Intraventricular administration of rt-PA in patients with intraventricular hemorrhage.

Objective: Intraventricular hemorrhage (IVH) represents a clinicopathologic entity with a dismal prognosis. The associated mortality rate has been reported as high as 80%; the morbidity is also quite high. The use of various fibrinolytic agents (streptokinase, urokinase, and recombinant tissue-type plasminogen activator [rt-PA]) has been reported in a small number of clinical series with a very limited number of participants, yielding significant variability regarding inclusion criteria, treatment protocol, and outcome analysis.

Methods: In our prospective study, we report our experience using rt-PA in 21 patients with IVH. Patients with IVH of aneurysmal or arteriovenous malformation origin were excluded. Intraventricular administration of rt-PA was initiated within 24 hours after the ictal event (dose, 3 mg every 24 hours) through a ventricular catheter. The patients' intracranial and cerebral perfusion pressures, cerebrospinal fluid (CSF) cell count, and head CT scans with emphasis to frontal horn dimension and inner cranium diameter at the same level ratio were collected and analyzed.

Results: Good outcome was observed in 47.5% of our patients, whereas 28.5% died and 24.0% survived with severe disability. The development of rt-PA-associated complications was as follows: new hemorrhage in 19%, infection in 14.3%, and CSF pleocytosis in 100% of patients. Permanent CSF shunt was required in 40%. The intermediate (3-month) follow up of our survivors showed no significant outcome changes compared with the immediate (1-month) follow up.

Conclusions: Intraventricular administration of rt-PA appears to be beneficial in cases of IVH even though it is occasionally associated with serious complications. Further multi-institutional studies are required for validating this treatment modality and standardizing its parameters.

Key Words: hydrocephalus, infection, intraventricular hemorrhage, outcome, rt-PA

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Intraventricular hemorrhage (IVH) can be differentiated into primary and secondary types. (1,2) In the primary type, IVH is an isolated phenomenon, whereas in the secondary type, it is the result of an expansion of intraparenchymal or subarachnoid hemorrhage into the ventricular system. (1) Occurrence of the secondary type (70%) significantly outnumbered the primary type (30%). (1,3) In the cases of primary IVH, the source is either ventricular or originates from a lesion extending to the ventricular wall. (1) The most common cause of secondary IVH is hypertensive intraparenchymal hemorrhage, and in these cases, the presence of IVH represents a strong independent indicator of poor prognosis. (4) The mortality rate of secondary IVH has been reported as high as 80%; the associated morbidity of the survivors is even higher. (3,5-8)

It has been well documented that the presence of IVH significantly compromises cerebrospinal fluid (CSF) absorption, with a consequent increase of the IC pressure (ICP). (1) The pathophysiologic mechanism of this phenomenon can be explained by the obliteration of the arachnoid villi by blood clots and by the development of adhesive arachnoiditis in response to irritative blood degradation products. (1,4,9) In addition to increased ICP, impaired CSF circulation and absorption directly compromises the periventricular microcirculation, with subsequent local ischemia, a phenomenon of significant clinical impact, especially when the third and fourth ventricles are involved, in which case ischemic changes affect the adjacent brainstem. (1,10)

The current treatment strategy for the management of IVH includes the establishment of an external ventriculostomy (usually bilateral, depending on the severity and the distribution of the IVH) and the early drainage of CSF. (1,3,11-13) Because blood clots often obstruct the external ventriculostomies, however, there are significant technical difficulties associated with this procedure, (1,3,11-13) Several investigators have reported the use of various fibrinolytic agents in the management of this problem, with varying results. (14-24) We are reporting our observations of the clinical use of intraventricularly administered recombinant tissue-type plasminogen activator (rt-PA) in patients with IVH.

Materials and Methods

Our retrospective, clinical study was performed under the approval of our institutional review board committee. A written consent form was signed by all the participants or their legal representatives. Patient data were appropriately analyzed according to the current HIPAA regulations.

