A Comparison of External Ventricular Drain Catheter Diameter on Occlusion and Replacement: A Randomized Trial
Phase: NA
Conditions: Occlusion
Sponsor: Wake Forest University Health Sciences

 
EVD Randomized Multi Center Protocol 
Version 1, 11.03.2019 
PROTOCAL ADDENDUM 
 
A Comparison of External Ventricular Drain Catheter Diameter on Occlusion and Replacement: A 
Multicenter Randomized Trial 
 
Primary Investigator:  
Dr. Kyle M. Fargen 
Sub-investigator:   
Dr. Robert K. Townsend 
 
 
 
Wendy Jenkins, RN BSN, CCRC 
 
 
 
Kim Hawley, RN BSN 
 
 
Background and Purpose: 
Ventriculostomy is a common neurosurgical procedure. A Nationwide Inpatient Sample (NIS) 
database study demonstrated a significant increase in ventriculostomy utilization from 1988-2010, with 
over 35,000 hospitalizations including a procedural code for ventriculostomy in 20101.  
Ventriculostomy occlusion is a common complication after external ventricular drain (EVD) 
placement. A review of published prospective and retrospective studies indicates that approximately 1-7% 
of EVDs require replacement secondary to occlusion2-8. Furthermore, in the NIS database study of over 
101,000 hospitalizations in which ventriculostomy was performed, nearly 6% of patients required at least 
one additional ventriculostomy procedure1. Studies have demonstrated non-patent EVD in 19-47% of 
patients8-10, however these studies did not prospectively evaluate EVD occlusion as a primary endpoint, 
report on number of catheter irrigations performed, or identify risk factors for EVD occlusion. 
Recently, we completed a retrospective review of a prospectively collected database of patients 
undergoing bedside EVD placement with the primary outcome of interest being catheter occlusion 
(published in Journal of Neurosurgery). This sample included 101 patients over a 1 year period. Two 
Codman (Codman & Shurtleff Inc., Raynham, MA) catheters were available for use (Clear Bactiseal ‘large’ 
catheter: outer diameter 3.4 mm, inner diameter 1.9 mm; and Orange Bactiseal ‘small’ catheter: outer 
diameter 3 mm, inner diameter 1.5 mm). The decision regarding which catheter to use was made at the time 
of the procedure based on resident preference and availability. Both temporary occlusion (requiring 
flushing but patency could be restored) and permanent catheter occlusion (requiring replacement) were 
common, occurring in 41% and 19% of patients, respectively. Over 25% of small catheters became 
occluded during the study period compared to 11% of large catheters. Small catheters were associated with 
a 3.4 times greater odds of occlusion than the larger diameter catheters on multivariable regression analysis 
(P= 0.04; Figure 1). This study suggests that the preferential use of larger diameter catheters may reduce 
the risk of ventriculostomy occlusion and need for replacement, however the study was not randomized and 
catheter selection may have been biased.  
Recently, a smaller retrospective study of patients with intraventricular hemorrhage performed by 
Gilard and colleagues demonstrated a lower rate of occlusion and no increased risk of hemorrhage with 
larger bore catheters11. Otherwise, there is no data in the literature supporting the preferential use of 
catheters based on size (clinical equipoise). Therefore, a randomized trial comparing small versus large 
catheters in terms of occlusion and need for replacement will be beneficial in confirming differential 
occlusion risk based on catheter size.  

 
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Figure 1: Kaplan-Meier curve demonstrating catheter survival for large and small catheters. 
 
 
 
