Neal Benedict

Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury

OBJECT Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI. METHODS Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency. RESULTS Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003). CONCLUSIONS Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis.

Virtual Patients and Problem-Based Learning in Advanced Therapeutics

Objective. To enhance student learning of a complex therapeutic concept through the incorporation of 2 case-based, active-learning strategies with lecture in a required advanced therapeutics course. Design. A virtual patient session using a branched-outcome decision-making model and a problem-based learning (PBL) practica were developed from the course learning objectives for severe sepsis and septic shock. Following lecture of this material, students were required to complete the simulation session and attend the PBL. Assessment. Student learning was assessed through review of examination scores, as well as quality and accuracy of the pharmaceutical care plan developed as part of the PBL. Satisfaction of the teaching format was assessed through a course evaluation survey. For questions pertaining to sepsis or septic shock on the final examination, the class average was 90%, despite an average of 76% on the examination as a whole. Class average for the pharmacuetical care plan was 90%. Sixty-three percent of students stated the simulation contributed to their learning, and 93% stated the PBL contributed to their learning. Conclusion. Using a multifaceted teaching approach, combining active- and passive-learning strategies, was well received by students and fostered an effective learning environment.

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.

Promotion of self-directed learning using virtual patient cases.

Objective. To assess the effectiveness of virtual patient cases to promote self-directed learning (SDL) in a required advanced therapeutics course. Design. Virtual patient software based on a branched-narrative decision-making model was used to create complex patient case simulations to replace lecture-based instruction. Within each simulation, students used SDL principles to learn course objectives, apply their knowledge through clinical recommendations, and assess their progress through patient outcomes and faculty feedback linked to their individual decisions. Group discussions followed each virtual patient case to provide further interpretation, clarification, and clinical perspective. Assessments. Students found the simulated patient cases to be organized (90%), enjoyable (82%), intellectually challenging (97%), and valuable to their understanding of course content (91%). Students further indicated that completion of the virtual patient cases prior to class permitted better use of class time (78%) and promoted SDL (84%). When assessment questions regarding material on postoperative nausea and vomiting were compared, no difference in scores were found between the students who attended the lecture on the material in 2011 (control group) and those who completed the virtual patient case on the material in 2012 (intervention group). Conclusion. Completion of virtual patient cases, designed to replace lectures and promote SDL, was overwhelmingly supported by students and proved to be as effective as traditional teaching methods.

Patient simulation software to augment an advanced pharmaceutics course.

Objective. To implement and assess the effectiveness of adding a pharmaceutical care simulation program to an advanced therapeutics course. Design. PharmaCAL (University of Pittsburgh), a software program that uses a branched-outcome decision making model, was used to create patient simulations to augment lectures given in the course. In each simulation, students were presented with a challenge, given choices, and then provided with consequences specific to their choices. Assessments. A survey was administered at the end of the course and students indicated the simulations were enjoyable (92%), easy to use (90%), stimulated interest in critically ill patients (82%), and allowed for application of lecture material (91%). A 5-item presimulation and postsimulation test on the anemia simulation was administered to assess learning. Students answered significantly more questions correctly on the postsimulation test than on the presimulation test (p < 0.001). Seventy-eight percent of students answered the same 5 questions correctly on the final examination. Conclusion. Patient simulation software that used a branched-outcome decision model was an effective supplement to class lectures in an advanced pharmaceutics course and was well-received by pharmacy students.

Evaluation of Adjunctive Ketamine to Benzodiazepines for Management of Alcohol Withdrawal Syndrome

