ICU患者影响万古霉素血药浓度的相关因素分析

目的 通过分析影响重症监护病房(ICU)患者万古霉素血药浓度的相关因素,探讨优化ICU患者万古霉素给药方案。方法 采用回顾性研究方法,收集东莞市人民医院ICU2016年1月至2018年9月使用并监测万古霉素血药浓度的出院患者。统计ICU患者万古霉素血药浓度分布情况,根据肌酐清除率(CrCl)将患者分为CrCl>90mL/min、CrCl 50~90mL/min、CrCl 10~50mL/min及CrCl<10mL/min 4组,分析不同肌酐清除率组对万古霉素血药浓度水平和达标率的影响以及比较指南推荐剂量与实际剂量的差别,并利用多重线性回归分析进一步探讨影响万古霉素血药浓度的相关因素。结果 99例ICU患者监测万古霉素血药浓度共230例次,45例次(19.57%)达到目标浓度(15~20mg/L),72例次(31.30%)未达标(<15mg/L),113例次(49.13%)超标(>20mg/L)。 CrCl 50~90mL/min和CrCl 10~50mL/min组平均血药浓度[(20.16±7.51)mg/L, (23.12±9.37)mg/L]、血药浓度超标比例(45.45%,62.79%)显著高于CrCl>90mL/min组[(14.65±9.07)mg/L, 19.15%]。CrCl>90mL/min、CrCl 50~90mL/min组实际剂量显著低于推荐剂量,而CrCl 10~50mL/min、CrCl<10mL/min组实际剂量显著高于推荐剂量。多重线性回归分析显示,给药剂量(B=11.631,95%CI=7.030~16.232,P<0.001)、肌酐清除率(B=-0.064,95%CI=-0.097~-0.032,P<0.001)、白蛋白水平(B=-0.334,95%CI= -0.634~-0.035,P=0.029)是影响ICU患者万古霉素血药浓度的主要相关因素。结论 ICU患者万古霉素血药浓度达标率较低,在优化ICU患者万古霉素给药方案时应考虑给药剂量、肌酐清除率和白蛋白水平因素的影响。     

肾功能亢进及低蛋白血症对用万古霉素谷浓度的影响

目的 探寻影响万古霉素谷浓度的主要因素,为万古霉素精准治疗提供参考。方法 采用回顾性方法,收集2014年7月到2019年7月中南大学湘雅医院收治的在住院期间使用了万古霉素抗感染治疗并监测了稳态谷浓度的患者的资料。分析影响万古霉素谷浓度的主要因素,探讨肾功能亢进(augmented renal clearance,ARC)和低蛋白血症对万古霉素谷浓度的影响。结果 最终78例患者纳入分析,其中万古霉素谷浓度<10mg/L者50例,10~15mg/L者13例,15~20mg/L者5例,>20mg/L者10例。单因素分析显示低浓度组的年龄较小、矫正肌酐清除率较高,而白蛋白在不同浓度组存在差异。一般线性模型分析表明,矫正肌酐清除率与万古霉素谷浓度负相关,是其浓度不达标的独立影响因素(P=0.018)。ARC组万古霉素谷浓度为(7.5±7.5)mg/L,达标率为11.1%,显著低于非ARC组(56.7%)。低蛋白组万古霉素谷浓度为(8.7±7.8)mg/L,达标率为12.5%,显著低于正常蛋白组(41.9%)。ARC+低蛋白血症组,万古霉素谷浓度为(6.0±1.2)mg/L,达标率为0。结论 肾功能亢进和低蛋血症是降低万古霉素谷浓度的重要因素。使用万古霉素治疗时,应及时识别该两种因素,做好药物浓度监测,优化给药方案。     

