基于三柱结构的股骨头坏死分型——中日友好医院分型

 目的 通过分析非创伤性股骨头坏死的进展规律, 创建新的股骨头坏死分型方法。方法 基于Herring 对Legg-Perthes 病的三柱概念, 将冠状面股骨头分为内侧柱、中央柱及外侧柱, 选择MR 检查T1WI 冠状位正中层面图像, 依据坏死灶占据三柱结构的位置, 建立中日友好医院(China-Japan Friendship Hospital, CJFH)股骨头坏死分型体系。依据此分型方法及日本骨坏死研究会(Japanese Investigation Committee, JIC)分型分别对严重急性呼吸综合征患者的股骨头坏死(153 髋)进行分型, 统计其自然转归, 比较两种分型方法的坏死塌陷率。结果 CJFH分型: 内侧型(A 型), 坏死灶累及内侧柱;中央型(B 型), 坏死灶累及中央柱和内侧柱;外侧型(C 型): 凡累及外侧柱的坏死。依据坏死灶累及外侧柱的不同位置将外侧型分为次外侧型(C1 型)、极外侧型(C2 型)及全股骨头型(C3 型)。股骨头坏死患者自然进展显示, 两种分型方法的A、B、C三型股骨头塌陷率不同;CJFH分型C3 型塌陷率94.4%, C2 型塌陷率100%, 均高于C1 型42.6%;CJFH分型C2、C3 型合并塌陷率95.3%, 高于JIC 分型C2 型塌陷率72.3%。差异均有统计学意义。结论 CJFH 分型C2、C3 型预测股骨头塌陷的敏感性高于JIC 分型C2 型。基于三柱结构的CJFH 分型对股骨头坏死预后的预测准确性高, 应用简便。     

儿童及青少年股骨颈骨折后股骨头坏死影像学特征与疾病进展的关系

目的分析儿童及青少年股骨颈骨折后股骨头坏死的影像学特点及其与疾病进展的关系。方法收集广州中医药大学第一附属医院治疗的58例儿童及青少年股骨颈骨折后股骨头坏死患者影像学资料。研究对象的入选标准包括:年龄小于18岁的儿童及青少年;明确股骨颈骨折病史;符合股骨头坏死诊断标准。排除标准包括:大剂量激素使用史或酗酒史;诊断Legg-Calve-Perthes病、戈谢氏病、镰状细胞性贫血症、先天性髋关节发育不良、类风湿性关节炎、强直性脊柱炎、股骨颈骨折骨不连、术后感染;已接受针对股骨头坏死治疗,或影像资料不完整的患者。其中男性38例,女性20例,平均年龄(14.7±2.9)岁,均为单侧坏死(左侧31例,右侧27例)。通过Steinberg分期评估疾病进展,Spearman相关性检验或Fisher精确检验分析坏死面积、日本厚生省骨坏死研究会(JIC)分型以及蛙位分型等影像学特点与疾病进展的关系。结果初次就诊时,根据Steinberg分期,Ⅰ期3例(5.2%),Ⅱ期21例(36.2%),Ⅲ期5例(8.6%),Ⅳ期25例(43.1%),Ⅴ期4例(6.9%)。Steinberg分期与坏死面积(r=0.5,P0.01)、JIC分型(r=0.5,P0.01)以及蛙位分型(r=0.5,P0.01)呈正相关。在已塌陷的29例患者中,19例出现髋关节失稳,表现为严重塌陷后头臼不匹配、关节半脱位。蛙位C2型失稳率为90.0%(18/20),蛙位C1型为11.1%(1/9),其差异具有统计学意义(P0.01);正位C2型失稳率为68.0%(17/25),正位C1型为50%(2/4),其差异无统计学意义(P0.05)。结论儿童及青少年股骨颈骨折后股骨头坏死塌陷风险极高,严重塌陷可导致髋关节失稳,尤其多见于蛙位C2型坏死。     

