可预防感染的组织工程骨在修复山羊大段骨缺损中的抗感染及成骨效果研究

 目的 构建可预防感染的组织工程骨并评估其在修复山羊大段骨缺损中的抗感染能力及成骨效果。方法 设计可控性缓释抗生素系统“纤维蛋白凝胶修饰的藻酸盐-万古霉素缓释微球”（FG-Vanco-AB）,以此为基础构建可预防感染的组织工程骨并进行检测,然后移植到山羊右侧股骨临界骨缺损的部位,对侧作为对照将组织工程骨（不含可控性缓释抗生素系统）移植到同样的临界骨缺损区。抗生素发挥抗菌作用的标准浓度为5 mg/ml,即对金黄色葡萄球菌的最低杀菌浓度,术后通过高效液相色谱法检测骨缺损区局部、周围及血液中万古霉素浓度,检测其缓释剂抗感染能力;组织学、CT、ECT检测骨愈合情况,以此来评价预防感染组织工程骨的成骨效果。结果 通过扫描电镜、激光共聚焦以及体内示踪等检测,种子细胞在体内及体外的存活情况与组织工程骨组类似;山羊股骨右侧局部、左侧局部及血液中持续超过杀菌浓度的时间分别为28 d、2 d和7 d。万古霉素在股骨中的浓度自移植部位向两侧逐渐递减。山羊双侧股骨术后第28天及56天ECT检查结果均提示无明显区别,CT及组织学检查证明在术后第14天、28天、112天,山羊双侧股骨缺损的修复是同步的,并且在第112天时均被新生骨组织覆盖。结论 成功构建抗感染的组织工程骨,FG-Vanco-AB在移植的部位可以发挥杀菌作用,并且不会影响组织的重建与修复。     

异烟肼聚乳酸缓释体的制备及体内外释药特性

目的探讨异烟肼聚乳酸微球的制备方法和体内外释药特性.方法用复乳法制备异烟肼聚乳酸微球,扫描电子显微镜观察微球的特征,高效液相色谱法测定其包封率、载药率;用溶出法、高效液相色谱法测定其体外释药特性.观测第3、6、9、12、15、18、25、32、39、42、49、56天的释药情况,并计算其日均释药率、累计释药率将异烟肼聚乳酸微球、异烟肼(INH)分别置入24只新西兰大白兔的左右股骨粗隆间髓腔内,测定微球在体内3、7、14、28、42、56d时的释药情况;实验组将第42、49、56天时的异烟肼聚乳酸微球洗涤液(空白组用磷酸缓冲液)与结核菌、钛块一起共同培养7d,扫描电子显微镜下观察结核菌生长情况.结果异烟肼聚乳酸微球呈比较完整的球形且分散性好,无明显聚集现象;微球平均直径为59.4±2.9μm,包封率为(67.51±0.57)%,载药率为(32.82±0.65)%.体外释药结果显示,最初14d累计释药达3.784±0.359mg,约占总量的30%,日平均释药0.270±0.024mg;随后42d累计释药5.328±0.203mg,约占总量的50%,日平均释药0.126±0.013mg,第56天时释药0.032±0.009mg.体内释药实验显示,3d时右侧股骨粗隆间骨质内INH浓度明显高于左侧(P＜0.01);7～56d右侧INH浓度明显降低并低于左侧(P＜0.01);7～56d左侧股骨粗隆间骨质内INH浓度持续在20±g/s以上.空白组钛块表面有大量结核菌生长,实验组钛块表面几乎无结核菌生长.结论异烟肼聚乳酸微球具有缓慢释放药物的特性.可以作为持久抗结核治疗的缓释体置入骨结核病灶清除术后病灶局部.     

万古霉素壳聚糖微球-大孔磷酸钙骨水泥支架的体外释放实验

目的构建具有缓释药物效能的大孔磷酸钙骨水泥(CPC)支架,并检测其药物缓释能力和对材料力学的变化。方法以乳化化学交联法制备万古霉素壳聚糖(CS)载药微球并测定药物包封率;CPC与不同质量载药微球(2 mg、6 mg、10 mg)混合制备CS-大孔CPC支架,测定载药微球-CPC的药物缓释曲线,并选择初始与8、72、168、216 h共5个时间点比较药物释放浓度。万能试验机检测载药CS-CPC支架的弹性模量变化。药物释放浓度比较和弹性模量采用单因素方差分析进行比较。结果 CS微球对万古霉素包封率约为30.6%;加入不同量的CS微球对弹性模量无明显改变,差异无统计学意义(P0.05)。2 mg、6 mg、10 mg的CS微球与大孔CPC复合后,均能缓慢稳定释放药物。初始、8 h、72 h、168 h时间点比较药物释放浓度,三组的浓度差异有统计学意义(F=234.91,7171.27,1161569,60.5;P0.05),其中6 mg组与2 mg和10 mg组的差异有统计学意义(P0.05);到216 h时,各组药物浓度差异均无统计学意义(P0.05)。结论万古霉素CS微球复合大孔CPC支架具有较为理想的药物缓释效果,并对支架的力学性能影响不大,是一种可选择的治疗骨缺损伴感染的载药材料。     

