Impact of Automated Best Practice Advisories on Provider Response to CYP2C19 Genotyping Results for Patients on Clopidogrel.

ObjectiveThe study objective was to examine provider acceptance and genotyping responses to a best practice advisory (BPA) concerning clopidogrel and CYP2C19 intermediate and poor metabolizers within the context of a new pharmacogenomics program at a Midwestern health system. Other secondary objectives analyzed included appropriate BPA firing, the distribution of alleles in study population, indications for clopidogrel use, and impact of indication on therapy change. Methods: In this study, the progress of this program was assessed by quantifying how providers respond to BPAs generated in the electronic medical record (EMR), in the context of a single representative gene-drug-outcome relationship. Patient data was pulled via reports yielding patients with genotyped information in the EMR and cross-referenced with a report evaluating BPA firing occurrences. Results: By capturing antiplatelet therapy changes in response to CYP2C19 genotyping results, 37 patients were found that had 73 BPAs fire. Nine of those patients had alternative antiplatelet therapy ordered. Of these, 6 alternative antiplatelet therapies were ordered from the BPA. Conclusion: Providers utilized BPAs, but responded differently based on individual knowledge of genotypes and indications. Information obtained from this study can be used for provider education and as reference for future design and wording of BPAs.

Pharmacist-managed multistep order transmittal for electronic specialty prescriptions reduces represcribing burden in ambulatory clinics: A retrospective cohort pilot study.

BACKGROUND: Specialty medications pose unique prescribing challenges, including complexities with drug dosing and safety monitoring, need for prior authorization and patient financial assistance, use of payer-mandated specialty pharmacies, and special requirements for storage and handling. These challenges can lead to higher rates of represcribing for specialty clinic providers, who may be operating with inadequate information or limited resources. Multistep order transmittal (MSOT) is an electronic medical record (EMR) prescription work queue functionality used by a specialty pharmacy service to support select ambulatory clinics. OBJECTIVE: To explore the relationship between an MSOT specialty pharmacy support service and represcribing burden of specialty medications for providers in an ambulatory care setting. METHODS: A retrospective cohort pilot study was performed before and after MSOT implementation. Prescription data were queried from Sanford Health's EMR for patients who were electronically issued at least 1 prescription for an injectable biologic medication at a dermatology and rheumatology clinic. The pre-intervention group included index prescriptions prescribed between October 1, 2017, and June 20, 2018. The post-intervention group included index prescriptions prescribed between October 1, 2018, and June 20, 2019. Retrospective EMR review was completed to identify any prescriptions that were represcribed and the reason for represcribing. The primary outcome was the rate of represcribing. Secondary endpoints explored reason for represcribing, when it occurred. Nominal data were compared using Pearson's chi-square tests. Regressions were performed to account for potential confounders. RESULTS: The pre-intervention group included 880 index biologic prescriptions, and the post-intervention group included 941 index biologic prescriptions. The aggregate represcribing rate decreased from 12.73% in the pre-intervention group to 9.56% in the postintervention group (P = 0.03). Represcribing directly by providers as a result of needing to modify the destination pharmacy decreased significantly from 6.25% of the pre-intervention group to 0.64% of the post-intervention group (P < 0.01). However, represcribing due to patient preferences and prescribing errors increased significantly between the pre- and post-intervention groups, with patient preferences increasing from 0.91% to 2.55% (P = 0.01) and prescribing errors from 0.68% to 1.70% (P = 0.05), respectively. Represcribing due to provider preferences and payer restrictions remained similar between groups. CONCLUSIONS: Within 2 ambulatory care clinics in an integrated health care system, the use of pharmacist-managed MSOT reduced overall represcribing burden. The need to represcribe owing to wrong destination pharmacy was nearly eliminated, while appropriate represcribing to accommodate patient preferences and correct prescribing errors increased. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to disclose.

Clinical and Financial Impact of Rapid Antimicrobial Susceptibility Testing in Blood Cultures.

The rapid identification of pathogens that cause bloodstream infections plays a vital role in the modern clinical microbiology laboratory. Despite demonstrating a significant reduction in turnaround time and a significant effect on clinical decisions, most methods do not provide complete antimicrobial susceptibility testing (AST) information. We employed rapid identification (ID) and AST using the Accelerate PhenoTest on positive blood cultures containing Gram-negative bacilli. The length of stay (LOS) significantly decreased from an average of 12.1 days prior to implementation to 6.6 days post-implementation (p = 0.02), representing potential total savings of USD 666,208.00. All-cause mortality did not differ significantly, 27 (19%) versus 18 (12%), p = 0.11. We also observed an associated decrease in the use of broad-spectrum antimicrobials, including meropenem and quinolones. The implementation of a rapid ID and AST method, along with a well-established antimicrobial stewardship program, has the potential to decrease LOS, broad-spectrum antibiotic use, and costs to the healthcare system, with no observable impact on mortality.

