右美托咪啶对重度颅脑损伤患者术后颅内压的影响

目的 探讨右美托咪啶对重度颅脑损伤患者术后颅内压(ICP)的影响.方法 急诊行开颅手术的重度颅脑损伤患者90例,性别不限,年龄19～64岁,ASA分级Ⅱ或Ⅲ级,格拉斯哥昏迷量表评分3～7分,采用随机数字表法,将患者随机分为3组(n=30):对照组(C组)和不同剂量右美托咪啶组(D1组和D2组).气管插管后,D1组或D2组分别静脉输注右美托咪啶0.3或0.7μg· kg-1 ·h-1,持续48 h.手术结束前,将微型传感器植入硬脑膜外,持续监测ICP,术后2d内若ICP≥30 mm Hg则静脉注射地塞米松0.2 mg/kg、甘露醇0.5 mg/kg和甘油果糖0.25 mg/kg.于麻醉诱导后(T0)、术后6 h(T1)、12 h(T2)、24 h(T3)时采集外周静脉血样,采用ELISA法测定血清IL-1β和TNF-α浓度;术后90 d采用格拉斯哥预后量表评分进行临床疗效分级;记录地塞米松、甘露醇和甘油果糖的用量.结果 与T0时比较,三组T1～T3时血清IL-1β和TNF-α浓度升高(P＜0.05);与C组比较,D1组和D2组T1～T3时血清IL-1β和TNF-α浓度、地塞米松、甘露醇、甘油果糖用量降低,临床疗效分级升高(P＜0.05);与D1组比较,D2组T1～T3时血清IL-1β和TNF-α浓度、地塞米松、甘露醇、甘油果糖用量降低,临床疗效分级升高(P＜0.05).结论 右美托咪啶可降低重度颅脑损伤患者术后ICP,有利于患者预后,且与剂量有关;其机制可能与降低TNF-α、IL-1β水平,抑制炎性反应有关.     

不同剂量右美托咪啶对单肺通气患者围术期炎性反应的影响

目的 探讨不同剂量右美托咪啶对单肺通气患者围术期炎性反应的影响.方法 择期行食管癌根治术患者36例,ASA分级Ⅰ或Ⅱ级,性别不限,年龄43～72岁,体重50～78 kg,采用随机数字表法,将其随机分为3组(n=12):对照组(C组)、低剂量右美托咪啶组(D1组)和高剂量右美托咪啶组(D2组).麻醉诱导前,D1组和D2组经10 min静脉输注右美托咪啶1 μg/kg,随后分别以0.2和0.5 μg·kg-1 ·h-1的速率输注至术毕前30 min,C组采用同样方法静脉输注等容量生理盐水.于麻醉诱导前(T0)、单肺通气前即刻(T1)、单肺通气30 min(T2)、90 min(T3)、膨肺后30 min(T4)和术后2 h(T5)时采集静脉血样,测定血清TNF-α、IL-8浓度.结果 与T0时比较,三组T3～T5时血清TNF-α、IL-8浓度升高(P＜0.05);与C组比较,D2组T3～T5时血清TNF-α、IL-8浓度降低(P＜0.05),D1组上述指标差异无统计学意义(P＞0.05).结论 麻醉诱导前给予右美托咪啶1 μg/kg,术中以0.5 μg·kg-1·h-1的速率输注可明显降低单肺通气患者围术期的炎性反应.     

不同剂量右美托咪定对妇科腹腔镜手术围术期炎症因子的影响

目的探讨不同剂量右美托咪定对妇科腹腔镜手术围术期炎症因子的影响。方法选择2012年1月至2013年12月择期妇科腹腔镜手术患者90例,按照随机数字表法将其分为高剂量右美托咪定组(D1组)、低剂量右美托咪定组(D2组)和对照组(C组),每组30例。D1组和D2组分别于麻醉诱导后持续静脉输注右美托咪定0.5和0.2μg·kg-1·h-1,C组则以等容量生理盐水代替。记录麻醉诱导前10 min(T1)、气管插管后1 min(T2)、气腹后1 min(T3)、术毕(T4)的MAP和HR,并检测血清TNF-α、IL-6、IL-10水平。结果与T1时比较,T2~T4时D2组和C组MAP明显升高,D1组HR明显减慢,T2、T3时C组HR明显增快(P0.05)。与C组比较,T2~T4时D1组和D2组MAP明显降低,HR明显减慢(P0.05)。与T1时比较,T2~T4时三组TNF-α、IL-6和IL-10水平明显升高(P0.05)。与C组比较,T2~T4时D1组和D2组TNF-α和IL-6水平明显降低,但D1组IL-10水平明显升高,T2、T3时D2组IL-10水平明显降低(P0.05)。结论持续输注右美托咪定可减轻妇科腹腔镜手术围术期炎症反应,且0.5μg·kg-1·h-1较0.2μg·kg-1·h-1更为明显。     

右美托咪定对食管癌根治术单肺通气患者肿瘤坏死因子-α和白细胞介素-6的影响

目的 观察右美托咪定对食管癌根治术单肺通气患者血浆肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平的影响.方法 60例拟行食管癌根治术的患者,随机分为D1组、D2组和C组,每组20例.D1组麻醉诱导前0.6μg/kg静脉泵注右美托咪定;D2组麻醉诱导后以0.3μg/(kg·h)静脉泵注右美托咪定;C组为对照组.分别测定麻醉诱导前20 min(T0),气管插管后10 min(T1),单肺通气30 min(T2),单肺通气90 min(T3)及再次双肺通气后10 min(T4)5个时间点血浆中TNF-α和IL-6浓度.结果 3组患者血浆TNF-α水平在T3、T4时点较T0高(P ＜0.05);D1组和D2组在T3(10.5±2.5,11.1 ±2.6)、T4(11.2±2.4,11.8±2.7)时点较C组增高(P＜0.05).3组患者血浆IL-6水平在T4时点较T0高(P ＜0.05);D1组和D2组在T4时点(23.2±3.3,23.9±3.2)较C组增高(P＜0.05).结论 术前静脉泵注0.6 μg/kg及术中持续以0.3μg,/(kg·h)静脉泵注右美托咪定均能抑制食管癌根治术单肺通气患者血浆中TNF-α和IL-6水平升高.     

右美托咪定对法洛四联症矫正术患儿心肌的保护效应

目的 评价右美托咪定对法洛四联症矫正术患儿心肌的保护效应.方法 择期体外循环下法洛四联症矫正术患儿40例,性别不限,年龄9个月～5岁,体重7～21 kg,ASA分级Ⅱ或Ⅲ级.采用随机数字表法,将其分为2组(n=20):对照组(C组)和右美托咪定组(D组).麻醉诱导气管插管后D组静脉输注右美托咪定0.6μg· kg-1 ·h-1至术毕,C组给予等容量生理盐水.分别于术前、术毕和术后24h取静脉血样,测定血浆TNF-α、IL-6的浓度.记录术中缺氧发作的发生情况.结果 与C组相比,D组术毕和术后24 h时血浆TNF-α、IL-6的浓度降低(P＜0.05);术中缺氧发作发生率D组为0而C组达20％.结论 对于体外循环下法洛四联症矫正术患儿,术中静脉输注右美托咪定0.6μg·kg-1 ·h-1可产生一定的心肌保护效应.     

