Characterizing Utilization and Outcomes of Digoxin Immune Fab for Digoxin Toxicity.

BACKGROUND: Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice. OBJECTIVES: The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity. METHODS: An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4 ng/mL, or serum K+ > 5 mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1. RESULTS: Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p < 0.05) including higher mean SDC (3.41 ± 1.63 vs 2.87 ± 1.17), higher mean potassium (5.33 ± 1.48 vs 4.55 ± 0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p < 0.01) and they had shorter intensive care unit lengths of stay (12.4 ± 20.3 vs 24.4 ± 28.7 days; p = 0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively. CONCLUSIONS: Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.

TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.

ABSTRACT: Objective: Compare changes in cholesterol and lipoprotein levels occurring in septic patients with and without acute respiratory distress syndrome (ARDS) and by survivorship. Methods: We reanalyzed data from prospective sepsis studies. Cholesterol and lipoprotein levels were analyzed using univariate testing to detect changes between septic patients with or without ARDS, and among ARDS survivors compared with nonsurvivors at enrollment (first 24 h of sepsis) and 48 to 72 h later. Results: 214 patients with sepsis were included of whom 48 had ARDS and 166 did not have ARDS. Cholesterol and lipoproteins among septic ARDS versus non-ARDS showed similar enrollment levels. However, 48 to 72 h after enrollment, change in median total cholesterol (48/72 h - enrollment) was significantly different between septic ARDS (-4, interquartile range [IQR] -23.5, 6.5, n = 35) and non-ARDS (0, -10.0, 17.5, P = 0.04; n = 106). When compared by ARDS survivorship, ARDS nonsurvivors (n = 14) had lower median total cholesterol levels (75.5, IQR 68.4, 93.5) compared with ARDS survivors (113.0, IQR 84.0, 126.8, P = 0.022), and lower median enrollment low-density lipoprotein cholesterol (LDL-C) levels (27, IQR 19.5-34.5) compared with ARDS survivors (43, IQR 27-67, P = 0.013; n = 33). Apolipoprotein A-I levels were also significantly lower in ARDS nonsurvivors (n = 14) (87.6, IQR 76.45-103.64) compared with ARDS survivors (130.0, IQR 73.25-165.47, P = 0.047; n = 33). At 48 to 72 h, for ARDS nonsurvivors, median levels of low-density lipoprotein cholesterol (9.0, IQR 4.3, 18.0; n = 10), LDL-C (17.0, IQR 5.0, 29.0; n = 9), and total cholesterol (59.0, 45.3, 81.5; n = 10) were significantly lower compared with ARDS survivors' (n = 25) levels of low-density lipoprotein cholesterol (20.0, IQR 12.0-39.0, P = 0.014), LDL-C (42.0, IQR 27.0-58.0, P = 0.019), and total cholesterol (105.0, IQR 91.0, 115.0, P = 0.003). Conclusions: Change in total cholesterol was different in septic ARDS versus non-ARDS. Total cholesterol, LDL-C, and apolipoprotein A-I levels were lower in ARDS nonsurvivors compared with survivors. Future studies of dysregulated cholesterol metabolism in septic ARDS patients are needed to understand biology and links to potential therapies.

A pilot study to identify pharmacogenomic and clinical risk factors associated with opioid related falls and adverse effects in older adults.

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid-related falls or serious adverse effects within older, opioid-treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain.