Safety of High-Dose Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Hospitalized Obese Patients.

BACKGROUND: Optimal dosing of unfractionated heparin (UFH) for thromboprophylaxis in the obese patient population is uncertain because of their high-risk, prothrombotic state and a complexity of pharmacokinetic considerations. Literature on the appropriateness of the use of a higher dose UFH regimen remains unclear and inconsistent. OBJECTIVE: To evaluate the safety of the use of 7500 units every 8 hours (high-dose) of subcutaneous UFH compared with the use of 5000 units every 8 hours (standard-dose) of subcutaneous UFH for thromboprophylaxis in obese patients (defined as BMI ≥30 kg/m2). METHODS: In a retrospective cohort study, 326 adult patients were included, with a BMI ≥30 kg/m2, who were admitted to a large, urban academic medical center between September 1, 2015, and September 1, 2018. Patients received either high-dose or standard-dose UFH for at least 48 hours. The primary end point was the incidence rate of bleeding events, defined as a ≥2-g/dL fall in hemoglobin level or receipt of transfusion of 2 or more units of packed red blood cells (pRBCs) from the start of the UFH order. RESULTS: The incidence rate of bleeding was significantly higher in those who received high-dose UFH (43%) compared with those who received standard-dose UFH (29%; P = 0.008). No significant difference was found between venous thromboembolism event rates. CONCLUSION AND RELEVANCE: High-dose UFH was associated with an increased bleeding event rate compared with standard-dose UFH in patients with a BMI ≥30 kg/m2. This raises safety concerns about the appropriateness of utilizing this regimen in this population.

Diabetes Insipidus After Discontinuation of Vasopressin Infusion for Treatment of Shock.

OBJECTIVES: Vasopressin has achieved common usage for the treatment of catecholamine-requiring and catecholamine-resistant shock. Diabetes insipidus is a syndrome characterized by excretion of abnormally large volumes of dilute urine. To date, very few reports of diabetes insipidus after discontinuation of vasopressin infusion have been published; the majority of previous reports describe neurosurgical patients. The purpose of the present study was to investigate the occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion among patients treated with vasopressin infusion for shock. DESIGN: Retrospective analysis of electronic health records of patients receiving continuous vasopressin infusion for the treatment of shock within a 5-year period (2012-2016). SETTING: Medical, surgical, and cardiothoracic ICUs within one academic medical center. PATIENTS: One-thousand eight-hundred ninety-six patients received vasopressin infusion for the treatment of shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion was 1.53% among all patients. Sixteen of 29 patients with diabetes insipidus after discontinuation of vasopressin infusion had undergone cardiothoracic intervention, such as coronary artery bypass graft and valve replacement surgery, extracorporeal membrane oxygenation, and placement of ventricular assist devices. No neurosurgical patients were identified in our cohort. In a control group of patients receiving norepinephrine but not vasopressin infusion for treatment of shock, criteria for diabetes insipidus were observed in two of 1,320 subjects (0.15%). CONCLUSIONS: Despite a paucity of published reports, diabetes insipidus after discontinuation of vasopressin infusion appears not to be a rare phenomenon, and is likely to be encountered by intensivists who regularly employ vasopressin for the treatment of vasoplegic shock. Previous reports consisted predominantly of neurosurgical patients. Our findings demonstrate the occurrence of diabetes insipidus after discontinuation of vasopressin infusion among patients with septic shock as well as vasoplegic shock after cardiothoracic intervention. The mechanism of diabetes insipidus after discontinuation of vasopressin infusion remains to be elucidated but may involve transient downregulation of V2 receptors induced by exposure to supraphysiological doses of vasopressin.

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. RESULTS: Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. CONCLUSION: Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Evaluation of Clinical Outcomes After Introduction of a Dedicated Infectious Diseases-Critical Care Medicine Service in Critical Care Units.

