严重烧伤家兔不同病理期丙泊酚的药代动力学差异

目的 了解严重烧伤家兔在休克期与高代谢期丙泊酚的药代动力学特征和差异.方法 将20只新西兰大白兔按随机数字表法分为烧伤组和假伤组,每组10只.将烧伤组家兔造成30%TBSA的Ⅲ度烫伤(以下称烧伤),伤后即刻复苏;6 h后静脉注射5.1 mg/kg丙泊酚,分别于注药后1、3、 5、 10、15、20、30、45、60、90 min于左侧颈外静脉取血1.5 mL;1周后重复上述注药及标本采集过程.假伤组家兔除致假伤外,其他处理同烧伤组.用高效液相色谱仪集中检测2组家兔血浆丙泊酚浓度,采用3P97实用药代动力学计算程序处理血浆药物浓度-时间数据,拟合药代动力学模型并求算参数. 结果 烧伤组家兔药物浓度-时间数据符合二房室模型,假伤组符合三房室模型.休克期,与假伤组家兔中央室分布容积[Vc,(3.1±1.5)L/kg]、曲线下面积[AUG,(25±7)mg·min·L~(-1)]、消除相半衰期[tl/2β,(113.4±93)min]、总清除率[CLs,(110±50)mL·kg~(-1)·min~(-1)]比较,烧伤组Vc[(8.8±4.2)L/kg]与AUC[(44±10)mg·min·L~(-1)]增大(t值分别为3.191与3.668,P值均小于0.01),tl/2β[(339±258)min]延长(t=2.932,P<0.05),CLs[(40±30)mL·kg~(-1)·min~(-1)]降低(t=-3.013,P<0.05).高代谢期,烧伤组家兔CLs[(180±40)mL·kg~(-1)·min~(-1)]显著高于假伤组[(90±30)mL·kg~(-1)·min~(-1),t=-3.013,P<0.05].与本组休克期比较,烧伤组家兔高代谢期Vc[(4.1±1.3)L/kg]与AUC[(24±5)mg·min·L~(-1)]显著减小(t值分别为2.979与3.766,P值均小于0.01),分布相半衰期[t1/2α,休克期为(16.1±13.1)min、高代谢期为(8.3±2.5)min]、t1/2β[(55±19)min]明显缩短(t值分别为9.065与8.795,P值均小于0.01),而CLs则显著增加(t=4.238,P<0.01). 结论 严重烧伤家兔休克期与高代谢期丙泊酚药代动力学差异较大,休克期以Vc、AUC增大,t1/2α、t1/2β延长,CLs降低为特点;高代谢期以CLs显著增加为特点.     

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.     

不同烧伤程度患者靶控输注丙泊酚的药代动力学

目的结合脑电双频指数(BIS)研究不同烧伤程度患者高代谢期靶控输注丙泊酚的药代动力学特征。方法选择烧伤手术患者58例,男45例,女13例,年龄18~60岁,ASAⅡ或Ⅲ级,按照烧伤程度将患者分为三组,A组(n=20)为对照组,瘢痕患者,行瘢痕切除修复植皮术;B组(n=20)为中度烧伤患者,行切痂植皮术;C组(n=18)为重度烧伤患者,行切痂植皮术。B、C组患者无休克表现,处于高代谢期(患者均在烧伤后6~14d施行手术,心排血量增高)。丙泊酚以3.5μg/ml的靶浓度TCI诱导并维持,辅以瑞芬太尼、罗库溴铵维持麻醉,维持BIS值40~60。于丙泊酚TCI前,TCI后1、2、5、10、15、20、30、40、50、60、90min,停止TCI时及停药后1、3、5、8、10、20、30min抽取动脉血3ml,采用高效液相色谱-荧光法(HPLC-FLD)测定丙泊酚血浆药物浓度(Cm),用DAS软件计算程序处理数据,拟合房室模型,计算药代动力学参数。结果三组实测丙泊酚Cm均高于靶浓度,在TCI后2min升高达到稳态,20min后开始逐渐下降,C组Cm明显低于A、B组(P0.05);C组的分布容积(V1、V2、V3)、清除率(CL)、消除速率常数(K10)均明显高于A、B组(P0.05);三组其余药代动力学参数差异均无统计学意义。结论重度烧伤患者应用丙泊酚TCI需要设定更高的靶浓度及输注速率。中度烧伤患者高代谢期药代动力学参数与非烧伤患者相似。     

