Sodasorb~LF降解七氟醚生成化合物A的临床研究

目的测定七氟醚与SodasorbLF反应生成的化合物A含量。方法30例ASAⅠ或Ⅱ级行七氟醚全身麻醉的择期手术病人随机均分为三组,吸入氧气的流量分别为2L/min(A组)、0.5L/min(B组)和0.3L/min(C组)。七氟醚呼气末浓度均为1MAC。分别在0(七氟醚呼气末浓度到达1MAC时)、1和2h从回路中抽取气体样本,以气相色谱法测定其中的化合物A含量,并同时测定吸收剂温度和含水量。结果各组均未测出化合物A的含量。结论气相色谱法检测不到七氟醚与SodasorbLF反应生成化合物A。     

七氟醚对肾小管功能影响的研究进展

本氟醚与碱石灰可产生降解反应生成以化合物Ａ为主的５种产物，化合物Ａ具有潜在的肾毒性，可与鼠肾小管蛋白质结合，致肾髓质外层带和皮质与髓质交界处坏死。临床上通过对肾小管功能较敏感的尿ＮＡＧ酶学检测未发现明显肾损害。     

七氟醚对肾小管功能影响的研究进展

七氟醚与碱石灰可产生降解反应生成以化合物A为主的5种产物,化合物A具有潜在的肾毒性,可与鼠肾小管蛋白质结合,致肾髓质外层带和皮质与髓质交界处坏死。临床上通过对肾小管功能较敏感的尿NAG酶学检测未发现明显肾损害。     

碱石灰对七氟醚的降解

卤化吸入麻醉药是一类常用的全麻药，此类药物可与碱石灰发生化学反应，产生对人体有毒的降解产物。近年来的研究结果表明：降解产物的毒性作用主要在肝肾功能的改变。本文主要综述碱石灰对七氟醚降解以及降解产物对肝肾功能的影响。     

二氧化碳吸收剂中水分对七氟醚分解反应的影响

目的　研究模拟紧闭反应器内干燥的二氧化碳 (CO2 )吸收剂及自身含水对七氟醚分解的影响。方法　在紧闭反应器 (1 6 0ml)内 ,分别装钠石灰、钡石灰、干燥钠石灰和干燥钡石灰 (各 2 5g)。在密闭状态下注入液态的七氟醚 4 0 0 μl,放入 5 0℃水浴内反应 6h ,分别在 5、1 5、30、4 5、6 0min、以后每 30分钟至 36 0分钟采样 ,用气相色谱法分析。测定七氟醚的分解产物。结果　钠石灰组出现复合物A、B ,在其他组七氟醚产生 5种分解产物。复合物A∶干燥钡石灰 >干燥钠石灰 >钡石灰和钠石灰组。干燥钡石灰组明显高于其他两组 (P <0 0 5 )。复合物B∶干燥钡石灰组 <钡石灰组 <干燥钠石灰组 (P <0 0 5 )。复合物C、D、E ,以干燥钡石灰组最为明显 (P <0 0 5 )。各组均未检测到CO。结论　在 5 0℃的紧闭反应器内 ,七氟醚与干燥的CO2 吸收剂反应剧烈 ,未产生CO ;国产钠石灰优于钡石灰 ,在紧闭容器内自身含水可以抑制分解反应     

比较七氟醚、异氟醚和安氟醚对颅内压的影响

目的：为了观察七氟醚对颅内压的影响。方法：选择２４例颅内肿胶病人,测定七氟醚麻醉的时颅内压变化并与异氟醚和安氟醚进行比较。术前用药、麻醉诱导及维持的静脉用药相同。于Ｌ３－４穿刺蛛网膜睛腔测脑脊液压（代表颅内压,ＩＣＰ）。依吸入药不同随机分为七的氟醚（Ｓ）组,异氟醚（１）组和安氟醚（Ｅ）组,监测ＢＰ、ＭＡＰ、ＥＣＧ、ＳｐＯ２、ＰＥＴ、ＣＯ２和ＭＡＣ,调整ＶＴ和ＲＲａＣＯ２维持在４～４．６６ＫＰＡ。三     

