心脏死亡器官捐献供肾与传统尸体供肾肾移植的疗效比较

目的 比较心死亡器官捐赠(DCD)供肾与传统尸体供肾肾移植的疗效.方法 回顾性分析单中心2007年2月至2012年6月的69例DCD供肾肾移植受者的资料,并根据受者年龄(相差10岁以内)、移植次数和免疫抑制剂应用情况,按1∶2的比例匹配同期138例传统尸体肾移植受者,进行资料比较.结果 DCD肾移植组术后移植肾功能恢复延迟(DGF)和原发性移植肾无功能(PNF)的发生率为29.0％和2.9％,而传统尸体肾移植组为13.8％和0,差异有统计学意义(P＜0.05).Kaplar-Meier分析结果表明,DCD肾移植组术后6个月、1年和3年的移植肾存活率分别为95.7％、95.7％和93.3％;而传统尸体肾移植组分别为97.8％、97.8％和96.8％,两组的差异无统计学意义(P＞0.05).两组受者存活率的差异也无统计学意义(P＞0.05).术后7和14d,DCD肾移植组的移植肾肾小球滤过率低于传统尸体肾移植组(P＜0.05),但术后1个月至1年,两组移植肾肾小球滤过率的差异无统计学意义(P＞0.05).结论 虽然术后DGF和PNF发生率较高,但DCD肾移植的长期疗效与传统尸体肾移植相当,DCD供肾可以作为替代传统尸体供肾的良好来源.     

不同免疫诱导方案在心脏死亡器官捐献肾移植中的应用研究

目的探讨不同免疫诱导方案应用于心脏死亡器官捐献(DCD)肾移植受者的有效性和安全性。 方法回顾性分析解放军第三〇九医院器官移植研究所2014年1月至2016年1月完成的121例DCD肾移植受者临床资料。根据免疫诱导方案的不同分为3组：巴利昔单抗组(61例)、兔抗人胸腺细胞球蛋白组(rATG组,18例)和抗人T淋巴细胞兔免疫球蛋白组(ATG-F组,42例)。观察3组受者急性排斥反应、移植肾功能延迟恢复(DGF)、感染发生情况,以及受者和移植肾1年存活率。 结果121例DCD肾移植受者中,17例发生急性排斥反应,巴利昔单抗组10例(16.4%),rATG组2例(11.1%),ATG-F 5例(11.9%),3组急性排斥反应发生率差异无统计学意义(χ²＝0.57,P>0.05)。共32例受者术后出现DGF,巴利昔单抗组16例(26.2%),ATG组6例(33.3%),ATG-F组10例(23.8%),3组DGF发生率差异无统计学意义(χ²＝0.57,P>0.05)。3组肺部感染发生率分别为14.8%,22.2%,26.2%,差异无统计学意义(χ²＝2.12,P>0.05)。共7例出现CMV感染,rATG组3例,ATG-F组4例,3组受者CMV感染发生率差异有统计学意义(χ²＝10.85,P<0.05),ATG组和ATG-F组高于巴利昔单抗组。3组受者和移植肾1年存活率分别为96.7%和95.1%、100.0%和100.0%,95.2%和95.2%,差异均无统计学意义(χ²＝0.89和0.91,P均>0.05)。 结论对于低免疫风险的DCD肾移植受者,ATG、ATG-F及巴利昔单抗3种免疫诱导方案有效性无明显差异,但与巴利昔单抗相比,ATG、ATG-F可能增加CMV感染风险。     

心脏死亡器官捐献肾移植两种免疫诱导方案疗效比较

目的比较在心脏死亡器官捐献(DCD)肾移植受者中分别应用IL-2受体拮抗剂(IL-2Ra)或抗胸腺细胞球蛋白(ATG)进行免疫诱导治疗的早期临床疗效,探讨DCD肾移植中如何选择合理的免疫抑制方案。方法回顾性分析2015年1月至2016年4月在武汉大学人民医院器官移植科完成的110例DCD供肾肾移植受者资料。其中应用IL-2Ra进行免疫诱导82例(IL-2Ra组),应用ATG进行免疫诱导28例(ATG组),所有受者均采用他克莫司+吗替麦考酚酯+糖皮质激素三联免疫抑制方案。两组受者术前及术后各时间点血清肌酐比较采用t检验。两组受者术后DGF、肺部感染、急性排斥反应(AR)发生情况以及移植肾/受者存活情况比较采用卡方检验。P0.05为差异有统计学意义。结果 IL-2Ra组和ATG组受者DGF发生率分别20.7%、42.9%,差异有统计学意义(χ2=5.263,P0.05),两组受者肺部感染、AR发生情况以及移植肾/受者存活比例差异均无统计学意义(P均0.05)。IL-2Ra组和ATG组肾移植受者术前及术后第90天血清肌酐水平差异无统计学意义(P均0.05),术后第1、2、4、7、14、21、30、60天血清肌酐水平差异均有统计学意义(P均0.05)。结论 IL-2Ra和ATG都能有效预防肾移植受者术后AR的发生,需综合考虑供、受者情况选择合适的免疫诱导药物。     

