Abstract Background Compared with vitamin K antagonists, direct acting oral anticoagulants (DOACs) have fixed dosing, limited drug interactions, and do not require therapeutic drug level monitoring. ...Dose adjustments are recommended for moderate renal dysfunction, low body weight, and select drug interactions. Objectives The aim of our study is to determine if DOAC dose reductions were appropriate based on the manufacturer labeling recommendations for each agent. We also followed patients’ treatment outcomes. Methods We retrospectively reviewed patients administered a DOAC at a reduced dose between January 2011 and August 2014. The primary outcome was adherence to current manufacturer dose recommendations. The secondary outcome measures were the incidence of thromboembolic events or any bleeding episodes, regardless of severity, while on therapy. Results Of 224 patients included in the analysis, 43.3% of patients fit criteria for a dose adjustment according to manufacturer recommendations. Only 3 out of 28 (10.7%) patients treated with apixaban met two out of three clinical criteria required for a dose reduction per manufacturer recommendations. Only 54.7% of rivaroxaban treated patients and 32.2% of dabigatran treated patients had renal insufficiency requiring a dose reduction. Half of our patient population received aspirin therapy, with 6.3% of patients on triple antithrombotic therapy (dual antiplatelet agents plus an anticoagulant). A past medical history significant for bleeding was prevalent in patients treated with a reduced dose DOAC (32.1%, 20.4%, and 25.4% of patients in the apixaban, rivaroxaban, and dabigatran treated groups, respectively). Thromboembolic events occurred in 10.7%, 3.6%, and 5.1% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. Frequency of bleeding complications, regardless of severity, was 17.9%, 18.2%, and 23.7% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. Conclusion We found that dose-adjusted DOAC therapy was often prescribed in a dose that was lower than package insert recommendations.
In patients with ischemic stroke who receive systemic recombinant tissue plasminogen activator (rt-PA), the risk of secondary hemorrhage is 1-7%. Fibrinogen supplementation with cryoprecipitate is ...recommended in patients with rt-PA-associated symptomatic hemorrhage. We examined whether fibrinogen concentrate can be used safely in this setting. A single-center retrospective case series was performed in patients who received fibrinogen concentrate for post-rt-PA hemorrhage between January-2012 and December-2017. The primary outcome was the incidence of in-hospital thromboembolic events and infusion reactions. Secondary outcomes included incidence of clinically significant ICH expansion within 24-hours and patient serum fibrinogen response to fibrinogen concentrate therapy. Thromboembolic events occurred in 3 (12.5%) of 24 patients included in the analysis. No patients experienced infusion-related reactions. Five of 22 patients with ICH experienced clinically significant hemorrhage expansion. Hypofibrinogenemia was corrected in 87.5%(7/8) of patients with baseline hypofibrinogenemia, with a median increase in serum fibrinogen 166 mg/dL. Median fibrinogen increase in patients without baseline hypofibrinogenemia was 18 mg/dL. Fibrinogen concentrate is a safe potential therapeutic option to restore fibrinogen levels in acute ischemic stroke patients with thrombolysis-associated hemorrhage.
In critically ill patients with neurologic disease, pupil examination abnormalities can signify evolving intracranial pathology. Analgesic and sedative medications (analgosedatives) target pupillary ...pathways, but it remains unknown how analgosedatives alter pupil findings in the clinical care setting. We assessed dexmedetomidine and other analgosedative associations with pupil reactivity and size in a heterogeneous cohort of critically ill patients with acute intracranial pathology.
Retrospective cohort study.
Two neurologic ICUs between 2016 and 2018.
Critically ill adult patients with pupil measurements within 60 minutes of analgosedative administration. Patients with a history of intrinsic retinal pathology, extracranial injury, inaccessible brain imaging, or no Glasgow Coma Scale (GCS) data were excluded.
None.
We used mixed-effects linear regression accounting for intrapatient correlations and adjusting for sex, age, GCS score, radiographic mass effect, medication confounders, and ambient light. We tested the association between an initiation or increased IV infusion of dexmedetomidine and pupil reactivity (Neurologic Pupil Index NPi) and resting pupil size (mm) obtained using NeurOptics NPi-200 (NeurOptics, Irvine, CA) pupillometer. Of our 221 patients with 9,897 pupil observations (median age, 60 interquartile range, 50-68; 59% male), 37 patients (166 pupil observations) were exposed to dexmedetomidine. Dexmedetomidine was associated with higher average NPi (β = 0.18 per 1 unit increase in rank-normalized NPi ± 0.04;
< 0.001) and smaller pupil size (β = -0.25 ± 0.05;
< 0.001). Exploratory analyses revealed that acetaminophen was associated with higher average NPi (β = 0.04 ± 0.02;
= 0.02) and that most IV infusion analgosedatives including propofol, fentanyl, and midazolam were associated with smaller pupil size.
Dexmedetomidine is associated with higher pupil reactivity (high NPi) and smaller pupil size in a cohort of critically ill patients with neurologic injury. Familiarity with expected pupil changes following analgosedative administration is important for accurate interpretation of pupil examination findings, facilitating optimal management of patients with acute intracranial pathology.
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