地氟醚、七氟醚和异氟醚对内源性一氧化氮的影响

目的：观察犬吸入地氟醚、七氟醚和异氟醚后血浆ＮＯ含量的变化，以进一步探讨ＮＯ在囱族吸入麻醉药扩血管作用中的地位。方法：犬麻醉后３０分钟，随机吸入地氟醚、一氟醚或异氟醚（ＭＡＣ ７．２％￣２．３％和１．２８％）使呼气末浓度达１ＭＡＣ，持续３０分钟。分别于呼气末浓度达１ＭＡＣ后５分钟、１５分钟和３０分钟和停吸后３０分钟分钟和１２０分钟抽取静脉血，用硝酸盐还原酶法测定ＮＯ。结果：ＮＯ水平在三组药物吸入过     

地氟醚、七氟醚和异氟醚对犬冠脉血流的影响

目的：采用超声血流量监测仪观察地氟醚、七氟醚和异氟醚对犬冠脉血流的影响。方法：犬１８只，腹腔注射１．５％硫喷妥钠２０ｍｇ／ｋｇ，静脉注射阿曲库铵０．８ｍｇ／ｋｇ麻醉诱导，气管插管后取正中开胸，分离冠状动脉左前降支，将３ｍｍ或３．５ｍｍ超声Ｄｏｐｐｌｅｒ血管探头置于分离血管处，连接超声多普勒冠脉血流量监测仪测定冠脉血流量，然后随机吸入地氟醚、七氟醚或异氟醚，ＭＡＣ分别为７．２％、２．３％和１．２８％     

七氟醚对罗库溴铵肌松效应的影响

目的 研究吸入不同浓度的七氟醚对不同剂量的罗库溴铵肌松效应的影响.方法 90例择期手术患者随机均分为六组.记录各组静注罗库溴铵后其起效时间、四个成串刺激(TOF)无反应时间、T1 25%恢复时间、T1 75%恢复时间及恢复指数(T1 25%恢复到75%的时间).结果 静注等效剂量的罗库溴铵Ⅲ组与Ⅰ组、Ⅳ组与Ⅱ组比较,起效时间差异无统计学意义.而静注等效剂量的Ⅴ组与Ⅰ组、Ⅵ组与Ⅱ组比较,起效时间明显缩短(P＜0.05);在无反应时间、T1 25%恢复时间、T1 75%恢复时间及恢复指数上,复合吸入七氟醚的Ⅲ到Ⅵ组较注入等效剂量的罗库溴铵Ⅰ组与Ⅱ组比较均有明显的延长(P＜0.05或P＜0.01);Ⅱ组与Ⅲ组之间以及Ⅳ组与Ⅴ组之间罗库溴铵的肌松维持时间差异无统计学意义.结论 七氟醚能明显延长罗库溴铵的作用时间,有时间依赖及剂量依赖趋势.     

Increases in coronary collateral blood flow produced by sevoflurane are mediated by calcium-activated potassium (BKCa) channels in vivo

