不同比例三联抗结核药物复合缓释材料的释药性能观察

目的 :观察不同比例三联抗结核药物复合缓释材料在模拟体液中的药物释药性能。方法 :以聚乳酸-羟基乙酸(PLGA)作为载体,采用双乳、喷涂、冷冻干燥溶剂挥发法制备不同比例抗结核药物的复合缓释材料:A组,异烟肼(INH,H)∶利福平(RFP,R)∶吡嗪酰胺(PZA,Z)=15∶15∶30;B组,H∶R∶Z=20∶30∶50;C组,H∶R∶Z=30∶30∶120;D组,H∶R∶Z=80∶120∶250。药物总质量与PLGA之比为1∶5。扫描电子显微镜(SEM)观察HRZ/PLGA复合缓释材料的表面形态,高效液相色谱法(HPLC)检测其在模拟体液中H、R、Z三种药物的释放浓度,计算药物累计释放量及释放率,分析其体外缓释性能。结果:A组和B组缓释材料表面分散均匀,空隙规则、分布均匀,直径分别为23.07±0.38μm和25.67±1.26μm;C组和D组缓释材料分散欠均匀,空隙不规则、分布欠均匀,直径分别为31.25±1.98μm和45.67±3.26μm。A组H、R、Z分别于42d、56d、42d的累计缓释度超过50%,于70d时的阶段释药量分别为157.43±057μg、129.29±0.14μg、196.43±0.28μg,浓度分别为28.486μg/ml、23.525μg/ml、39.265μg/ml。B组H、R、Z分别于35d、42d、35d的累计缓释度超过50%,于70d时阶段释药量分别为9.89±0.96μg、21.71±0.42μg、51.12±0.87μg,浓度分别为1.789μg/ml、1.618μg/ml、10.242μg/ml。C组H、R、Z分别于21d、35d、42d的累计缓释度均超过50%,于70d时阶段释药量分别为1.76±0.49μg、8.43±0.31μg、81.14±0.58μg,浓度分别为0.352μg/ml、1.618μg/ml、10.242μg/ml。D组H、R、Z分别于28d、42d、35d的累计缓释度均超过50%,于70d时阶段释药量分别为1.71±0.21μg、14.01±0.42μg、65.57±0.26μg,浓度分别为0.312μg/ml、2.128μg/ml、13.516μg/ml。70d时A组三种药物浓度均大于各自的10倍最低抑菌浓度(MIC),且A组分散均匀,空隙规则、分布均匀,直径约为23.07±0.38μm,三种药物在不同的时间段释放行为不相同,前14d药物缓释规律按Higuchi方程拟合最好,即前14d三种药物按照扩散的形式进行缓释,14d后三种药物按照零级动力学缓释曲线释放,即等量缓释。其余3组均有药物未达到10倍MIC。结论:复合HRZ/PLGA缓释材料具有优良的载药及药物缓释效果,是一种理想的复合药物缓释系统,其中H∶R∶Z=15∶15∶30的HRZ/PLGA缓释材料为较佳配方。     

载莫西沙星聚乳酸-羟基乙酸缓释微球的制备与体外释放研究

目的制备用于治疗脊柱结核的载莫西沙星聚乳酸-羟基乙酸(PLGA)缓释微球,观察其体外理化特性和缓释性能。方法以PLGA为药物载体,采用优化O/W乳化-溶剂挥发法制备载莫西沙星-PLGA缓释微球,用光学显微镜和扫描电子显微镜观察微球的形态特征。采用超声破碎法震碎微球,然后检测莫西沙星-PLGA缓释微球的载药率和包封率。采用恒温振荡法观察药物的体外释放规律。结果光学显微镜下观察莫西沙星-PLGA缓释微球成圆形,表面光滑,分散均匀。扫描电子显微镜下观察缓释微球成球良好,颗粒规整,大小均匀,微球间无粘连,微球聚集不明显且表面分布有较均匀的微孔。莫西沙星-PLGA缓释微球粒径为12～20(15.6±4.3)μm,载药率为(21.5±0.31)%,包封率为(77.4±1.6)%。莫西沙星-PLGA缓释微球的体外药物释放过程较为平稳,前14 d为突释期,突释期内累计释放率为55.3%,到50 d时体外累积释放率为92.3%。结论制备的载莫西沙星-PLGA缓释微球形态良好、大小均匀且体外释放性能良好。     