股骨头坏死的塌陷预测

目的比较坏死面积比例和坏死指数在股骨头坏死塌陷预测中的价值。方法根据27例(38髋)早期股骨头坏死患的MRI图像表现，分别计算坏死面积比例和坏死指数，并进行随访。未塌陷随访24个月以上。结果在38髋早期坏死股骨头中，有28髋塌陷(73．7％)，10髋未发生塌陷(26．3％)。坏死面积比例的相对危险度为1．043，P=0．000。坏死指数的相对危险度为1．020，P=0．000。结论坏死面积比例和坏死指数均可以用于股骨头坏死的塌陷预测，坏死面积比例较坏死指数更准确。     

股骨头髓芯减压带旋髂深血管蒂髂骨骨瓣植骨治疗股骨头缺血性坏死

目的　探讨股骨头髓心减压带旋髂深血管蒂髂骨骨瓣植骨术治疗股骨头缺血坏死的疗效及手术适应证。　方法　 1995年 10月～ 2 0 0 0年 8月共进行 18例 (2 6髋 )股骨头髓心减压带旋髂深血管蒂髂骨骨瓣植骨术。根据Harris髋关节评分系统进行关节功能评价 ,根据ARCO分期分型系统进行影像学评价。　结果　随访 16例 2 3髋 ,平均 3 1 5个月。Harris评分由术前平均 61 7改善为随访时 76 0分。 13髋 (5 6% )随访时Harris评分 >80 0分 (内侧型 8髋 ,中央型 3髋 ,外侧型 2髋 ) ,根据ARCO分期分型系统进行分类随访时优良率 ,内侧型 80 % ,中央型 60 % ,外侧型 2 5 %。 8髋分期发生进展。塌陷及失败率内侧型 2 0 % ,中央型 40 % ,外侧型 75 %。　结论　股骨头髓芯减压带旋髂深血管蒂髂骨骨瓣植骨术适用于ARCO分期分型系统中ⅠA中央型、ⅠB内侧型、ⅡA中央型、ⅡB内侧型股骨头缺血性坏死 ,并具有良好的近、中期疗效。对坏死范围较大的股骨头不能防止病程的进展 ,但可缓解症状 ,延缓全髋关节置换的时间     

坏死面积比例在预测股骨头塌陷中的价值

目的探讨股骨头的坏死面积比例在预测股骨头塌陷中的价值。方法测量9例(15髋)股骨头坏死标本的坏死面积比例,同时根据MRI计算该9例患者的坏死面积比例,两者进行比较。对8例(16髋)行2次及以上MR检查的患者进行研究,比较第一、二次MRI上股骨头坏死面积比例的相关性。两次MR检查间隔平均18.9个月。根据27例(38髋)早期股骨头坏死患者的MRI表现,计算坏死面积比例及坏死指数,并进行随访。对发生坏死塌陷的股骨头的坏死面积比例和坏死指数进行计算。结果标本和MRI上的坏死面积比例为63.23%±10.16%和63.60%±7.78%,两者比较差异无统计学意义,表明通过MRI计算出的坏死面积比例与标本测量所得的坏死面积比例一致。第一、二次MRI上的坏死面积比例分别为52.37%±19.91%和51.70%±21.29%,两者比较差异无统计学意义,表明股骨头的坏死面积比例不随病程的延长而变化。在38髋早期坏死的股骨头中,有28髋塌陷,10髋未塌陷,塌陷与未塌陷患者的ARCO分期比较差异无统计学意义,表明缺血性坏死的股骨头是否塌陷与其分期无关。坏死面积比例与坏死指数的相对危险度为1.043和1.020,表明坏死面积比例更能准确预测缺血性坏死的股骨头是否塌陷。结论股骨头的坏死面积比例可以较准确地预测缺血性坏死的股骨头是否塌陷。     

