J Neurosurg Pediatrics (Suppl) 14:8–23, 2014

©AANS, 2014

Pediatric hydrocephalus: systematic literature review and evidence-based

guidelines. Part 2: Management of posthemorrhagic hydrocephalus in
premature infants
Catherine A. Mazzola, M.D.,1 Asim F. Choudhri, M.D., 2,3 Kurtis I. Auguste, M.D., 4
David D. Limbrick Jr., M.D., Ph.D., 5 Marta Rogido, M.D., 6 Laura Mitchell, M.A.,7
and Ann Marie Flannery, M.D. 8

1
Division of Pediatric Neurological Surgery, Goryeb Children’s Hospital, Morristown, New Jersey; 2Departments of Radiology
and Neurosurgery, University of Tennessee Health Science Center, and 3Le Bonheur Neuroscience Institute, Le Bonheur Children’s
Hospital, Memphis, Tennessee; 4Department of Neurosurgery, University of California, San Francisco, California; 5Division of
Pediatric Neurosurgery, St. Louis Children’s Hospital, St. Louis, Missouri; 6Division of Neonatology, Department of Pediatrics,
Goryeb Children’s Hospital, Morristown; and Rutgers New Jersey Medical School, Newark, New Jersey; 7Congress of Neurological
Surgeons, Schaumburg, Illinois; and 8Department of Neurological Surgery, Saint Louis University, St. Louis, Missouri

Object. The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment
strategies for posthemorrhagic hydrocephalus (PHH) in premature infants?
Methods. Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH head-
ings and key words relevant to PHH. Two hundred thirteen abstracts were reviewed, after which 98 full-text publications that met inclusion
criteria that had been determined a priori were selected and reviewed.
Results. Following a review process and an evidentiary analysis, 68 full-text articles were accepted for the evidentiary table and 30
publications were rejected. The evidentiary table was assembled linking recommendations to strength of evidence (Classes I–III).
Conclusions. There are 7 recommendations for the management of PHH in infants. Three recommendations reached Level I strength,
which represents the highest degree of clinical certainty. There were two Level II and two Level III recommendations for the management
of PHH.
Recommendation Concerning Surgical Temporizing Measures: I. Ventricular access devices (VADs), external ventricular drains
(EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment
is required. Strength of Recommendation: Level II, moderate degree of clinical certainty.
Recommendation Concerning Surgical Temporizing Measures: II. The evidence demonstrates that VSG shunts reduce the need for
daily CSF aspiration compared with VADs. Strength of Recommendation: Level II, moderate degree of clinical certainty.
Recommendation Concerning Routine Use of Serial Lumbar Puncture: The routine use of serial lumbar puncture is not recommended
to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants. Strength of Recommendation:
Level I, high clinical certainty.
Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular thrombolytic agents including tissue plasminogen
activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants
with PHH. Strength of Recommendation: Level I, high clinical certainty.
Recommendation Concerning Nonsurgical Temporizing Agents. II. Acetazolamide and furosemide are not recommended as methods to
reduce the need for shunt placement in premature infants with PHH. Strength of Recommendation: Level I, high clinical certainty.
Recommendation Concerning Timing of Shunt Placement: There is insufficient evidence to recommend a specific weight or CSF pa-
rameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required. Strength of Recommendation:
Level III, unclear clinical certainty.
Recommendation Concerning Endoscopic Third Ventriculostomy: There is insufficient evidence to recommend the use of endoscopic
third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus. Strength of Recommendation: Level III, unclear
clinical certainty.
(http://thejns.org/doi/abs/10.3171/2014.7.PEDS14322)

Key Words      •      hydrocephalus      •      infant      •      case management      •      magnetic resonance imaging      •     

posthemorrhagic hydrocephalus       •      premature infant      •      preterm infant      •      ventriculomegaly      •     
intraventricular hemorrhage      •      meningitis      •     
Abbreviations used in this paper: AANS = American Association ventricular dilation      •      ventricular index      •     
of Neurological Surgeons; CDC = Centers for Disease Control and
Prevention; CNS = Congress of Neurological Surgeons; ELBW =
head circumference      •      in utero      •      shunt      •     
extremely low birth weight; ETV = endoscopic third ventriculos- reservoir      •      endoscopic third ventriculostomy       •   
tomy; EVD = external ventricular drain; HUS = head ultrasound; ventriculoperitoneal shunt      •      practice guidelines

IVH = intraventricular hemorrhage; LBW = low birth weight; LP
= lumbar puncture; OFC = occipitofrontal circumference; PHH =
posthemorrhagic hydrocephalus; PHVD = posthemorrhagic ventric-
ular dilation; tPA = tissue plasminogen activator; VAD = ventricular
access device; V/BP = ventricular/biparietal; VP = ventriculoperito-
neal; VSG = ventriculosubgaleal.
A
lthough reviews have been recently published,
there exists a paucity of guidelines or evidence-
based recommendations for the management of
posthemorrhagic hydrocephalus (PHH) in infants.62 Ac-

