Utility of the Cell Index in Predicting External Ventricular Drain-Related Ventriculo-Meningitis

OBJECTIVEThe objective of this study was to measure the concentration of nimodipine in CSF and plasma after intraventricular injection of a sustained-release formulation of nimodipine (EG-1962) in patients with aneurysmal subarachnoid hemorrhage (SAH).METHODSPatients with SAH repaired by clip placement or coil embolization were randomized to EG-1962 or oral nimodipine. Patients were classified as grade 2–4 on the World Federation of Neurosurgical Societies grading scale for SAH and had an external ventricular drain inserted as part of their standard of care. Cohorts of 12 patients received 100–1200 mg of EG-1962 as a single intraventricular injection (9 per cohort) or they remained on oral nimodipine (3 per cohort). Plasma and CSF were collected from each patient for measurement of nimodipine concentrations and calculation of maximum plasma and CSF concentration, area under the concentration-time curve from day 0 to 14, and steady-state concentration.RESULTSFifty-four patients in North America were randomized to EG-1962 and 18 to oral nimodipine. Plasma concentrations increased with escalating doses of EG-1962, remained stable for 14 to 21 days, and were detectable at day 30. Plasma concentrations in the oral nimodipine group were more variable than for EG-1962 and were approximately equal to those occurring at the EG-1962 800-mg dose. CSF concentrations of nimodipine in the EG-1962 groups were 2–3 orders of magnitude higher than in the oral nimodipine group, in which nimodipine was only detected at low concentrations in 10% (21/213) of samples. In the EG-1962 groups, CSF nimodipine concentrations were 1000 times higher than plasma concentrations.CONCLUSIONSPlasma concentrations of nimodipine similar to those achieved with oral nimodipine and lasting for 21 days could be achieved after a single intraventricular injection of EG-1962. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Clinical trial registration no.: NCT01893190 (ClinicalTrials.gov).

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A Comparative Analysis of Methods for Titering Reovirus

Pharmaceutical Nanotechnology ◽

10.2174/2211738508666200826103322 ◽

2020 ◽

Vol 8 (5) ◽

pp. 409-417

Author(s):

Yi-Chen Yang ◽

Xian-Yao Wang ◽

Yuan-Yuan An ◽

Chun-Xiang Liao ◽

Nian-Xue Wang ◽

...

Keyword(s):

Traditional Method ◽

Virus Titer ◽

Cell Analysis ◽

Half Cell ◽

L929 Cells ◽

Cell Index ◽

Standard Curve ◽

Analysis Technique ◽

Curve Method ◽

Standard Curve Method

Background: A key challenge in the process of virus amplification is the need for a simple and convenient method for measuring virus titers. Objective: Real-time unlabeled cell analysis (RTCA) was used to establish a standard curve of correlation between half-cell index time (CIT50) and virus titer. At the same time, the virus titer from tunable resistance pulse detection (TRPS) technology was compared with the traditional median tissue culture infectious dose (TCID50) method to evaluate the feasibility and application value of the RTCA technique and TRPS technology. Methods: : Cell index (CI) values for L929 cells under different culture conditions were detected, and the appropriate initial cell inoculation density was screened. The half-cell index (CI50) values of reovirus infected L929 cells with TCID50 titers were analyzed by RTCA, the CI50-TCID50 standard curve was created, and a regression equation was developed. RTCA, TCID50, and TRPS methods were used to detect the reovirus titer obtained by the amplification, and the sensitivity and feasibility of the CIT50-TCID50 standard curve method were analyzed. The virus titer was detected by TRPS technology and the TCID50 method. Results: L929 cells were best propagated at an initial density of 6 × 103 cells/well. After infecting L929 cells with different titers of reference reovirus, the linear correlation of CIT50 and TCID50 was y = -2.1806x + 71.023 (R2 = 0.9742). The titer resulting from the RTCA assay was 7×109.6821 pfu/mL, from the TRPS assay was 4.52×1010 pfu/mL, and from the TCID50 assay was 7×109.467 pfu/mL. Conclusion: The CIT50-TCID50 standard curve method established by the RTCA technique can be used to quantitatively detect reovirus titer with L929 cells. Compared with the TCID50 method, it takes a relatively short time and has high sensitivity and accuracy. The TRPS technology requires even less time to quantify the virus, but its precision is lower than that of the TCID50 method and RTCA technology. This study provides new technical methods for assessing the virulence of infectious live reovirus particles. Lay Summary: After amplification of the virus, we need to detect the virus titers (the virulence of the virus). The traditional method is to use the virus to infect cells, and then the virus titers can be calculated by 50% of the cells infected. However, this traditional method is time consuming. The ways of RTCA (a real-time cell analysis technique) and TRPS (a nano-bioparticle analysis technique) help us to detect viral titers. The consistency of these three methods determines their feasibility and accuracy. If they are feasible, then these two simple technologies will provide new ideas for detecting viral titers.

