阿米卡星在严重败血症患者体内的药代动力学研究

目的：初步探讨25 mg·kg －1的阿米卡星在重症监护室（ICU）患者体内的药代动力学。方法纳入符合条件的30例革兰阴性（G －）败血症患者进行阿米卡星药物治疗研究,通过非房室模型计算每名患者的阿米卡星的药代动力学。结果阿米卡星在 G －败血症患者体内平均药物分布为（0．36±0．07）L·kg －1,平均血液清除率为（3．88±0．97）mL·min －1·kg －1。肌酐清除率与血清肌酸酐（SCr）相关性具有统计学意义。结论对 ICU 患者应用高剂量阿米卡星（≥25 mg·kg －1）需要考虑败血症对血液动力学的影响,需要密切监测败血症血液药物浓度变化,关键要考虑到重症患者体内药代动力学与普通人群是不同的。     

危重症患者替加环素的群体药动学

目的: 建立替加环素在危重症患者中的群体药动学模型,探究该类人群中影响替加环素药动学的因素。方法: 收集静脉使用替加环素的危重症患者的血样,使用高效液相色谱-质谱联用技术测定替加环素的血药浓度。利用NONMEM软件估算替加环素的药动学参数,通过向前纳入法和逆向剔除法建立替加环素群体药动学模型,并对该模型进行验证和评价。结果: 收集54名患者的143个血药浓度建立替加环素的群体药动学模型,静脉给药的一室模型较好地描述替加环素的药动学特征,替加环素的清除率(CL)、表观分布容积(V_d)的群体典型值分别为11.3 L·h^-1和105 L,患者的APACHE Ⅱ评分和年龄对模型有显著影响。结论: 建立的替加环素群体药动学模型预测性能稳定良好,APACHE Ⅱ评分影响替加环素CL,年龄影响替加环素V_d,可为临床替加环素在危重症患者中的个体化给药提供参考。     

Pharmacokinetics of linezolid in critically ill patients

Introduction: Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion.

Areas covered: This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population.

Expert opinion: While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.     

Pharmacokinetics of cimetidine in critically ill patients

Summary Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15–35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30–50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p<0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.     

Implementation of the glucommander method of adjusting insulin infusions in critically ill patients

Background:

Intensive glycemic control has been associated with reduced morbidity and mortality in critically ill patients. Web-based, patient-specific insulin nomograms may facilitate improved glucose control.

Objective:

To compare 2 algorithms for individualizing insulin infusion therapy (a web-based system [Glucommander method] and a standard paper-based nomogram) in a cardiovascular surgery intensive care unit (ICU).

Methods:

In this prospective, before–after cohort study, measures of glycemic control for 50 patients receiving insulin according to the Glucommander system were compared with a control group (n = 50) who received insulin according to the standard paper-based nomogram used in the cardiovascular surgery ICU.

Results:

There was no significant difference between the 2 groups with respect to time to target blood glucose (5.1–8.0 mmol/L), percentage of time within the target range, or mean amplitude of glucose excursion. Patients in the intervention group spent less time above the target range (p = 0.007) and more time below the target range (p < 0.001), and the mean glucose was lower in this group compared with the control group (7.9 versus 8.6 mmol/L, p = 0.002). The percentage of blood glucose measurements below 4 mmol/L was higher in the intervention group than in the control group (3.7% versus 1.4%, p = 0.003). Satisfaction surveys revealed that the program was well accepted by the nursing staff in the cardiovascular surgery ICU.

Conclusions:

A web-based insulin nomogram was an easy-to-use instrument for achieving tighter glucose control for patients in the cardiovascular surgery ICU. Use of the Glucommander system led to lower mean blood glucose but an increase in episodes of hypoglycemia.     

