Pamela L. Smithburger

A critical evaluation of clinical decision support for the detection of drug–drug interactions

Introduction: Incorporation of clinical decision support systems (CDSSs) into computerized physician order entry assists prescribers with medication dosing, identification of duplicate therapies, drug-allergy alerts and drug–drug interactions (DDIs). The generation of DDI alerts is one aspect of CDSS that may improve patient safety and reduce adverse drug events. Areas covered: Currents issues with the generation of DDI alerts, such as alert fatigue, unclear clinical significance and database inconsistencies are a few of the problems that have been identified with DDI alerting. Research has shown that DDI alerting may be improved through the tiering of alerts, generation of patient-specific alert and directing some alerts to clinicians other than physicians. More research in this area, such as how to decrease the variability of database rating systems, improve the identification of clinically significant alerts and increase the patient specificity of the generated DDI alerts, should be conducted. Expert opinion: DDI knowledgebases need to take into account more patient-specific information. Strategies to avoid alert fatigue, such as DDI tiering and reducing signal:noise ratios, are important areas for future study. End-user participation and clinician feedback should be incorporated in the development of DDI knowledgebases to increase alert compliance.

Grading the Severity of Drug-Drug Interactions in the Intensive Care Unit: A Comparison Between Clinician Assessment and Proprietary Database Severity Rankings

Background: Computerized provider order entry with decision support software offers an opportunity to identify and prevent medication-related errors, including drug-drug interactions (DDIs), through alerting mechanisms. However, the number of alerts generated can overwhelm and lead to “alert fatigue.” A DDI alert system based on severity rankings has been shown to reduce alert fatigue; however, the best method to populate this type of database is unclear. Objective: To compare the severity ranking of proprietary databases to clinician assessment for DDIs occurring in critically ill patients. Methods: This observational, prospective study was conducted over 8 weeks in the cardiac and cardiothoracic intensive care unit. Medication profiles of patients were screened for the presence of DDIs and a severity evaluation was conducted using rankings of proprietary databases and clinician opinion using a DDI severity assessment tool. The primary outcome measure was the number of DDIs considered severe by both evaluation methods. Results: A total of 1150 DDIs were identified after 400 patient medication profiles were evaluated. Of these, 458 were unique drug pairs. Overall, 7.4% (34/458) were considered a severe interaction based upon proprietary database ratings. The assessment by clinicians ranked 6.6% (30/458) of the unique DDIs as severe. Only 3 interactions, atazanavir–simvastatin, atazanavir–tenofovir, and aspirin–warfarin, were considered severe by both evaluation methods. Conclusions: Since proprietary databases and clinician assessment of severe DDIs do not agree, developing a knowledge base for a DDI alert system likely requires proprietary database information in conjunction with clinical opinion.

Impact of a Clinical Pharmacy Admission Medication Reconciliation Program on Medication Errors in “High-Risk” Patients

Background: Medication errors are common upon hospital admission. Clinical pharmacist involvement in medication reconciliation is effective in identifying and rectifying medication errors. However, data is lacking on the economic impact, time requirements, and severity of errors resolved by clinical pharmacists. Objective: To determine the incidence of unintended admission medication discrepancies resolved by clinical pharmacists. Secondary objectives were to determine the type of discrepancies, potential severity, proximal cause, and economic impact of this clinical pharmacy program. Methods: This was a single-center, prospective, observational study conducted at a major teaching medical institution. Following institutional review board approval, data collection was conducted over a 4-week period (August 22, 2011, to September 16, 2011). Descriptive statistical methods were performed for all data analyses. Results: A total of 517 patients involving 5006 medications were included in this study. More than 25% (n = 132) of patients had at least 1 error associated with a medication ordered on hospital admission. Pharmacists resolved a total of 467 admission medication errors (3.5 ± 2.3 errors/patient). The most common type of medication error resolved was medication omission (79.6%). In regard to severity, 46% of medication errors were considered significant or serious. Overall, the mean total time was 44.4 ± 21.8 minutes per medication reconciliation. This clinical pharmacy program was estimated to carry a net present value of

Drug-drug interactions in cardiac and cardiothoracic intensive care units: an analysis of patients in an academic medical centre in the US.

