The Hydrocephalus Clinical Research Network

J Neurosurg Pediatrics 14:173 178, 2014 AA, 2014 Factors associated with ventricular catheter movement and inaccurate catheter location: post hoc analysis of the Hydrocephalus Clinical Research Network Ultrasound-Guided Shunt Placement study Clinical article William E. Whitehead, M.D., 1 Jay Riva-Cambrin, M.D., M.Sc., 2 John C. Wellons III, M.D., M.S.P.H., 3 Abhaya V. Kulkarni, M.D., Ph.D., 4 Samuel Browd, M.D., Ph.D., 5 David Limbrick, M.D., Ph.D., 6 Curtis Rozzelle, M.D., 7 Mandeep S. Tamber, M.D., Ph.D., 8 Tamara D. Simon, M.D., M.S.P.H., 5 Chevis N. Shannon, M.B.A., M.P.H., Dr.P.H., 3 Richard Holubkov, Ph.D., 2 W. Jerry Oakes, M.D., 5 Thomas G. Luerssen, M.D., 1 Marion L. Walker, M.D., 2 James M. Drake, F.R.C.S.C., 4 and John R. W. Kestle, M.D., 9 for the Hydrocephalus Clinical Research Network 1 Texas Children s Hospital, Houston, Baylor College of Medicine, Houston, Texas; 2 University of Utah, Salt Lake City, Utah; 3 Monroe Carell Jr. Children s Hospital, Vanderbilt University, Nashville, Tennessee; 4 Hospital for Sick Children, University of Toronto, Ontario, Canada; 5 Seattle Children s Hospital, University of Washington, Seattle, Washington; 6 St. Louis Children s Hospital, Washington University, St. Louis, Missouri; 7 Children s Hospital of Alabama, University of Alabama at Birmingham, Alabama; 8 Children s Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania; and 9 Department of Neurosurgery, University of Utah, Salt Lake City, Utah Object. Shunt survival may improve when ventricular catheters are placed into the frontal horn or trigone of the lateral ventricle. However, techniques for accurate catheter placement have not been developed. The authors recently reported a prospective study designed to test the accuracy of catheter placement with the assistance of intraoperative ultrasound, but the results were poor (accurate placement in 59%). A major reason for the poor accurate placement rate was catheter movement that occurred between the time of the intraoperative ultrasound image and the first postoperative scan (33% of cases). The control group of non ultrasound using surgeons also had a low rate of accurate placement (accurate placement in 49%). The authors conducted an exploratory post hoc analysis of patients in their ultrasound study to identify factors associated with either catheter movement or poor catheter placement so that improved surgical techniques for catheter insertion could be developed. Methods. The authors investigated the following risk factors for catheter movement and poor catheter placement: age, ventricular size, cortical mantle thickness, surgeon experience, surgeon experience with ultrasound prior to trial, shunt entry site, shunt hardware at entry site, ventricular catheter length, and use of an ultrasound probe guide for catheter insertion. Univariate analysis followed by multivariate logistic regression models were used to determine which factors were independent risk factors for either catheter movement or inaccurate catheter location. Results. In the univariate analyses, only age < 6 months was associated with catheter movement (p = 0.021); cortical mantle thickness < 1 cm was near-significant (p = 0.066). In a multivariate model, age remained significant after adjusting for cortical mantle thickness (OR 8.35, exact 95% CI 1.20 infinity). Univariate analyses of factors associated with inaccurate catheter placement showed that age < 6 months (p = 0.001) and a posterior shunt entry site (p = 0.021) were both associated with poor catheter placement. In a multivariate model, both age < 6 months and a posterior shunt entry site were independent risk factors for poor catheter placement (OR 4.54, 95% CI 1.80 11.42, and OR 2.59, 95% CI 1.14 5.89, respectively). Conclusions. Catheter movement and inaccurate catheter placement are both more likely to occur in young patients (< 6 months). Inaccurate catheter placement is also more likely to occur in cases involving a posterior shunt entry site than those involving an anterior shunt entry site. Future clinical studies aimed at improving shunt placement techniques must consider the effects of young age and choice of entry site on catheter location. (http://thejns.org/doi/abs/10.3171/2014.5.peds13481) Key Words ventriculoperitoneal shunt shunt insertion hydrocephalus ventricular catheter Abbreviation used in this paper: HCRN = Hydrocephalus Clinical Research Network. J Neurosurg: Pediatrics / Volume 14 / August 2014 The Hydrocephalus Clinical Research Network (HCRN) recently reported a prospective ultrasound study to evaluate the utility of intraoperative ultrasound guidance for the accurate placement of ventricular catheters. 