右美托咪定对重症颅脑损伤患者围术期血浆S蛋白100B及炎性细胞因子的影响

目的观察全麻期间持续应用右美托咪定对重症颅脑损伤患者围术期血浆S蛋白100B(S-100B)、肿瘤坏死因子(TNF-α)及白细胞介素-6(IL-6)的影响。方法重症颅脑外伤患者40例,随机均分为右美托咪定组(D组)和对照组(C组)。两组分别于麻醉诱导前(T0)、气管插管即刻(T1)、术毕(T2)、术后1d(T3)及3d(T4)晨抽取静脉血,测定S-100B、TNF-α和IL-6水平,同时监测各时点血流动力学的变化情况。结果与T0时比较,T1～T4时D组HR明显减慢,MAP明显降低(P<0.05),T1、T2时C组HR明显增快,MAP明显升高(P<0.05),T3、T4时HR明显减慢,MAP明显降低(P<0.05);T1～T4时D组HR明显慢于C组,T1、T2时MAP明显低于C组(P<0.05)。与T0时比较,T4时D组血浆S-100B明显降低(P<0.05),T2、T3时C组S-100B明显升高(P<0.05)。T3、T4时C组血浆S-100B明显高于D组(P<0.05)。T1～T3时C组血清TNF-α和IL-6明显高于T0时和D组(P<0.05)。C组患者中1例因并发神经源性肺水肿死亡。结论全麻期间持续应用右美托咪定可减缓重症颅脑损伤患者围术期血浆S-100B、血清TNF-α和IL-6浓度的升高,维持血流动力学稳定,减少应激反应。     

右美托咪定对胃癌根治术患者围术期白细胞介素-6、皮质醇及T淋巴细胞亚群的影响

目的观察右美托咪定对胃癌根治术患者围术期白细胞介素-6(IL-6)、皮质醇(Cor)及T淋巴细胞亚群的影响。方法 40例择期全麻下行胃癌根治术患者,随机均分为右美托咪定组(D组)和对照组(C组)。两组分别于麻醉诱导时在15min内静脉泵入1μg/kg右美托咪定和等容量的生理盐水,随后持续静脉输注右美托咪定0.2～0.7μg·kg-1·h-1和生理盐水0.125ml·kg-1·h-1。检测麻醉诱导前(T0)、切皮前(T1)、手术1h(T2)、术毕(T3)、术后1d(T4)和术后3d(T5)血清IL-6、血浆Cor浓度及外周血T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+)水平。结果与T0时比较,C组T2～T4时血清IL-6和T2、T3时血浆Cor浓度升高(P<0.05);T1～T5时CD3+、CD4+、CD8+、CD4+/CD8+显著下降(P<0.05);D组血清IL-6及血浆Cor浓度无明显变化,T2和T3时CD3+、CD4+、CD8+、CD4+/CD8+显著上升(P<0.05)。结论全麻期间持续静脉输注右美托咪定可有效抑制胃癌根治术患者围术期的应激反应,减少细胞免疫功能的抑制。     

右美托咪定在颅脑肿瘤手术中的应用

目的探讨右美托咪定在丙泊酚复合芬太尼麻醉下行颅脑肿瘤手术中的优化作用。方法拟行择期手术的小脑幕上肿瘤患者42例,ASAⅠ或Ⅱ级,随机均分为两组。麻醉诱导前,右美托咪定组(D组)于20min内静脉输注右美托咪定负荷剂量1μg/kg,随后静脉输注0.4μg·kg-1·h-1维持至手术结束;对照组(C组)静脉输注等量生理盐水。以丙泊酚、芬太尼、顺阿曲库铵完成麻醉诱导,气管插管。术中以BIS为指导,七氟醚静吸复合维持麻醉。记录麻醉诱导前(T0)、气管插管时(T1)、打开硬脑膜(T2)、关上硬脑膜(T3)、拔除气管插管即刻(T4)时MAP、HR、颅内压(ICP)的变化。记录呼气末七氟醚浓度和术中芬太尼总量、手术时间、术后拔管时间、术后止吐药的使用情况。结果 T1~T3时C组ICP,T1~T4时MAP明显高于T0时和D组,T4时两组ICP明显低于T0时,且D组明显低于C组(P0.01);T1~T4时D组HR明显慢于T0时和C组(P0.01)。D组芬太尼总量、呼气末七氟醚浓度明显低于C组,拔管时间明显短于C组(P0.01)。D组血管活性药物使用率明显低于C组(P0.01)。结论在颅脑肿瘤手术中,右美托咪定在稳定血流动力学、控制颅内压及术后复苏方面显著优化了常用的丙泊酚复合芬太尼全麻方案,同时减少了阿片药物及吸入麻醉药物用量。     

