Evaluation of medication-related problems in liver transplant recipients with and without an outpatient medication consultation by a clinical pharmacist: a cohort study.

BACKGROUND: Transplant recipients undergo significant changes in their medication regimen during follow-up and are at an increased risk for medication-related problems (MRPs). AIM: This study aimed to compare the prevalence and types of MRPs and interventions in liver transplant recipients with and without an outpatient medication consultation by a clinical pharmacist as well as the satisfaction with information about medicines and medication adherence. METHOD: We performed a single-center, observational cohort study. A retro- and prospective cohort were used and subdivided in a group that did and did not receive a medication consultation. The prevalence and types of MRPs and interventions were identified and categorized. The satisfaction parameters were evaluated using validated questionnaires. RESULTS: Included were 291 patients. In total, 368 MRPs were identified in 197 patients in the non-medication consultation cohort (median 1; range 1-3 per patient) and 248 MRPs in 94 patients in the medication consultation cohort (median 2; range 1-4 per patient). In the medication consultation cohort, significantly fewer MRPs as unnecessary drugs (17.3% versus 58.7%, p < 0.001), suboptimal therapy (2.4% versus 9.5%, p < 0.001), untreated indication (2.8% versus 6.8%, p = 0.040) and underdosed drugs (0.4% versus 6.3%, p < 0.001) were identified. In the non-medication consultation cohort significantly more patients used unnecessary drugs (72.1% versus 39.4%, p < 0.001) compared to the medication consultation cohort. Patients in both cohorts are satisfied with the information about medicines and reported a high medication adherence. CONCLUSION: Patients in the medication consultation cohort had significantly fewer MRPs and used significantly less unnecessary drugs. Including a clinical pharmacist to the post-transplant care has an added value.

Using Residual Blood from the Arterial Blood Gas Test to Perform Therapeutic Drug Monitoring of Vancomycin: An Example of Good Clinical Practice Moving towards a Sustainable Intensive Care Unit.

Background: Regarding sustainability in the intensive care unit (ICU), there is increasing interest in reducing material waste and avoiding unnecessary procedures. Therapeutic drug monitoring (TDM) of vancomycin, using a dedicated tube, is standard clinical care during treatment with vancomycin. Furthermore, in the ICU, on a daily basis, arterial blood gas (ABG) tests are frequently performed throughout the day. After analysis, a variable volume of blood is discarded. Lithium heparin (LiHep) syringes for ABG tests differ from normally used dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The primary objective was to compare both containers and validate the use of LiHep syringes. Secondary objectives were to evaluate the potential impact on saving materials, nursing time, and costs when implementing vancomycin TDM via LiHep syringes. Methods: Vancomycin analysis from sampling in lithium heparin (LiHep) syringes for ABG tests was validated and compared with the concentrations from conventional sampling in K2EDTA tubes. For method comparison, a Bland-Altman plot and Deming regression analysis were performed. The method was validated for inter- and intra-day precision and accuracy. Vancomycin was analyzed by means of the validated method using a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) autoanalyzer. Furthermore, an analysis was conducted to evaluate the potential impact of implementing vancomycin sampling via ABG tests on savings in materials, nursing time, and costs. Results: From 18 patients, 24 plasma samples in both K2EDTA tubes and LiHep syringes were obtained and compared. The mean relative difference between the two containers was -2.0% (-3.0 to -0.93%). Both the Deming regression analysis and the Bland-Altman plot met the acceptance criteria. Potentially, over 1000 blood draws and accompanying materials and packaging can be saved when vancomycin samples are obtained by means of scavenged LiHep syringes. The vancomycin analysis for LiHep syringes showed a total interday precision of 1.95% and an accuracy of 99.7%. The total intraday precision was 2.22%, and the accuracy was 99.2%. Accuracy and precision values were within the acceptance criteria of recovery 85 to 115% and ≤15%, respectively. Conclusion: No significant differences were found in vancomycin concentration between the two analyses, and the LiHep analysis was validated for further implementation in clinical care. Residual blood from ABG test samples can be used for TDM of vancomycin, resulting in a potential reduction of materials used and the number of blood draws. These results will contribute to a more sustainable TDM process with benefits for the patient.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Voluntarily reported prescribing, monitoring and medication transfer errors in intensive care units in The Netherlands.