ICU颅内感染患者血清及脑脊液中万古霉素浓度影响因素分析

目的探讨影响ICU颅内感染患者血清和脑脊液中万古霉素浓度的相关因素。方法收集48例ICU颅内感染患者的临床资料,采用简单线性回归和多重线性回归分析影响患者血清和脑脊液中万古霉素谷浓度的相关因素。结果 48例患者血清万古霉素谷浓度为(19.26±8.96) mg/L,血药浓度达标率为31.25%;脑脊液万古霉素谷浓度为(4.61±2.97) mg/L,脑脊液浓度达标率为16.67%;脑脊液中万古霉素穿透率为(18.84±9.47)%。简单线性回归分析结果显示,血清中万古霉素谷浓度与肌酐和白蛋白水平均呈正向线性关系(P<0.05),而与患者年龄、体重、性别不存在线性关系(P>0.05);脑脊液中万古霉素谷浓度与患者年龄、性别、体重、肌酐、白蛋白以及脑脊液白细胞计数之间均不存在线性关系(P>0.05)。多重线性回归分析结果显示,肌酐、白蛋白水平和血清万古霉素谷浓度均与脑脊液万古霉素谷浓度呈正向线性关系(P<0.05)。结论 ICU颅内感染患者万古霉素初始药物谷浓度达标率较低,采取万古霉素静脉给药治疗方案时应考虑血肌酐、白蛋白水平的影响。     

肾功能正常患者万古霉素稳态谷浓度分布及影响因素分析

目的 考察肾功能正常患者万古霉素稳态谷浓度的分布情况,明确影响万古霉素稳态谷浓度的相关因素。方法 收集肾功能正常(肌酐清除率≥50mL/min)且接受万古霉素常规给药方案(1g q12h)治疗的感染患者血样,采用酶免疫扩大法测定万古霉素稳态谷浓度,应用有序多元Logistic回归分析万古霉素稳态谷浓度与患者基本资料及生化指标的相关性。结果 纳入331例符合入排标准的感染患者,统计分析发现,41%(136/331)的患者万古霉素稳态谷浓度低于10μg/mL,而稳态谷浓度高于20μg/mL占15%(48/331),仅44%(147/331)的稳态谷浓度达到指南推荐的目标范围(10~20μg/mL)。有序多元Logistic回归结果显示,患者的年龄(P<0.001)、体重(P<0.001)、肌酐清除率(P<0.001)、重症感染(P=0.022)以及高血压(P=0.022)是影响万古霉素稳态谷浓度的危险因素。结论 可以根据患者的年龄、体重、肌酐清除率、感染类型及血压情况来综合调整万古霉素的给药方案,以更好地实现个体化用药。     

老年重症感染患者万古霉素高谷浓度用药方案的探讨

目的：探讨老年重症感染患者万古霉素高谷浓度用药方案,为临床合理用药提供参考。方法将56例年龄≥65岁的老年重症感染患者按照内生肌酐清除率（Ccr）分为A（Ccr≥50 ml/min）、B（Ccr 20～50 ml/min）两组。对每组患者万古霉素用药剂量、万古霉素稳态血药谷浓度,以及用万古霉素前、后肾功能变化进行统计分析。结果 A组患者31例（25例用万古霉素1 g、q 12 h;6例0．5 g、q 12 h）,B组患者25例（15例用万古霉素1 g、q 12 h;10例0．5 g、q 12 h）。 A组中两种用药方案的患者谷浓度在10～20 mg/L有效范围的比例分别为72％（18/25）和33．33％（2/6）,谷浓度＜10 mg/L的比例分别为12％（3/25）和66．67％（4/6）;B组中两种用药方案的患者谷浓度在10～20 mg/L有效范围的比例分别为20％（3/15）和60％（6/10）,谷浓度＞20 mg/L的比例分别为73．33％（11/15）和30％（3/10）;全部病例除B组万古霉素用量1 g,q 12 h的15例患者用药前、后血肌酐值明显升高（P＜0．05）,尿素氮无明显变化（P＞0．05）,其他患者用药前、后血肌酐和尿素氮均无明显变化（P＞0.05）。 B组有5例患者出现肾毒性,其万古霉素用量为1 g、q 12 h,谷浓度均＞30 mg/L;A组患者无肾毒性发生。结论老年重症感染患者应根据Ccr情况决定万古霉素用量。 Ccr≥50 ml/min者,万古霉素用量为1 g,q 12 h;Ccr在20～50 ml/min的患者,万古霉素用量为0．5 g,q 12 h;由于个体差异,老年患者应重视监测血药谷浓度,根据血药谷浓度及时调整用药方案。     

