Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU.

OBJECTIVE: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence. DATA SOURCE: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review. DATA SYNTHESIS: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin. CONCLUSIONS: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4-5 g for most adult patients), and 400-1,000 µg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

Role of intraarterial therapy for cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) accounts for a significant percentage of morbidity and mortality among patients admitted to neurosurgical centers throughout the world. Even for individuals surviving beyond the initial presentation and intervention for aneurysmal SAH, the occurrence of cerebral vasospasm has the potential to induce a second tier of complications that can be just as devastating as the inciting event. However, despite numerous studies and some initial advancements in management, therapeutic modalities are limited to help prevent or treat this complex entity. Historically, the mainstay of treatment for cerebral vasospasm has been a combination of hypervolemia, hemodilution, and hypertension. In addition, other systemic therapies such as oral nimodipine, statins, and intravenous magnesium, as well as intensive glucose control, appear to have some promise, although they are limited at times by adverse effects. To avoid these adverse consequences and perhaps gain some modicum of efficacy, attempts have been made to use endovascular techniques to physically dilate vessels or to administer drugs directly to the site of action and thus avoid many of the untoward effects of systemic pharmacotherapy. Controversy still remains over the success of intraarterial therapy, the drugs or techniques to be used, and the best timing of this therapy. Based on the currently available literature, it is impossible to assess the most effective intraarterial therapy. Randomized controlled trials that can control for baseline factors and technical expertise are needed to provide more conclusive data. Clinical pharmacists should be actively involved in assisting interventional radiologists and neurosurgeons in providing safe and appropriate pharmacotherapy in this promising but controversial arena of intraarterial drug delivery.