靶控输注丙泊酚时的瑞芬太尼群体药代动力学

目的建立靶控输注丙泊酚时的瑞芬太尼群体药代动力学,并探索协变量的影响。方法全麻择期手术患者50例,年龄25~93岁,27例患者持续输注瑞芬太尼0.3μg.kg-1.min-1或23例患者0.6μg.kg-1.min-1。采集动脉血分析血药浓度,NONMEM分析建立群体药代动力学模型。结果瑞芬太尼药代动力学适合用三室模型描述,性别和年龄显著影响中央室容积(V1)和深外周室容积(V3),瘦体重(LBM)、体表面积(BSA)和体重指数(BMI)不影响其药代动力学。患者瑞芬太尼药代动力学参数典型值为V18.76 L(男)、5.10 L(女),浅外周室容积(V2)5.93 L,V34.90 L,系统清除率(CL1)2.86 L/min,浅外周室清除率(CL2)0.70 L/min,深外周室清除率(CL3)0.23L/min。结论瑞芬太尼的药代动力学特点与其经血液和组织酯酶迅速水解的特点一致。女性V1比男性低42%,V3与年龄有关,体重、LBM、BSA和BMI不影响瑞芬太尼的药代动力学参数。     

国人靶控输注异丙酚的群体药代动力学

目的 运用非线性混合效应模型(NONMEM)软件计算国人异丙酚靶控输注(TCI)群体药代动力学参数并分析药代动力学特点。方法 61例行择期手术患者,ASAⅠ～Ⅱ级,男26例,女35例,年龄18～64岁,体重41～83kg。采用Tackley药代动力学参数,恒定靶血浆药物浓度(3μg·ml~(-1))变速输注60min,间断采血90min,共976个血标本,用气相色谱-质谱法测定异丙酚的血浆药物浓度。运用NONMEM软件估算异丙酚TCI群体药代动力学参数并分析药代动力学变化特点。结果 国人异丙酚TCI可用二室开放型药代动力学模型进行描述。最终药代动力学参数:K_(10)、K_(12)、K_(21)分别为0.111、0.064、0.023min~(-1);V_1、V_2分别为0.205、0.404L·kg~(-1);CL_1、CL_2分别为22.76、13.24ml·min~(-1)·kg~(-1)。最终回归模型中异丙酚血药浓度估算值与实测浓度间线性关系良好。在固定效应参数中,体重影响V_1、CL_1,年龄影响K_(21),性别对参数无影响。结论 国人异丙酚TCI的药代动力学特点为可用二室指数开放模型进行描述,中央室分布容积明显小于欧美人群,药物从中央室向外周室转运和消除速率较快。     

成人患者瑞芬太尼群体药代动力学初步研究

目的探讨影响成人患者瑞芬太尼药代动力学的可能因素,并初步建立其群体药代动力学模型。方法全麻择期腹部大手术患者11例,年龄25~86岁,随机确定瑞芬太尼输注速度为0.3μg·kg-1·min-1(R3组)或0.6μg·kg-1·min-1(R6组)。按预设时间采集动脉血样本分析血药浓度,非线性混合效应模型(NONMEM)建立群体药代动力学模型。结果瑞芬太尼药代动力学适合用三室模型描述,初期分析表明年龄、身高和BMI不影响药代动力学参数,而瘦体重(LBM)、体表面积(BSA)和性别有明显影响(P0.01);进一步以后退法验证仅体重显著影响瑞芬太尼的系统清除率(CL)和中央室容积(V)。60kg患者瑞芬太尼药代动力学参数典型值为V1=7.61L,V2=4.81L,V3=4.34L,CL1=2.74L/min,CL2=0.738L/min,CL3=0.0905L/min。结论瑞芬太尼的药代动力学特点与其经血液和组织酯酶迅速水解的特点一致。在研究涉及的协变量范围内,系统清除率和中央室容积随体重增加而增加,提示较大体重的患者需要较大剂量的初始输注速度和维持剂量以获得稳定的血浆浓度和临床效应。     

不同年龄患儿异丙酚的药代动力学

目的比较不同年龄患儿异丙酚的药代动力学。方法35例ASA Ⅰ或Ⅱ级患儿根据年龄不同分为3组,A组:<3岁;B组:≥3岁且<5岁;C组:≥5岁且<10岁。单次静脉注射异丙酚3 mg·kg-1后2、4、6、8、10、20、30、45、60、90、120、180 min抽取桡动脉血1 ml,高效液相色谱法检测血浆异丙酚浓度,经计算机软件拟合,得到各项药代动力学参数。结果三组患儿单次静脉注射异丙酚3 mg ·kg-1后血浆浓度下降迅速。与C组相比,A组的消除项指数常数较小,消除半衰期较长(P<0.01)。三组患儿的中央室分布容积分别为0.55、0.60、0.58 L·kg-1;总体清除率分别为0.015、0.016、0.020 L·kg-1·min-1;总体分布容积分别为8.0、6.5、6.2 L·kg-1,分布半衰期和速率常数(K12、K21、K10),组间比较差异均无统计学意义(P>0.05)。结论小于3岁患儿单次静脉注射3 mg·kg-1异丙酚后其药代动力学过程符合三室开放模型,除消除时间有所延长外,其余药代动力学参数与较大患儿一致。     