Over a period of 9 years (1995 to 2003), a total of 84 patients were admitted to the Neurointensive Care Unit (NICU) of our institution with the diagnosis of severe IVH. A subgroup of 21 patients (10 males and 11 females) met the inclusion criteria for participating in the rt-PA branch of our study. The inclusion criteria included the occurrence of a spontaneous IVH with or without accompanying intraparenchymal hemorrhage of nonaneurysmal or arteriovenous malformation origin, a minimum age of 18 years, normal clotting studies (taken on patient admission), the absence of any documented systemic coagulopathy, an admitting Glasgow Coma Scale (GCS) score less than or equal to 8, and a Graeb score greater than 5. The mean age of these patients was 56.4 years; age range was 31 to 78 years. In 18 patients (85.7%), the IVH was secondary, whereas in 3 patients (14.3%) it was of primary origin. Patients with a suspicion of aneurysmal or arteriovenous malformation subarachnoid hemorrhage and IVH were excluded from our study. The causes of IVH for our cases are summarized in Table 1. The patients excluded from the rt-PA branch of our study were traditionally treated by inserting external ventriculostomy and were considered a control group. This control group consisted of 63 patients (29 males and 34 females) with ages ranging from 28 to 81 years, with a mean age of 51.7 years. Among this control group, 28 patients had IVH secondary to an aneurysmal rupture, 5 patients had IVH as a result of a ruptured parenchymal arteriovenous malformation, 17 patients had primary IVH but were excluded from the rt-PA group because of coagulopathy, and 13 patients refused to be included in the rt-PA treatment branch of our study.

The patients' admitting GCS scores ranged from 5 to 7, with a mean score of 6.1. Their radiographic workup included head CT and brain MRI and MRA studies; on certain occasions, MRI of the cervical spine was also obtained (patients 12 and 20). Patient IVH was graded according to the Graeb classification system (Table 2). The mean IVH Graeb score in our series was 9.5, with a range from 6 to 12 (Table 1).

The admitting laboratory workup of our patients included cell blood count with differential, serum electrolytes, blood glucose, blood urea and nitrogen, serum protein, serum cholesterol, and lipids, whereas emphasis was given in the coagulation profile by obtaining PT and PTT. Patients with abnormal clotting studies were excluded from the study. No systemic anticoagulants were administered to our patients during their stay in the NICU.

All the patients underwent an external ventriculostomy within the first 24 hours after their ictal event. Using the standard sterile technique--and under local anesthesia and sedation whenever necessary--a frontal twist-drill hole was placed and a ventricular catheter (Codman, Raynham, MA) was inserted into the lateral ventricle, appearing more compromised on CT scan. In four patients (19.0%), bilateral external ventriculostomies were performed because of the presence of extensive intraventricular blood clots in both lateral ventricles. In these cases, IVH was symmetric, and the lateral ventricle ipsilateral to the nondominant hemisphere was chosen. The ventricular catheters were tunneled under the skin and externalized 2.5 cm distal to the entry point and were secured to the skin. Patient ICP and cerebral perfusion pressure (CPP) and waveforms, arterial blood pressure, central venous pressure, systemic temperature, and electrocardiography were monitored. All of the patients were placed on antibiotic prophylaxis (1 g ceftriaxone IV every 24 hours). Daily CSF specimens were obtained, and a sample was analyzed, measuring for glucose, protein, cell count with differentiation, Gram stain, cultures, and sensitivity.

