腰椎间盘突出症模型大鼠的疼痛与抑郁共病情况及氟西汀疗效的实验研究

目的 探讨腰椎间盘突出症大鼠模型中疼痛和抑郁共病情况及氟西汀的治疗效果.方法 将56只Wistar大鼠随机分为对照组、假手术组、模型组、氟西汀组四组,对照组大鼠未经任何特殊处理;假手术组经手术造模暴露右侧L5背根神经节;模型组和氟西汀组经手术造模形成椎间盘突出、压迫神经根.术后4周开始,氟西汀组大鼠给予20 mg/kg氟西汀灌胃,2次/d;对照组、假手术组、模型组给予等量生理盐水灌胃.术前、术后2周、4周、6周时,评估大鼠的机械缩爪阈值(MWT)和抑郁症行为(糖水偏爱实验、强迫游泳实验和旷场实验);末次给药完毕、检测完行为学实验后,采用酶联免疫吸附法(ELISA法检)测海马和前额叶皮质肿瘤坏死因子α(TNF-ɑ)和5羟色胺(5-HT)水平.结果 术后2周、4周、6周时,模型组和氟西汀组大鼠MWT阈值均显著低于对照组和假手术组(P<0.05);术后2周和4周时,模型组和氟西汀组MWT阈值差异无统计学意义(P>0.05);术后6周时氟西汀组MWT阈值显著高于模型组(P<0.05).术后2周、4周、6周时,模型组和氟西汀组糖水偏爱率、穿越格子数低于对照组和假手术组(P<0.05),漂浮不动时间高于对照组和模型组(P<0.05);术后2周和4周时,模型组和氟西汀组大鼠的糖水偏爱率、漂浮不动时间、穿越格子数差异均无统计学意义(P>0.05);术后6周时,氟西汀组糖水偏爱率和穿越格子数高于模型组,漂浮不动时间低于模型组,差异均有统计学意义(P<0.05).模型组和氟西汀组前额叶和海马组织TNF-ɑ水平均显著高于对照组和假手术组(P<0.05),5-HT水平均低于对照组和假手术组;氟西汀组前额叶和海马组织TNF-ɑ水平均显著低于模型组(P<0.05),5-HT水平均显著高于模型组(P<0.05).结论 腰椎间盘突出症大鼠模型存在抑郁和疼痛共病的表现,氟西汀可通过改善脑组织5-HT和TNF-ɑ水平改善抑郁和疼痛表现,为腰椎间盘突出症疼痛和抑郁共病的治疗提供了理论基础.     

剖宫产术后鸡矢藤与吗啡联合镇痛效果观察

将220例剖宫产病人随机分为两组,现察组(110例)给予鸡矢藤加吗啡行病人自控硬膜外镇痛(PCEA),对照组(110例)给予吗啡加氟哌啶行PCEA,观察两组镇痛效果及不良反应.结果镇痛效果观察组与对照组比较,差异无显著性意义(P＞0.05),不良反应观察组显著低于对照组(P＜0.01).提示鸡矢藤与吗啡联合镇痛效果确切,不良反应少.     

盐酸舍曲林治疗早泄的临床研究

目的:观察盐酸舍曲林(左洛复)治疗早泄的疗效和副作用。方法:以盐酸氟西汀(百忧解)为阳性对照,分别以口服盐酸舍曲林50mg/d和盐酸氟西汀20mg/d治疗早泄患者,疗程4周,通过问卷调查两种药物的疗效及副作用。结果:66例患者完成研究,两种药物治疗早泄的有效率盐酸舍曲林为73.7%(28/38)、盐酸氟西汀为71.4%(20/28),差异无统计学意义(P>0.05);两种药物的副作用发生率也无明显差异。结论:抗抑郁药盐酸舍曲林与盐酸氟西汀一样,也有良好的治疗早泄作用,但具有更好的患者依丛性。     

丁桂凝胶贴膏镇痛抗炎作用研究

目的 :观察丁桂凝胶贴膏对不同动物模型的镇痛抗炎作用,探讨其镇痛抗炎的作用机制。方法 :将84只4~5周龄,体重18~22 g的雄性KM小鼠随机分为7组:空白组、模型组、基质对照组、扶他林软膏组、丁桂凝胶贴膏高剂量组、丁桂凝胶贴膏等效剂量组和丁桂活络膏组,每组12只。除空白组与模型组外,其余各组小鼠于相应造模部位连续贴敷给药7 d,每日1次,基质对照组给予等剂量的空白基质凝胶贴膏。分别于末次给药后30、60、90、120 min测定其痛阈值。采用热板法实验予末次给药后在小鼠右后足跖部皮下注射5%甲醛溶液20μl,观察Ⅰ、Ⅱ相疼痛期内小鼠舔右后足的累计时间,并用ELISA方法测定血清中IL-1、TNF-α含量。采用耳肿胀法抗炎实验测量小鼠左右耳片重量的差值。结果:热板法实验中90 min时,丁桂凝胶贴膏等效剂量组痛阈值为(24.87±14.67)s,模型组痛阈值为(15.28±8.23)s;120 min时,高剂量组痛阈值为(26.33±15.45)s,模型组痛阈值为(15.31±5.02);丁桂凝胶贴膏两组分别与模型组比较差异均有统计学意义(P0.05)。Ⅰ相疼痛期,累积舔足时间丁桂凝胶贴膏高剂量组为(66.70±22.83)s,模型组为(101.80±33.65)s,两者比较差异有统计学意义(P0.01);Ⅱ相疼痛期的累积舔足时间模型组为(109.50±36.78)s,丁桂凝胶贴膏高剂量组为(51.30±43.60)s,等效剂量组为(64.00±47.27)s,与模型组比较差异有统计学意义(P0.05);模型组的IL-1含量为(28.70±8.24)ng/L,丁桂凝胶贴膏高剂量组为(13.33±2.20)ng/L,与模型组比较差异有统计学意义(P0.05);模型组的TNF-α含量为(93.60±23.65)ng/L,丁桂凝胶贴膏高剂量组为(63.21±10.54)ng/L,两组比较差异有统计学意义(P0.01),等效剂量组为(72.69±16.26)ng/L,与模型组比较差异有统计学意义(P0.05);模型组耳肿胀度为(5.73±0.80)mg,丁桂凝胶贴膏高剂量组为(5.42±0.68)mg,等效剂量组为(4.98±1.52)mg,两给药组与模型组比较均有消肿趋势,但无显著性差异。结论:丁桂凝胶贴膏能明显提高热板法实验中的痛阈值,能明显减少甲醛实验中的累积舔足时间,能降低二甲苯实验中的耳肿胀度,但不明显;而其对疼痛的缓解可能是通过调节血清中的IL-1及TNF-α水平来实现的。     

盐酸戊乙奎醚联合氟哌利多降低吗啡硬膜外术后镇痛的不良反应

目的观察盐酸戊乙奎醚联合氟哌利多对吗啡用于硬膜外术后镇痛不良反应发病率的影响。方法连续硬膜外麻醉行子宫下段剖宫产手术的患者96例,ASAⅠ或Ⅱ级,随机分为单纯吗啡组(A组)、吗啡 氟哌利多组(B组)、吗啡 盐酸戊乙奎醚组(C组)及吗啡 盐酸戊乙奎醚 氟哌利多组(D组),每组24例。术毕5min分别将各组吗啡混合液各自注入硬膜外腔后拔出硬膜外导管回病房,记录术后镇痛效果及术后恶心呕吐(PONV)、皮肤瘙痒、尿潴留、口干等不良反应。结果D组的镇痛效果明显优于A、B、C组(P<0.01),且PONV、皮肤瘙痒等不良反应发病率明显低于A、B、C组(P<0.05)。结论盐酸戊乙奎醚联合氟哌利多可明显降低吗啡用于硬膜外术后镇痛不良反应的发病率。     

伊木萨克片联合盐酸氟西汀治疗早泄的临床研究

目的 研究伊木萨克片和盐酸氟西汀联合治疗早泄的可行性和效果.方法 将114例早泄患者随机分为3组,每组38例.A组患者单用伊木萨克片,1.5 g/d;B组患者单用盐酸氟西汀,20 mg/d;C组患者同时服用伊木萨克片和盐酸氟西汀,剂量同A、B组,连续服用4周.比较3组治疗前后的平均阴道内射精潜伏期(IELT)、国际勃起功能指数(IIEF)问卷中的患者及配偶性交满意度评分,观察治疗期间的不良反应.结果 114例早泄患者全部完成临床研究,所有患者平均IELT、患者及其配偶的性交满意度评分在治疗后较治疗前均显著增加,差异具统计学意义(P<0.01),单用盐酸氟西汀B组患者的IELT和性交满意度评分略好于单用药伊木萨克片A组,但两组间差异无统计学意义(P>0.05).联合用药C组患者的IELT和性交满意度评分则显著高于单用药A组和B组,差异均具有统计学意义(P<0.05).联合用药患者出现不良反应7例(18.4%),与单用药组比较差异无统计学意义.结论 联合应用伊木萨克片和盐酸氟西汀治疗早泄,疗效显著高于单用两种药物.     

鞘内注射辣椒素对恩氟醚和七氟醚镇痛作用的影响

目的 研究瞬时感受器电位香草酸受体1 (transient receptor potential vanilloid 1,TRPV1),即辣椒素受体,在吸入麻醉药恩氟醚(enflurane,Enf)和七氟醚(sevoflurane,Sev)镇痛效果中的作用. 方法 实验分热板法和扭体法两轮进行,每轮实验昆明小鼠120只,完全随机法按腹腔注射(热板法)或皮下注射(扭体法)不同试剂分为生理盐水组、Enf组、Sev组三大组,建立小鼠注射吸入麻醉药镇痛模型.每大组再根据鞘内注射溶媒或不同剂量辣椒素(2.5、5、10 ng)分为4个亚组,观察鞘内注射不同剂量TRPV1激动剂辣椒素对Enf、Sev镇痛小鼠痛阈的影响. 结果 鞘内注射辣椒素2.5、5、10 ng对清醒小鼠热板法痛阈(pain threshold in hot-plate test,HPPT)和扭体次数的影响差异无统计学意义(P＞0.05);鞘内注射辣椒素2.5、5、10 ng可减少Enf、Sev镇痛小鼠HPPT(P＜0.05),增加扭体反应次数[Enf组:(22±7)、(24±5)、(29±6)次比(16±6)次;Sev组:(21±6)、(23±7)、(28±4)次比(13±5)次](P＜0.05). 结论 脊髓的TRPV1可能是吸入麻醉药Enf和Sev镇痛作用的重要靶位.     

