Loraine Lie-A-Huen

On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study

IntroductionPatients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting.MethodsA prospective study compared a baseline period with an intervention period. During the intervention period, an ICU hospital pharmacist reviewed medication orders for patients admitted to the ICU, noted issues related to prescribing, formulated recommendations and discussed those during patient review meetings with the attending ICU physicians. Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians.ResultsDuring the 8.5-month study period, medication orders for 1,173 patients were reviewed. The ICU hospital pharmacist made a total of 659 recommendations. During the intervention period, the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74%. The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period: 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days, respectively (P < 0.001). Preventable ADEs (patient harm, National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period (P = 0.25). Per monitored patient-day, the intervention itself cost €3, but might have saved €26 to €40 by preventing ADEs.ConclusionsOn-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm (preventable ADEs) at acceptable costs per monitored patient-day.Trial registration numberISRCTN92487665

Influence of Different Fat Emulsion-Based Intravenous Formulations on the Pharmacokinetics and Pharmacodynamics of Propofol

AbstractPurpose. The influence of different intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol was investigated using the effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. Methods. Propofol was administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats. Propofol was formulated as a 1% emulsion in an Intralipid 10%®-like fat emulsion (Diprivan-10®, D) or as a 1%- or 6% emulsion in Lipofundin® MCT/LCT-10% (Pl% and P6%, respectively). EEG was recorded continuously and arterial blood samples were collected serially for the determination of propofol concentrations using HPLC. Results. Following bolus infusion, the pharmacokinetics of the various propofol emulsions could adequately be described by a two-compart-mental pharmacokinetic model. The average values for clearance (Cl), volume of distribution at steady-state (Vd,ss) and terminal half-life (t1/2, λ2) were 107 ± 4 ml/min/kg, 1.38 ± 0.06 l/kg and 16 ± 1 min, respectively (mean ± S.E., n = 22). No significant differences were observed between the three propofol formulations. After continuous infusion these values were 112 ± 11 ml/min/kg, 5.19 ± 0.41 l/kg and 45 ± 3 min, respectively (mean±S.E., n = 20) with again no statistically significant differences between the three propofol formulations. Comparison between the bolus- and the continuous infusion revealed a statistically significant difference for both Vd,ss and t1/2, λ2 (p < 0.05), whereas Cl remained unchanged. In all treatment groups infusion of propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop was observed between blood concentrations and EEG effect for all formulations. The hysteresis was minimized by a semi-parametric method and resulted in a biphasic concentration-effect relationship of propofol that was described non-parametrically. For P6% a larger rate constant onset of drug effect (t,1/2, keo) was observed compared to the other propofol formulations (p<0.05). Conclusions. The pharmacokinetics and pharmacodynamics of propofol are not affected by to a large extent the type of emulsion nor by the concentration of propofol in the intravenous formulation.

Adverse Drug Events in Older Hospitalized Patients: Results and Reliability of a Comprehensive and Structured Identification Strategy

Background Older patients are at high risk for experiencing Adverse Drug Events (ADEs) during hospitalization. To be able to reduce ADEs in these vulnerable patients, hospitals first need to measure the occurrence of ADEs, especially those that are preventable. However, data on preventable ADEs (pADEs) occurring during hospitalization in older patients are scarce, and no ‘gold standard’ for the identification of ADEs exists. Methodology The study was conducted in three hospitals in the Netherlands in 2007. ADEs were retrospectively identified by a team of experts using a comprehensive and structured patient chart review (PCR) combined with a trigger-tool as an aid. This ADE identification strategy was applied to a cohort of 250 older hospitalized patients. To estimate the intra- and inter-rater reliabilities, Cohen’s kappa values were calculated. Principal Findings In total, 118 ADEs were detected which occurred in 62 patients. This ADE yield was 1.1 to 2.7 times higher in comparison to other ADE studies in older hospitalized patients. Of the 118 ADEs, 83 (70.3%) were pADEs; 51 pADEs (43.2% of all ADEs identified) caused serious patient harm. Patient harm caused by ADEs resulted in various events. The overall intra-rater agreement of the developed strategy was substantial (κ = 0.74); the overall inter-rater agreement was only fair (κ = 0.24). Conclusions/Significance The ADE identification strategy provided a detailed insight into the scope of ADEs occurring in older hospitalized patients, and showed that the majority of (serious) ADEs can be prevented. Several strategy related aspects, as well as setting/study specific aspects, may have contributed to the results gained. These aspects should be considered whenever ADE measurements need to be conducted. The results regarding pADEs can be used to design tailored interventions to effectively reduce harm caused by medication errors. Improvement of the inter-rater reliability of a PCR remains challenging.

