Objective To investigate the entry points for clinical work of intensive care unit (ICU) pharmacists. Methods Through combination with daily work and referring the domestic and foreign literature,the characteristics of ICU medications were discussed to find out the entry point for clinical work of ICU pharmacists. Results ICU patients particularly need individualized pharmaceutical care because of the special pathophysiological characteristics and medicine use. Conclusion ICU pharmacists should provide pharmaceutical care based on Pharmacokinetics/pharmacodynamics knowledge and focus on the drug dosage adjustment,drug interactions and adverse event prevention.
Key words:
Intensive care unit
;
Medication characteristics
;
Pharmacokinetics/pharmacodynamics
;
Pharmaceutical care
早在1970年,美国重症医学会在成立之际便提出药师是重症监护病房(intensive care unit,ICU)治疗团队中的一员[1]。随着我国临床药学事业的发展,国内临床药师的作用也逐步得到行业认可。2014年,中华医学会重症医学分会在年鉴中提出,临床药师是ICU治疗团队的新成员[2]。ICU是一个特殊的临床科室,强调多学科交叉,这也要求ICU药师需掌握比普通专科药师更广泛的临床治疗知识,以及针对危重症患者采取的特殊治疗手段。笔者从ICU患者用药复杂性出发,剖析ICU临床药师的工作切入点。
1.2.1 多药联用 重症患者往往合并有多种疾病或多脏器功能损伤,需要同时使用多种药物,潜在相互作用和配伍禁忌增多,致使药物不良事件(adverse drug event,ADE)发生率增加。据统计,ICU中发生ADE的患者平均用药种类多达15种[4]。同时有研究表明,服用5种以下药物,ADE的发生率为6%~8%,服用6~10种药物时,ADE发生率则上升至40%[10]。
目前,大多数用药指南与说明书中用法用量主要针对一般患者,ICU患者因严重的病理改变,使药物的分布、代谢、排泄过程发生显著改变,某些治疗药物在该类患者体内血药浓度与预期值存在较大偏差。因此,开展治疗药物浓度监测(therapeutic drug monitoring,TDM),通过体内药物浓度调整给药剂量,优化药物治疗效果,是ICU临床药师开展工作的一个切入点。一项针对医院获得性肺炎患者的临床对照研究表明,与未进行TDM和病原菌MIC监测的患者相比,测定的氨基苷类、氟喹诺酮类和β-内酰胺类药物浓度和病原菌MIC值调整用药方案组患者临床预后和病菌清除率显著增加[11]。对于部分ICU患者,仅一次监测结果并不能代表整个治疗期间的浓度值。如前所述,第三间隙效应强的患者,药物的Vd增加,峰谷浓度均受影响,随着患者病情好转,第三间隙效应逐渐消失,真实的峰谷浓度会发生改变,因此,对于发生SIRS等导致毛细血管渗漏严重的ICU患者,血药浓度的连续监测十分必要。
CANDICER,ISHAQL,ROBERTM,et al.Pharmacist con-tributions as members of the multidisciplinary ICU team[J].Chest,2013,144(5):1688-1695.
Critical care pharmacy services in the ICU have expanded from traditional dispensing responsibilities to being recognized as an essential component of multidisciplinary care for critically ill patients. Augmented by technology and resource utilization, this shift in roles has allowed pharmacists to provide valuable services in the form of assisting physicians and clinicians with pharmacotherapy decision-making, reducing medication errors, and improving medication safety systems to optimize patient outcomes. Documented improvements in the management of infections, anticoagulation therapy, sedation, and analgesia for patients receiving mechanical ventilation and in emergency response help to justify the need for clinical pharmacy services for critically ill patients. Contributions to quality improvement initiatives, scholarly and research activities, and the education and training of interdisciplinary personnel are also valued services offered by clinical pharmacists. Partnering with physician and nursing champions can garner support from hospital administrators for the addition of clinical pharmacy critical care services. The addition of a pharmacist to an interprofessional critical care team should be encouraged as health-care systems focus on improving the quality and efficiency of care delivered to improve patient outcomes.
MARILYNT,CAROLYNE,RICHARDJ,et al.Guidelines on critical care services and personnel:recommendations based on a system of categorization of three levels of care[J].Crit Care Med,2003,31(11):2677-2683.