Intraventricular fibrinolytic therapy was initiated within 24 hours after the ictal event. Three milligrams of appropriately prepared rt-PA was administered every 24 hours through the ventricular catheter. Two milliliters of sterile water was used to flush the system after the rt-PA administration. The catheter was kept closed for 60 minutes after each administration and then opened for draining under the following parameters; The draining chamber was set at 0 mm Hg, relative to the patient's external auditory meatus, and draining for 10 minutes was performed when an ICP of greater than 20 mm Hg persisted for more than 5 minutes. The end point for administering rt-PA was either the development of a new hemorrhage, the resolution of the initial IVH, or the attainment of a maximum dose of 15 mg. A thorough neurologic examination was performed on a twice-daily basis. Daily CT scans were obtained from all of our patients. The ratio FH/ID (where FH is the largest width of the frontal horns of the lateral ventricles, and ID is the internal diameter from inner table to inner table at the same level) was calculated before the administration of rt-PA and after completing the last dose.

The Glasgow Outcome Scale (GOS) score on discharge from the hospital and again 3 months later, the length of stay in the NICU, the time required for blood clot lysis, the length of draining time, the development of any procedure-related or treatment-related complications, the need for inserting a permanent ventriculoperitoneal (VP) shunt system, and, finally, the total length of hospitalization were all documented.

Results

The average total rt-PA dose in our series was 11 mg (range, 6 to 15 mg). The mean time required for intraventricular blood clot lysis was 4.5 days, with a range of 3 to 7 days. In four patients (19.0%) the administration of rt-PA did not dissolve the intraventricular blood clots. The range of the pre-rt-PA administration FH/ID ratio (based on the admitting CT scans) was between 0.5 and 0.7, with a mean of 0.6; after completing intraventricular administration of rt-PA, the range of this ratio grew to 0.4 to 0.8, with a mean of 0.5. The range of ventricular drainage time was 3 to 11 days, with a mean duration of 6.8 days; among surviving patients, the range of CSF drainage was 4 to 11 days, with a mean of 7.5 days.

Regarding the development of posthemorrhagic hydrocephalus, 6 of 15 patients (40%) required the placement of a permanent ventriculoperitoneal shunt during hospitalization, and one patient (6.7%) had a shunt inserted at another institution 2 weeks after discharge. The percentage of permanent VP shunt insertion among survivors of the control group treated only with ventriculostomy in our department during the same period was 62.5% (5 of 8). The same percentage in historic control groups has been reported from 40% (25) to 60%. (20) Among patients who survived, the range of the length of stay in the NICU was 7 to 13 days (mean, 10.1 days); the length of total hospitalization ranged from 11 to 32 (mean, 19.6 days).

The development of a new hemorrhage was documented in four patients (19.0%): two cases of intraparenchymal and two of intraventricular. Two of these patients died, whereas the other two were conservatively treated and finally discharged from the hospital. The average total dose of rt-PA among these patients was 12 mg (range, 9 to 15 mg); their admitting mean GCS score was 6 (range, 5 to 7) and their mean Graeb score was 10. (9-12) In three of these patients, the cause of the IVH was chronic arterial hypertension; the last had been diagnosed with systemic lupus erythematosus.

Three patients (14.3%) had positive CSF cultures, all of whom subsequently died. Characteristically, all of them had predisposing factors for development of infections (diabetes mellitus in two patients, chronic cocaine abuse in the third). In the control group treated solely with ventriculostomy in our institution, infection occurred in 11 of 58 patients (18.9%). All of the patients had various degrees of CSF pleocytosis, which was observed after the second day of rt-PA administration. This pleocytosis persisted for more than 4 days.

The mean GOS score on discharge was 3.0. More specifically, six patients (28.5%) died, one patient (4.7%) had a score of 2, four patients (19.0%) had a score of 3, six patients (28.5%) had a score of 4, and four patients (19.0%) had a score of 5. Comparatively, the mortality rate in the control group was significantly higher (87.3%, 55 of 63); among the survivors, 87.5% (7 of 8) had GOS scores of 2 and 3 and only 12.5% (1 of 8) had a score of 4. The mortality rate of historic control groups varies from 60 to 91%, which is indicative of the dismal prognosis of patients with severe IVH. (3,26-29) The GOS scores at 3 months presented minimal changes in our series: four patients (26.7%) had a score of 3, seven patients (46.7%) had a score of 4, and four patients (26.7%) had a score of 5.