9 All surgeons who participated in the study attempted to place the catheter tip into the frontal horn or trigone. The rate of accurate placement with ultrasound was only 59%. This was lower than expected. When the intraoperative ultrasound image was compared with 173

W. E. Whitehead et al. the first postoperative scan, which was acquired within days of the surgery, it was clear that a major reason for poor catheter location was catheter movement. Catheters moved from an accurate location in the frontal horn or trigone to an inaccurate location in 33% of the ultrasoundassisted cases. Examples of a catheter that moved significantly and a catheter that did not move are shown in Figs. 1 and 2, respectively. The ultrasound cohort was only slightly better than the control group of non ultrasound using surgeons who achieved accurate placement in 49% of the cases. In the control group, all surgeons used anatomical landmarks to determine the trajectory for catheter insertion; in no case was stereotactic image guidance used. Overall, these results indicate an inability to place shunt catheters accurately using routine surgical techniques. For the entire study group, a total of 53 (45.3%) of 117 evaluated catheters were placed inaccurately. If ventricular catheter placement is a risk factor for shunt failure, we remain unable to optimize our results with a reliable technique for catheter placement. We hypothesized that there were other factors af- Fig. 1. Images illustrating catheter migration after placement. Upper: Intraoperative ultrasound image taken from a left frontal bur hole through the frontal horns and anterior cranial fossa in the coronal plane. The linear catheter touches the floor of the left frontal horn and the septum pellucidum. The plane of this image is anterior to the third ventricle. Lower: Postoperative axial CT scans obtained 1 day after surgery. The tip of the catheter is now in the posterior body of the lateral ventricle adjacent to choroid plexus. Fig. 2. Images illustrating stable catheter placement (no movement). Upper: Intraoperative ultrasound image taken from a right frontal bur hole through the frontal horns and a portion of the anterior third ventricle, but anterior to the foramen of Monro and the choroid plexus, in the coronal plane. The catheter is within the frontal horn away from the septum pellucidum. Lower: Postoperative axial CT scans obtained 1 day after surgery. The tip of the catheter remains in the frontal horn, anterior to the thalamus and lateral to the septum pellucidum. 174 J Neurosurg: Pediatrics / Volume 14 / August 2014

Factors affecting shunt catheter placement fecting the placement of ventricular catheters. These factors would likely negate the advantages of intraoperative ultrasound guidance. We decided to conduct a post hoc exploratory analysis of patients in the ultrasound study to identify factors that may influence final catheter location. Methods Previous HCRN Ultrasound-Guided Shunt Placement Study The methodology of the ultrasound study has been previously published. 9 Briefly, the study was a prospective, controlled trial with the primary outcome (catheter location) assessed by a blinded pediatric neuroradiologist. It was conducted at 4 HCRN centers. Participating pediatric neurosurgeons were required to target the frontal horn or trigone for all ventricular catheter placements. All study patients met the following inclusion criteria: 1) clinical and radiographic evidence of hydrocephalus, as determined by a pediatric neurosurgeon, that requires a ventriculoperitoneal shunt (atrial, pleural, gallbladder, and other shunt systems were excluded); 2) no history of shunt insertion or endoscopic third ventriculostomy for hydrocephalus (a history of an external ventricular drain, subgaleal tapping reservoir, or subgaleal shunt was permissible); and 3) age less than 18 years at the time of shunt insertion. The primary outcome of the original study