Comparison of Amantadine, Modafinil, and Standard of Care in the Acute Treatment of Disorders of Consciousness After Severe Traumatic Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Many patients who experience severe TBI have persistent disorders of consciousness. Amantadine and modafinil are used for some neurological disorders; however, a comparison of the 2 medications in TBI has not been reported. This study compared the effectiveness of amantadine, modafinil, and standard of care (SOC) on disorders of consciousness after TBI. METHODS: All adult TBI patients admitted between January 1, 2017, and September 31, 2020 who received amantadine, modafinil, or SOC treatments were screened. Data collection included: demographics, change in Glasgow Coma Scale (GCS), location of hemorrhage, medication duration, intensive care unit and hospital length of stay, adverse drug reactions, and concomitant sedative medications. Patients in the amantadine and modafinil groups were matched 1:2 with patients who received SOC therapies. The primary outcome was change in GCS ≥ 3 from baseline to discharge. RESULTS: A total of 142 patients met inclusion criteria. Medications were initiated a median of 8 days from admission. Patients in the SOC group experienced a greater improvement in GCS and shorter hospital length of stay compared with amantadine. A change in GCS ≥ 3 from medication initiation to hospital discharge occurred in 46.5% of amantadine patients and 53.8% of modafinil patients. CONCLUSIONS: In this study, TBI patients did not benefit from amantadine or modafinil compared with SOC therapies, and no differences were found between medication groups. Further studies are warranted to determine whether the addition of amantadine or modafinil in the weeks after TBI provides benefit.

Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate.

BACKGROUND: Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. OBJECTIVES: The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. METHODS: This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. RESULTS: Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. CONCLUSION AND RELEVANCE: A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.