肝脏移植中门静脉机化血栓的外科对策

目的：探讨肝脏移植中门静脉机化皿栓的术中处理方法。方法：回顾分析我院41例肝移植门静脉机化血栓患者，22例在取栓后门静脉端端吻合，10例血栓段门静脉切除，8例门静脉与曲张内脏血管吻合，1例门腔半转位。结果：1例死于多脏器功能衰竭；1例死于肝动脉出血；1例术后门静脉血流不足，二次肝脏移植时缝扎分流的侧支后顺利康复；2例患者术后出现吻合口狭窄，均采用经皮肝穿刺门静脉支架置7、治愈，其余36例患者分别随访6～20个月，门静脉血流均保持通畅。结论：存在门静脉机化血栓的患者行肝脏移植，首选血栓段门静脉切除或取栓后门静脉重建，当不能进行时采用门静脉与曲张内脏静脉吻合可好效果。     

肝移植中门静脉-内脏曲张静脉吻合在门静脉机化血栓患者的应用

目的:探讨门静脉-内脏曲张静脉吻合在门静脉机化血栓患者肝移植中的应用。方法:对门静脉和肠系膜上静脉均完全被机化血栓阻塞的7例患者实施肝移植,其中3例供体门静脉-曲张冠状静脉吻合;2例髂静脉搭桥供体门静脉和脾门旁曲张的静脉吻合;1例采用供体门静脉-胆总管前曲张静脉吻合;1例供体门静脉—曲张的胃网膜右静脉吻合。结果:7例手术全部成功。1例术后7d死于多脏器功能衰竭,但是门静脉血流一直通畅。1例术后6个月发现吻合口狭窄,术后9个月采用经皮肝穿刺门静脉支架置入治愈;其余患者分别随访12～22个月,门静脉血流均通畅,无狭窄或血栓形成,肝、肾功能正常。结论:肝移植中对门静脉和肠系膜上静脉均完全被机化血栓阻塞的患者,行供体门静脉-曲张内脏静脉吻合可取得良好疗效。     

门静脉回流式肠道引流的同侧胰肾联合移植术四例

目的 改进门静脉回流式肠道引流的胰肾同侧联合移植术的动脉重建方法.方法 供者采用肝胰肾脾联合切取法,并切取供者髂血管备用.修整供者器官时,将肝总动脉与胃十二指肠动脉端端吻合,以重建胰十二指肠动脉弓;将髂总静脉与门静脉端端吻合,以延长门静脉1～2 cm;将髂外动脉与肠系膜上动脉和腹腔干共同的腹主动脉袖片行端端吻合,备用.胰腺移植时,将供者延长后的门静脉与受者肠系膜上静脉行端侧吻合,将供者髂总动脉及髂内动脉经末端同肠系膜打孔穿出后,供者髂总动脉与受者髂外动脉行端侧吻合,供者髂内动脉用血管夹暂时夹闭,准备与供肾动脉吻合.供者十二指肠与受者空肠用吻合器行侧侧吻合.肾移植时,将供肾静脉与受者髂外静脉行端侧吻合,肾动脉与夹闭备用的供者髂内动脉行端端吻合,开放肾血流后,将移植肾经切口置于右下腹部侧腹膜外同定,并在腹膜外吻合输尿管与膀胱.结果 除1例术后第50天时因腹腔感染导致多器官功能衰竭而死亡外,其他3例术后均恢复顺利.术后对3例存活患者随访了24～27个月,患者移植物功能良好,完全停用胰岛素,血清肌酐为72.5～119.7μmol/L.结论 门静脉回流式肠道引流的胰肾同侧联合移植术较传统术式操作简单,而十二指肠动脉弓的重建改善了胰腺及十二指肠的血液供应.术中利用供者髂总动脉搭桥,将供肾动脉吻合到供者髂内动脉的术式可以减少在受者严重钙化的周围血管上的操作次数,同时为患者保留了左侧髂动脉.     

活性供肝原位部分肝移植一例报告

对１例晚期肝癌伴肝硬变的患者施行活体供肝部分肝原位移植术，供者为受者之妻。供肝切取时不阻断血流，沿正中裂偏左２ｃｍ处切取左半肝。受者的肝全部切除，供受体的肝左静脉行端端吻合，供肝门静脉左支与受者的门静脉主干行端端吻全，供肝左动脉与受者的肝固有动脉在显微镜下行端端吻合，胆道用５ｍｍ硅胶管插入左肝管后行外引流。供肝热缺血时间为０，冷缺血时间为２．５小时。术后用环孢素Ａ与小剂量激素进行免疫抑制。供者术后     