右美托咪定对颅内肿瘤手术患者血流动力学的影响及脑保护作用

目的探讨右美托咪定对颅内肿瘤手术患者血流动力学的影响及对患者脑保护的作用。方法将60例择期行颅内肿瘤手术患者随机分为右美托咪定组和对照组,每组30例。右美托咪定组患者诱导后静脉注射右美托咪定1μg/kg,10min注射完毕,术中持续静脉泵注右美托咪定0.4μg·kg-1·h-1。对照组诱导后给予等量生理盐水。记录两组患者入室后(T0)、给药后(T1)、插管时(T2)、苏醒时(T3)、拔管时(T4)、出手术室(T5)的SBP、DBP、MAP及HR。并检测T0、手术完成(T6)、术后6h(T7)、术后12h(T8)和术后24h(T9)的血清S100β和NSE水平。结果与对照组比较,右美托咪定组T1~T5时SBP、DBP和MAP明显降低,HR明显减慢(P0.05)。与T0时比较,右美托咪定组T1~T5点MAP水平明显降低(P0.05)。与T0时比较,两组T6~T9时S100β和NSE水平明显增高(P0.05)。与对照组比较,右美托咪定组T6~T9时血清S100β和NSE水平明显降低(P0.05)。结论右美托咪定可较好维持颅内肿瘤患者术中血流动力学的稳定,术中、术后24h内S100β和NSE水平较低。     

右美托咪定、地佐辛单独或复合用药对开胸术患者苏醒期躁动的影响

目的 评价右美托咪定、地佐辛单独或复合用药对开胸术患者苏醒期躁动的影响.方法 择期拟行开胸术患者80例,ASA分级Ⅰ或Ⅱ级,年龄18～64岁,体重48～75 kg,采用随机数字表法,将其分为4组(n=20):对照组(C组)、右美托咪定组(DEX组)、地佐辛组(DEZ组)和右美托咪定+地佐辛组(DEX+ DEZ组).DEX组于麻醉诱导前15 min时静脉注射右美托咪定0.5 μg/kg,继静脉输注0.4 μg·kg-1·h-1至关胸开始,DEZ组于关胸开始静脉注射地佐辛0.1 mg/kg,DEX+ DEZ组于麻醉诱导前15 min时静脉注射右美托咪定0.5 μg/kg,继静脉输注0.4 μg· kg-1 ·h-1至关胸开始,静脉注射地佐辛0ˉ1 mg/kg,C组麻醉诱导前15 min开始至关胸开始时给予等容量生理盐水.每组缝皮开始时静脉注射氟比洛芬酯50 mg.分别于麻醉诱导前10 min (T1)、关胸完毕缝皮前(T2)、拔除气管导管即刻(T3)、拔除气管导管后15 min(T4)时抽取肘静脉血样,采用ELISA法测定血浆C-反应蛋白(CRP)、TNF-α和IL-10的浓度,记录患者苏醒期躁动等不良反应的发生情况,采用Ramsay评分评价镇静程度.结果 与C组比较,DEX组、DEZ组和DEX+ DEZ组T2-4时血浆CRP、TNF-α浓度降低,IL-10浓度升高,TNF-α/IL-10比值降低,躁动程度及发生率降低,镇静评分升高(P＜0.05);与DEX组和DEZ组比较,DEX+ DEZ组T2-4时血浆CRP、TNF-α浓度降低,IL-10浓度升高,TNF-α/IL-10比值降低,躁动程度及发生率降低(P＜0.05).四组患者苏醒期均无低血压、心动过缓、呼吸抑制、恶心呕吐等发生.结论 右美托咪定、地佐辛单独或复合用药均可降低开胸术患者苏醒期躁动程度及发生,同时可抑制炎性反应,且二者复合较单独用药效果更佳.     

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 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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

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.     

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.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.