DEXmedetomidine compared to PROpofol in NEurocritical Care [DEXPRONE]: A multicenter retrospective evaluation of clinical utility and safety.

PURPOSE: Although guidelines recommend dexmedetomidine (DEX) or propofol (PRO) as preferred sedatives in critically ill adults, comparisons in neurocritical care (NCC) are limited. We aimed to evaluate the clinical utility and safety of DEX compared with PRO in NCC setting. MATERIALS AND METHODS: This retrospective, multicenter, observational cohort study conducted at three tertiary academic hospitals with Level 1 Trauma Center and Comprehensive Stroke Center designations, compared the clinical indication and safety of DEX vs PRO in patients in NCC setting. RESULTS: 179 patients were included (94 DEX and 85 PRO), median age of 58, 49% were male (DEX) and 58% were male (PRO). PRO was more commonly used to manage agitation. DEX was more commonly used for facilitating extubation, alcohol withdrawal, and sedation during frequent neurologic assessments. Mean Glasgow Coma Scale scores were higher in DEX group (11 vs. 9; p = .04). The duration of either infusions, mechanical ventilation, and lengths of stay were similar. No difference was observed in hypotension or bradycardia rates. Death was significantly higher with PRO (DEX 10% vs. PRO 22%; p = .02). CONCLUSIONS: DEX and PRO were used for distinct indications in our cohort. Adverse effect profiles and clinical outcome, in the cohorts are largely similar.

Gram-negative Cranial Bone Flap Infection Treated with Continuous Gentamicin Irrigation: A Case Report.

A 57-year-old male presented with severely altered mental status in the setting of diabetic ketoacidosis. Neuroimaging revealed two intracranial masses. Days following surgical resection of an olfactory groove meningioma, the patient developed Serratia marcescens bacteremia along with an enlarging epidural and subgaleal fluid collection. Subgaleal fluid aspiration was also positive. The patient later returned to the operating room for wound washout where purulent collections were discovered in the subgaleal, epidural, and left subdural spaces. The wound was evacuated and the bone flap was thoroughly cleansed with betadine and soaked in peroxide prior to replacement. Four drains were placed (two subgaleal and two epidural) with two serving as inlets and two as outlets. Continuous irrigation of the subgaleal and epidural spaces with gentamicin solution was performed for five days. The bone flap was successfully salvaged and the patient was discharged from inpatient rehab three weeks following washout.

Cefepime challenge after piperacillin/tazobactam-induced thrombocytopenia.

Drug-induced thrombocytopenia (DITP) has been described as a sudden and severe hematologic complication of piperacillin/tazobactam. The proposed mechanism by which piperacillin/tazobactam causes DITP involves the formation of a covalent bond to platelet membrane protein thereby inducing a humoral immune response. Given the immunogenic nature of this adverse event and the structural similarities across beta-lactam antibiotics, the potential for cross-reactivity between agents within the class should be considered. However, the structural moiety of piperacillin/tazobactam responsible for this immunogenic response has not been identified-the relationship between structure and activity for this phenomenon remains unknown. Data on the safety and cross-reactivity of other beta-lactam agents in this setting is lacking. We report the first case of piperacillin/tazobactam DITP successfully challenged by the use of cefepime for the treatment of aspiration pneumonia. Further studies are needed to determine the structural moiety of piperacillin/tazobactam responsible for this immunogenic response and evaluate the safety of other beta-lactam antibiotics in this clinical setting.

Evaluation of Intravenous Vancomycin Pharmacokinetic Parameters in Patients With Acute Brain Injury.

BACKGROUND: Vancomycin is a glycopeptide antibiotic that is primarily cleared by renal elimination. Patients with acute brain injury often exhibit augmented renal clearance which has been associated with subtherapeutic vancomycin concentrations. OBJECTIVE: To determine whether population pharmacokinetics accurately predict vancomycin empiric dose frequency in patients with acute brain injury. METHODS: This was a single-center, retrospective cohort study conducted following institutional review board approval at Virginia Commonwealth University Health System. Data were collected from patients 18 years of age or older admitted with acute brain injury. The primary outcome was the difference in the elimination rate constant of vancomycin between population predicted pharmacokinetics and patient-specific pharmacokinetics. RESULTS: A total of 158 patients were included in the analysis. A test of the paired differences between the mean population predicted and patient-specific elimination rate constants showed that the mean population predicted elimination rate constant was larger by 0.0211 h-1 (95% confidence interval [CI]: -0.028 to -0.015). The difference between the mean population predicted and patient-specific half-lives showed that the mean population predicted half-life was shorter by 1.01 hours (95% CI: 0.7-1.3). Vancomycin was administered at a mean initial dose of 15.4 mg/kg (standard deviation [SD] = 2.2), with an average frequency of 12 hours (SD = 1.1). The average trough concentration at steady state was 9.9 µg/mL (SD = 4.9). CONCLUSIONS: The small clinical difference in population and patient-specific elimination rate constants demonstrates that population pharmacokinetics may be an accurate empiric dosing strategy for determining vancomycin dose frequency in patients with acute brain 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.

