个体化3D打印导向模板辅助胸腰椎椎弓根螺钉置入在强直性脊柱炎中的应用研究

目的 :评价个体化设计定制3D打印椎弓根螺钉导向模板辅助强直性脊柱炎(ankylosing spondylitis,AS患者胸腰椎椎弓根螺钉置入的准确性与安全性。方法:纳入2016年1月至2019年9月收治的8例AS患者的胸腰椎三维CT检查数据,利用Mimics 17.0、ideaMaker等计算机软件设计AS胸腰椎椎弓根螺钉导向模板,并利用3D打印机打印制作全部病例的实体模型(T_(10)-L_2),每例2份,分为导板辅助螺钉置入组(实验组)和徒手置钉组(对照组)。两组胸腰椎椎弓根螺钉均由同一名脊柱外科医师负责置入。根据术后CT影像结果评估两组椎弓根螺钉置入的准确性,并对螺钉置入情况进行分级:0级和1级螺钉为可接受置钉,2级和3级为不可接受置钉。同时比较术前3D打印软件虚拟设计的椎弓根螺钉的直径、长度、进钉点与后正中线的距离等指标与术中实际使用情况。结果:导板辅助螺钉置入组设计并打印出AS胸腰椎3D打印椎弓根螺钉导向模板23块,辅助置入螺钉46枚,可接受螺钉为44枚;置入单枚螺钉平均时间为(4.20±1.15) min,X线机透视次数为(5.00±1.25)次,置钉过程中螺钉和克氏针平均调整次数为(1.76±1.32)次。徒手置钉组使用传统影像学透视徒手方法置钉46枚,可接受螺钉30枚;置入单枚螺钉平均时间为(14.67±2.23) min,X线机透视次数为(14.46±2.21)次,螺钉和克氏针平均调整次数为(4.76±3.39)次。导板辅助螺钉置入组与徒手置钉组螺钉置入成功率分别为95.65%(44/46)和56.22%(30/46),差异有统计学意义(χ~2=13.538,P0.05);术前3D打印软件虚拟设计的椎弓根螺钉的直径、长度、进钉点与后正中线的距离,与术中实际使用情况差异无统计学意义(P0.05);导板辅助螺钉置入组置入单枚螺钉的时间、X线机透视次数及置钉过程中螺钉和克氏针平均调整次数均明显少于徒手置钉组(P0.01)。结论:3D打印技术定制个体化椎弓根螺钉导向模板显著提高了置钉的安全性、准确性及手术效率,尤其适用于AS合并骨折脱位等须行后路椎弓根螺钉固定的胸腰椎椎体。     

超声骨动力椎弓根寻路器的研制及其引导置钉的可行性研究

目的 :探讨自行研制的超声骨动力椎弓根寻路器辅助椎弓根螺钉置入的准确度及安全性。方法 :自行研制一种超声骨动力椎弓根寻路器,选择2具成年人脊柱标本(T1～L5节段),男性1具,年龄62岁,女性1具,年龄57岁,排除畸形、外伤及骨质疏松症等骨科疾病,将标本左侧椎弓根设置为实验组,通过超声骨动力椎弓根寻路器引导下置钉;右侧椎弓根设置为对照组,直视下徒手置钉。术中及术后即刻分别对两组标本行CT扫描,通过术中CT测量定位针长轴中线距椎弓根内外侧皮质距离;通过术后CT测量椎弓根螺钉穿出椎弓根皮质的距离并依据Neo法对置钉进行分级,统计两组精确置钉(0级置钉)、可接受置钉(Neo分级0级或1级)和不良置钉(Neo分级2级或3级)的情况。通过比较两组精确置钉率与不良置钉率上的整体差异,以及分别在上、中、下胸椎及腰椎的穿破皮质螺钉(Neo分级1、2、3级螺钉)的差异,评估两组间置钉精确性与安全性的差异。结果:两组各置入34枚定位针。实验组与对照组的定位针在上胸椎距皮质骨最小距离分别为2.77mm±1.05mm和0.59±2.31mm,中胸椎为1.97±1.01mm和0.98±1.70mm,下胸椎为3.02±0.93mm和2.53±0.83mm,腰椎为4.14±1.04mm和3.80±0.59mm。实验组有6枚定位针存在穿出的风险,对照组有14枚存在穿出的风险。在置钉方面,实验组与对照组的精确置钉率分别为82.36%和58.82%,可接受置钉率分别为97.06%和82.36%,不良置钉率分别为2.94%和17.64%。在所有穿破皮质螺钉中,实验组有1枚位于上胸椎(1级),2枚位于中胸椎(1级、2级各1枚),2枚位于下胸椎(1级2枚),1枚位于腰椎(1级);而对照组有6枚位于上胸椎(1级2枚、2级2枚、3级2枚),5枚位于中胸椎(1级3枚、2级1枚、3级1枚),3枚位于下胸椎(1级)。实验组在胸腰椎精确置钉率、可接受置钉率上明显高于对照组,而在不良置钉率上明显低于对照组,且差异均具有统计学意义(P0.05)。实验组与对照组在上胸椎节段(T1～T4)穿破皮质螺钉比率存在统计学差异(P0.05),而在中下胸椎及腰椎无统计学差异(P0.05)。结论:与徒手置钉相比,超声骨动力椎弓根寻路器引导下置钉在胸腰椎节段具有较高的准确性与安全性。     

脊柱手术机器人在胸腰段窄小椎弓根后路螺钉置入中的应用

目的 探讨Renaissance脊柱手术机器人在胸腰段窄小椎弓根后路螺钉置入中的应用。方法 对156例胸腰段窄小椎弓根的脊柱疾病患者行后路螺钉置入,窄小椎弓根双侧中一侧采用脊柱手术机器人辅助置入椎弓根螺钉,另一侧采用传统方法置入椎弓根螺钉。术后采用Abul-Kasimhierarchy分级系统评价椎弓根螺钉置入的优良性。结果 在T10～L3窄小椎弓根共置入椎弓根螺钉456枚,其中胸椎置钉60枚,置钉优良率机器人辅助侧为93. 3%(28/30),传统手术侧为80. 0%(24/30),两侧比较差异有统计学意义(P 0. 05);腰椎置钉396枚,置钉优良率机器人辅助侧为96. 0%(190/198),传统手术侧为81. 8%(162/198),两侧比较差异有统计学意义(P 0. 05)。结论 Renaissance脊柱手术机器人辅助胸腰段窄小椎弓根螺钉置入能提高置钉优良率。     

椎弓根镜下微创经皮椎弓根钉置入技术报道及初步应用

目的设计一种新型脊柱内窥镜系统——椎弓根镜系统,探讨在该系统下微创经皮置入椎弓根钉的可行性和安全性。方法椎弓根镜系统设计的工作通道为双通道,内镜通道用于放置小型内窥镜定位螺钉进入点,螺钉通道用于在内镜可视状态下置入椎弓根钉。回顾性分析自2014-01—2015-06接受微创腰椎融合术的16例腰椎间盘突出并退行性不稳,术中在椎弓根镜辅助下经皮置入长臂万向螺钉。记录单枚螺钉置钉时间、置钉出血量、置钉时X线暴露次数和置钉调整次数,术后行CT扫描评估螺钉位置。结果共置入78枚螺钉,单枚螺钉置钉时间7~26(9.8±5.6)min,置钉出血量5~33(10.3±7.8)ml,置钉时X线暴露次数1~5(2.5±1.6)次,置钉调整次数0~4(1.8±1.3)次。术后CT显示螺钉位置:0级72枚(92.3%),1级4枚(5.1%),2级2枚(2.6%)。3枚(3.8%)螺钉轻度侵犯小关节。本组术后随访6~18个月,无钉棒松动、断裂发生。结论新型椎弓根镜辅助下经皮置入椎弓根钉的安全性和精确性均较理想,在保证手术质量的同时还能有效降低术中对患者和医护人员的X线暴露量。     