BACKGROUND: Sevoflurane enhances coronary collateral blood flow independent of adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that this volatile anesthetic increases coronary collateral blood flow by either opening calcium-activated potassium channels or by directly stimulating nitric oxide synthesis in the canine coronary collateral circulation. METHODS: Twelve weeks after left anterior descending coronary artery ameroid constrictor implantation, barbiturate-anesthetized dogs (n = 22) were instrumented for measurement of hemodynamics and retrograde coronary flow. Dogs received sevoflurane ([0.5 and 1.0 minimum alveolar concentration [MAC]) during intracoronary infusions of drug vehicle (0.9% saline), the calcium-activated potassium channel antagonist iberiotoxin (13 microg/min), or the nitric oxide synthase inhibitor -nitro-l-arginine methyl ester (l-NAME, 300 microg/min). Retrograde coronary collateral blood flow was measured under baseline conditions, during and after administration of sevoflurane, and during intracoronary infusion of bradykinin. Data are mean +/- SEM. RESULTS: Sevoflurane increased (* < 0.05) retrograde coronary collateral blood flow (from 65 +/- 11 during control to 67 +/- 12* and 71 +/- 12* ml/min during 0.5 and 1.0 MAC, respectively). Iberiotoxin but not l-NAME attenuated these sevoflurane-induced increases in retrograde flow (6 +/- 1*, 7 +/- 2*, and 3 +/- 2 ml/min during vehicle, l-NAME, and iberiotoxin, respectively). After discontinuation of sevoflurane, retrograde flow returned to baseline values in each group. Bradykinin increased retrograde flow in vehicle- (63 +/- 12 to 69 +/- 12* ml/min) but not in iberiotoxin- (61 +/- 7 to 62 +/- 5 ml/min) or l-NAME-treated dogs (64 +/- 11 to 63 +/- 10 ml/min). CONCLUSIONS: The results demonstrate that sevoflurane increases coronary collateral blood flow, in part, through activation of calcium-activated potassium channels. This action occurs independent of nitric oxide synthesis.     

Effect of sevoflurane on the neuromuscular blockade produced by continuous mivacurium infusion

OBJECTIVE: To evaluate the effect of sevoflurane on a neuromuscular block from mivacurium in continuous infusion. PATIENTS AND METHODS: Fourteen ASA I-II patients receiving general anesthesia for orthopedic procedures on the knee. The neuromuscular block was monitored by acceleromyography in the adductor pollicis muscle after stimulation of the cubital nerve. Anaesthesia was induced with propofol and remifentanil. After orotracheal intubation, mivacurium was given in continuous infusion adjusted to obtain a stable submaximal block defined as a variation in the block of 3% more or less for 10 minutes (first response on a train of four [T1] between 40% and 60% of the calibrated value). Values for T1, the T4/T1 ratio (TR) and temperature over the thenar eminence were recorded at 3 moments: control moment (infusion of mivacurium and sevoflurane at an expired fraction of 1.5% for 30 minutes) and post-sevoflurane moment (perfusion of mivacurium and sevoflurane at an expired fraction of 0% for 15 minutes). Statistical analysis was by analysis of variance and post-hoc contrast (Tukey). RESULTS: Results are expressed as means with standard error between parentheses. We found that values at T1(%) and TR(%) were significantly lower at the sevoflurane moments (T1 = 43.11 [1]; TR = 25.68 [1]) and the post-sevoflurane moment (T1 = 36.29 [2]; TR = 25.06 [2]) than at the control moment (T1 = 53.18 [1]; TR = 38.93 [1]) (P < .05). T1 was significantly lower at the post-sevoflurane moment than at the sevoflurane moment (P < .05) but TR did not differ significantly. CONCLUSION: Sevoflurane causes a significant increase in the neuromuscular block maintained by mivacurium in continuous infusion and the increase lasts at least 15 minutes after the halogenated agent is cleared from blood.     

七氟醚紧闭循环麻醉时二氧化碳吸收剂对环路中compound A浓度的影响

目的比较七氟醚紧闭循环麻醉时二氧化碳吸收剂对环路中compound A浓度的影响。方法 42例神经外科择期手术患者随机分为Sofnolime组(S组)和Sodasorb LF组(LF组),每组21例。采用七氟醚紧闭循环麻醉,呼气末七氟醚的浓度保持在2.7%～3.5%。监测呼吸环路内compound A的浓度;采集术前、术毕、术后24、72h的血样,检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、肌酐(Cr)和尿素氮(BUN)的水平。留取术前、术毕、术后24、48、72h的尿样,检测总蛋白(TP)、β2微球蛋白(β2-MG)和β-N-乙酰氨基葡萄糖苷酶(NAG)。结果 LF组未检测出compound A,S组compound A平均最高浓度为(37.6±10.2)ppm。两组ALT、AST、TBIL、Cr和BUN水平组间、组内比较差异均无统计学意义。两组尿TP/Cr、β2-MG/Cr在术后增加(P0.05),但各时间点组间比较差异均无统计学意义。两组尿NAG/Cr无变化,组间比较差异无统计学意义。结论七氟醚紧闭循环麻醉时,呼吸环路中compound A的最大浓度低于50ppm,对肝、肾功能无明显影响。     

