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     

Effect of Nitrous Oxide on Neurologic and Neuropsychological Function after Intracranial Aneurysm Surgery

Background: Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

Methods: The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33[degrees]C) versus normothermia (temperature = 36.5[degrees]C) in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Anesthesia was dictated by a limited-options protocol with the use of nitrous oxide determined by individual anesthesiologists. All patients were assessed daily for 14 days after surgery or until hospital discharge. Neurologic and neuropsychological testing were conducted at 3 months after surgery. Outcome data were analyzed via both univariate tests and multivariate logistic regression analysis correcting for factors thought to influence outcome. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide.

Results: Outcome data were available for 1,000 patients, of which 373 received nitrous oxide. There was no difference between groups in the development of delayed ischemic neurologic deficit. At 3 months after surgery, there were no significant differences between groups in any outcome variable: Glasgow Outcome Score (OR, 0.84; 95% confidence interval [CI], 0.63-1.14; P = 0.268), National Institutes of Health Stroke Scale (OR, 1.29; 95% CI, 0.96-1.73; P = 0.087), Rankin Disability Score (OR, 0.84; 95% CI, 0.61-1.15; P = 0.284), Barthel Activities of Daily Living Index (OR, 1.01; 95% CI, 0.68-1.51; P = 0.961), or neuropsychological testing (OR, 1.26; 95% CI, 0.85-1.87; P = 0.252).     

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.     

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).     

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.     

Effect of Nitrous Oxide on Spike Activity During Epilepsy Surgery

Summary. There are controversies over the effect of nitous oxide on the electrocorticograms in patients with epilepsy. To clarify the effect of nitrous oxide on electrocorticograms, spike activities were compared with and without nitrous oxide under neuroleptoanesthesia in 10 patients with intractable epilepsy during surgery. Spikes decreased with nitous oxide significantly (P<0.01) and disappeared in 3 cases. We conclude that discontinuation of nitrous oxide should be taken into consideration during electrocorticographic monitoring in epilepsy surgery.     

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 Effect of Local Scavenging on Occupational Exposure to Nitrous Oxide

Despite evacuation of excess anaesthetic gases at the expiratory valve of the anaesthetic circuit and a general ventilation system producing 17–20 air changes per hour, mask anaesthesia often causes occupational exposure to anaesthetic gases exceeding the threshold limit values. The effect of a local air exhaust system, a local scavenger, on occupational exposure to nitrous oxide during paediatric mask anaesthesia was studied. The scavenger evacuated 140 m³ of air per hour and was placed at a distance of 20 cm from the face mask. In a very poorly ventilated operating theatre the exposure to nitrous oxide was reduced by 75% during the anaesthetic sessions and exposure to concentrations above 500 ppm was almost eliminated. The experiences from the installation and clinical use are discussed. Local scavenging is an excellent complement to the scavenging of excess gases at the expiratory valve, and it may be considered an alternative to expensive, high-capacity ventilation systems.     

Intracuff Pressure and Tracheal Morbidity: Influence of Filling Cuff with Saline during Nitrous Oxide Anesthesia

Background : Diffusion of nitrous oxide into the cuff of the endotracheal tube results in an increase in cuff pressure. Excessive endotracheal tube cuff pressure may impair tracheal mucosal perfusion and cause tracheal damage and sore throat. Filling the cuff of the endotracheal tube with saline instead of air prevents the increase in cuff pressure due to nitrous oxide diffusion. This method was used to test whether tracheal morbidity is related to excess in tracheal cuff pressure during balanced anesthesia.

Methods : Fifty patients with American Society of Anesthesiologists physical status I or II were randomly allocated to two groups with endotracheal tube cuffs initially inflated to 20-30 cm H2O with either air (group A) or saline (group S). Anesthesia was maintained with isoflurane and nitrous oxide. At the time of extubation, a fiberoptic examination of the trachea was performed by an independent observer, and abnormalities of tracheal mucosa at the level of the cuff contact area were scored. Patients assessed their symptoms (sore throat, dysphagia, and hoarseness) at the time of discharge from the postanesthesia care unit and 24 h after extubation on a 101-point numerical rating scale.

Results : Cuff pressure increased gradually during anesthesia in group A but remained stable in group S. The incidence of sore throat was greater in group A than in group S in the postanesthesia care unit (76 vs. 20%) and 24 h after extubation (42 vs. 12%;P < 0.05). Tracheal lesions at time of extubation were seen in all patients of group A and in eight patients (32%) of group S (P < 0.05).