七氟醚预处理对急性心肌缺血再灌注损伤大鼠认知功能的影响

目的 探讨七氟醚预处理对急性心肌缺血再灌注损伤大鼠认知功能的影响.方法 健康SD大鼠60只,雌雄各半,体重300～350 g,随机分为4组:正常对照组(C组,n=6),假手术组(S组,n=18)仅挂线不结扎左冠状动脉;急性心肌缺血再灌注组(IR组,n=18)结扎左冠状动脉30 min后恢复再灌注;七氟醚预处理组(SP组,n=18)吸入七氟醚1.0 MAC 60 min,停止吸入七氟醚后60 min结扎左冠状动脉,缺血30 min后恢复再灌注.分别于左冠状动脉结扎前(T1)、缺血30 min(T2)及再灌注120 min(T3)时抽取股动脉血1 ml,测定血浆丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性.C组随机取3只大鼠,其余各组于再灌注1、3、7 d各随机取3只大鼠测定海马长时程增强(LTP),C组取另外3只大鼠,其余各组于上述时点随机取3只大鼠,测定海马肿瘤坏死因子α(TNF-α)、TNF-α mRNA、白细胞介素1β(IL-1β)、IL-1β mRNA、血红素氧合酶(HO)-1的表达水平.结果 与C组和S组比较,IR组和SP组LTP降低;与IR组比较,SP组LTP升高(P＜0.05).与C组比较,IR组和SP组HO-1、IL-1β mRNA、IL-1β、TNF-α mRNA表达上调;与S组比较,IR组和SP组IL-1β mRNA及IL-1β表达上调;与IR组比较,SP组TNF-α mRNA、HO-1、IL-1β mRNA及IL-1β表达下调,血浆MDA浓度降低,SOD活性升高(P＜0.05).结论 七氟醚预处理可改善急性心肌缺血再灌注损伤大鼠认知功能,其机制可能与下调TNF-α、IL-1β表达有关.     

七氟醚和异丙酚对骨科手术患者止血带诱发肢体缺血再灌注损伤影响的比较

目的 比较七氟醚和异丙酚对骨科手术患者止血带诱发肢体缺血再灌注损伤的影响.方法 择期行膝关节韧带修复术患者54例,性别不限,年龄18～64岁,体重44 ～ 85 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将患者随机分为3组(n=18)∶对照组(C组)、异丙酚组(P组)和七氟醚组(S组).行腰丛联合坐骨神经阻滞后,P组静脉注射异丙酚2 ～4 mg/kg麻醉诱导,并置入喉罩,术中静脉输注异丙酚2～4 mg·kg-1·h-1维持麻醉.S组吸入8％七氟醚麻醉诱导,并置入喉罩,术中吸入2％七氟醚维持麻醉.异丙酚或七氟醚给药15 ～ 20 min时,C组于相应时点,应用止血带,充气压力为300mm Hg,术毕时放气.术后口服美洛昔康或肌肉注射哌替啶镇痛,维持VAS评分＜3分.分别于入室后(T1)和止血带放气后30 min (T2)时采集血样,测定血浆MDA和TNF-α浓度,计算其增长率.术后记录止血带相关不良事件的发生情况和术后24 h内镇痛药用量.结果 患者均未见止血带相关不良事件发生.与C组比较,P组和S组T2时血浆MDA和TNF-α浓度及其增长率降低(P＜0.05)；与P组比较,S组血浆MDA和TNF-α浓度及其增长率差异无统计学意义(P＞0.05)；与T1时比较,P组和S组T2时血浆MDA和TNF-α浓度差异无统计学意义(P＞0.05),C组明显升高(P＜0.05)；3组患者术后24 h内镇痛药用量比较差异均无统计学意义(P＞0.05).结论 七氟醚和异丙酚均可减轻骨科手术患者止血带诱发下肢缺血再灌注损伤,其效果无差异.     

