Small versus Large Catheters for Ventriculostomy in the Management of Intraventricular Hemorrhage

Accepted Manuscript Small versus large catheters for ventriculostomy in the management of intraventricular hemorrhage Vianney Gilard, MD, Ben Ousmanou Djoubairou, MD, Arnaud Lepetit, MD, Thomas Metayer, MD, Clement Gakuba, MD, PhD, Charlotte Gourio, PharmD, Stephane Derey, MD, PhD, François Proust, MD, PhD, Evelyne Emery, MD, PhD, Thomas Gaberel, MD, PhD PII:

S1878-8750(16)30962-7

DOI:

10.1016/j.wneu.2016.09.105

Reference:

WNEU 4645

To appear in:

World Neurosurgery

Received Date: 23 June 2016 Revised Date:

23 September 2016

Accepted Date: 26 September 2016

Please cite this article as: Gilard V, Djoubairou BO, Lepetit A, Metayer T, Gakuba C, Gourio C, Derey S, Proust F, Emery E, Gaberel T, Small versus large catheters for ventriculostomy in the management of intraventricular hemorrhage, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.09.105. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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ACCEPTED MANUSCRIPT

Small versus large catheters for ventriculostomy in the

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management of intraventricular hemorrhage

Vianney GILARD, MD1*; Ben Ousmanou DJOUBAIROU, MD2*; Arnaud LEPETIT, MD3; Thomas METAYER, MD2; Clement GAKUBA, MD, PhD3,4; Charlotte GOURIO, PharmD5; Stephane DEREY, MD, PhD1; François PROUST, MD, PhD6; Evelyne

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EMERY, MD, PhD2,4; Thomas GABEREL, MD, PhD2,4

1. Department of Neurosurgery, Rouen University Hospital, Rue de Germont, Rouen, FRANCE.

2. Department of Neurosurgery, University Hospital of Caen, Avenue de la Côte de Nacre, Caen, FRANCE.

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3. Department of Anesthesiology and Neurocritical Care, Caen University Hospital, Avenue de la Côte de Nacre, Caen, FRANCE.

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4. Normandie Univ, UNICAEN, INSERM, Sérine protéases et physiopathologie de l’unité neurovasculaire, 14000 Caen, FRANCE

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5. Department of Pharmacy, University Hospital of Caen, Avenue de la Côte de Nacre, Caen, FRANCE.

6. Department of Neurosurgery, Strasbourg University Hospital, 1 Avenue Moliere, Strasbourg, FRANCE.

*: These authors equally contributed to the elaboration of the manuscript.

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ACCEPTED MANUSCRIPT Corresponding Author Information Page: Name: Dr. Thomas Gaberel Address: Service de Neurochirurgie CHU de Caen

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Avenue de la Côte de Nacre F-14000 CAEN FRANCE

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E-mail address: [email protected] Telephone: +33 02 31 06 46 03

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Fax: +33 02 31 06 45 99

KEY WORDS: intraventricular hemorrhage, external ventricular drain, ventriculostomy,

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catheter obstruction, bacterial meningitis, intracerebral hemorrhage.

ABBREVIATIONS LIST

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AVM: arteriovenous malformation; CSF: cerebrospinal fluid; GCS: Glasgow coma scale; EVD: external ventricular drain; ICH: intracerebral hemorrhage; ICP: intracranial pressure;

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IVF: intraventricular fibrinolysis; IVH: intraventricular hemorrhage; LV: lateral ventricle; mRS: modified Rankin Scale; SD: standard deviation

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ACCEPTED MANUSCRIPT ABSTRACT Objective: intraventricular hemorrhage (IVH) often requires the insertion of an external ventricular drain (EVD), but blood clots could occlude the catheters. Large EVD catheters may help to reduce the risk of catheter occlusion. Here, we compared small catheters with

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large catheters for ventriculostomy in patients suffering from IVH.

Methods: We conducted a retrospective cohort study. Patients were included if they had IVH requiring EVD insertion. We then compared baseline characteristics and outcomes of patients

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treated with large catheters to patients treated with small catheters.

