Reversal of factor Xa inhibitors associated intracranial haemorrhage at a tertiary medical centre.

Prior to the approval of andexanet, there were no FDA-approved reversal agents indicated for the treatment of factor Xa inhibitor (FXaI) associated major bleed. Four-factor prothrombin complex concentrate (4F-PCC) has been widely used off-label for FXaI-associated bleeding. The purpose of this study was to compare the effectiveness and safety of andexanet and 4F-PCC for the reversal of FXaI-associated intracranial haemorrhage. The primary end point is in-hospital mortality; secondary endpoints include haemostatic efficacy and safety. This study is a singlecentre, retrospective chart review, including patients admitted between 1 January 2016 and 15 August 2019, who received 4F-PCC or andexanet for the management of FXaI-associated intracranial haemorrhage. Of the 45 patients included in this study, 23 patients were in the andexanet group and 22 were in the 4F-PCC group. At index admission, mean age was 76 years and the majority of patients (64%) were on apixaban with 33% presented with Glasgow Coma Scale 24 (GCS) score less than 12. At hospital discharge, 47% of patients in the andexanet group had died or discharged to hospice compared with 45% in the 4F-PCC group. No thromboembolic events were observed in either group within 5 days after administration of the reversal agent. The results of this study suggest that haemostasis and mortality at discharge during the index hospitalization appears to be similar between groups. Prospective randomized control trials comparing safety and efficacy of andexanet and 4F-PCC are needed.

Pharmacologic Treatment of Neurobehavioral Sequelae Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of disability in the United States. With decreasing mortality rates, a higher number of patients are impacted by long-term neuropsychiatric sequelae, such as cognitive deficits, depression, anxiety, and sleep-wake disorders. These sequelae are primarily driven by the disruption of key neurotransmitter homeostasis including dopamine, norepinephrine, serotonin, and acetylcholine. Neurostimulants are centrally acting medications used to assist in restoring these neurotransmitter abnormalities and are pharmacologic options to ameliorate symptoms in post-TBI patients. Examples of neurostimulants include amantadine, selective serotonin reuptake inhibitors, tricyclic antidepressants, central stimulants (ie, methylphenidate), modafinil, and donepezil. Large, well-powered studies have not been performed to validate their use in patients with TBI, leaving uncertainty for these agents' place in therapy. Current practice is driven by consideration of patient-specific factors to select the most appropriate agent. This review provides clinicians with a summary of the available literature on neurostimulants following TBI to guide appropriate usage to help improve patients' symptoms and optimize safety.

Acute Blood Pressure Management in Neurocritically Ill Patients.

Optimal blood pressure (BP) management is controversial in neurocritically ill patients due to conflicting concerns of worsening ischemia with decreased BP versus cerebral edema and increased intracranial pressure with elevated BP. In addition, high-quality evidence is lacking regarding optimal BP goals in patients with most of these conditions. This review summarizes guideline recommendations and examines the literature for BP management in patients with ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Practice variations in the management of status epilepticus.

BACKGROUND: Numerous anticonvulsant agents are now available for treating status epilepticus (SE). However, a paucity of data is available to guide clinicians in the initial treatment of seizures or SE. This study describes the current strategies being employed to treat SE in the U.S.A. METHODS: Fifteen American academic medical centers completed a retrospective, multicenter, observational study by reviewing 10-20 of the most recent cases of SE at their institution prior to December 31, 2009. A multivariate analysis was performed to determine factors associated with cessation of seizures. RESULTS: A total of 150 patients were included. Most patients with SE had a seizure disorder (58%). SE patients required a median of 3 AEDs for treatment. Three quarters of patients received a benzodiazepine as first-line therapy (74.7%). Phenytoin (33.3%) and levetiracetam (10%) were commonly used as the second AED. Continuous infusions of propofol, barbiturate, or benzodiazepine were used in 36% of patients. Median time to resolution of SE was 1 day and was positively associated with presence of a complex partial seizure, AED non-compliance prior to admission, and lorazepam plus another AED as initial therapy. Prolonged ICU length of stay and topiramate therapy prior to admission were negatively associated with SE resolution. Mortality was higher in patients without a history of seizure (22.2 vs. 6.9%, p = 0.006). CONCLUSIONS: The use of a benzodiazepine followed by an AED, such as phenytoin or levetiracetam, is common as first and second-line therapy for SE and appears to be associated with a shorter time to SE resolution. AED selection thereafter is highly variable. Patients without a history of seizure who develop SE had a higher mortality rate.

Sedation and analgesia in critically ill neurologic patients.

Critically ill neurologic patients can pose a challenge when it comes to providing sedation and analgesia, primarily with the balance of maintaining sedation to provide patient comfort while still allowing a neurological examination. Determination of the optimal agent requires assessment and understanding of the underlying requirement for sedation: provision of analgesia, anxiolysis, or treatment of delirium. Pharmacological options exist that can affect individual or multiple underlying sedation requirements. Numerous evaluation tools exist to monitor the efficacy of sedation as well as help clinicians titrate agents to predefined goals; these tools allow the safe administration of drugs that can otherwise have serious adverse effects. Sedation regimens must ultimately be individualized to each patient to account for differences in pharmacokinetics and dynamics of the various agents, and this is particularly true in sedating neurologically injured patients. The agents frequently used to provide sedation and analgesia in the critically ill neurologic patient will be reviewed.