Robert Neumann

Recognizing false ischemic penumbras in CT brain perfusion studies.

Computed tomography (CT) plays a pivotal role in the diagnosis of acute stroke and in treatment decision making. CT perfusion imaging performed with intravenous iodinated contrast material allows calculation of the time to peak enhancement, mean transit time, and cerebral blood volume, important parameters for differentiating between an ischemic penumbra, which might benefit from intravascular therapy with thrombolytic agents, and infarcted tissue, which would not benefit from such therapy. Differentiation between the two entities is important because thrombolytic therapy is associated with an increased risk for intracranial hemorrhage. A finding of delay in peak enhancement or increased mean transit time in a region with normal or only slightly abnormal cerebral blood volume is suggestive of an ischemic penumbra; however, accurate interpretation of the CT perfusion parameters may be difficult in the presence of a cerebrovascular anatomic variant or physiologic condition that produces benign oligemia leading to a false appearance of penumbra. For this reason, CT perfusion parameters must be correlated with the clinical history and findings at unenhanced head CT, angiography or CT angiography, and diffusion-weighted magnetic resonance imaging. The authors identify five possible causes of false penumbras, each of which produces a different pattern at imaging: upstream flow restriction, evolution of ischemic change, vascular dysregulation, positioning of the patients head at an angle during image acquisition, and variant anatomy in the circle of Willis. Familiarity with the imaging patterns and causes of false penumbras may increase the radiologists confidence in diagnosis and help avoid costly errors in treatment.

Stroke alert program improves recognition and evaluation time of in-hospital ischemic stroke.

An inpatient stroke alert program is effective in decreasing evaluation time for in-hospital strokes, although response times remain significantly longer than those in the emergency department. It is capable of increasing the percentage of ischemic strokes identified by the hospitals stroke team, at the cost of an increased percentage of false alarms.

Intraventricular Daptomycin and Intravenous Linezolid for the Treatment of External Ventricular-Drain—Associated Ventriculitis Due to Vancomycin-Resistant Enterococcus faecium

Objective: To report the successful treatment of external ventricular-drain (EVD)– associated infection due to vancomycin-resistant Enterococcus faecium (VRE) with intraventricular daptomycin and intravenous linezolid. Case Summary: A 64-year-old white male with a complicated medical history was admitted to the neurosurgical unit with Scedosporium apiospermum meningitis and hydrocephalus requiring management with a right and left EVD. On day 28, cerebrospinal fluid cultures from the right EVD grew VRE. Despite initiation of intravenous linezolid, cultures from the right EVD remained positive. Intraventricular daptomycin 5 mg daily was initiated and administered into the right EVD for 7 days. Cerebrospinal fluid was collected from EVD outputs and analyzed for daptomycin concentrations. VRE in cultures from the EVD cleared after 1 day of therapy and no adverse effects were noted. Right and left EVD daptomycin concentrations were discordant throughout therapy by at least a 3-fold difference. First-dose peak and trough daptomycin concentrations in the cerebrospinal fluid were 112.2 and 1.34 μg/mL, respectively, for the right EVD and 37.4 and 0.37 μg/mL, respectively, for the left EVD. Daptomycin accumulation was evident after 3 days of therapy. Discussion: Varying doses and frequencies of intraventricular daptomycin have been reported effective for VRE ventriculitis. Intraventricular drug distribution may not be homogeneous throughout the central nervous system. Therefore, daptomycin minimum inhibitory concentration for VRE, cerebrospinal fluid communication throughout the central nervous system, EVD output, and the potential for drug accumulation should be considered when selecting a dose and frequency. Conclusions: Intraventricular daptomycin may be an option for EVD-associated VRE infections that do not respond to conventional therapy. Intraventricular daptomycin 5 mg is a reasonable initial dose in adults with VRE ventriculitis, based on our experience in this patient.

Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage Undergoing Continuous Veno-Venous Hemofiltration

Patient: Male, 78 Final Diagnosis: Right thalamic intraparenchymal hemorrhage with intraventricular extension Symptoms: Altered mental status • left sided weakness Medication: Levetiracetam Clinical Procedure: Continuous renal replacement therapy Specialty: Critical Care Medicine Objective: Unusual or unexpected effect of treatment Background: Levetiracetam is an antiepileptic drug frequently used in critically ill patients. Levetiracetam is primarily eliminated as a parent compound via glomerular filtration and requires dose adjustment in renal insufficiency, but the literature on patients receiving continuous veno-venous hemofiltration (CVVH) is scant. Case Report: We report the levetiracetam pharmacokinetic profile of a patient being treated with levetiracetam 1000 mg intravenously every 12 h who required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was 250 ml/min, and the predilution replacement therapy fluid flow rate was 2000 ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6, 8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half-life, area under the concentration-time curve (AUC0–12), clearance (CL), and volume of distribution (Vd) were 30.7 μg/ml, 16.1 μg/ml, 12.9 h, 272 mg·hr/L, 3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03±0.08. CVVH represented 61.3% of the total levetiracetam clearance. The patient was maintained on CVVH for 24 consecutive days and then transitioned to intermittent hemodialysis and remained seizure-free. Conclusions: CVVH is highly effective in removing levetiracetam from circulating plasma. Due to the effective removal, standard doses of levetiracetam are required to maintain adequate plasma concentrations. Dose reductions utilizing HD or estimated creatinine clearance recommendations will likely lead to subtherapeutic levels, especially if higher CVVH flow rates are used.

Abstract WP363: Improvement in the Inpatient Acute Stroke Alert Process with a Consistent Response Team

Background and Purpose: It is publicly reported 2%-15% of all strokes occur in patients hospitalized for another procedure or diagnosis. The evidence suggests greater delays in the evaluation and t...

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients

Introduction Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury. Methods This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. Consent was obtained to measure concentrations of vaccine-specific IgG to 14 of 23 serotype capsule-specific IgG in serum prior to and 14–35 days following PPSV23. A successful immunologic response was defined as both a ≥2-fold rise in capsule-specific IgG from baseline and concentrations of >1 mcg/mL to 10 of 14 measured vaccine serotypes. Immunologic response was compared between burn and neurosurgical patients. Multiple variable regression methods were used to explore associations of clinical and laboratory parameters to immunologic responses. Results Among the 16 burn and 27 neurosurgical patients enrolled, 87.5% and 40.7% generated a successful response to the vaccine, respectively (p = 0.004). Both median post-PPSV23 IgG concentrations (7.79 [4.56–18.1] versus 2.93 [1.49–8.01] mcg/mL; p = 0.006) and fold rises (10.66 [7.44–14.56] versus 3.48 [1.13–6.59]; p<0.001) were significantly greater in burn compared with neurosurgical patients. Presence of burn injury was directly and days from injury to immunization were inversely correlated with successful immunologic response (both p<0.03). Burn injury was associated with both increased median antibody levels post-PPSV23 and fold rise to 14 vaccine serotypes (p<0.03), whereas absolute lymphocyte count was inversely correlated with median antibody concentrations (p = 0.034). Conclusion Critically ill burn patients can generate successful responses to PPSV23 during acute injury whereas responses among neurosurgical patients is comparatively blunted. Further study is needed to elucidate the mechanisms of differential antigen responsiveness in these populations, including the role of acute stress responses, as well as the durability of these antibody responses.