5.7 million over 5 years. Conclusion: Clinical pharmacist involvement within a multidisciplinary health care team during the admission medication reconciliation process demonstrated a significant improvement in patient safety and an economic benefit.

Common drug interactions leading to adverse drug events in the intensive care unit: management and pharmacokinetic considerations.

AbstractBackground: Mortality and morbidity are increased in patients experiencing drug-drug interactions. Unfortunately, there is a paucity of literature describing clinically significant drug-drug interactions occurring in the intensive care unit (ICU). Knowing the clinically significant drug-drug interactions allows the opportunity for prevention through knowledge and computer-assisted programmes. Objective: To identify significant potential drug-drug interactions occurring in the cardiovascular ICU (CCU) and the cardiothoracic ICU (CTICU). Study Design: Prospective, observational study conducted over a total of 8 weeks in February and March 2009. Setting: CCU and CTICU in a major academic medical centre (Presbyterian Hospital, University of Pittsburgh Medical Centre). Patients: All adult patients (≥18 years of age) admitted during 1 month in each ICU. Intervention: Micromedex® and Lexi-Interact™ interaction databases were used to screen each patient’s medication profile daily for the presence of potentially interacting drug pairs that would be considered a potential drug-drug interaction. A severity assessment using these databases was completed after a potential drug-drug interaction was identified. Primary Outcome Measure: The frequency of significant drug-drug interactions, including those that were considered major or contraindicated, according to two commercially available interaction databases. Results: Evaluations of 400 patient medication profiles were conducted, resulting in 225 profiles possessing one or more potential drug-drug interactions. A total of 1150 potential interactions were identified, resulting in 287.5 potential interactions per 100 patient-days. Of the 1150 potential drug-drug interactions, 458 were unique interacting drug pairs; 5–9% of the potential interactions were considered major or contraindicated. Many of the significant and frequent potential interactions involved blood coagulation modifiers, potential interactions that could result in QTc prolongation, and cytochrome P450 inhibition. Micromedex® and Lexi-Interact™ agreed on the severity ratings in 20.5% of the potential interactions. Conclusions: Significant potential drug-drug interactions occur in the CCU and CTICU, highlighting the need for active surveillance to potentially prevent patient harm. Clinicians should also consider using two references for identifying interactions, due to the lack of congruence between sources.

Drug-drug interactions contributing to QT prolongation in cardiac intensive care units

Critically ill patients are predisposed to drug interactions because of the complexity of the drug regimens they receive in the intensive care setting. Drugs may affect the absorption, distribution, metabolism, and/or elimination of an object drug and consequently alter the intended pharmacologic response and potentially lead to an adverse event. Certain disease states that afflict critically ill patients may also amplify an intended pharmacologic response and potentially result in an unintended effect. A team approach is important to identify, prevent, and address drug interactions in the intensive care setting and optimize patient outcomes.

The cost of opioid-related adverse drug events

PURPOSE To determine the most common drug-drug interaction (DDI) pairs contributing to QTc prolongation in cardiac intensive care units (ICUs). MATERIALS AND METHODS This retrospective evaluation included patients who were admitted to the cardiac ICUs between January 2009 and July 2009 aged ≥ 18 years with electrocardiographic evidence of a QTc ≥ 500 ms. Patients receiving at least two concomitant drugs known to prolong the QT interval were considered to experience a pharmacodynamic DDI. Drugs causing CYP450 inhibition of the metabolism of QT prolonging medications were considered to cause pharmacokinetic DDIs. The causality between drug and QTc prolongation was evaluated with an objective scale. RESULTS One hundred eighty-seven patients experienced QT prolongation out of a total of 501 patients (37%) admitted during the study period. Forty-three percent and 47% of patients experienced 133 and 179 temporally-related pharmacodynamic and pharmacokinetic interactions, respectively. The most common medications related to these DDIs were ondansetron, amiodarone, metronidazole, and haloperidol. CONCLUSION DDIs may be a significant cause of QT prolongation in cardiac ICUs. These data can be used to educate clinicians on safe medication use. Computerized clinical decision support could be applied to aid in the detection of these events.