Statistical analysis of our data was performed by using a Spearman rank order correlation test. Evaluating the relation between the admitting GCS score and the GOS score (after 1 month) revealed a significant positive correlation (= 0.51863 and P = 0.0160). Regarding the relation between the admitting Graeb score and the GOS score, there was a statistically significant negative correlation (= 0.83962 and P < 0.001) (Figs. 1 and 2).

Discussion

Fibrinolytic agents (urokinase, rt-PA, streptokinase) have been used in the treatment of lysis of intraparenchymal hematomas, (30) posthemorrhagic hydrocephalus in preterm infants, (31,32) IVH in preterm infants, (31,32) lysis of cisternal clots associated with aneurysmal subarachnoid hemorrhage, (33,34) and IVH of various etiologies in adults. (9,14-24,35-37) The body of evidence addresses the use of urokinase in the treatment of IVH, which increased significantly after the innovative work of Pang et al (9,35) regarding the lysis of intraventricular blood clots with urokinase in a canine experimental model. The discontinuation of the production of urokinase in the United States, however, directed clinical investigation to the use of rt-PA in treating IVH. Some limited clinical series, albeit with significant variability in their results and the causality of IVH and also in the dosology of the administered rt-PA, have been reported in the literature. (14,15,17,18,26)

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

The rationale for using rt-PA for intraventricular blood clot lysis has been adequately described by Goh and Poon (14): rt-PA is thought to enhance the normal fibrinolytic process within the CSF pathways and therefore can be considered more physiologic than the previously used fibrinolytic agents (eg, urokinase). (14) An increasing body of evidence, accumulated from the studying of neonatal IVH, demonstrates that plasminogen activator levels in CSF are low, with a median plasminogen level of 0.55% of normal adult plasma. (14) In addition, the intraventricular administration of rt-PA facilitates the clearance of the intraventricular blood clots. (15) Mayfrank et al (15) demonstrated in their porcine experimental model that the administration of rt-PA decreases the ventricular dilation associated with IVH.

Although the rationale for using rt-PA is well documented and widely accepted, the appropriate dosage remains controversial. In their protocol, Findlay et al (17) used an initial dose of 4 mg, and a sequential second dose was administered after 12 hours only if indicated by CT and ICP findings. Their mean total administered dose was 6.4 [+ or -] 3.3 mg; the total administered dose ranged from 2 mg to 12 mg. (17) Goh and Poon (14) used a mean total dose of 8.25 mg in a range of 6.5 mg to 12 mg. Mayfrank et al (15) administered a mean total dose of 12 mg (total dose range, 3 to 31 mg), whereas Rohde et al (38) used an average daily dose of 2 to 5 mg. In our treatment protocol, the average total administered dose was 11 mg (total administered dose range, 6 mg to 15 mg), which is slightly higher than previously used regimens. The rationale for administering an increased total dose was to facilitate earlier thrombolysis and consequently to decrease the risk of posthemorrhagic hydrocephalus. Animal experimental models have demonstrated, however, that a further increase of the administered dose could have detrimental effects on the brain, such as intraventricular leukocytosis and edema of periventricular tissues and choroid plexus. (39)

Comparison of different clinical series as reported in the literature is complicated because of the significant variability of the cause of IVH, the administered dose of rt-PA, and the methodology regarding CSF draining during the fibrinolytic process. Moreover, the limited number of patients included in all the reported clinical series makes the extraction of any statistically powerful conclusions regarding the efficacy of rt-PA extremely difficult if not impossible. In our series, the percentage of patients with good outcome (GOS scores of 4 and 5) was 47.5% (10 of 21), whereas Findlay et al (17) reported a good outcome in 60% (6 of 10). It needs to be emphasized, however, that the IVH was of hypertensive cause in our series, whereas in the Findlay (17) series it was solely of aneurysmal cause. In addition, the administered dose in our series was 3 mg every 24 hours, whereas in the Findlay series it was 4 mg every 12 hours. Our mean total dose was 11 mg, whereas the one in the Findlay series was 6.4 mg. Similarly, Goh and Poon reported a good outcome in 40% (4 of 10) using an rt-PA dose of 3 mg in treating IVH cases of primary origin only. (14)

