Status Epilepticus: An Update on Pharmacological Management.

Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the time and the treatment stage of SE. Benzodiazepines are considered the first-line therapy during the emergent treatment phase of SE. Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase. These drugs appear to have a similar safety and efficacy profile, and individualized therapy should be chosen based on patient characteristics. Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period. The most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Personalized antiseizure medication therapy in critically ill adult patients.

Precision medicine has the potential to have a significant impact on both drug development and patient care. It is crucial to not only provide prompt effective antiseizure treatment for critically ill patients after seizures start but also have a proactive mindset and concentrate on epileptogenesis and the underlying cause of the seizures or seizure disorders. Critical illness presents different treatment issues compared with the ambulatory population, which makes it challenging to choose the best antiseizure medications and to administer them at the right time and at the right dose. Since there is a paucity of information available on antiseizure medication dosing in critically ill patients, therapeutic drug monitoring is a useful tool for defining each patient's personal therapeutic range and assisting clinicians in decision-making. Use of pharmacogenomic information relating to pharmacokinetics, hepatic metabolism, and seizure etiology may improve safety and efficacy by individualizing therapy. Studies evaluating the clinical implementation of pharmacogenomic information at the point-of-care and identification of biomarkers are also needed. These studies may make it possible to avoid adverse drug reactions, maximize drug efficacy, reduce drug-drug interactions, and optimize medications for each individual patient. This review will discuss the available literature and provide future insights on precision medicine use with antiseizure therapy in critically ill adult patients.

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.

Systolic Blood Pressure Variability When Transitioning From Intravenous to Enteral Antihypertensive Agents in Patients With Hemorrhagic Strokes.

Background/Objective: Systolic blood pressure variability (SBPV) in patients with intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is associated with an increased risk of acute kidney injury (AKI) and mortality. SBPV is a strong predictor of poor functional outcomes in patients with ICH. Intravenous (IV) antihypertensive agents are commonly used to achieve sustained target blood pressure goals; however, this is not a feasible long-term option. The transition from IV to enteral antihypertensives is not yet well established in patients with ICH and SAH. This study aimed to assess the effect of the number of antihypertensive agents and overlap time during the transition period from IV to enteral route on SBPV in patients with ICH and SAH. Methods: This retrospective single-center study was conducted at a tertiary teaching hospital in Riyadh, Saudi Arabia. Data were extracted from electronic medical records after obtaining Institutional Review Board approval. Patients were included if they were >18 years old, admitted with spontaneous ICH or SAH, and received continuous infusion antihypertensives prior to transitioning to the enteral route. The major outcome was the effect of the number of antihypertensive agents and overlap time on SBPV during the transition process. Minor outcomes included the effect of the number of antihypertensive agents and overlap time on heart rate variability and the incidence of AKI on day 7. Results: After the screening, we included 102 patients. Based on our regression model, the number of enteral antihypertensive agents upon transitioning from IV to enteral antihypertensive therapy had no effect on SBPV in the intensive care unit (ICU) among our patients (p-value = 0.274). However, the prolonged overlap was associated with reduced SBPV in the ICU (p-value = 0.012). No differences were observed between the groups in heart rate variation or AKI rate. Conclusions: In patients with ICH and SAH, prolonged overlap of enteral antihypertensive agents to overlap with intravenous antihypertensive therapy may result in lower SBPV. This finding needs to be confirmed on a larger scale with more robust study designs for patients with ICH and SAH.

Time Is Brain: Acute Control of Repetitive Seizures and Status Epilepticus Using Alternative Routes of Administration of Benzodiazepines.

Time plays a major role in seizure evaluation and treatment. Acute repetitive seizures and status epilepticus are medical emergencies that require immediate assessment and treatment for optimal therapeutic response. Benzodiazepines are considered the first-line agent for rapid seizure control. Thus, various routes of administration of benzodiazepines have been studied to facilitate a quick, effective, and easy therapy administration. Choosing the right agent may vary based on the drug and route properties, patient's environment, caregiver's skills, and drug accessibility. The pharmacokinetic and pharmacodynamic aspects of benzodiazepines are essential in the decision-making process. Ultimately, agents and routes that give the highest bioavailability, fastest absorption, and a modest duration are preferred. In the outpatient setting, intranasal and buccal routes appear to be equally effective and more rapidly administered than rectal diazepam. On the other hand, in the inpatient setting, if available, the IV route is ideal for benzodiazepine administration to avoid any potential absorption delay. In this article, we will provide an overview and comparison of the various routes of benzodiazepine administration for acute control of repetitive seizures and status epilepticus.