Comparison of Anticoagulants for Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: A Pilot Study.

BACKGROUND: Direct-acting oral anticoagulants are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients after undergoing cardiac surgery is poorly defined despite a high prevalence of postoperative atrial fibrillation in this population. METHODS: Patients diagnosed with postoperative atrial fibrillation were prospectively randomized to warfarin or apixaban. Safety, efficacy, and economic outcomes were evaluated until their 4- to 6-week postoperative appointment. RESULTS: While this pilot study was not powered to determine a difference in safety or efficacy, adverse event rates were similar to the published literature. It was noted that a patient's course of therapy when utilizing apixaban was significantly less costly than warfarin when including medication, bridging, and laboratory expenses. CONCLUSION: Apixaban and warfarin both appeared to be safe and effective for anticoagulation throughout the duration of this pilot study in treating postoperative atrial fibrillation after coronary artery bypass grafting. Apixaban was associated with significantly less expense when bridging and monitoring costs were included in addition to medication expense.

Outcomes Associated With Standardized Ideal Body Weight Dosing of Intravenous Immune Globulin in Hospitalized Patients: A Multicenter Study.

Background: There are limited outcomes data for ideal body weight (IBW)-based dosing of intravenous immune globulin (human, IVIG) in hospitalized patients. Objective: To investigate clinical outcomes associated with a standardized change from total body weight to IBW-based dosing of IVIG. Methods: This was a retrospective, multicenter, pre-post sequential period analysis. Data from pre-implementation and post-implementation of an IBW-based dosing strategy for IVIG were collected in 2-year periods (October 1, 2012, to August 31, 2014, and October 2, 2014, to October 1, 2016, respectively). The primary outcome was incidence of 30-day hospital readmission. Length of stay (LOS) was analyzed as a secondary outcome. Results: For the 2 study periods, 297 patients were included for analysis. Both groups had similar demographics, IVIG indications, and body weight measurements, but the post-implementation period had a lower median grams per dose as compared with the pre-implementation period (40 vs 30 g, P ≤ 0.01). 30-Day hospital readmission rates were not significantly different (4% vs 9%, P = 0.07). In-hospital all-cause mortality was also not statistically significant (7.7% vs 3.4%, P = 0.11). The 2 study groups had a similar median hospital LOS (8 vs 7.6 days, P = 0.27). Conclusion and Relevance: The implementation of a standardized IBW IVIG dosing strategy was not associated with a statistically significant increase in 30-day hospital readmission or LOS but was associated with significantly fewer grams per dose given. Application of these data may aid in decreasing institutional drug spend without affecting patient outcomes. However, the study was underpowered, and further investigation is necessary to validate these findings.

Impact of a Comprehensive COPD Therapeutic Interchange Program on 30-Day Readmission Rates in Hospitalized Patients.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. The economic effect of COPD management is substantial, and the prevalence of the disease continues to rise with the growth of older populations. The purpose of this study was to evaluate the clinical and financial impact of a comprehensive therapeutic interchange program (CTIP) in hospitalized patients with COPD. The primary outcome was a 30-day readmission rate, with the following secondary outcomes: 30-day mortality and pharmacy-inhaled medication cost per patient. METHODS: This study was a multi-center, retrospective, electronic chart review of patients with a diagnosis of COPD admitted to two hospitals from July 1, 2016 to June 30, 2017. Our intervention group was admitted to a 550-bed tertiary care hospital and was managed with a pharmacist-led CTIP for inhaled products used in COPD. Our control group was admitted to a 545-bed tertiary care hospital, which did not have a CTIP in place. RESULTS: 2,885 hospitalized patients with a diagnosis of COPD were included in the analysis (1,350 in the intervention group and 1,535 in the control group). Univariable analysis demonstrated that the intervention group was associated with a lower 30-day readmission rate (5.8% vs. 8.3%; P = 0.012) and a lower average pharmacy-inhaled medication cost ($221 vs. $311; P = < 0.01). There was no statistical difference in 30-day mortality. CONCLUSION: This study demonstrates that the use of a pharmacist-led CTIP of COPD inhalers does not worsen patient outcomes and may provide pharmacy cost savings. The cohort managed with a CTIP was statistically associated with a lower 30-day readmission rate and lower pharmacy-inhaled medication costs without any difference in 30-day mortality.