梗阻性黄疸患者吗啡-红细胞载体时效及药代动力学特征

目的研究梗阻性黄疸患者吗啡-红细胞载体(RBC-M)静脉注射的药代动力学特征。方法20例择期拟行腹部探查手术的梗阻性黄疸患者随机均分为研究组(T组)和对照组(C组)。T组和C组手术结束时分别静注RBC-M溶液(含吗啡2mg/kg)和单纯吗啡溶液(2mg/kg)。记录术后患者首次出现手术部位疼痛的时间。两组中随机选取5例患者进行药代动力学研究,采用高效液相色谱法测定并计算药代动力学参数。结果T组和C组患者术后手术部位首次出现疼痛的时间分别为(2.6±1.5)h和(5.1±2.7)h(P<0.01)。两组均符合二室模型,T组吗啡的血浆清除率(CL)为(518.1±165.4)ml/min,消除半衰期(T1/2β)为(4.6±1.8)h,平均驻留时间(MRT)为(6.8±2.4)h,血药浓度时间曲线下面积(AUC)为(321.7±102.6)ng·h-1·L-1;C组的CL为(282.6±96.8)ml/min,T1/2β为(3.7±1.3)h,MRT为(5.3±2.1)h,AUC为(589.5±114.6)ng·h-1·L-1。两组药代动力学参数之间的差异均有统计学意义(P<0.01)。结论将红细胞载体应用于梗阻性黄疸患者可显著延长吗啡的作用时效。     

丙泊酚诱导时雷米芬太尼对老年患者意识消失的影响

目的研究靶控输注丙泊酚麻醉诱导时雷米芬太尼对老年人意识消失的影响。方法30名老年患者,随机分两组靶控输注雷米芬太尼4ng/ml组(R组)和生理盐水对照组(C组)。10min后同时靶控输注丙泊酚,效应浓度逐步上升(1,2,4μg/ml)。记录BIS、OAA/S、血液动力学变化、丙泊酚效应浓度及用量。结果OAA/S1分时,R组BIS值为62±18,C组为61±11。R组丙泊酚效应浓度为(1·1±0·4)μg/ml,C组为(2·0±0·4)μg/ml(P<0·05)。R组丙泊酚用量为(63±24)mg,C组为(141±34)mg(P<0·01)。结论雷米芬太尼能协同丙泊酚加强对老年人意识消失的作用。     

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。     

大鼠无肝状态下丙泊酚药代动力学的变化

目的 研究大鼠无肝状态下丙泊酚药代动力学的变化.方法 SPF级雄性SD大鼠10只,乙醚麻醉后,分别于肝门阻断前后经右颈深静脉注入丙泊酚10 mg/kg,注射后2、4、6、8、10、15、20、30、45、60 min采血100 μl,反相高效液相色谱法检测各时点血药浓度变化,并应用3P-87药代动力学软件测箅比较无肝期前后丙泊酚药代动力学参数的变化.结果 无肝期前后,丙泊酚单次剂量注射血药浓度变化趋势相似,药代动力学各参数中分布半衰期(T1/2α)、消除半衰期(T1/2β)与表观分布容积(Vd)无明显改变,药-时曲线下面积(AUC)明显增大(P<0.05),清除率(CL)显著减少(P<0.01).结论 无肝期丙泊酚的肝外代谢明显增强.     

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。     

单次注射舒芬太尼在腹部手术与心脏手术患者的药代动力学比较

目的比较舒芬太尼在腹部手术与心脏手术患者的药代动力学特征。方法随机选择腹部手术(A组)与心脏手术(C组)患者各8例,全麻后分别静注舒芬太尼2μg/kg和5μg/kg。采用液相色谱-质谱联用法测定静注舒芬太尼后1、3、5、10、20、30、60、120、240和360 min血浆舒芬太尼浓度,并用3p97药理学程序计算药代动力学参数。结果舒芬太尼药代动力学三指数函数方程:A组为Cp(t)=2.86e-0.824t+0.75e-0.060t+0.14e-0.005t,C组为Cp(t)=18.81e-0.492t+4.35e-0.050t+0.28e-0.003t。A组药代动力学参数P、A、B、t1/2β和AUC分别是C组的6.6、5.8、2.0、1.8和4.6倍(P<0.05或P<0.01);而A组中心分布容积(Vc)和清除率(CL)大于或快于C组(P<0.05或P<0.01)。结论舒芬太尼在腹部手术和心脏手术患者药代动力学均可用三室模型描述,疾病性质、CPB与血液稀释可影响其药代动力学特征,临床用药应根据手术患者的具体情况调整用药剂量以做到用药个体化。     

国人老年人丙泊酚的药代动力学

目的 观察老年手术病人丙泊酚单次静脉注射的药代动力学特征。方法7例ASAⅠ～Ⅱ级、年龄67～81岁的择期老年手术病人，经前臂静脉注射丙泊酚1mg／kg，分别于注射前和注射后1、2、4、6、10、15、30、45、60、75、90、120、150、180、240、300、360min从右颈内静脉采血3ml，肝素抗凝，离心后取上层血浆于4℃下保存。用高效液相色谱荧光法检测血浆中丙泊酚浓度，3P87软件计算药代动力学参数。结果 7例老年病人丙泊酚的药代动力学特征均符合三室开放模型，快速分布半衰期(T1／2pi)、中央室分布容积(Vc)、分布速率常数(K12、K13、K10)、全身清除率(CL)等值均与文献报道一致，缓慢分布半衰期(T1/2α)、消除半衰期(T1/2β)则较短。与文献报道中的成人值相比，Vc和CL较低。结论 丙泊酚用于老年人麻醉具有起效快、维持时间短、恢复迅速的特点，但体内Vc较小，CL减慢，故临床用药时需参考年龄因素减少剂量，减轻不良反应和防止药物蓄积。     

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.