危重病患者的加强胰岛素治疗

目的观察危重病人加强胰岛素治疗后的的疗效。方法将116例危重病人随机分为两组,传统治疗组(CT)和加强胰岛素治疗组(IT)。CT组:当血糖>215mg/dl,诺和R笔芯皮下注射,控制血糖180～200mg/dl;IT组:当血糖>110mg/dl,控制血糖80～110mg/dl。结果CT组死亡率44.83%远远高于IT组的12.07%,病人的ICU住院时间、使用呼吸机日数、每日6:00的平均血糖、每日TISS-28评分均明显高于IT组(P<0.05);CT组每日胰岛素用量、HLA-DR、CD4+/CD8+明显小于IT组(P<0.05)。两组并发症比较,CT组病人发生肾损害、输注红细胞、发热的人数均明显高于IT组(P<0.05)。结论加强胰岛素治疗控制危重病人血糖80～110mg/dl,能降低病人的死亡率。     

成人危重症患者利奈唑胺相关性血小板减少症的危险因素分析

目的:了解ICU危重症患者使用利奈唑胺治疗后并发血小板减少症的情况,并进行相关危险因素分析,为临床的合理安全用药提供依据。方法:采用回顾性研究方法,选取广州市某三甲医院ICU病房2013年1月-2014年12月使用利奈唑胺注射剂或片剂的成人患者病例,调查利奈唑胺治疗中并发血小板减少症的情况,并用单因素和多因素逐步Logistic回归分析其相关危险因素。结果:通过统一的纳入和排除标准筛选符合要求的病例共57例,利奈唑胺治疗中并发血小板减少症的发生率为28.07%,并发血小板减少组与未并发组相比,血小板基线值较低[(174.06±53.21)×10⁹/L:(228.93±81.86)×10⁹/L,P=0.019],APACHEⅡ评分较高[(22.12±8.66):(16.20±4.77),P=0.039],血清肌酐清除率(Ccr)较低[(中位数41.86,四分位数间距26.26):(中位数71.84,四分位数间距56.40),P=0.003];多因素逐步Logistic回归显示利奈唑胺治疗中并发血小板减少症的危险因素包括血小板基线值(OR 5.02,95%CI 1.01~17.95,P=0.043),CCr(OR 5.16,95%CI 1.21~22.03,P=0.027)和APACHEⅡ评分(OR 3.92,95%CI 1.08~14.14,P=0.037)。结论:危重症患者在使用利奈唑胺治疗的过程中应警惕血小板减少症的发生,尤其是血小板基线值<200×10⁹/L、肾功能不全(Ccr<50 mL·min^-1)和APACHE Ⅱ≥20分的患者。     

多黏菌素B对于耐碳青霉烯类鲍曼不动杆菌感染重症患者的疗效和安全性分析

目的: 围绕耐碳青霉烯类鲍曼不动杆菌(carbapenem-resistant Acinetobacter baumannii,CRAB)感染的重症患者,探索影响多黏菌素B(polymyxin B,PMB)疗效与安全性的相关因素。方法: 收集南京大学医学院附属鼓楼医院重症监护室2020年1月至2021年12月感染CRAB患者的基本特征、感染情况、治疗方案等信息,首先以细菌清除率和感染缓解率作为主要结局指标开展单因素分析,而后以28 d全因死亡率为次要结局指标开展单因素分析及Logistic回归,并比较部分患者的治疗药物监测结果。结果: 共纳入68例以PMB治疗的患者,其细菌清除率、感染缓解率分别为39.7%,44.1%,而28 d全因死亡率为41.2%。围绕主要结局指标,使用PMB疗程＞7 d的患者相较于疗程3~7 d患者,有更高的细菌清除率与感染缓解率。对于次要结局指标,PMB疗程以及PMB治疗过程中采用的连续性肾脏替代治疗,是患者28 d全因死亡的主要相关因素。结合治疗药物监测结果的单因素分析结果显示,CRAB清除患者的PMB峰浓度以及平均稳态血药浓度更高,同时发生肾毒性患者具有更高的PMB谷浓度,差异均具有统计学意义(P＜0.05)。结论: PMB治疗中,患者疗程应大于7 d以保证疗效,同时应重点关注采用连续性肾脏替代治疗患者的治疗结局;安全性方面PMB引起的肾毒性则可通过测定PMB谷浓度进行监测。     

