BACKGROUND: We developed a noninvasive biomarker to quantify the rate of ventricular blood clearance in patients with intracerebral hemorrhage and extension to the ventricles-intraventricular hemorrhage.
METHODS: We performed magnetic resonance imaging in 26 patients at 1, 14, 28, and 42 days of onset and measured their hematoma volume (HV), ventricular blood volume (VBV), and two diffusion metrics: fractional anisotropy (FA), and mean diffusivity (MD). The ipasilesional ventricular cerebral spinal fluid\'s FA and MD were associated with VBV and stroke severity scores (National Institute of Health Stroke Scale [NIHSS]). A subcohort of 14 patients were treated with external ventricular drain (EVD). A generalized linear mixed model was applied for statistical analysis.
RESULTS: At day 1, the average HVs and NIHSS scores were 14.6 ± 16.7 cm3 and 16 ± 8, respectively. A daily rate of 2.1% and 1.3% blood clearance/resolution were recorded in HV and VBV, respectively. Ipsilesional ventricular FA (vFA) and ventricular MD (vMD) were simultaneously decreased (vFA = 1.3% per day, posterior probability [PP] > 99%) and increased (vMD = 1.5% per day, PP > 99%), respectively. Patients with EVD exhibited a faster decline in vFA (1.5% vs. 1.1% per day) and an increase in vMD (1.8% vs. 1.5% per day) as compared with patients without EVD. Temporal change in vMD was associated with VBV; a 1.00-cm3 increase in VBV resulted in a 5.2% decrease in vMD (PP < 99%). VBV was strongly associated with NIHSS score (PP = 97-99%). A larger cerebral spinal fluid drained volume was associated with a greater decrease (PP = 83.4%) in vFA, whereas a smaller volume exhibited a greater increase (PP = 94.8%) in vMD.
CONCLUSIONS: In conclusion, vFA and vMD may serve as biomarkers for VBV status.

Meropenem penetration into the cerebrospinal fluid (CSF) is subject to high interindividual variability resulting in uncertain target attainment in CSF. Recently, several authors recommended administering meropenem as a continuous infusion (CI) to optimize CSF exposure. This study aimed to compare the concentrations and pharmacokinetics of meropenem in CSF after intermittent infusion (II) and CI. This prospective, observational study (NCT04426383) included critically ill patients with external ventricular drains who received either II or CI of meropenem. Meropenem pharmacokinetics in plasma and CSF were characterized using population pharmacokinetic modeling (NONMEM 7.5). The developed model was used to compare the concentration-time profile and probability of target attainment (PTA) between II and CI. A total of 16 patients (8 CI, 8 II; samples: nplasma = 243, nCSF = 263) were recruited, with nine patients (5 CI, 4 II) suffering from cerebral and seven patients from extracerebral infections. A one-compartment model described the plasma concentrations adequately. Meropenem penetration into the CSF (partition coefficient (KP), cCSF/cplasma) was generally low (6.0%), exhibiting substantial between-subject variability (coefficient of variation: 84.0%). There was no correlation between the infusion mode and KP, but interleukin (IL)-6 measured in CSF showed a strong positive correlation with KP (P < 0.001). Dosing simulations revealed no relevant differences in CSF concentrations and PTA in CSF between CI and II. Our study did not demonstrate increased penetration rates or higher concentrations of meropenem in the CSF with CI compared with II.
RESULTS: This study is registered with ClinicalTrials.gov as NCT04426383.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.
METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.
CONCLUSIONS: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.
BACKGROUND: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

OBJECTIVE: External ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD.
METHODS: This was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome.
RESULTS: Out of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039).
CONCLUSIONS: Gradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

OBJECTIVE: The objective of this study was to determine risk factors predictive of external ventricular drain (EVD)-related hemorrhage and the association of such hemorrhages with mortality, discharge disposition, length of stay (LOS), and total cost.
METHODS: After Institutional Review Board approval, data was collected retrospectively for adult patients requiring EVD placement from 2015 to 2018 at the authors\' institution. Collected data included demographic patient information, peri-procedural factors, and relevant post-procedural measures. Computerized tomography (CT) images and associated radiologic reports were independently reviewed, identifying hemorrhages accompanying EVD placement.
RESULTS: From this 487-patient sample, 85 (17.5 %) patients had hemorrhages, including asymptomatic hemorrhages identified on imaging alone. A univariable analysis of patient parameters in the overall cohort was performed to identify possible predictors of hemorrhage. Age (p = 0.002), Charlson Comorbidity Index (CCI) (p < 0.001), platelet count (p = 0.002), presence of uremia (p = 0.035), and the number of times the EVD was replaced (p < 0.001) were associated with hemorrhage in univariable models. The experience of the resident surgeon based on post-graduate year (PGY level) and the number of attempts/passes needed for EVD placement were not associated with hemorrhage risk. Significant predictor of hemorrhage confirmed in a multivariable analysis only included the number of times the EVD was replaced (OR = 2.78, adjusted p < 0.001). Outcomes between EVD-related hemorrhage versus no hemorrhage groups, including mortality, discharge disposition, LOS, and cost, were compared. EVD-related hemorrhage was found to be associated with increased mortality (OR = 3.58, adjusted p < 0.001) and decreased likelihood of discharge home (OR = 0.13, adjusted p = 0.030) in the associated multivariable regressions.
CONCLUSIONS: The number of times an EVD was replaced was associated with EVD-related hemorrhage outcome. EVD-related hemorrhage is associated with increased mortality and a decreased likelihood of being discharged home.