Background Medication errors occur frequently in intensive care units (ICU). Voluntarily reported medication errors form an easily available source of information. Objective This study aimed to characterize prescribing, monitoring and medication transfer errors that were voluntarily reported in the ICU, in order to reveal medication safety issues. Setting This retrospective data analysis study included reports of medication errors from eleven Dutch ICU's from January 2016 to December 2017. Method We used data extractions from the incident reporting systems of the participating ICU's. The reports were transferred into one database and categorized into type of error, cause, medication (groups), and patient harm. Descriptive statistics were used to calculate the proportion of medication errors and the distribution of subcategories. Based on the analysis, ICU medication safety issues were revealed. Main outcome measure The main outcome measure was the proportion of prescribing, monitoring and medication transfer error reports. Results Prescribing errors were reported most frequently (n = 233, 33%), followed by medication transfer errors (n = 85, 12%) and monitoring errors (n = 27, 4%). Other findings were: medication transfer errors frequently caused serious harm, especially the omission of home medication involving the central nervous system and proton pump inhibitors; omissions and dosing errors occurred most frequently; protocol problems caused a quarter of the medication errors; and medications needing blood level monitoring (e.g. tacrolimus, vancomycin, heparin and insulin) were frequently involved. Conclusion This analysis of voluntarily reported prescribing, monitoring and medication transfer errors warrants several improvement measures in these processes, which may help to increase medication safety in the ICU.

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION: EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

Pharmacist interventions during patient rounds in two intensive care units: Clinical and financial impact.

INTRODUCTION: The risk of prescribing errors and related adverse drug events (ADE) on the intensive care unit (ICU) is high. Based on studies carried out in North America or the UK, a clinical pharmacy service can reduce ADEs and lower overall costs. This study looks into the clinical and financial impact of interventions made by pharmacists during patient rounds in two ICU settings in the Netherlands. MATERIALS AND METHODS: A quality improvement study was performed in a general teaching hospital (GTH) and a university hospital (UH) in the Netherlands. The improvement consisted of a review of medication orders and participation in patient rounds by an ICU-trained pharmacist. The main outcome measure was the proportion of accepted pharmacist interventions. Secondary outcome measures were the clinical relevance of the accepted interventions, the proportion of prevented potential ADEs (pADE) and a cost-benefit ratio. RESULTS: In the GTH 160 patients and in the UH 174 patients were included. A total of 332 and 280 interventions were analysed. Acceptance of the interventions was 67.3% in the GTH and 61.8% in the UH. The accepted interventions were mostly scored as clinically relevant, resulting in 0.16 and 0.11 prevented pADEs per patient. The cost benefit was €119 (GTH) and €136 (UH) per accepted intervention. CONCLUSION: This clinical pharmacy service in two ICUs resulted in high numbers of accepted and clinically relevant interventions. Our model appeared to be cost-effective in both ICU settings.

Avoiding crystallization of lorazepam during infusion.

Lorazepam is a strong sedative for intensive care patients and a commonly used method of administering it to the patient is by infusion of a freshly prepared lorazepam solution. During lorazepam infusion often unwanted lorazepam crystallization occurs, resulting in line obstruction and reduced lorazepam concentrations. With the aid of solubility measurements a solid-liquid phase diagram for lorazepam in mixtures of a commercially available lorazepam solution and an aqueous glucose solution was determined. This confirmed that the glucose solution acts as an anti-solvent, greatly reducing the lorazepam solubility in the infusion solution. Three approaches are proposed to obtain stable lorazepam solutions upon mixing both solutions and thus to prevent crystallization during infusion: (1) using a high lorazepam concentration, and thus a lower glucose solution volume fraction, in the mixed solution; (2) using an elevated temperature during solution preparation and administration; (3) reducing the lorazepam concentration in the commercial lorazepam solution.

Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors.

BACKGROUND: The occurrence and the clinical relevance of rebound acid hypersecretion after discontinuation of proton pump inhibitors is unclear. AIM: To perform a systematic review of rebound acid hypersecretion after discontinuation of proton pump inhibitors. METHODS: PubMed, Embase and Central were searched up to October 2005 with indexed terms. RESULTS: Eight studies were included, sample size was 6-32. The studies used both basal and stimulated acid output as parameters to study rebound acid hypersecretion and assessed these at different time points and with variable methods. Five studies (including four randomized studies) did not find any evidence for rebound acid hypersecretion after proton pump inhibitor therapy. Of the remaining three studies, the duration of proton pump inhibitor therapy was the longest and two of these studies were the only to assess Helicobacter pylori status of their study subjects. These two studies suggested that rebound acid hypersecretion may occur in H. pylori-negatives after 8 weeks of proton pump inhibitors. CONCLUSIONS: Studies that have investigated rebound acid hypersecretion after cessation of proton pump inhibitor treatment are heterogenic in design, methods and outcome. There is some evidence from uncontrolled trials for an increased capacity to secrete acid in H. pylori-negative subjects after 8 weeks of treatment. There is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy.

Quetiapine in overdosage: a clinical and pharmacokinetic analysis of 14 cases.

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.