聚乳酸聚乙醇酸／RNAⅢ抑制肽缓释微球的制备及评价

目的探讨聚乳酸聚乙醇酸（PLGA）／RNAⅢ抑制肽（RIP）缓释微球的合理制备方法,测定其载药率和体外释药特征。方法采用改良复乳－溶剂挥发法制备PLGA／RIP缓释微球,观察其表征,测定缓释微球的载药率和包封率。采用高效液相色谱法测定不同时点PLGA／RIP的释放速度,观察PLGA／RIP微球的体外释药特点。结果采用改良复乳－溶剂挥发法制备的PLGA／RIP缓释微球粒径均匀、表面光滑,包封率约为（68．22±6．20）％,载药率为（15．35±3．26）％。PLGA／RIP释药动力学方程为y=31．016x＋59．611,符合Huguchi方程。结论采用改良复乳-溶剂挥发法制备的PLGA／RIP缓释微球粒径均匀、表面光滑,包封率和载药率较高,体外释放动力学符合Huguchi方程,是理想的缓释载药体系。     

异烟肼聚乳酸缓释体的制备及体内外释药特性

目的探讨异烟肼聚乳酸微球的制备方法和体内外释药特性.方法用复乳法制备异烟肼聚乳酸微球,扫描电子显微镜观察微球的特征,高效液相色谱法测定其包封率、载药率;用溶出法、高效液相色谱法测定其体外释药特性.观测第3、6、9、12、15、18、25、32、39、42、49、56天的释药情况,并计算其日均释药率、累计释药率将异烟肼聚乳酸微球、异烟肼(INH)分别置入24只新西兰大白兔的左右股骨粗隆间髓腔内,测定微球在体内3、7、14、28、42、56d时的释药情况;实验组将第42、49、56天时的异烟肼聚乳酸微球洗涤液(空白组用磷酸缓冲液)与结核菌、钛块一起共同培养7d,扫描电子显微镜下观察结核菌生长情况.结果异烟肼聚乳酸微球呈比较完整的球形且分散性好,无明显聚集现象;微球平均直径为59.4±2.9μm,包封率为(67.51±0.57)%,载药率为(32.82±0.65)%.体外释药结果显示,最初14d累计释药达3.784±0.359mg,约占总量的30%,日平均释药0.270±0.024mg;随后42d累计释药5.328±0.203mg,约占总量的50%,日平均释药0.126±0.013mg,第56天时释药0.032±0.009mg.体内释药实验显示,3d时右侧股骨粗隆间骨质内INH浓度明显高于左侧(P＜0.01);7～56d右侧INH浓度明显降低并低于左侧(P＜0.01);7～56d左侧股骨粗隆间骨质内INH浓度持续在20±g/s以上.空白组钛块表面有大量结核菌生长,实验组钛块表面几乎无结核菌生长.结论异烟肼聚乳酸微球具有缓慢释放药物的特性.可以作为持久抗结核治疗的缓释体置入骨结核病灶清除术后病灶局部.     