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The Use of Staples for External Ventricular Drain Catheter Fixation: A Single Institution Case Series

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2021.106761 ◽

2021 ◽

pp. 106761

Author(s):

Mohamed M. Salem ◽

Luis C. Ascanio ◽

Alejandro Enriquez-Marulanda ◽

Santiago Gomez-Paz ◽

Charles E. Mackel ◽

...

Keyword(s):

External Ventricular Drain ◽

Case Series ◽

Single Institution

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Simultaneous Cranioplasty and External Ventricular Drain Implantation in Patients with Hydrocephalus: Case Series and Literature Review

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0041-1730332 ◽

2021 ◽

Author(s):

Lívio Pereira de Macêdo ◽

Arlindo Ugulino Netto ◽

Kauê Franke ◽

Pierre Vansant Oliveira Eugenio ◽

John Anderson da Silva Rocha ◽

...

Keyword(s):

External Ventricular Drain ◽

Neurological Complication ◽

Case Series ◽

Neurological Deficits ◽

Time Interval ◽

Automobile Accidents ◽

Decompressive Hemicraniectomy ◽

Cerebral Herniation ◽

Intraoperative Period ◽

The Brain

Abstract Introduction The increase in intracranial pressure (ICP) is a neurological complication resulting from numerous pathologies that affect the brain and its compartments. Therefore, decompressive craniectomy (DC) is an alternative adopted to reduce ICP in emergencies, especially in cases refractory to clinical therapies, in favor of patient survival. However, DC is associated with several complications, including hydrocephalus (HC). The present study presents the results of an unusual intervention to this complication: the implantation of an external ventricular drain (EVD) in the intraoperative period of cranioplasty (CP). Methods Patients of both genders who presented with HC and externalization of the brain through the cranial vault after decompressive hemicraniectomy and underwent EVD implantation, to allow the CP procedure, in the same surgical procedure, were included. Results Five patients underwent DC due to a refractory increase in ICP, due to automobile accidents, firearm projectiles, falls from stairs, and ischemic strokes. All evolved with HC. There was no uniform time interval between DC and CP. The cerebrospinal fluid (CSF) was drained according to the need for correction of cerebral herniation in each patient, before undergoing cranioplasty. All patients progressed well, without neurological deficits in the immediate postoperative period. Conclusion There are still several uncertainties about the management of HC resulting from DC. In this context, other CP strategies simultaneous to the drainage of CSF, not necessarily related to ventriculoperitoneal shunt (VPS), should be considered and evaluated more deeply, in view of the verification of efficacy in procedures of this scope, such as the EVD addressed in this study.

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Prognostic Nomogram of Predictors for Shunt-Dependent Hydrocephalus in Patients with Aneurysmal Subarachnoid Hemorrhage Receiving External Ventricular Drain Insertion: A Single-Center Experience and Narrative Review

World Neurosurgery ◽

10.1016/j.wneu.2021.01.138 ◽

2021 ◽

Author(s):

Yao-Chung Yang ◽

Chun-Hao Yin ◽

Kuan-Ting Chen ◽

Pei-Chin Lin ◽

Ching-Chih Lee ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

External Ventricular Drain ◽

Narrative Review ◽

Single Center ◽

Single Center Experience

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External Ventricular Drain Infection

