肝移植术后西罗莫司的替换治疗

目的 探讨肝移植术后应用西罗莫司的抗排斥替换治疗效果。方法 回顾性分析50例肝移植或肝肾联合移植患者替换西罗莫司前后肝肾功能的改善情况及副作用和排斥反应的发生率。34例联合应用小剂量FK506，9例联合应用骁悉，2例联合应用新山地明。5例术后远期患者，替换前仅用FK506，替换后单用西罗莫司。结果 24例患者因肝功能不良而替换西罗莫司，其中16例（66．7％）肝功能明显改善；18例患者肾功能不良，其中13例（72．2％）在2个月内肾功能明显好转；8例患者因大剂量应用FK506但其浓度未达到6ng／ml而替换西罗莫司，移植术后肝肾功能恢复良好，未出现排斥反应。本组中应用西罗莫司后出现急性排斥反应3例（6％），改用FK506后急性排斥反应治愈。11例（22％）出现白细胞及血小板减少，9例（18％）胆固醇和甘油三酯升高。这些副作用均在西罗莫司应用1月后出现，当停药或对症处理后消失。本组中未出现肝动脉血栓形成、伤口愈合不良等并发症。结论 肝移植术后应用钙调磷酸酶抑制剂发生肝肾功能不良或不能达到理想药物浓度时，西罗莫司是有效的抗排斥替代药物。     

西罗莫司替代钙调磷酸酶抑制剂方案治疗肾移植后“爬行肌酐”患者的疗效观察（附28例报告）

目的探讨采用西罗莫司替代钙调磷酸酶抑制剂（CNI）方案治疗肾移植后＂爬行肌酐＂患者的临床疗效。方法具有＂爬行肌酐＂表现的28例患者中,术后采用以环孢素（CsA）为主的三联免疫抑制方案20例,采用以他克莫司（FK506）为主的三联免疫抑制方案8例。患者确诊后即停用CsA或FK506,24h后给予西罗莫司,初始剂量6mg,维持剂量为2mg/d,以后根据西罗莫司的血药浓度来调整剂量,使其血药谷浓度维持在5～9μg/L,药物替代前后麦考酚吗乙酯（MMF）及肾上腺皮质激素（激素）的用量不变。随访6个月,定期观察移植物肾功能,记录排斥反应的发生情况,并监测血常规、血糖、血脂、肝功能等指标。结果移植物肾功能明显改善16例,患者的血清肌酐（Scr）由替代前（205±20）μmo1/L降为替代后的（153±18）μmo1/L,内生肌酐清除率（Ccr）由（51±3）ml/min升高为（56±3）ml/min（均为P〈0.05）;移植物肾功能维持稳定8例,移植物肾功能继续恶化2例。治疗中,1例发生急性排斥反应,移植肾失功并恢复血液透析,1例西罗莫司替代后出现明显骨髓抑制而放弃替代治疗,恢复替代前的免疫抑制方案。结论西罗莫司替代CNI治疗肾移植后＂爬行肌酐＂患者是一种比较安全并有效的方法,可明显改善移植物肾功能,但会使患者血脂升高。     

西罗莫司治疗心脏死亡器官捐献肾移植术后急性排斥反应(附1例报告并文献复习)

目的探讨西罗莫司在心脏死亡器官捐献(donation after cardiac death,DCD)肾移植术后急性排斥反应中的应用。方法回顾性分析1例接受同种异体DCD供肾受者肾移植术后发生急性排斥反应,早期应用西罗莫司治疗的临床资料并复习相关文献。结果 1例DCD供肾肾移植受者,采用他克莫司(FK506)+吗替麦考酚酯(MMF)+泼尼松三联抗排斥免疫方案(FK506每次3mg,每日2次;MMF每次750mg,每日2次;泼尼松每次15mg,每日1次),术后即出现无尿,诊断为移植物功能延迟恢复(DGF)。行血液透析治疗,每周3次。术后35d发现尿量减少,移植肾彩色多普勒超声提示急性排斥反应,经肾上腺皮质激素冲击治疗无效后,血清肌酐(Scr)升高,提示治疗无效,改为西罗莫司+FK506+MMF+泼尼松的四联方案(西罗莫司每次0.5mg,每日1次;FK506每次2mg,每日2次;MMF每次250mg,每日2次;泼尼松每次15mg,每日1次),并减少他克莫司剂量。改用方案后3d患者Scr逐渐下降至正常,至出院后未再出现排斥反应。患者随访至2013年4月移植肾功能稳定,生活质量良好。结论西罗莫司有利于DCD供肾肾移植患者肾功能早期恢复,对术后急性排斥反应有一定疗效。     

西罗莫司在肝移植术后钙调素类抑制剂相关肾损病人中的应用

目的 探讨西罗莫司对肝移植术后钙调素类免疫抑制剂相关肾功能损害病人的肾功能的改善作用及安全性.方法 对11例肝移植术后出现钙调素类免疫抑制剂相关肾损害病人进行西罗莫司转换治疗,同时减少或完全停止钙调素类免疫抑制剂的应用.观察转换治疗后病人的肾功能、肝功能、急性排斥反应的发生及药物副作用等情况.结果 随访至今所有病人均存活,随访时间6～23个月.转化治疗后所有病人的肾功能均有不同程度的改善,6个月后血肌酐从(163.8±47.9)μmol/L降为(108.1±26.6)μtmol/L(P<0.05);除1例病人出现转氨酶升高,加用钙调素类免疫抑制剂后恢复正常外,其余病人肝功能无明显变化;药物副作用有高脂血症、贫血、溃疡型口疮等.结论 西罗莫司可以安全地应用于肝移植术后钙调素类免疫抑制剂相关肾功能损害的病人,改善病人的肾功能,同时对移植肝功能无明显影响.     

西罗莫司在肾移植后初始免疫抑制治疗中的应用

目的探讨西罗莫司预防肾移植后急性排斥反应的有效性和安全性。方法36例肾移植患者,31例在术后即开始应用西罗莫司,其中30例应用减剂量环孢素A(CsA)、西罗莫司及泼尼松预防排斥反应,1例应用他克莫司、两罗莫司及泼尼松预防排斥反应;5例在术后1个月内因CsA的不良反应而将CsA替换为西罗莫司,其中1例改为减剂量CsA、西罗莫司及泼尼松,3例改为西罗莫司、霉酚酸酯及泼尼松,1例改为西罗莫司及泼尼松。观察移植肾功能以及急性排斥反应、感染、移植肾功能恢复延迟(DGF)等的发生情况。结果术后随访18～40个月,有2例移植肾功能丧失,恢复血液透析,移植肾分别存活1.6年、1.8年;3例血肌酐>200μmol/L,发展成为慢性移植肾肾病;31例移植肾功能良好。4例发生急性排斥反应,经甲泼尼龙冲击治疗后逆转;8例发生感染,经抗感染处理后全部康复;6例发生DGF,免疫抑制方案未做调整,术后14～80 d恢复泌尿。西罗莫司后的不良反应包括血脂升高、一过性白细胞减少及蛋白尿等。结论肾移植后采用西罗莫司与减剂量CsA和泼尼松联用可取得较好的免疫抑制效果。     

治疗肝移植术后顽固性排斥反应的新尝试

目的探讨一种治疗肝移植术后顽固性排斥反应的新方法。方法经病理证实的肝移植术后急性排斥反应2例、慢性排斥反应2例，这4例患者在应用常规治疗方法无效的情况下，应用低剂量他克莫司（FK506）＋西罗莫司（SRL）进行治疗，FK506和SRL的血药浓度分别控制在3～5μg／L和6～12μg／L。排斥反应纠正后停用SRL，并将FK506调整至常规用量。结果4例患者的排斥反应均得以纠正，在应用本方案的过程中出现巨细胞病毒性肺炎1例，经抗病毒治疗后痊愈；原有糖尿病加重1例，新发生糖尿病1例，停用SRL同时应用胰岛素控制血糖，治疗后血糖恢复正常水平。结论肝移植术后经常规治疗方法无效的急、慢性排斥反应，应用低剂量FK506＋SRL进行治疗，排斥反应可以得到逆转。     

接受老龄亲属活体供肾移植者采用小剂量西罗莫司的近期临床观察

目的为降低老龄活体供肾移植后免疫抑制剂对移植肾的毒性作用，探讨应用小剂量西罗莫司的临床效果及其对移植肾的影响。方法19例亲属活体供肾移植，供者的年龄均超过55岁，受者的年龄均在30岁以下。9例肾移植后采用小剂量西罗莫司、霉酚酸酯（MMF）及泼尼松（Pred）联合用药预防急性排斥反应，10例采用环孢素A（或他克莫司）、MMF（或硫唑嘌呤）及Pred联合用药预防急性排斥反应。两种用药方案者在供、受者年龄方面的差异无统计学意义。统计术后1年、2年、3年时的血肌酐平均值，爬行肌酐的发生率，排斥反应发生率，不良事件发生率，慢性移植肾肾病（CAN）发生率。结果术后1年、2年、3年，采用小剂量西罗莫司者的血肌酐水平低于使用环孢素A（CsA）或他克莫司（FK506）者，其术后2、3年时的血肌酐水平明显低于使用CsA或FK506者（P〈0．05）。使用西罗莫司者高尿酸血症发生率为11．1％，而使用CsA或FK506者这一比例为40．0％，差异有统计学意义（P〈0．05）；使用西罗莫司者爬行肌酐及慢性移植肾肾病的发生率均为11．1％，使用CsA或FK506者均为30．0％，差异有统计学意义（P〈0．05）；二者在急性排斥反应、肾功能恢复延迟、少尿、蛋白尿、血尿等不良事件发生率方面的差异无统计学意义。结论对于老龄活体供肾，移植后受者采用小剂量西罗莫司联合霉酚酸酯、泼尼松预防急性排斥反应是安全、有效的，其远期效果有待进一步观察。     