应用供者髂动脉行腹主动脉搭桥重建移植肝动脉的临床分析

目的探讨应用供者髂动脉行腹主动脉搭桥重建移植肝动脉对肝移植受者预后的影响。 方法回顾性分析中国医科大学附属第一医院2006年1月至2018年4月应用供者髂动脉行腹主动脉搭桥重建肝动脉的肝移植受者临床资料,观察其术后肝功能恢复情况及肝动脉血栓等并发症的发生情况,分析采用搭桥方式进行移植肝动脉重建的原因。 结果共纳入8例受者,其中1例存在脾动脉盗血综合征导致肝总动脉供血不足,3例肝总动脉纤细,4例肝总动脉壁薄弱或分层。重建后肝动脉平均血流为(315±178)mL/min。术后2例受者分别因肝脏流出道和胆管吻合口狭窄导致黄疸,其余受者移植肝功能恢复良好。1例受者术后2个月出现肝动脉血栓形成,继发肝脓肿,半年后因多脏器功能衰竭死亡。其余7例受者随访至2018年11月均存活,肝动脉均通畅,无狭窄或血栓形成。 结论当供、受者常规肝动脉端端吻合无法实施时,应用供者髂动脉行腹主动脉搭桥重建移植肝动脉是一种可行的肝动脉重建方法。     

活体右半肝移植的流出道重建21例

目的 探讨活体右半肝移植中的流出道重建技术,预防肝静脉淤血的发生.方法 回顾分析21例成人活体右半肝移植的临床资料.供者标准肝体积为1150.1～1629.8 cm3,供肝重量为585～920 g,与受者标准肝体积比为43%～67%,与受者重量比为0.82%～1.59%,供者残肝体积百分比为32%～55%,供肝大泡脂肪变性均＜10%.对于含肝中静脉的供肝,将肝中静脉和肝右静脉开口修整成尽可能大的三角形开口,供肝植入时,与受者肝右静脉扩大的三角形开口行端侧吻合.不含肝中静脉的供肝,如存在粗大的肝中静脉属支(直径超过5 mm),则用自体或异体血管搭桥(无粗大的肝中静脉属支者采用肝右静脉)与受者腔静脉直接吻合.供肝门静脉右支直接与受者门静脉主干吻合,供肝动脉与受者肝动脉行端端吻合,供肝右肝管与受者肝管行端端吻合.结果 21例供肝中,4例含肝中静脉,17例不含肝中静脉,其中有2例采用自体大隐静脉搭桥,5例采用冷冻的异体髂动脉搭桥,10例采用肝右静脉直接与受者腔静脉吻合.术后1个月,重建肝中静脉属支的7例受者流出道均通畅.含肝中静脉者、不含肝中静脉的血管搭桥者及不含肝中静脉且未使用血管搭桥者术后1年存活率分别为75%、85.7%和70%,三者间比较,差异均无统计学意义(P＞0.05).术后受者发生胆道并发症7例;发生小肝综合征1例,经脾动脉栓塞治疗后痊愈.术后供者未发生严重并发症,随访6～31个月,均恢复正常工作生活,无一例死亡.结论 含肝中静脉与不含肝中静脉的右半供肝植入后均可取得良好的临床效果.如果右半供肝不含肝中静脉,采用自体或异体血管重建肝中静脉属支是预防肝淤血和保证移植肝功能的有效方法.     

活体右半供肝Ⅴ和Ⅷ段静脉回流的重建方法

目的 总结活体右半供肝移植中,不含肝中静脉的右半供肝Ⅴ、Ⅷ段静脉回流的重建方法.方法 回顾性分析55例活体右半供肝移植中,不含肝中静脉的右半供肝Ⅴ、Ⅷ段静脉回流重建的临床资料.所有供者均通过了受者标准肝体积、供肝与受者体重比(GRWR)、供肝与受者标准肝体积比及供肝内血管解剖等指标的综合评估.供肝在切取、灌注及修整后,51例采用尸体髂静脉作为重建材料,其他4例分别采用受者的大隐静脉、曲张的脐静脉、肝内门静脉和肝静脉作为重建材料,以串联的方式重建供肝断面Ⅴ、Ⅷ段静脉回流.肝移植时,供肝肝右静脉与受者肝右静脉开口吻合,重建的Ⅴ、Ⅷ段静脉与受者肝中、肝左静脉汇合部吻合,供肝门静脉与受者门静脉右支或主干吻合.门静脉开放血流后依次重建肝动脉及胆道.术后对供、受者进行常规监测.结果 1例受者术后发生流出道梗阻,术后第43天死亡;1例受者术后第7天出现不明原因的急性重型肝组织坏死,行尸体供肝肝移植后痊愈.其余53例受者恢复顺利,术后4周时腹部CT检查显示重建的移植肝Ⅴ、Ⅷ段静脉回流通畅.55例供者术后均恢复顺利,术后2周出院.结论 不含肝中静脉的活体右半供肝Ⅴ、Ⅷ段静脉回流的重建在活体肝移植中是可行的,应选择合适的重建材料及手术方式.受者肝移植后临床效果良好.     