固载去甲万古霉素缓释微球补片对切口疝金黄色葡萄球菌感染的预防作用

目的补片修补切口疝术后可能发生感染,采用载药补片预防感染是解决方法之一。通过制备大鼠切口疝金黄色葡萄球菌感染模型,观察固载去甲万古霉素缓释微球聚丙烯补片修补切口疝术后对感染的预防作用。方法采用复乳溶剂挥发法制备去甲万古霉素缓释微球,并将其固载至聚丙烯补片(50 mg/片)。扫描电镜观察去甲万古霉素缓释微球形态,采用高效液相色谱法检测微球中去甲万古霉素含量以及补片中去甲万古霉素释放率。取健康10～11周龄雄性SD大鼠40只,体重200～250 g;制备切口疝金黄色葡萄球菌感染模型,分别植入固载去甲万古霉素缓释微球聚丙烯补片(实验组,n=20)和聚丙烯补片(对照组,n=20)。术后观察两组大鼠切口愈合情况,3周时处死大鼠取补片及周围组织进行组织学观察,并进行炎症程度分级。结果扫描电镜观察示去甲万古霉素缓释微球形态完整,表面平滑;微球粒径较均一,64%微球粒径位于60～100μm;去甲万古霉素载药量为19.79%。固载去甲万古霉素缓释微球聚丙烯补片表面均匀,载药量为(7.90±0.85)mg/cm2,去甲万古霉素体外释放达28 d以上,累计释放率达72.6%。两组大鼠术后均存活至实验完成。22只大鼠切口发生感染,其中实验组2只(10%),对照组20只(100%);两组感染率比较,差异有统计学意义(χ2=32.727 3,P=0.000 0)。实验组镜下见局部炎性反应不明显,炎症程度分级Ⅰ级16只,Ⅱ级4只;对照组补片有大量炎性细胞浸润,炎症程度分级Ⅱ级3只,Ⅲ级17只。两组炎症程度分级比较,差异有统计学意义(Z=32.314,P=0.000)。结论固载去甲万古霉素缓释微球聚丙烯补片对大鼠切口疝金黄色葡萄球菌污染具有抗感染作用。     

带旋髂深血管蒂髂骨瓣联合万古霉素BAM骨诱导人工骨治疗胫骨骨髓炎

目的探讨带旋髂深血管蒂髂骨瓣移植联合万古霉素BAM(biological artificial material)骨诱导人工骨治疗胫骨远端骨髓炎的方法及临床疗效。方法 2013年1月至2014年12月采用带旋髂深血管蒂髂骨瓣移植联合万古霉素BAM骨诱导人工骨治疗胫骨远端骨髓炎3例。根据Cierny-Mader分型:ⅢA型2例,ⅢB型1例。分泌物及病灶细菌培养均为革兰氏金黄色葡萄球菌。骨瓣切取面积1.5cm×1.5cm至1.5cm×5cm。结果伤口均Ⅰ期愈合。经过16个月至24个月随访。3例患者移植骨全部骨性愈合。结论带旋髂深血管蒂髂骨瓣联合万古霉素BAM骨诱导人工骨治疗胫骨骨髓炎疗效确切。值得临床使用。     

重组人骨形态发生蛋白-2/万古霉素/硫酸钙药物缓释系统体外释放的实验研究

目的 研究生物可降解材料硫酸钙对万古霉素和重组人骨形态发生蛋白-2( rhBMP-2)体外缓释特性. 方法 利用高效液相色谱分析和抑菌实验检测缓释材料中万古霉素的浓度及活性,利用ELISA试验和ALP实验检测缓释材料中rhBMP-2的浓度及生物活性. 结果 rhBMP-2/万古霉素/硫酸钙药物缓解系统可释放高于55.8 μg/mL万古霉素长达144h,活性达70％以上;可释放活性rhBMP-2长达30d,对骨髓基质干细胞无抑制增殖作用,具有较高的生物安全性. 结论 rhBMP-2/万古霉素／硫酸钙药物缓解系统能缓慢释放活性万古霉素与rhBMP-2,且不会抑制骨髓基质干细胞的增殖,具有较高的临床应用前景.     