Prevention of Clostridium difficile Infection in Critically Ill Adults.

The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.

Effectiveness of Umeclidinium-Vilanterol for Protocolized Management of Chronic Obstructive Pulmonary Disease Exacerbation in Hospitalized Patients: A Sequential Period Analysis.

Background: Bronchodilator therapy is a foundation of chronic obstructive pulmonary disease (COPD) exacerbation treatment. Although international guidelines recommend short-acting formulations given multiple times per day, long-acting formulations have not been adequately evaluated. The objective of our study was to determine the effectiveness of umeclidinium-vilanterol (UME/VIL), long-acting beta2-agonist/long-acting muscarinic antagonist (LABA/LAMA) as a once-daily alternative for treating COPD exacerbations in hospitalized patients. Methods: In this retrospective sequential period analysis, we reviewed electronic medical records of patients hospitalized for COPD exacerbations before (September 1, 2015 to February 29, 2016) and after (April 1, 2016 to September 30, 2016) incorporation of UME/VIL into our standard COPD protocol. Before implementation, patients received a daily anticholinergic plus twice-daily long-acting beta2-agonist therapy (tiotropium plus formoterol, n=65). After implementation, UME/VIL replaced the previous regimen (n=58). No other changes were made to the COPD protocol. The primary outcome was 30-day hospital readmission rate. Hospital length of stay, 30-day mortality, and cost of care were analyzed as secondary outcomes. Results: A trend toward increased 30-day readmission rates in the post-intervention group (24.1% versus 10.8%, p=0.049) was no longer statistically significant after adjustment for severity of illness (based on case-mix index) and complications or comorbidities based on diagnosis-related group codes (adjusted odds ratio: 2.499; 95% confidence interval: 0.916-7.380; p=0.074). Conclusion: After adjustment for potential confounders,the implementation of a LABA/LAMA combination product was not statistically associated with an increased 30-day readmission rate but was associated with lower cost of care.

Failure of a Best Practice Alert to Reduce Antibiotic Prescribing Rates for Acute Sinusitis Across an Integrated Health System in the Midwest.

BACKGROUND: Antimicrobial resistance is a growing concern, and in recent years, there has been increased interest in ambulatory antimicrobial stewardship. Acute rhinosinusitis (ARS) is one of the most common outpatient diagnoses that results in an antibiotic prescription. OBJECTIVE: To determine if a best practice alert (BPA) will affect the percentage of oral antibiotic prescriptions for adults with ARS. METHODS: A prospective, pre/post study was initiated to evaluate the percentage of oral antibiotic prescriptions for ARS in 117 primary care clinics in the Midwest. Included in the study results were 16,570 adults who had an office visit for ARS: 8,106 patients from December 1, 2015, to February 28, 2016, were in the pre-intervention group without an active BPA, and 8,464 patients from December 1, 2016, to February 28, 2017, were in the post-intervention group when the BPA was active. The primary outcome was the number of oral antibiotic prescriptions for ARS compared with the number of office visits for ARS in the pre- and postintervention groups. RESULTS: The percentage of oral antibiotics prescribed for the pre- and postintervention groups were 94.8% and 94.3%, respectively (P = 0.152). The BPA displayed for 7,780 visits, prompting discontinuation of an antibiotic for 10 (0.1%) visits in the postintervention group. CONCLUSIONS: This study suggests that, although an electronic alert may be attractive to facilitate antimicrobial stewardship, it may be ineffective. These results warrant alternative measures to facilitate ambulatory antimicrobial stewardship. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to declare. Study concept and design were contributed by Hansen, D. Leedahl, and N. Leedahl. Hansen and N. Leedahl took the lead in data collection, with assistance from Carson and D. Leedahl. Data interpretation was performed by all the authors. The manuscript was written by Hansen, along with the other authors, and revised by all the authors.

A Pilot Study for Antimicrobial Stewardship Post-Discharge: Avoiding Pitfalls at the Transitions of Care.

PURPOSE: Lack of patient follow-up is a major concern during care transitions, and the role of an antimicrobial stewardship program (ASP) in assessing antimicrobial regimens after hospital discharge is not well described. We implemented an expanded ASP to include patients recently discharged from the hospital and measured its impact on inappropriate antimicrobial therapy 72 hours after inpatient culture data were finalized. METHODS: A prospective cohort study was conducted at a 583-bed tertiary care center in the Upper Midwest of America. All patients discharged from our facility on antimicrobial therapy with pending culture results between February 3, 2016, and March 2, 2016, were included for review. If a pathogen nonsusceptible to all prescribed antimicrobials was identified post-discharge, a recommendation for therapy modification was communicated to the prescriber. RESULTS: Thirty-eight patients discharged from our hospital on antimicrobial therapy with pending culture results were evaluated for intervention. When final culture susceptibilities were considered, 5 of 38 patients had been prescribed an inappropriate antimicrobial agent. An ASP pharmacist intervened on 4 of 5 patients, resulting in 3 of 5 patients transitioning to appropriate antimicrobial therapy. When compared to a historical cohort, our transitions-of-care ASP yielded a 3.6-fold increase in antimicrobial-related interventions among discharged patients while reducing inappropriate outpatient antimicrobial therapy by 39%. CONCLUSION: We believe this is the first pharmacist-driven ASP represented in the medical literature which evaluated all available inpatient culture data to serve patients discharged from the hospital. Antimicrobial stewardship for patients in care transitions may provide an opportunity to increase ASP interventions and reduce inappropriate antimicrobial therapy.

A Case Series of 18 Patients Receiving Ticagrelor After Carotid Stenting.

PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is often used to prevent thrombotic complications after endovascular stent placement. Most of the published experience surrounding DAPT after carotid stenting is with clopidogrel. Ticagrelor may be a promising alternative, especially in patients who may be considered nonresponders to clopidogrel. However, clinical outcomes utilizing DAPT with ticagrelor in a cohort with carotid stenting is lacking. In this case series, we describe our experience with systematic prescribing of ticagrelor after carotid stent placement in 18 patients. METHODS: A retrospective review of 18 patients prescribed ticagrelor who underwent carotid stenting between November 2015 and January 2017 was performed. All eligible patients were included in the review. The primary end point of interest was any ischemic stroke or death within 30 days following the procedure. Intracranial hemorrhage was a secondary end point. RESULTS AND CONCLUSIONS: No patients experienced the primary end point of ischemic stroke or death within 30 days. No intracranial hemorrhages were observed. The use of ticagrelor after carotid stenting may be a reasonable alternative to clopidogrel after carotid stent placement. Randomized trials to support our findings are needed.

Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series.

BACKGROUND: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12-receptor antagonist is often used to prevent thrombotic complications after placement of a Pipeline embolization device (PED) for cerebral aneurysm. Although clopidogrel is common in this setting, high rates of nonresponse to this drug have made ticagrelor a potentially attractive alternative. OBJECTIVE: To describe safety and efficacy outcomes for ticagrelor following PED placement, including measurement of platelet function. METHODS: A retrospective analysis of data was completed for patients who underwent PED placement for cerebral aneurysm at a single centre between November 2015 and March 2017, with subsequent prescription of ticagrelor and ASA as dual antiplatelet therapy. The primary end point was any ischemic stroke or death within 1 year after the procedure. Intracranial hemorrhage was a secondary end point. Additionally, measurement of and values for platelet reactivity units (PRUs) during receipt of ticagrelor and ASA were evaluated. RESULTS: A total of 29 patients were included in this retrospective study. One patient experienced ischemic stroke 226 days after placement of the PED. In addition, 3 patients died during the 1-year follow-up period for causes unrelated to stroke or bleeding complications. No cases of intracranial hemorrhage were observed. Samples for measurement of P2Y12 levels were drawn at the discretion of the neurointerventionalists, and the PRU value was measured at least once for 28 (97%) of the 29 patients. The mean number of PRU measurements per patient after initiation of ticagrelor was 2.1 (standard deviation [SD] 1). Mean PRU value after initiation of ticagrelor was 65 (SD 57). CONCLUSIONS: In this case series describing the use of ticagrelor and ASA as dual antiplatelet therapy after PED placement for cerebral aneurysm, there was just one ischemic stroke, which occurred after the dual antiplatelet therapy had been discontinued. Further prospective trials are needed to describe the utility of ticagrelor use after PED placement, as well as its dosing and monitoring.

CONTEXTE: Une bithérapie antiplaquettaire composée d'acide acétylsalicylique (AAS) et d'un inhibiteur du récepteur P2Y12 est fréquemment utilisée pour prévenir les complications thrombotiques après la mise en place d'un dispositif d'embolisation Pipeline pour traiter un anévrisme cérébral. Quoique le clopidogrel soit souvent utilisé dans ce contexte, des taux élevés d'absence de réponse à ce médicament ont fait du ticagrélor une solution de rechange potentiellement intéressante. OBJECTIF: Décrire les résultats relatifs à la sécurité et à l'efficacité du ticagrélor après la mise en place d'un dispositif d'embolisation, y compris l'analyse de la fonction plaquettaire. MÉTHODES: Une analyse rétrospective de données a été réalisée dans un seul centre entre novembre 2015 et mars 2017 à l'aide des dossiers médicaux de patients chez qui a été posé un dispositif d'embolisation Pipeline comme traitement pour un anévrisme cérébral et à qui a ensuite été prescrite une bithérapie antiplaquettaire de ticagrélor et d'AAS. Le critère d'évaluation principal était les cas d'infarctus cérébral ou de décès durant l'année suivant l'opération. Les cas d'hémorragie intracrânienne ont servi de critère d'évaluation secondaire. De plus, l'analyse a porté sur l'évaluation de la réactivité plaquettaire et sa quantification en unités de réaction au P2Y12 pendant la prise de ticagrélor et d'AAS. RÉSULTATS: Au total, 29 patients ont été admis à la présente étude rétrospective. Un patient a subi un infarctus cérébral 226 jours après la mise en place d'un dispositif d'embolisation Pipeline. De plus, 3 patients sont décédés au cours de la période de suivi d'un an en raison de causes sans lien avec des complications liées à un accident vasculaire cérébral ou à une hémorragie. Aucun cas d'hémorragie intracrânienne n'a été observé. Les échantillons destinés à la mesure des unités de réaction au P2Y12 ont été prélevés selon le jugement des neuro-intervenants et l'évaluation de la réactivité plaquettaire a été réalisée au moins une fois chez 28 (97 %) des 29 patients. Le nombre moyen de mesures des unités de réaction au P2Y12 par patient était de 2,1 (écart-type de 1). Après l'amorce d'un traitement par ticagrélor, le résultat moyen en unités de réaction au P2Y12 était de 65 (écart-type de 57). CONCLUSIONS: Dans la présente série de cas décrivant l'utilisation d'une bithérapie antiplaquettaire composée de ticagrélor et d'AAS après la mise en place d'un dispositif d'embolisation Pipeline comme traitement pour un anévrisme cérébral, seul un cas d'infarctus cérébral a été observé et il s'est produit après l'arrêt de la bithérapie antiplaquettaire. De plus amples études prospectives sont nécessaires pour décrire l'utilité et la posologie du ticagrélor ainsi que le suivi du traitement après la mise en place d'un dispositif d'embolisation Pipeline.

Ketamine Infusion Therapy as an Alternative Pain Control Strategy in Patients with Multi-Trauma including Rib Fracture; Case Report and Literature Review.

Ketamine is a promising alternative agent for pain control that offers benefit to traditional strategies, particularly in the setting of rib fracture. Current pharmacologic therapies have clear adverse effects, and other options may be invasive, cost prohibitive, or marginally effective. We describe three consecutive patients with traumatic injuries including rib fracture for which a ketamine infusion was utilized as part of their pain control strategy.  For each patient, use of a ketamine infusion trended toward reduced opioid requirements with stable pain scores. One patient experienced a dissociative adverse effect prompting decrease and discontinuation of ketamine. No pulmonary complications in the form of emergent intubation or new diagnosis of pneumonia were observed. We believe the addition of ketamine infusion to be a valid alternative strategy for managing pain associated with rib fracture.

Association Between Updated Guideline-Based Palivizumab Administration and Hospitalizations for Respiratory Syncytial Virus Infections.