Journal of Neurosurgery ◽

10.3171/jns-07/07/0248 ◽

2007 ◽

Vol 107 (1) ◽

pp. 248 ◽

Cited By ~ 3

Author(s):

George K. C. Wong ◽

Wayne W. S. Poon

Keyword(s):

Major Trauma ◽

Independent Predictor ◽

External Ventricular Drain ◽

Significant Risk ◽

Significant Risk Factor ◽

External Ventricular Drainage ◽

Infection Rates ◽

The Mean ◽

The Relationship ◽

Shed Light

Object The authors explored the relationship among the duration of external ventricular drainage, revision of external ventricular drains (EVDs), and cerebrospinal fluid (CSF) infection to shed light on the practice of electively revising these drains. Methods In a retrospective study of 199 patients with 269 EVDs in the intensive care unit at a major trauma center in Australasia, the authors found 21 CSF infections. Acinetobacter accounted for 10 (48%) of these infections. Whereas the duration of drainage was not an independent predictor of infection, multiple insertions of EVDs was a significant risk factor. Second and third EVDs in previously uninfected patients were more likely to become infected than first EVDs. An EVD infection was initially identified a mean of 5.5 ±0.7 days postinsertion (standard error of the mean); these data—that is, the number of days—were normally distributed. Conclusions This pattern of infection is best explained by EVD-associated CSF infections being acquired by the introduction of bacteria on insertion of the drain rather than by subsequent retrograde colonization. Elective EVD revision would be expected to increase infection rates in light of these results, and thus the practice has been abandoned by the authors' institution.

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Chlorhexidine dressings could reduce external ventricular drain infections: results from a systematic review and meta-analysis

Journal of Hospital Infection ◽

10.1016/j.jhin.2021.06.006 ◽

2021 ◽

Author(s):

Mueez Waqar ◽

Aswin Chari ◽

Abdurrahman I. Islim ◽

Benjamin Davies ◽

Daniel M. Fountain ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

External Ventricular Drain

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Use of a cyanoacrylate skin adhesive to reduce external ventricular drain infection rates

Journal of Neurosurgery ◽

10.3171/2013.12.jns13700 ◽

2014 ◽

Vol 121 (1) ◽

pp. 189-194 ◽

Cited By ~ 9

Author(s):

Markus J. Bookland ◽

Vishad Sukul ◽

Patrick J. Connolly

Keyword(s):

Wound Care ◽

External Ventricular Drain ◽

Positive Skin ◽

Liquid Polymer ◽

Intensive Care Patients ◽

Neurological Intensive Care ◽

Cyanoacrylate Adhesive ◽

Skin Flora ◽

Lower Infection ◽

The One

Object Ventriculitis related to external ventricular drain (EVD) placement is a significant source of morbidity in neurological intensive care patients. Current rates of EVD-related infections range from 2% to 45% in the literature. The authors sought to determine if a 2-octyl cyanoacrylate adhesive would result in lower infection rate than standard semiocclusive dressings. Methods The authors tracked ventriculitis rates via CSF cultures among 259 patients whose EVD sites were dressed with sterile semiocclusive dressings and underwent routine sterile dressing exchanges every 48 hours. They analyzed data obtained in an additional 113 patients whose EVD sites were dressed one time with a surgical adhesive, 2-octyl cyanoacrylate. Results Ventriculitis rate in patients with standard bioocclusive dressings and wound care was 15.1%, whereas that in patients with a 2-octyl cyanoacrylate dressing was 3.54% (p = 0.002). Staphylococcus genus accounted for 79.5% of instances of ventriculitis among patients with bioocclusive dressings and routine wound care, whereas it accounted for 25.0% of the instances of ventriculitis among patients with a liquid polymer sealant dressing. A 90% reduction in Staphylococcus infection completely accounts for the observed effect (p = 0.04). Conclusions The one-time application of 2-octyl cyanoacrylate to EVD wounds and exit sites provided superior protection against EVD-related ventriculitis compared to conventional EVD-site wound care. Likely this protection results from a barrier to the entry of gram-positive skin flora along the EVD exit tract. The results should be validated in a randomized trial.

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