Age-dependent alterations in nitrous oxide requirement of mice

To determine the relationship of nitrous oxide requirement to age in mice, the authors repeatedly tested the righting-reflex response in stock CD-1 mice at 50 to 703 days of age. Over this age range, nitrous oxide requirement (+/- SE) progressively decreased from 1.48 +/- 0.02 atm to 1.09 +/- 0.06 atm. A second set of experiments measured changes in nitrous oxide requirement with age in mice selectively bred for resistance (HI mice) and susceptibility (LO mice) to nitrous oxide anesthesia. When tested at two months of age, selected HI and LO mice had nitrous oxide ED50 values of approximately 2.0 and 1.1 atm, respectively. At 11 to 14 months, the nitrous oxide ED50 of the HI mice had decreased to approximately 1.5 atm. In contrast, the nitrous oxide ED50 of the LO mice showed a much smaller decrease over this age range. Thus, the separation in nitrous oxide requirement between the HI and LO lines tended to disappear with age. By correlating the difference in anesthetic requirement between the HI and LO mice with biochemical and biophysical alterations in the central nervous system, studies on aging that use selectively bred lines may be helpful in investigating the mechanism of anesthetic action and the mechanism by which aging affects anesthetic action.     

Potencies of barbiturates in mice selectively bred for resistance or susceptibility to nitrous oxide anesthesia

To test the possibility that mice selectively bred for resistance (HI mice) and susceptibility (LO mice) to nitrous oxide anesthesia have general differences in central nervous system sensitivity to other depressants, we examined the effects of four barbiturates in these two lines of mice. LO mice given intraperitoneal injections of barbital (275 mg/kg), hexobarbital (120 mg/kg), pentobarbital (65 mg/kg), or secobarbital (50 mg/kg) had significantly (16-46%) longer sleep times than HI mice. Concentrations of barbiturates were significantly (12-73%) greater in the serum and 3-55% greater in the brain on awakening in HI mice than in LO mice. The largest separations in potency between the HI and LO lines occurred with pentobarbital and hexobarbital and the smallest separations with barbital and secobarbital. We concluded that HI and LO mice do have a general resistance and susceptibility to barbiturates, but that the magnitude of the difference in central nervous system sensitivity between the two lines varies among barbiturates.     

Effects of sevoflurane anesthesia and surgery on plasma catecholamine levels

Effects of sevoflurane-nitrous oxide-oxygen anesthesia and surgery on plasma levels of epinephrine, norepinephrine and dopamine were evaluated in twenty four patients who ranged in ages from 15 to 65 years. They underwent non-abdominal surgery (orthopedic surgery) or abdominal surgery (gastrointestinal or gynecological surgery). Anesthesia was induced and maintained with sevoflurane in 50% nitrous oxide and 50% oxygen. Succinylcholine was administered intravenously to facilitate tracheal intubation and pancuronium was given intravenously during surgery. Lactated Ringer's solution at a speed of 5-15 ml.kg-1.h-1 was also administered intravenously throughout the procedures. Neither plasma epinephrine, norepinephrine nor dopamine levels changed significantly during the anesthetic induction with sevoflurane anesthesia. Plasma catecholamines were unchanged during and after surgery in patients who underwent non-abdominal surgery, while plasma epinephrine and norepinephrine levels increased significantly during and after abdominal surgery. Plasma dopamine levels, however, were unchanged during and after surgery in these patients. The findings suggest that epinephrine and norepinephrine secretion was significantly stimulated with abdominal intervention but not with orthopedic one under sevoflurane anesthesia.     

