of midazolam-induced sedation by flumazenil is not associated with an increase in oxygen uptake. Except for the sedation score, which significantly improved after flumazenil, there Table 2 Sedation score, pain score, shivering occurrence of nausea, of vomiting before and after flumazenil or placebo. Placebo (n = 24) Before Body temperature ("C) Sedation score Pain score Shivering score Vomiting Mean f s.d.
After
35.7 f 0.7 35.9 f 0.7 2.5 f 1.0 2. I f 0.9 1.2f0.4 1 . 5 t 0 . 8 1.5 f 0.8 1.5 f 0.8 0/24 1/24
* P < 0.05 versus before.
Flumazenil (n = 24) Before
After
35.4 f 0.9 35.6 f 1.0 2.9 f 1.0 1.3 0.8* 1.4f0.7 1.8+ 1.0 1.7f0.9 1.4f0.7 1/24 4/24
were no differences between the two groups. The changes in oxygen uptake and body temperature were similar between the placebo and flumazenil groups. Comparison with placebo in a controlled randomized trial allows the evaluation of the specific effect of reversal. For example, an increase in oxygen uptake throughout the study corresponding to the times of recovery could be attributed to the resetting of the thermoregulatory process which was blunted by anesthesia (5). The state of sedation observed before the administration of flumazenil or placebo may be due not only to midazolam but also to lorazepam which was given preoperatively as premedicant. The present findings are in agreement with the previous observations that reversal of profound midazolam sedation by flumazenil was not followed by abrupt adrenergic and hemodynamic responses (6, 7). In addition, we did not observe abrupt anxiety reactions, as previously described in some patients after flumazenil reversal by Ricou et al. (3). However, in the study of Ricou et al. (3) a large dose of 100 pg * kg- of flumazenil was administered and this dose was given less than 60 min after benzodiazepine administration. These differences in drug dosage and delay may explain some of the differences between the results of the study of Ricou et al. (3) and those of the present study. Fentanyl which was administered peroperatively might still blunt the metabolic response caused by flumazenil reversal. However, the dose of fentanyl given was moderate and the sedative effect observed postoperatively was almost completely due to benzodiazepine, since it almost completely returned to a normal score after reversal in contrast to the placebo group. The method of measurement of oxygen uptake using the Deltatrac@monitor is questionable in patients who have been anesthetized with nitrous oxide. The measure of oxygen uptake with this equipment uses the Haldane transformation as algorithm which states that in the lungs, the nitrogen input equals the nitrogen output (8). We assume that 30 min after discontinuing
'
594
P. DUVALDESTIN ET AL.
the administration of nitrous oxide, the amount of nitrous oxide still present in the body is negligible and that the nitrogen stores can be considered as constant. In addition, since oxygen uptake was measured at an FIO, of 0.21, errors in its measurement induced by trace anesthetic gases are minimal (9). We have observed that the oxygen uptake measured using this method remains unchanged 30 min after the administration of 60% nitrous oxide in oxygen for 20 min in healthy patients (10). If residual nitrous oxide stores or an uneven nitrogen balance had been present at the time of the study, a change in the respiratory quotient would have been observed throughout the study because the carbon dioxide production is not influenced by the nitrogen exchange in the lungs, in contrast to oxygen uptake (1 1). This was not observed. In addition, the same principle of measurement was used in the two groups, and therefore intergroup comparison with this method remains valid. In this study, reversal of benzodiazepine sedation by flumazenil resulted in no significant change in oxygen uptake. We therefore suggest that flumazenil may be used in patients in whom a sudden increase in oxygen uptake could be harmful, such as patients with cardiac or coronary insufficiency.
REFERENCES 1. Wolff J, Carl P, Clausen G, Mikkelsen B. Ro 15-1788 for postoperative recovery. Anaesthesia 1986: 41: 1001-1006. 2. Alon E, Baitella L, Hossli G. Double-blind study of the reversal of midazolam-supplemented general anaesthesia with Ro 151788. B7 j Anaesth 1987: 5 9 455-458.