To describe three levels of hospital-based critical care centers to optimally match services and personnel with community needs, and to recommend essential intensive care unit services and personnel for each critical care level.A multidisciplinary writing panel of professionals with expertise in the clinical practice of critical care medicine working under the direction of the American College of Critical Care Medicine (ACCM).Relevant medical literature was accessed through a systematic Medline search and synthesized by the ACCM writing panel, a multidisciplinary group of critical care experts. Consensus for the final written document was reached through collaboration in meetings and through electronic communication modalities. Literature cited included previously written guidelines from the ACCM, published expert opinion and statements from official organizations, published review articles, and nonrandomized, historical cohort investigations. With this background, the ACCM writing panel described a three-tiered system of intensive care units determined by service-based criteria.Guidelines for optimal intensive care unit services and personnel for hospitals with varying resources will facilitate both local and regional delivery of consistent and excellent care to critically ill patients.
CAMIRÉE,MOYENE,STELFO XH,et al.Medication errors in critical care:risk factors,prevention and disclosure[J].Can Med Assoc J,2009,180(9):936-941.
The article discusses the risk factors, prevention and the need for disclosure of the incidence of medication errors in the intensive care units in Canada. It explores several components that contribute to the incidence of medication errors including the situation of the patients, inexperience and lack of knowledge of healthcare providers, and the existing environment in the health care facilities. It highlights various techniques and strategies on how to prevent medication errors such as the provision of medical education for patients, pharmacology education and risk factor awareness for nurses, and an effective health care administration. It suggests clinicians that disclosure of harmful errors and medical errors is an ethical imperative.
BURKHARDTO,KUMARV,KATTERWED,et al.Erta-penem in critically ill patients with early-onset ventilator-associated pneumonia:pharmacokinetics with special consi-deration of free-drug concentration[J].J Antimicrob Chemother,2007,59(2):277-284.
[本文引用:1]
[6]
ROBERTSJ,ABDUL-AZIZM,LIPMANJ,et al.Individua-lised antibiotic dosing for patients who are critically ill:challenges and potential solutions[J].Lancet Infect Dis,2014,50(2):99-110.
Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.
GONÇALVES-PEREIRAJ,PÓVOAP.Antibiotics in criti-cally ill patients:a systematic review of the pharmaco-kinetics of β-lactams[J].Crit Care,2011,15(5):R206.
[本文引用:1]
[8]
VARGHESEJ,ROBERTSJ,LIPMANJ.Antimicrobial pha-rmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock[J].Crit Care Clin,2011,27(1):19-34.
Antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) are important considerations, particularly in critically ill patients with severe sepsis and septic shock. The pathophysiologic changes that occur in these conditions can have a major effect on pharmacokinetic parameters, which in turn could result in failure to achieve pharmacodynamic targets for antimicrobials thus adversely affecting clinical outcome. This paper discusses the pathophysiologic changes that occur during severe sepsis and septic shock and the consequent effects on antimicrobial PK and PD. The effect of PK/PD on specific antimicrobial classes is discussed and a rational framework for antimicrobial dosing is provided. Knowledge of PK/PD properties of antimicrobials can be used to personalize dosing regimens not only to maximize antimicrobial activity but also to minimize toxicity and reduce the development of antimicrobial resistance.
UDYA,VARGHESEJ,ALTUKRONIM,et al.Subtherape-utic initial β-lactam concentrations in select critically ill patients:association between augmented renal clearance and low trough drug concentrations[J].Chest,2012,142(1):30-39.
β-Lactams are routinely used as empirical therapy in critical illness, with extended concentrations above the minimum inhibitory concentration (MIC) of the infecting organism required for effective treatment. Changes in renal function in this setting can significantly impact the probability of achieving such targets.Analysis was made of trough plasma drug concentrations obtained via therapeutic drug monitoring, compared with renal function, in critically ill patients receiving empirical β-lactam therapy. Drug concentrations were measured by means of high-performance liquid chromatography and corrected for protein binding. Therapeutic levels were defined as greater than or equal to MIC and greater than or equal to four times MIC (maximum bacterial eradication), respectively. Renal function was assessed by means of an 8-h creatinine clearance (CLCR).Fifty-two concurrent trough concentrations and CLCR measures were used in analysis. Piperacillin was the most frequent β-lactam prescribed (48%), whereas empirical cover and Staphylococcus species were the most common indications for therapy (62%). Most patients were mechanically ventilated on the day of study (85%), although only 25% were receiving vasopressors. In only 58% (n = 30) was the trough drug concentration greater than or equal to MIC, falling to 31% (n = 16) when using four times MIC as the target. CLCR values ≥ 130 mL/min/1.73 m2 were associated with trough concentrations less than MIC in 82% (P < .001) and less than four times MIC in 72% (P < .001). CLCR remained a significant predictor of subtherapeutic concentrations in multivariate analysis.Elevated CLCR appears to be an important predictor of subtherapeutic β-lactam concentrations and suggests an important role in identifying such patients in the ICU.