Regarding the development of hydrocephalus requiring permanent CSF shunting, 40% of the survivors required a permanent VP shunt insertion. Similarly, both Findlay et al and Goh and Poon reported a 40% VP shunt insertion rate. (14) Contrariwise, Mayfrank et al (26) reported a VP shunt rate of only 8.3% (1 of 12). In the previously published clinical series in which urokinase was administered for IVH lysis, posthemorrhagic hydrocephalus requiring shunting varied from as high as 55%, reported by Rohde et al, (38) and 33.3%, reported by Todo et al, (5) to a low of 6.25%, as reported by Rainov et al. (25)

The use of fibrinolytic agents in the treatment of IVH has been occasionally associated with serious side effects. Induction of a new hemorrhage after the administration of rt-PA has been previously reported. (40) Schwarz et al (40) reported two cases of secondary hemorrhage after intraventricular fibrinolysis with rt-PA; interestingly, in both cases, the administered doses were relatively small (2 and 4 mg) and occurred early in the fibrinolysis process (after the first and the second doses, respectively). They speculated that the underlying pathophysiologic mechanism of this secondary hemorrhage might well be associated not only with the pharmacologic effect of the rt-PA but also to the mechanical irritation from repeated injections and flushing maneuvers. (40) In our series, we observed four cases of secondary hemorrhage (two cases of new IVH and two cases of intraparenchymal hemorrhage); the average total dose of rt-PA in these patients was 12 mg. Neither Findlay et al (17) nor Goh and Poon (14) reported any rt-PA-associated hemorrhages in either of their series.

The observed infection rate in our series was 14.3% (3 of 21); it is worth noting that all these patients had predisposing factors for developing infections. Again, neither Findlay et al (17) nor Goh and Poon (14) reported any infections in their patients, although their studies involved only half the number of patients involved in our own. The observed CSF pleocytosis, found in all of our patients, has also been reported by Wang et al, (39) who also reported edema of the periventricular tissues and choroid plexi and brain tissue injury. (39) Neither Findlay et al (17) nor Goh and Poon (14) comment specifically on the development of CSF pleocytosis in their studies.

The analysis of our data revealed a positive, statistically significant relation between the patient outcome (GOS score) and their admitting GCS score and a negative relation between the patient GOS score and their admitting Graeb scores; these findings reflect the importance of the severity of the initial ictal event. The intermediate follow-up of our patients (3 months later) did not differ significantly from the immediate outcome.

The analysis and comparison of the results of our own limited study with previously published limited clinical series makes the designing and execution of a large, multi-institutional, prospective, randomized, clinical study mandatory. Such a study would address the appropriate dosology of rt-PA, the appropriate CSF drainage pattern during the fibrinolytic process, and the accurate incidence of posthemorrhagic hydrocephalus among the survivors, none of which can be determined from the limited studies done to date. The definition of these parameters will increase the efficacy of this treatment modality and will minimize the associated complications; in addition, the scientific-based therapeutic guide-lines, which may well emerge from such a study, will provide a valid treatment option to those patients harboring IVH.

Conclusion

Intraventricular hemorrhage carries a dismal prognosis. The current standard of treatment, with external ventriculostomy placement and CSF drainage, is associated with significant difficulties, largely caused by obstruction of the ventriculostomy by blood clots. The intraventricular administration of rt-PA, in a dose of 3 mg every 24 hours, has been shown to be therapeutically efficient, significantly improving the outcome of these patients. The use of rt-PA also decreased the necessity for permanent VP shunt insertion in survivors. This treatment was associated with complications such as induction of new hemorrhage, infections, and CSF pleocytosis in our series. Further multi-institutional, prospective clinical studies are needed for statistical validation of the efficacy of this methodology and for defining the optimal dosology and CSF draining patterns.