8 J Neurosurg: Pediatrics / Volume 14 / November 2014

Part 2: Management of posthemorrhagic hydrocephalus in infants
cording to 2007 data provided by the Division of Vital
Statistics of the Centers for Disease Control and Preven-
tion (CDC), infants born with very low birth weight and
gestational age have a significantly higher risk of mortal-
ity.49 In fact, more than 50% of all infant deaths in 2007
occurred in infants born before 32 weeks’ gestation.49
In 2008, the reported preterm birth rate declined for the
second consecutive year to 12.3%, but this decrease pri-
marily involved those infants born in the later preterm
period (34–36 weeks).47 Low birth weight (LBW) also
contributes to increased infant mortality, and the CDC
has reported that the percentage of LBW infants, or in-
fants born weighing less than 2500 g, increased by 24%
between 1984 and 2006.47
A recent study of 15,454 extremely low birth weight
(ELBW) infants, each weighing between 401 g and 1000
g, was undertaken to assess neurodevelopmental out-
come.1 More than 5000 infants died while in the hospital
or before the follow-up visit. Among the 7693 children in
whom follow-up studies were available, 2530 (33%) had
a history of intraventricular hemorrhage (IVH). The IVH
was Grade III or IV for 998 (13%) of the 7693 infants.
Remarkably, in only 246 (3%) of the 7693 ELBW infants
with follow-up was a shunt placed for PHH.1 There are
still many questions about the optimal time to intervene
for infants with PHH, and there are many different opin-
ions about the best temporizing mechanism for symp-
tomatic infants too small or unstable for permanent shunt
placement.
The objective of this systematic review and analy-
sis was to answer the following question: What are the
optimal treatment strategies for posthemorrhagic hydro-
cephalus (PHH) in premature infants? We evaluated the
current literature and constructed evidence-based recom-
mendations supported by the strength of the available
data for the management of PHH in premature infants.
Specifically, we wanted to investigate relevant evidence
for the following:
• Use of surgical temporizing methods such as ventric-
ular reservoirs, external ventricular drains (EVDs),
ventriculosubgaleal (VSG) shunts, and lumbar punc-
tures (LPs).
• Routine use of serial LPs to reduce the need to shunt
or to avoid the progression of hydrocephalus in pre-
mature infants.
• Use of intraventricular thrombolytic agents, includ-
ing tissue plasminogen activator (tPA), urokinase,
and streptokinase, to reduce the need for shunt place-
ment in premature infants with PHH.
• Use of acetazolamide or furosemide to reduce the need
for shunt placement in premature infants with PHH.
• Efficacy of endoscopic third ventriculosomy (ETV)
in this population.
• Specific CSF parameters to direct the timing of shunt
placement in premature infants with PHH.
Methods
Search Criteria
Both the US National Library of Medicine and the
J Neurosurg: Pediatrics / Volume 14 / November 2014
Cochrane Database of Systematic Reviews were queried
using MeSH headings and key words relevant to PHH.
Key Words. The following key words were used in this
study: (((preterm[All Fields] AND Intraventricular[All
Fields] AND (“haemorrhage”[All Fields] OR “hemor­
rhage”[MeSH Terms] OR “hemorrhage”[All Fields])) OR
((“infant, premature”[MeSH Terms] OR (“infant”[All
Fields] AND “premature”[All Fields]) OR “premature
infant”[All Fields] OR (“preterm”[All Fields] AND
“infant”[All Fields]) OR “preterm infant”[All Fields])
AND (“hydrocephalus”[MeSH Terms] OR “hydro­ceph­
alus”[All Fields]))) OR ((preterm[All Fields] AND (“heart
ventricles”[MeSH Terms] OR (“heart”[All Fields] AND
“ventricles”[All Fields]) OR “heart ventricles”[All Fields]
OR “ventricular”[All Fields]) AND reservoir[All Fields]))
AND shunt[All Fields].
Strategy
Two hundred thirteen abstracts were reviewed, after
which 98 publications that met the inclusion criteria were
selected. In addition to the overall inclusion/exclusion cri-
teria specified in the Methods section of the Guidelines
(Part 1), additional inclusion criteria included studies in
which infants younger than 12 months with all forms
of hydrocephalus—both congenital and acquired—were
evaluated to ensure that the maximum number of studies
were reviewed. The analysis focused on studies evaluat-
ing infants with PHH because of the treatment strategies
and challenges unique to this patient population.
As a result of the US National Library of Medicine’s
search engine functionalities, additional search terms
(heart ventricles) not relevant to topics addressed in this
chapter were added to the search strategy. Although these
search terms remained in the search strategy, we did not
recall any references retrieved using them for full-text
review. We excluded those references because they were
not relevant to the overall scope of this project or the pa-
tient population addressed in this chapter and, therefore,
did not meet the article inclusion criteria specified in the
methodology section of this guideline (Part 1).23
Following an evidentiary analysis and a review of the
98 full-text articles, 68 publications were accepted for in-
clusion in the evidentiary table and 30 publications were
excluded. 2,7,12–14,21,22,27,30,33,35,38,48,50–53,55,57,58,62–64,66–68,70,73,75
The evidentiary table was assembled linking recommen-
dations to the strength of the evidence (Levels I–III).
Search Results
Of the 98 full-text articles selected for review, 30
full-text publications were rejected based on the criteria
listed above and only 68 articles were used to construct
the evidentiary table (Fig. 1). The criteria for the decision
to treat were quite variable among different institutions
and different study groups. For example, we evaluated 1
Class II study in which hydrocephalus was defined as the
atrium of the lateral ventricle measuring > 10 mm on the
horizontal plane of a head ultrasound (HUS) study or the
body of the lateral ventricle at the level of the midthala-
mus measuring > 10 mm on a sagittal ultrasound image.10
We reviewed another Class III study in which hydroceph-
9