BACKGROUND: Ventriculostomy-related infections (VRIs) are reported in about 10 % of patients with external ventricular drains (EVDs). VRIs are difficult to diagnose due to clinical and laboratory abnormalities caused by the primary neurological injury which led to insertion of the EVD. Polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) may enable more accurate diagnosis of VRI. We performed a prospective cohort study to measure the incidence of VRI as diagnosed by 16S rRNA PCR.
METHODS: Patients admitted to intensive care with a primary diagnosis of subarachnoid haemorrhage (SAH), traumatic brain injury (TBI), or intracerebral haemorrhage (ICH), who required an EVD, were assessed for inclusion in this study. Data were extracted from the electronic medical record, bedside charts, or from a prospectively collected database, the Neuroscience Outcomes in Intensive CarE database (NOICE). 16S rRNA PCR was performed on routinely collected CSF as per laboratory protocol. VRI was also diagnosed based on pre-existing definitions.
RESULTS: 237 CSF samples from 39 patients were enrolled in the study. The mean patient age was 55.7 years, and 56.4 % were female. The most common primary neurological diagnosis was SAH (61.5 %). The incidence of a positive PCR was 2.6 % of patients (1 in 39) and 0.8 % of CSF samples (2 in 237). The incidence of VRI according to pre-published diagnostic criteria was 2.6 % - 41 % of patients and 0.4 % - 17.6 % of CSF samples. 28.2 % of patients were treated for VRI. Pre-published definitions which relied on CSF culture results had higher specificity and lower false positive rates for predicting a PCR result when compared to definitions incorporating non-microbiological markers of VRI. In CSF samples with a negative 16S rRNA PCR, there was a high proportion of non-microbiological markers of infection, and a high incidence of fever on the day the CSF sample was taken.
CONCLUSIONS: The incidence of VRI as defined as a positive PCR was lower than the incidence of VRI according to several published definitions, and lower than the incidence of VRI as defined as treatment by the clinical team. Non-microbiological markers of VRI may be less reliable than a positive CSF culture in diagnosing VRI.

UNASSIGNED: External ventricular drain (EVD) insertion is a common neurosurgical procedure used to treat acute hydrocephalus. In this report, we present a rare case of an EVD that was initially correctly placed within the frontal horn but subsequently migrated to the cisterna magna, the first to be reported in the literature.
UNASSIGNED: A 46-year-old man with postoperative meningitis and hydrocephalus underwent EVD insertion using an improvised EVD system. The EVD was also used as a route for the administration of intraventricular antibiotics. The patient was restless and agitated during his treatment, causing him to move his head frequently. Serial computed tomography scans showed that the EVD was initially correctly placed within the frontal horn and then migrated to the cisterna magna.
UNASSIGNED: Inward catheter migration is a rare complication of EVD insertion and is an important concern since it may cause neurologic deficits and potentially harmful sequelae. We have also highlighted measures that can be taken to prevent a similar event in the future.