Results: Between 2011 and 2015, 227 IVH patients were admitted to our 2 hospitals. Among

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them, 28 were treated in first intention with large catheters and 46 controls were identified. Insertion of large catheter decreased the risk of temporary and permanent catheter occlusion without impact on the occurrence of ICH related to catheter insertion. There was 38.5% more catheter-related infection in the small catheter group when compared with the large catheter

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group, but this result was not significant. There was no impact on functional outcomes. Surprisingly, the rate of death was higher in the large catheter group. Conclusions: In patients suffering from IVH, the use of large catheters for EVD reduced the

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risk of catheter occlusion without increasing the risk of ICH related to catheter insertion. The risk of catheter-related infection may subsequently be decreased by using large catheters. A

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prospective randomized trial would appear to be necessary to seek out any benefits that large catheters may provide for the risk of death and functional outcome.

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ACCEPTED MANUSCRIPT INTRODUCTION In cases of intracranial hemorrhage, blood can sometimes raise the cerebral ventricles, and induce intraventricular hemorrhage (IVH). IVH is a devastating form of intracranial bleeding, and can be caused by hypertensive hemorrhagic stroke, aneurysm rupture, arteriovenous

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malformation (AVM) rupture or head trauma.1 When blood enters the ventricles, it starts to clot, thus impairing the cerebrospinal fluid (CSF) flow, leading to obstructive hydrocephalus. Moreover, blood clots have toxic properties on the ependymal and adjacent parenchyma, and

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exert a mass effect on the adjacent brain structures.2 To control a rise in acute intracranial pressure (ICP) caused by hydrocephalus, and to remove the blood from the ventricles, an

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external ventricular catheter often has to be inserted .3 The catheters used for ventriculostomy usually have a small diameter (i.e. inner diameter = 1.5 mm) to limit parenchymal injury during insertion.4 But because of the blood clots, small catheters often become obstructed, which may induce: (1) Poor control of the ICP, because ICP cannot be monitored, and CSF

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cannot be removed; (2) An increased risk of bacterial meningitis because obstruction requires catheter irrigation and/or changing the catheter; (3) An increased risk of iatrogenic intracerebral hemorrhage (ICH) in case of repeated catheter changes; (4) For all of these

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reasons, worse clinical outcome.

To limit the risk of catheter obstruction, a large catheter with an inner diameter = 2.3 mm was

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developed and gave interesting results in a prospective cohort of patients with hydrocephalus with or without IVH .5 Here, we hypothesized that in patients with IVH, the use of large catheters could decrease the risk of obstruction, in turn reducing the risk of complications related to catheter manipulation and insertion, and, lastly, the outcome. To evaluate this, we performed a retrospective cohort study comparing IVH patients treated with small catheters to patients treated with large catheters.

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ACCEPTED MANUSCRIPT MATERIAL AND METHODS Reporting on this cohort study is in accordance with the STROBE statements. It was reviewed and approved by the Institutional Ethics Committee of Caen University Hospital (Caen, France).

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Setting and study design

This study is based on data provided by two prospective registries from two tertiary neurosurgical units (University Hospital of Caen and University Hospital of Rouen, France).

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These registries prospectively included all the adult patients suffering from IVH admitted to our hospitals. Using these registries, we performed a retrospective cohort study in which IVH

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patients treated with large catheters were matched with IVH patients treated with small catheters (1:2 ratio) to compare their outcomes. Participants

All the adult patients (≥ 18 years old) suffering from IVH diagnosed on CT-Scan, whatever

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the etiology of the IVH, and admitted to our departments from January 2011 to September 2015 were prospectively included in the registries. EVD was inserted if patients had hydrocephalus on their CT-scans associated with a decreased level of consciousness (Glasgow

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Coma Scale [GCS] ≤ 13). The choice to insert large catheters (2.3 mm inner diameter, 4 mm outer diameter, Sophysa, France) or small catheters (1.5 mm inner diameter, 3 mm outer