胸腰椎经皮椎弓根螺钉置钉的准确性分析

目的:分析胸腰椎经皮椎弓根螺钉固定术的置钉准确性.方法:回顾分析2010年7月～2012年12月我院53例胸腰椎经皮椎弓根螺钉固定术患者,男31例,女22例;年龄18～73岁,平均51.2岁.腰椎退变性疾病24例,胸腰椎骨折29例.置钉节段为T8～S1.根据术后CT轴位扫描图像以及患者是否出现椎弓根螺钉相关并发症,将椎弓根螺钉位置分级:0级,螺钉位于椎弓根皮质内;1级,螺钉突破椎弓根骨壁但≤2mm;2级,螺钉突破椎弓根骨壁＞2mm,但无神经受压等症状;3级,出现螺钉相关并发症.结果:共置入椎弓根螺钉212枚,平均4.0枚/例.212枚螺钉中,0级175枚(82.5％);1级32枚(15.1％);2级4枚(1.9％);3级1枚(0.5％),患者出现神经受压症状,行翻修术.37枚位置不佳的螺钉中,24枚向内侧切出椎弓根,13枚向外侧切出.结论:胸腰椎经皮椎弓根螺钉固定技术虽置钉位置欠佳率较高,但很少发生2级以上置钉位置不佳者.     

带预警装置椎弓根螺锥的临床应用

目的探讨带预警装置椎弓根螺锥在胸腰椎手术应用中的优越性。方法回顾性研究自2010年9月~2011年10月收治的需进行椎弓根钉系统内固定的胸腰椎疾病30例,其中腰椎间盘突出16例,胸腰椎骨折10例,椎体滑脱4例。在减压解除神经压迫或复位椎体的同时利用带预警装置椎弓根螺锥行椎弓根钉固定。结果共置入160枚螺钉,术中及术后X线片评估椎弓根钉置钉准确度为100%,术后三维影像评估螺钉位置准确率为94.4%,螺钉平均置入时间(4.5±0.7)min/枚,未出现螺钉置入相关的近期并发症。结论在胸腰椎手术中应用带预警装置椎弓根螺锥行椎弓根钉置入,可有效提高置钉的精确性、安全性,缩短手术时间、减少术中出血量及放射线的暴露强度。     

引导通道辅助下经皮椎弓根置钉与传统经皮椎弓根置钉的比较

目的 :比较引导通道辅助下经皮椎弓根置钉与传统透视下经皮椎弓根置钉的手术时间、射线暴露时间和置钉准确性。方法:70例无神经症状的胸腰椎骨折患者,随机分为A、B两组,A组35患者采用传统透视下经皮置入椎弓根螺钉,共置入180枚椎弓根螺钉;B组35例患者采用引导通道辅助下经皮置入椎弓根螺钉,共置入178枚椎弓根螺钉,均由同一术者完成置钉。记录两组椎弓根置钉时间、射线暴露时间,术后连续2次复查手术节段CT对两组病例置钉准确性进行评估并分级。比较两组患者单枚椎弓根螺钉置钉时间、射线暴露时间和置钉准确性。结果:两组患者年龄、体重指数、合并疾病、骨折类型、性别比例均无统计学差异(P0.05)。A组单枚椎弓根螺钉平均置钉时间为14.11±3.32min,B组为11.35±2.82min,两组比较差异有统计学意义(P=0.0042)。A组平均射线暴露时间为12.07±3.06s,B组为8.06±2.15s,两组比较差异有统计学意义(P=0.0031)。A组155枚(86.11%)螺钉为A级置钉,23枚螺钉(12.78%)为B级置钉,1枚螺钉(0.56%)为C级置钉,1枚螺钉(0.56%)为D级置钉;B组156枚螺钉(87.64%)为A级置钉,20枚螺钉(11.24%)为B级置钉,1枚螺钉(0.56%)为C级置钉,1枚螺钉(0.56%)为D级置钉,两组比较差异无统计学意义(P0.05)。结论 :引导通道辅助下经皮椎弓根置钉与传统经皮椎弓根置钉具有相同的准确性,但能明显减少置钉时间及辐射暴露时间。     

