抗凝药比伐卢定临床应用研究进展

比伐卢定(bivalirudin)作为一种新型凝血酶抑制剂,具有抗凝效果的可预测性、不诱导血小板减少等优势。本文收集整理了比伐卢定在经皮冠状动脉介入术、颈动脉支架、球囊主动脉瓣成形术、肝素诱导的血小板减少、体外膜肺氧合等领域的最新研究近况,深入分析了其在临床应用方面的不足,为比伐卢定在使用中的安全性及疗效提供参考依据。     

阿加曲班与普通肝素在重度心肺功能不全患者体外膜肺氧合治疗中的抗凝比较及临床评价

目的通过研究阿加曲班与普通肝素在重度心肺功能不全患者体外膜肺氧合治疗(ECMO)中的抗凝作用,比较2种药物疗效及不良反应,评价阿加曲班的抗凝效果及安全性。方法回顾性分析我院2016年1月至2018年12月40例ECMO患者,按照当时ECMO抗凝方式不同分为普通肝素(Hep)组25例和阿加曲班(Arg)组20例。比较住院期间血小板(PLT)计数,血液流变学、血凝指标及并发出血疾病、穿刺部位并发症、泵管凝血程度情况和膜肺使用寿命。结果 2组患者血液流变学、血凝指标治疗后24及48 h较治疗前差异有统计学意义(P<0.05);而Arg组血液流变学较Hep组降低更明显(P<0.05),血小板计数显著高于Hep组(P<0.05);膜肺,泵及管路凝血程度评分明显降低(P<0.05);出血和穿刺部位不良情况明显降低(P<0.05),膜肺使用寿命显著延长。结论 Arg在重度心肺功能不全患者ECMO治疗中有良好的抗凝疗效,对血小板计数无影响,发生不良事件少,使膜肺使用寿命延长。     

不同抗凝强度体外膜肺氧合治疗中的血管并发症

目的 回顾分析静脉-动脉体外膜肺氧合治疗中不同抗凝强度下血管并发症、住院存活率以及输注血制品的情况。方法 将2019年1月至2022年7月就诊的使用静脉-动脉体外膜肺氧合(venous-arterial extracorporeal membrane oxygenation, V-A ECMO)且运转时间>24 h的68例心肺衰竭的成人患者纳入本研究,以活化凝血时间(activated clotting time, ACT)进行分组,ACT基础值为140～180 s的患者列为低强度抗凝组,ACT基础值为180～220 s的患者列为高强度抗凝组,比较2组患者的血管并发症的发生率、住院存活率以及输血制品情况。结果 共有37例病例纳入本研究标准,其中低强度抗凝组的患者共计22例,高强度抗凝组患者共计15例,低强度抗凝组的住院生存率明显高于高强度抗凝组(72.72%vs 33.33%),差异有统计学意义(P=0.042)。高强度抗凝组发生出血并发症的比例显著高于低强度抗凝组患者(53.33%vs 18.18%),差异有统计学意义(P=0.026)。并且高强度抗凝组中死亡原因由出血引起的占...     

儿童心胸重症监护室接受体外膜肺氧合治疗患儿的抗感染治疗情况分析

摘 要 目的：分析儿童心胸重症监护室接受体外膜肺氧合（ECMO）治疗患儿的病例特点及抗感染治疗情况。方法：回顾性纳入2017年12月至2021年11月本院心胸重症监护室接受ECMO治疗的患儿,记录ECMO适应证、置入方式、支持时间和感染相关数据,以及抗感染药物的使用情况。结果：研究共纳入21例患儿,平均年龄（3.99 ± 3.96）岁,其中4例为新生儿。ECMO的主要适应证为呼吸衰竭5例、重症肺炎4例、爆发性心肌炎4例、各种原因导致的心力衰竭4例、复杂先心术后低心排3例。ECMO的置入方式为静脉-动脉-ECMO18例、静脉-静脉-ECMO3例,ECMO支持时长为（7.90 ± 4.89）d。临床结局好转14例,死亡7例。所有病例中有6例发生了经培养证实的院内感染,最常见的感染部位是血流与下呼吸道感染,最常见的分离菌是鲍曼不动杆菌。所有病例均使用了抗菌药物,总计47例次,其中预防性使用31例次;平均每位患儿接受的抗菌药物品种数为2.2种;使用排名前三位的抗菌药物为头孢哌酮舒巴坦、万古霉素、美罗培南。结论：本院心胸重症监护室接受ECMO治疗患儿的抗感染治疗存在预防用药比例高、联合用药品种数多、抗菌药物级别高等问题,有必要进一步优化抗感染治疗方案以保障临床安全合理用药。     

体外膜肺氧合下儿童抗感染治疗最新研究现状

体外膜肺氧合(ECMO)作为一种医疗急救设备,用于心肺功能衰竭时为患者提供体外的呼吸与循环生命支持,以维持危重患者生命.目前,随着ECMO技术逐渐成熟,ECMO在儿科领域的应用也日益广泛,尤其用于心肺功能不全的危重症患儿的辅助支持治疗.应用ECMO的患者常伴有严重感染的发生,然而ECMO会影响部分抗感染药物的体内过程,...     