BACKGROUND: Since its introduction, palivizumab has been used to prevent respiratory syncytial virus (RSV) infection in high-risk populations. Recommendations for palivizumab administration changed in 2014. We examined whether adherence to 2014 palivizumab guidelines affected RSV hospitalization rates. METHODS: This was a retrospective sequential period analysis comparing the incidence of RSV hospitalization in patients younger than 2 years of age before and after implementation of 2014 palivizumab use criteria. Hospitalization data were prospectively collected through age-based surveillance for the post-2014 guideline period (November 1, 2014 to April 1, 2015 RSV season). Comparative data were collected retrospectively for hospitalizations during the pre-2014 guideline period of 2 previous RSV seasons (November 1, 2012 to April 1, 2013 and November 1, 2013 to April 1, 2014). The primary outcome was RSV hospitalization rate, and number of palivizumab doses administered was analyzed as a secondary outcome. RESULTS: During the study period, 194 RSV hospitalizations occurred. The rate of RSV hospitalization was 5.37 per 1000 children <24 months in the pre-2014 guideline period versus 5.78 per 1000 children <24 months in the post-2014 guideline period (difference of +0.4, 95% confidence interval: -1.2 to +2, P = 0.622). During the pre-2014 guideline period, 21.7 doses per 1000 children <24 months of palivizumab were administered, which decreased to 10.3 doses per 1000 children <24 months in the post-2014 guideline period, yielding a reduction of 11.4 doses per 1000 children <24 months (95% confidence interval: 14.3-8.4, P < 0.001). CONCLUSIONS: The implementation of 2014 palivizumab use criteria was not associated with an increased incidence of RSV hospitalization for children younger than 2 years of age but was associated with significantly less use of palivizumab.

Successful hemostasis and reversal of highly elevated PT/INR after dabigatran etexilate use in a patient with acute kidney injury.

Dabigatran etexilate is a novel oral anticoagulant indicated for anticoagulation in the management of atrial fibrillation and venous thromboembolism. Before its approval by the US Food and Drug Administration, warfarin, a vitamin K antagonist, was one of few oral anticoagulant options. The burden of therapeutic drug monitoring, dietary restrictions, and various drug interactions associated with warfarin have countered its extensive history of efficacy. Although dabigatran etexilate may alleviate some concerns encountered with warfarin therapy, there remains a paucity of evidence surrounding emergent reversal strategies in severe hemorrhage. We report here a 71-year-old man who presented to the emergency department with gastrointestinal hemorrhage precipitated by acute kidney injury while on dabigatran etexilate, with laboratory derangements highly uncharacteristic of dabigatran therapy (international normalized ratio, > 10, and activated partial thromboplastin time, 93 seconds). After admission to the intensive care unit and 7 U of fresh frozen plasma, the patient remained hemodynamically unstable due to blood loss. Other observations were made that are poorly characterized in medical literature related to dabigatran: refractory hemorrhagic shock after 7 U of fresh frozen plasma, rapid correction of coagulation parameters (international normalized ratio, 1.7, and activated partial thromboplastin time, 44 seconds) achieved 4 hours after 26 U/kg of 4-factor prothrombin complex concentrate (Kcentra; CSL Behring, King of Prussia, PA), and with subsequent achievement of hemostasis. The patient was discharged to home 7 days later without sequelae.

Key Controversies in Colloid and Crystalloid Fluid Utilization.

Nearly 2 centuries have passed since the use of intravenous fluid became a foundational component of clinical practice. Despite a steady stream of published investigations on the topic, questions surrounding the choice, dose, timing, targets, and cost-effectiveness of various fluid options remain insufficiently answered. In recent years, 2 of the most debated topics reference the role of albumin in acute care and the safety of normal saline. Although albumin has a place in therapy for specific patient populations, its high cost relative to other fluids makes it a less desirable option for hospitals and health systems with escalating formulary scrutiny. Pharmacists bear responsibility for reconciling this disparity and supporting the rational use of albumin in acute care through a careful evaluation of recently published literature. In parallel, it has become clear that crystalloids should no longer be considered a homogenous class of fluids. The past reliance on normal saline has been questioned due to recent findings of renal dysfunction attributable to the solution's supraphysiologic chloride concentration. These safety concerns with 0.9% sodium chloride may result in a practice shift toward more routine use of "balanced crystalloids," such as lactated Ringer's or Plasma-Lyte, that mimic the composition of extracellular fluid. The purpose of this review is to summarize the evidence regarding these 2 important fluid controversies that are likely to affect hospital pharmacists in the coming decades - the evidence-based use of human albumin and the rising role of balanced salt solutions in clinical practice.

Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

PURPOSE: The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. SUMMARY: A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. CONCLUSION: Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects.

Derivation of urine output thresholds that identify a very high risk of AKI in patients with septic shock.

BACKGROUND AND OBJECTIVES: To promote early detection of AKI, recently proposed pretest probability models combine sub-Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality. RESULTS: Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%). CONCLUSIONS: Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.