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diameter, Sophysa, France) was at senior surgeon’s discretion. Of note, the two types of catheter were not antibiotic-impregnated. Patients were then managed according to a predefined protocol following current recommendations, depending on the underlying cause of bleeding.6,7 We used the register from the hospital pharmacy to identify patients who had large catheters inserted. These patients, with IVH and large catheters for the first EVD insertion, were defined as large catheter group. Small catheter group were defined as patients with IVH and small catheters inserted in first intention. Every large catheter group patient

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ACCEPTED MANUSCRIPT was, if possible, matched with two small catheter group patients, based on: (a) the initial Graeb score on CT-scan (+/- 1 point)8, (b) the etiology of the IVH (Supratentorial ICH, Infratentorial ICH, Ruptured aneurysm, Ruptured AVM, Other). It should be pointed out that

received intraventricular fibrinolysis (IVF)1 were excluded. Variables

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patients who received both types of catheter during their hospitalization, and patients who

The following baseline characteristics were retrospectively reviewed: age; sex; historical

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modified Rankin Scale (mRS), defined as the mRS before the ictus (mRS 0 versus mRS ≥ 1); use of anti-platelet and/or anticoagulant therapy; the IVH etiology: supratentorial ICH,

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infratentorial ICH, ruptured aneurysm, ruptured AVM, other; the initial GCS (3-7; 8-12; 1315); the pupillary status on admission: bilateral myosis, unilateral mydriasis, bilateral mydriasis; the presence of hemiplegia or hemiparesis on admission; the Graeb score (0-12) on the initial brain CT-scan8; the presence of blood in the third and/or fourth ventricle on the

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initial CT-Scan; the degree of hydrocephalus evaluated by the Evans ratio (Bi-caudate distance / Bi-parietal distance at the level of the foramen of Monroe); the presence of an associated intracerebral hematoma; the ICH volume in case of an associated ICH (measured

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with the ABC/2 method)9; the presence of blood within the lateral ventricle (LV) receiving the catheter on the initial CT-scan; and the total duration of EVD (until definitive removal or

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insertion of an internal shunt). The following outcomes data were then collected: temporary catheter occlusion, defined as occlusion of the catheter requiring catheter irrigation5; permanent catheter occlusion, defined as a persistent occlusion despite irrigation, and requiring the change of the catheter5; the occurrence of an intracranial hematoma related to EVD placement, defined as a new ICH identified on a CT-scan performed after EVD insertion that was not present before EVD insertion4; symptomatic intracranial hematoma related to EVD placement, defined as a new

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ACCEPTED MANUSCRIPT ICH related to EVD insertion associated with a new clinical manifestation (deficit, major ICP rise, mydriasis)4; occurrence of a catheter-related infection defined as a clinical picture of infection – i.e. cranial nerve signs, headache, photophobia, seizures, stiff neck, altered mental status, irritability, inflammation at the catheter site, and fever - associated with a positive CSF

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culture; the need for placing an internal CSF shunt10; functional outcomes at 6 months in survivals using the mRS (0-5), with individualization of a good functional outcome (mRS = 0-3) and a poor functional outcome (mRS = 4-5); the rate of death at 6-month follow-up.

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Statistical Analysis

For the analysis, we used SAS v9 software. Characteristics of large and small catheter groups

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were compared using the Fisher’s exact tests for discrete variables and the Wilcoxon-MannWhitney test was used for continuous variables. Statistical significance was set at the 0.05

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RESULTS Participants (Figure 1) Between January 2011 and September 2015, 118 patients with IVH were admitted to the

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University Hospital of Caen, and 109 were admitted to the University Hospital of Rouen, amounting to a total of 227 ICH patients. Among these 227 patients, 33 patients had a large EVD inserted. Five were excluded as they received IVF, leaving 28 patients. We matched

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these patients with 46 patients treated with small catheters: 18 patients in the large catheter group were effectively matched with 2 patients treated with small catheter , but 10 patients in

We then compared these two groups. Baseline characteristics (Table 1)

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the large catheter group could only be matched with one patient treated with small catheter.

