大鼠膀胱内灌注125 Ⅰ脱氧尿嘧啶核苷的药代动力学及组织分布

目的探讨^125Ⅰ-脱氧尿嘧啶核苷（^125Ⅰ-UdR）在大鼠膀胱内灌注后药代动力学及组织分布情况。方法将8只SD大鼠随机分成2组，每组4只。A组每只大鼠单纯^125Ⅰ-UdR（7．5MBq／kg体重）膀胱内灌注给药，B组每只大鼠单纯^125Ⅰ-UdR（7．5MBq／kg体重）经尾静脉注射给药。连续采集血液，用7计数仪测定其放射性；12只SD大鼠随机分为3组，每组4只。每只膀胱内灌注^125Ⅰ-UdR1．5MBq，经0．5、2、24h后分组处死，取相关脏器后测量放射性计数。结果膀胱灌注^125Ⅰ-UdR后的大鼠体内代谢符合二房室分布模型，按化学剂量100μg／kg体重灌注后测得，平均T1／2α为3．34h，T1／2β为36．78h，Cmax为0．54μg/L，Tmax为1．72h。静脉注射^125Ⅰ-UdR后的大鼠体内代谢符合一房室分布模型，按化学剂量100μg/kg体重静注后测得，平均T1／2为0．09h，Cmax为14．55μg／L，Tmax为0．00h，膀胱灌注的绝对生物利用度F为38．4696。膀胱灌注后找^125ⅠUdR主要分布在大鼠膀胱，肝脏，脾脏中。结论^125Ⅰ-UdR用于膀胱灌注可以提高局部组织药物浓度，延长其在靶器官的滞留时间，并可减少对周围组织的毒副作用。     

肝动脉灌注和外周静脉输注5-FU在大鼠肝脏和血液中的浓度分布的实验研究

目的探讨经肝动脉区域灌注和外周静脉注射5-FU在大鼠血液和肝脏组织中的浓度分布规律及差异。方法本研究将24只Wistar大鼠随机分为两组：A组为肝动脉灌注组;B组为外周静脉（颈静脉）输注组,分别经肝动脉插管区域灌注与经颈静脉注射5-FU,剂量为20mg/kg体重,每组均有6只大鼠取血,6只取肝组织样本。采用高效液相色谱法测定血浆及肝脏组织中5-FU的含量,并计算5-FU在肝脏和血浆中的药动学参数、穿透比率、穿透指数和相对治疗优势度。结果经外周静脉注射后肝脏组织的药物峰浓度（Cmax）和药物时量曲线下面积（AUC）分别为13.79±4.56μg/g,342.20±108.20μg·h/g;血浆Cmax和AUC分别为36.85±5.96μg/ml,842.00±158.00μg·h/ml。肝动脉灌注5-FU后肝脏组织药物Cmax和AUC分别为29.58±4.30μg/g,794.60±115.40μg·h/g;血浆Cmax和AUC分别为24.39±4.63μg/ml,639.70±133.80μg·h/ml。结论与外周静脉注射全身化疗比较,区域性肝动脉灌注5-FU可显著提高肝脏组织中的药物浓度,同时减少化疗药物在外周血中的分布。     

125I-脱氧尿嘧啶核苷治疗膀胱癌

125I标记的脱氧尿嘧啶核苷[(125I)iododeoxyuridine 125I-UdR]是脱氧胸嘧啶核苷(TdR)的类似物,是实现125I在DNA靶点定位的良好载体,实现125I的DNA靶向放射治疗,在分子水平对恶性肿瘤治疗提供了一种新方法[1].我们在前期研究大鼠膀胱内灌注125I-UdR后药代动力学及组织分布基础上[2],通过本实验构建裸鼠皮下膀胱癌模型,瘤内注射125I-UdR,观察125I-UdR对膀胱癌的治疗作用.     

32P-玻璃微球间质给药体内生物学分布与代谢

目的 观察32P-玻璃微球(32P-GMS)间质给药后体内生物学分布与代谢.方法 120只小鼠分别经肝脏或肌肉注射32P-GMS,每只(1.80±0.05)MBq/50μl,不同时间点处死取血及脏器计算每克组织百分注射剂量率(%ID/g);12只大鼠肝脏、肌肉每只注射(18.0±0.5)MBq/0.5 ml,收集排泄物测累积排泄率.结果 小鼠肝脏组给药肝叶%ID/g 0时最高为1.38,15 nin降至0.71,非给药肝叶峰值15 min为0.52,4 h之后左右肝叶无区别;肺组织计数率值1 h内上升,肝肺累积分流率为37.9%.肌肉组注射点%ID/g0时为31.47,15 nin～8 h为25.06～11.92(中值20.97),12 h为8.70,24 h～14 d为3.54～2.02(中值2.51),其他主要脏器放射性接近本底水平.大鼠肝脏组粪便和尿液14 d累积排泄率分别为0.0751%和0.0586%;肌肉组分别为0.0401%和0.0385%.结论 32P-GMS间质注射适用于除肝脏以外的体内组织脏器恶性实体瘤的治疗.     

舒芬太尼预先给药对大鼠急性局灶性脑缺血-再灌注损伤的保护作用

目的 观察舒芬太尼预先给药对大鼠大脑中动脉栓塞(MCAO)所致局灶性脑缺血-再灌注损伤的保护作用.方法 40只雄性大鼠随机均分为四组,分别于缺血造模前腹腔注射舒芬太尼3μg/kg(S_1组)、6μg/kg(S_2组)、9μg/kg(S_3组)和等容积生理盐水为对照组(C组).给药后30 min,所有动物用右侧颈内动脉尼龙线线栓法致MCAO,120 min后恢复再灌注.再灌注24 h后记录神经功能障碍评分(NDS).随后取大脑切片行TTC染色,计算脑梗死容积百分比.结果 再灌注后24h,S_1组NDS评分明显高于其他三组(P<0.05),梗死容积百分比明显低于其他三组(P<0.05),S_2、S_3、C组间NDS评分和梗死容积百分比差异均无统计学意义.结论 舒芬太尼3μg/kg预先给药可明显减轻大鼠局灶性脑缺血-再灌注损伤.     

右美托咪定预处理对糖尿病大鼠心肌缺血-再灌注损伤的作用和机制

目的探讨右美托咪定(Dex)预处理对糖尿病大鼠心肌缺血-再灌注损伤(MIRI)的作用及其机制。方法诱导建立糖尿病模型大鼠40只,体重150~170g,8周后随机分为四组:假手术组(S组),缺血-再灌注组(IR组),缺血-再灌注+Dex给药组(IRD组),缺血-再灌注+育亨宾与Dex复合给药组(IRYD组),每组8只。S组和IR组以等量生理盐水作预处理,IRD组先以5μg/kg的速度输注Dex 10 min,后以5μg·kg-1·h-1的速率再输注60 min,IRYD组先静脉输注1mg/kg的育亨宾,15min后改为0.5mg·kg-1·h-1继续输注60min,育亨宾开始输注5min后以与IRD组相同的方法输注Dex。除假手术组外,各组均采用结扎-放松大鼠冠状动脉左前降支的方法使局部心肌缺血30min、继而再灌注2h。分别记录缺血前(T0)、结扎30 min(T1)、再灌注1h(T2)和再灌注2h(T3)时的HR、左室收缩压(LVSP)、左室内压最大上升速率(+dp/dtmax)和左室内压最大下降速率(-dp/dtmax)和左室舒张末压(LVEDP);测定再灌注2h后的心肌梗死面积并检测血浆肌钙蛋白I(cTnI)含量和一氧化氮(NO)浓度。结果与S组、IR组和IRYD组比较,T0-T3时IRD组的HR明显减慢(P0.05)。与IR组和IRYD组比较,T3时IRD组LVSP、+dp/dtmax和-dp/dtmax明显升高(P0.05),LVEDP明显降低(P0.05),IRD组缺血坏死区/缺血危险区(AN/AAR)明显缩小(P0.05),cTnI含量明显降低(P0.05),NO浓度明显升高(P0.05)。T3时IRYD组与IR组大鼠各指标差异无统计学意义。结论 Dex预处理能改善糖尿病大鼠MIRI后的心脏收缩和舒张功能、减少心肌细胞坏死,其保护机制可能与α2受体激动和血浆NO浓度升高有关。     

环孢素A在透明质酸诱导大鼠间质性膀胱炎/膀胱疼痛综合征中的治疗作用

目的观察环孢素A(Cs A)在透明质酸酶诱导的大鼠间质性膀胱炎/膀胱疼痛综合征(IC/BPS)中的治疗作用。方法将45只成年雌性Sprague-Dawley(SD)大鼠(200~250 g),分为对照组15只(膀胱灌注生理盐水),模型组15只(膀胱灌注透明质酸酶),Cs A治疗组15只(膀胱灌注透明质酸酶+Cs A)。采用长期(1个月)间歇灌注透明质酸酶(4 g/L)构建大鼠IC/BPS模型,尿流动力学检测膀胱功能,Von Frey刷检测泌尿生殖区疼痛变化,硝酸还原酶法测定膀胱组织NO的含量,逆转录聚合酶链反应(RT-PCR)检测i NOS、IL-6、IL-10及IL-17 m RNA表达,ELISA法检测膀胱组织IL-6、IL-10及IL-17含量。结果与对照组相比,模型组膀胱大鼠膀胱i NOS、IL-6、IL-10、IL-17 m RNA表达均显著升高(P0.001),在予以Cs A治疗后,其m RNA表达均显著下调(P0.05)。模型组膀胱NO含量为9.73±2.62μmol/g;IL-6含量为125.4±11.25μg/g;IL-10含量为64.05±6.26μg/g;IL-17含量为90.61±10.49μg/g;排尿时间间隔为148.23±40.75 s;膀胱容量为0.41±0.06 m L。对照组膀胱NO含量为1.31±0.55μmol/g;IL-6含量为55.18±5.07μg/g;IL-10含量为32.12±3.82μg/g;IL-17含量为44.45±4.92μg/g;排尿时间间隔为441.90±34.96 s;膀胱容量为1.27±0.10 m L。与对照组比较,模型组大鼠膀胱NO、IL-6、IL-10、IL-17含量均明显升高,排尿时间间隔缩短,膀胱容量降低,疼痛评分显著增加(P0.05)。与模型组相比,Cs A治疗组大鼠的膀胱组织NO、IL-6、IL-10、IL-17含量均显著减少(P0.001),分别为3.97±1.71μmol/g;62.29±6.68μg/g;33.51±5.77μg/g;51.88±6.67μg/g,排尿时间间隔及膀胱容量明显增加(P0.05),分别为422.06±42.22 s、1.14±0.15 m L,疼痛评分也明显下调(P0.05)。结论在透明质酸酶诱导的IC/BPS大鼠模型中,Cs A膀胱灌注治疗能显著改善大鼠的尿流动力学及疼痛症状,这可能与其下调i NOS、NO、IL-6、IL-10及IL-17等炎症介质的表达有关。     