活体肾移植前对致敏患者的处理经验及疗效分析

目的 总结活体肾移植前对致敏患者的处理经验,并对移植效果进行分析.方法 回顾性分析609例活体肾移植受者的临床资料.根据移植前群体反应性抗体(PRA)水平将受者分为高致敏组(41例,PRA≥30％),低致敏组(102例,PRA为0～30％)和非致敏组(466例,PRA为0).所有受者经HLA抗体检测和淋巴细胞毒交叉配合试验(CDC)确认没有针对供者的HLA抗体后进行肾移植.高致敏组给予抗胸腺细胞球蛋白诱导治疗,低致敏组给予抗白细胞介素2受体单抗诱导治疗.随访1年以上,观察各组术后移植肾功能、急性排斥反应发生率、受者和移植肾存活率及并发症发生率.结果 高致敏组、低致敏组和非致敏组受者术后移植肾恢复正常的时间和1年时肾小球滤过率均无明显差异;3组均未发生超急性排斥反应,急性排斥反应发生率分别为9.76％(4/41)、8.82％(9/102)和8.15％(38/466),术后1年移植肾存活率分别为97.6％(40/41)、97.1％(99/102)和98.1％(457/466),受者存活率分别为97.6％(40/41)、98.0％(100/102)和98.9％(461/466),3组间上述指标的差异均无统计学意义(P＞0.05).高致敏组的感染发生率为31.7％(13/41),明显高于低致敏组的26.5％(27/102)和非致敏组的21.6％ (101/466) (P＜0.05).结论 致敏受者肾移植前经HLA抗体检测和CDC配型,避开受者体内供者特异性抗体针对的供肾,并给予免疫诱导治疗,可以获得与非致敏受者相似的良好效果.     

肾移植受者预防性应用兔抗人胸腺细胞免疫球蛋白的有效性和安全性

目的 探讨肾移植受者预防性应用兔抗人胸腺细胞免疫球蛋白(ATG-R)的有效性和安全性.方法 选择2003年5月至2006年12月期间的肾移植受者655例,分为试验组(84例)和对照组(571例).两组受者在年龄、性别、群体反应抗体(PRA)、HLA配型、常规免疫抑制剂的应用等方面比较,差异无统计学意义.对试验组受者采取术前1次较大剂量(1.5 mg/kg)和术后短时间小剂量(0.5～1 mg/kg)预防性应用ATG-R;对照组受者仅采用常规免疫抑制方案.分析和比较两组受者术后移植物功能延迟恢复(DGF)发生率、术后6个月内急性排斥反应(AR)发生率、术后6个月内感染发生率及人/肾1年存活率等指标.结果 试验组和对照组DGF发生率分别为2.38%和8.40%,试验组明显低于对照组,差异有统计学意义(P＜0.01);术后6个月内AR发生率分别为4.76%和11.03%,试验组低于对照组,差异有统计学意义(P＜0.05);试验组和对照组术后6个月内感染发生率分别为10.71%和9.81%,两组比较,差异无统计学意义(P＞0.05).两组的人/肾1年存活率比较,差异也无统计学意义(P＞0.05).结论 肾移植受者预防性应用ATG-R能够明显降低DGF和AR发生率,且不增加感染发生率,是一种有效和安全的免疫诱导措施.     

肾移植后早期应用咪唑立宾的有效性及安全性

目的 探讨肾移植后早期应用咪唑立宾( MZR)的有效性和安全性.方法 采用前瞻性临床随机对照研究.将61例首次肾移植受者按随机数字表法分为2组:(1)MZR组:33例,应用他克莫司(Tac)+ MZR+泼尼松(Pred)预防排斥反应;(2)吗替麦考酚酯组(MMF)组:28例,应用Tac+ MMF+ Pred预防排斥反应.MZR的用法为:体重＜50 kg者为150mg/d,早餐后口服;体重≥50kg者为200 mg/d,分早、晚2次口服.MMF、Tac和Pred按常规剂量服用.2组受者均于术前2h和术后4d接受巴利昔单抗(20mg/d)诱导治疗.观察并比较2组受者术后6个月内的急性排斥反应(AR)发生率、移植肾存活率以及高尿酸血症、骨髓抑制、巨细胞病毒感染、胃肠道反应等的发生率.结果 术后6个月内,MZR组AR发生率为15.2％,MMF组AR发生率为10.7％ (P＞0.05);MZR组移植肾存活率为97.0％,MMF组移植肾存活率为89.3％(P＞0.05).MZR组和MMF组间高尿酸血症、骨髓抑制、胃肠道反应和肺部感染的发生率的差异无统计学意义(P＞0.05).其中,MZR组未发生巨细胞病毒感染,而MMF组则发生4例(36.4％),差异有统计学意义(P＜0.05).结论 在严密监测下,MZR可应用于肾移植术后早期抗排斥反应治疗.     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

