Scott A. Chapman

Prothrombin Complex Concentrate Versus Standard Therapies for INR Reversal in Trauma Patients Receiving Warfarin

Background: Prothrombin complex concentrate (PCC) is recommended as a therapy to be considered for the reversal of warfarins effects. Few published data are available on the use of PCC for this indication in traumatically injured patients. Objective: To determine whether the addition of PCC to standard approaches to warfarin reversal more rapidly corrects the international normalized ratio (INR) in injured patients. Methods: A retrospective analysis was performed in trauma patients who were on warfarin preinjury from January 2007 to September 2009 at North Memorial Medical Center. Data were collected from medical records and the trauma registry. Patients were separated based on whether or not they received PCC. The groups were compared on the basis of demographics, units of fresh frozen plasma (FFP), vitamin K use, units of PCC, number of patients achieving an INR of 1.5 or less, time to an INR of 1.5 or less, mortality, intensive care unit (ICU) and hospital length of stay, and the incidence of thromboembolic events during hospitalization. Results: Thirty-one patients were included in the analysis; 13 patients who received a total mean (SD) dose of 2281 (1053) units (25.6 [12.2] units/kg) of PCC (Profilnine SD) were compared to 18 patients who did not receive PCC. There was no significant difference between groups in FFP units received or the number of patients who received vitamin K. Most patients in both groups achieved an INR of 1.5 or less (92% PCC vs 89% no PCC). However, the mean time to achieve an INR of 1.5 or less was 16:59 (20:53) hours in the PCC group versus 30:03 (23:10) hours in the no PCC group (p = 0.048). There were 3 deaths in the PCC group and no deaths in the no PCC group (p = 0.06). ICU and hospital length of stay and number of thromboembolic events did not differ significantly between the 2 groups. Conclusions: PCC, when added to FFP and vitamin K, resulted in a more rapid time to reversal of the INR.

Acute Renal Failure and Intravenous Immune Globulin: Occurs with Sucrose-Stabilized, but Not with D-Sorbitol–Stabilized, Formulation

OBJECTIVE To report 2 cases of acute renal failure (ARF) following administration of sucrose-stabilized intravenous immune globulin (IVIG), one of which did not recur following subsequent doses of d-sorbitol–stabilized formulation, and review the relevant literature. CASE SUMMARIES A 44-year-old white man awaiting heart transplantation developed ARF requiring hemodialysis following administration of sucrose-stabilized IVIG for high alloreactivity to population human leukocyte antigens. Following a return of renal function to baseline, subsequent doses of d-sorbitol–stabilized IVIG were administered without incident. A 90-year-old white man developed ARF after administration of sucrose-stabilized IVIG for monoclonal gammopathy. Renal function returned to baseline, and no subsequent IVIG doses were administered. An objective causality assessment revealed that sucrose-stabilized IVIG was the probable cause of the adverse drug event for both cases. DISCUSSION Several case reports of ARF secondary to IVIG have been published. Recent publications note that sucrose-stabilized IVIG products have a disproportionately high rate of ARF occurrence (∼88%) versus non–sucrose-stabilized formulations. Recent market data for IVIG products indicate that sucrose-stabilized products account for approximately 40% of the total IVIG market. When administered intravenously, sucrose is excreted unchanged in the urine. ARF has been reported in patients receiving large doses of intravenous sucrose. CONCLUSIONS ARF secondary to IVIG may be more likely to occur with sucrose-stabilized formulations. Before prescribing IVIG, clinicians should consider other nephrotoxic medications, preexisting renal function, age, diabetes mellitus, and rate of infusion. In patients at risk, it may be best to avoid sucrose-stabilized formulations.

Pancreatitis associated with valproic acid: A review of the literature

Black box warnings for valproic acid caution clinicians of the potential for fatal hepatotoxicity and teratogenicity. Since 1979, case reports of pancreatitis induced by valproic acid have been published in the medical literature. As a result, pancreatitis was added to the black box warnings for valproic acid. We performed searches of MEDLINE and International Pharmaceutical Abstracts and found valproic acid‐induced pancreatitis in 45 patients from 31 published articles. Demographics, clinical characteristics, and outcomes of these patients are summarized. Recommendations for monitoring the potential for pancreatitis to develop in patients receiving valproic acid therapy are described, as are potential mechanisms for inducement of pancreatitis by valproic acid.

Entrustable Professional Activities for Pharmacy Practice

The profession of pharmacy is facing a shifting health system context that holds both opportunity and risk. If the profession of pharmacy is to advance, pharmacists must be recognized as a consistent member of the health care team in all clinical settings, contributing at the fullest extent of licensure and education. One part of achieving this broad goal is to implement a new way of defining and assessing pharmacy practice skills, such as entrustable professional activities (EPA). Assessment of professional tasks and practice activities with EPAs has been successfully implemented in medical education for assessing trainee preparation for practice. This EPA model is being applied to pharmacy education to develop an assessment framework across the advanced pharmacy practice experience (APPE) curriculum. The APPE course directors, practice faculty members, and the Office of Experiential Education collaboratively defined a set of universal EPAs critical for pharmacists in any practice setting and would be assessed in all practice experience types.