was the location of the ventricular catheter tip on the first postoperative scan (CT, MRI, or ultrasound). The ventricular catheter tip was defined as the proximal 2 cm of the catheter (the hole-bearing segment). The ventricular catheter location was defined by 1 of the following 8 compartments: frontal horn, trigone, body, temporal horn, third ventricle, fourth ventricle, cistern, or brain. Variables and Data Collection for the Current Study Data collected during the study were reviewed and the following variables were analyzed for their possible association with catheter movement and inaccurate catheter location: experience of attending surgeon (< 10 years vs 10 years); number of ultrasound sound procedures performed by the attending surgeon prior to the study (< 50 vs 50 procedures); patient age (< 6 months vs 6 months); frontal occipital ratio (< 0.55 vs 0.55) 4 ; cortical mantle thickness (< 1 cm vs 1 cm); shunt entry site (anterior vs posterior); shunt equipment at entry site (no right angle device vs right angle device); catheter length; and use of an ultrasound probe guide to pass the catheter (yes vs no). Anterior shunts were defined as those with ventricular catheter entry site near the coronal suture (that is, frontal shunt); posterior shunts were defined as those near the lambdoid suture (that is, occipital or parietal shunts). A right angle device was defined as a right angle connector, a right angle guide, a prefabricated right angle ventricular catheter, or a reservoir with a bottom inlet and a side outlet (for example, a Rickham reservoir). Most bur hole ultrasound transducers are equipped with a built-in guide or groove to assist with catheter placement along a selected trajectory, and data on the use of a guide were collected prospectively during the trial. These variables J Neurosurg: Pediatrics / Volume 14 / August 2014 were selected by review of the literature and by consensus opinion among the HCRN investigators. 2,3,8 Outcomes of the Current Study There were 2 primary outcomes for the current study. The first was ventricular catheter movement. This was defined as a change in catheter location between the intraoperative ultrasound image and the first postoperative scan (for example, frontal horn location on ultrasound and body location on the first postoperative CT [see Fig. 1]). For this analysis, only the ultrasound-guided ventricular placement cohort from the original study was used (n = 55), because in this group both intraoperative images (in the form of an ultrasound printout) and postoperative images had been collected. These two points in time were required for us to determine if catheter movement had occurred. The second primary outcome for the current study was inaccurate catheter location. This outcome was defined as a catheter location on the first postoperative scan that was neither frontal horn nor trigone. For this analysis, both the ultrasound-guided and the non ultrasound guided control group were used (n = 117). Statistical Analysis Each variable defined above was separately compared with each of the 2 primary outcomes (catheter movement and inaccurate catheter location) using chisquare analysis for categorical variables and the t-test for continuous variables. Any variable found to be significant (p < 0.05) or nearly significant (p < 0.10) was included in the multivariate analysis. Logistic regression was used to determine which variables were independently associated with catheter migration or inaccurate catheter location. Results Catheter Movement Results of the univariate analyses for factors associated with catheter migration are shown in Table 1. Of all the factors, only age < 6 months correlated with a higher risk of movement (p = 0.021). Cortical mantle thickness < 1 cm was nearly significant (p = 0.066). A multivariate logistic regression model testing these 2 factors was created. Age < 6 months was identified as an independent risk factor for catheter movement (exact estimate of OR 8.35; exact 95% CI 1.20 infinity); cortical mantle thickness was not predictive in the model. Inaccurate Catheter Location The results of the univariate analyses for factors associated with inaccurate catheter location are shown in Table 2. Age < 6 months and a posterior shunt entry site were both associated with poor catheter placement (p = 0.001 and p = 0.021, respectively). A predictive model was developed using multivariate logistic regression. Both age < 6 months and shunt entry site were tested in this model. Age < 6 months (OR 4.54, 95% CI 1.80 11.42) and posterior shunt entry (OR 2.59, 95% CI 1.14 5.89) were both found to be independent risk factors for inaccurate catheter placement (Table 3). 175