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24. Murry KR, Rhoney DH, Coplin WM. Urokinase in the treatment of intraventricular hemorrhage. Ann Pharmacol 1998;32:256-258.

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38. Rohde V, Schaller C, Hassler WE. Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry 1995;58:447-451.

39. Wang YC, Lin CW, Shen CC, et al. Tissue plasminogen activator for the treatment of intraventricular hematoma: the dose-effect relationship. J Neurol Sci 2002;202:35-41.

40. Schwarz S, Schwab S, Steiner HH, et al. Secondary hemorrhage after intraventricular fibrinolysis: a cautionary note; a report of two cases. Neurosurgery 1998;42:659-663.

K. N. Fountas, MD, PHD, E. Z. Kapsalaki, MD, PHD, D. C. Parish, MD, MPH, B. Smith, MPH, H. F. Smisson, MD, FACS, K. W. Johnston, MD, FACS, AND J. S. Robinson, MD, FACS

From the Departments of Neurosurgery, Neuroradiology, and Internal Medicine, The Medical Center of Central Georgia, Mercer University, School of Medicine, Macon, GA.

None of the participants of this study have financial support or provision of supplies for any material presented. Also, no commercial or proprietary interest in any drug, device, or equipment mentioned in this article has been held by any of the participants of this study.

Reprint requests to Dr. Kostas N. Fountas, 840 Pine Street, Suite 880, Macon, GA 31201. Email: [e-mail]

Accepted January 31, 2004.

RELATED ARTICLE: Key Points

* Intraventricular hemorrhage (IVH) is a clinicopathologic entity with a dismal prognosis.

* The standard care of treatment in patients with severe IVH has been the insertion of an external ventriculostomy and draining of cerebrospinal fluid. Obstruction of the ventricular catheter is frequent in these cases because of the presence of blood clots.

* Various fibrinolytic agents have been used in limited clinical series addressing the technical difficulties associated with the functioning of an external ventriculostomy.

* Our retrospective clinical study showed better short- and intermediate-term outcome in patients with IVH treated with intraventricularly administered rt-PA.

* Intraventricular recombinant tissue-type plasminogen activator can also decrease the necessity for permanent ventriculoperitoneal shunting among the survivors.

Table 1. Demographic data and cause of IVH in our series

                                       GCS        Graeb
Patient                                admitting  admitting
No.      Age  Sex  Cause               score      score

 1       63   F    Hypertension        6          12
 2       69   M    Hypertension        7          10
 3       74   M    Hypertension        5          12
 4       31   M    Cocaine abuse       6           9
 5       49   F    Hypertension        5          11
 6       72   F    Hypertension        6          10
 7       58   M    Hypertension        5          12
 8       60   F    Hypertension        7           7
 9       71   M    Hypertension        6           9
10       45   F    Hypertension        7           7
11       50   M    Hypertension        6          11
12       78   M    Trauma related      6           6
13       49   F    Hypertension        7           9
14       51   F    Catheter insertion  5           8
15       68   F    Hypertension        5          12
16       49   M    Hypertension        7           9
17       26   M    Cocaine abuse       6          11
18       72   F    Hypertension        7           9
18       44   M    Hypertension        6          10
20       65   F    Unknown             7           7
21       42   F    SLE vasculitis      6           8

                                No. of
Patient                         ventricular  rt-PA total  Length of
No.      Comorbidity            catheters    dose         CSF draining

