Annals of Pharmacotherapy最新文献

Background: Cyclosporine is an immunosuppressant extensively used for the prevention and treatment of graft-vs-host disease (GvHD) in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Converting the administration route of cyclosporine from intravenous to oral is common in the early period of allo-HSCT. Various factors may have an impact on the conversion ratio of cyclosporine.

Objective: To evaluate the effect of converting administration route from intravenous to oral on cyclosporine exposure in pediatric allo-HSCT recipients.

Methods: Children who underwent allo-HSCT and were administered with cyclosporine for the prevention of GvHD were included. The cyclosporine trough concentration (C0), the trough concentration-dose ratio (CDR), and the conversion ratio were evaluated. Meanwhile, factors related to the bioavailability of cyclosporine were also investigated.

Results: A total of 67 children with 280 concentrations were involved. The conversion ratio used in the study was approximately 1:2, and a significant decrease in cyclosporine CDR (110.5 vs 41.4 mg/kg per μg/L, P < 0.001) was observed. The overall bioavailability of cyclosporine was approximately 35%. Age younger than 3 years old (β = -10.70, 95% CI = -18.45 to -2.96, P = 0.007) and moderately increased transaminases (β = -17.95, 95% CI = -25.42 to -10.48, P < 0.001) had a significant impact on cyclosporine bioavailability.

Conclusions and relevance: A conversion ratio of 1:3 was found to be more appropriate for pediatric allo-HSCT recipients when switching cyclosporine from intravenous to oral administration. Children younger than 3 years old or with moderately increased transaminases had significant lower cyclosporine bioavailability. These results can assist in an individualized approach for patients undergoing cyclosporine formulation switching.

Background: There is limited data regarding the use of clinical assessment alone for neuromuscular blockade (NMB) titrations in the setting of acute respiratory distress syndrome (ARDS).

Objective: To compare the amount of cisatracurium (CIS) consumed when utilizing train-of-four (TOF)-guided NMB titrations or clinical assessment alone without TOF for continuous infusion (CI) administration.

Methods: A retrospective analysis was performed evaluating TOF-guided titrations compared with clinical assessment alone (non-TOF) for CI NMB with CIS. Individuals within the TOF group were assessed from January 2013 to December 2018 while those within the clinical assessment alone group were assessed from January 2021 to December 2024. Patients were excluded if they were less than 18 years old, had documentation of COVID-19 infection, were receiving extracorporeal membrane oxygenation, or had NMB initiated at an outside hospital. The primary objective was assessing drug utilization between groups.

Results: A total of 1047 and 553 individuals were screened resulting in 99 and 65 included for analysis in the TOF and non-TOF groups, respectively. The median cumulative CIS dose was 665 (472, 927) mg in the TOF group and 536 (400, 699) mg in the clinical assessment alone group, P = 0.011. The median infusion rate was 32% higher in the TOF group: 2.5 (1.8, 3.6) versus 1.9 (1.8, 2.4) µg/kg/min, P < 0.001, despite similar starting rates. Median drug costs were also significantly reduced when comparing the TOF group with the non-TOF group: $178 (126, 247) versus $143 (107, 187), P = 0.011.

Conclusion and relevance: This study assesses drug utilization when comparing TOF-guided NMB titration with clinical assessment alone in the modern ARDS era. Utilization of clinical assessment alone without TOF monitoring for CI CIS resulted in significantly reduced drug utilization and costs. Further studies are needed to assess the impact of clinical assessment alone on improvement of oxygenation.

Background: Levetiracetam administration via intravenous push (IVP) may improve outcomes in status epilepticus (SE) by decreasing time to administration. However, there is a paucity of literature describing the safety of IVP administration of higher loading doses used for early management of SE.

Objective: The purpose of this evaluation was to investigate the safety of high-dose IVP levetiracetam.

Methods: This was a retrospective, single-arm cohort study conducted at an academic medical center. Patients were included if they received IVP levetiracetam ≥3000 mg. The primary outcome was a composite of clinically significant adverse events (AEs) within 1-hour post-administration of levetiracetam: hypotension, hypertension, bradycardia, tachycardia, arrhythmia, and/or injection site reaction.

Results: A total of 140 patients met inclusion criteria, receiving a median levetiracetam dose of 4000 mg (interquartile range [IQR] = 3000, 4500). Seventeen (12.1%) patients experienced a clinically significant AE. The most common clinically significant AE was hypotension (9.2% [10/109]), followed by tachycardia (3.6% [4/112]), arrhythmia (1.8% [2/112]), hypertension (0.9% [1/109]), and injection site reaction (0.7% [1/140]). Eighty percent [8/10] of patients who experienced clinically significant hypotension were on at least 1 medication with potential confounding hemodynamic effects.

Conclusion and relevance: In this retrospective, single-arm analysis, high-dose (≥3000 mg) IVP levetiracetam was relatively well-tolerated but associated with a higher rate of clinically significant hypotension than has been reported in the previous literature, although several confounding factors may have contributed to this outcome. Our findings support the continued use of high-dose IVP levetiracetam with appropriate hemodynamic monitoring; hemodynamic effects should be further explored in future studies.