兔异丙酚靶控输注的药代动力学

目的测定兔靶控输注(TCI)异丙酚药代动力学参数及引起不同麻醉深度所需的异丙酚血浆靶浓度。方法日本大耳兔20只,耳缘静脉注射10 mg·kg~(-1)异丙酚,抽取静脉注射后1、2、5、8、10、15、20、30、45、60 min动脉血各2 ml,通过高效液相色谱法测定异丙酚血药浓度,应用3P87药代动力学程序分析兔异丙酚药代动力学房室模型结构；随后将药代动力学参数代入TCI控制程序Stelpump中,以咀嚼反射消失作为浅麻醉标志,以夹尾后无体动反应为深麻醉标志,确定达到不同麻醉深度所需的异丙酚血浆靶浓度。结果兔异丙酚药代动力学模型为两室模型,中央室表观分布容积为(0．331±0．007)L·kg~(-1),中央室消除速率常数为(0．263±0．019)min~(-1),室间分布速率常数K_(12)、K_(21)分别为0．083±0．004、(0．060±0．009)min~(-1)。浅麻醉状态及深麻醉状态所需异丙酚血浆靶浓度分别为9．25±0．12、(11．63±0．29)μg·ml~(-1)。结论本研究确定了兔TCI异丙酚的药代动力学参数及维持不同麻醉水平血浆靶浓度。     

不同年龄患儿顺式阿曲库铵药代动力学的比较

目的 比较不同年龄患儿顺式阿曲库铵的药代动力学.方法 择期行唇腭裂修复术的患儿24例,ASA分级Ⅰ或Ⅱ级,年龄＜5岁,体重9～ 26 kg.根据年龄将患儿分为2组(n=12),A组:年龄＜2岁;B组:2岁≤年龄＜5岁.麻醉诱导后经10 s静脉注射顺式阿曲库铵0.15 mg/kg.于顺式阿曲库铵给药后2、4、6、8、10、15、20、30、45、60、90和120 min时取桡动脉血样,采用高效液相色谱法检测血浆顺式阿曲库铵浓度,将所得时间-血药浓度数据应用3P97计算机软件处理,得到各项药代动力学参数:消除半衰期、系数常数(A,B)、分布速率常数、消除速率常数、中央分布容积、血浆清除率、表观分布容积、速率常数(K10、K12、K21).结果 顺式阿曲库铵药代动力学过程符合二室模型;与B组比较,A组中央分布容积、表观分布容积和血浆清除率升高(P＜0.05),其余药代动力学参数差异无统计学意义(P＞0.05).结论 患儿顺式阿曲库铵药代动力学过程符合二室模型,2岁以下患儿顺式阿曲库铵中央室分布容积、表观分布容积、血浆清除率明显高于2～5岁患儿.     

靶控输注芬太尼对异丙酚药代动力学的影响

目的 探讨靶控输注芬太尼对异丙酚药代动力学的影响。方法 24例行结肠或直肠癌根治术患者,AsAⅠ-Ⅱ级,随机分为异丙酚复合硬膜外组(A组,n=8),异丙酚复合2 ng·ml-1芬太尼组(B组,n=8),异丙酚复合4 ng·ml-1芬太尼组(C组,n=8),三组患者均采用靶控方式输注芬太尼与异丙酚,异丙酚靶浓度均为3μg·ml-1。测定靶控输注中及停止输注后异丙酚的血浆浓度,并拟合得到各项药代动力学参数。结果 异丙酚药代动力学模型符合三室开放模型。药代动力学参数:快速分布半衰期(t1/2α)、慢速分布半衰期(t1/2β)、消除半衰期(t1/2γ)、浓度-时间曲线下面积(AUC)、清除率(CL)及中央室容积(Vc),各组间比较差异无显著性(P>0.05)。结论 靶控输注临床剂量的芬太尼(2ng·ml-1与4 ng·ml-1)并不影响异丙酚的药代动力学特性。     