非重症感染患儿万古霉素初始稳态谷浓度分布及其影响因素分析

目的 对万古霉素在非重症感染患儿中的初始稳态谷浓度(C_(ss,min))的分布情况及其影响因素进行分析,为临床安全合理使用万古霉素提供参考。方法 回顾性选取2020年1月至2021年6月我院接受万古霉素治疗的非重症感染患儿的病历资料,分析万古霉素初始C_(ss,min)分布情况,并采用多因素线性回归方法分析影响万古霉素C_(ss,min)的因素。结果 共纳入83例非重症感染患儿及对应的102个万古霉素C_(ss,min),平均万古霉素C_(ss,min)为(5.7±3.1) mg/L。<5 mg/L、5~10 mg/L、10~15 mg/L组各有36例(43.4%)、40例(48.2%)、7例(8.4%)。多因素线性回归分析显示,初始万古霉素日剂量、血清肌酐值对万古霉素C_(ss,min)有显著影响。结论 按照目前40 mg/(kg·d)、q6h的给药方案,非重症感染患儿万古霉素C_(ss,min)达到目标范围(5~15 mg/L)的比例较低,临床应根据肾功能、临床疗效等综合因素进行剂量调整。     

万古霉素治疗革兰阳性球菌血流感染患者的血药浓度监测

目的了解本院革兰阳性球菌血流感染患者万古霉素的临床应用及血清谷浓度的监测。方法采用荧光偏振免疫偏振法测定万古霉素血清谷浓度,并结合住院患者的临床资料(基础疾病、病原学结果、万古霉素血清谷浓度、疗效、肾功能情况等),对血流感染革兰阳性球菌并应用万古霉素的25例患者进行回顾性分析。结果血流感染耐甲氧西林金黄色葡萄球菌(MRSA)11例(44.0%),屎肠球菌14例(56.0%);临床治愈率32.0%。25例患者共进行万古霉素血清谷浓度测定38例次,血清谷浓度范围2.99~39.1μg/mL,均值(14.96±7.83)μg/mL,其中达到靶浓度15~20μg/mL者8例(21.0%)。临床治愈组与临床无效组万古霉素血清谷浓度分别为(14.69±7.20)、(15.13±8.53)μg/mL(P=0.85)。肾毒性发生6例(24.0%),APACHEⅡ评分均值17分,均为临床无效组。11例MRSA血流感染中,1例万古霉素最低抑菌浓度(MIC)值为2 mg/L,其余万古霉素MIC值均为1 mg/L;临床治愈组万古霉素曲线下面积(AUC)与MIC浓度比值(AUC/MIC)为209±114。结论按照指南的标准,25例血流感染患者万古霉素血清谷浓度达标率低,需加强对这一类患者血清谷浓度的监测力度,并随时调整用药,给出个体化的用药方案。     