2019年河北省体外膜肺氧合开展情况调查分析

目的 调查2019年河北省体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)开展情况.方法河北省急诊质控中心于2020年初委托河北省11个地级市急诊质控中心负责人对各地区2019年1月1日至12月31日的ECMO开展情况进行调查分析.结果2019年8家医院上报总例数为65例...     

比伐芦定与肝素在经皮冠状动脉介入治疗中有效性及安全性的Meta分析

摘 要 目的：通过Meta分析方法比较比伐芦定与肝素在经皮冠状动脉介入治疗（PCI）患者中的有效性及安全性。 方法：计算机检索PubMed、The Cochrane Library、Embase、Clinical Trials.gov、CNKI、WanFang Data、VIP数据库,收集关于比伐芦定与肝素应用于PCI患者的随机对照试验（RCTs）,检索时限均为建库至2017年7月,由两位研究员独立筛选文献、提取资料并对纳入研究进行偏倚风险评估后,采用RevMan 5.0软件进行Meta分析。结果：纳入18项研究,共52 203例患者。Meta分析结果显示：对比肝素,比伐芦定不增加30 d主要心血管不良事件（MACE）的发生率[RR=1.07,95%CI(1.00,1.14),P=0.05];但可减少30 d大出血事件的发生率[RR=0.69,95%CI(0.57,0.84),P<0.001];与肝素相比,比伐芦定增加30 d支架内血栓事件的发生率[RR=1.40,95%CI(1.10,1.77),P=0.006],亚组分析显示术后延长使用比伐芦定不增加30 d支架内血栓事件的发生率[RR=1.17,95%CI(0.55,2.52),P=0.68],而术后即刻停用比伐芦定会明显增加30 d支架内血栓事件的发生率[RR=1.74,95%CI(1.23,2.47),P=0.002]。〖HTH〗结论：〖HTK〗PCI围手术期使用比伐芦定抗凝的有效性不劣于肝素;但比伐芦定可减少30 d大出血事件,安全性方面优于肝素;如此却以增加30 d支架内血栓事件的发生风险为代价,而术后延长使用比伐芦定不增加30 d支架内血栓的发生风险。     

体外膜肺氧合治疗儿童重症肺炎中抗感染药物的治疗体会

为探讨体外膜肺氧合治疗的重症肺炎儿童患者的抗感染药物治疗方案及药学监护要点,笔者选择2018年11月-2019年5月因重症肺炎合并急性呼吸窘迫综合征,在本院接受体外膜肺氧合治疗的2例患者为研究对象。采用回顾性分析方法,采集患者的临床病例资料,对药学监护过程进行分析和总结。临床药师利用循证医学思维,从重症肺炎感染性病原分析,2例患者分别给予不同的经验用药、调整用药及口服序贯用药方案,并选择恰当的抗菌药物疗程,治疗成功。对于体外膜肺氧合治疗的儿童重症肺炎患者,临床应重视抗菌药物的合理使用。临床药师应根据患者病情与药物特点,协助临床医师制订个体化方案。     

Pharmacokinetics of Sulfamethoxazole and Trimethoprim During Venovenous Extracorporeal Membrane Oxygenation: A Case Report

Extracorporeal membrane oxygenation (ECMO) therapy could affect drug concentrations via adsorption onto the oxygenator and/or associated circuit. We describe a case of a 33-year-old man with severe respiratory failure due to Pneumocystis jirovecii infection on a background of recently diagnosed human immunodeficiency virus infection. He required venovenous ECMO therapy for refractory respiratory failure. Intravenous sulfamethoxazole-trimethoprim (100 and 20 mg/kg/day) was administered in a dosing regimen every 6 hours. Pre-oxygenator, post-oxygenator, and arterial blood samples were collected after antibiotic administration and were analyzed for total sulfamethoxazole and trimethoprim concentrations. The peak sulfamethoxazole and trimethoprim concentrations were 122 mg/L and 5.3 mg/L, respectively. The volume of distribution for sulfamethoxazole was 0.37 and 2.30 L/kg for trimethoprim. The clearance for sulfamethoxazole was 0.35 ml/minute/kg and for trimethoprim was 1.64 ml/minute/kg. The pharmacokinetics of sulfamethoxazole and trimethoprim appear not to be affected by ECMO therapy, and dosing adjustment may not be required.     

Altered Pharmacokinetics and Dosing of Liposomal Amphotericin B and Isavuconazole during Extracorporeal Membrane Oxygenation

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2-fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.     

Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.     

