Effect of a Pharmacy-based Centralized Intravenous Admixture Service on the Prevalence of Medication Errors:A Before-and-After Study

Intravenous admixture preparation errors (IAPEs) may lead to patient harm. The primary aim of this study was to assess the effect of a pharmacy-based centralized intravenous admixture service (CIVAS) on IAPEs. METHODS: We conducted a before-and-after study in 3 clinical wards before CIVAS implementation and in the CIVAS unit 18 months after implementation. Intravenous admixture preparation error data were collected by disguised observation. The primary outcome was the proportion of admixtures with 1 or more IAPEs. Secondary outcomes were the type and potential severity of IAPEs, noncompliance to hygiene procedures, and nursing staff satisfaction with the CIVAS. The primary outcome was analyzed using a multivariable mixed-effects logistic regression model. RESULTS: One or more IAPEs were identified in 14 of 543 admixtures (2.6%) in the CIVAS unit and in 148 of 282 admixtures (52.5%) in the clinical wards (odds ratio, 0.02; 95% confidence interval, 0.004–0.05). The most common IAPE types were wrong solvent or diluent (n = 95) and wrong volume of infusion fluid (n = 45). No potentially harmful IAPEs occurred in the CIVAS unit as opposed to 22 (7.8%) in the clinical wards. Disinfection procedures were better adhered to in the CIVAS unit. Overall nurse satisfaction with the CIVAS increased from a median of 70 (n = 166) 5 months after intervention to 77 (n = 115) 18 months after intervention (P < 0.001) on a 100-point scale. CONCLUSIONS: Centralized intravenous admixture service performed notably better than the clinical wards with regard to IAPEs and noncompliance to hygiene procedures. Nurses were satisfied with the CIVAS. Hence, the implementation of CIVAS is an important strategy to improve medication safety in hospitals

Prevalence and determinants of intravenous admixture preparation errors:A prospective observational study in a university hospital

Background Intravenous admixture preparation errors (IAPEs) may lead to patient harm. Insight into the prevalence as well as the determinants associated with these IAPEs is needed to elicit preventive measures. Aim The primary aim of this study was to assess the prevalence of IAPEs. Secondary aims were to identify the type, severity, and determinants of IAPEs. Method A prospective observational study was performed in a Dutch university hospital. IAPE data were collected by disguised observation. The primary outcome was the proportion of admixtures with one or more IAPEs. Descriptive statistics were used for the prevalence, type, and severity of IAPEs. Mixed-effects logistic regression analyses were used to estimate the determinants of IAPEs. Results A total of 533 IAPEs occurred in 367 of 614 admixtures (59.8%) prepared by nursing staff. The most prevalent errors were wrong preparation technique (n = 257) and wrong volume of infusion fluid (n = 107). Fifty-nine IAPEs (11.1%) were potentially harmful. The following variables were associated with IAPEs: multistep versus single-step preparations (adjusted odds ratio [OR(adj)] 4.08, 95% confidence interval [CI] 2.27–7.35); interruption versus no interruption (OR(adj) 2.32, CI 1.13–4.74); weekend versus weekdays (OR(adj) 2.12, CI 1.14–3.95); time window 2 p.m.-6 p.m. versus 7 a.m.-10 a.m. (OR(adj) 3.38, CI 1.60–7.15); and paediatric versus adult wards (OR(adj) 0.14, CI 0.06–0.37). Conclusion IAPEs, including harmful IAPEs, occurred frequently. The determinants associated with IAPEs point to factors associated with preparation complexity and working conditions. Strategies to reduce the occurrence of IAPEs and therefore patient harm should target the identified determinants

Pharmacokinetics of Haloperidol in Critically Ill Patients:Is There an Association with Inflammation?

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing. One hundred and thirty-nine samples from 22 patients were collected in a single-center study in adults with ICU delirium who were treated with low-dose intravenous haloperidol (3–6 mg per day). We conducted a population pharmacokinetic analysis using Nonlinear Mixed Effects Modelling (NONMEM). A one-compartment model best described the data. The mean population estimates were 51.7 L/h (IIV 42.1%) for clearance and 1490 L for the volume of distribution. The calculated half-life was around 22 h (12.3–29.73 h) for an average patient. A negative correlation between C-Reactive Protein (CRP) and haloperidol clearance was observed, where clearance decreased significantly with increasing CRP up to a CRP concentration of 100 mg/L. This is the first step towards haloperidol precision dosing in ICU patients and our results indicate a possible role of inflammation

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors:An Evaluation of Treatment Options

Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given

Dynamics of the QTc interval over a 24-h dose interval after start of intravenous ciprofloxacin or low-dose erythromycin administration in ICU patients

QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (>= 18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed.Clinical Pharmacy and Toxicolog

The effect of a medication reconciliation program in two intensive care units in the Netherlands: a prospective intervention study with a before and after design

Background: Medication errors occur frequently in the intensive care unit (ICU) and during care transitions. Chronic medication is often temporarily stopped at the ICU. Unfortunately, when the patient improves, the restart of this medication is easily forgotten. Moreover, temporal ICU medication is often unintentionally continued after ICU discharge. Medication reconciliation could be useful to prevent such errors. Therefore, the aim of this study was to determine the effect of medication reconciliation at the ICU. Methods: This prospective 8-month study with a pre- and post-design was carried out in two ICU settings in the Netherlands. Patients were included when they used ≥ 1 chronic medicine and when the ICU stay exceeded 24 h. The intervention consisted of medication reconciliation by pharmacists at the moment of ICU admission and prior to ICU discharge. Medication transfer errors (MTEs) were collected and the severity of potential harm of these MTEs was measured, based on a potential adverse drug event score (pADE = 0; 0.01; 0.1; 0.4; 0.6). Primary outcome measures were the proportions of patients with ≥ 1 MTE at ICU admission and after discharge. Secondary outcome measures were the proportions of patients with a pADE score ≥ 0.01 due to these MTEs, the severity of the pADEs and the associated costs. Odds ratio and 95% confidence intervals were calculated, by using a multivariate logistic regression analysis. Results: In the pre-intervention phase, 266 patients were included and 212 in the post-intervention phase. The proportion of patients with ≥ 1 MTE at ICU admission was reduced from 45.1 to 14.6% (ORadj 0.18 [95% CI 0.11–0.30]) and after discharge from 73.9 to 41.2% (ORadj 0.24 [95% CI 0.15–0.37]). The proportion of patients with a pADE ≥ 0.01 at ICU admission was reduced from 34.8 to 8.0% (ORadj 0.13 [95% CI 0.07–0.24]) and after discharge from 69.5 to 36.2% (ORadj 0.26 [95% CI 0.17–0.40]). The pADE reduction resulted in a potential net cost–benefit of € 103 per patient. Conclusions: Medication reconciliation by pharmacists at ICU transfers is an effective safety intervention, leading to a significant decrease in the number of MTE and a cost-effective reduction in potential harm. Trial registration Dutch trial register: NTR4159, 5 September 2013, retrospectively registered

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

INTRODUCTION: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. METHODS AND ANALYSIS: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. ETHICS AND DISSEMINATION: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings

Safe use of proton pump inhibitors in patients with cirrhosis

AimsProton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. MethodsA systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification. ResultsA total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. ConclusionsWe suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients

Early Production of IL-22 but Not IL-17 by Peripheral Blood Mononuclear Cells Exposed to live Borrelia burgdorferi: The Role of Monocytes and Interleukin-1

If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-γ but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1β as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection