A systematic review of therapeutic enoxaparin dosing in obesity.

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75-0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

Gabapentin to treat acute alcohol withdrawal in hospitalized patients: A systematic review and meta-analysis.

BACKGROUND: Gabapentin is an antiepileptic medication with evidence of benefit in alcohol use disorder patients. The mechanism of action of gabapentin may also benefit patients suffering from acute alcohol withdrawal syndrome (AWS). METHODS: A systematic review and meta-analysis were conducted to examine if gabapentin can effectively replace/reduce the use of benzodiazepines for the treatment of acute alcohol withdrawal symptoms in hospitalized patients. Time to alcohol withdrawal symptom resolution, amount of benzodiazepines administered, rate of resolution of alcohol withdrawal symptoms, serious withdrawal-related complications, and hospital length of stay (LOS) were examined. RESULTS: Eight retrospective studies (n = 2030) were included in this meta-analysis. There were no studies that examined study outcomes for patients who received only gabapentin and no benzodiazepines; in all studies, gabapentin-treated patients may have received benzodiazepines prior to gabapentin. There were no significant differences between gabapentin-treated and benzodiazepine-treated groups in time to symptom resolution, amount benzodiazepines administered, withdrawal-related complications, or LOS. There was a significant difference in the rate of symptom resolution favoring gabapentin-treated patients (p = 0.05); however, this analysis included only one study. Subgroup analyses of severe AWS patients revealed a significant decrease in LOS (p = 0.04) and a decrease in amount of benzodiazepines administered (p = 0.02) in gabapentin-treated patients, but these analyses included only one study. Subgroup analysis of patients receiving only gabapentin without benzodiazepines found a significantly decreased LOS in the gabapentin group compared to the benzodiazepine group (p < 0.001), but this analysis included only two studies. CONCLUSIONS: There is insufficient evidence to support the widespread use of gabapentin to treat inpatients suffering AWS. All studies included in this meta-analysis are retrospective with high risk of confounding. Well-designed, randomized, controlled studies of gabapentin to treat patients with AWS are required.

Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19.

Introduction: Coronavirus disease 2019 is a global health threat often accompanied with coagulopathy. Despite use of thromboprophylaxis in this population, thrombotic event rates are high. Materials and methods: This was a multicenter, retrospective cohort study comparing the safety and effectiveness of thromboprophylaxis strategies at 2 institutions in hospitalized patients with coronavirus disease 2019. Regimen A utilized a higher-than-standard thromboprophylaxis dosage and Regimen B received full-dose anticoagulation for any D-dimer 3 mcg/mL or greater and prophylactic for less than 3 mcg/mL. The primary outcome compared the rate of thrombotic events between treatment groups. Secondary endpoints compared rates of major or clinically relevant non-major bleeding as well as the proportion of patients in each group experiencing thrombotic events within 30 days of discharge. Results: One-hundred fifty-three patients were included in the analysis, 64 receiving Regimen A and 89 receiving Regimen B. Seven (4.6%) thrombotic events occurred, 3 (4.7%) in patients receiving Regimen A, and 4 (4.5%) in Regimen B (P = 1.0). Twelve patients (13.5%) receiving Regimen B had a bleeding event versus 2 (3.1%) in Regimen A (P = .04), half of which were major in each group. All patients who bled in either treatment group were receiving mechanical ventilation, and 12 of 14 were receiving full-dose anticoagulation. One patient receiving Regimen A was readmitted with a pulmonary embolism. Conclusions: In this study, the thromboprophylactic regimen impacted bleeding, but no significant difference was seen with thrombotic outcomes. Almost all patients who experienced a bleed were mechanically ventilated and receiving full-dose anticoagulation. The use of full-dose anticoagulation should be cautioned in this population without an additional indication.

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Evaluation of a Computerized Insulin Dosing Tool for the Treatment of Diabetic Ketoacidosis.

PURPOSE: Computerized insulin dosing tools (CIDT) have been shown to improve the care of critically ill patients with hyperglycemia. Application of a CIDT in addition to a diabetic ketoacidosis (DKA) order set for the treatment of DKA has not been evaluated. Our goal was to determine the effects the CIDT would have on the treatment of a patient with DKA. METHODS: In this retrospective, pre-post chart review, a provider-driven insulin dosing strategy (pregroup) was compared to the CIDT (postgroup) with 24-hour pharmacist monitoring. The CIDT utilized an equation that incorporated a patient's most recent blood glucose (BG) value and recommended a rate of insulin (units/hour) every hour. RESULTS: All baseline characterizes were similar between the 2 groups. There were no significant differences in average time to anion gap closure (≤ 12 mEq/L) or intensive care unit length of stay between the pregroup and postgroup (12.5 [6] hours vs 10.5 [7] hours, P = 0.235; 40.6 [24] hours vs 40.8 [24] hours, P = 0.945). Although not statistically significant, 17 hypoglycemic events (BG < 70 mg/dL) occurred in the pregroup with 4 being severe (BG < 50 mg/dL) while 5 hypoglycemic events occurred in the postgroup, none of which were severe. CONCLUSION: This study suggests, when compared to a provider-driven insulin dosing strategy, the CIDT with 24-hour pharmacist monitoring is efficacious and safe for treatment of patients with a primary diagnosis of DKA.

Stability of 2 mg/mL Adenosine Solution in Polyvinyl Chloride and Polyolefin Infusion Bags.

Adenosine is a potent endogenous mediator of vasodilation. Compounded sterile solutions of adenosine are used in cardiac catheterization lab to perform stress tests on the heart. These tests are used to determine the fractional flow reserve (FFR) and are commonly used in the management and diagnosis of cardiovascular conditions. The purpose of this study was to assess the physical and chemical stability of 2 mg/mL adenosine in 0.9% Sodium Chloride Injection, USP in polyvinyl chloride [PVC]) and polyolefin infusion bags stored at room temperature (20°C-25°C) and under refrigeration (2°C-8°C). The compounding and analytical methods used in this study were very similar to those described in the prior publications from the authors' laboratory. To ensure a uniform starting concentration of all stability samples, a batch of 2 mg/mL adenosine solution was prepared and then packaged into empty PVC and polyolefin infusion bags. These stability samples were prepared in triplicate for each bag type and storage temperature (a total of 12 samples). The infusion bag samples were assessed for stability immediately after preparation and after 1 day, 3 days, 7 days, and 14 days. At each time point, the infusion bags were first visually inspected against a light background for color change, clarity, and particulates. Aliquots were drawn from each sample at each time point for pH analysis and high-performance liquid chromatography (HPLC) analysis. Over 14 days of storage at room temperature or refrigeration, no considerable change in visual appearance or pH was observed in any bags. All samples retained 90% to 110% of the initial drug concentration. No significant degradation peaks were observed in the HPLC chromatograms.

Efficacy and Safety of High-Dose Subcutaneous Unfractionated Heparin Prophylaxis for the Prevention of Venous Thromboembolism in Obese Hospitalized Patients.

BACKGROUND: Obese patients experience a higher risk of venous thromboembolism (VTE) than their nonobese counterparts, which may warrant a more aggressive approach to thromboprophylaxis in this population. OBJECTIVE: The purpose of this study was to compare rates of nosocomial VTE in obese patients treated with high-dose versus conventional-dose subcutaneous unfractionated heparin sodium (UFH) for thromboprophylaxis. METHODS: A retrospective, single-center, cohort study was conducted to evaluate obese, adult, hospitalized patients admitted between April 2011 and April 2014 who received heparin 5,000 or 7,500 units subcutaneously every 8 hours for thromboprophylaxis. The primary outcome assessed the rate of nosocomial VTE in obese patients treated with high-dose heparin (7,500 units subcutaneously q 8 h) versus conventional-dose heparin (5,000 units subcutaneously q 8 h). Additionally, a secondary outcome assessed safety by quantifying bleeding events. RESULTS: Nosocomial VTE occurred in 2/196 (1.02%) patients who received high-dose heparin thromboprophylaxis and in 5/2,182 (0.23%) patients who received conventional-dose heparin (p = .05). Bleeding occurred in 0/196 (0%) patients in the high-dose heparin group and in 2/2,182 (0.09%) patients in the conventional-dose heparin group (p = .67). All bleeding events were minor. CONCLUSIONS: This study failed to demonstrate a statistically significant reduction in the rate of nosocomial VTE in obese patients who received high-dose heparin thromboprophylaxis. Despite receiving a higher heparin dose, no increased risk of bleeding was observed in the high-dose group. Further investigation is needed to identify the optimal heparin dose for thromboprophylaxis in obese patients.

Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin.

Enoxaparin is a low molecular weight heparin (LMWH) that has been shown to be effective in deep vein thrombosis, pulmonary embolism, and unstable angina. Because renal function plays an important role in the clearance of LMWH, the authors sought to investigate the effect of renal function on enoxaparin. This prospective multiple-dose study evaluated 18 patients with varying degrees of renal function initiated on enoxaparin 1 mg/kg subcutaneously every 12 hours. Peak blood levels of anti-Xa concentrations were obtained 4 +/- 0.5 hours postdose after receiving at least three doses of enoxaparin. The median antifactor Xa levels were higher in patients with creatinine clearance (CLCr) < or = 30 mL/min compared to CLCr > or = 31 mL/min (1.34 IU/mL vs. 0.91 IU/mL, respectively, p < 0.05). A linear correlation was established between creatinine clearance and anti-Xa concentrations (p < 0.0005). On the basis of the data, the authors believe that a dose adjustment is necessary in patients receiving repeated doses of enoxaparin with CLCr < or = 30 mL/min.