FASOLINOT,SNYDERR.Linking nurse characteristics,team member effectiveness,practice environment,and medication error incidence[J].J Nurs Care Qual,2012,27(2):E9-E16.
Abstract Clinical unit nurse characteristics, practice environment, and team member effectiveness are assumed to play a critical role in medication safety. This study used a multimethod approach to examine the association of these factors with medication errors. Findings suggested that older, more experienced registered nurses made less medication errors. Environment and team member effectiveness were not strongly associated with medication error incidence. Numerous system factors limited implementation and outcomes of this safety study and are discussed.
SCAGLINOEF,ESPOSITOS,LEONES,et al.Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia[J].Eur Respir J,2009,34(2):394-400.
Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes.
Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of -lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8 the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these -lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.
DE ROSAF,CORCIONES,BAIETTOL,et al.Pharmaco-kinetics of linezolid during extracorporeal embraneoxy-genation[J].Int J Antimicrob Agents,2013,41(6):590-591.
[本文引用:1]
[14]
GONGY,CHENY,LIQ,et al.Population pharmacokinetic analysis of digoxin in Chinese neonates and infants[J].J Pharmacol Sci,2014,125(2):142-149.
To obtain more information regarding the influence of various covariates on the disposition of digoxin in Chinese neonates and infants, routine clinical pharmacokinetic data were retrospectively collected from 131 hospitalized patients. A nonlinear mixed effects modeling (NONMEM) method was applied to the data. A one-compartment/first-order absorption model was employed to estimate the influence of total body weight (allometric power model), postnatal age, serum creatinine, gender, presence of heart congestive failure, and concomitant medications on apparent total clearance and apparent drug distribution of digoxin. Pharmacokinetic parameter estimates for CL/F and V/F were 0.147 L (-1) g(-1) and 15.7 L/kg, respectively. Total body weight and postnatal age were identified as the important factors affecting total clearance of digoxin; total body weight was the covariate identified to influence the apparent distribution volume. Both internal (bootstrap method, visual predictive checks, and normalized prediction distributed error) and external validation supported the stable and predictive performance of the final model. We concluded that the model can be used to choose an appropriate dose regimen in Chinese neonates and infants.
JASONA,MOHDH,JEFFREYL,et al.Challenges and potential solutions-individualized antibiotic dosing at the bed-side for critically ill patients:a structured review[J].Lancet Infect Dis,2014,14(6):498-509.
Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes indude altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.
RESAR RK,ROZICH JD,CLASSEND.Methodology and rationale for the measurement of harm with trigger tools[J].Qual Saf Health care,2003,12(Suppl 2):ii39-ii45.
The growing recognition of harm as an unwelcome and frequently unrecognized byproduct of health care has initiated focused efforts to create highly reliable organizations for safe healthcare delivery. While debate continues over the exact magnitude of harm, there is a general acceptance of the need to improve our ability to deliver care in a safer manner. A major barrier to progress in safety has been the ability to effectively measure harm consistently and thus develop effective and targeted strategies to prevent its occurrence. This has resulted in a shift from initiatives focused exclusively on analysis of errors to those targeting events linked to harm. There is a growing recognition of a distinction between errors and adverse events as they often represent unique concepts fostering different strategies for improvement of safety. Conventional approaches to identifying and quantifying harm such as individual chart audits, incident reports, or voluntary administrative reporting have often been less successful in improving the detection of adverse events. As a result, a new method of measuring harm--the trigger tool--has been developed. It is easily customized and can be readily taught, enabling consistent and accurate measurement of harm. The history, application, and impact of the trigger tool concept in identifying and quantifying harm are discussed.
KENNERLY DA,KUDYAKOVR,GRACAB,et al.Chara-cterization of adverse events detected in a large health care delivery system using an enhanced global trigger tool over a five-year interval[J].Health Serv Res,2014,49(5):1407-1425.
Objective. To report 5 years of adverse events (AEs) identified using an enhanced Global Trigger Tool (GTT) in a large health care system.<br/>Study Setting. Records from monthly random samples of adults admitted to eight acute care hospitals from 2007 to 2011 with lengths of stay >= 3 days were reviewed.<br/>Study Design. We examined AE incidence overall and by presence on admission, severity, stemming from care provided versus omitted, preventability, and category; and the overlap with commonly used AE-detection systems.<br/>Data Collection. Professional nurse reviewers abstracted 9,017 records using the enhanced GTT, recording triggers and AEs. Medical record/account numbers were matched to identify overlapping voluntary reports or AHRQ Patient Safety Indicators (PSIs).<br/>Principal Findings. Estimated AE rates were as follows: 61.4 AEs/1,000 patient-days, 38.1 AEs/100 discharges, and 32.1 percent of patients with >= 1 AE. Of 1,300 presenton- admission AEs (37.9 percent of total), 78.5 percent showed NCC-MERP level F harm and 87.6 percent were "preventable/possibly preventable." Of 2,129 hospital-acquired AEs, 63.3 percent had level E harm, 70.8 percent were "preventable/possibly preventable"; the most common category was "surgical/procedural" (40.5 percent). Voluntary reports and PSIs captured <5 percent of encounters with hospital-acquired AEs.<br/>Conclusions. AEs are common and potentially amenable to prevention. GTT-identified AEs are seldom caught by commonly used AE-detection systems.