低分子肝素联合糖皮质激素治疗小儿肾病综合征疗效及安全性的Meta 分析

目的:评估低分子肝素联合糖皮质激素治疗小儿肾病综合征(NS)的疗效及安全性。 方法:检索 PubMed、the Cochrane Library、EMBase、中国知网、中国生物医学文献数据库、维普、万方数据库,检索时间从建库至 2021 年 3 月,收集低分子肝素联合 糖皮质激素治疗小儿 NS 的临床随机对照试验(RCT),根据 Cochrane 推荐的偏倚风险评估方法对纳入的 RCT 研究进行风险评估,使用 RevMan 5. 3 软件进行统计学分析。 结果:共纳入 16 篇 RCT,病例共计 1 348 例。 Meta 分析结果显示:与单用糖皮质激素(泼尼松)治疗小儿 NS 相比,低分子肝素+泼尼松治疗在活化部分凝血活酶时间、血浆凝血酶原时间、不良反应发生率方面差异无统计学意义(P 均>0. 05),在改善 24 h 尿蛋白定量、血清白蛋白、尿素氮、血肌酐清除率、血肌酐及血浆胆固醇水平方面差异有统计学意义(P 均<0. 05)。 结论:低分子肝素联合糖皮质激素较单用激素治疗小儿 NS 疗效更优,但仍需大样本、多指标的RCT 对远期疗效及药物不良反应等展开深入评估。     

Cost-effectiveness of Argatroban Versus Heparin Anticoagulation in Adult Extracorporeal Membrane Oxygenation Patients

Purpose: The purpose of this study was to evaluate the cost effectiveness of argatroban compared to heparin during extracorporeal membrane oxygenation (ECMO) therapy. Methods: This was a retrospective study of patients who received argatroban or heparin infusions with ECMO therapy at a community hospital between January 1, 2017 and June 30, 2018. Adult patients who received heparin or argatroban for at least 48 hours while on venovenous (VV) or venoarterial (VA) ECMO were included. Patients with temporary mechanical circulatory assist devices were excluded. Each continuous course of anticoagulant exposure that met the inclusion criteria was evaluated. The primary endpoint was the total cost of anticoagulant therapy for heparin versus argatroban, including all administered study drugs, blood or factor products, and associated laboratory tests. Secondary endpoints included safety and efficacy of anticoagulation with each agent during ECMO. Documentation of bleeding events, circuit clotting, and ischemic events were noted. Partial thromboplastin time (PTT) values were evaluated for time to therapeutic range and percentage of therapeutic PTTs. Results: A total of 11 courses of argatroban and 24 courses of heparin anticoagulation were included in the study. The average cost per course of argatroban was less than the average cost per course of heparin ($7,091.98 vs $15,323.49, respectively; P value = 0.15). Furthermore, argatroban was not associated with an increased incidence of bleeding, thrombotic, or ischemic events. Conclusion: Argatroban may be more cost-effective during ECMO therapy in patients with low antithrombin III levels without increased risk of adverse events.     

一例体外膜肺氧合及肾脏替代治疗并行患者的美罗培南药动学/药效学

目的：测定一例体外膜肺氧合（extracorporeal membrane oxygenation,ECMO）及肾脏替代治疗（renal replacement therapy,RRT）并行患者不同时间点的美罗培南血药浓度,得出药动学参数,将浓度值与最低抑菌浓度（MIC）作比较,探讨ECMO及RRT同时进行治疗对美罗培南药动学/药效学（PK/PD）的影响。方法：选自重症监护室（ICU）的一位进行体外膜肺氧合及肾脏替代治疗的急性循环衰竭患者,按美罗培南1 g q8h,静脉滴注30 min。采用HPLC法测定美罗培南给药前和给药后0.25、0.5、0.75、1、2、4、8h的血药浓度。将测得的血药浓度代入药代动力学软件Winnonlin5.2,求出该患者的药代动力学参数。计算不同MIC值时PK/PD靶目标100%T>MIC的达标情况。结果：该患者美罗培南给药后30 min的峰浓度（Cmax）为44.94μg·mL-1,经8 h谷浓度（Cmin）为9.79μg·mL-1,0~8 h药-时曲线下面积（AUC0-8）为133.69 h·μg-1·mL-1,半衰期（t1/2）为2.68 h,表观分布容积（Vd）为33.12 L,清除率（CL）为4.38 L·h-1。当MIC为敏感值2μg·mL-1或中介值8μg·mL-1时,PK/PD靶目标100%T>MIC均达标。结论：进行体外膜肺氧合及肾脏替代治疗的急性循环衰竭患者使用美罗培南时,药动学参数发生了一定变化,但常规剂量1 g q8h/30 min延长静脉滴注能够满足抗感染的PK/PD靶目标,提示该类患者治疗初期可经验性给予常规剂量的美罗培南进行抗感染的治疗,之后根据血药浓度监测进行剂量的调整。