多层螺旋CT三维重建技术在胸腰椎骨折经椎弓根螺钉内固定术中的应用价值

目的:探讨多层螺旋CT(MSCT)三维重建技术在胸腰椎骨折患者经椎弓根螺钉内固定术中的应用价值。方法:2007年1月~2008年12月,78例胸腰椎骨折患者在我院行椎弓根螺钉内固定术,其中38例使用传统置钉法(Weinstein法或AO法)进行椎弓根螺钉置入(A组),40例采用MSCT三维重建设计钉道的置钉方法进行螺钉置入(B组),术后两组均复查胸腰椎正、侧位X线片和CT了解置入螺钉位置情况,应用Lonstein等的方法评判置钉准确率。结果:78例患者共置入椎弓根螺钉436枚,A组38例共置入212枚,12例32枚螺钉穿破椎弓根皮质,其中穿破椎弓根内外皮质21枚,穿破椎弓根上下皮质11枚,置钉准确率84.91%;B组40例共置入224枚,5例6枚螺钉穿破椎弓根皮质,其中穿破椎弓根内外皮质4枚,穿破椎弓根上下皮质2枚,置钉准确率97.33%。两组置钉准确率有统计学差异(P<0.05)。结论:胸腰椎骨折患者行椎弓根螺钉内固定时应用MSCT三维重建设计钉道的置钉方法较传统置钉方法成功率高。     

角度控制组合式椎弓根螺钉植入工具的临床应用

目的观察角度控制组合式椎弓根螺钉植入工具在腰椎椎弓根螺钉植入中的应用价值。方法将行后路椎弓根螺钉植入内固定术的61例腰椎疾患患者按随机区组设计分为角度组(使用角度控制组合式椎弓根螺钉植入工具,31例)和目测组(依靠术者目测角度,30例)。比较两组患者在置钉时间、准确率、穿出率等方面是否存在差异。结果角度组共置入椎弓根螺钉182枚,置钉用时(2. 5±1. 2) min/枚,置钉准确率为97. 2%;目测组共置钉178枚,置钉用时(3. 0±1. 5) min/枚,准确率为88. 2%。角度组置钉时间明显短于目测组(P 0. 05),置钉准确率明显高于目测组(P 0. 01),螺钉穿出率明显低于目测组(P 0. 01)。结论在腰椎椎弓根螺钉植入术中,采用角度控制组合式椎弓根螺钉植入工具的置钉准确率有明显优势,具有临床应用价值。     

辅助经皮胸腰椎弓根螺钉置入激光定位仪在腰椎压缩性骨折手术中的应用

目的探讨辅助经皮胸腰椎弓根螺钉置入激光定位仪(简称激光定位仪)在经皮椎弓根内固定术治疗单节段腰椎压缩性骨折中的可行性和临床应用。方法前瞻性地纳入32例拟行经皮椎弓根螺钉内固定的单椎体腰椎压缩性骨折病人,随机分为两组,每组16例。观察组采用激光定位仪引导置钉,对照组采用正侧位透视置钉。记录并比较两组的置钉时间、辐射量、手术前后疼痛视觉模拟量表(visual analogue scale,VAS)评分差值;术后通过腰椎CT扫描评价置钉准确度。结果随访时间为3~10个月。观察组和对照组的置钉时间分别为(13.33±2.22)min、(17.81±5.01)min,辐射量分别为(295.28±48.61)μGy、(396.34±89.77)μGy,观察组均显著低于对照组,差异均有统计学意义(P均<0.05);但两组手术前后的VAS评分差值比较,差异无统计学意义(P>0.05)。置钉准确度方面,观察组42钉Ⅰ级、22钉Ⅱ级;对照组23钉Ⅰ级、39钉Ⅱ级、2钉Ⅲ级,观察组的置钉准确度更高,两组数据比较,差异有统计学意义(Z=3.442,P=0.001)。结论辅助经皮胸腰椎弓根螺钉置入激光定位仪引导下经皮椎弓内固定术治疗腰椎压缩性骨折,方法可行,效果满意,可缩短置钉时间,减少术中辐射量,提高置钉准确度。     

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.