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。     

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。     

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.     

频谱熵和双频指数用于测定依托咪酯血浆效应室平衡速率常数的比较

目的 比较用熵指数和脑电双频指数(BIS)测定依托咪酯单次注射后的最大效应时间(TpEAK),并藉以估计依托咪酯的血浆-效应室平衡速率常数(Ke0).方法 22例患者静脉注射最大效应负荷剂量依托咪酯后,用熵指数模块和听觉诱发电化监测仪测定从注射开始至反应熵(RE)、状态熵(SE)、BIS最低的时间(TPEAK),用TpEAx和Arden等报道的依托咪酯药代学模型,按照Minto等提出的方法计算KeO.结果 RE、SE、BIS的TpEAx中位数分别为70、70和80 s,Ke0中位数分别是1.10/min、1.10/min和1.02/min.结论 单次注射依托咪酯后,熵指数和BIS监测的TpESK和计算的Ke0相同,且有别于国外研究报道的结果.     

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。     

七氟醚和依托咪酯镇静催眠效应的相互作用

目的 评价七氟醚和依托咪酯镇静催眠效应的相互作用.方法 择期全麻手术患者24例,ASA Ⅰ或Ⅱ级,年龄18～59岁,体重指数17～27 kg/m2.试验Ⅰ 12例患者靶控输注依托咪酯,效应室靶浓度依次为0.05、0.1、0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录反应熵(RE)、状态熵(SE)和警觉/镇静(OAA/S)评分,然后停止输注依托咪酯.随机分为3组(n=4),A1组、B1组、C1组吸入七氟醚,呼气末浓度分别为0.5%、1%、2%.七氟醚呼气末浓度达预定浓度的95%或以上时,靶控输注依托咪酯,效应室靶浓度依次为0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录RE、SE和OAA/S评分.试验Ⅱ 12例患者吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分,然后停止吸人七氟醚,吸氧洗脱七氟醚.随机分为3组(n=4),A2组、B2组、C2组靶控输注依托咪酯,效应室靶浓度分别为0.05、0.1、0.2 μg/ml.效应室浓度达到预设浓度2 min时,吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分.采用反应曲面法评价RE、SE和OAA/S评分,判断七氟醚和依托咪酯镇静催眠效应的相互作用.结果 RE和SE的相互作用指数的拟合值及其95%可信区间分别为0.32(-0.07～0.71)、0.25(-0.12～0.63)(P>0.05).OAA/S评分的相互作用指数的拟合值及其95%可信区间为2.25(0.58～3.93)(P<0.05).结论 以脑电熵指数反映镇静催眠效应时七氟醚和依托咪酯为相加作用;以OAA/S评分反映镇静催眠效应时七氟醚和依托咪酯为协同作用.     

依托咪酯对大鼠海马脑片突触长时程增强的影响

目的 评价依托咪酯对大鼠海马脑片突触长时程增强(LTP)的影响.方法 雄性SD大鼠,断头后取出海马组织,制备厚400 μm的海马脑片.采用细胞外微电极记录技术,记录海马脑片CA1区细胞外群体峰电位(PS).取42张脑片,随机分为6组(n=7):用正常的人工脑脊液(ACSF)灌流海马脑片记录正常的PS,待其稳定后,对照组继续灌流ACSF,不同浓度依托咪酯组分别用含依托咪酯1μmol/L(依托咪酯 1 μol/L组)、2/μmol/L(依托咪酯2 μmol/L组)、5 μmol/L(依托咪酯5 μmol/L组)、10μmol/L(依托咪酯10 μmol/L组)、20 μmol/L(依托咪酯20 μmol/L组)的ACSF灌流,记录PS幅值.另取84张脑片,随机分为12组(n=7):用正常ACSF灌流海马脑片,记录稳定正常的PS 30 min,LIT组继续灌流ACSF,其余各组分别用含依托咪酯l μmol/L(LTP-依托咪酯 1 μmol/L组)、2 μmol/L(LTP-依托咪酯2μmol/L组)、5 μmol/L(LTP-依托咪酯 5 μmol/L组)、10μmol/L(LTP-依托咪酯 10 μmol/L组)、20 μmol/L(LTP-依托咪酯20 μmol/L组)、印防己毒素50 μmol/L(印防己毒素组)、荷包牡丹碱10 μmol/L(荷包牡丹碱组)、CGP35348 5 μmol/L(CGP35348 组)、印防己毒素50 μmol/L+依托咪酯10 μmol/L(印防己毒素+依托咪酯组)、荷包牡丹碱10 μmol/L+依托咪酯10 μmol/L(荷包牡丹碱+依托咪酯组)、CGP35348 5 μmol/L+依托咪酯10 μmol/L(CGP35348+依托咪酯组)的ASCF灌流,记录PS 30 min后,施以100 Hz的高频刺激(HPS),记录PS幅值.结果 与LTP组比较,LTP-依托咪酯2 μmol/L组、LTP-依托咪酯5 μmol/L组、LTP-依托咪酯10 μmol/L组、LTP-依托咪酯20 μmol/L组和CGP35348+依托咪酯组HIS后PS幅值降低(P＜0.05或0.01),印防己毒素组、荷包牡丹碱组、CGP35348组HFS后PS幅值差异无统计学意义(P＞0.05);与依托咪酯LTP 10μmol/L组比较,印防己毒素+依托咪酯组和荷包牡丹碱+依托咪酯组HIS后PS幅值增加(P＜0.01).结论 依托咪酯可通过激活大鼠海马GABAA受体抑制LTP的形成,从而影响学习和记忆功能.     