成人间活体右半肝移植术中变异门静脉右支切取与重建技术

目的 探讨成人间活体右半肝移植术中变异门静脉支(APVB)切取与重建的技巧.方法 2002年1月至2007年4月,共实施70例成人间活体右半肝移植.术前肝脏血管三维CT成像显示供肝动脉及静脉走向,70例右半供肝中有9例门静脉分支变异,其中7例为Ⅱ型变异,2例为Ⅲ型变异.除1例供者行狭窄桥状连接单口切取APVB外,其余8例均采用供者优先的原则即距门静脉主干2～3mm处双口切断APVB.Ⅱ型变异中有2例双口切取其右前、右后支成形为一个开口后与受者门静脉主干吻合,4例右前、右后支分别与受者门静脉左、右支吻合,1例行右前、右后支间狭窄桥状组织连接单口切取后与受者门静脉主干单口吻合.Ⅲ型变异中有1例双口切取其右前、右后支分别与受者门静脉支双口吻合,1例双口切取后行新型的U形血管移植物间置与受者门静脉主干单口吻合.结果 9例受者均无门静脉狭窄或血栓、肝动脉狭窄或血栓以及肝静脉流出道狭窄等血管并发症发生.1例供者术后3 d并发门静脉血栓,手术取栓及门静脉壁修补成形后痊愈.新型的U形血管移植物间置重建术后通畅,无并发症发生.结论 成人间活体右半肝移植术中采用供者优先的原则双口切取APVB、双口吻合重建以及新型的U形血管间置等门静脉重建技术是安全可行的,未增加手术难度,且临床效果良好.     

存在门静脉血栓及癌栓的肝癌患者的肝移植

目的　探讨存在门静脉血栓或癌栓的肝癌患者进行肝移植的处理要点。方法　对10例存在门静脉血栓或癌栓的肝癌患者施行原位肝移植术,术前常规准备供者的髂静脉,供肝保留较长的门静脉;术中注意取尽受者门静脉内的血栓或癌栓,门静脉壁存在水肿、增厚、变硬者,尽可能切除这段门静脉;9例行低位门静脉对端吻合,1例行门静脉下腔静脉的对端吻合;术后根据患者的凝血功能状态决定是否进行抗凝治疗。结果　1例术后第6 d发生门静脉血栓形成,溶栓术后因腹腔内出血、失血性休克死亡;另9例术后门静脉血流通畅,随访2~31个月,其中1例术后2个月死于感染,4例术后7、12、13、25个月肿瘤复发,其余4例无肿瘤复发。结论　术前存在门静脉血栓或癌栓的肝癌患者,只要处理得当,采用肝移植治疗可以取得较好结果。     

合并Ⅳ级门静脉血栓的肝移植六例报告

目的 探讨合并Ⅳ级门静脉血栓(PVT)者肝移植时门静脉重建的方法.方法 合并Ⅳ级PVT的乙型肝炎后肝硬化(失代偿期)患者6例,4例并发上消化道出血,1例并发肾功能不全,1例并发肾功能不全和肝性脑病.术前4例曾接受脾切除+门奇断流术,1例曾接受脾切除+门奇断流术+脾肾分流术+经颈静脉肝内门腔内支架分流术,1例曾接受脾切除术.术前均明确诊断为Ⅳ级PVT.6例均行经典非转流原位肝移植术.4例采取门静脉-内脏曲张静脉吻合重建门静脉,其中2例将门静脉与扩张的胃冠状静脉吻合,2例将门静脉与胆总管旁曲张静脉吻合.另2例采取门静脉动脉化重建门静脉,1例将结肠中动脉与供肝门静脉吻合,供肝肝动脉与受者的肝动脉吻合,另1例将供肝门静脉与受者的肝总动脉吻合,供肝肝动脉与受者的胃十二指肠动脉远端吻合.结果 采取内脏曲张静脉吻合重建门静脉者,术中检测门静脉血流量为(1258±345) ml/min,1例术后2个月死于腹腔感染,其余3例分别随访14、16和17个月,门静脉血流均保持通畅,无狭窄及血栓形成,肝功能正常,食管胃底静脉曲张有所减轻.采取门静脉动脉化重建者,术中检测门静脉血流量为(2275±247)ml/min,1例术后反复出现上消化道出血,术后47 d死于腹腔感染;另1例目前已随访33个月,肝肾功能良好,食道胃底静脉曲张程度加重.采取门静脉动脉化重建者各时间点的AST和ALT均优于采取内脏曲张静脉吻合重建者.结论 合并Ⅳ级PVT者肝移植时采用供肝门静脉-内脏曲张静脉吻合重建门静脉临床效果满意;门静脉动脉化重建门静脉通道有利于移植肝功能的早期恢复,但只能作为合并PVT者肝移植时的一种有效的补救措施.     

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.     

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.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.