基于5-羟色胺调控的翘芍方干预早泄大鼠的实验研究

目的:观察翘芍方对运用5-羟色胺1A(5-HT1A)受体激动剂8-羟基-2-(二丙基氨基)四氢萘氢溴酸盐(8-OH-DPAT)建立的早泄动物模型的干预效果,并探讨其可能的作用机制。方法:将雄性Wistar大鼠72只随机分为空白组、模型组、翘芍方组(高、中、低剂量)和达泊西汀组,各12只,以8-OH-DPAT腰骶脊髓节段蛛网膜下腔囊内注射建立早泄动物模型。造模成功后连续给药干预4周,模型组、空白组每天用生理盐水[10 ml/(kg·d)]灌胃;翘芍方低[5 g/(kg·d)]、中[10 g/(kg·d)]、高[20 g/(kg·d)]剂量组,每天灌胃1次;达泊西汀组合笼前3 h给予300 mg/kg盐酸达泊西汀灌胃。雌性Wistar大鼠45只,摘除双侧卵巢后,于合笼前36 h皮下注射苯甲酸雌二醇20μg/只以诱导雌鼠发情。在第2周和第4周时,分别将雄性大鼠和激素诱导的雌性大鼠合笼,进行交配实验,每次30 min。检测指标:观察和记录雄鼠的交配行为,包括骑跨潜伏期(ML)、插入潜伏期(IL)、射精潜伏期(EL)、骑跨次数(MF)、插入次数(IF)、射精次数(EF)。第4周交配试验后,分离出下丘脑并称重,测定5-羟色胺(5-HT)含量。结果:与空白组相比,模型组5-HT含量923.4 ng/g,ML(8.69±2.48)s、IL(12.08±1.39)s、MF(7.53±1.84)次、EL(502.35±46.72)s分别低于空白组的5-HT含量1 257.1 ng/g,ML(11.22±3.60)s,IL(22.33±2.45)s、MF(13.28±.24)次、EL(712.35±36.77)s,差异均有统计学意义(P0.05);药物干预后,与模型组比较,翘芍方高剂量组和达泊西汀组的5-HT含量均升高,差异有统计学意义(P0.05);与模型组比较,翘芍方各剂量组和达泊西汀组EL明显延长,差异有统计学意义(P0.05)。结论:翘芍方可延长早泄大鼠的射精潜伏期,这可能与其增加了下丘脑5-HT含量有关,具体机制还需进一步研究。     

老年全膝关节置换术应用连续骨神经阻滞联合单次硬膜外腔吗啡镇痛的效果观察

目的分析和评价老年全膝关节置换术(TKA)应用连续骨神经阻滞(CFNB)联合单次硬膜外腔吗啡镇痛的效果。方法选取2015-03—2016-03间在河南中医药大学第三附属医院接受单侧TKA治疗的82例老年患者。随机分为2组,每组41例。对照组行CFNB镇痛,观察组在对照组基础上联合单次硬膜外腔吗啡镇痛。应用视觉模拟量法(VAS)评测2组患者术后静息、活动状态下的疼痛情况。分析2组术后患侧关节弯曲度及镇痛泵按压次数。结果术后第1、5天观察组患者静息、活动状态的VAS评分低于对照组,患侧关节弯曲度大于对照组,差异均有统计学意义(P0.05)。观察组术后第1、2天的镇痛泵按压次数显著少于对照组,差异有统计意学意义(P0.05)。结论在老年TKA术中采取CFNB联合单次硬膜外腔吗啡镇痛,优于单一CFNB镇痛,且有助于患侧关节功能恢复。     

硬膜外吗啡术后镇痛更优模式的探讨

目的观察比较硬膜外不同浓度布比卡因、氟哌利多、新斯的明和小剂量吗啡协同用药以减少吗啡传统用药引起的副作用。方法80例患者随机分成4组并使用不同剂量吗啡和不同浓度布比卡因进行对比观察。结果协同用药各组副作用发生率远较吗啡传统用药低，差异有显著性；0．2％布比卡因协同组与0．375％布比卡因协同组镇痛与副作用相似，组问比较差异无显著性。结论低浓度(0．2％)布比卡因与氟哌利多、新斯的明协同小剂量吗啡(1.0mg)用于术后镇痛为更优良的方法。     

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.     

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.