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。     

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。     

患者靶控输注瑞芬太尼时血药浓度稳定的时间

瑞芬太尼是μ受体激动剂,其特点为起效快、作用时间短、消除快,主要由血液和组织中的非特异性酯酶水解,时量相关半衰期短,适合于靶控输注(TCI).TCI泵均嵌有欧美人的瑞芬太尼药代动力学参数(Minto药代动力学参数).国外研究表明,采用Minto药代动力学参数TCI瑞芬太尼时,输注30 min左右时血药浓度稳定[1],而不同种人种群体间药代动力学参数可能存在差异[2].确定国人TCI瑞芬太尼时血药浓度达稳定时间有助于临床麻醉中调节瑞芬太尼靶浓度,使麻醉过程更趋于平稳.本研究拟确定患者TCI瑞芬太尼时血药浓度稳定的时间,为临床上TCI瑞芬太尼提供参考.     

小儿和成年患者全麻时瑞芬太尼药代动力学的比较

目的 比较小儿和成年患者全麻时瑞芬太尼的药代动力学.方法 择期全麻患者,ASA分级Ⅰ或Ⅱ级,根据年龄不同分为2组(n=8):成年组(年龄19～60岁,体重45～81 kg)和小儿组(年龄10月～7岁,体重7.2～21.0 kg).麻醉诱导时静脉注射瑞芬太尼5 μg/kg,于注射后1、2、3、5、7、10、15、20、25、30、45、60 min时分别采集上肢动脉血样1.0 ml,采用液-液萃取毛细管气相色谱-质谱法测定瑞芬太尼的血药浓度,应用3P97药理学程序软件计算药代动力学参数.结果 与成年组比较,小儿组消除半衰期缩短,表观分布容积和清除率升高(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 小儿和成年患者全麻时瑞芬太尼药代动力学存在差异,应用相同剂量后小儿较成年患者血药浓度偏低,应适当增加剂量.

Abstract：

Objective To compare the pharmacokinetics of remifentanil during general anesthesia in children and adults.Methods Eight children(4 male,4 female)and 8 adults(4 male,4 female),undergoing elective operation under general anesthesia,were randomly divided into 2 groups(n=8 each):group adults(aged 19-60 yr,weighing 45-81 kg)and group children(aged 10 months-7 yr,weighins 7.2-21.0 kg).Remifentanil 5μg/kg was injected intravenously during induction of anesthesia.Arterial blood samples 1.0 ml were taken at 1,2,3,5,7,10,15,20,25,30,45 and 60 min after injection for determination of the plasma concentrations of remifentanil.The pharmacokinetic parameters were calculated using software 3P97.Results Elimination half-life was significantly shorter and apparent volume of distribution and clearance were significantly greater in children than in adults(P<0.05),while no significant change was found in the other pharmacokinetic parameters between the two groups(P>0.05).Conclusion There is difference in the pharmacokineties of remifentanil during general anesthesia between children and adults.The plasma concentration of remifentanil is lower in children than in adults after using the same dose,and the dose should be increased appropriately.     

下腹部手术病人硬膜外注射甲磺酸罗哌卡因的药代动力学

目的测定下腹部手术病人硬膜外注射甲磺酸罗哌卡因的血浆浓度,探讨其药代动力学特征。方法ASAⅠ或Ⅱ级择期行下腹部手术病人12例。硬膜外注射甲磺酸罗哌卡因2 mg·kg~(-1) (8．94 mg·ml~(-1)),注药前及注药后2、4、6、10、20、30、45、60、90、120、180、240、300、360、720和1440 min取中心静脉血3 ml,用高效液相色谱仪测定甲磺酸罗哌卡因血浆浓度,DAS软件分析药代动力学参数。结果甲磺酸罗哌卡因的药代动力学模型符合二室开放模型,血浆浓度达峰值时间为(15±8)min,峰浓度为(1656±717)μg·L~(-1),吸收半衰期为(28±16)min,消除半衰期为(366±104)min,清除率为(0．005 0±0．001 5)L·min~(-1)·kg~(-1),表观分布容积为(2．5±0．6)L·kg~(-1)。研究期间未观察到不良反应。结论甲磺酸罗哌卡因适合于硬膜外麻醉,其药代动力学特征与报道的盐酸罗哌卡因相似,但消除半衰期延长。     