Reduced anesthetic requirement after electrical stimulation of periaqueductal gray matter

To determine whether electrical stimulation of the periaqueductal gray region decreases anesthetic requirement, the authors studied the effect of such stimulation on the MAC of halothane and 60% nitrous oxide in 33 patients. These patients, who were undergoing implantation of a radio-frequency-coupled receiver and connection of that receiver to electrodes previously implanted in the periaqueductal gray area, were assigned randomly to receive (n = 16) or not receive (n = 17) electrical stimulation 1 h before surgery. The mean value (+/- SEM) for the minimum alveolar concentration of halothane combined with 60% nitrous oxide was significantly less (P less than 0.001) for patients who were stimulated preoperatively (0.15 +/- 0.05%) than for those who were not (0.51 +/- 0.02%). The authors conclude that stimulation of the periaqueductal gray region decreases anesthetic requirements and believe that at least three mechanisms are possible: a nonspecific narcotic-like effect, a specific effect on a pain pathway, or an effect on specific neural pathways that affect anesthetic requirements secondary to changes in regional concentrations of neurotransmitters.     

Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia

Background: The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency.

Methods: Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles.

Results: Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations.     

The relationship of brain catecholamine levels to enflurane requirements among three strains of mice with different anesthetic sensitivities

Purpose. It has been reported that brain catecholamines alter the minimum alveolar concentration (MAC) of anesthetics. The extent of the relation between the levels of brain catecholamine and anesthetic sensitivity should be evaluated by excluding several factors. Methods. Anesthetic sensitivity was measured by using loss of the righting reflex in three strains of mice with different sensitivities. The mice were decapitated without any anesthesia, adding on ddN and C57BL/6J mice in 2% enflurane, their brains were divided into three parts, and dopamine and norepinephrine levels were analyzed by high-performance liquid chromatography (HPLC). Results. The values of enflurane requirement (%) were 1.30 ± 0.05 in ddN, 1.10 ± 0.02 in C57BL/6J, and 1.05 ± 0.02 in MSM mice. The values of dopamine (μg · g⁻¹) in the mesencephalon were 0.23 ± 0.02 in ddN, 0.15 ± 0.02 in C57BL/6J, and 0.12 ± 0.02 in MSM (mean ± SE). No statistical significance in the values in 2% enflurane could be obtained between ddN and C57BL/6J. The stepwise regression line showed a significant correlation: enflurane requirement (%) = −0.89 + 1.60 × (dopamine levels of mesencephalon) (r ² = 0.571, P < 0.0001). Conclusion. Dopamine in the mesencephalon seems to play an important role in the production of different anesthetic sensitivities, and the anesthetic mechanism might be related to the regulation of dopamine levels that promote arousal. Received: September 4, 2000 / Accepted: December 20, 2000     

Rapidly developing tolerance to acute exposures to anesthetic agents.

Following the observation that mice manifest a characteristic withdrawal syndrome after an hour of exposure to nitrous oxide, the authors reasoned that there might be a very rapidly developing tolerance to nitrous oxide. Thus, they determined the inspired concentrations that cause loss of the righting reflex in mice (i.e, the ED50), in the presence of 1 atm of oxygen, of: 1) nitrous oxide alone; 2) cyclopropane alone; 3) nitrous oxide plus 13.6 atm helium; 4) ethylene plus 13.6 atm helium. In each instance the ED50 was determined after averages of 6,34 and 64 min of exposure to the anesthetic agents. For nitrous oxide alone the ED50 at 6 min was 1.18 +/- 0.049 atm, increasing to 1.39 +/- 0.061 atm at 64 min. For ethylene plus helium the ED50 increased from 1.21 +/- 0.033 atm at 6 min to 1.31 +/- 0.039 atm at 64 min, indicating the development of acute tolerance. Neither cyclopropane alone nor nitrous oxide plus helium caused acute tolerance. This absence of tolerance may have resulted from a slower development of an alveolar anesthetic concentration.     

Effect of N-methyl-d-aspartate Receptor ε1 Subunit Gene Disruption of the Action of General Anesthetic Drugs in Mice

Background: Recent molecular strategies demonstrated that the N-methyl-d-aspartate (NMDA) receptor is a major target site of anesthetic agents. In a previous article, the authors showed that knocking out the NMDA receptor [epsilon]1 subunit gene markedly reduced the hypnotic effect of ketamine in mice. In the current study, the authors examined the in vivo contribution of the NMDA receptor [epsilon]1 subunit to the action of other anesthetic drugs.