 1       Diabetes mellitus      2            4 X 3 mg      4
 2       None                   1            3 X 3 mg      6
 3       Diabetes mellitus,     2            5 X 3 mg      7
           coronary disease
 4       None                   1            4 X 3 mg      8
 5       None                   1            5 X 3 mg     11
 6       Diabetes mellitus      1            3 X 3 mg      9
 7       Diabetes mellitus      2            3 X 3 mg      3
 8       None                   1            3 X 3 mg      5
 9       Coronary disease       1            3 X 3 mg      6
10       None                   1            3 X 3 mg      7
11       None                   1            5 X 3 mg      9
12       Atrial fibrillation    1            2 X 3 mg      4
13       None                   1            3 X 3 mg      6
14       Hydrocephalus          1            3 X 3 mg      8
15       Coronary disease,      2            5 X 3 mg      5
           chronic obstructive
           pulmonary disease
16       None                   1            3 X 3 mg      7
17       None                   1            5 X 3 mg      7
18       None                   1            4 X 3 mg     10
18       None                   1            5 X 3 mg      9
20       None                   1            3 X 3 mg      7
21       SLE                    1            3 X 3 mg      4

         Time                                          NICU
         required for                                  length
Patient  blood         FH/ID before    FH/ID after     of
No.      clot lysis    administration  administration  stay

 1       N/A           0.7             0.8              4
 2       4             0.6             0.4              8
 3       N/A           0.6             0.7              7
 4       5             0.6             0.4             10
 5       6             0.6             0.5             15
 6       4             0.7             0.4             10
 7       N/A           0.7             0.7              3
 8       4             0.6             0.7              8
 9       4             0.6             0.6              9
10       4             0.6             0.4             12
11       6             0.6             0.6             11
12       3             0.5             0.4              7
13       4             0.7             0.4              8
14       4             0.6             0.6             11
15       N/A           0.7             0.7              5
16       4             0.6             0.4              8
17       6             0.5             0.4              7
18       5             0.6             0.7             13
18       7             0.6             0.4             11
20       4             0.5             0.4             10
21       3             0.5             0.6              4

                                                          GOS    GOS
                              VP                          score  score
Patient  New         CSF      shunt      Length of        at 1   at 3
No.      hemorrhage  culture  insertion  hospitalization  month  months

 1       Y           Staph    N          N/A              1      1
                       epi
 2       N           N/A      N          20               3      3
 3       N           Pseud    N          N/A              1      1
                       ae
 4       N           N/A      N          22               4      4
 5       Y           N/A      Y          27               2      3
 6       N           N/A      N          18               3      4
 7       N           N/A      N          N/A              1      1
 8       N           N/A      Y          15               5      5
 9       N           N/A      Y          17               4      4
10       N           N/A      N          28               4      4
11       N           N/A      Y          32               3      3
12       N           N/A      N          11               5      5
13       N           N/A      N          14               4      4
14       N           N/A      Y          13               5      5
15       N           N/A      N          N/A              1      1
16       N           N/A      N          14               4      4
17       N           Staph    N          N/A              1      1
                       au
18       Y           N/A      Y          25               4      4
18       N           N/A      N          20               3      3
20       N           N/A      N          18               5      5
21       Y           N/A      N          N/A              1      1

(a) IVH, intraventricular hemorrhage; GCS, Glasgow Coma Scale; CSF,
cerebrospinal fluid; FH, frontal horns of the lateral ventricles; ID,
internal diameter from inner table to inner table at the same level;
NICU, neurointensive care unit; VP, ventriculoperitoneal; GOS, Glasgow
Outcome Scale; M, male; F. female; SLE, systemic lupus erythematosus.
rt-PA, recombinant tissue-type plasminogen activator. Staph epi,
Staphylococcus epidermidis; Pseud ae, Pseudomonas aeruginosa; Staph au,
Staphylococcus aureus.

Table 2. Graeb classification system

Score                        Characteristic

Lateral Ventricles
1                            Trace of blood or mild bleeding
2                            Less than half of the ventricle filled with
                               blood
3                            More than half of the ventricle filled with
                               blood
4                            Ventricle filled with blood and expanded

Third and fourth ventricles
1                            Blood present, ventricle size normal
2                            Ventricle filled with blood and expanded