重症患者转运前核查程序的设计及应用研究

目的 评价重症患者转运前核查程序对重症患者转运质量的影响.方法 自行设计、应用重症患者转运前核查程序.观察重症患者院内转运708例次,逢单数进入对照组,双数进入观察组.对照组转运人员凭经验完成转运前准备,观察组按书面核查程序执行.结果 观察组患者主要不良事件发生率分别为心血管系统0.57%、呼吸系统1.98%、呼吸机适应0.00%及医疗设备相关0.28%,都低于对照组（P＜0.05）.转运前准备时间缩短,物品携带齐全率100%;患者或家属及转运人员对转运服务质量满意度分别为99.44%、98.87%,都优于对照组（P＜0.01）.结论 重症患者转运前核查程序可行,有效,可显著降低危重患者转运风险,提高转运效率,保证转运质量.     

Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients

Objectives Serum creatinine (Scr) is not a reliable marker of renal function in critically ill patients because of an enhancement of protein catabolism, which makes it difficult to adjust the dosage of renally eliminated drugs such as antibiotics. This study aimed to investigate whether serum cystatin C (Scys‐C) could be used as a reliable marker of renal function. Methods We investigated whether Scys‐C was a reliable marker of renal function in 56 critically ill patients. Subsequently, the usefulness of Scys‐C to determine the initial loading and the maintenance dose of vancomycin was examined in 18 patients. Crea‐ tinine clearance (Ccr) was assessed from Scr and creatinine in urine collected over 24 h (24‐h Ccr). Key findings There was a good correlation between 24‐h Ccr and 1/Scys‐C (r² = 0.616), whereas less marked correlation was observed between 24‐h Ccr and 1/Scr (r² = 0.221). On the other hand, vancomycin concentration was predicted from population pharmacokinetic parameters based on a two‐compartment linear model. There were significant correlations between real trough concentrations of vancomycin and the values predicted from Scys‐C using various equations (r² = 0.416–0.488), while less pronounced relationships were observed between real concentrations and the values predicted from Scr (r² = 0.134–0.187). Conclusions These findings suggest that Scys‐C is a reliable marker reflecting renal function in critically ill patients and is applicable to determine the initial loading dose as well as the maintenance dose of vancomycin.     

静脉留置针接真空采血器在内科急危重患者的应用

目的 探讨通过静脉留置针接采血器为急危重患者抽血,以及建立静脉通道,对穿刺成功率、完成时间及病人满意度的影响.方法 将2008年5月-2010年9月我科收治的危重病人220例随机分成两组,观察组采用行外周浅静脉留置针穿刺,同时接真空采血器抽血化验、输液,对照组按常规分别行外周静脉输液及真空采血器抽血化验.观察2组在完成...     

临床药师优化危重症患者万古霉素给药方案的药学实践

目的:探讨临床药师在万古霉素个体化治疗中药学监护的模式和作用。方法:临床药师参与危重症患者的救治,协助医师监测万古霉素血药浓度,优化万古霉素给药方案。危重症患者初始给予1g,ivgtt,q12h常规剂量,后经血药浓度监测万古霉素谷浓度均不达标(<15mg·L^-1),临床药师建议:为避免肾毒性等不良反应的增加,不宜提高每日总剂量,建议调整万古霉素给药方式为24h持续输注(0.5g,持续静推,q6h)。结果:优化给药方案后,患者万古霉素谷浓度均已达标,且未见肾毒性等不良反应,经过治疗,感染较前明显控制,转至普通病房继续治疗。结论:临床药师参与临床药物治疗,对危重症患者展开药学服务,制定个体化给药方案,能最大程度减少药物的不良反应,确保临床治疗安全、有效。     