复合三联抗结核药聚乳酸-羟基乙酸缓释微球的制备及体外释药特性

目的 :制备复合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)的聚乳酸-羟基乙酸(HRZ/PLGA)缓释微球,观察其理化性质和体外缓释特性。方法:以PLGA(450mg)为载体,避光条件下称取H(40mg)、R(60mg)、Z(125mg),采用复乳-溶剂挥发法制备HRZ/PLGA缓释微球,应用扫描电镜观察微球的形态特征;应用高效液相色谱法(HPLC)测定其载药量、包封率;采用溶出法、HPLC于3h、6h、12h、1d、2d、3d、6d、9d、12d、15d、20d、25d、30d、40d、50d测定H、R、Z三种药物的浓度,观察其是否均大于10倍最低抑菌浓度(MIC),计算其日均释药率、累计释药率。结果:HRZ/PLGA微球在电镜下观察呈圆球形,平均粒径为10.3±4.7μm;H、R、Z三种药物的载药量分别为(18.02±0.36)%、(22.46±0.24)%、(21.68±0.37)%,包封率分别为(54.79±1.13)%、(72.35±0.39)%、(67.21±0.68)%;体外缓释试验显示微球缓释前12d左右,三种药物的累计缓释度均超过了50%,日均释药率分别为5.05%、4.89%、6.86%;第12天后三药的缓释基本趋于稳定,日均释药率分别为0.17%、0.26%、0.16%;三种药物缓释到50d时均大于10倍MIC。结论:HRZ/PLGA微球具有优良的载药及药物缓释效果,是一种理想的复合抗结核药物缓释系统。     

rhBMP-2明胶纳米微球制备及体外缓释效果研究

目的制备重组人骨形态发生蛋白2(recombinant human bone morphogenetic protein-2,rhBMP-2)明胶纳米微球并检测其体外缓释效果。方法 "二次凝聚法"制备明胶纳米微球,扫描电镜、透射电镜和粒径分析仪检测纳米微球的表面形态、内部结构、粒径,计算其溶胀率;将rhBMP-2与明胶纳米微球复合,计算其包封率和载药量,并对其体外缓释效果进行检测。结果明胶纳米微球的表面形态良好,分散均一,内部结构多孔隙、通道,平均粒径(171.49±50.12)nm,溶胀率为1.83;rhBMP-2明胶纳米微球的包封率为(98.13±0.131)%,载药量为(58.89±0.079)ng/mg;rhBMP-2明胶纳米微球释药时间在1个月以上,呈"双相缓释",第1天为"突释相",释药量约为7%,以后平缓释放呈"缓释相",40%左右的药物于28 d内释放,约60%的药物在1个月以后释放。结论成功制备rhBMP-2明胶纳米微球,不但包封率高,而且体外缓释效果好。     

纤维多孔钛微球复合纳米锶磷灰石修复骨缺损的实验研究

目的 探讨纤维多孔钛微球复合纳米锶磷灰石修复骨缺损的能力及其作用机制.方法 6月龄雄性SD大鼠24只,体重(545±22)g.在双侧股骨髁部使用慢速钻钻取直径2 mm贯通双侧皮质的冠状轴洞性骨缺损.以纤维多孔钛微球复合纳米锶磷灰石填充左侧骨缺损,以单纯纤维多孔钛微球填充右侧.术后1、2、4、8周分别处死6只大鼠行X线、组织学及骨组织形态计量学观察,并进行比较分析.结果 影像学结果表明,两侧骨缺损修复效果均良好.组织学显示,纤维多孔钛微球允许骨长入,且左侧微球内新生骨多于右侧.骨组织形态计量学观察显示,随时间延长,左侧新生骨量逐渐增多,2、4、8周新生骨量存在差异,而4、8周时左侧与右侧的新生骨量比较,差异有统计学意义.结论 纤维多孔钛微球具有良好的生物相容性及骨传导性,可作为骨缺损修复的支架材料;纳米锶磷灰石可增强纤维多孔钛微球修复骨缺损的能力.     

高压静电场技术制作藻酸钙载药微球及其性能研究

目的探索高压静电场技术制备藻酸钙微球的最佳参数组合,以期微球直径更小更均匀,并研究其载药后的缓释行为。方法设置不同的电压、CaCl_2浓度、藻酸钠浓度、离心机转速、针头直径,观察微球直径和表面形态,以直径更小更均匀为标准,筛选最佳参数组合。负载低(L组)、中(M组)、高(H组)3种浓度的牛血清白蛋白,对比3组的包封率和载药率,并绘制累计缓释曲线,观察其体外缓释行为。结果 16 KV电压、1M CaCl_2浓度、0.5%藻酸钠浓度、200 r/min和30 G的针头是最佳参数组合。L、M、H各组的包封率分别为(91±1.46)%、(85±1.63)%和(79±3.29)%,载药率分别为(0.89±0.04)%、(2.56±0.57)%和(4.10±1.21)%。3组药物都可以持续释放超过28 d,缓释时间较长,释放行为稳定、规律。结论利用最佳参数组合制备的藻酸钙微球是一种优良的药物缓释载体。     

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.