Levetiracetam-associated behavioral adverse events in neurocritical care patients.

STUDY OBJECTIVES: The objective of this study was to identify the incidence of levetiracetam-associated BAEs in NCC patients. DESIGN: Single-center retrospective cohort analysis. DATA SOURCE: Patient charts. PATIENTS: 965 adult ICU patients with a neurological injury receiving levetiracetam that were admitted to an intensive care unit. MEASUREMENTS AND MAIN RESULTS: There were 965 patients included; 52% males with a median GCS of 13. Injury types included TBI (43.1%), ICH (21.8%), SAH (20.5%), and CI (14.6%). BAEs were identified in 46% of patients. Of these, 60% had documentation of agitation/restlessness, delirium, or anxiety while receiving levetiracetam, only 25% had a positive CAM-ICU, 13% had restraints ordered, and 42% received antipsychotics. Patients with TBI had the highest incidence of BAEs (52.4%). The median time to initiation of levetiracetam after hospital admission was 6.4 hours and BAEs occurred after 1.3 days of levetiracetam initiation. CONCLUSIONS: In this study, we found that almost half of our NCC population experienced levetiracetam associated BAEs which were mostly hyperactive in nature. We believe that the incidence of BAEs in our specific patient population cannot solely be attributed to ICU delirium given the lower risk of developing hyperactive delirium in ICU patients as compared to other subtypes. Therefore, monitoring and determination of the benefit versus risk in those experiencing BAEs is highly encouraged.

Principles of Pharmacotherapy of Seizures and Status Epilepticus.

Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided by robust evidence. Optimal pharmacotherapy selection for individual patients is essential in the management of seizures and status epilepticus with careful evaluation of pharmacokinetic and pharmacodynamic factors. With the addition of newer antiseizure agents to the market, understanding their role in the management of status epilepticus is critical. Etiology-guided therapy should be considered in certain patients with drug-induced seizures, alcohol withdrawal, or autoimmune encephalitis. Some patient populations warrant special consideration, such as pediatric, pregnant, elderly, and the critically ill. Seizure prophylaxis is indicated in select patients with acute neurological injury and should be limited to the acute postinjury period.

Control of Shivering During Targeted Temperature Management.

Targeted temperature management (TTM) is used frequently in patients with a variety of diseases, especially those who have experienced brain injury and/or cardiac arrest. Shivering is one of the main adverse effects of TTM that can often limit its implementation and efficacy. Shivering is the body's natural response to hypothermia and its deleterious effects can negate the benefits of TTM. The purpose of this article is to provide an overview of TTM strategies and shivering management.

Anticoagulation reversal for intracranial hemorrhage in the era of the direct oral anticoagulants.

PURPOSE OF REVIEW: This review focuses on recent relevant literature that examines the reversal of direct oral anticoagulants (DOACs) in patients with intracranial hemorrhage (ICH). The aim of this review is to provide an insightful description of available reversal agents and their clinical utility. RECENT FINDINGS: Increases in prescribing of DOACs has led to the introduction of drug-specific reversal agents. The clinical trials that evaluated these agents did not include a comparator arm making it difficult to determine if they are clinically superior to nonspecific reversal agents. SUMMARY: Numerous options for reversal of DOAC-associated ICH are currently available. Recent clinical trials have demonstrated drug-specific reversal agents are effective in this setting, but additional research is needed to determine whether these agents should be routinely preferred over nonspecific reversal agents.

High-Dose Intravenous Ascorbic Acid: Ready for Prime Time in Traumatic Brain Injury?

Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise. Secondary brain injury occurs in the first hours and days after the initial impact and is the most effective target for intervention. Inflammatory processes and oxidative stress play an important role in the pathomechanism of TBI and are exacerbated by impaired endogenous defense mechanisms, including depletion of antioxidants. As a reducing agent, free radical scavenger, and co-factor in numerous biosynthetic reactions, ascorbic acid (AA, vitamin C) is an essential nutrient that rapidly becomes depleted in states of critical illness. The administration of high-dose intravenous (IV) AA has demonstrated benefits in numerous preclinical models in the areas of trauma, critical care, wound healing, and hematology. A safe and inexpensive treatment, high-dose IV AA administration gained recent attention in studies demonstrating an associated mortality reduction in septic shock patients. High-quality data on the effects of high-dose IV AA on TBI are lacking. Historic data in a small number of patients demonstrate acute and profound AA deficiency in patients with central nervous system pathology, particularly TBI, and a strong correlation between low AA concentrations and poor outcomes. While replenishing deficient AA stores in TBI patients should improve the brain's ability to tolerate oxidative stress, high-dose IV AA may prove an effective strategy to prevent or mitigate secondary brain injury due to its ability to impede lipid peroxidation, scavenge reactive oxygen species, suppress inflammatory mediators, stabilize the endothelium, and reduce brain edema. The existing preclinical data and limited clinical data suggest that high-dose IV AA may be effective in lowering oxidative stress and decreasing cerebral edema. Whether this translates into improved clinical outcomes will depend on identifying the ideal target patient population and possible treatment combinations, factors that need to be evaluated in future clinical studies. With its excellent safety profile and low cost, high-dose IV AA is ready to be evaluated in the early treatment of TBI patients to mitigate secondary brain injury and improve outcomes.

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit.

The diagnosis and management of seizures in the critically ill patient can sometimes present a unique challenge for practitioners due to lack of exposure and complex patient comorbidities. The reported incidence varies between 8% and 34% of critically ill patients, with many patients often showing no overt clinical signs of seizures. Outcomes in patients with unidentified seizure activity tend to be poor, and mortality significantly increases in those who have seizure activity longer than 30 min. Prompt diagnosis and provision of medical therapy are crucial in order to attain successful seizure termination and prevent poor outcomes. In this article, we review the epidemiology and pathophysiology of seizures in the critically ill, various seizure monitoring modalities, and recommended medical therapy.