Fig. 1.  Flowchart showing the process involved in identifying relevant literature. The criteria for “records excluded” and “full-
text articles excluded with reasons” are detailed in Part 1 of the Guidelines.
alus was defined as anterior cortical mantle thickness <
20 mm at an average postnatal age of 21 days along with
increasing occipitofrontal circumference (OFC) as an in-
dicator of hydrocephalus that should be treated.5 Bada et
al.5 reported that of 10 infants requiring shunts, 5 (50%)
experienced normal development, which was defined by
physical and neurological assessment and evaluation us-
ing the Denver developmental screening tool. Evan’s ra-
tio, which is described as the lateral measurement of the
ventricle across the frontal horns divided by the lateral
measurement across the brain (biparietal diameter; also
known as the ventricular/biparietal [V/BP] ratio) can also
be used to describe the severity of PHH.16 The majority
of studies that were evaluated based on an initial diag-
nosis of PHH on HUS, CT, and MRI studies were also
used. Choudhury described mild hydrocephalus as a V/
BP ratio of 0.26–0.40, moderate hydrocephalus as a V/
BP ratio of 0.40–0.60, severe hydrocephalus as a V/BP
ratio of 0.60–0.90, and extreme hydrocephalus as a V/
BP ratio of 0.91–1.0.16 These authors also reported that
the thickness of the cortical mantle was not a statistically
significant indicator of outcome because several infants
with extreme hydrocephalus displayed normal motor de-
velopment.16 One Class II and 1 Class III study indicated
that when ventriculoperitoneal (VP) shunts were placed,
10
C. A. Mazzola et al.
even in cases of severe or extreme hydrocephalus, there
were some infants with normal development and motor
outcome (50 of 82 patients in the Choudhury study). 5,16
Numerous studies have reported that good neurodevelop-
mental outcomes may be seen if and when infants with
hydrocephalus are aggressively treated and cortical man-
tle thickness is restored.
Results
Surgical Temporizing Measures
Recommendation: Ventricular access devices (VADs),
external ventricular drains (EVDs), ventriculosubgaleal
(VSG) shunts, or lumbar punctures (LPs) are treatment op-
tions in the management of PHH. Clinical judgment is re-
quired. Strength of Recommendation: Level II, moderate
degree of clinical certainty.
Recommendation: The evidence demonstrates that
VSG shunts reduce the need for daily CSF aspiration
compared with VADs. Strength of Recommendation:
Level II, moderate degree of clinical certainty.
The evidence demonstrates that VADs reduce mor-
bidity and mortality compared with EVDs. Three Class II
and 7 Class III studies were included as evidence to sup-
port the first recommendation, and these lower-quality
J Neurosurg: Pediatrics / Volume 14 / November 2014
Part 2: Management of posthemorrhagic hydrocephalus in infants
studies documented the safety and efficacy of VADs, or
Ommaya reservoirs, for the aspiration of CSF, ventricu-
lar decompression, and lowering of intracranial pres-
sure.3,8,11,25,26,29,31,39,78,80 The authors of 2 Class II studies
reported that ventricular reservoirs may reduce the inci-
dence of shunt infection as well as noninfectious shunt
complications.8,26 In one Class II study and one class III
study, repeated aspiration of CSF from a VAD did not sig-
nificantly increase the risk of infection.26,39 Three Class
III studies reported that ventricular reservoirs did not
significantly reduce the need for permanent shunt place-
ment.29,31,78 One Class III study reported that the use of
VADs, compared with the use of continuous ventricular
drainage, significantly reduced morbidity and mortality
rates that were associated with the surgical treatment of
PHH in LBW infants with reservoirs, instead of EVDs
(Table 1).26
The placement of an EVD has also been used to treat
hydrocephalus in preterm infants with PHH and is an op-
tion for these children, as shown in 1 Class II and 7 Class
III studies.9,17,28,36,40,59,60,69 Three Class III studies reported
that an EVD obviated the need for VP shunt placement
in fewer than one-third of infants treated.9,40,60 More than
50% of preterm infants with PHH did require permanent
VP shunt placement following removal of an EVD (95 out
of 132 survivors required a shunt).9,40,59,60,69
It has been reported that placement of a VSG shunt
may reduce the need for permanent shunt placement. The
authors of Class II and Class III studies reported trends
toward shunt independence, but the studies only enrolled
32 and 95 patients, respectively, and the results were not
statistically significant.41,43 In their report of a Class II,
retrospective historical cohort study, Lam and Heilman
demonstrated that VSG shunting significantly reduced
the need for daily CSF aspiration, which may decrease
the risk of introducing a de novo CSF infection.41 A chi-
square test performed on their data indicated that a VSG
shunt did significantly reduce the need for daily CSF as-
piration when compared with a VAD (c2 = 19.2, df = 1,
p = 0.000016, p < 0.05).41 This may reduce the risk of
infection or other complications. A larger, prospective
study reported a statistically significant decreased need
for permanent CSF diversion in infants treated with VSG
shunts.43 This study reported that 66% of infants (20 of
30) treated with VSG shunts required VP shunts and 33%
(10 of 30) remained shunt free; this was compared with a
group of infants treated with VADs in which 75% (49 of
65) required VP shunts and only 25% of infants (16 of 65)
remained shunt free.43
In 2 studies, 1 intervention was compared to another
with specific recommendations about the timing of the
intervention for temporizing measures for the treatment
of PHH in very LBW infants. In 1 Class III study, the au-
thors compared early versus late intervention, as assessed
by ventricular dilation in 5 collaborating neonatal cen-
ters.18 Ninety-five patients were subdivided into early in-
tervention or late intervention groups, depending on their
ventricular index at the time of initial treatment. Early
treatment was safe and effective regardless of whether
LP and/or reservoir placement was used. Early interven-
tion was associated with a reduced requirement for a VP
J Neurosurg: Pediatrics / Volume 14 / November 2014
shunt (OR = 0.22) and reduced risk of moderate-to-severe
disability.18 Additionally, there was a single Class III ob-
servational study of outcomes in which LPs, EVD, VSG
shunts, and reservoirs were used.57 All interventional
studies were found to be safe and effective.57
Routine Use of Serial Lumbar Puncture
Recommendation: The routine use of serial lumbar
puncture (LP) is not recommended to reduce the need for
shunt placement or to avoid the progression of hydroceph-
alus in premature infants. Strength of Recommendation:
Level I, high degree of clinical certainty.
One Class I study was included, and it reported no
statistical differences in outcomes of preterm infants with
PHH treated with observation alone or infants treated
with daily LP (Table 2).4 Lumbar puncture is often used
early in the treatment of PHH, despite the fact that there
is no statistically significant reduction in the need for a
shunt or progression of PHH.4,54 In fact, LP neither pre-
dicts nor prevents the need for a permanent VP shunt.36
A second study, a Class III study, also reported no dif-
ference in adverse outcome regardless of whether infants
were untreated or treated with serial LP.15 Without ag-
gressive treatment of hydrocephalus and with persistent
ventricular dilation, outcome was poor.15 Additionally,
there was a single Class III study that concluded that re-
peated LPs may cause or contribute to subsequent shunt
infection.6 Although LP may be useful for drawing off
CSF as an immediate treatment for elevated intracranial
pressure in infants with PHH, or for sampling CSF, we
do not recommend the routine use of LP to eliminate the
need for a VP shunt.15
Nonsurgical Temporizing Agents
Intraventricular Thrombolytic Agents. Recommen-
dation: Intraventricular thrombolytic agents including
tissue plasminogen activator (tPA), urokinase, or strepto-
kinase are not recommended as methods to reduce the
need for shunt placement in premature infants with PHH.
Strength of Recommendation: Level I, high clinical cer-
tainty.
Based on 1 high-quality Class I study, the DRIFT
procedure—DRainage, Irrigation, and Fibrinolytic Ther­­
apy (intraventricular tPA)—is not recommended for
PHH.71 DRIFT did not significantly reduce shunt surgery
or death, but it was associated with an increased rate of
secondary IVH (Table 3).71 Forty-four percent (15 of 34)
of infants in the DRIFT group died or required a shunt,
compared with 50% (19 of 36) of infants who received
standard treatment. Thirty-five percent (12 of 34) of pre-
term infants in the DRIFT study had secondary IVH,
compared with 8% (3 of 34) who received standard treat-
ment.71 These results differ from those of earlier Class
II and Class III studies in which a decreased rate for the
need for permanent shunt placement was reported when
low-dose urokinase or fibrinolytic therapy with tPA was
used for ventricular irrigation and clot reduction.32,61,75,77
Reviews conducted by Whitelaw and Odd74 have also
revealed that intraventricular injection of streptokinase
has not been shown to be beneficial.74 A single case re-
11
12
TABLE 1: Surgical temporizing measures: summary of evidence*

Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
Cornips et al., Retrospective review of 14 pts w/ Grade III or Grade IV IVH Class II Ventricular drainage is a safe option for infants w/ PHH.
1997 diagnosed on HUS study & treated w/ EVD. Retrospective review of 2 cohorts: premature infants
14 pts were compared w/ a historical cohort of 15 infants w/ treated w/ EVD vs those treated medically.
similar Grade III/IV IVH.
Gurtner et al., Retrospective consecutively enrolled study of 736 LBW infants Class II Frequency & mortality of Grades III & IV hemorrhage
1992 (< 1500 g). Consecutive, but not a randomized controlled study. in infants weighing btwn 500 & 700 g remained
After exclusion of some infants for various reasons, 547 infants A nonrandomized historical cohort, compared by yr of relatively constant over the 3-yr period.
were included in the retrospective consecutive review. treatment & treatment type. 1st yr: EVD. Authors concluded that there was a significant reduc-
Shunts were placed for progressive hydrocephalus & OFC > 2nd & 3rd yr: subcutaneous reservoir was used. tion in morbidity & mortality associated w/ LBW
95 percentile. Outcomes evaluated: morbidity, mortality, & need for infants when they began using reservoirs instead of
3 yrs of data examined by yr, by analyses of variance, & shunt revision. EVDs.
Duncan’s mean comparison tests.
Chi-square analyses on discrete variables such as rates of
complication & mortality. Student t-test w/ Bonferroni cor-
rections. Spearman correlation coefficients were computed
when appropriate. Quantitative data are presented.
Hudgins et al., Class II
Use of urokinase via reservoir to treat PHH in 18 pts. 4 differ- “Low dose” urokinase reduced shunt rate (71% vs 92%)
1997 Prospective, nonrandomized, case-control series.
ent doses of urokinase; ultimately grouped into “high” (n = compared to historical controls. Fewer shunt revi-
9) & “low” dose (everyone else, n = 9). Division of 9 pts into “low” dose group would appear to sions in both groups compared to control group.
Both groups compared to historical control group w/ respect to dilute statistical power despite statistical significance
outcome & need for shunt. Prospective, case control. obtained.
Lam & Heil- Single-institution, retrospective historical cohort study of 32
Class II There was a trend toward VP shunt independence
man, 2009 preterm infants w/ PHH. This study compared 2 cohorts of A chi-square test was performed (χ2 = 19.2, df = 1, p = in the VSG shunt group, as compared to the VAD
infants: those treated w/ VAD/Ommaya placement vs those 0.000016, p < 0.05), which showed that VSG shunts group, but it did not reach significance.
treated w/ VSG shunts. significantly reduced the need for daily CSF aspira- VSG shunts decreased the need for daily taps. There
There were no statistical differences in age or birth weight of tion compared to VADs. was a slightly higher rate of complications in the
The higher rate of complications of VSG shunts was not
the infants in the 2 groups. The groups were studied for IVH VSG shunt group, but it was not significant.
grade, need for daily CSF withdrawal, CSF leak from the statistically significant compared w/ the VAD group
scalp, CSF infection, & need for a VP shunt. (p = 0.17).
93.75% (15 of 16 pts) in the VAD group required VP
shunts while 71.42% (10 of 14 pts) in the VSG shunt
group needed VP shunts.
Anwar et al., Consecutive, nonrandomized study of 19 preterm infants w/ Class III The authors concluded that reservoirs provide safe &
1986 PHH who underwent placement of reservoirs for symptom- Study was a case series of infants weighing <2000 g, effective treatment for infants w/ PHH & symptom-
atic hydrocephalus. w/ clear CSF & treated w/ reservoirs. atic hydrocephalus.
Symptomatic hydrocephalus was defined as infants w/ rapidly There was only limited presentation of qualitative &
increasing OFC, ventriculomegaly, & signs of increased ICP quantitative data. Data included: morbidity, mortality,
present, such as tense fontanelle, splayed sutures, apnea, & need for shunt placement in these infants.
bradycardia, seizure, feeding difficulties, or lethargy. There was no comparison w/ a cohort of nontreated
infants or infants treated w/ ventricular drains.
(continued)