Introduction Patients with subarachnoid hemorrhages (SAH) with external ventricular drains (EVD) can develop chronic hydrocephalus (HCP), requiring permanent cerebrospinal fluid (CSF) diversion via an external shunt. Two different strategies have been used to assess for dependence on EVD: 1) prompt closure, and 2) gradual weaning. Gradual weaning of EVDs is performed by increasing drainage resistance to outflow over days. However, when to start one strategy or the other is up to the physician. No uniform guidelines exist raising a question: Are standardized criteria necessary to initiate the EVD weaning process for SAH patients to increase the safety of EVD discontinuation and reduce the need for a shunt? This study shares criteria used to initiate EVD weaning that displayed increased safety of EVD discontinuation for patients with subarachnoid hemorrhage requiring EVD, particularly with regards to length of hospital stay (LOS), hospital-acquired infection rates, and ventriculoperitoneal shunt/endoscopic third ventriculostomy (VPS/ETV) placement. Methods One hundred and fifty-one SAH patients from January 2016 to January 2019 were analyzed. 60 aneurysmal SAH (aSAH) and 18 non-aneurysmal nontraumatic SAH (naSAH) patients required EVD placement. A gradual EVD weaning protocol was initiated if patients met the following criteria: 1. The reason for EVD placement has resolved or is resolving, 2. The quantity of CSF output is <250mL over 24 hours, 3. Quality of CSF is nonbloody, 4. Intracranial Pressure (ICP) must be within normal limits, and 5. The patient must be neurologically stable. It was acceptable to initiate the weaning process when the patient had mild cerebral vasospasm, but not moderate to severe cerebral vasospasm. EVD weaning was performed by increasing the drain (chamber) height by 5 millimeters of mercury every 24 hours if the criteria were met. Charts were reviewed for LOS, infection rates, and rate of VPS/ETV. Gender, age, race, wean failure incidence, Hunt-Hess scores, modified Fisher scores, and syndrome of inappropriate antidiuretic hormone/cerebral salt wasting (SIADH/CSW) rates were obtained. Results The average LOS for aSAH patients with EVD was 20.35 days. The incidence of VPS/ETV was 11%. A chi-square analysis revealed that aSAH patients had higher rates of VPS/ETV placement (p<0.001) and EVD wean failures (p<0.001) than naSAH patients. aSAH patients had a lower incidence of VPS/ETV placement of 11% compared to 21% nationally. Conclusions Standardized criteria to initiate EVD weaning provided a reduction in VPS/ETV placement among aSAH patients compared to national averages and provided a uniform approach to EVD management. Comparable infection rates and LOS for SAH patients requiring EVDs compared to national averages were found.

UNASSIGNED: Nosocomial infectious ventriculitis caused by multidrug-resistant (MDR) Gram-negative bacilli associated with external ventricular drainage (EVD) placement poses a significant mortality burden and hospital costs.
UNASSIGNED: This study aims to analyze the characteristics, ventriculitis evolution, treatment, and outcomes of patients with ventriculitis due to MDR Gram-negative bacilli associated with EVD placement.
UNASSIGNED: A retrospective cohort study focusing on patients with nosocomial infection caused by MDR Gram-negative bacilli while on EVD was conducted from 2019 to 2022. Medical, laboratory, and microbiological records were collected. The antibiotic resistance of the Gram-negative bacilli isolated in the cerebrospinal fluid (CSF) of patients was analyzed. The risk factors were identified using univariate risk models and were analyzed using survival curves (Cox regression). An adjusted Cox proportional hazards model was also constructed.
UNASSIGNED: Among 530 patients with suspected EVD-associated ventriculitis, 64 patients with isolation of Gram-negative bacilli in CSF were included. The estimated mortality was 78.12%. Hemorrhages (intracranial, subarachnoid, and intraventricular) were observed in 69.8% of patients. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequently isolated bacilli. In the univariate analysis, significant risk factors for mortality included arterial hypertension, a Glasgow Coma Scale (GCS) score of ≤ 8, invasive mechanical ventilation (IMV) upon hospital admission and during hospitalization, septic shock, and ineffective treatment. The adjusted Cox proportional hazards model revealed that septic shock (HR = 3.3, 95% CI = 1.5-7.2; p = 0.003) and ineffective treatment (HR = 3.2, 1.6-6.5, 0.001) were significant predictors. A high resistance to carbapenems was found for A. baumannii (91.3%) and P. aeruginosa (80.0%). Low resistance to colistin was found for A. baumannii (4.8%) and P. aeruginosa (12.5%).
UNASSIGNED: Ineffective treatment was an independent hazard factor for death in patients with ventriculitis caused by MDR Gram-negative bacilli associated with EVD.

OBJECTIVE: The most common method for external ventricular drain (EVD) placement is the freehand approach, which has reported inaccuracy rates of 12.3%-44.9%, especially in the case of altered ventricular anatomy. Current assistive devices require added time or equipment or do not account for shifted ventricles. To improve the accuracy of emergent EVD placement in the setting of altered ventricular anatomy, the authors designed a patient-specific EVD (PS-EVD) guide.
METHODS: The PS-EVD guide has a tripod base and a series of differently angled inserts that lock in place at multiple rotational positions, allowing for numerous insertion angles. For testing, the authors designed a 3D-printed phantom skull with a gelatin brain analog containing ventricles simulating normal and altered ventricular anatomy. Low-resolution CT scans of the phantom were used to calculate the insertion angle in relation to the standard perpendicular entry. The corresponding insert at the correct rotational position within the base unit was positioned over the entry point on the phantom, and the catheter was inserted. Accuracy was evaluated with repeat CT scans.
RESULTS: With normal ventricular anatomy, as well as abnormally shifted ventricles, proper use of the PS-EVD guide led to accurate catheter insertion into the ventricle in trials, as confirmed on coronal and sagittal CT images, including cases in which a perpendicular trajectory, such as with the Ghajar guide, was insufficient.
CONCLUSIONS: The PS-EVD guide allows consistent and accurate EVD placement in phantom skulls with both normal and altered ventricular anatomy. Further trials comparing this device to the freehand approach are required.