W. E. Whitehead et al. TABLE 1: Univariate analysis for ventricular catheter movement ultrasound for 55 patients* Variable Catheter Movement (%) Movement No Movement p Value no. of patients 18 37 surgeon experience <10 yrs 14 (77.8) 32 (86.5) experience w/ US (<50 cases) 4 (22.2) 4 (10.8) patient age <6 mos 18 (100.0) 27 (73.0) 0.021 frontal occipital horn ratio >0.55 10 (55.6) 24 (64.9) cortical mantle thickness <1 cm 6 (33.3) 3 (8.1) (0.066) shunt entry site anterior 15 (83.3) 32 (86.5) posterior 3 (16.7) 5 (13.5) equipment at entry site no rt angle device 4 (22.2) 6 (16.2) rt angle device 14 (77.8) 31 (83.8) catheter length ± SD (cm) 5.25 ± 1.004 5.14 ± 0.822 probe guide guide used 16 (88.9) 36 (97.3) guide not used 2 (11.1) 1 (2.7) * = not significant; US = ultrasound. Boldface indicates statistical significance. Discussion This exploratory, post hoc analysis of patients in our recently reported ultrasound study identifies age < 6 months as an independent risk factor for shunt catheter movement after initial ultrasound-guided placement. We also identify age < 6 months and posterior shunt entry site as independent risk factors for poor catheter placement. Despite these results, the reasons for catheter migration between the time of intraoperative ultrasound imaging and the first postoperative imaging remain unclear. We know that the movement occurs early because 15 of the 18 patients with catheter migration underwent postoperative imaging on or before postoperative Day 1 (minimum postoperative Day 0, maximum Day 20). A number of events occur between these two time periods, including removal of the catheter stylet and manipulation of the proximal catheter for attachment to the distal shunt, changes in head position, and flow of CSF through the shunt. These factors may affect catheter location. Factors such as use of right angle hardware, choice of entry site, cortical mantle thickness, ventricular size, and surgeon experience may also contribute to movement, but our analysis failed to show a significant effect. Other factors such as skull contour at the point of entry and catheter stiffness were not accounted for. Reasons for movement may also be due to a combination of factors that work differently from patient to patient. For example, the use of a right angle guide may have a beneficial effect in some patients and a detrimental effect in others due to variations in skull contour and entry point. Regardless, this analysis suggests that whatever factors are influencing movement they are less significant after the age of 6 months. Catheter movement did not occur in any patient older than 6 months. The changes in cerebral water content and degree of myelination that occur as the brain matures may explain this observation. As far as we know, movement of the catheter after guided placement has not been reported, although data from the Endoscopic Shunt Insertion Trial also suggested that this movement occurs. 1 We had a unique opportunity to look at this because the study included both an intraoperative image in ultrasound-treated patients and an early postoperative image in these same patients. Catheter movement in our study has implications for the use of image-guided stereotaxy or any other surgical technique for targeting catheter placement. It is possible that the same factors leading to movement of the ventricular catheter after ultrasound-guided placement may also cause the catheter to migrate after image-guided stereotactic placement. Another possible explanation for the movement of the catheter is error in the interpretation of the intraoperative ultrasound image (or in interpretation of the postoperative image). Misclassification of catheter location on one image or the other could make it seem like the catheter was moving when no movement occurred. We do not have the data required to determine if this occurred; one would need to obtain simultaneous intraoperative ultrasound and cross-sectional images. We believe, however, that this is an unlikely source of significant error. With experience, it is fairly easy to distinguish the compartments of the lateral ventricle using ultrasound. The frontal horn, body, and trigone can be distinguished based on the anatomy of the ventricular walls, the presence of a hyperechoic choroid plexus, and the presence of the thalamus. Based on our interpretation of the images, an example of a catheter that moved after placement and a catheter that 176 J Neurosurg: Pediatrics / Volume 14 / August 2014

