Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products.

To analyze the efficacy and safety of activated prothrombin complex concentrates (aPCC) and four-factor prothrombin complex concentrates (4F-PCC) to prevent hematoma expansion in patients taking apixaban or rivaroxaban with intracranial hemorrhage (ICH). In this multicenter, retrospective study, sixty-seven ICH patients who received aPCC or 4F-PCC for known use of apixaban or rivaroxaban between February 2014 and September 2018 were included. The primary outcome was the percentage of patients who achieved excellent/good or poor hemostasis after administration of aPCC or 4F-PCC. Secondary outcomes included hospital mortality, thromboembolic events during admission, and transfusion requirements. Excellent/good hemostasis was achieved in 87% of aPCC patients, 89% of low-dose 4F-PCC [< 30 units per kilogram (kg)], and 89% of high-dose 4F-PCC (≥ 30 units per kg). There were no significant differences in excellent/good or poor hemostatic efficacy (p = 0.362). No differences were identified in transfusions 6 h prior (p = 0.087) or 12 h after (p = 0.178) the reversal agent. Mortality occurred in five patients, with no differences among the groups (p = 0.838). There were no inpatient thromboembolic events. Both aPCC and 4F-PCC appear safe and equally associated with hematoma stability in patients taking apixaban or rivaroxaban who present with ICH. Prospective studies are needed to identify a superior reversal agent when comparing andexanet alfa to hospital standard of care (4F-PCC or aPCC) and to further explore the optimal dosing strategy for patients with ICH associated with apixaban or rivaroxaban use.

Dexmedetomidine for Refractory Intracranial Hypertension.

Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.

Neurologic Examination Facilitated by Reversal of Rocuronium with Sugammadex.

Background: Patients with neurologic injuries often receive neuromuscular blocking agents to facilitate airway management. The urgent nature of intubation may result in paralytic administration prior to neurologic examination, delaying clinical assessment, prognostication, and surgical interventions. Objective: In October 2018, an institutional guideline was implemented to extend institutional sugammadex use to include patients with uncertain neurologic examinations with recent rocuronium administration. The guideline allowed for a dose range of 2 mg/kg to 16 mg/kg. The objective of this continuous quality improvement project was to describe the use of sugammadex after implementation of an institutional guideline. Methods: Patient records between October 2018 and March 2020 were reviewed for guideline adherence and outcomes. Information assessed included patient weight, injury mechanism, the dosage and timing of rocuronium and sugammadex administration, and neurologic examination findings. Descriptive statistics were used to assess outcomes. Results: During the study period, eleven patients received sugammadex to facilitate neurologic examinations. The most common dose of sugammadex was 4 mg/kg with a mean total dose of 498.4 ± 333.5 mg. The mean time between rocuronium and sugammadex administration was 73.9 ± 41 minutes. Most patients (72.7%) had definitive changes in neurologic examination after sugammadex administration. Five patients had neurosurgical interventions offered and performed, with 1 of the patients surviving. Conclusions: This case series suggests that sugammadex is useful for reversing rocuronium induced paralysis to facilitate neurologic examination needed to determine management strategies for patients with a neurologic injury.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

Activated Partial Thromboplastin Time Versus Anti-Factor Xa Monitoring of Heparin Anticoagulation in Adult Venoarterial Extracorporeal Membrane Oxygenation Patients.

The preferred assay for measuring and adjusting unfractionated heparin (UFH) infusion to achieve optimal outcomes during extracorporeal membrane oxygenation (ECMO) is not well established. This retrospective cohort study explored safety and efficacy outcome differences between anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) for UFH in adult venoarterial ECMO. Forty-one patients were included and analyzed. The UFH rate at first goal and time to goal were both higher in the aPTT versus anti-Xa cohort but did not achieve statistical significance (12.14 vs. 9.58 unit/kg/hour (p = 0.29), 20.22 vs. 12.05 hours (p = 0.11)). The aPTT cohort was in target goals 35.0% of the time versus 47.7% in the anti-Xa cohort (p = 0.13), above goal 41.0% vs. 17.3% (p = 0.02), and below-goal 24.0% versus 35.0% of the time (p = 0.34). Minimum heparin rates in the aPTT cohort were 6.28 vs. 3.33 unit/kg/hour in the anti-Xa cohort (p = 0.07), and the maximum UFH rate was 18.77 unit/kg/hour vs. 15.48 unit/kg/hour (p = 0.10). Our findings suggest that aPTT monitoring may result in a delay to target attainment, higher UFH rates, and overall exposure.

Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study.

To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission. DESIGN: This was a single-center, double-blinded, randomized placebo-controlled pilot study. SETTING: Adult ICUs at a large academic medical center in the United States. PATIENTS: Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment. INTERVENTIONS: Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium. MEASUREMENTS AND MAIN RESULTS: The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred. CONCLUSIONS: This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.