局部用雷帕霉素聚乳酸乙醇酸共聚物缓释微球的制备及释药研究

目的：介绍雷帕霉素（RAPA）聚乳酸乙醇酸共聚物（PLGA）缓释微球的制备方法,建立高效液相色谱法（HPLC）测定体系以检测微球中雷帕霉素含量,检测微球性状并进行体外释药实验。方法：以聚乳酸乙醇酸共聚物为载体,采用W/O/W乳剂-扩散溶剂挥发法制备雷帕霉素缓释微球,扫描电镜检测微球外观及微球粒径,HPLC检测微球载药量、包封率及体外释药量。结果：所制微球光滑圆整,大小均一,平均粒径：（121.18±27.83）μm,载药率：（14.39±1.32）%,包封率：（72.92±4.29）%,体外释放实验显示1～4天有突释,随后平稳释药至第10天累积释药率达80%。结论：采用制备工艺稳定,所制微球载药量及包封率均较高,形态完整,大小均一,体外释药较为平稳并且具有明显的缓释作用。     

复合HRZ/PLGA缓释抗结核药涂层材料在兔脊柱结核病灶释药研究

目的 :观察复合HRZ/PLGA缓释抗结核药涂层材料在兔脊柱结核病灶的释药特性。方法 :应用兔脊柱结核模型120只,按三联抗痨药异烟肼(INH,H)、利福平(RFP,R)和吡嗪酰胺(PZA,Z)给药剂型及途径不同,随机分为4组(各30只):A组(复合HRZ/PLGA缓释材料局部给药组);B组(局部给药组);C组(灌胃给药组);D组(假手术灌药组)。其中A、B、C三组行L4/5脊柱结核病灶清除及自体髂骨植骨术,D组行假手术。采用高效液相色谱(HPLC)检测术后3d、7d、14d、28d、56d、84d各组病灶骨组织中H、R及Z的浓度,绘制药物浓度-时间曲线;使用DAS 3.2.1统计软件对药动学参数进行分析。结果:A组病灶骨组织中H、R及Z的浓度均在术后3d时达最高,此后随检测时间点的后移三种药物浓度均逐渐下降,至给药后84d时最低(H为6.69±1.42μg/ml;R为6.28±0.77μg/ml;Z为19.88±0.90μg/ml),三种药物浓度在各检测时间点均≥10倍的MIC(即杀菌浓度),对同种药物在不同时间检测的浓度进行两两比较,均有统计学意义(P0.05);B组病灶骨组织中H、R及Z的浓度在术后3d时均明显增高,此后较快衰减,至给药后14d时三种药物浓度均检测不到,对同种药物在3d与7d检测的浓度进行比较,差异有统计学意义(P0.05);C组及D组随检测时间点的后移,病灶骨组织中H、R及Z的药物浓度均维持在相对平稳的较低水平,对同组中同种药物在不同时间检测的浓度进行两两比较均无统计学意义(P0.05),术后84d检测时C组H为3.21±0.32μg/ml、R为3.68±0.42μg/ml、Z为6.68±0.25μg/ml,D组H为3.24±0.33μg/ml、R为3.53±0.44μg/ml、Z为6.39±0.45μg/ml。对A、B、C、D四组同时间点同种药物浓度进行比较:C、D两组间同时间点同种药物浓度比较均无统计学差异(P0.05);A组病灶骨组织中H、R及Z的浓度均高于C组及D组的浓度,84d检测时A组中的H、R及Z的浓度分别为C组的3.02、1.70及2.97倍,差异有统计学意义(P0.05);A、C、D三组药物浓度-时间曲线平缓,均未见突释现象;B组存在明显突释现象,药物浓度衰减较快,术后14d后检测不到H、R及Z的浓度。药动学数据分析:A组的曲线下面积、生物半衰期均显著高于B组及C组,差异有统计学意义(P0.05)。结论:复合HRZ/PLGA缓释抗结核药涂层材料在兔脊柱结核病灶局部可实现三药同时长程、高效、平缓释药。     