Factors affecting shunt catheter placement TABLE 2: Univariate analysis for catheter placement accuracy in all 117 study patients Variable Catheter Accuracy Inaccurate Accurate did not move are shown in Figs. 1 and 2, respectively. In Fig. 1 upper, the catheter tip is in the frontal horn on the intraoperative ultrasound image, but on the postoperative CT (Fig. 1 lower) the majority of the catheter tip is in the body of the ventricle, adjacent to the choroid plexus and above the thalamus. In Fig. 2 the catheter stays in the frontal horn on both sets of images. The results of our analysis of poor catheter placement suggest that most of the inaccurate placements occurred in young patients (< 6 months) and that an anterior shunt entry site (that is, a frontal shunt) may provide better accuracy. The association with young age is not surprising since our first analysis links young age to catheter movement. In contrast, the association with entry site is particularly interesting since the choice of entry site is usually at the discretion of the operating surgeon and, therefore, is easily modifiable. Wan and colleagues 8 conducted a retrospective review of 141 pediatric and adult patients to identify possible risk factors for poor catheter placement. They identified young age (< 3 years) and small ventricular size as significant factors affecting poor placement. Shunt entry site was analyzed in this study as well, but the authors made a distinction between a parietal entry site and an occipital entry site. Interestingly, the authors found that a parietal and a frontal entry were associated with similar outcomes, but occipital entry site tended to be associated with a worse outcome. Wan and colleagues also defined catheter placement on a novel 5-point scale based on the amount of the hole-bearing segment of the catheter within the ventricle (2 cm of catheter within ventricle being excellent and 0 cm being poor). Our catheter scoring system is based on the compartments of the lateral ventricles and is derived from the paper by Tuli et al., which showed longer shunt survival when catheter tips were within the frontal horn or trigone. 7 The inclusion of adult patients and the differences in scoring catheter placement make comparisons between our studies unreliable. The present analysis is limited by the small number J Neurosurg: Pediatrics / Volume 14 / August 2014 p Value* no. of patients 53 64 surgeon experience <10 yrs 44 (83.0) 46 (71.9) patient age <6 mos 45 (84.9) 36 (56.3) 0.001 frontal occipital horn ratio >0.55 26 (49.1) 31 (49.2) cortical mantle thickness <1 cm 7 (13.2) 5 (7.8) shunt entry site 0.021 anterior 28 (52.8) 47 (73.4) posterior 25 (47.2) 17 (26.6) equipment at entry site no rt angle device 10 (18.9) 9 (14.1) rt angle device 43 (81.1) 55 (85.9) catheter length ± SD (cm) 6.00 ± 1.47 6.00 ± 1.57 * Boldface indicates statistical significance. TABLE 3: Multivariate regression analysis for inaccurate catheter placement Variable OR (95% CI) p Value patient age <6 mos 4.54 (1.80 11.42) 0.0013 posterior shunt entry site 2.59 (1.14 5.89) 0.023 of patients. We also selected factors based on limited data in the literature. There are multiple factors, as discussed above, that might affect both movement and accurate placement of the catheter that we did not analyze because of our limited sample size and lack of data. Accurate catheter placement is significant because of its association with prolonged shunt survival. 1,7 If reliable techniques for catheter placement can be developed, shunt survival may improve. This study has identified young age (< 6 months) as a population in which accurate catheter placement is difficult to achieve. Young age is already known to be a risk factor for shunt failure based on multiple pediatric hydrocephalus studies. 