An evidence based systematic review of remifentanil associated opioid-induced hyperalgesia.

ABSTRACT Opioids are the cornerstone of pain management; however, their use is associated with a variety of adverse drug events (ADEs) ranging from nausea and vomiting to urinary retention and respiratory depression. The purpose of this review is to describe the frequency and cost associated with different types of opioid-related ADEs to better understand their economic impact. A search of studies published in journals from 1946 to December, 2013, was conducted using MEDLINE and EMBASE. A total of 20 articles were reviewed. Data reflect a substantial economic burden of opioid-related ADEs resulting in high hospital costs, prolonged hospital stays, and substantial health care resource usage. Nausea, vomiting, and constipation are frequent and increased costs occur in all types of pain (surgical, nonsurgical, cancer, noncancer) in both inpatients and outpatients. Given the large economic burden of opioid-related ADEs, prevention rather than treatment may be the most effective strategy.

Advancing interprofessional education through the use of high fidelity human patient simulators

Introduction: Therapeutic opioid use continues to grow, with greater than a fivefold increase in usage of fentanyl-based products over a 10-year period. Opioids are known for their side-effect profile, including bradycardia and respiratory depression; questions remain, however, regarding lesser known side effects such as opioid-induced hyperalgesia (OIH). Areas covered: A systematic review of published literature addressing remifentanil OIH in the surgical setting was completed. A search was conducted of PubMed, Embase and Ovid from 1946 until June 2013. Inclusion criteria consisted of age ≥ 18 years, humans, full-text articles and English language. A total of 35 unique articles were included. Sixteen articles reported outcomes that supported remifentanil OIH and 6 that refuted and 22 were focused on prevention. Expert opinion: There is conflicting evidence regarding the existence of remifentanil OIH. Outcomes evaluating measures of hyperalgesia frequently conclude that remifentanil OIH exists, while those evaluating opioid consumption do not. Therefore, remifentanil does induce a degree of hyperalgesia, but we do not believe that it reaches a level of clinical significance that requires prevention. If a significant concern for the development of remifentanil OIH is suspected, we suggest using the least possible effective dose of remifentanil as the primary prevention strategy.

Drug–drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved

Background Modern medical care increasingly requires coordinated teamwork and communication between healthcare professionals of different disciplines. Unfortunately, healthcare professional students are rarely afforded the opportunity to learn effective methods of interprofessional (IP) communication and teamwork strategies during their education. The question of how to best incorporate IP interactions in the curricula of the schools of health professions remains unanswered. Objective We aim to solve the lack of IP education in the pharmacy curricula through the use of high fidelity simulation (HFS) to allow teams of medical, pharmacy, nursing, physician assistant, and social work students to work together in a controlled environment to solve cases of complex medical and social issues. Methods Once weekly for a 4-week time period, students worked together to complete complex simulation scenarios in small IP teams consisting of pharmacy, medical, nursing, social work, and physician assistant students. Student perception of the use of HFS was evaluated by a survey given at the conclusion of the HFS sessions. Team communication was evaluated through the use of Communication and Teamwork Skills (CATS) Assessment by 2 independent evaluators external to the project. Results The CATS scores improved from the HFS sessions 1 to 2 (p = 0.01), 2 to 3 (p = 0.035), and overall from 1 to 4 (p = 0.001). The inter-rater reliability between evaluators was high (0.85, 95% CI 0.71, 0.99). Students perceived the HFS improved: their ability to communicate with other professionals (median =4); confidence in patient care in an IP team (median=4). It also stimulated student interest in IP work (median=4.5), and was an efficient use of student time (median=4.5) Conclusions The use of HFS improved student teamwork and communication and was an accepted teaching modality. This method of exposing students of the health sciences to IP care should be incorporated throughout the curricula.