γ-亚麻酸膀胱灌注治疗大鼠膀胱癌的实验研究

为了探讨γ-亚麻酸诱导大鼠膀胱癌细胞凋亡的机制,我们采用γ-亚麻酸对膀胱癌荷瘤大鼠行膀胱灌注,观察灌注前后肿瘤细胞中丙二醛(MDA)浓度的变化,增殖细胞核抗原(PCNA)以及Fas和FasL的表达情况,现报告如下. 材料与方法 8～10周龄SPF级雌性SD大鼠60只,体质量250～300 g,由上海斯莱克实验动物有限责任公司提供.应用N-甲基亚硝基脲(MNU,美国Sigma公司)膀胱灌注,9周后诱导出大鼠膀胱癌动物模型[1].1％戊巴比妥钠腹腔内注射麻醉,手术切取部分膀胱癌组织,缝合膀胱.术后1周,60只大鼠随机分为2组,每组30只.实验组:膀胱灌注浓度为2.5 mg/ml的γ-亚麻酸(美国Sigma公司),每只每次用量0.4 ml(1mg/次),保留2h.隔日1次,共3次.     

慢性低灌注性脑缺血再灌注后大鼠血脑屏障通透性的改变

目的通过敏感的荧光方法,定量分析慢性低灌注性脑缺血再灌注后大鼠血脑屏障(BBB)的通透性。方法雄性Wistar大鼠35只。大鼠分为模型再灌注组(n=25),模型不灌注组(n=5)和对照组(n=5)。模型再灌注组和模型不灌注组行右侧颈总动脉和颈外静脉端端吻合,同时结扎上矢状窦,建立大鼠脑动静脉瘘的动物模型;对照组单纯行右侧颈总动脉结扎。2周后,每组大鼠实验结束前2h尾静脉注射伊文思蓝(EB)。模型再灌注组阻断右侧颈总动脉和颈外静脉吻合部位形成缺血再灌注,采用EB荧光定量的方法分别观察再灌注2、3、9、24、48h时BBB的通透性。结果再灌注2h时,脑组织EB的含量为(0.935±0.166)μg/g,与对照组(0.489±0.132)μg/g相比显著增高(P<0.05),与模型不灌注组(0.713±1.217)μg/g相比显著增高(P<0.05)。再灌注24h达高峰,为(5.231±1.183)μg/g,再灌注48h趋于平稳,为(5.522±1.124)μg/g。结论慢性低灌注性脑缺血BBB通透性2周后增高;再灌注后2hBBB的通透性增高更具明显,再灌注24h达高峰,再灌注48h趋于稳定。     

舒芬太尼对多发伤术后机械通气患者镇痛镇静效果的观察

目的：观察舒芬太尼对多发伤术后机械通气患者镇痛镇静的效果。方法将30例多发伤术后机械通气患者患者随机分为2组,舒芬太尼组给予负荷剂量0．2μg／kg 后,维持量以每小时0．1μg／kg 持续泵入;芬太尼组给予负荷剂量2μg／kg 后,维持量以每小时1μg／kg 持续泵入。记录两组患者入 ICU 后给药前（T0）,给药后1 h（T1）,给药后4 h（T2）,给药后8 h（T3）,给药后24 h （T4）患者生命指征、VAS 评分、Ramsay 评分、机械通气时间与 ICU 住院时间。结果舒芬太尼组在 T2、T3、T4时刻平均血压、心率、呼吸均低于芬太尼组（P ＜0．05）,镇痛镇静评分优于芬太尼组（P ＜0．05）,机械通气时间与 ICU 住院时间较芬太尼组明显减少（P ＜0．05）。结论舒芬太尼对多发伤术后机械通气患者镇痛镇静有良好的效果。     

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.     

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.     

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.