3. Ricou B, Forster A, Bruckner A, Chastonay P, Gemperle M. Clinical evaluation of a specific benzodiazepine antagonist (Ro 15-1788). B r J Anaesfh 1986: 58: 1005-1011. 4. Weissman Ch, Sardar A, Kemper M. Techniques, materials and devices. In vitro evaluation of a compact metabolic measurement instrument. 3 Parent Ent Nut7 1990: 14: 216-221. 5. Takala J, Keinanen 0, Vaisanen P, Karl A. Measurement of gas exchange in intensive care: laboratory and cliniral validation of a new device. Crit Care M e d 1989: 17: 1041-1 104. 6. Kinney J M, Morgan A P, Domingues F J, et al. A method for continuous measurement of gas exchange and radioactivity in acutely ill patients. Metabolism 1964: 13: 205-2 I 1. 7. Sessler D I, Olofsson C I, Rubinstein E H, Beebe J J. The thermoregulatory threshold in humans during halothane anesthesia. Anesthesiolou 1988: 68: 836-842. 8. Duka T, Ackenheil M, Noderer J, Doenicke A, Dorow R. Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15- 1788. Psychopharmarcology 1986: 90: 351-357. 9. White P F, Shafer A, Boyle W A, Doze V A, Duncan S. Benzodiazepine antagonism does not provoke a stress response. Anesthuiology 1989: 70: 636-639. 10. Mudd C P. Propagation of measurement errors in oxygen consumption algorithms. M e d Bid Eng Comput 1987: 26: 361-365. 11. Aukburg S J, Geer R T, Wollman H, Neufeld G R. Erron in measurement of oxygen uptake due to anesthetic gases. Anesthesiology 1985: 62: 54-59. 12. Delaunay L, Bonnet F, Duvaldestin P. Clonidine decreases postoperative oxygen consumption in patients recovering from general anaesthesia. B r 3 Anaesth. In press.
Address:
P Duvaldestin, M.D. Department of Anesthesiology HBpital Henri Mondor 94010 Creteil France
Oxygen consumption after flumazenil reversal P. DUVALDESTIN', C. LEBRAULT~, H. COSTES", N. BARRAL*and E. RAIMBAULT, Departments of Anesthesiology, 'Hospital Henri Mondor, Creteil and 'Hospital Ambroise ParC, Boulogne, France
The eKect of flumazenil reversal of midazolam-induced anesthesia on whole body oxygen uptake (Vo,) was investigated in a double-blind trial in 48 patients (ASA, 1 or 2) undergoing elective surgery under gcneral anesthesia. Vo, was measured in spontaneously breathing patients during recovery from anaesthesia induced with midazolam 0.25 mg. kg-' and maintained with nitrous oxide 60% in oxygen and halothane. The level of sedation was evaluated by a subjective score. To reverse midazolam-induced anesthesia, patients were randomly allocated to receive placebo or flumazenil (6 p g ' k g - ' ) . No significant changes in Vo, (160 t 53 vs 150 k 39 ml.min-l.m-2 or sedation score (2.5 k 1.0 vs 2.1 f 0 . 9 ) were observed in the placebo group. After flumazenil administration, the sedation score significantly ( P c 0 . 0 5 ) improved (2.9 f I .O vs I .3 f 0.8) whereas no significant change in Vo, was observed (158k 67 vs 157 f 6 1 ml O,.min " I T - ' ) . These data show that reversal of benzodiazepine effects with flumazenil resulted in no significant change in oxygen uptake. Received 24 August 1991, accepted for publication 12 February 1992
Key words: Anesthesiology: postop. care; benzodiazepinr antagonists: flumazenil; henzodiazepines: midazolam. care; metabolism; oxygen consumption.
Recovery from anaesthesia is usually associated with excitatory phenomena, shivering, pain and increased autonomic nervous system discharge, all of which contribute to a sudden increase in oxygen uptake (Vo,). Rapid emergence from anesthesia induced by benzodiazepines can be achieved with flumazenil ( 1, 2). Abrupt awakening and anxiety reactions have been observed in some patients after flumazenil (3). Such a situation may cause a sudden increase in oxygen consumption, which is potentially harmful in patients with coronary artery disease or cardiac insufficiency. This study was designed to examine in a doubleblind, randomized controlled trial, the effect of flumazenil reversal of midazolam sedation on oxygen uptake in patients without pre-existing cardiovascular disease.