肝移植术后长期存活慢性肾功能损害受者的免疫抑制方案个体化应用

目的探讨肝移植术后长期存活慢性肾功能损害受者应用个体化免疫抑制方案的疗效。方法选择18岁以上、肝移植术后2年以上、入组前采用以他克莫司(FK506)为基础免疫抑制方案、肝功能正常而肾功能损害的受者,共32例。根据免疫功能评分和白细胞计数制定个体化免疫抑制方案,以FK06用量最小化为原则,转换为麦考酚吗乙酯(MMF)或西罗莫司,并调整其用量。调整后至少每个月随访1次,进行肝功能、肾功能、血常规检查和免疫功能评估。结果 32例受者经个体化免疫抑制方案治疗,随访(24.3±7.6)个月,个体化治疗后各时段的肾小球滤过率(GFR)均较此前有明显提高(均为P<0.01),以调整用药后1个月最明显。无发生排斥反应。结论根据免疫功能评分和白细胞计数制定个体化免疫方案,使FK506用量最小化,可以有效改善肝移植术后长期存活的受者的肾功能,并不增加排斥反应的发生率。     

肝移植术后患者应用免疫抑制剂的单中心经验总结(附1400例分析)

目的总结对肝移植术后患者应用免疫抑制剂的经验,探讨个体化治疗的可行性。方法回顾分析2002年4月至2010年8月单中心1400例肝移植患者的临床资料。术后免疫抑制治疗方案的制定按时间发展经历了3个阶段:(1)第1阶段(2002年4月至2004年12月)311例患者采用传统免疫抑制治疗方案;(2)第2阶段(2005年1月至2007年12月)618例患者采用部分传统免疫抑制剂减量的方案;(3)第3阶段(2008年1月至2010年8月)471例患者采用个体化免疫抑制治疗方案。再按术前终末期肝病模型(modelforend-stageliverdisease,MELD)评分及肿瘤是否超出米兰标准分为常规组、超米兰标准组和重症组。收集3个阶段肝移植患者的生存情况,绘制生存曲线。观察第3阶段3组患者的排斥反应发生情况,了解免疫抑制剂其他不良反应及药物替换情况。结果第1、第2、第3阶段患者生存率呈逐渐升高趋势。第3阶段采用个体化治疗,3组的免疫抑制剂用量不同,但3组间免疫排斥反应发生率差异无统计学意义(均为P>0.05)。第3阶段共将12例患者的他克莫司(FK506)转换为环孢素(CsA),32例患者因肾功能损害将FK506转换为小剂量FK506+麦考酚吗乙酯(MMF)或西罗莫司,病情得以缓解。因肿瘤因素或肾功能异常应用单独应用西罗莫司27例,3例因为高脂血症或口腔溃疡不能耐受西罗莫司。结论肝移植术后免疫抑制剂的个体化治疗是可行的,可减少免疫抑制剂的用量,又不增加排斥反应发生率,有利于提高患者生存率。     

西罗莫司对肝移植术后肾功能和血脂的影响

目的探讨原发性肝细胞癌（肝癌）肝移植患者术后使用西罗莫司（sirolimus）对肾功能和血脂的影响。方法 56例肝癌肝移植患者分为两组。研究组（33例）采用西罗莫司＋小剂量他克莫司（FK506）＋肾上腺皮质激素（激素）方案,对照组（23例）采用FK506＋激素方案。动态监测两组患者术前,术后1、3、6、9、12个月的血清肌酐（Scr）、血清总胆固醇、甘油三酯及高密度脂蛋白的变化情况,分别行组内不同时点比较和同时点组间比较。结果术前两组患者的Scr水平差异无统计学意义（P〉0.05）,术后9个月时的Scr比较差异有统计学意义（P〈0.05）,研究组的Scr水平低于对照组,且研究组术后Scr呈先升高再降低的变化趋势,对照组Scr呈缓慢上升的趋势。术前两组患者的血脂水平相当（P〉0.05）。两组患者术后1个月的甘油三酯水平,术后6个月时的总胆固醇水平和高密度脂蛋白水平比较差异有统计学意义（P〈0.05）,研究组均高于对照组。两组患者未发现与高脂血症相关的心脑血管疾病。结论西罗莫司是一种低肾毒性的免疫抑制剂,与小剂量的FK506合用时可以减少FK506的肾毒性。西罗莫司的主要的不良反应是高脂血症。     

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.     

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.     

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.