抗结核药缓释涂层在兔脊柱结核模型体内的释药性能及组织分布研究

目的 :观察抗结核药缓释涂层在兔脊柱结核模型体内的释药性能及组织分布特性。方法 :选取新西兰大白兔(雌雄不限)体重3.00±0.25kg,通过椎体钻孔、浸注结核杆菌法构建并筛选脊柱结核模型120只,按"异烟肼(INH,H)、利福平(RFP,R)和吡嗪酰胺(PZA,Z)"给药剂型及途径不同,将模型分为4组,每组各30只:A组,缓释材料组,病灶局部置入缓释抗结核药缓释涂层(300mg/kg)+自体髂骨;B组,局部给药组,病灶局部置入HRZ药物晶体(H,12.5mg/kg;R,12.5mg/kg;Z,25.0mg/kg);C组,灌喂给药组,每日固定时间灌喂给药(H,12.5mg/kg/d;R,12.5mg/kg/d;Z,25.0mg/kg/d);D组,假手术灌药组,每天固定时间给药(剂量:H,12.5mg/kg/d;R,12.5mg/kg/d;Z,25.0mg/kg/d)。四组单次给药剂量相同,其中A、B两组单次给药,C、D两组研究期间连续多次给药。采用高效液相色谱法测定给药后(7d、14d、28d、84d)各组静脉血、腰大肌以及骨组织(病灶椎体)中H、R及Z的药物浓度,绘制药物浓度-时间曲线,观察其释药性能及组织分布特性。结果:4组单次给药剂量相同,A、B两组HRZ各药的给药总剂量均显著小于C、D两组(P0.01)。A组术后(7d、14d、28d、84d)腰大肌及骨组织中H、R及Z的药物浓度均显著高于C、D两组(P0.01)。A组术后(7d、14d、28d、84d)静脉血中H、R及Z药物浓度均极低或检测不到(P0.05)。A组在腰大肌及骨组织中的药物浓度-时间曲线平缓,无突释现象出现。A组腰大肌H(14.22±1.07μg/ml)、R(12.66±1.12μg/ml)、Z(28.93±1.30μg/ml)的浓度和骨组织中H(12.46±0.29μg/ml)、R(10.34±0.32μg/ml)及Z(26.21±0.82μg/ml)的浓度在给药后第7d时最高,至给药后第84d时H、R及Z的浓度降至最低,此时病灶骨组织中H(6.69±1.42μg/ml)、R(6.28±0.77μg/ml)及Z(19.88±0.90μg/ml)的浓度在各检测时间点均≥10倍的最低抑菌浓度。B组术后7d时腰大肌H(8.19±1.98μg/ml)、R(16.87±3.03μg/ml)、Z(91.18±11.12μg/ml)及骨组织H(5.70±1.25μg/ml)、R(13.06±1.26μg/ml)、Z(79.00±8.68μg/ml)中的药物浓度较高,此后急剧下降,至术后28d时腰大肌及骨组织中已检测不到药物(H、R及Z)浓度。B组静脉血中的药物(H、R及Z)浓度极低或检测不到。C、D两组静脉血、腰大肌及骨组织在各检测时间点均可测得药物(H、R及Z)浓度。C组及D组骨组织中药物(H、R及Z)的浓度均维持在相对平稳的较低水平。结论:缓释HRZ材料在兔脊柱结核病灶局部释药性能满意,组织分布特征为病灶局部高药物浓度而外周低药物浓度。     