Background: Adjunctive medications to manage alcohol withdrawal syndrome (AWS) in patients not adequately responding to escalating doses of benzodiazepines (BZDs) are limited. The use of the N-methyl-d-aspartate antagonist ketamine, may serve as an effective adjunct agent; however, no published data currently exist for this practice. Objective: To determine the safety and efficacy of adjunct ketamine for management of AWS. Methods: The study was a retrospective review of adult patients from April 2011 to March 2014 who were administered ketamine specifically for management of AWS. Outcomes included changes in BZD requirements and ketamine-related adverse reactions. Results: Of 235 patients screened, 23 patients met study eligibility. Ketamine was initiated primarily with toxicology consultation for significant BZD requirements or delirium tremens. The mean time to initiation of ketamine from first treatment of AWS, and total duration of therapy were 33.6 and 55.8 hours, respectively. Mean initial infusion dose and median total infusion rate during therapy were 0.21 and 0.20 mg/kg/h, respectively. There was no change in sedation or alcohol withdrawal scores in patients within 6 hours of ketamine initiation. The median change in BZD requirements at 12 and 24 hours post–ketamine initiation were −40.0 and −13.3 mg, respectively. The mean time to AWS resolution was 5.6 days. There was one documented adverse reaction of oversedation, requiring dose reduction. Conclusions: Ketamine appears to reduce BZD requirements and is well tolerated at low doses. Prospective dose range evaluations in the management of AWS would be helpful in determining its place as an adjunctive agent.

Use of virtual patients in an advanced therapeutics pharmacy course to promote active, patient-centered learning

Objective. To assess student satisfaction and learning of course objectives following the integration of virtual patient cases designed to promote active, patient-centered learning in an advanced therapeutics pharmacy course. Design. A dynamic virtual patient platform that incorporated a branched-narrative, decision-making teaching model was used in an advanced therapeutics course to supplement lecture content. Assessment. Presimulation and postsimulation tests were used to assess student learning. The use of virtual patients significantly enhanced student learning for both higher- and lower-level test questions (p<0.001 and p=0.01, respectively). Students agreed or strongly agreed that the virtual patient cases provided an effective way to learn (72%), were enjoyable (69%), and were appropriate in content (80%), and that more should be incorporated (59%). Conclusion. The use of virtual patients in an advanced therapeutics practicum effectively promoted active, patient-centered learning; engaged students in an interactive and dynamic educational technology; encouraged teamwork; enhanced higher-level student learning; and improved student satisfaction in the course.

Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol☆

BACKGROUND Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW. METHODS Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use. RESULTS Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions. CONCLUSIONS The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.

Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal

INTRODUCTION A subset of patients with alcohol withdrawal syndrome does not respond to benzodiazepine treatment despite escalating doses. Resistant alcohol withdrawal (RAW) is associated with higher incidences of mechanical ventilation and nosocomial pneumonia and longer intensive care unit (ICU) stay. The objective of this study is to characterize pharmacologic management of RAW and outcomes. METHODS Adult patients were identified retrospectively via International Classification of Diseases, Ninth Revision codes for severe alcohol withdrawal from 2009 to 2012 at 3 hospitals. Data collected included pharmacologic management and clinical outcomes. RESULTS A total of 184 patients met inclusion criteria. Sixteen medications and 74 combinations of medications were used for management. Propofol was the most common adjunct agent, with dexmedetomidine and antipsychotics also used. One hundred seventy-five patients (96.2%) were admitted to the ICU, with 149 patients (81.9%) requiring ventilator support. Median time to resolution of alcohol withdrawal syndrome from RAW designation was 6.0 days. Median ICU and hospital length of stay were 9.0 and 12.7 days, respectively. CONCLUSION Diverse patterns exist in the management of patients meeting RAW criteria, indicating lack of refined approach to treatment. High doses of sedatives used for these patients may result in a high level of care, illustrating a need for evidence-based clinical guidelines to optimize outcomes.

Effect of critical care pharmacist's intervention on medication errors: A systematic review and meta-analysis of observational studies

Pharmacists are integral members of the multidisciplinary team for critically ill patients. Multiple nonrandomized controlled studies have evaluated the outcomes of pharmacist interventions in the intensive care unit (ICU). This systematic review focuses on controlled clinical trials evaluating the effect of pharmacist intervention on medication errors (MEs) in ICU settings. Two independent reviewers searched Medline, Embase, and Cochrane databases. The inclusion criteria were nonrandomized controlled studies that evaluated the effect of pharmacist services vs no intervention on ME rates in ICU settings. Four studies were included in the meta-analysis. Results suggest that pharmacist intervention has no significant contribution to reducing general MEs, although pharmacist intervention may significantly reduce preventable adverse drug events and prescribing errors. This meta-analysis highlights the need for high-quality studies to examine the effect of the critical care pharmacist.