Overall, the small catheter group and the large catheter group had similar baseline

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characteristics, except for the associated ICH volume. Age, sex, anticoagulant therapy and etiology of the IVH were similar among the two groups. But even if the differences were not significant, patients treated with large catheters may have a more severe initial status than

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those treated with small catheters: they had a worse initial GCS (GCS 3-7: 46.4% versus 28.3% respectively, p=0.13; GCS 8-12: 32.1% versus 41.3% respectively, p=0.46; GCS 13-

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15: 21.4% versus 30.4% respectively, p=0.43), they had more unilateral mydriasis (21.4% versus 15.2% respectively, p=0.54), more hemiplegia (46.4% versus 34.8% respectively, p=0.34) and had associated ICH more often (78.5% versus 63.0% respectively, p=0.20), with an associated ICH volume significantly higher in the large catheter group (22.9+/-18.4 ml versus 14.6+/-19.1 ml, p=0.03) On the other hand, the characteristics related to the risk of catheter occlusion were similar among the two groups: the initial Graeb score (7.3 +/- 2.4 in the large catheter group versus

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ACCEPTED MANUSCRIPT 7.2 +/- 2.6 in the small catheter group, p=0.68), presence of blood in the third and/or fourth ventricle (92.8% in the large catheter group versus 89.1% in the small catheter group, p=0.70), the Evans ratio (0.33 +/- 0.07 in the large catheter group versus 0.31 +/- 0.07 in the small catheter group, p=0.94), the presence of blood in the lateral ventricle ipsilateral to the

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catheter (71.4% in the large catheter group versus 76.1% in the small catheter group, p=0.78) and the EVD duration (19.8 +/- 14.5 days in the large catheter group versus 16.6 +/- 8.3 days in the small catheter group, p=0.63).

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Outcomes data and main results (Table 2, Figure 2)

The number of temporary occlusions was 5.8 times higher in the small catheter group (0.41

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+/- 0.65) than in the large catheter group (0.07 +/- 0.26, p=0.01). The same finding was observed concerning the number of permanent occlusions requiring catheter changes, which was 2.2 times higher in the small catheter group (0.54+/-0.65) than in the large catheter group (0.25+/-0.52, p=0.04). The type of catheter did not influence the risk of ICH related to EVD

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insertion (8.7% in the small catheter group versus 7.1% in the large catheter group, p=1), or the risk of symptomatic ICH related to EVD insertion (p=1). The risk of catheter-related infection was similar among the two groups, although there was a slight increase in the small

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catheter group (17.4% versus 10.7%, p=0.52). The rate of permanent CSF shunting was similar among the two groups (p=1). Surprisingly, the rate of death was higher in the large

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catheter group (42.8%) than in the small catheter group (19.5%, p=0.04). Among the survivals, the rate of good functional outcome (mRS 0-3) was similar among the two groups (91.9% in the small catheter group versus 89.5% in the large catheter group, p=0.63).

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DISCUSSION Main results and limits The present cohort study comparing large catheters versus small catheters in the management

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of IVH showed that large catheters had fewer temporary and permanent occlusions than small catheters, which may lead to a decreased risk of catheter-related infection. It should be pointed out that ICH related to catheter insertion did not increase in the large catheter group.

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Despite the interesting benefits of large catheters to the aforementioned intermediary outcomes, patients treated with large catheters had a higher rate of death and there was no

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benefit to functional outcomes. We believe that this effect was not related to the catheter per se, but to a selection bias. The choice between large or small catheters was at the surgeon’s discretion, and we hypothesized that patients who received large catheters were perceived by physicians as more severe cases, and therefore more prone to EVD complications, than the

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patients treated with small catheters. This selection bias is also suggested by the baseline characteristics of the two groups: patients in the large catheter group seemed to have a worse initial status, although this was mainly not significant. They had a lower initial GCS and more

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frequently displayed mydriasis, hemiplegia, ICH and larger-sized ICHs. The sum of these small differences may explain the increased rate of death in the large catheter group,