5,6 It is plausible that the higher shunt failure rate in this population is partially due to the added difficulty of achieving ideal catheter placement in this age group. Clearly, additional study of this group of patients is necessary to improve shunt outcomes. The variables mentioned above (catheter stiffness, catheter length, skull contour at entry site, brain turgor or stiffness, and shunt hardware) could all play a role in limiting our ability to accurately place catheters, and future studies should attempt to measure the effects of these variables and correct for those that adversely affect accuracy. This study also identified shunt entry site as a possible modifiable risk factor for poor catheter placement. The choice of entry site is usually at the surgeon s discretion. Future protocols to improve the accuracy of shunt catheter placement should evaluate the effect of anterior entry site on accuracy and on shunt survival. Conclusions Catheter movement and inaccurate catheter placement are both more likely to occur in young patients (< 6 months). Inaccurate catheter placement is also more likely to occur when a posterior shunt entry site, compared with an anterior shunt entry, has been chosen. Future clinical studies aimed at improving shunt placement techniques must consider the effect of young age and choice of entry site on catheter location. Acknowledgments This work would not have been possible without the outstanding support of the dedicated clinical research personnel at each clinical site and at the Data Coordinating Center. Special thanks go to Sheila Ryan, Amita Bay, Tracey Bach, Arlene Luther, Deanna Mercer, Amy Anderson, Lindsay O Donnel, Brittany Aziz, and Marcie Langley. Disclosure The HCRN has been funded by philanthropy and by a grant from the National Institute of Neurological Disorders and Stroke (grant no. 1RC1068943 01). 177

W. E. Whitehead et al. Author contributions to the study and manuscript preparation include the following. Conception and design: Whitehead, Holubkov, Kestle. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: Whitehead, Holubkov. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Whitehead. References 1. Kestle JR, Drake JM, Cochrane DD, Milner R, Walker ML, Abbott R III, et al: Lack of benefit of endoscopic ventriculoperitoneal shunt insertion: a multicenter randomized trial. J Neurosurg 98:284 290, 2003 2. Lind CR, Tsai AM, Law AJ, Lau H, Muthiah K: Ventricular catheter trajectories from traditional shunt approaches: a morphometric study in adults with hydrocephalus. J Neurosurg 108:930 933, 2008 3. Lind CR, Tsai AM, Lind CJ, Law AJ: Ventricular catheter placement accuracy in non-stereotactic shunt surgery for hydrocephalus. J Clin Neurosci 16:918 920, 2009 4. O Hayon BB, Drake JM, Ossip MG, Tuli S, Clarke M: Frontal and occipital horn ratio: a linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus. Pediatr Neurosurg 29:245 249, 1998 5. Piatt JH Jr, Carlson CV: A search for determinants of cerebrospinal fluid shunt survival: retrospective analysis of a 14- year institutional experience. Pediatr Neurosurg 19:233 242, 1993 6. Tuli S, Drake J, Lawless J, Wigg M, Lamberti-Pasculli M: Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus. J Neurosurg 92:31 38, 2000 7. Tuli S, O Hayon B, Drake J, Clarke M, Kestle J: Change in ventricular size and effect of ventricular catheter placement in pediatric patients with shunted hydrocephalus. Neurosurgery 45:1329 1335, 1999 8. Wan KR, Toy JA, Wolfe R, Danks A: Factors affecting the accuracy of ventricular catheter placement. J Clin Neurosci 18:485 488, 2011 9. Whitehead WE, Riva-Cambrin J, Wellons JC III, Kulkarni AV, Holubkov R, Illner A, et al: No significant improvement in the rate of accurate ventricular catheter location using ultrasoundguided CSF shunt insertion: a prospective, controlled study by the Hydrocephalus Clinical Research Network. Clinical article. J Neurosurg Pediatr 12:565 574, 2013 Manuscript submitted September 25, 2013. Accepted May 7, 2014. Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.5.PEDS13481. Address correspondence to: William E. Whitehead, M.D., M.P.H., Texas Children s Hospital, Clinical Care Center, 6621 Fannin St., Ste. 1230.01, Houston, TX 77030. email: wewhiteh@ texaschildrenshospital.org. 178 J Neurosurg: Pediatrics / Volume 14 / August 2014