Comparison of Different CSF Sampling Sites on External Ventricular Drains (CSF3S)

The aim of the current study is to evaluate the difference between proximal and distal CSF sampling. If the characteristics of distally and proximally sampled CSF are similar or correlate well, it may be possible to only sample CSF distally in the future, thereby avoiding the risks mentioned above.

Study Overview

• Status: Recruiting
• Conditions: Cerebrospinal Fluid
• Intervention / Treatment: Procedure: Analyses of proximal and distal samples

Detailed Description

Insertion of an external ventricular drain (EVD) is a common neurosurgical procedure, for example in patients with intracranial bleeding, head trauma of tumours. The aim of an external ventricular drain is either to drain cerebrospinal fluid (CSF) or to measure intracranial pressure. In patients with external ventricular drains, it is a common practice in many centres, including UZ Leuven, to routinely sample CSF two or three times a week. The following tests are routinely performed: protein level, glucose level, lactate level, white cell count, red cell count, and cultures. Gram stain is performed in case white blood cell count exceeds 5 cells/mm³. This regular sampling (1) permits early detection of ventriculitis, which may be rather asymptomatic, especially in sedated patients,and (2) may guide neurosurgeons to the ideal timeframe to either taper the external ventricular drainage, or replace it by a ventriculoperitoneal shunt.

A typical external ventricular drainage system consists of a ventricular catheter, which is nowadays usually impregnated with antibiotics (e.g. Codman Bactiseal - coated with clindamycin and rifampicin), an extension tube, a drip chamber, and a collection bag. Multiple three-way taps and access ports along its course allow for CSF sampling (or injection of therapeutics, such as tissue plasminogen activator, or saline to flush the catheter in case of blockage).

From a practical perspective, CSF sampling from the external ventricular drain is possible at all of these three-way taps and access ports. Broadly, one may sample CSF as proximally (close to the ventricle) as possible (e.g. by using the access port), or distally (at the level of the drip chamber, e.g. by using the three-way tap between the drip chamber and the collection bag). There is no consistency in for CSF collection site amongst different institutions. Traditionally, in UZ Leuven, we have been sampling CSF proximally until now.

The main theoretical advantage of proximal sampling is that actively aspirated "fresh" CSF close to the ventricle likely closely resembles the true characteristics of our study object, i.e. intraventricular CSF. Nevertheless, this approach is not without risk. First, it requires to directly access the sterile inside of the extension tube. This inherently comes with a risk of iatrogenic infection. Secondly, by aspirating the external ventricular catheter, the neurosurgeon may induce an iatrogenic haemorrhage in the brain parenchyma or the ventricle, and/or direct trauma to the brain parenchyma, as in suboptimally positioned catheters or small ventricles, white matter or choroid plexus may be aspirated along with CSF. Because of the risk of iatrogenic infections, haemorrhage or trauma, it is our institutional policy that CSF sampling from external ventricular drains is performed by neurosurgeons only. This also poses practical problems and may delay sampling, especially in patients who are not admitted to neurosurgical wards (e.g. paediatric cases).

From a theoretical perspective, distal CSF sampling, at the level of the drip chamber, has multiple advantages. First, the risk of iatrogenic infections induced by CSF sampling is likely to be lower, as there is no direct contact between the CSF in the drip chamber and the intraventricular CSF. Secondly, there is no risk of inducing haemorrhages or brain trauma, as no "active" aspiration is required for CSF sampling. Hence, distal CSF sampling can perhaps also be carried out by physicians from other fields than neurosurgery, or by trained nurses. However, theoretically, it is possible that the characteristics of CSF sampled distally do not sufficiently resemble those of intraventricular CSF.

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

• Study Contact: Name: Philippe De Vloo, prof.dr.; Phone Number: 016 344290; Email: neurochirurgie@uzleuven.be
• Study Contact Backup: Name: Tom Deleu, dr.; Phone Number: 016 344290; Email: neurochirurgie@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Philippe De Vloo, prof.dr.; Phone Number: 016 344290; Email: neurochirurgie@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with an external ventricular drain (EVD) presenting to the Neurosurgery ward.

Description

Inclusion Criteria:

• Patients with an EVD in place regardless of the underlying pathology.
• Written informed consent to participate in the study must be obtained from the subject. If the subject is not capable of self-consent, all efforts will be made to locate a legally acceptable representative to act on behalf of the subject.

When the patient is considered capable to consent but physically unable to sign an informed consent form and a representative is not available an impartial witness can attend the informed consent process.

- Males and females of all ages, including children and pregnant females

Exclusion Criteria:

• Patients in whom the removal of the drain is planned within 48 hours, before routine sampling, will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with EVD	Procedure: Analyses of proximal and distal samples; Evaluate the difference between proximal and distal CSF samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the CSF white cell count at day 1-4 and day 5-9 when comparing both sampling methods	The aim of the current study is to evaluate the difference between proximal and distal CSF sampling.	Day 1-4 and day 5-9 after placement of EVD

Secondary Outcome Measures

Outcome Measure	Time Frame
White cell count correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Gram stain correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Culture correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Protein correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Glucose correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Lactate correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Red cell count correlation for all the available time points	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
Absolute difference between white blood cell count, protein, glucose, lactate, and red blood cell count	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)
AEs likely related to CSF sampling, irrespective of the method (new or increased haemorrhage, infection)	Samples will be taken every 2-3 days after placement until removal of EVD (estimated between 7 and 28 days)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Philippe De Vloo, prof.dr., UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: neurosurgery; CSF; EVD
• Other Study ID Numbers: S65845

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No