PATIENTS AND METHODS The protocol was approved by the Institution's Ethics Committee and written informed consent was obtained from all subjects. Fortyeight ASA physical status I or I1 patients scheduled for elective surgery including inguinal hernia repair, stripping of varices, thyroid or orthopedic surgery participated in the study. The expected duration of surgery was 1-3 h. Patients between 18 and 65 years old whose body weight did not exceed 20% of the ideal value were selected for the study. The patients were premedicated with lorazepam 2.5 mg orally 2 h before induction of anesthesia. Anesthesia was induced with midazolam 0.25 mg. kg-' and fentanyl 2 pg. kg-' intravenously. When tracheal intubation was judged necessary, vecuronium 0.1
L
mg. kg-' was given. Ventilation was maintained by controlled or assisted ventilation to keep end-tidal CO, (Capnomac Datex", Helsinki, Finland) between 4 and 5%. Anesthesia was maintained with nitrous oxide 60% in oxygen and halothane 0.5% end-tidal delivered in a semi-closed circuit with a fresh gas flow of 1.5 1.min-l and repeated doses of 1 pg .kg- of fentanyl. During recovery from anesthesia, the patients were treated in a double-blind manner. Placebo (saline) was given 15 min after the start of the study in the recovery room (see below) to 24 patients, or flumazenil 6 pg. kg-' bolus was given at the same time to 24 patients. No patient received any sedative or central analgesics during recovery. The study started in the recovery room in spontaneously breathing patients 30-50 min after halothane and nitrous oxide were discontinued and 120-150 min after midazolam administration. Two sets of measures each lasting 15 min were performed before and after the administration of flumazenil or placebo. Central body temperature was estimated by measuring the tympanic temperature. Sedation, pain, and shivering were assessed by an independent observer unaware of the drug administerrd. The degree of sedation was scored from 1 to 4 with the following scale: awake and tense = 1, drowsy = 2, asleep but arousable = 3, asleep and not arousable= 4. The intensity of pain was scored subjectively as follows: pain recall absent = 1, transient and provoked recall= 2, spontaneous recall = 3, intense requiring immediate relief= 4.Shivering was scored as: absent = I, mild but discernible as artifacts on the baseline of the electrocardioscope = 2, present and discernible by simple observation = 3, intense and generalized = 4.The incidence of vomiting was also recorded. Vo, was measured with a Deltatrac" (Datex, Helsinki, Finland) monitor (4, 5) using the canopy mode (6). This instrument allowed the simultaneous measurement of Vo,, of carbon dioxide production (Vco,) and of the respiratory quotient (RQJ. The measurement of R Q during the combustion of methanol (RQ=0.67) was used to calibrate the monitor (4).Results are expressed as mean & s.d. Data (for these groups) were analyzed using one-way analysis or varianre. The paired and unpaired t-test were used for comparison of mean intra-group and inter-group values, respectively. Values of P < 0.05 were defined as significant.
'
593
OXYGEN CONSUMPTION AFTER FLUMAZENIL REVERSAL Table I Demographic data in the flumazenil and the placebo groups
Age (Yr) Weight (kg) Sex (M/F) Total fentanyl dose (pg) during anesthesia Duration of anesthesia (min)
Placebo rn = 24)
Flumazenil ( n = 24)
4 5 f 14 6 5 f 10 10/14
43f 13 67f 12 15/9
215 f 90 95 f 37
225 f 85 98f37
Mean f s.d.
Table 3 Oxygen uptake (Vo,), carbon dioxide production (Vco,) and respiratory quotient (R) before and after placebo or flumazenil. Placebo (n = 24)
vo,
(ml.rnin-'.m-') vco, (rnl.min-'.m-') QR
Flumazenil (n = 24)
Before
After
Before
After
160f53
1.50539
158f67
157f61
130k48 126532 132f63 133+45 0.82+0.100.85+0.05 0.83f0.100.88f0.07
Mean s.d. No significant intra- and inter-group changes were found.
RESULTS There were no significant differences between the treatment groups with respect to age, body weight, sex distribution, duration of anesthesia and fentanyl dose (Table 1 ) . At the time of the pretreatment evaluation, there were no differences in the sedation score, pain score, shivering score, or body temperature (Table 2). The Vos values were similar between the two groups before treatment (Table 3). After administration of flumazenil, there was a significant reduction of the sedation score from 2.9 f 1.0 to 1.3 f 1.8, whereas it remained unchanged after placebo. The pain score and shivering score were unaffected by the administration of flumazenil or placebo. Tympanic temperatures increased progressively in the two groups throughout the time of the study, although the change was not significant. There was no increase in Vo2 after either flumazenil or placebo. Vomiting was observed in 4 out of 24 patients after flumazenil compared to 1 out of 24 after placebo. DISCUSSION Our data show that reversal of midazolam-induced sedation by flumazenil is not associated with an increase in oxygen uptake. Except for the sedation score, which significantly improved after flumazenil, there Table 2 Sedation score, pain score, shivering occurrence of nausea, of vomiting before and after flumazenil or placebo. Placebo (n = 24) Before Body temperature ("C) Sedation score Pain score Shivering score Vomiting Mean f s.d.
After
35.7 f 0.7 35.9 f 0.7 2.5 f 1.0 2. I f 0.9 1.2f0.4 1 . 5 t 0 . 8 1.5 f 0.8 1.5 f 0.8 0/24 1/24
* P < 0.05 versus before.