Methods: The authors determined the anesthetic effects of nitrous oxide on sevoflurane potency in NMDA receptor [epsilon]1 subunit knockout mice compared with those in wild-type mice. They then tested the hypnotic effect of [gamma]-aminobutyric acid-mediated agents, such as propofol, pentobarbital, diazepam, and midazolam, in knockout mice and wild-type mice.

Results: The anesthetic action of sevoflurane itself was unaffected by the abrogation of the NMDA receptor [epsilon]1 subunit. Adding nitrous oxide reduced the required concentration of sevoflurane to induce anesthesia in wild-type mice, whereas this sparing effect was diminished in knockout mice. Furthermore, propofol, pentobarbital, diazepam, and midazolam also had markedly attenuated effects in knockout mice.     

Genetic background differences between FVB and C57BL/6 mice affect hypnotic susceptibility to pentobarbital, ketamine and nitrous oxide, but not isoflurane

BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying much of the inherited variability in drug response. There have been several reports of strain-dependent anesthetic actions in rodents, indicating that significant genetic differences exist in the hypnotic and antinociceptive effects of various anesthetics. METHODS: Loss of righting reflex was used to compare the hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between two genetically different populations of mice, C57BL/6 with black hair and Friends virus B (FVB) with white hair. RESULTS: C57BL/6 mice were more susceptible than FVB mice to the hypnotic effects of ketamine, pentobarbital and nitrous oxide. However, the sensitivity to isoflurane did not differ between C57BL/6 and FVB mice. CONCLUSION: Genetic background affects the hypnotic susceptibility to some anesthetic agents in mice. Our results indicate that there may be a different genetic basis for the operation of hypnosis between isoflurane and other anesthetics, such as pentobarbital, ketamine and nitrous oxide.     

The effect of nitrous oxide on in vitro fertilization success rate

The authors studied the effect of nitrous oxide on success rates for in vitro fertilization and pregnancy in women undergoing laparoscopy for oocyte retrieval. Ninety-eight patients in an in vitro fertilization program were randomly assigned to an anesthetic regimen including either 0.7% (end-tidal) isoflurane with 60% nitrous oxide in oxygen, or 1.4% (end-tidal) isoflurane in oxygen. Success rates for fertilization and pregnancy in 44 additional patients who declined randomization were also studied. Among the 51 randomized patients who did not receive nitrous oxide, 192 oocytes were obtained and 122 fertilized (63.5%), resulting in eight pregnancies (16.3%). From the 47 randomized patients given nitrous oxide, 168 oocytes were retrieved and 114 fertilized (67.9%), resulting in nine pregnancies (19.1%). No significant differences between rates of fertilization or pregnancy emerged between groups. Such differences would have been found with an 80% probability had nitrous oxide had a 20% effect on oocyte fertilization.     

Effect of N-methyl-D-aspartate receptor epsilon1 subunit gene disruption of the action of general anesthetic drugs in mice

BACKGROUND: Recent molecular strategies demonstrated that the N-methyl-d-aspartate (NMDA) receptor is a major target site of anesthetic agents. In a previous article, the authors showed that knocking out the NMDA receptor epsilon1 subunit gene markedly reduced the hypnotic effect of ketamine in mice. In the current study, the authors examined the in vivo contribution of the NMDA receptor epsilon1 subunit to the action of other anesthetic drugs. METHODS: The authors determined the anesthetic effects of nitrous oxide on sevoflurane potency in NMDA receptor epsilon1 subunit knockout mice compared with those in wild-type mice. They then tested the hypnotic effect of gamma-aminobutyric acid-mediated agents, such as propofol, pentobarbital, diazepam, and midazolam, in knockout mice and wild-type mice. RESULTS: The anesthetic action of sevoflurane itself was unaffected by the abrogation of the NMDA receptor epsilon1 subunit. Adding nitrous oxide reduced the required concentration of sevoflurane to induce anesthesia in wild-type mice, whereas this sparing effect was diminished in knockout mice. Furthermore, propofol, pentobarbital, diazepam, and midazolam also had markedly attenuated effects in knockout mice. CONCLUSIONS: Although it has been demonstrated that knocking out the expression of receptors may induce changes in the composition of the subunits, the network circuitry, or both, the current findings show consistently that the NMDA receptor epsilon1 subunit mediates nitrous oxide but not sevoflurane anesthesia. Furthermore, the attenuated anesthetic impact of propofol, pentobarbital, diazepam, and midazolam as well as ketamine in knockout mice suggests that the NMDA receptor epsilon1 subunit could be indirectly involved in the hypnotic action of these drugs in vivo.     

Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement

Besides having important hormonal effects, progesterone has depressant and hypnotic effects on the brain. In this study, we compared women in the follicular phase with low progesterone levels and in the luteal phase with high progesterone levels regarding their anesthetic requirements. Twenty patients with menstrual cycle days from 1 to 10 (follicular group) and 20 patients with menstrual cycle days from 18 to 24 (luteal group) were included in the study. Anesthesia was induced with fentanyl and thiopental; relaxation was secured with rocuronium, and anesthesia was maintained with a mixture of nitrous oxide 2 L/min and oxygen 2 L/min plus sevoflurane. The delivered sevoflurane concentration was adjusted to sustain a constant bispectral index value that averaged 46 in both groups. To determine the progesterone levels, blood samples were taken from all patients before surgery. We found that progesterone levels were 0.86 +/- 0.30 ng/mL in the follicular group and 7.48 +/- 3.86 ng/mL in the luteal group. The minimum alveolar anesthetic concentration (MAC)-hour (MAC-h) value of sevoflurane in the follicular group (1.55 +/- 0.18 MAC-h) was significantly larger than in the luteal group (1.3 +/- 0.13 MAC-h) (P < 0.0001). The sevoflurane requirements were larger in the follicular group during the maintenance phase of anesthesia. In conclusion, high progesterone levels during the luteal phase might be the cause of decreased anesthetic requirement. IMPLICATIONS: The aim of this study was to determine the effect of high progesterone levels on anesthetic requirement. We measured progesterone levels before surgery and calculated the sevoflurane dose (MAC-h) required to maintain a constant bispectral index value. The dose of sevoflurane correlated inversely with serum progesterone concentrations.     

Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.     

Effects of nitrous oxide on spike activity on electrocorticogram under sevoflurane anesthesia in epileptic patients

We sought to investigate the effects of nitrous oxide on intraoperative electrocorticogram (ECoG) spike activities in 11 patients with intractable epilepsy. Grid electrodes were placed on the brain surface, and ECoG was recorded under the following conditions: 1.5 minimal alveolar anesthetic concentration (MAC) sevoflurane without nitrous oxide and 1.5 MAC sevoflurane with 50% nitrous oxide. The number of spikes for 5 minutes and the percentage of leads with spikes of total leads measured were assessed in each condition. The median numbers (25-75th) of spikes without and with nitrous oxide were 127 (87-368) and 61 (43-247), respectively. The numbers of spikes with nitrous oxide were significantly lower than those without nitrous oxide (P<0.05). The median percentages of leads with spikes without and with nitrous oxide were 68 (25-81) and 61 (28-70), respectively, and there were no significant differences in percentages of leads with spikes between the conditions. These results indicate that nitrous oxide attenuated the frequency of spikes on ECoG in epileptic patients, although it did not affect the extent of areas with spike activity.     

The involvement of the nociceptin receptor in the antinociceptive action of nitrous oxide

Nociceptin and its receptor are widely expressed in the central nervous system and are involved in the modulation of nociception. We have previously reported that the minimum anesthetic alveolar concentrations for volatile anesthetics do not differ between nociceptin receptor knockout (NOP-/-) mice and wild-type (NOP+/+) mice. In the present study, we investigated whether the nociceptin system is involved in the antinociceptive action of nitrous oxide. Using the acetic acid-induced writhing test, we showed that nitrous oxide had significantly less analgesic action in NOP-/- mice than in NOP+/+ mice. Furthermore, when anesthetized with a mixture of halothane and nitrous oxide (70%), intraperitoneal injection of acetic acid resulted in an increase of plasma adrenocorticotropic hormone concentrations in NOP-/- mice but not in NOP+/+ mice. An immunohistochemical study showed that nitrous oxide exposure induced c-Fos expression in the spinal cords of NOP+/+ mice but not in those of NOP-/- mice. These results together suggest that the antinociceptive action of nitrous oxide is, at least partly, mediated by the nociceptin system.     

Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat

BACKGROUND: Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia. METHODS: For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia. RESULTS: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were made in the cortex. CONCLUSIONS: Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.     

Subjective, Psychomotor, Cognitive, and Analgesic Effects of Subanesthetic Concentrations of Sevoflurane and Nitrous Oxide

Background: Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations.

Methods: A crossover design was used to test the effects of two end-tidal concentrations of sevoflurane (0.3% and 0.6%), two end-tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold-water test.

Results: Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects.     

Sympathetic Ganglionic Blockade Masks Beneficial Effect of Isoflurane on Histologic Outcome from Near-complete Forebrain Ischemia in the Rat

Background: Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia.

Methods: For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mmHg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 [micro sign]g [middle dot] kg-1 [middle dot] h-1) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia.

Results: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P < 0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P < 0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43 +/- 22% vs. 87 +/- 10%; P < 0.001). Trimethaphan abolished the beneficial effects of isoflurane (91 +/- 6%; P < 0.001). Similar observations were made in the cortex.     

Halothane anesthetic requirements are not affected by aminophylline treatment in rats and dogs

The authors determined the effects of aminophylline on the anesthetic requirements for halothane in rats and dogs. MAC for halothane was determined in rats (n = 24) before and after aminophylline, 100 mg X kg-1 ip, or an equal volume of saline. Because changes in central noradrenergic neurotransmission have been linked to drug-induced changes in the depth of the anesthetic state, we investigated the effect of aminophylline on the turnover of norepinephrine in discrete brain regions of halothane-anesthetized rats. To facilitate testing at steady-state aminophylline conditions and to permit frequent blood sampling, halothane MAC was determined in dogs (n = 7) before and after a therapeutic level of aminophylline (15 +/- 2 micrograms X ml-1) was obtained. Neither in the rats (1.0 vs. 1.0%) nor in the dogs (1.04 +/- 0.14 vs. 1.01 +/- 0.14%) was halothane MAC affected by aminophylline treatment. Commensurate with the lack of change of anesthetic depth, aminophylline treatment did not affect noradrenergic neurotransmission in the brain of halothane-anesthetized rats. Furthermore, the anticipated increase in circulating catecholamines following aminophylline treatment in dogs did not materialize. The authors conclude that halothane anesthetic requirements are not altered by aminophylline treatment, possibly because of the attenuation of the putative sympathomimetic effects of aminophylline by halothane.     

Quantitation of the Effect of Nitrous Oxide on Rocuronium Infusion Requirements Using Closed-loop Feedback Control

Background: Nitrous oxide has a minor effect on the effective dose 50% values of bolus doses of rocuronium. The authors have studied the effect of nitrous oxide on the infusion requirements of rocuronium using closed-loop feedback control of rocuronium infusion.

Methods: The authors obtained institutional approval and informed consent to study 70 patients. The patients were given total intravenous anesthesia with propofol and remifentanil by target-controlled infusion and were randomly assigned to one of two groups, one receiving nitrous oxide with 30% oxygen (n = 35) and the other group receiving air with 30% oxygen (n = 35). The possible interaction of rocuronium with nitrous oxide was quantitated by determining the asymptotic steady state rate of infusion of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium.

Results: Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set point, did not differ significantly between the groups. The administration of nitrous oxide did not affect rocuronium infusion requirements. The mean steady state rates of infusion were 33.0 +/- 9.8 and 36.9 +/- 13.2 mg/h in the nitrous oxide-total intravenous anesthesia and air-total intravenous anesthesia groups, respectively.