Jacqueline M. Bos

Interaction between tramadol and selective serotonin reuptake inhibitors: are doctors aware of potential risks in their prescription practice?

Objectives The combination of a selective serotonin reuptake inhibitor (SSRI) or serotonin–norepinephrine reuptake inhibitor (SNRI) with tramadol can result in serotonin syndrome, characterised by neuromuscular and autonomic nervous system excitation and altered mental state. The incidence of serotonin syndrome with this combination of drugs is low, and the serotonin syndrome is generally mild or moderate in form, but can be life threatening and is more easily prevented than treated. We aimed to investigate whether prescribers in a general hospital were aware of this risk and if it influenced their prescriptions. Methods A questionnaire was sent to 194 physicians in a general teaching hospital with over 650 beds in The Netherlands. The questionnaire presented four cases, two of whom used an SSRI or SNRI among other medications, and asked the respondents to prescribe an opioid in each case. The respondents were not aware of the focus of our research. Actual prescription rates of tramadol in admitted patients who did or did not use an SSRI or SNRI were assessed using the hospital pharmacy database. Results Based on the questionnaire, respondents prescribed tramadol equally in patients with or without concomitant use of SSRIs/SNRIs. About one-third of respondents who prescribed tramadol indicated they were aware of the potential interaction with SSRIs/SNRIs. About one-fifth deliberately avoided tramadol because a potential interaction with SSRIs/SNRIs was identified. However, there was no difference in actual tramadol prescriptions, as recorded in the hospital pharmacy database: 23.8% of SSRI/SNRI users received tramadol versus 24.6% of non-SSRI/SNRI-users (calculated OR 0.96; 95% CI 0.78 to 1.17). Conclusions In total, 20–30% of prescribers in a general hospital were aware of the potential interaction between tramadol and SSRIs or SNRIs, yet this did not translate to a difference in tramadol prescriptions between SSRI/SNRI users and non-users, as documented in the hospital pharmacy database. A physicians decision to prescribe tramadol to SSRI/SNRI users may be guided by a comprehensive individual benefit–risk assessment; expected benefits of tramadol may outweigh the small risk of serotonin syndrome. In order to increase awareness of the potential risk of a serotonin syndrome, hospital pharmacies may play an important role in signalling the potential interaction and providing information on the benefits and risks of tramadol and alternative analgesics in the presence of SSRIs or SNRIs.

The effect of prescriber education on medication-related patient harm in the hospital: A systematic review

Aims Educating prescribers is a strategy to reduce prescription errors in hospitals. The present systematic review gives an overview of original research papers on the education of prescribers and reporting outcomes on (potential) patient harm. Methods A search of the databases Embase and Medline, using the Ovid interface, was performed. Research on the effect of physician education in order to prevent medication‐related problems in inpatients, and on reporting original data and outcomes on prescribing errors and/or (potential) patient harm, was included. The assessment of methodological quality and risk of bias was performed using the Methodological Index for Non‐Randomized studies (MINORS) checklist and the suggested risk of bias criteria for Effective Practice and Organization of Care (EPOC) reviews. Results Eight studies investigated an intervention on education alone, and in seven studies education was the main part of a multifaceted intervention. All studies were small and had short follow‐up periods. The educational programmes varied and were given to physicians of different specialties and levels of experience. Most studies reported intermediate process parameters as the outcome. The risk of performance and reporting bias were high. Conclusion All included studies suffered from poor methodology. The majority, especially studies in which education was part of a multifaceted intervention, reported effectiveness on intermediate outcome markers as prescription errors and potential adverse drug events. However, we found no firm evidence that educating prescribers in the hospital leads to a decrease in patient harm. Further work is needed to develop educational programmes, accompanied by more high‐quality research with outcomes on the improvement of patient care.

