Annals of Pharmacotherapy最新文献

Background: Patients with substance use disorders (SUD) are at an increased risk of admission to intensive care units (ICUs) and the relationship between SUD and commonly used sedative and analgesic medications remains understudied.

Objective: The objective of this study was to describe associations between substance use disorder (SUD) and medication dose requirements in patients with critical illness requiring invasive mechanical ventilation (IMV).

Methods: This was a single center, retrospective study of adult patients admitted to an ICU between January 1, 2017, to October 31, 2022 who were initiated on IMV within 48 hours. The primary outcome was median total daily dose of each sedative and analgesic medication received, grouped as follows: parenteral opioids, benzodiazepines, propofol, and dexmedetomidine. Multivariable median regression was used to determine associations between SUD and median daily dose after adjustment for demographic and clinical covariables.

Results: Of 1290 included patients, 358 (27.8%) had a documented SUD present on admission. In unadjusted analyses, patients with SUD received higher median daily doses of parenteral opioids (197.5 MME [IQR 61.9-344.3] vs 162.2 MME [IQR 60.3-324.6]) and propofol (26 640 µg/kg [IQR 11 659-43 518] vs 23 248 µg/kg [IQR 10 510-38 870). No differences in median daily dose were noted for parenteral benzodiazepines or dexmedetomidine. In adjusted analyses, associations between SUD and median daily dose of parenteral opioids (β, 18.1 MME; 95% CI, -13.6 to 49.4) or propofol (β, 1699.9 µg/kg; 95% CI, -2477.1 to 5882.8) were no longer present.

Conclusion and relevance: Results of unadjusted analyses aligned with prior studies reporting increased dose requirements of sedation and analgesia in patients with SUD; however, associations were diminished after adjustment for clinical and demographic covariables. Our results suggest the presence of SUD alone may not necessitate empirically higher medication doses in patients with SUD receiving IMV during critical illness.

Background: Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that has an off-label indication for arrhythmias in pediatric patients.

Objectives: The primary objective was identification of the line of therapy and type of arrhythmia for which ivabradine was initiated. The secondary objective was to evaluate the initial and peak ivabradine doses, tolerance in partially fed patients (i.e., patients not receiving full feeds at the time of ivabradine initiation), number of patients continued home on ivabradine, concomitant drug interactions with a class C, D, or X classification, and adverse effects.

Methods: A retrospective study of hospitalized patients <18 years of age receiving ivabradine for arrhythmias between January 1, 2021 and November 30, 2023. Data variables included demographics, ivabradine dosing regimens, concomitant anti-arrhythmic medications, percentage of ivabradine course while receiving full enteral feeds, concomitant medications with drug-drug interactions, and adverse effects (bradycardia [defined as <100 beats/min in neonates and <50 beats/min in infants and children], atrial fibrillation, vision changes, and emesis attributed to ivabradine).

Results: Seventeen patients were included. The most frequent arrhythmia indication was atrial tachycardia and ivabradine was most frequently used as a third-line anti-arrhythmic. Ten (58.8%) received ivabradine despite not being on full enteral feeds. The median initial and peak ivabradine doses were 0.05 mg/kg/dose and 0.07 mg/kg/dose, respectively, and it was most frequently administered every 12 hours. Only 1 patient required a dose decrease for a noted adverse effect. Most patients (94.1%) had a Class C drug-drug interaction, and 3 had a Class X interaction. Ten (58.8%) were discharged home on ivabradine.

Conclusions and relevance: Ivabradine was safe and effective as additive therapy for the treatment of pediatric arrhythmias. Larger studies of ivabradine use in pediatric arrhythmias are needed.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for diabetes and obesity. Yet, the role of comorbidities on adherence, and variability due to drug subtype or indication remains understudied.

Objective: Study objective was to (a) evaluate association between baseline comorbidities and digestive system adverse events on first-year GLP-1 RA adherence and (b) assess how associations differ across GLP-1 RA subtypes and between patients with diabetes and obesity.

Method: We conducted a retrospective cohort study of adults with type 1 or type 2 or obesity initiating GLP-1 RAs between 2018 and 2023 using the University of California Health Data Warehouse. Primary outcome was first-year adherence association with baseline comorbidity and digestive system adverse event status. Adherence odds ratios based on exposure were estimated using regression. Analyses were stratified by indication and drug type.

Result: Among 69 049 adults who initiated a GLP-1 RAs between 2018 and 2023, 59.3% had diabetes and 74.4% had obesity. Among patients with diabetes, hypertensive disorder (OR: 1.06, 95% CI: 1.01-1.10), hyperlipidemia (OR: 1.17, 95% CI: 1.12-1.22), and chronic kidney disease (CKD) (OR: 1.14, 95% CI: 1.08-1.21) increased adherence likelihood. Among patients with obesity, hyperlipidemia (OR: 1.10, 95% CI: 1.05-1.15) and CKD (OR: 1.09, 95% CI: 1.02-1.16) were associated with increased adherence. In patients with diabetes, atherosclerotic cardiovascular disease (ASCVD) and digestive system adverse events reduced adherence likelihood (OR: 0.90, 95% CI: 0.86-0.95) and (OR: 0.94, 95% CI: 0.90-0.98), respectively. Results were similar for patients with obesity. Findings remained consistent overall in brand-specific analyses.

Conclusion and relevance: Comorbidities affected GLP-1 RA adherence with variation by drug and indication. Further research is needed to understand drivers of these patterns and how they may inform future strategies to support adherence.

Background: The 2016 Surviving Sepsis Campaign (SSC) guidelines recommended tapering corticosteroids once vasopressors were no longer needed, while the 2021 update suggested IV hydrocortisone for patients with ongoing vasopressor needs but offered no guidance on tapering. Evidence on steroid taper duration remains limited.

Objective: This study evaluates corticosteroid tapering strategies in septic shock patients.

Methods: A retrospective analysis, approved by the UNC Human Research Review Committee, was conducted on adult critically ill patients with septic shock who received vasopressors and hydrocortisone between January 1, 2016, and April 1, 2024. Patients were divided into 2 groups based on the duration of their steroid taper: rapid taper (<72 hours) and prolonged taper (≥72 hours). The primary outcome was vasopressor reinitiation within 72 hours of all vasopressors being stopped. Secondary outcomes included vasopressor reinitiation within 24 hours of all vasopressors being stopped, length of stay (LOS), mortality, and adverse effects. The study was approved by the University of North Carolina Human Research Review Committee.

Results: A total of 312 patients were analyzed: 222 received a rapid taper and 90 received a prolonged taper. Vasopressor reinitiation within 72 hours occurred in 48% of the rapid taper group and 66% of the prolonged group (P = 0.006). Within 24 hours, reinitiation was 42% in the rapid group versus 56% in the prolonged group (P = 0.039). Mortality was 32% in the rapid group and 41% in the prolonged group (P = 0.185). Mean intensive care unit (ICU) LOS was 215 hours for the rapid group and 418 for the prolonged group (P < 0.001). Mean hospital LOS was 447 hours for the rapid group and 734 for the prolonged group (P < 0.001). Hypernatremia was less frequent in the rapid group (29% vs 47%, P = 0.004). Hyperglycemia was similar between groups (24% vs 21%, P = 0.327). Limitations included the retrospective design and potential for selection bias, temporal bias, and missing or inconsistently documented clinical variables.

Conclusion and relevance: Rapid corticosteroid tapering in septic shock patients was associated with a reduced incidence of vasopressor reinitiation, shorter ICU and hospital stay, and a lower incidence of hypernatremia. These findings enhance our understanding of tapering strategies and suggest that rapid tapering (<72 hours) in septic shock may improve patient outcomes, informing future clinical guidelines.