Respiratory Mechanics during Xenon Anesthesia in Pigs: Comparison with Nitrous Oxide

Background: Because of its high density and viscosity, xenon (Xe) may influence respiratory mechanics when used as an inhaled anesthetic. Therefore the authors studied respiratory mechanics during xenon and nitrous oxide (N2O) anesthesia before and during methacholine-induced bronchoconstriction.

Methods: Sixteen pentobarbital-anesthetized pigs initially were ventilated with 70% nitrogen-oxygen. Then they were randomly assigned to a test period of ventilation with either 70% xenon-oxygen or 70% N2O-oxygen (n = 8 for each group). Nitrogen-oxygen ventilation was then resumed. Tidal volume and inspiratory flow rate were set equally throughout the study. During each condition the authors measured peak and mean airway pressure (Pmax and Pmean) and airway resistance (Raw) by the end-inspiratory occlusion technique. This sequence was then repeated during a methacholine infusion.

Results: Both before and during methacholine airway resistance was significantly higher with xenon-oxygen (4.0 +/- 1.7 and 10.9 +/- 3.8 cm H2O [middle dot] s-1 [middle dot] l-1, mean +/- SD) when compared to nitrogen-oxygen (2.6 +/- 1.1 and 5.8 +/- 1.4 cm H2O [middle dot] s-1 [middle dot] l-1, P < 0.01) and N2O-oxygen (2.9 +/- 0.8 and 7.0 +/- 1.9, P < 0.01). Pmax and Pmean did not differ before bronchoconstriction, regardless of the inspired gas mixture. During bronchoconstriction Pmax and Pmean both were significantly higher with xenon-oxygen (Pmax, 33.1 +/- 5.5 and Pmean, 11.9 +/- 1.6 cm H2O) when compared to N2O-oxygen (28.4 +/- 5.7 and 9.5 +/- 1.6 cm H2O, P < 0.01) and nitrogen-oxygen (28.0 +/- 4.4 and 10.6 +/- 1.3 cm H2O, P < 0.01).     

Spinal Cord Motoneuron Excitability during Isoflurane and Nitrous Oxide Anesthesia

Background: Recent evidence suggests that the spinal cord is an important site of anesthesia that is necessary for surgical immobility, but the specific effect of anesthetics within the spinal cord is unclear. This study assessed the effect of isoflurane and nitrous oxide on spinal motoneuron excitability by monitoring the H-reflex and the F wave.

Methods: Eight adult patients, categorized as American Society of Anesthesiologists physical status 1 or 2, who were undergoing elective orthopedic surgery were anesthetized with 0.6, 0.8, 1.0, and 1.2 times the estimated minimum alveolar concentration (MAC) of isoflurane. Nitrous oxide was added in graded concentrations of 30%, 50%, and 70%, whereas the isoflurane concentration was decreased to maintain a total MAC of 1. The H-reflex of the soleus muscle and the F wave of the abductor hallucis muscle were measured before anesthesia and 15 min after each change of anesthetic concentration. Four or more trials of the H-reflex and 18 trials of the F wave were recorded at each concentration of anesthesia. The effect of the anesthetics on the H-reflex and F wave was analyzed using Dunnett's test.

Results: H-reflex amplitude was decreased to 48.4 +/- 18.6% of preanesthesia level at 0.6 MAC isoflurane and to 33.8 +/- 19.1% when isoflurane concentration increased from 0.6 MAC to 1.2 MAC. F wave amplitude and persistence decreased to 52.2 +/- 33.6% and 44.4 +/- 26% of baseline at 0.6 MAC isoflurane, and to 33.8 +/- 26% and 21.7 +/- 22.8% at 1.2 MAC isoflurane. Isoflurane plus nitrous oxide (total 1 MAC) decreased H-reflex amplitude to 30.4-33.3% and decreased F wave persistence to 42.8-56.3% of baseline.     

Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Homocysteine Concentrations after Nitrous Oxide Anesthesia

Background: Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene (677C>T, 1298A>C) cause elevated plasma homocysteine concentrations and have been linked to fatal outcomes after nitrous oxide anesthesia. This study tested the hypothesis that patients with common MTHFR 677C>T or 1298A>C mutations develop higher plasma homocysteine concentrations after nitrous oxide anesthesia than wild-type patients.

Methods: In this prospective, observational cohort study with blinded, mendelian randomization, the authors included 140 healthy patients undergoing elective surgery. All patients received 66% nitrous oxide for at least 2 h. The main outcome variable, plasma total homocysteine, and folate, vitamin B12, and holotranscobalamin II were measured before, during, and after surgery. After completion of the study, all patients were tested for their MTHFR 677C>T or 1298A>C genotype.