References 
 
 
1. 
Rosenbaum BP, Vadera S, Kelly ML, Kshettry VR, Weil RJ. Ventriculostomy: Frequency, length 
of stay and in-hospital mortality in the United States of America, 1988-2010. Journal of 
clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 
2014;21(4):623-632. 
2. 
Abla AA, Zabramski JM, Jahnke HK, Fusco D, Nakaji P. Comparison of two antibiotic-
impregnated ventricular catheters: a prospective sequential series trial. Neurosurgery. 
2011;68(2):437-442; discussion 442. 
3. 
Tse T, Cheng K, Wong K, Pang K, Wong C. Ventriculostomy and Infection: A 4-year-review in 
a local hospital. Surgical neurology international. 2010;1:47. 
4. 
Bauer DF, McGwin G, Jr., Melton SM, George RL, Markert JM. The relationship between INR 
and development of hemorrhage with placement of ventriculostomy. The Journal of trauma. 
2011;70(5):1112-1117. 
5. 
Fichtner J, Guresir E, Seifert V, Raabe A. Efficacy of silver-bearing external ventricular 
drainage catheters: a retrospective analysis. Journal of neurosurgery. 2010;112(4):840-846. 
6. 
Kakarla UK, Kim LJ, Chang SW, Theodore N, Spetzler RF. Safety and accuracy of bedside 
external ventricular drain placement. Neurosurgery. 2008;63(1 Suppl 1):ONS162-166; 
discussion ONS166-167. 
7. 
Khanna RK, Rosenblum ML, Rock JP, Malik GM. Prolonged external ventricular drainage with 
percutaneous long-tunnel ventriculostomies. Journal of neurosurgery. 1995;83(5):791-794. 
8. 
Bogdahn U, Lau W, Hassel W, Gunreben G, Mertens HG, Brawanski A. Continuous-pressure 
controlled, external ventricular drainage for treatment of acute hydrocephalus--evaluation 
of risk factors. Neurosurgery. 1992;31(5):898-903; discussion 903-894. 
9. 
Olson DM, Zomorodi M, Britz GW, Zomorodi AR, Amato A, Graffagnino C. Continuous cerebral 
spinal fluid drainage associated with complications in patients admitted with subarachnoid 
hemorrhage. Journal of neurosurgery. 2013;119(4):974-980. 
10. 
Chi H, Chang KY, Chang HC, Chiu NC, Huang FY. Infections associated with indwelling 
ventriculostomy catheters in a teaching hospital. International journal of infectious diseases : 
IJID : official publication of the International Society for Infectious Diseases. 2010;14(3):e216-
219. 
11. 
Gilard V, Djoubairou BO, Lepetit A, et al. Small versus large catheters for ventriculostomy in 
the management of intraventricular hemorrhage. World Neurosurg. 2016. 

 
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12. 
Rahman M WJ, Fauerbach LL, Archibald L, Friedman WA. Reducing ventriculostomy-related 
infections to near zero: the eliminating ventriculostomy infection study. Jt Comm J Qual 
Patient Saf. 2012;38(10):459-464. 
 
 
Study Design: Prospective, multicenter, randomized controlled trial. 
 
Primary Coordinating Site: Wake Forest University, Winston-Salem, NC. 
 
Participating Study Centers: 
Wake Forest University, site PI: Kyle Fargen, MD MPH 
 
Mount Sinai Hospital, New York, NY; site PI: Christopher Kellner, MD 
 
Treatment Arms 
Patients will be randomized 1:1 to receive either a small (ID 1.5 mm) antibiotic impregnated catheter or a 
large (ID 1.9 mm) antibiotic impregnated catheter.  
 
Study Population 
 
Detailed inclusion and exclusion criteria are shown in Table 1. All adult patients with spontaneous 
intracranial hemorrhage requiring placement of a frontal external ventricular drain at a study center will be 
potential candidates for inclusion. Patients may undergo placement of the EVD either at the bedside or in 
the operating room or angiography suite. Patient (if able to consent) or next of kin must be immediately 
available in person or by phone, if approved procedure for individual center’s IRB, to consent for 
randomization for the patient to be included in the study.  
 
Based on occlusion data from the previously referenced prospective study, as well as a P-value of 
0.05 and power of 0.80, the study will need to include 90 patients to demonstrate statistical significance. To 
ensure that power is adequate, we will plan to enroll 120 patients (60 in each arm).  
 
Randomization 
 
Randomization will be performed through the use of real-time, internet-based randomization 
procedure contained within RedCap to achieve a distribution balance for age, sex, diagnosis, and 
intraventricular hemorrhage distribution.   
 
Primary Outcome Measure 
 
The primary outcome measure will be permanent catheter occlusion, defined by a non-functioning 
(non-patent) EVD where patency cannot be restored through catheter manipulation or flushing.  
 