老年住院患者万古霉素用药情况分析CSCD

目的：调查万古霉素在老年住院患者中的应用情况。方法收集1011年9月至1013年11月在北京大学第一医院、卫生部北京医院、首都医科大学附属北京朝阳医院、首都医科大学宣武医院、解放军总医院等5家医院住院期间应用过万古霉素、年龄≥60岁且病历资料完整者的临床资料,将患者分为肾功能正常与肾功能不全1组,主要就万古霉素用药情况（给药方案、药物利用情况和血药浓度监测）、临床疗效以及药物对患者肾功能影响等进行回顾性分析。药物利用情况以药物利用指数（DUI）反映;肾功能检测指标为血清肌酐（Scr）、尿素氮（BUN）和内生肌酐清除率（Ccr）。结果共149例患者纳入分析,男性60例,女性89例;年龄60~91（76±7）岁。肾功能正常组87例,肾功能不全组61例。万古霉素给药方案肾功能正常组应用最多者为0.50 g,1次/11 h （19/87,33.33%）;肾功能不全组为0.50 g,1次/d（30/61,48.39%）。万古霉素总用药量为1135.15 g,总用药时间为1919.5 d,DUI 为0.56。149例患者中进行血药浓度监测者111例（74.50%）,肾功能正常组与肾功能不全组行血药浓度监测者占比差异无统计学意义[70.11%（61/87）比80.65%（50/61）,χ1=1.113,P=0.146]。行血药浓度监测者均监测了万古霉素谷浓度,监测峰浓度者7例。万古霉素谷浓度以﹤10 mg/L者占比最大,肾功能正常组和肾功能不全组分别为30例（49.18%）和15例（50.00%）。各组间数据差异均无统计学意义（χ1=1.16,P =0.54）。149例患者用药前后Scr[（117±79）μmol/L比（119±81）μmol/L]、BUN[（10.5±5.7）mmol/L比（11.5±8.0）mmol/L]和Ccr[（69±37）ml/min比（67±36）ml/min]比较,差异均无统计学意义（均P﹥0.05）。肾功能正常组和肾功能不全组患者用药前后 Scr[（59±16）μmol/比（70±30）μmol/L,（189±110）μmol/L 比（103±113）μmol/L]、BUN[（7.4±3.5）mmol/L 比（9.1±5.8）mmol/L,（14.8±6.5）mmol/L比（17.4±9.0）mmol/L]和Ccr[（107±19）ml/min比（96±16）ml/min,（44±30）ml/min比（33±16）ml/min]比较,差异也均无统计学意义（均P﹥0.05）。结论万古霉素在老年住院患者中的应用相对谨慎。应用该药时可根据血药浓度和肾功能监测结果及时调整给药方案,实行个体化给药,提高药物有效性和安全性。     

万古霉素在ICU中浓度监测的临床决策分析

目的 探讨重症监护病房(ICU)中万古霉素谷浓度与临床疗效和肾毒性之间的关系。方法 回顾性收集2016年1月-2017年12月期间入住我院ICU且使用万古霉素患者的基本信息，用决策分析法寻求万古霉素谷浓度与疗效和肾毒性之间的相关性。结果 谷浓度在5~20mg/L范围内疗效的似然比(LR)为1.19~2.38，事后概率P(D/SDC)为66.67%~80%，而浓度＞20mg/L时疗效的LR为0.52，P(D/SDC)为46.67%，出现明显下降。谷浓度在5~25mg/L范围内ADR的LR为0.5~0.82，P(D/SDC)为0.02%~0.04%。浓度＞25mg/L时ADR的LR为4.68，P(D/SDC)为0.19%，出现明显上升。万古霉素谷浓度在10~20mg/L时临床可取得较好的疗效，谷浓度＜25mg/L时肾毒性轻。结论 ICU患者中万古霉素谷浓度可控制在10~20mg/L内。     

重症感染患者万古霉素不同给药方式血药浓度影响因素分析

目的 探讨不同给药方式下重症感染患者万古霉素血药浓度的影响因素。方法 回顾性分析医院重症医学科2020年2月至2021年2月收治的96例予万古霉素连续静脉注射（CIV,45例）或间歇静脉注射（IIV,51例）治疗的重症感染患者的临床资料,采用简单线性与多重线性回归分析2种给药方式下重症感染患者万古霉素血药浓度的影响因素。结果 CIV患者的血药浓度达标率为73.33%,明显高于IIV患者的49.02%(P <0.05)。简单线性回归分析显示,白蛋白水平、肌酐清除率、首日体质量剂量及年龄、中重度水肿、白蛋白水平、肌酐清除率、首日体质量剂量分别为CIV及IIV患者万古霉素血药浓度的影响因素;多重线性回归分析结果显示,肌酐清除率、首日体质量剂量及肌酐清除率、中重度水肿、首日体质量剂量、白蛋白水平分别为CIV及IIV患者万古霉素血药浓度的独立影响因素。结论 对需使用万古霉素的重症感染患者,CIV相较IIV更易达到有效浓度,独立影响因素（首日体质量剂量、肌酐清除率）更少,且可通过肾功能支持和调整首日给药剂量优化万古霉素的个体化给药方案。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.