BACKGROUND: Infection is a leading cause of admission to intensive care units (ICUs), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-critical care medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. METHODS: In this single-site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during the postintervention period from January 1 to December 31, 2017, and compared it to antibiotic utilization in the same ICUs during the preintervention period from January 1 to December 31, 2015. RESULTS: Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam, and cefepime during the intervention period. When compared to the preintervention period there was no difference in-hospital mortality, hospital length of stay, and readmission. CONCLUSIONS: With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

Clinical Pharmacists: An Invaluable Part of the Coronavirus Disease 2019 Frontline Response.

Although coronavirus disease 2019 was first identified in December 2019, it rapidly spread and became a global pandemic. The number of patients infected with the novel coronavirus (severe acute respiratory syndrome coronavirus 2) rose rapidly in New York State, placing great stress on healthcare systems. The traditional roles and practices of healthcare providers were dramatically redefined to meet the demand to care for the large number of ill patients. While literature reports on the experiences of many frontline staff, there is a scarcity of reports on the role of clinical pharmacists during this crisis. We report the role of critical care clinical pharmacists at a large academic medical center in New York City during this pandemic. Effective crisis management required clinical pharmacists to employ a wide array of skills and knowledge. Areas included clinical expertise, education, data analysis, health informatics infrastructure, and inventory management in times of surging medication use and manufacturer shortages. Clinical pharmacists fulfilled an essential service during the coronavirus pandemic by working to ensure the best possible outcomes for the patients they served on the frontline.

Angiotensin II (Giapreza): A Distinct Mechanism for the Treatment of Vasodilatory Shock.

Septic shock, a form of vasodilatory shock associated with high morbidity and mortality, requires early and effective therapy to improve patient outcomes. Current management of septic shock includes the use of intravenous fluids, catecholamines, and vasopressin for hemodynamic support to ensure adequate perfusion. Despite these interventions, hospital mortality rates are still greater than 40%. Practitioners are continuously faced with cases of refractory shock that are associated with poor clinical outcomes. In December of 2017, the Food and Drug Administration approved the first synthetic human angiotensin II, a potent vasoconstrictor, to increase blood pressure in adults with septic or other distributive shock. This approval was based (ATHOS) on the results from the Angiotensin II for the Treatment of High Output Shock study. In this randomized, double-blind, placebo-controlled trial, patients in the angiotensin II group achieved higher rates of target mean arterial pressure and had lower catecholamine requirements in the first 3 hours of therapy compared with patients in the placebo group. There was no significant difference in the 28-day mortality. Safety issues including the risk of thromboembolic events, infection, and delirium have made clinicians cautious in adopting angiotensin II into practice. Ongoing studies are needed to more clearly define the role of this agent and its utility in the management of shock.

Canagliflozin: a new class of antidiabetic agent targeting the sodium-glucose cotransporter.

Diabetes is a chronic disease that leads to multiple microvascular and macrovascular complications. It is the seventh leading cause of death in the United States with increased prevalence worldwide. There are multiple antihyperglycemic medication classes available on the market with advantages and disadvantages. Canagliflozin, a novel agent that lowers plasma glucose by decreasing glucose reabsorption at the proximal tubules of nephrons, inhibits the sodium-glucose cotransporter 2. Data suggest a decrease in hemoglobin A1C by about 1% in both fasting and postprandial plasma glucose levels, when canagliflozin was studied as monotherapy or with various combinations of metformin, pioglitazone, sulfonylurea, and insulin. Interestingly, canagliflozin use in geriatric patients and in those with renal impairment showed decreased efficacy and an increased risk of adverse reactions. These include, but are not limited to, hypotension, renal impairment, hyperkalemia, hypoglycemia, genital mycotic infections, hypersensitivity reactions, and increases in low-density lipoproteins. Hypoglycemia is a rare occurrence when canagliflozin is used alone but can occur more frequently when used in combination with sulfonylurea or insulin. This article reviews the pharmacology of canagliflozin, examines available clinical trials for efficacy and safety, and describes its role in diabetes management.