 

 
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Table 1: Inclusion and exclusion criteria.  
Inclusion Criteria 
Exclusion criteria 
Adult patient (18-85 years) requiring frontal EVD 
placement 
Patient cannot consent and next of kin cannot 
provide consent prior to procedure 
Diagnosis of spontaneous subarachnoid 
hemorrhage, intraventricular hemorrhage, 
intraparenchymal (or cerebellar) hemorrhage due 
to aneurysm, vascular malformation (arteriovenous 
malformation or arteriovenous fistula), 
hypertension, or idiopathic etiology 
Diagnosis of traumatic brain injury (EVD often 
times remain clamped for prolonged periods) 
Attending neurosurgeon decides that frontal EVD 
indicated for patient treatment with planned CSF 
drainage for 72 hours or more 
Anticoagulated prior to admission and not fully 
reversed with Coumadin (warfarin), Effient, 
Plavix, therapeutic heparin infusion, therapeutic 
subcutaneous Lovenox, therapeutic subcutaneous 
Arixtra, or other therapeutic anticoagulant or 
antiplatelet agent (ASA not included) 
Glasgow Coma Score of 5 or higher within 12 
hours of  EVD insertion 
Best Glasgow Coma Scale of 4 or less within 12 
hours of EVD insertion 
 
Hunt and Hess subarachnoid hemorrhage grade of 
5 
 
Age 86 or greater 
 
Plan for placement of EVD through non-frontal 
burr hole approach 
 
 
Secondary Outcome Measures 
1. Catheter replacement: defined by replacement of the ipsilateral EVD due to permanent 
occlusion, or placement of a contralateral EVD in the setting of a non-functioning ipsilateral 
catheter. Catheters placed contralaterally in the setting of a functioning ipsilateral catheter will 
not be considered replacements. 
2. Temporary occlusion: defined by non-functioning (non-patent) catheter requiring 
neurosurgeon flushing or manipulation in order to restore patency. By definition, such 
maneuvers must restore patency of the EVD such that it is functioning normally afterwards. 
Multiple temporary occlusions may be possible.  
3. Procedure-related hemorrhage: Presence of new catheter-related intraparenchymal 
hemorrhage, subdural hematoma, or intraventricular hemorrhage on CT scan after placement. 
4. Symptomatic hemorrhage: Presence of new neurologic deficits as a result of EVD-related 
hemorrhage, or resulting in need for further procedures due to new EVD-related hemorrhage 
(craniotomy for hematoma evacuation, ICP monitoring, etc). 
5. Administration of intraventricular tPA (Tissue Plasminogen Activator) regardless if catheter 
patency is restored. 
 
 
Protocol 

 
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Once EVD is deemed indicated by the attending neurosurgeon, the patient becomes a candidate 
for enrollment. At this point, research staff will determine candidacy by reviewing inclusion and exclusion 
criteria. Patients that meet inclusion criteria, in the absence of exclusion criteria, will be consented and 
randomized by enrolling the patient in RedCap. Patients who meet inclusion criteria and have no exclusion 
criteria but cannot be consented before treatment will undergo placement of an EVD, with catheter size 
based on surgeon preference, and will be enrolled in an ongoing prospective database.  
 
Procedural technique 
 
All EVD will be placed by neurological surgeons in either the major operating suite or in an ICU 
setting using a previously published protocol12. This protocol includes using a burr hole entry point 1 cm 
anterior to the coronal suture in the mid-pupillary line, prep and sterile drape, pre-procedural antibiotic 
administration, and tunneling the catheter to an exit site at least 5 cm from the incision. Following EVD 
insertion, physicians will document procedural factors on the procedural data sheet (Appendix A) 
 
Flushing technique 
 
No formal published protocols exist for catheter irrigation. In general, physicians are instructed to 
first attempt distal irrigation of the drainage chamber using sterile techniques (rarely effective), followed by 
gentle aspiration of the proximal system and catheter if distal flushing is not effective. If these do not 
restore patency, a small volume of sterile saline, 3 ml or less, is flushed proximally into the catheter. 
Patency is checked by lowering the EVD drainage system and evaluating for spontaneous flow through the 
EVD. Each irrigation will be recorded on the daily record sheet (Appendix B). 
 
Treatment Arms 
Enrolled patients will be randomized to one of two catheters in a 1:1 randomization scheme. These 
include the antibiotic-impregnated ‘large’ catheter (outer diameter 3.4 mm, inner diameter 1.9 mm) and an 
antibiotic-impregnated ‘small’ catheter (outer diameter 3 mm, inner diameter 1.5 mm). After placement of 
the EVD catheter, all clinical and radiographic follow-up will be the same for both treatment arms. 
 