Pharmacist con-tributions as members of the multidisciplinary ICU team
1
2013
... 早在1970年,美国重症医学会在成立之际便提出药师是重症监护病房(intensive care unit,ICU)治疗团队中的一员[1].随着我国临床药学事业的发展,国内临床药师的作用也逐步得到行业认可.2014年,中华医学会重症医学分会在年鉴中提出,临床药师是ICU治疗团队的新成员[2].ICU是一个特殊的临床科室,强调多学科交叉,这也要求ICU药师需掌握比普通专科药师更广泛的临床治疗知识,以及针对危重症患者采取的特殊治疗手段.笔者从ICU患者用药复杂性出发,剖析ICU临床药师的工作切入点. ...
1
2014
... 早在1970年,美国重症医学会在成立之际便提出药师是重症监护病房(intensive care unit,ICU)治疗团队中的一员[1].随着我国临床药学事业的发展,国内临床药师的作用也逐步得到行业认可.2014年,中华医学会重症医学分会在年鉴中提出,临床药师是ICU治疗团队的新成员[2].ICU是一个特殊的临床科室,强调多学科交叉,这也要求ICU药师需掌握比普通专科药师更广泛的临床治疗知识,以及针对危重症患者采取的特殊治疗手段.笔者从ICU患者用药复杂性出发,剖析ICU临床药师的工作切入点. ...
Guidelines on critical care services and personnel:recommendations based on a system of categorization of three levels of care
... 1.2.1 多药联用 重症患者往往合并有多种疾病或多脏器功能损伤,需要同时使用多种药物,潜在相互作用和配伍禁忌增多,致使药物不良事件(adverse drug event,ADE)发生率增加.据统计,ICU中发生ADE的患者平均用药种类多达15种[4].同时有研究表明,服用5种以下药物,ADE的发生率为6%~8%,服用6~10种药物时,ADE发生率则上升至40%[10]. ...
Erta-penem in critically ill patients with early-onset ventilator-associated pneumonia:pharmacokinetics with special consi-deration of free-drug concentration
Subtherape-utic initial β-lactam concentrations in select critically ill patients:association between augmented renal clearance and low trough drug concentrations
Linking nurse characteristics,team member effectiveness,practice environment,and medication error incidence
1
2012
... 1.2.1 多药联用 重症患者往往合并有多种疾病或多脏器功能损伤,需要同时使用多种药物,潜在相互作用和配伍禁忌增多,致使药物不良事件(adverse drug event,ADE)发生率增加.据统计,ICU中发生ADE的患者平均用药种类多达15种[4].同时有研究表明,服用5种以下药物,ADE的发生率为6%~8%,服用6~10种药物时,ADE发生率则上升至40%[10]. ...
Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia
1
2009
... 目前,大多数用药指南与说明书中用法用量主要针对一般患者,ICU患者因严重的病理改变,使药物的分布、代谢、排泄过程发生显著改变,某些治疗药物在该类患者体内血药浓度与预期值存在较大偏差.因此,开展治疗药物浓度监测(therapeutic drug monitoring,TDM),通过体内药物浓度调整给药剂量,优化药物治疗效果,是ICU临床药师开展工作的一个切入点.一项针对医院获得性肺炎患者的临床对照研究表明,与未进行TDM和病原菌MIC监测的患者相比,测定的氨基苷类、氟喹诺酮类和β-内酰胺类药物浓度和病原菌MIC值调整用药方案组患者临床预后和病菌清除率显著增加[11].对于部分ICU患者,仅一次监测结果并不能代表整个治疗期间的浓度值.如前所述,第三间隙效应强的患者,药物的Vd增加,峰谷浓度均受影响,随着患者病情好转,第三间隙效应逐渐消失,真实的峰谷浓度会发生改变,因此,对于发生SIRS等导致毛细血管渗漏严重的ICU患者,血药浓度的连续监测十分必要. ...
β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy:a case-control study
, 师少军, 黄怡菲