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especially because we did not identify any intermediate phenomena (catheter insertion-related ICH, catheter obstruction, catheter-related infections, etc.) that could explain such differences. Of note, we have initially tried to match patients based on the initial GCS to limit the differences of initial neurological status among the two groups. But unfortunately it dramatically decreased the number of patient in the small catheter group. Given the fact that our study was exploratory, and that the first hypothesis we wanted to test was that large

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ACCEPTED MANUSCRIPT catheter are less subject to occlusion, we decided to match our patients according to the factors influencing catheter occlusion. One could argue that such a selection bias could preclude any interpretation of our study. We believe that the interpretation of functional outcomes and the rate of death are not possible

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due to this bias. But as we matched patients using the Graeb score and the etiology of the IVH, the factors influencing EVD occlusion and ICH related to catheter insertion were comparable in the two groups. Moreover, regarding the fact that patients in both groups had

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the same duration of EVD (16.6 versus 19.8 days), we think that comparison between these two groups for the intermediary outcomes remains useful.

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We should also point out other limits to this study. First, there is the fact that the data were collected retrospectively, which per se induces a risk of bias. We reduced the risk of recruitment bias, however, because the patients included in this study were extracted from a prospective registry. Another limit of this study is its small sample size, which reduces its

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statistical power and also did not allow us to perform multivariate analysis. But on the other hand, its external validity appears satisfactory to us, as our study was conducted at two different centers.

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Moreover, we used non impregnated antibiotics catheter, which may in part explain our relatively high level of catheter related infection. Maybe the use of impregnated antibiotic

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catheter could decrease this risk, even if this has to be more thoroughly evaluated.11 Finally, the use of large catheter in IVH patients has to be evaluated when associated to intraventricular fibrinolysis, a promising treatment evaluated by the CLEAR-IVH trial and for which the final report of this study is expected soon.12 Interpretation This study confirmed the fact that, in cases of intraventricular hemorrhage, the risk of EVD obstruction, probably by blood clots, is decreased when large catheters are used. Our results

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ACCEPTED MANUSCRIPT confirmed those obtained in a cohort of patients requiring EVD and suffering from different pathologies, with or without IVH.5 In their interesting study, Fargen et al. showed that the risk of permanent occlusion was increased when small catheters were used, which is similar to our results in IVH patients. Moreover, small and large catheters had the same impact on the risk

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of ICH related to catheter insertion, which in most cases has little clinical impact, but can sometimes be deleterious.4

Temporary catheter occlusion requires catheter irrigation in the ICU, a procedure that is not

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perfectly aseptic in most cases. For this reason, we hypothesized that temporary catheter occlusion may increase the risk of catheter-related infection. Moreover, permanent catheter

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occlusion requiring EVD change is known to increase the risk of catheter-related infection.13 We can therefore postulate that the use of large catheters may reduce the risk of catheterrelated infection, as suggested by our data: there was 1/3 fewer infections in the large catheter group when compared with the small catheter group, although this did not reach statistical

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significance. We believe, however, that this constitutes an interesting preliminary result for further investigations. Lastly, despite the encouraging results on the intermediate criteria, we failed to show a beneficial effect on functional outcomes, and we even demonstrated an

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increased risk of death in the large catheter group. As mentioned previously, we believe that this finding is related more to a selection bias than to a real effect of large catheter use,

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particularly because there is no obvious causal relationship between these two facts, and also because it is known that the risk of death increases with the number of EVD insertions.14 Another benefit using large catheters in IVH patients may be economical: it has been reported that, due to additional catheter insertions and CT-scans, the cost of occlusion is $615 per patient.5 Reducing the risk of catheter occlusion by using large catheters could help to reduce this cost.

