Apixaban and rivaroxaban anti-Xa level utilization for guidance of administration of andexanet alfa: a case series.

BACKGROUND: Andexanet alfa, a modified recombinant factor Xa (FXa), was FDA approved in 2018 for anticoagulant reversal in patients with life-threatening bleeding associated with FXa inhibitors (FXaI). The ANNEXA-4 investigators administered andexanet alfa to patients within an 18-h from last dose of oral FXaI. In practice, time from last dose is often unknown. Previous studies have shown that clearance of these agents may be impaired by renal and hepatic dysfunction, as well as drug-drug interactions. Decision for use of andexanet alfa is also complicated by its high cost, limited drug availability, and thrombotic risk. This study aimed to describe the utility of anti-Xa DOAC levels as a decision point to administer andexanet alfa. METHODS: This is a case series of four patients with an anti-Xa DOAC level that received andexanet alfa for oral FXaI reversal in the setting of life-threatening bleeding or prior to procedure. RESULTS: Four patients were included in the study. Two patients had a known time since last dose of oral FXaI. All patients had a detectable anti-Xa DOAC levels prior to administration of andexanet alfa. Two patients had levels within the peak range, one patient had a level below the peak range, and one patient had a level above the peak range. Andexanet alfa was administered after anti-Xa DOAC level return in all patients. CONCLUSION: In our case series, obtaining anti-Xa DOAC levels prior to administration of andexanet alfa was achievable and facilitated use of reversal agents in patients with major bleeding or emergent procedural need.

Ruptured intraventricular brain abscesses due to Fusobacterium nucleatum with obstructive hydrocephalus: illustrative case.

BACKGROUND: Fusobacterium spp. are strictly anaerobic microorganisms and normal flora of the oropharyngeal, gastrointestinal, and female genital tracts. It is commonly associated with periodontal disease, pharyngitis, mastoiditis, and tonsillitis, with a tendency to abscess formation. OBSERVATIONS: The authors report a case of brain abscesses complicated by ventriculitis and obstructive hydrocephalus caused by Fusobacterium nucleatum of suspected odontogenic source. While repeated bacterial cultures remained negative, the isolate was identified using bacterial sequencing. LESSONS: Empirical antimicrobial coverage for F. nucleatum should be considered in patients presenting with brain abscess. Genetic bacterial sequencing utilizing 16S ribosomal RNA molecular diagnostic testing may assist in microorganism identification to guide antimicrobial therapy.

Pharmacokinetic and Pharmacodynamic Principles for Toxicology.

Pharmacokinetic and pharmacodynamic interactions between drugs and the body play a vital role in the therapeutic effects of drugs as well as their toxicity. Toxic effects may evolve from high doses of drugs or from alterations in the absorption, distribution, metabolism, and excretion of those drugs. The effective dose of a drug is influenced by the initial dose, route of administration, drug formulation, and bioavailability. This effective dose, in conjunction with the frequency of dosing, duration of exposure, and pharmacodynamic variability, directly affects the toxicity experienced in the body.

Outcomes Associated With 4-Factor Prothrombin Complex Concentrate Administration to Reverse Oral Factor Xa Inhibitors in Bleeding Patients.

Compared with vitamin K antagonists (VKAs), oral factor Xa inhibitors are associated with at least equivalent efficacy and a lower incidence of major bleeding. Despite this benefit, bleeding remains the most common adverse event. Prior to the approval of andexanet alfa, alternative agents such as 4-factor prothrombin complex concentrate (4F-PCC) were utilized for reversal. This was a retrospective, descriptive study conducted on patients 18 years of age or older who received 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Patients were excluded if they received a VKA or dabigatran in the previous 48 hours. A subgroup analysis comparing 4F-PCC with andexanet alfa was conducted on patients who met the inclusion and exclusion criteria of the ANNEXA-4 trial. The primary end point of this study was to evaluate the incidence of hemostasis and associated dosing strategies in patients receiving 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Thirty-eight patients were included, and 28 patients (74%) achieved hemostasis. The median dose of 4F-PCC was 50 units/kg. In patients who achieved hemostasis, the median dose was 50 units/kg, and in those who failed to reach hemostasis, a median dose of 30 units/kg was seen. Within the subgroup analysis, there was no difference in overall rates of hemostasis between the 4F-PCC and andexanet alfa groups. Remaining a reasonable option to utilize for reversal of oral factor Xa inhibitors is 4F-PCC, especially when andexanet alfa is unavailable, with 50 units/kg appearing to be the most effective dose to achieve hemostasis. Further studies are needed to determine a preferential agent.

Volume-Based Feeding Enhances Enteral Delivery by Maximizing the Optimal Rate of Enteral Feeding (FEED MORE).

BACKGROUND: The importance of enteral nutrition (EN) in critically ill patients is well documented. However, actual administration of EN frequently does not amount to prescribed nutrition goals. Persistent underfeeding may lead to impaired immune response, increased mortality, and higher costs. Traditionally, EN uses a rate-based approach, utilizing slow titration to goal and a final fixed hourly rate, regardless of interruptions in feeding. Volume-based feeding (VBF) establishes a 24-hour EN goal volume, and the rate varies to achieve this daily goal when interruptions occur. MATERIALS AND METHODS: This was a retrospective, single-center, quasi-experimental study comparing traditional rate-based feeding (RBF) to VBF in adult patients admitted to the medical and neurosurgical intensive care units (ICUs). The primary outcome was mean percentage of total goal energy received after EN initiation until 7 days, transfer from ICU, removal of feeding tube, or oral diet order placed. Secondary outcomes included mean percentage of total goal protein received, percentage of patients meeting 80% of nutrition goals, incidence of gastric residual volumes >400 mL, and incidence of moderate hyperglycemia (>250 mg/dL). RESULTS: The study enrolled 189 patients. Mean percentage of goal energy delivered (75% RBF, 102% VBF; P < .001) and goal protein delivered (68% RBF, 87% VBF; P < .001) was significantly higher with VBF compared with RBF. CONCLUSION: VBF demonstrated a significant increase in energy and protein delivery with no major safety or tolerability issues. VBF should be considered for use in ICU patients to optimize nutrition delivery.