腔镜手术患者舒芬太尼靶控输注的药动学研究

目的探讨腔镜手术临床常用浓度舒芬太尼靶控输注(target-controlled infusion,TCI)的药动学特点。方法2011年6~9月,择期全麻下腔镜手术30例(24~65岁,ASAⅠ级或Ⅱ级),应用内嵌Gepts药动学参数的TCI系统输注舒芬太尼,效应室靶浓度随机采用0.2、0.3和0.4μg/L各10例,复合吸入七氟烷维持麻醉。于不同时点经桡动脉取血至停止TCI后24小时,以液相色谱-质谱联用法测定舒芬太尼的血药浓度。运用非线性混合效应模型分析舒芬太尼群体药动学数据。结果舒芬太尼TCI的药动学模型为三室模型,其药动学参数为:中央室容积(V_1)=15.7 L,快速分布容积(V_2)=50.4 L,慢速分布容积(V_3)=213.0 L,稳态分布容积(Vdss)=279.2 L;药物总清除率(Cl_1)=0.80 L/min,快速分布相清除率(Cl_2)=1.09 L/min,慢速分布相清除率(Cl_3)=0.27 L/min;快速分布半衰期(t_(1/2)α)=4.6 min,慢速分布半衰期(t_(1/2)β)=68.7 min,清除半衰期(t_(1/2)γ)=739.5 min。年龄、性别和体重对药动学参数无显著影响(P0.05)。结论腔镜手术患者临床常用浓度舒芬太尼TCI的药动学可用三室模型描述。年龄、性别和体重对药动学参数无显著影响。     

利多卡因超声雾化吸入给药药代动力学研究

目的研究利多卡因经超声雾化吸入给药的药代动力学。方法12例择期全麻病人,随机分为两组,分别吸入利多卡因100mg(Ⅰ组)、200mg(Ⅱ组),不同时间点静脉取血,采用高效液相色谱技术测定利多卡因的血药浓度,用药代动力学计算程序(3p87)处理。结果利多卡因雾化吸入后血药浓度随着雾化吸入剂量的增加而增加,两组峰值浓度(Cmax)分别为(311.5±51.3)和(639.8±9.9)ng/ml;达峰浓度时间(Tpeak)分别为(0.22±0.04)和(0.31±0.06)h,半衰期(T1/2Ke)分别为(0.73±0.07)和(0.74±0.08)h。结论利多卡因雾化吸入的药代动力学符合一级吸收的一房室模型。     

肝硬化患者复合瑞芬太尼时异丙酚的药代动力学

目的 研究肝硬化患者复合瑞芬太尼时异丙酚的药代动力学.方法拟在内镜下行食道静脉曲张套扎术的肝硬化患者10例(试验组);拟行胃镜检查术患者10例(对照组),肝功能未见异常,男女各半,年龄18～55岁,体重40～75 kg.静脉注射异丙酚1.5 mg/kg和瑞芬太尼0.5 μg/kg,5 min后再次静脉注射异丙酚0.5 mg/kg和瑞芬太尼0.2 μg/kg.分别于给药前、给药后2、5、10、15、20、30、45、60、80、120 min时采集桡动脉血样,采用气相色谱质谱联用法测定血浆异丙酚浓度,采用DAS 2.0软件计算药代动力学有关指标.结果 异丙酚的血药浓度.时间曲线符合开放性三室模型;与对照组比较,试验组分布半衰期、消除半衰期、终末半衰期、血药浓度-时间曲线下面积和转运速率常数差异无统计学意义(P＞0.05),表观分布容积和清除率升高(P＜0.01).结论 肝硬化患者复合瑞芬太尼麻醉时,异丙酚的表观分布容积和清除率升高,而其他药代动力学参数无明显变化.

Abstract：

Objective To investigate the pharmacokinetics of propofol when combined with remifentanil in patients with liver cirrhosis.Methods Ten patients (5 males, 5 females) with liver cirrhosis scheduled for endoscopic esophageal varix ligation (test group) and 10 cases (5 males, 5 females) with normal liver function scheduled for gastroscopy (control group), aged 18-55 yr, weighing 40-75 kg, were studied. The patients were unpremedicated. All the patients received iv injection of propofol 1.5 mg/kg and remifentanil 0.5 μg/kg, and 5 min later propofol 0.5 mg/kg and remifentanil 0.2 μg/kg was given again. Blood samples were taken from radial artery before administration and at 2, 5, 10, 15, 20, 30, 45, 60, 80 and 120 min after administration for determination of the plasma propofol concentration using gas chromatography-mass spectrography. The pharmacokinetic parameters were calculated using DAS 2.0 software.Results The pharmacokinetics of propofol was best described by a three-compartment open model. There was no significant difference in the distribution half-life, elimination halflife , terminal half-life, area under the curve and transfer rate constant between the two groups ( P ＞ 0.05) . The apparent volume of distribution of propofol and clearance were significantly increased in test group compared with control group (P ＜0.01) .Conclusion When propofol combined with remifentanil is used in patients with liver cirrhosis, the apparent volume of distribution of propofol and clearance are significantly increased, while no changes in the other pharmacokinetic parameters are found.     

瑞芬太尼靶控输注时靶浓度和实测血药浓度的差异-靶控输注系统的性能评价

目的比较瑞芬太尼血浆靶浓度(Cp)6、8 ng·ml-1 复合异丙酚靶控输注(TCI)时瑞芬太尼Cp和实测血药浓度(Cm)的差异,并评价思路高TCI-Ⅰ型系统(Minto药代动力学参数)的性能。方法择期行肺叶或肺段切除术病人36例,ASA Ⅰ或Ⅱ级,年龄40-60岁,体重50-70kg,随机分为2 组,组18例。麻醉诱导:Ⅰ、Ⅱ组瑞芬太尼血浆靶浓度分别为6、8 ng·ml-1,异丙酚效应室靶浓度为3 μg·ml-1,待病人意识消失后静脉注射维库溴铵0.1 mg·kg-1,3 min后行气管插管。麻醉维持:两组瑞芬太尼Cp保持不变,调节异丙酚靶浓度,维持脑电双频指数(BIS)45-55,间断静脉注射维库溴铵维持肌松。分别在瑞芬太尼TCI前及TCI 5、10、20、40、60、90、120 min时用高效液相色谱法测定瑞芬太尼Cm。采用执行误差(PE)、PE的中位数(MDPE)、PE绝对值的中位数(MDAPE)及摆动度评价TCI系统的性能。结果在TCI 5、10、20 min时,两组瑞芬太尼Cm均低于Cp(P<0.05)。Ⅰ、Ⅱ组瑞芬太尼总体血样瑞芬太尼Cm分别为5.1、6.9 ng·ml-1,均低于Cp(P<0.05)。Ⅰ、Ⅱ组MDPE、MDAPE、摆动度分别为-17.2%、29.6%、15.1%和-15.5%、27.8%、12.5%,组间比较差异无统计学意义(P>0.05)。结论瑞芬太尼Cp为6、8 ng·ml-1在国人TCI时,思路高TCI-Ⅰ型系统(Minto药代动力学参数)的精确度在临床可接受范围内,其Cm比Cp低约15%。     

盐酸罗比卡因腰丛-坐骨神经阻滞的药代动力学研究

目的采取反相高效液相法测定盐酸罗比卡因血药浓度,观察该药腰丛-坐骨神经阻滞病人的药代动力学指标。方法8例择期单下肢手术病人,使用0.375%盐酸罗比卡因行腰丛-坐骨神经阻滞,分别在给药前及给药后5、10、15、20、25、30、40、50、60、90、120、180、240、360、720、1 440 min采取静脉血。采用Agilent Zorbax SB-C18反相色谱柱(4.6 mm×250 mm,5μm)分离,并用3P97计算药代动力学参数。结果线性范围10~8 000 ng/ml,仪器灵敏度AUFS为1 ng/ml,所得药代动力学参数结果为:Cmax1(3.09±0.89)mg/L,Cmax2(3.84±1.58)mg/L,t1/2Kα(7.56±4.65)min,t1/2β(890.3±365.8)min。结论腰丛-坐骨神经阻滞后,用反相高效液相色谱法行血浆盐酸罗比卡因浓度的测定,方法稳定、简便、灵敏度高,适用于该药在此种条件下的药代动力学研究。     

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.     

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.     

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.