J Neurosurg: Pediatrics / Volume 14 / November 2014

C. A. Mazzola et al.
 TABLE 1: Surgical temporizing measures: summary of evidence* (continued)
Authors & Year Study Description
Benzel et al., 41 pts requiring ventricular drainage for hydrocephalus/PHH
1993 were evaluated retrospectively.
All drainage procedures were performed on pts w/ IVH & hy-
drocephalus (Grade III [25 pts]) & pts w/ IVH & IPH (Grade
IV [16 pts]) in whom medical management had failed.
Berger et al., Retrospective review of outcomes after placement of EVDs
2000 in 37 premature infants (51 drains). PHH diagnosed by
J Neurosurg: Pediatrics / Volume 14 / November 2014
ultrasound.
Brouwer et al., Single-center retrospective review of 76 preterm infants
2007 treated for PHVD w/ ventricular reservoirs.
Infection rates were measured in 2 successive 6-yr intervals.
No. of reservoir punctures also examined.
de Vries et al., Retrospective review of consecutive preterm infants (EGA
2002 ≤34 wks) w/ Grade III IVH treated for posthemorrhagic
ventricular dilatation in 5 collaborating NICUs (n = 95). Pts
were subdivided into early intervention or late intervention
groups, depending on their ventricular index at the time of
initial treatment.
Gaskill et al., The use of a subcutaneous reservoir was studied in a con-
1988 secutive, nonrandomized series of 38 infants w/ preterm
IVH & PHH. In all infants LP & medical treatment had failed.
Harbaugh et Retrospective review of 11 premature infants w/ IVH & PHH
al., 1981 who were treated w/ tunneled EVD. The mean duration of
drainage for this group was 20.7 days.
No morbidity or mortality occurred as a result. 7 of 11 pts
required a shunt. 2 of 11 did not require a VP shunt.
13
Data Class, Quality, & Reasons
Class III
Retrospective case series of 41 consecutive premature
infants.
26 ventricular reservoirs (Rickham or McComb reser-
voirs) were placed in neonates weighing <1500 g,
allowing for safe but intermittent ventricular access.
18 of these reservoirs were subsequently converted
to VP shunts. 32% of pts developed a VP shunt &/or
reservoir infection & 59% required a shunt revision
during the 1st yr of life.
No Grade IV pts achieved normal functional level, while
10 Grade III pts did. The incidence of severe devel-
opmental delay (44% vs 28%) & death (38% vs 12%)
was greater in Grade IV than in Grade III pts.
Class III
Single-institution retrospective review.
Class III
Single-center retrospective review.
Class III
Multicenter study, retrospective case series.
Treatments were not standardized treatments.
LPs, reservoir, & shunt.
Class III
Retrospective study of a series of premature infants
who required temporizing measures (reservoir place-
ment) after medical treatment/LP for PHH had failed.
There were 28 survivors overall (8 died before a shunt
could be placed, 2 died after shunt placement). 4
survivors (15%) did not require a shunt.
Class III
Small retrospective case review.
Results & Conclusions
Authors state, “The placement of ventricular reservoirs
is acceptable as an alternative to early placement
of ventriculo-peritoneal shunts. This approach may
reduce the incidence of shunt infection as well as
noninfectious shunt complications.”
Neurodevelopmental outcome dependent on extent of
parenchymal injury.
Infection rates: 5.4% pts, 3.9% drain. 11 of 37 pts did
not require shunt placement.
While the no. of reservoir punctures did not change,
the infection rate was lower in the 2nd, more recent
interval (2 of 50 pts [4%] vs 5 of 26 pts [19.2%]).
Conclusion: Risks associated w/ ventricular reservoirs
are w/in acceptable limits.
Early treatment was associated w/ a reduced require-
ment for VP shunt (OR = 0.22) & reduced risk of
moderate-to-severe disability.
Part 2: Management of posthemorrhagic hydrocephalus in infants
The authors concluded that early reservoir placement
is a feasible, safe, & effective treatment for PHH
associated w/ preterm IVH.
EVD via a subcutaneously tunneled catheter was
found to be a safe & reliable initial method of treat-
ing PHH in premature infants.
(continued)
14
TABLE 1: Surgical temporizing measures: summary of evidence* (continued)
Authors & Year Study Description
Heep et al., Safety/efficacy of Rickham reservoir placement for pts w/
2001 PHH.
Hudgins et al., Use of VAD in 149 pts w/ PHH. Daily taps for 1st “several”
1998 days (10–15 cm3/kg).
Kazan et al., Retrospective review of preterm & LBW infants diagnosed w/
2005 IVH by ultrasound (n = 42).
11 infants who required VP shunts were compared w/ 31 who
did not. All pts received acetazolamide & furosemide as an
initial medical treatment.
Kormanik et Retrospective review of the outcome of infants receiving a
al., 2010 ventricular reservoir for PHH.
Kreusser et al., Study of 19 consecutive infants w/ PHH documented by CT
1984 or cranial ultrasound, & ICP measurement by an indwelling
ICP monitor.
5 of 19 pts were initially treated w/ LP, 30–40 ml CSF drained
daily for 5–7 days.
Surviving pts were evaluated w/ the Bayley Scale of Infant
Development, the Cartell Infant Intelligence Scale, or the
Stanford-Binet Intelligence Test, based on the child’s age at
evaluation. Developmental quotient (DQ) was determined
using the Denver Developmental Screening Test.
Limbrick et al., Large single-center retrospective review of 325 preterm
2010 infants w/ Grade III or IV IVH. The development of PHH &
the need for a temporizing device (VAD or VSG shunt) were
studied. Infections, complications, & need for VP shunt
were analyzed, as was the mortality rate.
J Neurosurg: Pediatrics / Volume 14 / November 2014
Data Class, Quality, & Reasons
Class III
Retrospective review. Broad inclusion criteria for
reservoir placement.
No comparison w/ pts managed w/ other methods.
Class III
Single-institution retrospective case series.
Shunts placed at 2 kg if pt was still symptomatic, but
criteria not otherwise clear on when to stop VAD
aspirations.
Class III
Small, single-center retrospective case series w/
grouping of pts despite variable treatments.
Class III
Retrospective observational study: a review of medical
records of all infants who received a ventricular
reservoir in 1 center between 2000 & 2007.
Class III
Case series of a group of 19 consecutive infants
treated w/ external ventricular drainage. There
was no randomization to treat or not treat, & no
randomization of type of treatment. There was no
case-controlled comparative cohort or group.
Class III
Retrospective analysis showed 75.4% of the 65 infants
treated w/ VAD needed a shunt; 66.7% of the 30
treated w/ VSG shunts required a shunt.
There was no significant difference in the infection rate
between VAD & VSG shunts, revision rate, or VP
shunt infection afterwards.
Results & Conclusions
Ommaya/Rickham reservoir is a safe, effective option
for managing PHH until pt is ready for a shunt. 5%
infection rate, 85% of pts needed a shunt.
8% infection & 20% revision rates. 88% shunt implanta-
tion rate.
Risk factors for VP shunt included IVH grade, later
EGA at birth, & age (days) at time of IVH, but not
treatment for IVH/PHH (acetazolamide, furosemide,
LP, & external ventricular drainage).
35 ventricular reservoirs were placed. 6 pts (17%) were
excluded. 29 pts had a total of 681 taps. There was
no increased risk of infection from repeated or daily
aspiration.
Only 1 CSF culture-proven reservoir infection: Candida
albicans.
External ventricular drainage decreased ventricular
size.
3 infants did not develop recurrent hydrocephalus & did
not require a shunt. 16 infants suffered recurrent hy-
drocephalus, w/in 1 wk after drain removal. Another
EVD was placed in 10 pts.
Following repeated EVDs, 9 of the 10 infants were
stable enough for a shunt. The authors conclude
that EVD is a safe & effective treatment for PHH.
There was no significant difference in outcome be-
tween infants treated w/ VAD or VSG shunts.
(continued)
C. A. Mazzola et al.
 TABLE 1: Surgical temporizing measures: summary of evidence* (continued)

Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
Rahman et al., Single-institution, small retrospective review of 37 pts w/ PHH,
Class III Suggested LP, VSG, Ommaya reservoir, & VP shunts
1993 31 of whom required VP shunt. Observational study of outcomes. LP, EVD, VSG are safe & effective. Of 26 infants w/ PHH treated w/
shunts, & Ommaya reservoirs were used. EVD, 20 did require shunts. 6 did not require further
No statistical data available. treatment.
Rhodes et al., 37 premature infants w/ PHH were treated w/ an EVD. Compli- Class III Level III
1987 cations, including morbidity, are presented. Retrospective, consecutive case series. Ventricular drainage is a safe & effective mechanism
32 pts did not require a permanent shunt. Neurodevelopmen- for treating infants w/ PHH & may obviate the need
tal & neuromuscular outcomes are presented. for a shunt.
Weninger et Study of 27 consecutive infants w/ an average gestational age Class III PHH was successfully treated in all pts; the EVD was
al., 1992 of 31 wks, who had PHH & increased ICP & were treated w/ The study is a case series report. left in situ for an average of 23 ± 9 days. 4 pts died

J Neurosurg: Pediatrics / Volume 14 / November 2014

a tunneled EVD. of unrelated causes, & 23 pts survived. 16 required
PHH was defined as ventricular dilation, progressively in­ shunts.
creas­ing OFC, bulging fontanelle, widening of the sutures, Neurological outcome correlated w/ severity of the
apnea, or bradycardia. Grade of IVH. Grade IV IVH infants had the worst
neurological outcomes, despite treatment.
The authors conclude that EVD is a safe & effective
treatment for PHH in premature infants.
Willis et al., 32 premature infants w/ PHH were treated w/ shunts or Class III Initially reservoirs were placed in 46.8% of pts & shunts
2009 reservoirs. Retrospective, consecutive case series of 32 infants in 53% of pts. The groups were not comparable.
who needed treatment for PHH. Multivariate analysis Permanent shunts were needed in 90.6% of cases.
Part 2: Management of posthemorrhagic hydrocephalus in infants

& time series were used to identify factors that influ- Infants who were treated w/ a shunt initially had more
ence the outcome in terms of shunt revisions. revisions. p = 0.0027.
CSF reservoirs are a safe & effective method of treat-
ment in infants considered too small for VP shunt
placement, but this does not obviate the need for a
shunt.
Yu et al., 2009 The authors performed a retrospective case study of 11 pre- Class III The authors concluded that CSF reservoir treatment is
mature infants w/ PHH who were all treated w/ a subcutane- Retrospective case series. safe & effective for infants w/ PHH.
ous reservoir for CSF aspiration.

*  EGA = estimated gestational age; ICP = intracranial pressure; IPH = intraparenchymal hemorrhage; NICU = neonatal intensive care unit; pts = patients.

15
 C. A. Mazzola et al.
TABLE 2: Serial lumbar punctures: summary of evidence

Authors & Year Study Description
Anwar et al., Randomized controlled study of 47
1986 consecutive preterm infants w/ PHH &
Grade III or Grade IV IVH.
Infants enrolled in the study were random-
ized to observation only or daily LP.
Cohorts were studied for morbidity,
mortality, & need for a shunt.
Behjati et al., Case series study that investigated risk
2011 factors for VP shunts in infants w/ hydro- Case series of 97 infants w/ IVH associated
cephalus following IVH in 97 consecu-
tive preterm infants w/ IVH.
Chaplin et al., Retrospective review of 22 consecutive
1980 LBW infants w/ PHH.
All pts developed hydrocephalus after 2
wks of age. The first 12 required VP
shunts. In 10 infants born after Septem-
ber 1974, an attempt was first made to
control the hydrocephalus w/ repeated
LPs & diuretics prior to placing a shunt.
In 7 of 10 pts hydrocephalus was success-
fully arrested by medical therapy alone.
Kazan et al., Single-center retrospective review of pre- Class III
2005 term & LBW infants w/ IVH diagnosed
by ultrasonography (n = 42).
11 infants who required VP shunts were
compared w/ 31 who did not. All pts
received acetazolamide & furosemide
as an initial medical treatment.
Müller et al., Effect of aggressive LP schedule on PHH. Class III
1998 LPs started at 0–4 days; on average 11
LPs performed per pt, 15 ml/kg or end
of CSF flow per LP.
Used protein, red blood cell count, glu­
cose, & ventricle size to determine end
point.
Data Class, Quality, & Reasons
Class I
Consecutively enrolled infants randomized to
treatment (daily LP) (n = 24) or observation
only (n = 23).
10 of 24 infants treated w/ LP required shunts
& 9 of 23 infants in the observation-only
group required shunt placement for progres-
sive PHH & hydrocephalus.
Class III
w/ prematurity. Risks factors associated w/
need for a shunt were investigated. Infants
were followed for 1 yr.
Morbidities & mortalities were reported in a
quantitative fashion. Pts treated medically w/
acetazolamide showed no benefit; however,
infants treated w/ repeated CSF drainage
through LP did have a higher shunt infection
rate once the shunts were placed.
Class III
Retrospective review of 22 infants w/ PHH.
There were 2 cohorts: 12 pts treated w/ VP
shunt, & 10 pts treated w/ LP & diuretics.
Small, retrospective case series w/ grouping of
pts despite variable treatments.
Single-institution nonrandomized prospective
study.
16% complete resolution, 65% ventriculomega-
ly but no shunts, 19% w/ shunts.
Results & Conclusions
There were no statistical differences
in outcomes studied in infants
treated w/ observation alone &
infants treated w/ daily LP.
Although LP was safe, there was no
statistically significant reduction in
the need for shunt or progression
of PHH.
Infants w/ Grade III or IV IVH are at
the highest risk of PHH & hydro-
cephalus.
11 of 31 pts who required a shunt
developed shunt infection, which
was significantly associated w/
repeated LPs.
Follow-up when pt was 1–8 yrs of
age in 18 infants.
2 of 12 pts treated w/ permanent
shunts & 3 of 6 pts treated medi-
cally had IQ scores ≥85. These
results indicate a poor long-term
outlook for the LBW infant who de-
velops clinically overt hydrocepha-
lus after intracranial bleeding.
Risk factors for VP shunt included
IVH grade, later EGA at birth, &
age (days) at time of IVH, but not
treatment for IVH/PHH (acetazol-
amide, furosemide, LP, or external
ventricular drainage).
Serial LP should be started early for
treatment of hydrocephalus.