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CONCLUSION

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In patients with IVH, the use of large catheters for EVD reduced the risk of temporary and permanent occlusion of the catheter. In turn, this may reduce the risk of catheter-related infection without increasing the risk of ICH related to catheter insertion. Despite

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disappointing results on the risk of death, this study highlights the interest of large catheters in the management of IVH patients. To complete the data described here, we believe that a

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randomized controlled trial is needed to address with a sufficient power whether or not the use of large catheters decreases the risk of catheter-related infection, but more generally to

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evaluate their impact on the death rate and functional outcomes in the same population.

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The authors declare that they have no conflicts of interest.

FINANCIAL DISCLOSURE

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None.

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CONFLICTS OF INTEREST

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FUNDING

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This work was supported by the Société Française de Neurochirurgie [2015].

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REFERENCES

1-Gaberel T, Magheru C, Emery E. Management of adult intraventricular hemorrhage. Neurosurg Rev. 2012; 35: 485-494.

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2-Hanley DF. Intraventricular hemorrhage and ICH outcomes: severity factor and treatment

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target. Stroke. 2009; 40: 1533–1538.

3-Nieuwkamp DJ, de Gans K, Rinkel GJ, Algra A. Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: A systematic review of the literature. J Neurol. 2000; 247: 117-121.

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4-Miller C, Tummala RP. Risk factors for hemorrhage associated with external ventricular drain placement and removal. J Neurosurg [Epub ahead of print April 1, 2016. DOI:

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10.3171/2015.12.JNS152341].

5-Fargen KM, Hoh BL, Neal D, O'Connor T, Rivera-Zengotita M, Murad GJ. The burden and

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risk factors of ventriculostomy occlusion in a high-volume cerebrovascular practice: results of an ongoing prospective database. J Neurosurg. 2016; 124: 1805-1812.

6-Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012; 43: 1711-1737.

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ACCEPTED MANUSCRIPT 7-Hemphill JC, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman, M et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

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Stroke. 2015; 46: 2032-2060.

8-Graeb DA, Robertson WD, Lapointe JS, Nugent RA, Harrison PB. Computed tomographic diagnosis of intraventricular hemorrhage. Etiology and prognosis. Radiology. 1982; 143: 91-

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96.

9-Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral

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hemorrhage: a powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993; 24: 987993.

10-Lewis A, Wahlster S, Karinja S, Czeisler BM, Kimberly WT, Lord AS. Ventriculostomy-

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related infections: The performance of different definitions for diagnosing infection. Br J Neurosurg. 2016; 30: 49-56.

11-Root BK, Barrena BG, Mackenzie TA, Bauer DF. Antibiotic Impregnated External

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Ventricular Drains: Meta and Cost Analysis. World Neurosurg. 2016; 86: 306-315.

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12-Ziai WC, Tuhrim S, Lane K, McBee N, Lees K, Dawson J et al. A multicenter, randomized, double-blinded, placebo-controlled phase III study of Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III). Int J Stroke. 2014; 9: 536-542.

13-Lo CH, Spelman D, Bailey M, Cooper DJ, Rosenfeld JV, Brecknell JE. External ventricular drain infections are independent of drain duration: an argument against elective revision. J Neurosurg. 2007; 106: 378-383.

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ACCEPTED MANUSCRIPT 14-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. J Clin

FIGURE LEGENDS:

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Figure 1: Flowchart of the patient selection process.

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Neurosci. 2014; 21: 623-632.

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Figure 2: Main outcomes of IVH patients treated with small or large catheters for EVD. (a) The risk of temporary occlusion of the catheter requiring irrigation decreased in the large catheter group when compared with the small catheter group. *: p ≤ 0.05. (b) The same observation was made for permanent catheter occlusion: large catheters decreased the risk of

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catheter changes. *: p ≤ 0.05. (c) The use of large or small catheters for EVD had no impact on the risk of symptomatic intracerebral hemorrhage related to catheter insertion. ns: nonsignificant. (d) Even if non-significant, the use of large catheters may reduce the risk of

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catheter related infection. ns: non-significant. (e) The type of catheter used had no impact on functional outcomes evaluated by mRS at six-month follow-up in surviving patients. ns: non-

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significant. (f) Unexpectedly, the rate of death was higher in the large catheter group when compared with the small catheter group. *: p ≤ 0.05.