Prediction of clinically relevant adverse drug events in surgical patients

Background Risk stratification of hospital patients for adverse drug events would enable targeting patients who may benefit from interventions aimed at reducing drug-related morbidity. It would support clinicians and hospital pharmacists in selecting patients to deliver a more efficient health care service. This study aimed to develop a prediction model that helps to identify patients on the day of hospital admission who are at increased risk of developing a clinically relevant, preventable adverse drug event during their stay on a surgical ward. Methods Data of the pre-intervention measurement period of the P-REVIEW study were used. This study was designed to assess the impact of a multifaceted educational intervention on clinically relevant, preventable adverse drug events in surgical patients. Thirty-nine variables were evaluated in a univariate and multivariate logistic regression analysis, respectively. Model performance was expressed in the Area Under the Receiver Operating Characteristics. Bootstrapping was used for model validation. Results 6780 admissions of patients at surgical wards were included during the pre-intervention period of the PREVIEW trial. 102 patients experienced a clinically relevant, adverse drug event during their hospital stay. The prediction model comprised five variables: age, number of biochemical tests ordered, heparin/LMWH in therapeutic dose, use of opioids, and use of cardiovascular drugs. The AUROC was 0.86 (95% CI 0.83–0.88). The model had a sensitivity of 80.4% and a specificity of 73.4%. The positive and negative predictive values were 4.5% and 99.6%, respectively. Bootstrapping generated parameters in the same boundaries. Conclusions The combined use of a limited set of easily ascertainable patient characteristics can help physicians and pharmacists to identify, at the time of admission, surgical patients who are at increased risk of developing ADEs during their hospital stay. This may serve as a basis for taking extra precautions to ensure medication safety in those patients.

The effects of substitution of hospital ward care from medical doctors to physician assistants on non-adherence to guidelines on medication prescribing

Aim This study determined the effect of substitution of inpatient care from medical doctors (MDs) to physician assistants (PAs) on non-adherence to guidelines on medication prescribing. Methods A multicenter matched-controlled study was performed comparing wards on which PAs provide medical care in collaboration with MDs (PA/MD model), with wards on which only MDs provide medical care (MD model). A set of 17 quality indicators to measure non-adherence to guidelines on medication prescribing by PAs and MDs was composed by 14 experts in a modified Delphi procedure. The indicators covered different pharmacotherapeutic subjects, such as gastric protection in case of use of NSAID or prevention of obstipation in case of use of opioids. These indicators were expressed in proportions by dividing the number of patients in which the prescriber did not adhere to a guideline, by all patients that were applicable. Multivariable regression analysis was performed in order to adjust for potential confounders. Results 1021 patients from 17 hospital wards in the ‘PA/MD model’ group and 1286 patients from 17 hospital wards in the ‘MD model’ group were included. Two of the 17 quality indicators showed significantly less non-adherence to guidelines for the PA/MD model; the indicators concerning prescribing gastric protection in case of use of NSAID in combination with corticosteroids (OR 0.42, 95% CI 0.19–0.90) and in case of use of NSAID in patients older than 70 years (OR 0.47, 95% 0.23–0.95). For none of the other quality indicators for prescribing of medication a difference between the MD model and the PA/MD model was found. Conclusion This study suggests that the non-adherence to guidelines on medication prescribing on wards with the PA/MD model does not differ from wards with traditional house staffing by MDs only. Further research is needed to determine quality, efficiency and safety of prescribing behavior of PAs.

QTc prolongation during erythromycin used as prokinetic agent in ICU patients

Background High-dose erythromycin used as antibiotic prolongs QTc interval. Low-dose erythromycin is frequently used as a prokinetic agent, especially in patients in the intensive care unit (ICU). It is unknown whether low-dose erythromycin affects cardiac repolarisation and puts patients at risk for torsades de pointes. Methods In this prospective study, we included ICU patients treated with erythromycin as prokinetic in a dose of 200 mg twice a day. An ECG was performed before, 15 min and 24 hours after the start of erythromycin. Cardiac repolarisation was assessed by rate-corrected analysis of the QT interval (QTc) on the ECG by two independent investigators. Starting or stopping other possibly QTc prolonging drugs during the study period was an exclusion criterion. Wilcoxon signed-rank test and Friedmans test were used for statistical analysis to assess prolongation of QTc. Primary outcome was defined by the prolongation of QTc after 15 min and 24 hours. Results 51 patients were eligible for this study. In these patients, QTc increased significantly from 430 ms at baseline to 439 ms (p=0.03) after 15 min and 444 ms (p=0.01) after 24 hours. After 15 min and 24 hours, the upper limit of 95% CI for prolongation of QTc was well above 10 ms. No QTc-related arrhythmias were seen. Conclusions During treatment with erythromycin in a dose of 200 mg twice a day. QTc prolonged mildly but significantly. Sequential ECG registration should be performed when low-dose erythromycin is prescribed, especially in the presence of other risk factor for QTc prolongation.

A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals

Background Despite the potential of clinical practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before–after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain management, antithrombotics, fluid and electrolyte management, prescribing in case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophylaxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consultations, combining medication review of patients who are at risk for drug related problems with visits to ward physicians. Main outcome measure The outcome measure was the proportion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49–0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.