Results: Patients with a homozygous MTHFR 677C>T or 1298A>C mutation (n = 25) developed higher plasma homocysteine concentrations (median [interquartile range], 14.9 [10.0-26.4] [mu]m) than wild-type or heterozygous patients (9.3 [7.5-15.5] [mu]m; n = 115). The change in homocysteine after nitrous oxide anesthesia was tripled in homozygous patients compared with wild-type (5.6 [mu]m [+60%] vs. 1.8 [mu]m [+22%]). Only homozygous patients reached average homocysteine levels considered abnormal (> 15 [mu]m). Plasma 5-methyl-tetrahydrofolate concentrations increased uniformly by 20% after nitrous oxide anesthesia, indicating the inactivation of methionine synthase and subsequent folate trapping. Holotranscobalamin II concentrations remained unchanged, indicating no effect of nitrous oxide on vitamin B12 plasma concentrations.     

紧闭式氧化亚氮麻醉方法的探讨

２５例选择期手术病人采用紧闭式氧化亚氮麻醉方法，术中持续监测呼气末氧和氧化亚氮浓度，脉搏血氧饱和度和呼吸循环指标，术中观察紧闭式麻醉后呼吸末氧化亚氮，氧浓度变化，结果：紧闭式麻醉１，２，３ｈ后氧化亚氮浓度分别为５２．７％，５６％，６４．９％，氧浓度为４２．１％，３４．４％，３０．８％，随麻醉时间的延长，气道压力先降后回升，约３ｈ恢复至紧闭麻醉前的水平，紧闭式麻醉前后在本组观察时间内动脉血气分析提示     

Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting: A Meta-Analysis

Background: Postoperative nausea and vomiting are important causes of morbidity after general anesthesia. Nitrous oxide has been implicated as an emetogenic agent in many studies. However, several other trials have failed to sustain this claim. The authors tried to resolve this issue through a meta-analysis of randomized controlled trials comparing the incidence of postoperative nausea and vomiting after anesthesia with or without nitrous oxide.

Methods: Of 37 published studies retrieved by a search of articles indexed on the MEDLINE database from 1966 to 1994, 24 studies (26 trials) with distinct nitrous-oxide and non-nitrous oxide groups were eligible for the meta-analysis. The pooled odds ratio and relative risk were calculated. Post hoc subgroup analysis was also performed to qualify the result.

Results: The pooled odds ratio was 0.63 (0.53 to 0.75). Omission of nitrous oxide reduced the risk for postoperative nausea and vomiting by 28% (18% to 37%). In the subgroup analysis, the maximal effect of omission of nitrous oxide was seen in female patients. In patients undergoing abdominal surgery and general surgical procedures, the effect of omission of nitrous oxide, although in the same direction, was not significant.     

Effect of Nitrous Oxide Anesthesia on Plasma Homocysteine and Endothelial Function

Background: Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide.

Methods: The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, l-arginine, l-citrulline, asymmetric dimethylarginine, and nitrate concentrations.

Results: The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 [mu]m; 95% confidence interval, 2.8-7.0 [mu]m; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates.     

Esmolol Reduces Anesthetic Requirement for Skin Incision during Propofol/Nitrous Oxide/Morphine Anesthesia

Background: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta1 -receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision.

Methods: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micro gram [center dot] kg-1 min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micro gram [center dot] kg (-1) min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression.

Results: The propofol Cp50 with nitrous oxide was 3.85 micro gram/ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micro gram/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive bias. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found.     

Prediction of Movement during Propofol/Nitrous Oxide Anesthesia: Performance of Concentration, Electroencephalographic, Pupillary, and Hemodynamic Indicators

Background: Movement in response to painful stimulation is the end point classically used to assess the potency of anesthetic agents. In this study, the ability of modeled propofol effect-site concentration to predict movement in volunteers during propofol/nitrous oxide anesthesia was tested, then it was compared with the predictive abilities of the Bispectral Index and 95% spectral edge frequency of the electroencephalogram, pupillary reflex amplitude, and systolic arterial blood pressure. In addition, the relationships between simple end points of loss and recovery of consciousness, and pupillary, hemodynamic, and propofol concentration indicators were studied.

Methods: Ten healthy volunteers were anesthetized with an infusion of propofol, which was increased in three equal steps to 21 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1. After loss of the ability to hold a syringe and of the eyelash reflex, 60% nitrous oxide was introduced and the trachea was intubated without the use of muscle relaxants. The propofol infusion rate then was decreased to 15.4 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1. Ten minutes later, tetanic electrical stimulation was administered to the thigh via needle electrodes: if movement was observed within 1 min, the propofol infusion rate was increased by 1.75 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1 5 min after the stimulus; if not, it was similarly decreased. This 15-min sequence was repeated until volunteers "crossed over" from movement to no movement (or vice versa) four times. The propofol infusion rate then was increased to 21 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1, nitrous oxide was discontinued, the trachea was extubated, and the infusion rate was decreased in five equal steps over 50 min. The times at which the eyelash reflex returned and the birth date was recalled were recorded. The electroencephalogram was monitored continuously (FP1, FP2, ref: nasion, ground: mastoid). Measurements of the pupillary response, arterial blood pressure, and heart rate were recorded during induction and awakening, just before and for 5 min after each stimulation. Arterial blood samples were obtained for propofol assay, and propofol effect-site concentrations were calculated at each time. The predictive value of indicators was compared using a new statistic, the prediction probability (PK).