Flumazenil (n = 24) Before
After
35.4 f 0.9 35.6 f 1.0 2.9 f 1.0 1.3 0.8* 1.4f0.7 1.8+ 1.0 1.7f0.9 1.4f0.7 1/24 4/24
were no differences between the two groups. The changes in oxygen uptake and body temperature were similar between the placebo and flumazenil groups. Comparison with placebo in a controlled randomized trial allows the evaluation of the specific effect of reversal. For example, an increase in oxygen uptake throughout the study corresponding to the times of recovery could be attributed to the resetting of the thermoregulatory process which was blunted by anesthesia (5). The state of sedation observed before the administration of flumazenil or placebo may be due not only to midazolam but also to lorazepam which was given preoperatively as premedicant. The present findings are in agreement with the previous observations that reversal of profound midazolam sedation by flumazenil was not followed by abrupt adrenergic and hemodynamic responses (6, 7). In addition, we did not observe abrupt anxiety reactions, as previously described in some patients after flumazenil reversal by Ricou et al. (3). However, in the study of Ricou et al. (3) a large dose of 100 pg * kg- of flumazenil was administered and this dose was given less than 60 min after benzodiazepine administration. These differences in drug dosage and delay may explain some of the differences between the results of the study of Ricou et al. (3) and those of the present study. Fentanyl which was administered peroperatively might still blunt the metabolic response caused by flumazenil reversal. However, the dose of fentanyl given was moderate and the sedative effect observed postoperatively was almost completely due to benzodiazepine, since it almost completely returned to a normal score after reversal in contrast to the placebo group. The method of measurement of oxygen uptake using the Deltatrac@monitor is questionable in patients who have been anesthetized with nitrous oxide. The measure of oxygen uptake with this equipment uses the Haldane transformation as algorithm which states that in the lungs, the nitrogen input equals the nitrogen output (8). We assume that 30 min after discontinuing
'
594
P. DUVALDESTIN ET AL.
the administration of nitrous oxide, the amount of nitrous oxide still present in the body is negligible and that the nitrogen stores can be considered as constant. In addition, since oxygen uptake was measured at an FIO, of 0.21, errors in its measurement induced by trace anesthetic gases are minimal (9). We have observed that the oxygen uptake measured using this method remains unchanged 30 min after the administration of 60% nitrous oxide in oxygen for 20 min in healthy patients (10). If residual nitrous oxide stores or an uneven nitrogen balance had been present at the time of the study, a change in the respiratory quotient would have been observed throughout the study because the carbon dioxide production is not influenced by the nitrogen exchange in the lungs, in contrast to oxygen uptake (1 1). This was not observed. In addition, the same principle of measurement was used in the two groups, and therefore intergroup comparison with this method remains valid. In this study, reversal of benzodiazepine sedation by flumazenil resulted in no significant change in oxygen uptake. We therefore suggest that flumazenil may be used in patients in whom a sudden increase in oxygen uptake could be harmful, such as patients with cardiac or coronary insufficiency.
REFERENCES 1. Wolff J, Carl P, Clausen G, Mikkelsen B. Ro 15-1788 for postoperative recovery. Anaesthesia 1986: 41: 1001-1006. 2. Alon E, Baitella L, Hossli G. Double-blind study of the reversal of midazolam-supplemented general anaesthesia with Ro 151788. B7 j Anaesth 1987: 5 9 455-458.
3. Ricou B, Forster A, Bruckner A, Chastonay P, Gemperle M. Clinical evaluation of a specific benzodiazepine antagonist (Ro 15-1788). B r J Anaesfh 1986: 58: 1005-1011. 4. Weissman Ch, Sardar A, Kemper M. Techniques, materials and devices. In vitro evaluation of a compact metabolic measurement instrument. 3 Parent Ent Nut7 1990: 14: 216-221. 5. Takala J, Keinanen 0, Vaisanen P, Karl A. Measurement of gas exchange in intensive care: laboratory and cliniral validation of a new device. Crit Care M e d 1989: 17: 1041-1 104. 6. Kinney J M, Morgan A P, Domingues F J, et al. A method for continuous measurement of gas exchange and radioactivity in acutely ill patients. Metabolism 1964: 13: 205-2 I 1. 7. Sessler D I, Olofsson C I, Rubinstein E H, Beebe J J. The thermoregulatory threshold in humans during halothane anesthesia. Anesthesiolou 1988: 68: 836-842. 8. Duka T, Ackenheil M, Noderer J, Doenicke A, Dorow R. Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15- 1788. Psychopharmarcology 1986: 90: 351-357. 9. White P F, Shafer A, Boyle W A, Doze V A, Duncan S. Benzodiazepine antagonism does not provoke a stress response. Anesthuiology 1989: 70: 636-639. 10. Mudd C P. Propagation of measurement errors in oxygen consumption algorithms. M e d Bid Eng Comput 1987: 26: 361-365. 11. Aukburg S J, Geer R T, Wollman H, Neufeld G R. Erron in measurement of oxygen uptake due to anesthetic gases. Anesthesiology 1985: 62: 54-59. 12. Delaunay L, Bonnet F, Duvaldestin P. Clonidine decreases postoperative oxygen consumption in patients recovering from general anaesthesia. B r 3 Anaesth. In press.
Address:
P Duvaldestin, M.D. Department of Anesthesiology HBpital Henri Mondor 94010 Creteil France
