Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH. METHODS: We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U. We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months. RESULTS: Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL (P=0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL (P=0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% (P=0.5). CONCLUSIONS: Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00059332.

Reversal of the novel oral anticoagulants dabigatran, rivoraxaban, and apixaban.

PURPOSE OF REVIEW: We summarize the available data related to reversing the anticoagulant effect of the oral direct thrombin and factor Xa inhibitors and provide our opinion on treating patients presenting with severe and life-threatening hemorrhage related to these agents. RECENT FINDINGS: No specific antidotes are currently available for the oral direct thrombin and factor Xa inhibitors but two promising agents are under investigation in phase 3 trials. No data are available on reversing these agents in bleeding patients. Activated charcoal may be effective in reducing factor Xa inhibitor absorption up to 6 h after ingestion. Animal models suggest that unactivated 4-factor prothrombin complex concentrate may be an effective reversal agent. Recent data in warfarin-treated patients suggest that 4-factor prothrombin complex concentrate may provide more rapid and effective hemostasis than fresh frozen plasma. SUMMARY: In the absence of evidence in bleeding patients, animal models and ex-vivo studies suggest administration of coagulant factors in the form of hemostatic agents may be of benefit in reversing the effect of direct thrombin and factor Xa inhibitors. Specific reversal agents and clinical data in patients with hemorrhage remain an unmet need.

Predictors of 30-day readmission after subarachnoid hemorrhage.

BACKGROUND: Readmission within 30 days is increasingly evaluated as a measure of quality of care. There are few data on the rates of readmission after subarachnoid hemorrhage (SAH). OBJECTIVE: We sought to determine the predictors of 30-day readmission in patients with SAH. METHODS: We prospectively identified 283 patients with SAH admitted between 2006 and 2012. Readmission was determined by means of an automated query with confirmation in the electronic medical record. RESULTS: Overall, 21 (8 %) patients were readmitted for infection (n = 8), headache (n = 5), hydrocephalus (n = 4), cardiovascular causes (n = 2), medication-related complications (n = 1), and cerebral ischemia (n = 1). Readmission was associated with longer intensive care unit (ICU) length of stay (LOS) (15.4 [13.4-19.3] vs. 12.2 [8.2-18.5] days, P = 0.02), hospital LOS (22.2 [17.4-23.0] vs. 16.8 [12.0-24.1] days, P = 0.01), and placement of an external ventricular drain (EVD, OR 3.9, 95 % CI 1.3-12.0, P = 0.01). Readmission was not associated with admission neurologic grade, NIH Stroke scale at 14 days, modified Rankin scale at 3 months, history of cardiovascular disease, or radiographic cerebral infarction (P > 0.1). CONCLUSIONS: Demographics, severity of neurologic injury, radiographic cerebral infarction, and outcomes were not associated with readmission after SAH. Markers of a more complicated hospital course (ICU and hospital LOS, EVD placement) were associated with 30-day readmission. Most readmissions were for infections acquired after discharge. Readmission within 30 days is difficult to predict, and, since the most common reason was infection acquired after discharge, it may be difficult to prevent without an integrated health system and coordinated care.