Results: Loss and return of the eyelash reflex occurred at greater propofol effect-site concentrations than either dropping the syringe or recall of the birthday. The propofol effect-site concentration (in the presence of 60% nitrous oxide) predicted to prevent movement after a supramaximal stimulus in 50% of volunteers was 1.80 micro gram/ml (95% confidence limits: 1.40-2.34 micro gram/ml). The Bispectral Index (PK = 0.86), 95% spectral edge frequency (PK = 0.81), pupillary reflex amplitude (PK = 0.74), and systolic arterial blood pressure (PK = 0.78) did not differ significantly from modeled propofol effect-site concentration (PK = 0.76) in their ability to predict movement.     

The Influence of Cuff Volume and Anatomic Location on Pharyngeal, Esophageal, and Tracheal Mucosal Pressures with the Esophageal Tracheal Combitube

Background: The authors determined the influence of cuff volume and anatomic location on pharyngeal, esophageal, and tracheal mucosal pressures for the esophageal tracheal combitube.

Methods: Twenty fresh cadavers were studied. Microchip sensors were attached to the anterior, lateral, and posterior surfaces of the distal and proximal cuffs of the small adult esophageal tracheal combitube. Mucosal pressure for the proximal cuff in the pharynx was measured at 0- to 100-ml cuff volume in 10-ml increments, and for the distal cuff in the esophagus and trachea were measured at 0- to 20-ml cuff volume in 2-ml increments. The proximal cuff volume to form an oropharyngeal seal of 30 cm H2O was determined. In addition, mucosal pressures for the proximal cuff in the pharynx were measured in four awake volunteers with topical anesthesia.

Results: There was an increase in mucosal pressure in the trachea, esophagus, and pharynx at all cuff locations with increasing volume (all:P < 0.001). Pharyngeal mucosal pressures were highest posteriorly (50-ml cuff volume: 99 +/- 62 cm H2O; 100-ml cuff volume: 255 +/- 161 cm H2O). Esophageal mucosal pressures were highest posteriorly (10-ml cuff volume: 108 +/- 55 cm H2O; 20-ml cuff volume: 269 +/- 133 cm H2O). Tracheal mucosal pressures were highest anteriorly (10-ml cuff volume: 98 +/- 53 cm H2O; 20-ml cuff volume: 236 +/- 139 cm H2O). The proximal cuff volume to obtain an oropharyngeal seal of 30 cm H2O was 47 +/- 12 ml. Pharyngeal mucosal pressures were similar for cadavers and awake volunteers.     

Women Emerge from General Anesthesia with Propofol/Alfentanil/Nitrous Oxide Faster than Men

Background: Recovery from general anesthesia is governed by pharmacodynamic and pharmacokinetic factors. Gender has not previously been recognized as a factor influencing the time to emergence from general anesthesia.

Methods: This multicenter study was originally designed to measure the effects of the bispectral index on intraoperative anesthetic management and patient recovery. We compared the wake-up and recovery times of 274 adults after propofol/alfentanil/nitrous oxide anesthesia. Patients were randomly assigned to have the titration of propofol performed with or without the use of bispectral index monitoring. Specific guidelines were given for the titration of drugs. The aim in all cases was to provide a safe anesthetic with the fastest possible recovery.

Results: There was a significant reduction in propofol dose, time to eye opening, and response to verbal command when the anesthetic was titrated using the bispectral index. Unexpectedly, gender proved to be a highly significant independent predictor for recovery time. Women woke significantly faster than men: the time from end of anesthesia to eye opening was 7.05 versus 11.22 min, P < 0.05, and response to verbal command was 8.12 versus 11.67 min, P < 0.05. These differences were significant at all four study sites and in each treatment group. Men consistently had prolonged recovery times compared to women, P < 0.001. There was no difference in the dose of anesthetic used between gender.     

Pharmacokinetics of Cisatracurium in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia

Background: Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED95.

Methods: Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus dose of 0.1 or 0.2 mg *symbol* kg sup -1 (2 or 4 times the ED95, respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio greater or equal to 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite.

Results: The clearances (5.28+/-1.23 vs. 4.66+/- 0.67 ml *symbol* min sup -1 *symbol* kg sup -1) and terminal elimination half-lives (22.4+/-2.7 vs. 25.5+/-4.1 min) were not statistically different between patients receiving 0.1 mg *symbol* kg sup -1 and 0.2 mg *symbol* kg sup -1, respectively. Maximum concentration values for laudanosine averaged 38+/-21 and 103+/-34 ng *symbol* ml sup -1 for patients receiving the 0.1 and 0.2 mg *symbol* kg sup -1 doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101+/-27 and 253+/-51 ng *symbol* ml sup -1, respectively. Monoquaternary acid was not quantified in any plasma sample.