Characterization of the Effect of Prolonged Therapeutic Hypothermia on Serum Magnesium and Potassium Following Neurological Injury.

Current American Heart Association/American Stroke Association guidelines for the management of spontaneous intracerebral hemorrhage suggest therapeutic hypothermia (TH) as a salvage therapy in patients with elevated intracranial pressure. Electrolyte disorders may develop at any stage of the cooling process. Such deregulation can place patients at an increased risk for arrhythmias and worsened neurologic outcomes. The impact of TH on serum electrolyte concentration has been described, but electrolyte changes and repletions are yet to be quantified. The primary objective of this study was to quantify the trends in serum potassium and magnesium concentrations during TH and determine the median amount of electrolyte repletions administered. This study was a single-center retrospective cohort conducted at Virginia Commonwealth University Health. Data were collected from neurosurgical patients with intracranial hypertension who underwent TH (<36°C) for ≥48 hours. Patients with a primary neurological insult cooled with the Arctic Sun® 5000 Temperature Management System, who were ≥13 years of age at the time of therapy with a core body temperature of ≥36°C before therapeutic hypothermia, were eligible for inclusion. Forty-three patients meeting the inclusion criteria were analyzed. A total of 42 patients (98%) experienced hypokalemia (<3.5 mEq/L) during TH. A median of 45 mEq per day of potassium repletion was administered during the maintenance phase of cooling. Despite those repletions, patients remained hypokalemic 30% of the time. Median serum magnesium concentrations during the maintenance phase of TH remained consistently within goal range of 1.8-2.5 mg/dL. Five patients (12%) experienced at least one episode of cardiac dysrhythmia during the cooling period. Standard potassium electrolyte repletion protocols did not adequately maintain serum potassium concentrations above our target of 3.5 mEq/L in neurosurgical patients undergoing TH. Standard magnesium repletion protocols were sufficient to maintain a normal serum concentration in this patient population when magnesium sulfate was not used for other indications.

Clevidipine Versus Nicardipine for Acute Blood Pressure Reduction in a Neuroscience Intensive Care Population.

BACKGROUND: Currently, a lack of published literature exists regarding the use of clevidipine in the neuroscience population. This agent may be preferred in some patients because of its short half-life, potentially leading to more narrow blood pressure (BP) control in comparison with other agents. The purpose of this study was to compare the difference in time to achieve target systolic blood pressure (SBP) goals with clevidipine versus nicardipine infusions in patients admitted to the neuroscience intensive care unit (NSICU) at our institution. METHODS: A retrospective review was performed on patients receiving clevidipine or nicardipine infusions while in the NSICU between July 1, 2011 and June 30, 2014. Patients were matched based on indication for BP lowering and target SBP. Primary endpoints included time to target SBP and percentage of time within target BP range. RESULTS: Of the 57 patients included in the study, the median time to target SBP was 30 min in the clevidipine group and 46 min in the nicardipine group (p = 0.13). The percentage of time spent within target BP range was 79 versus 78% (p = 0.64). Clevidipine administration resulted in significantly less volume administered per patient versus nicardipine (530 vs. 1254 mL, p = 0.02). CONCLUSIONS: There were no statistically significant differences in acute BP management between the two agents; however, there was a trend toward shorter time to target and significantly less volume administered in the clevidipine group. Either agent should be considered a viable option in a NSICU population.

Medical management of epileptic seizures: challenges and solutions.

Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs), with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical-psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and "pseudoseizure" patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who deals with the acute management of seizures may encounter. The document also highlights the numerous avenues for new research that would help practitioners optimize epilepsy management.

Treatment of Super-Refractory Status Epilepticus.

Super-refractory status epilepticus (SRSE) is a devastating neurological condition with limited treatment options. We conducted an extensive literature search to identify and summarize the therapeutic options for SRSE. The search mainly resulted in case reports of various pharmacologic and non-pharmacologic treatments. The success rate of each of the following agents, ketamine, inhaled anesthetics, intravenous immunoglobulin G (IVIG), IV steroids, ketogenic diet, hypothermia, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and vagal nerve stimulation (VNS), are discussed in greater detail. The choice of appropriate treatment options for a given patient is based on clinical presentation. This review focuses on evidence-based, pharmacotherapeutic strategies for patients in SRSE.

Reduction in time to first action as a result of electronic alerts for early sepsis recognition.

The use of an electronic alerting system to notify practitioners when a patient meets modified systemic inflammatory response syndrome criteria was hypothesized to decrease the time to goal-directed therapy initiation. This retrospective, before-and-after study analyzed adult patients identified with sepsis or septic shock and compared 30 patients prior to electronic alert initiation with 30 patients after initiation. The primary endpoint was time to any sepsis-related intervention. Patients in the post-alert group demonstrated a shorter time to any sepsis-related intervention by a median difference of 3.5 hours (P = .02). Using computerized medical records to create an electronic alerting system has the potential to identify high-risk patients and initiate interventions sooner. At our institution, the creation of an alerting system with real-time data has decreased the time it takes to begin sepsis workup and treatment.