安氟醚、异氟醚对大鼠肺组织NF-κB和血浆TNF-α的影响

目的比较安氟醚、异氟醚对大鼠肺组织核因子-κB(NF-κB)和血浆肿瘤坏死因子α(TNF-α)的影响。方法选用72只SD大鼠随机均分为安氟醚组(E组)和异氟醚组(I组)。两种麻醉药吸入浓度均为1.0 MAC。分别于麻醉前(T1)、麻醉诱导后即刻(T2)、麻醉2 h(T3)、4 h(T4)、6 h(T5)和停药2 h(T6)各处死6只大鼠,开胸取肺组织并经左心室取血5 ml。光镜下观察肺组织病理形态的改变。结果两组在T4时可见少量中性粒细胞及肺巨噬细胞渗出,其后明显增多,可见肺毛细血管轻度扩张、充血及肺间质水肿。与T1时比较,E组在T4~T6时肺组织NF-κB的含量增加(P<0.05),I组在T4、T5时增加(P<0.05)。T4~T6时,E组肺组织NF-κB的含量和血浆TNF-α的浓度均明显高于I组(P<0.05)。与T1时比较,两组TNF-α在T2时降低(P<0.05),其后增加(P<0.05)。结论吸入安氟醚、异氟醚后血浆TNF-α的含量增加,尤以吸入安氟醚更为明显。其作用机制可能与吸入安氟醚、异氟醚后肺组织NF-κB的表达增强有关。     

异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响

目的 探讨异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响.方法 成年雄性SD大鼠24只,体重180～220 g,随机分为3组(n=8):假手术组(S组)吸人纯氧30 min,间隔30 min后仅开腹;肝脏缺血再灌注组(IR组)吸入纯氧30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h;异氟醚预处理组(Iso组)吸入1.4%异氟醚30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h.于再灌注4 h时处死大鼠,留取肝脏及腹主动脉血5ml.测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)浓度,血清及肝组织匀浆上清液中肿瘤坏死因子α(TNF-α)的浓度,肝组织髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,观察肝组织病理学改变.结果 与S组比较,IR组、Iso组血清ALT、AST和TNF-α水平明显升高,肝组织TNF-α含量升高,肝组织MPO活性升高,MDA含量升高,SOD活性降低(P＜0.05或0.01),肝组织病理损伤明显;与IR组比较,Iso组血清ALT、AST和TNF-α水平降低,肝组织TNF-α含量降低,肝组织MPO活性降低,MDA含量降低,SOD活性升高(P＜0.05或0.01),肝组织病理损伤程度减轻.结论 1.4%异氟醚预处理可明显减轻大鼠肝脏缺血再灌注损伤,其机制可能与抑制TNF-α的释放、减少中性粒细胞在肝组织的浸润有关.     

毒扁豆碱对异氟醚麻醉大鼠炎性反应和认知功能的影响

目的探讨毒扁豆碱对异氟醚麻醉大鼠认知功能的影响及其机制。方法 2月龄SD大鼠80只,随机分为四组,每组20只。对照组(C组)吸入含有30%氧气的空氧混合气体6h;异氟醚组(I组)吸入1.4%的异氟醚6h;毒扁豆碱+异氟醚组(PI组)与毒扁豆碱组(P组)腹腔注射毒扁豆碱100μg/kg,每8小时一次,共3次。首次给药后,PI组吸入1.4%异氟醚6h;P组吸入同浓度载气6h。麻醉结束行动脉血气分析,12h后取海马组织,ELISA法检测TNF-α、IL-1β、IL-6含量,RTPCR法检测capase-3mRNA的表达。光镜下观察海马CA1区锥体细胞形态学变化。麻醉后第2~7天评估认知功能。结果四组大鼠动脉血气指标、血糖和海马TNF-α含量差异均无统计学意义。与C组和P组比较,I组和PI组大鼠海马IL-1β、IL-6含量、capase-3mRNA明显升高,第4~6天逃避潜伏期明显延长,探索时间明显缩短(P0.05)。与I组比较,PI组大鼠海马IL-1β、IL-6含量、caspase-3mRNA表达明显降低,第4~6天逃避潜伏期明显缩短,探索时间明显延长(P0.05)。结论毒扁豆碱改善了异氟醚麻醉引起的大鼠认知功能损害,其机制可能与抑制海马炎性反应及神经元凋亡有关。     