两种舒芬太尼靶控输注系统的准确性

目的 评价两种舒芬太尼靶控输注系统的准确性.方法 择期手术患者18例,年龄21～64岁,ASA Ⅰ或Ⅱ级,均采用舒芬太尼、异丙酚及维库溴铵行麻醉诱导和维持.随机选择6例患者行体重修正舒芬太尼Gepts药代动力学参数研究,靶控输注舒芬太尼(血浆靶浓度0.8 ng/ml)10 min,输注异丙酚(血浆靶浓度3～4 mg/L),意识消失后静脉注射维库溴铵0.1 mg/kg,靶控输注舒芬太尼(血浆靶浓度0.2～0.8 ng/ml),术毕前30 min停止输注.分别于靶控输注舒芬太尼前、输注舒芬太尼1、3、5、10、20、40、60、90、120和150 min时取桡动脉血3 ml/次,采用ELISA法测定舒芬太尼血药浓度.计算偏离度、准确度,中央室容积(V1)与体重(m)作直线回归分析,并修正药代动力学参数.余12例患者选用上述体重修正后药代动力学参数行临床麻醉,计算舒芬太尼靶控输注系统的偏离度、准确度、分散度、摆动度.结果 采用舒芬太尼Gepts药代动力学参数靶控输注舒芬太尼时,偏离度为16.7%、准确度为42.0%;体重修正后参数为:V1(L)=0.147 m+2.82,K10=0.064 5 min-1、K12=0.108 6 min-1、K21=0.024 5 min-1、K13=0.022 9 min-1、K31=0.001 3 min-1;采用体重修正后药代动力学参数靶控输注舒芬太尼时,偏离度、准确度分别为4.0%、22.3%,较Gepts药代动力学参数靶控输注舒芬太尼时小(P＜0.05),分散度、摆动度分别为-4.4%/h、20.4%.结论 舒芬太尼Gepts药代动力学参数的中央室容积偏大,体重修正后嵌入靶控输注系统,可提高靶控输注的精确度及稳定性,可维持较准确的血药浓度.     

室间隔缺损修补术患儿异丙酚的药代动力学

目的观察心肺转流术(CPB)下室间隔缺损(VSD)修补术患儿异丙酚的药代动力学特点。方法择期常温CPB下行VSD修补术患儿40例,ASAⅠ或Ⅱ级,年龄1～6岁,体重10～22 kg。术前口服咪达唑仑0.5 mg·kg-1。静脉注射芬太尼20μg·kg-1、咪达唑仑0.1 mg·kg-1、维库溴铵0.1 mg·kg-1麻醉诱导后气管插管,机械通气。间断静脉注射芬太尼复合吸入混合气体异氟醚-N2O-O2(1:49: 50)麻醉维持。CPB开始前上肢静脉注射异丙酚3mg·kg-1(30 s注射完毕)。于注药前即刻、注药后1、2、4、6、10、15、30、60、90、150、210、300、420 min抽取静脉血,采用反相高效液相色谱技术(HPLC)测定血浆药物浓度。应用药代动力学软件3P87进行数据分析。结果CPB下VSD修补术患儿异丙酚呈二室模型分布,一级速率过程进行消除,清除率(0.070±0.021)L·kg-1·min-1,中央室分布容积(1.24±0.25)L·kg-1,表观分布容积(Vd)(38±6)L·kg-1,分布半衰期(t1/2α)(4.5±0.8)min,消除半衰期(t1/2β) (148±26)min,其二指数方程为C(t)=2.3e-0.154 2t 0.151e-0.005 22t。除身高与β之间有关系外,体重等变量和各个药代动力学参数间无线性回归关系。结论常温CPB下VSD修补术患儿异丙酚的药代动力学与成人不同,异丙酚的t1/2α、t1/2β延长,Vd增大,CL减慢。     

全麻下儿童丙泊酚的药代动力学特征

目的 研究全麻下儿童丙泊酚的药代动力学特征.方法 选择拟在全麻下行择期手术的患儿19例,ASA Ⅰ或Ⅱ级.丙泊酚3 mg/kg在上肢静脉约30 S左右注射完毕,注药后1、2、4、6、10、15、30、60、90、150、210、300、420 min从右颈内静脉抽取1.5 ml全血.血浆药物浓度的测定方法采用反相高效液相色谱技术,应用3p87软件包拟合总的药代动力学参数.结果 最终药代动力学参数：清除速率常数（k10）0.1616/min,1室向2室转运速率常数（k12）0.0640/min,2室向1室转运速率常数（k21）0.0062/min,分布半衰期（T1/2α）4.1176 min,清除半衰期（T1/2β）123.9559 min,清除率（CL）0.0745 L·min^-1·kg^-1,中央室分布容积（Vc）0.9505 L/kg,表观分布容积（Va）27.4100 L/kg.未发现体重等变量和各个药代动力学参数间有线性方程可建立.结论 丙泊酚在儿童的药代学模型呈二室模型,符合线性药代动力学特点.儿童丙泊酚的药代动力学特征明显不同于成人.     

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.