Towards evidence-based pharmacotherapy in children

In daily practice, it is difficult to find a registered drug for children, because about 70% of the drugs prescribed in children are not studied, off‐label or unlicensed in this age group. Clinical trials have usually been performed in adults, and then in daily practice dosages are adjusted for children without proper studies in that age group. In some countries, national formularies are being established to overcome the existing variance in prescribing between physicians. Complicating factors in finding the correct dosage for children include the heterogeneity between different age groups in the developmental stages of the organs influencing the absorption, distribution, metabolism, and excretion as well as differences in body composition during growth. Growth may also influence the effects and adverse effects of a drug used in a child. For oral administration of drugs in children, the bioavailability, the taste, the composition, and the absence of toxic ingredients for that age group are additional important factors. The EU has recently introduced legislation to stimulate the pharmaceutical industry to investigate the pharmacological effect and safety of new medicines in children. In response to this legislation, research networks are being established to provide the optimal infrastructure for pediatric drug investigation. The goals of this paper are to review the current problems in daily practice and to address the needs for evidence based pharmacotherapy in children.

Application of the Bow-Tie Model in Medication Safety Risk Analysis: Consecutive Experience in Two Hospitals in the Netherlands

AbstractBackground: To improve medication safety effectively, one should systematically analyse and assess the risks for medication errors and determine the possible causes. So far, no risk-analysis instrument exists in healthcare that can be used to analyse and visualize risks, causes and consequences of potential adverse events in a prospective manner. In high-risk industries such as petrochemistry and aviation, the Bow-Tie model is frequently used. This model combines causes, errors, preventive and recovery measures, and consequences in one model and gives insight into the magnitude and causes of existing safety risks. The aim of our project was to study the usefulness of the Bow-Tie model in the hospital setting for prospective analysis of risks in the medication process in order to develop a practicable method. Methods: The model was first adapted to the clinical setting. Thereafter, the risk-analysis model was applied in a large tertiary teaching hospital in multi-disciplinary sessions. The sessions and risk-analysis method were evaluated on the following aspects: applicability, comprehensibility, creation of awareness in and motivation of participants, and the capability of the ‘system approach’ (the approach taken by the Bow-Tie model, which focuses on the conditions under which individuals work and tries to build defences to avert errors or mitigate their effects, in contrast to a ‘person approach’, which focuses on errors of individuals, blaming them for forgetfulness, inattention etc.). Based on this evaluation, the risk analysis method was adjusted and consecutively applied in a general teaching hospital. After evaluation of the sessions in the second hospital a recommended method for risk analysis with the Bow-Tie model was defined. Results: The risk-analysis method with the Bow-Tie model in the first hospital gave insight into many medication safety-related risks. However, the method was insufficient on comprehensibility and on the creation of awareness and motivation owing to a great number of determined risks which made thorough analysis, drawing of Bow-Ties and prioritizing difficult. The adjusted method in the second hospital focused more on the in-depth analysis of a small number of important safety issues of a department with specific attention for underlying causes. This approach was considered better in applicability, comprehensibility and the creation of awareness. Furthermore, by analyzing underlying causes, more attention could be paid to latent conditions (which can translate into error-provoking conditions) within the system. Conclusion: We found the Bow-Tie to be an appropriate model for prospective risk analysis of medication safety in a hospital. By applying the model in two hospitals consecutively we developed a feasible method for risk-analysis sessions. Key factors of this recommended method are a focus on the prioritized selection of safety issues and specific attention to latent conditions within the system by analysing these safety issues in depth to the root causes with the help of the Bow-Tie model.

Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery

AbstractObjective: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). Methods: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery. Results: The average pharmacokinetic parameter estimates of clearance (Cl), volume of distribution at steady state (Vd,ss), elimination half-life (t1/2,β) and distribution half-life (t1/2,α) observed in the three groups were 28 ± 1.1 ml/kg/min, 1.8 ± 0.12 l/kg, 94 ± 4.1 min and 3.1 ± 0.26 min, respectively (mean ± SEM, n=24) and no significant differences were noted between the three formulations (P > 0.05). In one patient receiving propofol 6% SAZN, in two patients receiving propofol 1% SAZN and in three patients receiving Diprivan-10, the level of sedation was inadequate and additional sedative medication had to be given. In all other 18 patients, the level of sedation was adequate. The mean propofol concentration in these six inadequately sedated patients was lower than the adequately sedated patients (P=0.015). The serum triglyceride concentrations were not significantly different between the groups studied. No adverse events occurred in any of the patients. Conclusions: The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN are in good agreement with those of the 1% formulations. Propofol 6% SAZN therefore provides a useful alternative to the commercially available 1% formulation for short-term sedation in the intensive care unit. Expected advantages in long-term sedation of the 6% over 1% formulation are the subject of an ongoing study.

Improving medication administration in nursing home residents with swallowing difficulties: sustainability of the effect of a multifaceted medication safety programme†

Crushing solid oral dosage forms is an important risk factor for medication administration errors (MAEs) in patients with swallowing difficulties. Nursing home (NH) residents, especially those on psychogeriatric wards, have a high prevalence of such difficulties.

Occurrence and preventability of adverse drug events in surgical patients: a systematic review of literature.