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ACCEPTED MANUSCRIPT Table 1: Comparison of baseline characteristics of IVH patients treated with small or large EVDs. Small catheter (n=46) 54.9 +/- 14.7 23 (50.0) 7 (15.2) 7 (15.2)

Large catheter (n=28) 52.8 +/- 12.8 12 (42.8) 4 (14.2) 4 (14.2)

p value 0.54 0.63 1 1

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Age, years (mean +/- SD) Female sex, n (%) Historical mRS≥1, n (%) Anti-platelet / Anticoagulant therapy, n (%) Etiology: Supratentorial ICH, n (%) 16 (34.8) 9 (32.1) 1 Infratentorial ICH, n (%) 7 (15.2) 4 (14.1) 1 Ruptured aneurysm, n (%) 20 (43.4) 12 (42.8) 1 Ruptured AVM, n (%) 2 (4.3) 2 (7.1) 0.63 Other, n (%) 1 (2.2) 1 (3.6) 1 Initial GCS, (%) 3-7 13 (28.3) 13 (46.4) 0.13 8-12 19 (41.3) 9 (32.1) 0.46 13-15 14 (30.4) 6 (21.4) 0.43 Pupil status on admission: Bilateral myosis, n (%) 39 (84.8) 22 (78.5) 0.54 Unilateral mydriasis, n (%) 7 (15.2) 6 (21.4) 0.54 Bilateral mydriasis n (%) 0 (0) 0 (0) 1 Hemiplegia, n (%) 16 (34.8) 13 (46.4) 0.34 Graeb score (mean +/- SD) 7.2 +/- 2.6 7.3 +/- 2.4 0.68 Presence of blood in the third 41 (89.1) 26 (92.8) 0.70 and/or fourth ventricles, n (%) Evans ratio (mean +/- SD) 0.31 +/- 0.07 0.33 +/- 0.07 0.94 Associated intracerebral 29 (63.0) 22 (78.5) 0.20 hematoma, n (%) Associated ICH volume (mean 14.6 +/- 19.1 22.9 +/- 18.4 0.03 +/- SD) Blood within the LV receiving 35 (76.1) 20 (71.4) 0.78 the catheter, n (%) Total duration of EVD, days 16.6 +/- 8.3 19.8 +/- 14.5 0.63 (mean +/- SD) mRS, modified Rankin Scale; SD, standard deviation; ICH, intracerebral hemorrhage; AVM, arteriovenous malformation; GCS, Glasgow Coma Scale; LV, lateral ventricle; EVD, external ventricular drainage.

ACCEPTED MANUSCRIPT Table 2: Comparison of outcomes in IVH patients treated with small or large EVDs. Small catheter (n=46) 0.41 +/- 0.65 0.54 +/- 0.65 4 (8.7)

Large catheter (n=28) 0.07 +/- 0.26 0.25 +/- 0.52 2 (7.1)

p value

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Temporary occlusion (mean +/- SD) 0.01 Permanent occlusion (mean +/- SD) 0.04 Intracranial hematoma related to EVD 1 placement, n (%) Symptomatic intracranial hematoma 1 (2.2) 1 (3.5) 1 related to EVD placement, n (%) Catheter-related infection, n (%) 8 (17.4) 3 (10.7) 0.52 Internal CSF shunting, n (%) 14 (30.4) 8 (28.5) 1 mRS 0-3 at 6 months in survivals, n (%) 34/37 (91.9) 14/16 (87.5) 0.63 Death, n (%) 9 (19.5) 12 (42.8) 0.04 SD, standard deviation; EVD, external ventricular drainage; CSF, cerebrospinal fluid; mRS, modified Rankin scale

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ACCEPTED MANUSCRIPT Highlights

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External ventricular drain occlusion is frequent in intraventricular hemorrhage The use of large catheter decreases the risk of catheter occlusion The use of large catheter may decrease the risk of catheter related infection Large catheter may be useful for the management of intraventricular hemorrhage

AC C

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