亲属活体供肾动脉轻度狭窄对肾移植受者术后早期肾功能和并发症的影响

目的探讨亲属活体供肾动脉轻度狭窄对肾移植受者术后早期肾功能和并发症的影响。方法回顾性分析14例供肾动脉轻度狭窄的亲属活体肾移植与50例标准亲属活体肾移植供、受者的临床资料。比较两组供者术后血清肌酐(Scr)水平。比较两组受者术后1、3、6个月的Scr水平;比较两组受者移植肾存活率及移植物功能延迟恢复(DGF)、急性排斥反应、肺部感染的发生率。结果两组供者术后Scr水平比较,差异均无统计学意义(均为P0.05)。两组术后1、3、6个月Scr水平比较,差异均无统计学意义(均为P0.05)。两组受者移植肾存活率,DGF、急性排斥反应、肺部感染的发生率比较,差异亦均无统计学意义(均为P0.05)。结论亲属活体供肾动脉轻度狭窄对肾移植受者术后肾功能和并发症的影响不大,可纳入标准供体供肾范围。     

乙型肝炎免疫球蛋白预防肾移植后新发乙型肝炎

目的 探讨肾移植受者应用小剂量乙型肝炎免疫球蛋白(HBIG)预防术后新发乙型肝炎的安全性和有效性.方法 回顾性分析单中心2007年1月至2010年6月间肾移植受者的资料,将术前无乙型肝炎的138例受者作为试验组,术前肌肉注射小剂量HBIG,术后定期监测乙型肝炎表面抗体(HBsAb)滴度,根据其滴度调整术后应用HBIG的剂量,持续应用1年或1年以上.将2004年1月至2006年12月间术前无乙型肝炎的196例肾移植受者作为对照组,不采用乙型肝炎预防措施.观察两组移植后新发乙型肝炎的发病率,并记录急性排斥反应发生情况、受者和移植肾1年存活率.结果 随访12个月,试验组仅1例(0.7％)于术后6个月出现新发乙型肝炎,对照组11例(5.6％)出现新发乙型肝炎,其中2例因爆发性肝功能衰竭而死亡.两组新发乙型肝炎发病率的差异有统计学意义(P＜0.05).术后6个月内,试验组有19例(13.8％)发生急性排斥反应,对照组有34例(17.3％)发生急性排斥反应,两组急性排斥反应发生率的差异无统计学意义(P＞0.05).试验组受者1年存活率为97.8％(135/138),移植肾1年存活率为(96.4％,133/138);对照组受者1年存活率为(91.8％,180/196),移植肾1年存活率为(90.3％,177/196).两组受者和移植肾1年存活率的差异有统计学意义(P＜0.05.P＜0.05).结论 小剂量HBIG用于肾移植后预防新发乙型肝炎是安全、有效的.     

再次肾移植受者和移植肾长期预后影响因素分析

目的探究再次肾移植受者和移植肾存活情况及长期预后影响因素。 方法回顾性分析1991年1月1日至2017年12月31日于浙江大学医学院附属第一医院肾脏病中心接受肾移植受者临床资料。共纳入再次肾移植受者37例,首次肾移植受者5 374例。根据再次肾移植受者移植肾存活时间长短,将其分为长期存活组(19例,>5年)和短期存活组(18例,≤5年)。采用成组t检验比较长期和短期存活组供受者年龄、首次与再次肾移植间隔时间、HLA错配数和再次移植供肾冷/热缺血时间。采用卡方检验比较长期和短期存活组受者性别、再次移植供肾类型、再次移植前后群体反应性抗体阳性比例、首次移植失功移植肾切除比例、再次移植前免疫诱导比例及再次移植后移植肾功能延迟恢复(DGF)和急性排斥反应发生比例。采用Kaplan-Meier法分析再次和首次肾移植受者/移植肾1、5和10年存活率。采用Cox比例风险模型分析影响再次肾移植术后移植肾长期存活影响因素。P<0.05为差异有统计学意义。 结果截至2018年3月1日,37例再次肾移植受者中位随访时间为152个月(11～323个月),2例死亡,18例发生移植肾失功,17例移植肾功能稳定。5 374例首次肾移植受者中位随访时间为108.9个月(0.1～350.0个月),459例死亡,1 343例发生移植肾失功。再次移植组受者/移植肾1、5和10年存活率分别为86%/81%、86%/62%和82%/36%,首次移植组受者/移植肾1、5和10年存活率分别为99%/98%、93%/89%和88%/80%。再次移植组移植肾1、5和10年存活率均低于首次移植组(χ²＝60.816、25.110和43.900,P均<0.05);再次移植组受者1年存活率低于首次移植组,差异有统计学意义(χ²＝40.409,P<0.05)。长期和短期存活组受者再次移植后移植肾DGF和急性排斥反应发生比例差异均有统计学意义(χ²＝4.039和4.748,P均<0.05)。Cox回归分析结果示DGF和急性排斥反应是影响再次肾移植受者移植肾长期存活的独立危险因素,差异有统计学意义(RR＝4.317和4.571,P均<0.05)。 结论再次肾移植受者移植肾存活率低于首次肾移植受者,DGF和急性排斥反应是影响再次移植受者移植肾存活的独立危险因素。     

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.     

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.     

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.     

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.     

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.