Influence of sevoflurane on the metabolism and renal effects of compound A in rats

BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in rats. In contrast, patient exposure to compound A during sevoflurane anesthesia has no clinically significant renal effects. The mechanism for this difference is incompletely understood. One possibility is that the metabolism and toxicity of compound A in humans is prevented by sevoflurane. However, the effect of sevoflurane on compound A metabolism and nephrotoxicity is unknown. Thus, the purpose of this investigation was to determine the effect of sevoflurane on the metabolism and renal toxicity of compound A in rats. METHODS: Male rats received 0.25 mmol/kg intraperitoneal compound A, alone and during sevoflurane anesthesia (3%, 1.3 minimum alveolar concentration, for 3 h). Compound A metabolites in urine were quantified, and renal function was evaluated by serum creatinine and urea nitrogen, urine volume, osmolality, protein excretion, and renal tubular histology. RESULTS: Sevoflurane coadministration with compound A inhibited compound A defluorination while increasing relative metabolism through pathways of sulfoxidation and beta-lyase-catalyzed metabolism, which mediate toxicity. Sevoflurane coadministration with compound A increased some (serum creatinine and urea nitrogen, and necrosis) but not other (urine volume, osmolality, and protein excretion) indices of renal toxicity. CONCLUSIONS: Sevoflurane does not suppress compound A nephrotoxicity in rats in vivo. These results do not suggest that lack of nephrotoxicity in surgical patients exposed to compound A during sevoflurane anesthesia results from an inhibitory effect of sevoflurane on compound A metabolism and toxicity. Rather, these results are consistent with differences between rats and humans in compound A exposure and inherent susceptibility to compound A nephrotoxicity.     

Carbon dioxide absorbents containing potassium hydroxide produce much larger concentrations of compound A from sevoflurane in clinical practice

We investigated the concentrations of degraded sevoflurane Compound A during low-flow anesthesia with four carbon dioxide (CO(2)) absorbents. The concentrations of Compound A, obtained from the inspiratory limb of the circle system, were measured by using a gas chromatograph. In the groups administered 2 L/min fresh gas flow with 1% sevoflurane, when the conventional CO(2) absorbents, Wakolime(TM) (Wako, Tokyo, Japan) and Dr?gersorb(TM) (Dr?ger, Lübeck, Germany), were used, the concentrations of Compound A increased steadily from a baseline to 14.3 ppm (mean) and 13.2 ppm, respectively, at 2 h after exposure to sevoflurane. In contrast, when the other novel types of absorbents containing decreased or no potassium hydroxide/sodium hydroxide, Medisorb(TM) (Datex-Ohmeda, Louisville, CO) and Amsorb(TM) (Armstrong, Coleraine, Northern Ireland), were used, Compound A remained at baseline (<2 ppm) throughout the study. In the groups administered 1 L/min fresh gas flow with 2% sevoflurane, Wakolime(TM) and Dr?gersorb(TM) produced much larger concentrations of Compound A (35.4 ppm and 34.2 ppm, respectively) at 2 h after exposure to sevoflurane. Medisorb(TM) showed measurable concentrations of Compound A (8.6 ppm at 2 h), but they were significantly smaller than those produced by the two conventional absorbents. In contrast, when Amsorb(TM) was used, Compound A concentrations remained at baseline throughout the study period. IMPLICATIONS: Carbon dioxide absorbents containing potassium hydroxide/sodium hydroxide produce much larger concentrations of Compound A from sevoflurane in clinical practice. An absorbent containing neither potassium hydroxide nor sodium hydroxide produces the smallest concentrations of Compound A.