复合三联抗结核药涂层材料(HRZ/PLGA)在大鼠体内释药特性观察

目的:观察复合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)三联抗结核药的聚乳酸-羟基乙酸(PLGA)涂层材料(HRZ/PLGA)在大鼠体内的释药特性。方法:将84只成年SD大鼠随机分为A、B、C三组,每组28只。A组为复合抗结核药HRZ/PLGA涂层材料植入组;B组为抗结核药HRZ植入组;C组为空白未载药PLGA涂层材料植入组,于术后1d、3d、1w、2w、4w、6w、8w时分别麻醉各组大鼠4只,抽取腹腔静脉血液5ml,处死后取体内植入材料或药物周边1cm的肌肉组织,应用高效液相色谱法(HPLC)检测肌肉组织及血清中H、R、Z三种药物的浓度,并于1w、4w时取血检测肝、肾功(AST、ALT、Ur、Cr),2w及6w时取植入局部肌肉组织进行形态学观察。结果:A组在术后3d时HRZ/PLGA涂层材料周边肌肉组织中三药浓度均达最高,2w后药物浓度下降趋势平稳,8w时H、R、Z三药平均浓度分别为0.87、0.92、1.61μg/g,均能达到各自10倍最低抑菌浓度(MIC);B组在术后3d时植入HRZ周边肌肉组织中三药物浓度均达最高,但药物浓度下降较快,4w时三种药物均不能检测到;C组不能检测到三种药物。A组肌肉检测药物浓度曲线较B组明显平稳、长程。A组静脉血中三种药物浓度明显低于植入HRZ/PLGA涂层材料周边的肌肉组织(P0.05)。术后1w、4w时各组AST、ALT、Ur、Cr与术前比较差异均无统计学意义(P0.05)。2w时A组及C组植入局部肌肉组织HE染色观察镜下见炎症细胞及PLGA降解产生空泡存在,6w时炎症细胞及空泡减少,A、B、C三组未见明显细胞坏死。结论:HRZ/PLGA涂层材料在SD大鼠体内释药平稳,持续时间较长,可实现体内局部用药的有效缓释;直接植入体内后组织生物相容性及可塑形性良好,为脊柱结核病灶清除后复合自体骨的局部有效给药提供了新方法。     

高压静电场技术制作藻酸钙载药微球及其性能研究

目的探索高压静电场技术制备藻酸钙微球的最佳参数组合,以期微球直径更小更均匀,并研究其载药后的缓释行为。方法设置不同的电压、CaCl_2浓度、藻酸钠浓度、离心机转速、针头直径,观察微球直径和表面形态,以直径更小更均匀为标准,筛选最佳参数组合。负载低(L组)、中(M组)、高(H组)3种浓度的牛血清白蛋白,对比3组的包封率和载药率,并绘制累计缓释曲线,观察其体外缓释行为。结果 16 KV电压、1M CaCl_2浓度、0.5%藻酸钠浓度、200 r/min和30 G的针头是最佳参数组合。L、M、H各组的包封率分别为(91±1.46)%、(85±1.63)%和(79±3.29)%,载药率分别为(0.89±0.04)%、(2.56±0.57)%和(4.10±1.21)%。3组药物都可以持续释放超过28 d,缓释时间较长,释放行为稳定、规律。结论利用最佳参数组合制备的藻酸钙微球是一种优良的药物缓释载体。     

rhBMP-2明胶纳米微球制备及体外缓释效果研究

目的制备重组人骨形态发生蛋白2(recombinant human bone morphogenetic protein-2,rhBMP-2)明胶纳米微球并检测其体外缓释效果。方法 "二次凝聚法"制备明胶纳米微球,扫描电镜、透射电镜和粒径分析仪检测纳米微球的表面形态、内部结构、粒径,计算其溶胀率;将rhBMP-2与明胶纳米微球复合,计算其包封率和载药量,并对其体外缓释效果进行检测。结果明胶纳米微球的表面形态良好,分散均一,内部结构多孔隙、通道,平均粒径(171.49±50.12)nm,溶胀率为1.83;rhBMP-2明胶纳米微球的包封率为(98.13±0.131)%,载药量为(58.89±0.079)ng/mg;rhBMP-2明胶纳米微球释药时间在1个月以上,呈"双相缓释",第1天为"突释相",释药量约为7%,以后平缓释放呈"缓释相",40%左右的药物于28 d内释放,约60%的药物在1个月以后释放。结论成功制备rhBMP-2明胶纳米微球,不但包封率高,而且体外缓释效果好。     

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.     

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.     

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.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Utilisation des médicaments prokinétiques en réanimation : indications et limites ?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.     

Anesthésie générale chez l’enfant : quid des pratiques en 2010 ?

Introduction

The practice of pediatric anesthesia requires a regular update of scientific knowledge and technical skills. To provide the most adequate Continuing Medical Education programs, it is necessary to assess the practices of pediatric anesthesiologists. Thus, the objective of this survey was to draw a picture of the current clinical practices of general anesthesia in children, in France.

Material and methods

One thousand one hundred and fifty questionnaires were given to anesthesiologists involved in pediatric cases. These questionnaires collected information on various aspects of clinical practice relative to induction, maintenance, recovery from general anaesthesia and also classical debated points such as children with Upper Respiratory Infection (URI), emergence agitation, epileptoid signs or anaesthetic management of adenoidectomy. Differences in practices between CHG (general hospital), CHU (teaching hospital), LIBERAL (private) and PSPH (semi-private) hospitals were investigated.

Results

There were 1025 questionnaires completed. Fifty-five percent of responders worked in public hospitals (CHG and CHU); 77% had a practice that was 25% or less of pediatric cases. In children from 3 to 10 years: 72% of respondents used always premedication and two thirds performed inhalation induction in more than 50% of cases. For induction, 53% used sevoflurane (SEVO) at 7 or 8%. Respondents from LIBERAL used higher SEVO concentrations. Tracheal intubation was performed with SEVO alone (37%), SEVO and propofol (55%) and SEVO with myorelaxant (8%), 93% of respondents used a bolus of opioid. For maintenance, the majority of respondents used SEVO associated with sufentanil; desflurane and remifentanil were more frequently used in CHU. Two thirds of respondents used N₂O. Depth of anesthesia was commonly assessed by hemodynamic changes (52%), end tidal concentration of halogenated (38%) or automated devices based on EEG (7%). In children with URI, 98% of respondents used SEVO for anesthesia. To control the airway 42% used a tracheal tube, 30% a laryngeal mask and 20% a facial mask. Emergence agitation was an important concern for two thirds of respondents, while epileptoid signs were considered as important by only 20%. Eighty-nine percent of respondents practiced anesthesia for adenoidectomy. Anesthesia was induced by inhalation of SEVO 7–8% (41%), 6% (39%) or 4% (12%), 66% put an intravenous line (less frequently in LIBERAL). 67% of the responders managed adenoidectomy without any device to control the airway (more frequently in LIBERAL), 32% administrated a bolus of opioid (less frequently in LIBERAL).

Discussion

This survey demonstrated that the practices regarding general anesthesia in children are relatively homogenous. Most of the differences appeared between LIBERAL and the others structures; the anaesthetic management for adenoidectomy illustrates these findings.     

Intérêt d’une rééducation précoce pour les patients neurologiques

Rehabilitation improves the functional prognosis of patients after a neurologic lesion, and tendency is to begin rehabilitation as soon as possible. This review focuses on the interest and the feasibility of very early rehabilitation, initiated from critical care units. It is necessary to precisely assess patients’ impairments and disabilities in order to define rehabilitation objectives. Valid and simple tools must support this evaluation. Rehabilitation will be directed to preventing decubitus complications and active rehabilitation. The sooner rehabilitation is started; the better functional prognosis seems to be.     

Risiko Schlaganfall — Öffentlichkeitsarbeit und Aufklärung dringend erforderlich

Zusammenfassung Das wesentliche — und zugleich noch wenig ausgeschöpfte — Potenzial der Schlaganfallmedizin liegt in der langfristigen Prophylaxe. Durch Beeinflussung von Lifestylefaktoren wie Ernährungsgewohnheiten, Zigarettenkonsum und körperlichem Training durch entsprechende Aufklärung ließe sich ein erheblicher Teil an zerebralen Ereignissen vermeiden. Ein weiterer in Deutschland noch zu wenig beachteter Faktor ist die konsequente Blutdruckeinstellung. Breitgestreute Aufklärung könnte außerdem potenziellen Patienten helfen, bereits auftretende Warnsymptome wie die transiente ischämische Attacke richtig einzuschätzen, um eine rechtzeitige Behandlung zu ermöglichen.