BackgroundAdverse drug events (ADEs) are a considerable cause of inhospital morbidity and mortality. Patient flow differs substantially for surgical and nonsurgical patients: surgical patients are subjected to multiple medication changes related to surgical intervention or postoperative care. The objective of this study is to systematically review the occurrence and nature of ADEs in surgical patients. Also, a comparison with nonsurgical patients was made.MethodsA search was conducted in Embase and Medline identifying studies that reported observational data on the occurrence and nature of ADEs in surgical hospitalised adult patients. If sufficient data were available, the occurrence of (preventable) ADEs was compared between surgical and nonsurgical patients.ResultsSix studies fulfilled the inclusion criteria. The occurrence of ADEs in surgical patients ranged from 2.0 to 27.7 per 100 admissions, from 4.7 to 8.9 per 1,000 patient days, or involved 8.9% of the patients. Proportions of preventable ADEs in surgical patients were 18% and 54%, described in two studies. A head-to-head comparison of surgical patients and nonsurgical patients was possible for five of six studies. The occurrence of ADEs in nonsurgical patients was significantly higher than in surgical patients in three studies.ConclusionsADEs are a relevant problem in surgical patients and nonsurgical patients, with a high proportion of preventable ADEs. The occurrence of ADEs appears to be higher in nonsurgical patients than in surgical patients. However, studies lack details on the differences in nature of ADEs between hospital populations. To improve medication safety this knowledge is essential.

Cost-effectiveness of ward-based pharmacy care in surgical patients: protocol of the SUREPILL (Surgery & Pharmacy In Liaison) study

BackgroundPreventable adverse drug events (pADEs) are widely known to be a health care issue for hospitalized patients. Surgical patients are especially at risk, but prevention of pADEs in this population is not demonstrated before. Ward-based pharmacy interventions seem effective in reducing pADEs in medical patients. The cost-effectiveness of these preventive efforts still needs to be assessed in a comparative study of high methodological standard and also in the surgical population. For these aims the SUREPILL (Surgery & Pharmacy in Liaison) study is initiated.Methods/DesignA multi-centre controlled trial, with randomisation at ward-level and preceding baseline assessments is designed. Patients admitted to the surgical study wards for elective surgery with an expected length of stay of more than 48 hours will be included. Patients admitted to the intervention ward, will receive ward-based pharmacy care from the clinical pharmacy team, i.e. pharmacy practitioners and hospital pharmacists. This ward-based pharmacy intervention includes medication reconciliation in consultation with the patient at admission, daily medication review with face-to-face contact with the ward doctor, and patient counselling at discharge. Patients admitted in the control ward, will receive standard pharmaceutical care.The primary clinical outcome measure is the number of pADEs per 100 elective admissions. These pADEs will be measured by systematic patient record evaluation using a trigger tool. Patient records positive for a trigger will be evaluated on causality, severity and preventability by an independent expert panel. In addition, an economic evaluation will be performed from a societal perspective with the costs per preventable ADE as the primary economic outcome. Other outcomes of this study are: severity of pADEs, number of patients with pADEs per total number of admissions, direct (non-)medical costs and indirect non-medical costs, extra costs per prevented ADE, number and type of pharmacy interventions, length of hospital stay, complications registered in a national complication registration system for surgery, number of readmissions within three months after initial admission (follow-up), quality of life and number of non-institutionalized days during follow-up.DiscussionThis study will assess the cost-effectiveness of ward-based pharmacy care on preventable adverse drug events in surgical patients from a societal perspective, using a comparative study design.Trial registrationNetherlands Trial Register (NTR): NTR2258

Quality of pharmaceutical care in surgical patients

Background Surgical patients are at risk for preventable adverse drug events (ADEs) during hospitalization. Usually, preventable ADEs are measured as an outcome parameter of quality of pharmaceutical care. However, process measures such as QIs are more efficient to assess the quality of care and provide more information about potential quality improvements. Objective To assess the quality of pharmaceutical care of medication-related processes in surgical wards with quality indicators, in order to detect targets for quality improvements. Methods For this observational cohort study, quality indicators were composed, validated, tested, and applied on a surgical cohort. Three surgical wards of an academic hospital in the Netherlands (Academic Medical Centre, Amsterdam) participated. Consecutive elective surgical patients with a hospital stay longer than 48 hours were included from April until June 2009. To assess the quality of pharmaceutical care, the set of quality indicators was applied to 252 medical records of surgical patients. Results Thirty-four quality indicators were composed and tested on acceptability and content- and face-validity. The selected 28 candidate quality indicators were tested for feasibility and ‘sensitivity to change’. This resulted in a final set of 27 quality indicators, of which inter-rater agreements were calculated (kappa 0.92 for eligibility, 0.74 for pass-rate). The quality of pharmaceutical care was assessed in 252 surgical patients. Nearly half of the surgical patients passed the quality indicators for pharmaceutical care (overall pass rate 49.8%). Improvements should be predominantly targeted to medication care related processes in surgical patients with gastro-intestinal problems (domain pass rate 29.4%). Conclusions This quality indicator set can be used to measure quality of pharmaceutical care and detect targets for quality improvements. With these results medication safety in surgical patients can be enhanced.