七氟醚对在体大鼠肺缺血-再灌注损伤的影响

目的研究七氟醚对在体大鼠肺缺血-再灌注(I-R)损伤的影响。方法40只Wistar大鼠建立在体大鼠肺I-R模型,随机分为四组,每组10只:A组,假手术组,开胸后机械通气120 min;B组,I-R组,阻断左肺门60 min,开放再通气60 min;C组,七氟醚加I-R组,缺血前吸入1 MAC七氟醚30 min,开放再通气同时吸入1 MAC七氟醚60 min;D组,七氟醚组,持续吸入1 MAC七氟醚120min。观察各组实验结束时肺组织的湿/干重比(W/D)、肺丙二醛(MDA)、超氧化物歧化酶(SOD)和肺组织病理学的改变。结果B组及C组肺W/D较A组和D组显著升高(P<0.01,P<0.05),SOD含量显著低于A组和D组(P<0.05);B组肺MDA含量较A组和D组显著升高(P<0.01),C组肺MDA含量较B组低(P<0.05);C组肺W/D、肺MDA显著低于B组(P<0.05),SOD高于B组(P<0.05);病理切片见B组、C组部分肺泡结构破坏,肺泡间隔增宽,肺泡腔内水肿并有出血,以B组改变较为严重,炎症积分显著高于C组(P<0.01)。结论七氟醚对在体大鼠肺I-R损伤有一定的保护作用。     

异氟醚对大鼠缺血-再灌注损伤肝脏细胞黏附分子-1表达及中性粒细胞浸润的影响

目的 观察常温下异氟醚麻醉对大鼠部分肝脏缺血--再灌注(IR)损伤的影响,探讨异氟醚抗炎作用参与减轻肝脏IR损伤的可能机制.方法 雌性SD大鼠32只,随机均分为四组,A组,大鼠行腹腔注射1%戊巴比妥钠40mg/kg麻醉,进行手术但不阻断入肝血流;B组,1%戊巴比妥钠麻醉后行部分肝脏IR;C组,大鼠仅接受1.0 MAC异氟醚吸入麻醉,不阻断血流;D组,采用1.0 MAC异氟醚麻醉,并建立肝脏IR模型.肝脏IR损伤模型通过夹闭肝动脉和门静脉左支(支配肝左叶和中叶)建立,造成约70%肝脏缺血60min,再灌注3h,立刻取肝组织和血液标本.检测血清丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)、肝组织内髓过氧化物酶(MPO)活性、肝组织细胞间黏附分子(ICAM-1)表达及肿瘤坏死因子α(TNF-α) mRNA转录水平,并进行HE染色行病理学检查.结果 B组血清ALT、AST水平和ICAM-1的表达、MPO活性明显高于A、C、D组(P<0.05),而D组明显高于A、C组(P<0.05);抑制肝脏再灌注后ICANI-1的表达以及MPO的活性(P<0.05).结论 异氟醚麻醉减轻肝脏IR损伤,可能与抑制ICANI-1和减少中性粒细胞(PMN)浸润有关.     

脾切除术对大鼠海马tau表达的影响

目的 评价脾切除术对大鼠海马tau表达的影响.方法 SD大鼠105只,随机分为3组,正常对照组(A组,n=15)不给予任何处理,麻醉组(B组,n=45)仅吸入1.5%异氟醚2 h,手术+麻醉组(C组,n=45)吸入1.5%异氟醚(吸入2 h)麻醉下实施脾切除术.B组和C组分别于麻醉后或术后1、3、7 d时处死15只大鼠,取海马组织,测定海马IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、苏氨酸第205位点磷酸化tau(pT205 tau)、丝氨酸第396位点磷酸化tau(pS396 tau)、总糖原合成酶-3β(GSK-3β)和磷酸化GSK-3β(p-GSK-3β)的表达水平.结果 与A组比较,B组各时点IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、pT205 tau、pS396 tau、GSK-3β和p-GSK-3β的表达水平差异无统计学意义(P＞0.05),C组术后IL-1βmRNA、TNF-α mRNA、IL-1β、pT205 tau和pS396 tau的表达上调,p-GSK-3β表达下调(P＜0.05或0.01).结论 手术创伤可导致大鼠海马tau磷酸化,其机制与手术创伤诱发炎性反应,从而激活GSK-3β有关.     

异丙酚异氟醚静吸复合麻醉法与氯胺酮静脉麻醉在小儿手术中的比较

本文通过对异丙酚异氟醚静吸复合麻醉与传统的氯胺酮静脉麻醉这两种小儿手术中的复合麻醉法的比较,探讨怎么样更有效和安全的对小儿手术进行麻醉.方法:200例小儿外科病儿用异丙酚异氟醚静吸复合麻醉法(PI组=100)和氯胺酮静脉麻醉法(KT组=100),P1组用异丙酚2mg/kg静脉注射至患儿入睡后,再通过回路或加压面罩半开放吸入吸氧和异氟醚至手术结束.KT组用咪唑安定0.1-0.2 mg/kg,氯胺酮1-2mg/kg缓慢静脉注射至患儿睡后,再以0.1％的氯胺酮液,术中维持直至术毕前10分钟停掉.通过对麻醉时间,麻醉的苏醒时间,循环,小儿的呼吸,以及在小儿手术中以及手术后的副作用和并发症的对比,得出结论:异丙酚异氟醚静吸复合麻醉法的麻醉时间和氯胺酮静脉麻醉法麻醉时间相似.异丙酚异氟醚静吸复合麻醉法的苏醒时间明显短于氯胺酮静脉麻醉法的苏醒时间.异丙酚异氟醚静吸复合麻醉法的呼吸抑制比较明显,异丙酚异氟醚静吸复合麻醉法在麻醉期间的血压,心率明显比氯胺酮静脉麻醉法低.所以异丙酚异氟醚静吸复合麻醉法更适合应用在小儿手术中,它的安全性高,而且在小儿手术中和手术后的不良反应小,并发症少.     

氯化锂预先给药对异氟醚麻醉诱发老龄大鼠认知功能障碍及海马炎性反应的影响

目的 评价氯化锂(LiCl)预先给药对异氟醚麻醉诱发老龄大鼠认知功能障碍及海马炎性反应的影响.方法 老龄雄性SD大鼠80只,20月龄,体重350 ～400g,采用随机数字表法,将大鼠随机分为4组(n=20):对照组(C组)吸入30％O2-70％ N26h;异氟醚麻醉组(I组)吸入1.4％异氟醚6h,以30％O2-70％N2作为载气;LiCl+异氟醚麻醉组(L+I组)腹腔注射LiC1 100 mg/kg,1次/d,连续3d,第4d行异氟醚麻醉;LiCl组(L组)腹腔注射LiCl 100 mg/kg,1次/d,连续3d,第4d吸入30％ O2-70％ N26h.麻醉结束即刻行动脉血气分析,麻醉结束后24h取海马组织,采用Western blot法测定海马糖原合成酶激酶-3β(GSK-3β)和核因子κB第310赖氨酸乙酰化蛋白[acetyl-NF-κB (Lys310)]的表达,采用实时定量PCR和ELISA法分别检测海马TNF-α、IL1β和IL-6的mRNA表达及其含量;麻醉结束后第2d评估认知功能.结果 与C组比较,I组GSK-3β和acetyl-NF-κB (Lys310)表达上调,TNF-α、IL-1β及IL-6含量及其mRNA表达水平升高,逃避潜伏期延长,探索时间缩短(P＜0.05),L+I组和L组上述指标差异无统计学意义(P＞0.05);与I组比较,L+I组GSK-3β、acetyl-NF-κB (Lys310)表达下调,TNF-α、IL-1β、IL-6含量及其mRNA表达水平降低,逃避潜伏期缩短,探索时间延长(P＜0.05).结论 氯化锂预先给药可改善异氟醚麻醉诱发老龄大鼠认知功能障碍,其机制与抑制海马炎性反应有关.     

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.     

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.