基于中日友好医院分型的股骨头坏死保髋手术疗效的影响因素分析

目的探讨基于中日友好医院(China-Japan Friendship Hospital,CJFH)分型的保髋手术疗效的影响因素。方法2012年6月至2016年9月接受保髋手术治疗的非创伤性股骨头坏死患者325例432髋。依据CJFH分型行髓芯减压自体骨髓单个核细胞移植141髋(髓芯减压组)和头颈部开窗减压病灶清除植骨术291髋(开窗减压组)。采用Harris髋关节功能评分评估临床疗效,摄X线片观察坏死修复、股骨头塌陷及关节退变。临床失败定义为末次随访时Harris评分较术前评级降低和(或)影像学上股骨头塌陷进展(ARCO分期增加)。终点事件为疼痛明显加重、Harris评分为差(<70分)和(或)股骨头进行性塌陷。采用Cox比例回归模型分析临床失败的危险因素。结果髓芯减压组67髋临床失败(47.5%,67/141),其中CJFH分型C+M型3髋(13.0%,3/23)、L1型24髋(38.1%,24/63)、L2型14髋(82.4%,14/17)、L3型26髋(68.4%,26/38)。开窗减压组106髋临床失败(36.4%,106/291),C+M型1髋(33.3%,1/3)、L1型41髋(31.3%,41/131)、L2型22髋(84.6%,22/26)、L3型42髋(32.1%,42/131)。髓芯减压组中不同年龄(χ2=3.887,P=0.049)、不同术前CJFH分型(χ2=40.943,P=0.000)的临床失败率的差异有统计学意义;Cox回归模型分析显示年龄≥40岁[HR=2.325,95%CI(1.398,3.866),P=0.000]、术前Harris评分70~80分[HR=2.163,95%CI(1.140,4.105),P=0.018]和<70分[HR=2.597,95%CI(1.173,5.749),P=0.019]、术前CJFH分型L2型[HR=35.052,95%CI(7.721,159.133),P=0.000)和L3型[HR=13.242,95%CI(3.104,56.491),P=0.000]是临床失败的危险因素。开窗减压组中不同年龄(χ2=8.437,P=0.004)、不同术前Harris评分(χ2=19.737,P=0.000)、不同术前CJFH分型(χ2=29.265,P=0.000)的临床失败率的差异有统计学意义;Cox回归模型分析显示术前Harris评分<70分[HR=5.102,95%CI(2.339,11.129),P=0.000]、术前CJFH分型L2型[HR=32.761,95%CI(6.165,43.507),P=0.000]是临床失败的危险因素。结论股骨头坏死保髋手术治疗效果受年龄、术前Harris评分和CJFH分型的影响;术前临床症状越明显,受累股骨头负重关节面及外侧柱支撑结构未得到有效重建,保髋手术的预后越差。     

SARS后双侧股骨头坏死进展前瞻性分析

目的通过对SARS患者随访,了解应用激素后双侧股骨头坏死的发生发展状况,观察股骨头坏死的影象学变化。方法自2003年7月～2008年7月对北京市的使用激素治疗的539例SARS患者进行了随访,全部患者在开始使用激素后2～6个月行双髋MRI检查、X线摄片以及体格检查等,检出后定期行坏死关节的X线摄片及CT扫描,如出现关节疼痛等则及时摄片观察。股骨头坏死按照ARCO国际骨循环协会分期,III期作为观察终点。结果 539例应用激素者检出骨坏死176例(32.7%),其中累及股骨头为130例,双侧股骨头骨坏死86例;病例占股骨头坏死的66.2%。73例得到连续随访。目前进入III期为6～46个月,73例146髋中塌陷27髋,23髋为IIC期进展,4髋为IIB期进展;双侧塌陷4例。负重面外侧型(49髋)塌陷23髋,负重面中央型(61髋)塌陷4髋,负重面内侧型(36髋)无塌陷。早期MRIT1中低信号带的形态:开放型-开放型27例,塌陷12例16髋;开放型-包含型25例,开放型塌陷9例9髋,包含型塌陷2例2髋;包含型-包含型21例,无塌陷髋。开放型塌陷比例为25/79;包含型塌陷比例为2/67。结论坏死灶的大小位置影响双侧股骨头坏死的预后;坏死灶上负重面外侧型更易早塌陷;对于双侧股骨头坏死的病例,MRI显示相似的面积,T1低信号带包含型者,预后相对较好;CT显示软骨下骨均匀增厚或明显的"焊接"现象是延迟塌陷的因素;但是软骨下骨没有或有不均匀(不连续)硬化是危险因素。     