多黏菌素B治疗危重患者泛耐药革兰阴性菌感染的疗效和影响因素分析

目的：通过分析多黏菌素B治疗危重患者泛耐药革兰阴性菌感染的疗效及其影响因素,为多黏菌素B的合理应用提供参考依据。方法：回顾性收集2018年1月至2019年12月期间在中山大学附属第一医院重症监护病房住院感染泛耐药革兰阴性菌,且使用多黏菌素B治疗≥3 d的患者资料,观察患者使用多黏菌素B的疗效,并对相关的影响因素进行统计学分析。结果：共纳入患者91例,平均年龄为（56.76±18.57）岁,多黏菌素B平均给药剂量为（118.04±32.23） mg·d^-1,给药疗程中位和四分位数间距为11（7,16） d,患者细菌清除率为40.7%（37/91）,临床有效率为52.8%（48/91）,30 d死亡率为48.4%（44/91）,住院死亡率为60.4%（55/91）;多因素logistic回归分析显示患者接受连续性肾脏替代治疗（OR=0.32,95% CI：0.12~0.82,P=0.018）及给药时机（OR=0.28,95% CI：0.10~0.77,P=0.013）是影响多黏菌素B临床疗效的独立危险因素;序贯器官衰竭评分（OR=1.30,95% CI：1.12~1.51,P=0.001）及血流感染（OR=10.49,95% CI：2.35~46.93,P=0.002）是患者在多黏菌素B治疗期间30 d内死亡的独立危险因素。结论：对于多黏菌素B应用于危重患者泛耐药革兰阴性菌感染,恰当的给药时机是治疗成功的关键因素,而接受连续性肾脏替代治疗是临床疗效的独立影响因素,患者器官功能的衰竭程度以及伴随血流感染是治疗预后不良的独立危险因素。     

老年危重病人早期肠内营养支持

目的探讨早期肠内营养（EN）在老年危重病人中的临床应用。方法85例老年危重病患者,随机分为入院后1周内开始实施EN的45例为EN组;行完全胃肠外营养的40例为对照组,并分别在营养支持前后测肝肾功能、血糖、电解质、血清蛋白、血红蛋白、免疫球蛋白及淋巴细胞计数等。结果EN组血清白蛋白、前白蛋白、转铁蛋白营养支持后显著增高（P〈0．05）,免疫球蛋白和淋巴细胞计数在营养支持后明显升高（P〈0．01）。结论对危重病人进行早期肠内营养支持是可行、安全和有效的。能改善危重病人的营养状况及免疫功能。     

持续质量控制对危重患者压疮发生率的影响

目的探讨持续质量控制对危重患者压疮发生率的影响,为其临床预防提供可参考依据。方法共纳入170例ICU病房的危重症患者作为控制前组,同时应用持续质量改进的管理理念和先进的管理方法。按计划、实施、检查与处理循环的方法实施早期目标控制,选择180例ICU病房的危重症患者作为控制后组,观察2组患者压疮的发生情况。结果持续质量控制后操作技能达标率93．89％及Braden评分复合率83．33％均明显高于持续质量控制前达标率87．64％、复合率73．53％,2组比较差异有统计学意义（P＜0．05）。控制前组170例患者中31例患者发生压疮,占18．23％,其中1期13例,占7．65％,2期11例,占6．47％,3期5例,占2．94％,4期2例,占1．18％。控制后组180例患者中8例发生压疮,占4．44％,其中1期5例,占2．78％,2期3例,占1．67％,无3期、4期发生。2组压疮发生情况比较差异有统计学意义（P＜0．05）。ICU出院患者中,实施持续质量控制的患者满意率明显升高,且满意度评分亦明显高于实施前,2组比较差异有统计学意义（P＜0．05）。结论在ICU病房预防压疮管理中引进持续质量控制,可以有效地提高护理人员压疮护理技能,最大限度降低压疮的发生风险,同时有效提高了患者的出院满意度,值得临床推广应用。     