梗阻性黄疸病人靶控输注异丙酚的药代动力学

目的 探讨梗阻性黄疸病人靶控输注（TCI）异丙酚的药代动力学。方法 择期手术病人24例，ASAI或Ⅱ级，按胆红素水平分成3组（n=8），对照组：血清总胆红素（sTBL）〈17.1μmol／L；轻度梗阻性黄疸组（B组）：17．1／μmol／L≤sTBL≤171．1μmol／L；中重度梗阻性黄疸组（C组）：sTBL〉171．1μmol／L。三组均以血浆靶浓度3．0μg／ml TCI异丙酚直至手术结束。分别于以下时点取桡动脉血：TCI开始后0．5、1、2、4、6、8min、麻醉维持过程中每隔15min、停止TCI后即刻、2、4、6、8、10、20、30、40、50、60、90、120、180、240、300、360min，用高效液相色谱荧光法测定血浆异丙酚浓度，用NONMEM软件分析药代动力学参数。结果 TCI异丙酚的群体药代动力学大部分（18／24）最适合用三室模型来描述，小部分（6／24）最适合用二室模型来描述。三组间异丙酚的药代动力学参数比较差异无统计学意义（P〉0．05）。结论 TCI异丙酚药代动力学绝大部分适合用三室模型，小部分适合用二室模型来描述；梗阻性黄疸对异丙酚的药代动力学没有影响。     

患者静脉输注羟乙基淀粉130/0.4或羟乙基淀粉200/0.5的药代动力学

目的 比较患者静脉输注6%羟乙基淀粉(HES)130/0.4和HES 200/0.5的药代动力学.方法 择期手术患者20例,ASA Ⅰ级,随机分为2组,HES 130/0.4组和HES 20010.5组,每组10例.分别在30min内静脉输注500 ml HES 130/0.4或HES 200/0.5,蒽酮比色法测定输注后各时点血清中胶体浓度,采用3P97软件计算其药代动力学参数.结果 二室模型权重为1时计算药代动力学参数最符合HES 130/0.4和HES 200/0.5的体内特点,HES 130/0.4主要的药代动力学参数如下:t1/2α=1.7 h、t1/2β=10 h、K10:0.13 h-1、K12=0.133 h-1、K21=0.210 h-1、CL(s)=10.77 L/h、AUC=46 mg·h·ml-1.HES200/0.5主要药代动力学参数如下:t1/2α=3.2 h、t1/2β=164 h、K10=0.09 h-1、K12=0.120 h-1、K21=0.010h-1、CL(s)=0.19 L/h、AUC=53 mg·h·ml-1.结论 HIES 130/0.4和HES 200/0.5在血管内停留时间均较长,HES 130/0.4较HES 200/0.5具有更好的药代动力学特点,其消除半衰期短、在血液内无蓄积.     

依托咪酯靶控输注时靶浓度与实测血药浓度的差值分析和系统性能评价

目的分析靶控输注(TCI)依托咪酯血浆靶浓度(Cp)0.5μg/ml与实测血浆浓度(Cm)的差异,并评价内嵌Arden药代动力学参数的思路高TCI-Ⅲ型输注系统的性能。方法择期全麻下行颈椎前路或腰椎侧路减压植骨内固定术患者12例,男7例,女5例,年龄19～59岁,BMI 18～29 kg/m~2,ASAⅠ或Ⅱ级。麻醉诱导前将0.5μg/kg右美托咪定10 min恒速泵注完毕,诱导时先以舒芬太尼0.3μg/kg缓慢地静脉注射,设定依托咪酯血浆靶浓度为0.5μg/ml持续泵注,待意识消失后,静脉注入顺式阿曲库铵0.3 mg/kg,行气管插管。麻醉维持期间依托咪酯血浆靶浓度维持0.5μg/ml恒定不变,同时辅以瑞芬太尼、右美托咪定静脉泵注,维持患者BIS 40～60。于依托咪酯TCI前即刻、TCI后1、3、5、10、20、30、60、90、120 min采集桡动脉血样,采用前期试验已验证的超高效液相色谱串联质谱(UPLC-MS/MS)法测定血浆依托咪酯浓度。分析计算TCI依托咪酯的系统性能评价指标,包括精确度、偏离度、摆动度和分散度。结果 TCI后1、3、10 min时,依托咪酯Cm均明显低于Cp(P0.05),依托咪酯总体血样Cm为0.42μg/ml,明显低于Cp 16%(P0.05)。输注期间TCI系统的偏离度为-15.9%,精确度为21.9%,摆动度为22.0%,分散度为-0.72%/h。结论 TCI依托咪酯恒定靶血浆浓度(Cp)0.5μg/ml时,内嵌Arden药代动力学参数TCI系统的偏离度和摆动度稍大,但系统分散度小,能维持稳定的血浆浓度,精确度在临床可接受范围内。     

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.     

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.