Data collection 
  
Data will be collected prospectively by the research team. Trial data will be reported via RedCap.  
Collected data will included a number of factors, such as: age, gender and underlying diagnosis; procedural 
data including faculty versus resident physician as primary proceduralist, number of passes, side of 
placement; radiographic data including ventricular size (based upon Evan’s ratio: maximum bifrontal 
ventricular distance divided by maximal intracranial biparietal distance), pre-procedural midline shift, 
presence of intraventricular hemorrhage, catheter location, and presence of catheter-related hemorrhage; 
and clinical data including symptomatic hemorrhage, number and type of catheter irrigations, catheter 

 
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occlusion and replacement, number of catheter days, catheter endpoint, cerebrospinal fluid analysis and 
incidence of catheter-related infection (Appendices). 
 
 
 
Imaging Review 
 
A blinded physician at each treatment center will review brain imaging to document all 
radiographic data into RedCap, including: Evan’s ratio, midline shift, presence of intraventricular 
hemorrhage, catheter location, and presence of catheter-related hemorrhage. At time of site activation for 
each center, the radiographic reviewer will undergo a training session via conference call, performed by the 
study PI (KF), which will ensure consistent interpretation of imaging across centers. The primary center 
may ask for select image series to be uploaded into RedCap for review by the PI.  
 
Study Endpoint 
 
Patients will have met the study endpoint when the EVD is intentionally removed by the supervising 
physician, in any of the following scenarios: 1) The EVD is removed due to resolution of hydrocephalus; 2) 
The EVD is removed because it is non-functional but not replaced; 3) The EVD is removed and is replaced 
with a shunt. Once the endpoint has been reached, no further data collection will occur for that study subject. 
 
Adverse Events 
  
Adverse events will be recorded. Adverse events include: symptomatic intracranial 
intraparenchymal or subdural hemorrhage (with new neurologic deficit or need for surgery), symptomatic 
intraventricular hemorrhage (defined as new neurologic deficit, need for surgery, or catheter occlusion within 
2 hours of placement requiring contralateral EVD placement), meningitis (confirmed by positive CSF 
cultures and initiation of antibiotic therapy), catheter in extraventricular position on placement, and catheter 
malposition after confirmation of correct positioning requiring replacement (ie. catheter is unintentionally 
pulled out by nurse, patient, or due to loose sutures).   
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX A:  
EVD Insertion Procedure Datasheet 
 
Subject No: _____________ 
Date: __________________ 
Side (Circle one):   
Right 
 
Left 
 
Year of Physician Performing Procedure (Circle one): 
PGY1 
PGY2 
PGY3 
PGY4 
PGY5 
PGY6 
PGY7 
Faculty 
 
Number of Passes Required (Circle one):    
1 
2 
3 
4 
5  
6 
7 
8 
9 
10 
11 or more 
 
Degree of Confidence Ventricular Catheter in Ipsilateral Lateral Ventricle, from 1-5 (Circle one): 
 
1 
 
2 
 
3 
 
4 
 
5 
(Poor Confidence) 
 
(Moderate Confidence) 
 
(Highly Confident) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX B: 
STUDY SUBJECT DAILY RECORD SHEET 
Subject No: _____________ 
 
 
 
Date: __________________ 
Side (Circle one):   
R 
L 
At time 00:00, EVD is (Circle one): 
Clamped 
Open to Drain 
At time 00:00, Height of EVD (cm of water): ___________________ 
 
RECORD ANY EVD HEIGHT OR CLAMPING ORDER CHANGES:  
Height Change #1:   Changed to: ___________ cm water  
Time:    
Height Change #2:   Changed to: ___________ cm water  
Time:  
Height Change #3:   Changed to: ___________ cm water  
Time:  
Clamping/Unclamping #1:   ☐Clamped   ☐Unclamped 
Time: 
Clamping/Unclamping #2:    ☐Clamped   ☐Unclamped 
Time: 
Clamping/Unclamping #3:    ☐Clamped   ☐Unclamped 
Time: 
  
 
RECORD ANY EVD FLUSHING EVENTS: 
1. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
2. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
3. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
4. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
5. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          

 
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6. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
7. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
8. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
9. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
10. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
11. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
12. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
13. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
14. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded          
15. Time:  
 
☐Distal system flushed only   
☐Proximal system aspirated only 
 
 
 
☐Proximal system flushed  - number of times:  ________ 
RESULT: 
 ☐EVD functioning 
☐EVD occluded