CYP2C19基因多态性对侵袭性真菌感染重症患者伏立康唑血药浓度的影响

目的:研究CYP2C19基因多态性与侵袭性真菌感染重症患者伏立康唑标准化血药浓度的关系,为临床合理用药提供参考。方法:运用PCR-RFLP方法对患者CYP2C19 2(681G→A)和CYP2C19 3(636 G→A)位点进行基因型分析;使用HPLC法检测49名侵袭性真菌感染患者的伏立康唑血药浓度;并对伏立康唑血药浓度检测结果、药物疗效和不良反应与基因分型结果进行统计学分析。结果:49名患者中,同时分析CYP2C19两个位点,共有5种双位点基因型组合,包括强代谢型(extensive metabolizer,EM)的681GG-636GG、中等代谢型(intermediate metabolizer,IM)的681GA-636GG和681GG-636GA以及慢代谢型(poor metabolizer,PM)的681AA-636GG和681GA-636GA,其分布频率分别为14.29%,53.06%,8.16%,14.29%和10.2%。EM组、IM组和PM组的标准化血药浓度存在显著性差异(P<0.05),且PM组显著高于IM组,IM组显著高于EM组(P<0.05)。此外,基因多态性对各组间的药物疗效(P<0.05)和不良反应(P<0.05)均具有显著性影响。结论:CYP2C19基因多态性对伏立康唑血药浓度、疗效和不良反应产生显著影响,表明药物遗传学研究对伏立康唑临床合理用药具有重要的指导意义。     

Optimal teicoplanin loading regimen to rapidly achieve target trough plasma concentration in critically ill patients

Teicoplanin is used for the treatment of Methicillin‐resistant Staphylococcus aureus infection. It has been demonstrated that conventional loading regimen was insufficient for teicoplanin to achieve target trough plasma concentration (C_min > 10 mg/L). Therefore, a Chinese expert group recommended an optimal loading dose regimen of teicoplanin to treat severe Gram‐positive infection. However, there was no report about the teicoplanin concentration, and the safety and efficacy of teicoplanin therapy in Chinese patients since the consensus was published. The objective of this study was to compare the teicoplanin C_min and clinical response in critically ill Chinese patients after the administration of conventional or optimal loading regimen, and to reveal the potential factors that may affect teicoplanin C_min in addition to loading regimen. Fifty‐five patients were retrospectively divided into two groups based on teicoplanin loading regimen: (a) CD group (conventional loading dose group, n = 18, loading dose was 400 mg); (b) OD group (optimal loading dose group, n = 37, loading dose was 800 mg). Initially, three loading doses were administered every 12 hours, while the fourth loading dose was injected 24 hours after the third dose. The maintenance dose was 400 mg (CD group) or 800 mg (OD group), respectively. The mean teicoplanin C_min on day 2 and day 4 in the OD group was significantly higher than those in the CD group, which were 14.75 ± 5.93 mg/L vs 8.26 ± 4.87 mg/L (P < .001) and 14.90 ± 5.20 mg/L vs 9.13 ± 4.75 mg/L (P = .019), respectively. The percentages of patients in the OD group achieving the target teicoplanin C_min on day 2 and day 4 were also significantly higher than those in the CD group, which were 83.7% vs 33.3% (P < .001) and 82.4% vs 28.6% (P = .0013), respectively. Furthermore, multivariate linear regression analysis showed that body‐weight exerted significant effect on teicoplanin C_min in the OD group. The percentage of favourable clinical response in the OD group was significantly higher than that in the CD group (83.8% vs 55.6%, P = .025). There was no difference between teicoplanin adverse effects in the two groups. The study demonstrated that the optimal loading dose regimen of teicoplanin can rapidly reach target C_min, and result in a good clinical efficacy and low adverse effect in critically ill Chinese patients.     

精细化护理在老年急危重症急救护理中的应用

目的 研究探讨精细化护理在急危重症老年患者中的应用效果.方法 将本院2014年3月至2015年3月收治的急危重症老年患者78例,按照统计学原理分为对照组和观察组,每组39例.对照组患者在急救护理的过程中展开常规化的护理措施,观察组患者在急救护理的时候实行精细化护理模式,比较两组患者各项急救措施所花时间与抢救成功率.结果 急救护理结果表明,观察组患者接诊时间、抢救室护理时间以及总急救时间都要短于对照组患者,差异有统计学意义(P＜ 0.05);与此同时,观察组患者基本生命支持5 min内完成率与抢救成功率分别为87.2％、92.3％,对照组患者基本生命支持5 min内完成率与抢救成功率为56.4％、71.8％,差异有统计学意义(P＜0.05).结论 在为急危重症老年患者实行急救护理的过程中,采用精细化护理模式,可以为患者迸一步抢救赢得时间,促使患者在最短的时间内恢复生命支持,提高抢救成功率,精细化护理在老年急危重症患者急救护理中具有重要的临床意义.