port of intravenous streptokinase, published in 1998, sug-
gested that there may be some benefit.45 This report was
followed by an early Class III study that found benefit in a
nonrandomized cohort of preterm infants with PHH who
were treated with intravenous low-dose streptokinase.76
However, data from a later Class II study led to the con-
clusion that routine use of intraventricular streptokinase
in PHH was not recommended.79 These studies were in-
cluded in the 2007 Whitelaw and Odd Cochrane review,74
which argues against intravenous streptokinase for the
treatment of PHH in preterm infants (Table 3).
Despite increased short-term morbidity and recurrent
IVH, some benefits were noted in the DRIFT survivors.72
In the most recent Whitelaw study,72 the reduction in the
primary long-term outcome—death or severe disability—
at 2 years in the DRIFT group reached statistical signifi-
cance when adjusted for sex, birth weight, and grade of
IVH. Severe cognitive disability also was reduced, and
this improvement in cognitive function was statistically
significant. There was also a reduction in severe senso-
rimotor disability with DRIFT, but this clinical improve-
ment did not reach statistical significance. The authors
hypothesized that the greater effect on cognitive rather
than sensorimotor function may be attributed to paren-

16 J Neurosurg: Pediatrics / Volume 14 / November 2014

Part 2: Management of posthemorrhagic hydrocephalus in infants
TABLE 3: Intraventricular thrombolytic agents: summary of evidence
Authors & Year Study Description
Whitelaw et Randomized multicenter clinical trial com-
al., 2007 paring standard treatment to DRIFT.
70 infants enrolled (34: DRIFT; 36: stan-
dard treatment).
Outcomes: pts at 6 mos of age or at
hospital discharge: death or VP shunt
surgery, secondary IVH, & infection.
Hudgins et al., Use of urokinase via reservoir to treat
1997 PHH in 18 pts. 4 different doses of
urokinase; pts ultimately grouped into
“high” (n = 9) & “low” dose (everyone
else, n = 9).
Both groups compared to historical control
group w/ respect to outcome & need for
shunt. Prospective, case control.
Whitelaw & Review & meta-analysis of 2 prospective
Odd, 2007 case-control studies (Luciano et al.,
1997 & Yapicioğlu et al., 2003).
Both source studies included total of 12
pts: 6 cases, 6 controls.
Meta-analysis.
Yapicioğlu et Single-blind prospective study.
al., 2003 12 preterm infants who developed PHH
were randomly assigned to the control
group (no treatment) or to receive
intraventricular streptokinase (×3 days).
Note: the streptokinase group also had
an LP (10–15 ml) prior to treatment &
then daily LPs (5–10 ml). They also
received intraventricular vancomycin.
Primary outcome: VP shunt placement.
Richard et al., Single-institution experience w/ Ommaya
2001 reservoir in 64 pts.
17 pts received fibrinolytic therapy through
Ommaya reservoir.
Whitelaw et Prospective Phase I trial of new treatment
al., 2003 methodology (DRIFT) for prevention of
PHH of prematurity.
Data from 24 pts compared w/ historical
controls. Outcome measures: death,
need for shunt, secondary IVH, infec-
tion, & neurodevelopmental outcome.
J Neurosurg: Pediatrics / Volume 14 / November 2014
Data Class, Quality, & Reasons
Class I
Multicenter randomized controlled trial.
Class II
Prospective nonrandomized case-
control series.
Division of 9 pts into “low” dose group
would appear to dilute statistical
power, despite statistical significance
obtained.
Class II
Both sources’ studies were Class II
(both were small randomized, pro-
spective case-control studies).
Class II
Small randomized, prospective study
Class III
Retrospective case series.
Statistics performed on fibrinolytic
therapy subgroup, which consisted of
2 different agents w/ multiple doses.
Fibrinolytic subgroup then mixed
back into overall outcome analysis.
Class III
Prospective Phase I trial in 24 pts &
compared w/ historical controls.
Results & Conclusions
15 of 34 pts (44%) in the DRIFT group
died or required a shunt, compared
w/ 19 of 36 pts (50%) who received
standard treatment.
12 of 34 pts (35%) in DRIFT group had
secondary IVH compared w/ 8% of pts
who received standard treatment.
Conclusion: DRIFT did not reduce shunt
surgery or death but was associated w/
an increased rate of secondary IVH.
“Low dose” urokinase reduced shunt rate
(71% vs 92%) compared to historical
controls.
Fewer shunt revisions in both groups
compared to control group.
No difference in mortality or VP shunt
rate was observed w/ intraventricular
streptokinase.
Intraventricular fibrinolytic therapy cannot
be recommended for infants following
IVH.
5 of 6 infants in the streptokinase group &
3 of 6 in the control group required VP
shunts.
No complications were noted.
Routine use of intraventricular streptoki-
nase in PHH was not recommended.
Fibrinolytic therapy led to statistically sig-
nificant lower rate of shunt placement
(31% vs 87%).
1 pt died. 17 of 23 (74%) did not require
a shunt. 2 pts experienced secondary
IVH, & 2 experienced infections. 19 pts
>12 mos had neurodevelopmental test-
ing: 8 (42%) were normal; 7 (37%) had
a single disability; 4 (21%) had multiple
disabilities.
Conclusion: Compared w/ historical
controls, DRIFT reduced the need for
shunts & showed a trend toward lower
rates of mortality & disability.
(continued)
17
 C. A. Mazzola et al.
TABLE 3: Intraventricular thrombolytic agents: summary of evidence (continued)