Team science as interprofessional collaborative research practice: a systematic review of the science of team science literature

The National Institute of Healths concept of team science is a means of addressing complex clinical problems by applying conceptual and methodological approaches from multiple disciplines and health professions. The ultimate goal is the improved quality of care of patients with an emphasis on better population health outcomes. Collaborative research practice occurs when researchers from >1 health-related profession engage in scientific inquiry to jointly create and disseminate new knowledge to clinical and research health professionals in order to provide the highest quality of patient care to improve population health outcomes. Training of clinicians and researchers is necessary to produce clinically relevant evidence upon which to base patient care for disease management and empirically guided team-based patient care. In this study, we hypothesized that team science is an example of effective and impactful interprofessional collaborative research practice. To assess this hypothesis, we examined the contemporary literature on the science of team science (SciTS) produced in the past 10 years (2005–2015) and related the SciTS to the overall field of interprofessional collaborative practice, of which collaborative research practice is a subset. A modified preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach was employed to analyze the SciTS literature in light of the general question: Is team science an example of interprofessional collaborative research practice? After completing a systematic review of the SciTS literature, the posed hypothesis was accepted, concluding that team science is a dimension of interprofessional collaborative practice.

Non–weight-based enoxaparin dosing subtherapeutic in trauma patients

BACKGROUND We report our experience dosing and monitoring enoxaparin with anti-factor Xa activity (anti-FXaA) levels for venous thromboembolism prophylaxis in trauma patients (TP). MATERIALS AND METHODS TP receiving standard, non-weight-based dosed enoxaparin administered every 12 h for venous thromboembolism prophylaxis with peak anti-FXaA levels measured were prospectively monitored and evaluated and those whose first anti-FXaA levels ≥ or <0.2 IU/mL were compared. Anti-FXaA levels and enoxaparin dose (mg/kg actual body weight) were evaluated for correlation. RESULTS Of the fifty-one TP included, initial anti-FXaA levels were <0.2 IU/mL in 37 (72.5%) whose dose was lower than those within target range (0.38 [0.32-0.42] mg/kg versus 0.45 [0.39-0.48] mg/kg, P = 0.003). Thirty-seven TP achieved anti-FXaA level ≥0.2 IU/mL (23 requiring dose increases) at a dose of 0.49 [0.44-0.54] mg/kg. Correlation between dose and anti-FXaA levels for the initial 51 anti-FXaA levels (r = 0.360, P = 0.009) and for all 103 anti-XaA levels (r = 0.556, P < 0.001) was noted. CONCLUSIONS Non-weight-based enoxaparin dosing did not achieve target anti-FXaA levels in most TP. Higher anti-FXaA levels correlated with larger weight-based enoxaparin doses. Weight-based enoxaparin dosing (i.e., 0.5 mg/kg subcutaneously every 12 h) would better achieve target anti-FXaA levels.

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

IntroductionProthrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation.MethodsData were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety.ResultsSeventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost.ConclusionsBased on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa.

Safety and Effectiveness of a Modification of Diet in Renal Disease Equation-Based Potassium Replacement Protocol

Background: No data exist regarding the safety and effectiveness of a potassium replacement protocol for hospitalized patients when potassium replacement dosing regimens (KRDRs) are adjusted to Modification of Diet in Renal Disease estimation of glomerular filtration rate (MDRD GFR). Objective: To evaluate the effectiveness and safety of a potassium replacement protocol in which KRDRs are prescribed based on MDRD GFR and serum potassium deficiency (Kdef). Methods: Patients prescribed the potassium replacement order set were identified in a retrospective fashion. Serum potassium, prescriber-defined goal serum potassium, and MDRD GFR data were collected for patients who received protocol KRDRs. The KRDR to be administered is selected based on Kdef (goal serum potassium minus measured serum potassium) of 0.1–0.2, 0.3–0.5, or more than 0.5 mEq/L and the patients’ MDRD GFR of greater than 70, 40–70, or less than 40 mL/min/1.73 m2 (any patient undergoing dialysis is included in the <40 mL/min/1.73 m2 group). Efficacy was evaluated by determining the change in serum potassium level (AK) following potassium replacement, the number of KRDRs needed to achieve goal serum potassium, and the milliequivalents of potassium needed to achieve goal serum potassium levels. Safety was assessed by the incidence of serum potassium values greater than 5.0 mEq/L following replacement. Results: One hundred forty-nine patients were evaluated. There were 184 protocol initiations and 257 KRDRs administered to achieve goal serum potassium levels. The AK was 0.50 ± 0.40 mEq/L (mean ± SD) following KRDR. The AK was similar between MDRD GFR groups. One hundred thirty six (73.9%) protocol initiations required 1 KRDR, and 168 (91.3%) protocol initiations required 1 or 2 KRDRs to achieve goal serum potassium. Patients whose MDRD GFR was 40–70 mL/min/1.73 m2 were less likely to achieve goal serum potassium value after 1 KRDR (58.2% vs 79.6% >70 group and 84.6% <40 group). This was true regardless of the patients goal serum potassium. One (0.54%) serum potassium greater than 5.0 mEq/L occurred following a KRDR, Conclusions: Our potassium replacement protocol based on MDRD GFR and Kdef effectively corrects hypokalemia. Fewer protocol initiations achieved goal serum potassium levels in the group with MDRD GFR 40–70 mL/min/1.73 m2. Hyperkalemia rarely occurred following KRDR.

