极化液对严重烫伤伴多器官功能障碍综合征大鼠炎性细胞因子水平及预后的影响

目的观察早期极化液治疗对烫伤伴多器官功能障碍综合征(MODS)大鼠炎性细胞因子水平及预后的影响,探讨其防治机制。方法将120只SD大鼠造成30%TBSAⅢ度烫伤,伤后2h腹腔注射内毒素,制作烫伤伴MODS大鼠模型,随机分为极化液组、葡萄糖组和盐水组,每组40只。观察3组大鼠伤后1~7d血浆中血糖、乳酸、肿瘤坏死因子α(TNF-α)、一氧化氮(NO)以及白细胞介素6(IL-6)含量的变化;并计算伤后7d内各组大鼠的死亡率。结果极化液组大鼠伤后1~7d血糖、乳酸、TNF-α、IL-6和NO含量均明显低于其他组(P<0.01),伤后6~7d其TNF-α、IL-6和NO含量达到最低值,分别为(2.37±0.54)μg/L、(0.28±0.17)μg/L及(29±9)μmol/L;葡萄糖组血糖、乳酸含量明显高于盐水组(P<0.01),而两组TNF-α、IL-6和NO含量相近(P>0.05).极化液组伤后7d内死亡率为20.0%,明显低于葡萄糖组与盐水组(分别为37.5%、47.5%,P<0.05).结论极化液通过改善烫伤引起的糖代谢障碍,降低机体炎性细胞因子水平,可作为防治烫伤伴MODS的辅助措施。     

胰岛素强化治疗对严重创伤患者炎性反应及预后的影响

目的 了解胰岛素强化治疗对严重创伤患者炎性反应及预后的影响.方法 将80例严重创伤患者按随机配对原则分为治疗组(40例)和对照组(40例).治疗组患者入院后立即行胰岛素强化治疗,从胰岛素泵泵入胰岛素2～4 U/h,控制血糖值在6～8 mmol/L;对照组按临床常规治疗,不给予胰岛素.观察2组患者的发热、器官损伤情况,统计病死率.于开始治疗后1、3、5、7 d晨抽取2组患者静脉血,检测血浆TNF-α、IL-2、IL-10、C反应蛋白(CRP)水平.结果 治疗组患者9例发生高热,低于对照组(29例).治疗组和对照组各有31例和30例患者出现1个脏器功能不全.治疗组和对照组同一患者出现3个脏器功能不全的分别为10、19例,出现4个脏器功能不全的分别为7、12例.治疗组伤后3 d内死亡4例,3 d以后死亡1例,病死率为12.5%;对照组伤后3 d内死亡5例,3 d以后死亡4例,病死率为22.5%.治疗后3～7 d,治疗组患者TNF-α、CRP值均低于对照组(P<0.05或P<0.01),而IL-2、IL-10值则均高于对照组(P<0.05或P<0.01).治疗后7 d,治疗组TNF-α、CRP值最低,分别为(1.3±0.6)μg/L、(55±16)mg/L,且明显低于对照组的(3.0±0.8)μg/L、(89±20)mg/L(P<0.01).结论 严重创伤后行胰岛素强化治疗,可以减轻患者全身性炎性反应程度,改善创伤患者预后.     

强化胰岛素治疗对严重多发伤患者炎症因子水平及预后的影响

目的观察强化胰岛素治疗对严重多发伤患者炎症因子及预后的影响。方法将53例严重多发伤患者随机分为治疗组(27例)和对照组(26例)。治疗组患者在基础治疗的基础上,加用胰岛素微量泵强化治疗,对照组血糖控制在11.1 mmol/L以下,分别在治疗前、后测定患者的肿瘤坏死因子(TNF-α)、白细胞介素(IL-1β)、IL-6、C反应蛋白(CRP)水平,并观察多器官功能障碍综合征、院内感染发生率和病死率。结果治疗组患者的TNF-α、IL-1β、IL-6、CRP水平显著低于对照组,差异有统计学意义(P0.05或P0.01),治疗组多器官功能障碍综合征、院内感染发生率及病死率低于观察组(P0.05)。结论强化胰岛素治疗可降低严重多发伤患者的炎症因子的表达水平,改善患者预后,降低院内感染的发生率及死亡率。     