Authors & Year Study Description
Whitelaw et Prospective study of 9 preterm infants
al., 1992 w/ progressive posthemorrhagic
ventricular dilation who underwent a
48- to 72-hr continuous intraventricular
infusion of streptokinase.
Outcomes: death, need for shunt, second-
ary IVH, & infection.
Whitelaw et Phase I study to evaluate safety of tPA in
al., 1996 22 preterm infants w/ posthemorrhagic
ventricular dilation.
Dose-finding data reported.
Outcome measures: death & need for
shunt prior to discharge & secondary
IVH.
Data Class, Quality, & Reasons
Class III
Small, prospective, nonrandomized
cohort study (Phase I trial).
Class III
Small, prospective, nonrandomized
cohort study (Phase I trial).
Results & Conclusions
All pts survived; only 1 of 9 required a
shunt prior to discharge (later reports
indicated that a total of 4 of 9 ultimately
required shunts).
No infections, 1 repeat hemorrhage.
Dose-finding & pharmacokinetic data
reported ([tPA], half-life tPA).
21 (95%) of 22 pts survived. 9 (43%) of 21
pts required shunts. 1 pt experienced
secondary IVH.
Conclusion: tPA resulted in survival w/o
shunt in most pts.

chymal infarction in the periventricular white matter,
which was seen in about half of the infants enrolled in
the trial.72
Acetazolamide and Furosemide. Recommendation:
Acetazolamide and furosemide are not recommended as
methods to reduce the need for shunt placement in pre-
mature infants with PHH. Strength of Recommendation:
Level I, high clinical certainty.
After our review of the literature, we found two
Class I studies that reported that preterm infants with a
diagnosis of PHH who were treated with acetazolamide
and furosemide demonstrated higher risks of neurologi-
cal complications, morbidity, and mortality (Table 4).34,37
The International Posthemorrhagic Ventricular Dilation
(PHVD) Drug Trial Group reported that administration
of acetazolamide plus furosemide leads to higher rates of
shunt placement (relative risk 1.42) and morbidity (84%
vs 60%) compared with standard therapy.34 Kennedy et
al.37 reported that treatment of PHVD with acetazolamide
and furosemide did not decrease the rate of shunt place-
ment (64% in the acetazolamide/furosemide group vs
52% in the control group, not treated with acetazolamide/
furosemide).37 However, treatment was associated with an

TABLE 4: Acetazolamide/furosemide: summary of evidence*

Authors & Year Study Description
International Use of acetazolamide & furosemide in pts
PHVD Drug w/ PHH.
Trial Group, Comparison w/ standard therapy for shunt
1998 placement & neurological outcome.
Kennedy et al., Multicenter randomized controlled trial
2001 designed to test the hypothesis that
treatment of PHVD w/ acetazolamide &
furosemide (vs standard therapy) would
reduce: 1) risk of shunt placement or
death before 1 yr; & 2) death or dis-
ability at 1 yr.
177 pts recruited from 55 centers world-
wide.
Kazan et al., Single-center retrospective review of
2005 preterm & LBW infants diagnosed w/
IVH by ultrasonography (n = 42).
11 infants who required VP shunts were
compared w/ 31 infants who did not. All
pts received acetazolamide & furose-
mide as an initial medical treatment.
Data Class, Quality, & Reasons
Class I
Randomized controlled multicenter, well
designed.
Class I
Multicenter randomized controlled trial.
Positive: Excellent subject retention.
Therapeutic CSF removal in 56% of
pts (equivalent in both groups).
Negative: Acetazolamide & furosemide
administration was stopped in many
pts due to adverse effects. Also,
furosemide was given in the standard
therapy group in some cases.
Class III
Small retrospective case series w/ group-
ing of pts despite variable treatments.
Results & Conclusions
Acetazolamide & furosemide led to higher
rates of shunt placement (RR 1.42) &
higher morbidity (84% vs 60%) com-
pared w/ standard therapy
Treatment of PHVD w/ acetazolamide &
furosemide did not decrease the rate
of shunt placement (64% in acetazol-
amide/furosemide group vs 52% in
standard therapy group; RR = 1.23,
95% CI = 0.95–1.59) & was associated
w/ increased neurological morbidity
(81% vs 66%).
Authors concluded: “Treatment of PHVD
w/ acetazolamide & furosemide cannot
be recommended.”
Risk factors for VP shunt included IVH
grade, later EGA at birth, & age (days)
at time of IVH, but not treatment for
IVH/PHH (acetazolamide, furosemide,
LP, or external ventricular drainage).

*  RR = relative risk.

18 J Neurosurg: Pediatrics / Volume 14 / November 2014

Part 2: Management of posthemorrhagic hydrocephalus in infants

increased rate of neurological morbidity (81% vs 66%).37
Treatment of PHVD with acetazolamide and furosemide
was not recommended.37 One Class III study reported
this treatment was not associated with VP shunt place-
ment, but the severity of IVH (based on IVH grade) and
the patient age at the time of IVH were significantly asso-
ciated with the need for permanent CSF diversion.36 Ken-
nedy et al. also noted that the ventricular index at time of
entry into trial was the only factor significantly predictive
of death or need for shunt, after multiple logistic regres-
sion analysis.37
Timing of Shunt Placement
Strength of Recommendation: There is insufficient
evidence to recommend a specific infant weight or CSF
parameter to direct the timing of shunt placement in pre-
mature infants with PHH. Strength of Recommendation:
Level III, unclear degree of clinical certainty.
There were two Class III studies which evaluated the
lower limits of infant weight at time of initial shunt inser-
tion (Table 5).4,8 A weight of 1500 g was safely used as a
criterion for VP shunt placement in the Benzel study.8 A
single Class III study showed that CSF cell count, protein,
and glucose levels were not statistically related to the oc-
currence of shunt failure or infection in the study popula-
tion.24 The authors recommended that placement of the
shunt be timed when the infant’s age, weight, and overall
stability allow.24
Endoscopic Third Ventriculostomy
Recommendation: There is insufficient evidence to
recommend the use of endoscopic third ventriculostomy
(ETV) in premature infants with PHH. Strength of Rec-
ommendation: Level III, unclear degree of clinical cer-
tainty.
Although ETV was discussed in several full-text ar-

TABLE 5: Timing of shunt placement—specific weight or CSF parameter: summary of evidence

Authors & Year Study Description
Anwar et al., Consecutive, nonrandomized study of 19
1986 preterm infants w/ PHH who underwent
placement of reservoirs for symptom-
atic hydrocephalus.
Symptomatic hydrocephalus was defined
as presence of rapidly increasing OFC,
ventriculomegaly, & signs of increased
ICP, such as tense fontanelle, splayed
sutures, apnea, bradycardia, seizure,
feeding difficulties, or lethargy.
Benzel et al., 41 pts requiring ventricular drainage for
1992 hydrocephalus/PHH were evaluated
retrospectively. All drainage proce-
dures were performed in pts w/ IVH &
hydrocephalus (Grade III [25 pts]) & in
pts w/ IVH & IPH (Grade IV [16 pts]) in
whom medical management failed.
26 ventricular reservoirs were placed
in neonates weighing <1500 g; 18 of
these reservoirs were subsequently
converted to VP shunts.
Fulkerson et Premature infants w/ PHH have a high
al., 2011 risk of shunt obstruction & infection.
Risk factors for complications include
grade of IVH & age at shunt insertion.
There is anecdotal evidence that the
amount of red blood cells or protein
levels in the CSF may also increase
shunt complications.
This study examined whether any rela-
tionship exists between CSF constitu-
ents & shunt malfunction or infection.
Data Class, Quality, & Reasons
Class III
Case series study of infants who
weighed <2000 g & were treated w/
reservoirs. Data include morbidity,
mortality, & need for shunt place-
ment in these infants.
There was no comparison w/ a cohort
of nontreated infants or infants
treated w/ ventricular drains.
Class III
Retrospective case series of 41 con-
secutive premature infants.
Class III
Retrospective cohort study evaluating
the risk factors for shunt failure in
preterm infants w/ IVH & PHH.
Inclusion criteria & preintervention
data points (baselines) were well
documented. Outcomes reported
included early shunt failure or infec-
tion w/in 3 mos of shunt.
“Each CSF parameter was modeled as
a possible predictor of the presence
or absence of shunt malfunction or
infection. Statistical significance was
set at a probability level < 0.05.”
Results & Conclusions
Authors concluded that reservoirs provide safe
& effective treatment for infants w/ PHH &
symptomatic hydrocephalus.
Authors endorse reservoirs as an alternative to
early shunts & report that this strategy may
“reduce the incidence of shunt infection as
well as noninfectious shunt complications.”
There was a VP shunt &/or reservoir infection
in 32% of pts.
59% of pts required a shunt revision during the
1st yr of life.
No Grade IV pts achieved normal functional
level, while 10 Grade III pts did. The inci-
dence of severe developmental delay (44%
vs 28%) & death (38% vs 12%) was greater
in the Grade IV than in Grade III pts.
Authors concluded that neither CSF cell count
nor protein or glucose levels were statisti-
cally related to the occurrence of shunt
failure or infection in the study population.
The authors recommend that placement of
the shunt be timed when age, weight, & the
overall stability of the infant allow.