钽棒置入治疗早期股骨头坏死近期疗效分析

目的:探讨钽棒置入治疗早期股骨头坏死的近期临床疗效。方法:回顾分析2008年1月至2008年11月接受钽棒置入术治疗且随访资料完整的早期股骨头坏死患者25例(39髋),男9例(11髋),女16例(28髋);年龄18～54岁,平均37岁。酒精性4例(6髋),激素性6例(8髋),创伤性2例(2髋),特发性13例(23髋)。Steinberg术前分期:Ⅰ期7髋,Ⅱ期24髋,Ⅲ期8髋。疗效分析包括术前、术后Harris评分,影像学变化及以接受髋关节置换术为随访终点的股骨头生存率。结果:25例患者术后获得随访,时间6～47个月,平均37.4个月。12髋影像学出现进展,包括钽棒退出1髋,股骨头塌陷3髋,股骨头坏死面积增加8髋。6髋行全髋关节置换术,包括有影像学进展5髋占41.7%(5/12),无影像学进展1髋3.7%(1/27)。所有髋关节Kaplan-Meier生存曲线显示钽棒置入后6个月生存率为(97.4±2.5)%,1年生存率为(94.7±3.6)%,2年生存率为(88.6±5.4)%,3年生存率为(72.5±11.2)%。结论:钽棒治疗SteinbergⅠ、Ⅱ期股骨头坏死近期疗效确切,能有效延缓股骨头置换时间。     

多孔重建钽棒内固定治疗早期股骨头坏死疗效观察与分析

目的探讨多孔金属钽棒在早期股骨头坏死治疗中的应用,评价其临床效果,分析失败病例。方法对17例(23髋)早期股骨头坏死(SteinbergⅠ、Ⅱ期)采用髓芯减压联合多孔重建钽棒内固定治疗,以髋关节Harris评分及影像学进行临床疗效评估。结果本组均获9～39个月随访,平均22个月。切口均一期愈合;3例(4髋)在术后随访期内股骨头坏死进展发生塌陷,其中2例(3髋)行全髋关节置换手术,1例行非手术治疗;末次随访Harris评分优良率78.3%。结论股骨头坏死髓芯减压联合重建钽棒内固定术对早期股骨头坏死(SteinbergⅠ、Ⅱ期)的治疗效果是比较满意的,但对疼痛明显的患者应慎用。     

钽棒治疗早期非创伤性股骨头坏死的回归性研究

[目的]分析钽棒治疗早期股骨头坏死的临床疗效,探讨影响钽棒治疗早期股骨头坏死临床疗效的因素.[方法]钽棒治疗早期股骨头坏死病例149例(168髋),男96例,女53例;平均年龄32.36岁.Ⅰ期和Ⅱ期(塌陷前)88髋,Ⅲ期(塌陷后)80髋,其中双侧19例.根据ARCO分期,进行Harris评分和影像学评估.将Harris评分70分以下、再次手术、影像学病变进展(股骨头由非塌陷变塌陷或塌陷加重,关节间隙狭窄加重)视为钽棒失败.[结果]共随访到130例138髋,平均随访时间(31.47±5.78)(8～61)个月,术前平均Harris评分为62.65,术后为79.50(P<0.05).优良率为68.12%.Cox风险模型分析显示大病灶、外侧病灶、植骨与否是手术失败的风险因素,病因、性别、年龄、病灶是否在股骨头骺板内,对钽棒治疗早期股骨头坏死的临床疗效无明显影响.[结论]影响钽棒治疗早期股骨头坏死临床疗效的因素是病灶大小(大于30%)、坏死灶位置(外侧型)、植骨与否,钽棒治疗早期股骨头坏死需要清除死骨、联合植骨.     

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.