微波对慢性牙周炎患者龈沟液中多项因子水平影响研究

目的 探讨研究微波对慢性牙周炎患者龈沟液中多项因子水平影响.方法 选取2008-06～2010-06于我院进行治疗的44例慢性牙周炎患者为研究对象,将其随机分为对照组(常规治疗组)22例和观察组(辅助微波治疗组)22例,后将2组患者治疗前后的龈沟液PGE2、IL-6、IL-8、IL-17、CRP及sICAM-1水平进行...     

胰岛素强化治疗对胃癌手术患者临床结局的影响

目的 研究胰岛素强化治疗对胃癌手术患者临床结局的影响.方法 46例胃癌手术患者随机分为术后胰岛素强化治疗组(n=23,血糖控制在4.4～6.1 mmool/L)和常规治疗组(n=23,血糖控制在10.0～11.1 mmol/L).动态监测比较两组围手术期空腹血糖(FBG)、空腹胰岛素定量(FINS)、白细胞介素-6(IL-6)、肿瘤坏死因子-α[(TNF-α)及C-反应蛋白(CRP)水平,并根据稳态模式评估法(HOMA)计算胰岛素抵抗指数(HOMA-IR);记录两组患者术后并发症发生情况.结果 两组患者均无低血糖发生,胰岛素强化治疗组术后发热天数、抗生素使用天数、住院天数及并发症发生率均明显低于常规治疗组(P＜0.05);强化治疗组术后1 d、3 d血清InHOMA-IR、IL-6、TNF-α及术后1、3、7 d的CRP均明显低于常规治疗组(P＜0.05).结论 胰岛素强化治疗可拮抗术后机体的高炎状态,抗炎效应可能是胰岛素强化治疗又一改善手术创伤患者预后的重要机制.     

蛋白酶抑制剂对外科高危病人SIRS与MODS作用的研究

目的评价蛋白酶抑制剂乌司他丁（UTI）对外科高危病人的疗效，通过观察细胞因子的变化和临床转归的影响来探讨其作用机制。方法选择符合入选标准共58例，随机分为乌司他丁治疗组（U组，n=30）和对照组（C组，EL=28）：U组病人在接受标准常规治疗的同时接受蛋白酶抑制剂（UTI）治疗，术后12h内开始静脉注射UTI，每次20万单位，每天两次，连续5d。C组病人接受常规治疗＋安慰剂（生理盐水）。在治疗前后24、48、72h测定TNF-d、IL-6、IL-8，一氧化氮（NO）、血乳酸、肌酐（Cr），并进行治疗前、后APACHEⅡ评分，观察住院时间和病死率：结果u组病人IL-6、IL-8、TNF-α、APACHEⅡ评分的平均值较C组显著降低。Cr、NO、血乳酸的浓度在治疗后两组间差异无显著性意义。两组住院时间和病死率差异无显著性意义。结论UTI可抑制外科高危病人促炎因子IL-6、IL-8、TNFα，降低病人APACHEⅡ评分，但对临床转归有无影响，有待于进一步观察研究.     

巨噬细胞极化在脊髓损伤中的作用机制

脊髓损伤是脊柱神经系统严重的创伤,损伤后局部组织破坏和微循环障碍,引起局部损伤加重和周围神经细胞广泛坏死。脊髓损伤后常常伴随炎症反应产生各种细胞因子和生物活性物质,引起巨噬细胞极化,巨噬细胞在IFN-γ、LPS、TNF-α等刺激极化成M1巨噬细胞,主要表现为促炎和损伤作用;在IL-4、IL-10、IL-13刺激下极化为M2巨噬细胞,主要表现出抗炎和修复作用。目前脊髓损伤后的治疗手段非常有限,通过调控脊髓损伤后M1和M2巨噬细胞抑制其促炎损伤作用,促进神经修复作用是脊髓损伤后治疗的一个新方向。本文将对巨噬细胞在脊髓损伤后的极化表型及其功能特点的研究进展做一综述。     

多发伤患者炎性因子变化及其临床意义

目的 探讨多发伤患者外周血中细胞因子变化及其临床意义.方法 采用ELISA法检测39例多发伤患者(创伤严重度>16)人院时,入院后1、3、5、7 d,CRP、TNF-α、IL-6、IL-8水平变化(重伤组),并与同期创伤程度较轻(创伤严重度<16)的48例进行动态比较(轻伤后).结果 重伤组入院后CRP、TNF-α、IL-6、IL-8均显著升高,重伤组患者血清CRP释放高峰在入院后1 d,其余三种炎性介质释放高峰期均在入院后3～5 d;重伤组入院后24 h IL-6水平与患者创伤严重度评分呈正相关关系(r=0.83,P<0.05);重伤组10例发生多器官功能障碍综合征(MODS)和轻伤组相比,IL-6、IL-8在人院后1、3、5、7 d升高具有统计学差异,而TNF-α只有在入院时、入院后1 d才具有显著性差异性,CRP在两组之间没有差异性.结论 创伤引起的炎性介质的大量释放在多发伤患者的病情发展中起着重要作用,及时检测患者体内炎性因子的变化,可以更好的观察患者的治疗效果.准确的预测患者的病情发展.     

川芎嗪注射液对早期糖尿病肾病患者IL-6、TNF-α和CRP的影响

目的:探讨川芎嗪注射液对早期糖尿病肾病(Diabetic nephropathy,DN)患者白细胞介素-6(Interleukin-6.IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和C反应蛋白(C- reactive protein,CRP)的影响.方法:将80例早期DN患者随机分为对照组(40例)和治疗组(40例),对照组为常规西药治疗,治疗组在此基础上加用川芎嗪注射液,连用15天.采用ELISA法检测两组患者治疗前后血清IL-6、TNF-α和CRP水平,同时观察空腹血糖、血脂、24h尿蛋白等指标的变化.结果:与治疗前比较,治疗组患者血清IL-6、TNF-α和CRP水平均下降(P＜0.01),而对照组无明显变化(P＞0.05).结论:川芎嗪注射液可能通过减低DN患者血清IL-6、TNF-α和CRP水平,抑制炎症反应,起到对DN的保护作用.     

连续性血液净化联合乌司他丁治疗重症脓毒症的临床研究

目的:探讨连续血液净化(CBP)联合鸟司他丁治疗重症脓毒症的疗效。方法:选择重症脓毒症患者120例,随机分为对照组和观察组。两组均给予常规抗感染、液体复苏、穿刺引流控制感染灶,应用多巴胺、去甲肾上腺素等血管活性药物,必要时给予机械通气。同时两组在确诊脓毒症4 h内均采用CBP治疗。在此基础上,观察组静脉注射乌司他丁50万IU/d,连续应用7 d。检测入院时和入院后第1、3、5天取血检测血浆C反应蛋白(CRP)、血清乳酸(Lac)、血清降钙素原(PCT)、白细胞介素-10(IL-10)水平。在患者入院时及入院后第1、3、5天分别进行序贯器官衰竭评估(SOFA)和急性生理学与慢性健康状况评分Ⅱ(APACHE II)。结果:两组患者治疗后第1、3、5天的CRP、Lac、PCT、IL-10均低于治疗前(均P<0.05);且观察组治疗后各时点的CRP、Lac、PCT和IL-10显著低于对照组。两组患者治疗后第1、3、5天的SOFA评分和APACHElI评分均显著低于治疗前;且观察组在入院第1、3、5天的SOFA评分和APACHElI评分均显著低于对照组,差异有统计学意义(均P<0.05)。结论:CBP联合乌司他丁能够清除炎症介质、纠正机体缺血缺氧、改善组织细胞和器官低灌注,维持血流动力学稳定,减少器官的损伤,值得重症脓毒症患者早期应用。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.