Background: The standard of care for alcohol withdrawal syndrome (AWS) is symptom-triggered benzodiazepines. There is an interest in utilizing phenobarbital first line for AWS in trauma-surgical patients.

Objective: The objective of this study was to compare a preemptive phenobarbital monotherapy protocol to symptom-triggered benzodiazepines for the prevention or treatment of AWS in the trauma-surgical patients.

Methods: This was a single-center, retrospective study to evaluate the AWS standard of care for the Trauma Surgical Critical Care Service. Patients were divided into groups based on AWS protocol. The primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes included: hospital mortality, hospital LOS, use of adjunctive agents for sedation, and incidence of mechanical ventilation rates.

Results: A total of 514 patients were screened for eligibility, and 200 patients met inclusion criteria, with 100 patients being in each group. Patients who received the symptom-triggered benzodiazepine protocol had similar ICU LOS (median [IQR], 2.6 days [1.4-5.6 days] vs 2.9 days [1.8-4.7 days]; P = 0.4) and hospital LOS (8.1 days [3.9-16.9 days] vs 7.1 days [3.9-11.2 days]; P = 0.05) compared with the phenobarbital protocol. Hospital mortality was significantly lower in those who received phenobarbital (4% vs 14%; P = 0.02), as was use of adjunctive sedative agents (22% vs 46%; P < 0.001), and mechanical ventilation rates (9% vs 31%; P < 0.001) when compared with symptom-triggered benzodiazepines.

Conclusion and relevance: Trauma-surgical patients receiving phenobarbital for prevention or treatment of AWS had similar ICU and hospital LOS compared with symptom-triggered benzodiazepines. The use of a phenobarbital protocol was associated with lower mortality, mechanical ventilation, and adjunctive sedative medication use.

Background: There are very limited data studying strategies designed to enhance environmentally conscious MDI prescribing habits. This study aimed to evaluate the impact of a multicomponent strategy promoting more environmentally responsible inhaler prescribing practices on the use of long-acting MDIs.

Objectives: What is the impact of a multicomponent eco-responsible inhaled medication prescribing awareness program on the prescription rate of long-acting MDIs in hospitalized patients?

Methods: This interrupted time series was conducted by retrospectively collecting long-acting inhaler metrics from digitalized records before and after awareness raising interventions. The primary outcome was to assess the impact of the multicomponent awareness campaign on the proportion of long-acting MDIs relative to the total number of long-acting inhalers prescribed on all in-patient hospital wards. The secondary endpoint was to evaluate the difference in proportion of long-acting MDI prescriptions between hospital admission and discharge in selected wards.

Results: A total of 7452 inhalers was collected. A significant relative decrease in level of 20.1% (P = 0.017) was observed between the preintervention and postintervention periods (27.9% and 22.3%, respectively). The slope of the proportion of long-acting MDIs was not significantly different (-0.2%, P = 0.319). There was no significant difference in the level or slope between admission and discharge for the secondary outcome.

Conclusion and relevance: A 20.1% reduction in the prescription rate of MDIs could be observed following awareness interventions focused on eco-responsible inhaler prescribing in a hospital setting. This is explained mainly by an initial decrease in the number of prescriptions postintervention and that change remained stable over time.

The reversal of anticoagulants can be a complex process with limited data describing the optimal overall approach beyond a specific reversal agent. Recent advances in anticoagulation stewardship have created opportunities to standardize and optimize the reversal of anticoagulants, especially in urgent life-threatening bleeding events. This article explores how pharmacists provided anticoagulation stewardship activities positively impact outcomes related to urgent anticoagulation reversal.

Background: Heart failure (HF) places a significant burden on the health care system, driven primarily by HF hospitalizations. While HF guidelines recommend initiation of quadruple guideline-directed medical therapy (GDMT) in patients with HF with reduced ejection fraction (HFrEF), in-hospital initiation of quadruple therapy remains a clinical challenge, particularly in patients with additional high-risk comorbidities.

Objective: The purpose of this study was to compare the efficacy and safety of triple GDMT with a sodium-glucose cotransporter inhibitor (SGLTi) vs mineralocorticoid receptor antagonist (MRA) added to beta blocker and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNi).

Methods: This retrospective cohort study was conducted in hospitalized patients with acute HFrEF. Patients who received triple GDMT therapy with a SGLTi or MRA added to beta blocker and ACEi/ARB/ARNi therapy at discharge were compared. The primary outcome was 90-day readmission for HF with secondary outcomes of 30-day readmission for HF and 90-day readmission for GDMT-associated adverse events.

Results: A total of 210 patients were included (SGLTi group, n = 105; MRA group, n = 105). Rates of 90-day readmission for HF between SGLTi and MRA groups were 23 (21.90%) vs 15 (14.29%); P = 0.1516. After adjusting for co-variables associated with 90-day readmission, 90-day readmission for HF was not significantly different in patients in the SGLTi vs MRA group (adjusted hazard ratio = 1.742, 95% confidence interval [CI] = 0.833 to 3.434; P = 0.1092). Rates of 90-day readmission for GDMT-associated adverse events were similar between groups.

Conclusion and relevance: In this cohort of patients receiving triple GDMT at discharge after hospitalization for acute HFrEF, triple therapy with an SGLTi vs MRA resulted in similar rates of 90-day HF hospitalization.