Angiotensin-converting enzyme inhibitor induced angioedema: predictors of mechanical ventilation and treatment approaches

Dear Editor, Angioedema is a rare, but very serious, adverse effect associated with angiotensin-converting enzyme inhibitors (ACEIs) [1, 2]. Despite the increasing incidence and severity of angioedema secondary to ACEI use, there is a lack of literature surrounding the risk factors for mechanical ventilation and effective treatment strategies of cases requiring ICU level of care. Treatment of these patients often includes epinephrine, corticosteroids, and histamine antagonists, despite limited reported efficacy to support their use [3]. The purpose of this pilot study was to identify specific predictors of mechanical ventilation and describe the role of corticosteroids. Adult patients suspected of having ACEI-induced angioedema admitted to the ICU over a 4-year period were reviewed for this study. Predictors of mechanical ventilation were determined by multivariate logistic regression using backward elimination. All variables with p\ 0.15 on univariate analysis were included in the multivariate analysis. Correlation of corticosteroid use and time to extubation and ICU length of stay were analyzed using Spearman rank correlation. All significant tests were two-sided with a p value of\0.05 being significant. Statistical analysis was completed using JMP software v.11.1. Forty-five patients were admitted to the ICU for ACEI-induced angioedema; 22 (49 %) of whom required mechanical ventilation. Multivariate analysis found history of COPD or asthma and angioedema of the pharynx to be independently associated with the need for mechanical ventilation (Table 1). While in the ICU, the majority of patients received treatment with corticosteroids and histamine antagonists. There was no correlation between the dose of corticosteroids and a decreased time to extubation (r = 0.05; p = 0.3) or ICU length of stay (r = 0.07; p = 0.22). However, duration of corticosteroid use was correlated with an increased time to extubation (r = 0.8; p\ 0.001) and longer ICU length of stay (r = 0.75; p\ 0.001). This is currently one of the only studies that has examined characteristics and treatment approaches of severe cases of ACEI-induced angioedema necessitating ICU level of care. Independent predictors of mechanical ventilation were history of COPD or asthma and pharyngeal angioedema. Non-Caucasian race and soft palate edema may also be important predictors of mechanical ventilation; however, statistical significance was only found on univariate analysis. Having a greater number of sites of angioedema was not an independent risk factor for mechanical ventilation, placing more emphasis on the specific location of edema, particularly pharyngeal angioedema [4]. Despite being very high risk medications, corticosteroids were used at high doses (methylprednisolone 186 mg/day) and for a long duration of time (4 days) in these patients despite their limited efficacy. The reason behind the aggressive corticosteroid prescribing patterns cannot be determined by our study methodology, however the controversy regarding the pathophysiology of ACEI-induced angioedema may be a contributing factor. It was previously thought to be an allergic or histaminemediated angioedema, making corticosteroids, epinephrine, and histamine antagonists the mainstay of therapy. However, emerging literature has found that these agents may be ineffective. A potentially more effective approach to managing these patients may be the use of

Ondansetron‐Induced Aminotransferase Level Elevation: Case Report and Review of the Literature

Elevation of aminotransferase levels is a rarely reported adverse effect of ondansetron. Increased aminotransferase levels, however, have been observed in patients receiving concurrent cisplatin chemotherapy and ondansetron. We describe a 44‐year‐old woman with no oncologic history or treatment with chemotherapy who received intravenous ondansetron on three separate occasions in the emergency department and subsequently experienced aminotransferase level abnormalities. Her baseline aspartate aminotransferase levels were within normal limits on each occasion, but increased to several times the upper limit of normal within 1 day of admission. After a diagnostic evaluation and drug review were performed, ondansetron appeared to be the most likely cause. On discontinuation of ondansetron, her aminotransferase levels trended downward, and the patient was discharged in stable condition. The Naranjo adverse drug reaction probability scale score for this event was 9, indicating that ondansetron was a definite cause of the elevated aminotransferase levels. Some studies describe a higher rate of increased aminotransferase levels in patients with cancer who are treated with ondansetron compared with those receiving metoclopramide. These elevations are not dose related and have not been associated with liver injury. Furthermore, the chemotherapeutic agent administered may play a role in aminotransferase level elevations. Since cisplatin was administered in most of these studies and is known to independently cause hepatotoxicity, the overall contribution of ondansetron to aminotransferase level elevation is not fully known. With the increased use of ondansetron outside of oncologic medicine, it is important that clinicians are aware of this rare adverse effect when determining the cause of elevated aminotransferase levels.