J Neurosurg: Pediatrics / Volume 14 / November 2014 19

 C. A. Mazzola et al.

ticles that we reviewed, there was insufficient evidence
available for us to make a recommendation for or against
its use for the treatment of PHH in premature infants
(Table 6). Endoscopic third ventriculostomy for the treat-
ment of hydrocephalus in infants and children will be
discussed more thoroughly in subsequent chapters (in
particular, Part 4).42
Excluded Studies
We excluded 1 Class III study for low “preterm” pa-
tient representation (7 patients); in the review of 52 con-
secutive ETV procedures in 49 infants with hydrocepha-
lus, most infants (31 patients) had aqueductal stenosis.20
Of the 7 infants with preterm PHH, 6 required a shunt
even after ETV. Infants with PHH from premature birth
did not benefit from ETV.20 We excluded another Class
III study including patients with different etiologies for
hydrocephalus.44 Although ETV was successful in 57%
of patients (8 of 14), the majority of those infants had
congenital aqueductal stenosis without PHH. In the re-
maining 6 patients, a VP shunt was needed. In 1 Class III
single-institution retrospective case series, 18 preterm in-
fants with PHH were treated initially with Ommaya res-
ervoir placement: 1 patient died, 5 patients received a VP
shunt, and 9 patients underwent ETV.56 Three patients did
not require any further intervention. While overall, 59%
were shunt free at the last follow-up, 5 of the 9 patients
who were treated with ETV had to undergo repeated sur-
gery for VP shunt placement. The authors recommended
combining placement of an Ommaya reservoir with ETV
to reduce shunt dependency for preterm infants with
PHH.56 There was a large (101 patients) Class III multi-
center, retrospective study evaluating the success rate of
ETV in patients with hydrocephalus from subarachnoid
hemorrhage, IVH, and/or CSF infection; a minority of
the patients (25% [25 of 101]) had PHH of prematurity.65
Overall, ETV was successful in 52% of the infants with
PHH of prematurity. Endoscopic third ventriculostomy
was successful in 100% (13 of 13) of children with a his-

TABLE 6: Endoscopic third ventriculostomy for PHH in premature infants: summary of evidence*

Authors & Year Study Description
Elgamal et al., Review of 52 consecutive ETV procedures
2011 in 49 infants w/ hydrocephalus not nec-
essarily associated w/ preterm IVH.
Most infants (n = 31) had aqueductal
stenosis. The remaining infants w/
hydrocephalus had other causes for it
including Chiari II, Dandy-Walker cysts,
quadrigeminal lipoma, & cerebellopon-
tine angle arachnoid cyst. Only 6 pts
had PHH caused by preterm IVH.
Lipina et al., Retrospective consecutive case series of
2008 14 infants <6 mo of age presenting w/
obstructive hydrocephalus.
8 of 14 pts had PHH.
ETV was considered successful when a
VP shunt was not necessary.
Peretta et al., Single-institution retrospective review of
2007 18 consecutive preterm infants w/ PHH.
Pts were treated w/ placement of an Om-
maya reservoir for temporizing ventricu-
lar decompression. When necessary,
pts later underwent VP shunt placement
(n = 5) or ETV (n = 9).
Siomin et al., Multicenter retrospective case series of
2002 101 pts who underwent ETV for hemor-
rhage or infection. Both pediatric &
adult pts included.
Of the 101 pts, 25 were treated for PHH
of prematurity, & specific data were
reported for this cohort.
Successful ETV was defined as no further
hydrocephalus operations required.
Data Class, Quality, & Reasons
Class III
Case series of infants treated w/ an ETV.
Infants were followed up for 68 mos on
average.
6 of the 7 infants w/ PHH from premature
birth required a shunt.
Class III
This study included a small number of
pts w/ very different etiologies for
hydrocephalus.
Class III
Small single-institution retrospective case
series w/ variable treatment patterns.
3 of the surviving 17 infants (17.6%)
treated w/ Ommayas did not require
additional surgery. 14 of 17 required VP
shunt (n = 5) or ETV (n = 9).
While additional surgeries were required
in the majority of cases, 59% of pts
were shunt free at the last follow-up.
Class III
Multicenter study w/ a minority of pts
(25%) w/ PHH of prematurity.
Results & Conclusions
Authors concluded that the success rate
of 69.4% indicates that ETV is safe &
effective in infants w/ hydrocephalus
not associated w/ PHH & prematurity.
Infants w/ PHH from premature birth did
not benefit from ETV.
ETV was successful in 57% of pts—the
majority of them w/ primary aqueductal
stenosis. In the remaining 6 pts, a VP
shunt was needed.
Recommended combining Ommaya
placement w/ ETV. It reduces shunt
dependency in this condition.
ETV was successful in 52% of pts w/ PHH
of prematurity.
Note: ETV was successful in 13 of 13
of pts w/ PHH who were previously
treated w/ a shunt, whereas it was
unsuccessful in 12 of 12 pts treated w/
ETV as the first-line treatment.
ETV was not successful in pts w/ both
hemorrhage & infection.

20 J Neurosurg: Pediatrics / Volume 14 / November 2014

Part 2: Management of posthemorrhagic hydrocephalus in infants
tory of preterm PHH, even though these patients were
initially treated with a shunt. Endoscopic third ventricu-
lostomy was unsuccessful in 12 of 12 infants treated with
ETV as the first-line treatment, following preterm PHH.
In patients with both hemorrhage and infection, ETV was
not successful.65
Conclusions
Surgical Temporizing Measures
Recommendation: Ventricular access devices (VADs),
external ventricular drains (EVDs), ventriculosubgaleal
(VSG) shunts, or lumbar punctures (LPs) are treatment
options in the management of posthemorrhagic hydro-
cephalus (PHH). Clinical judgment is required. Strength
of R ecommendation: Level II, moderate degree of clini-
cal certainty.
Recommendation: The evidence demonstrates that
VSG shunts reduce the need for daily CSF aspiration com-
pared with VADs. Strength of Recommendation: Level II,
moderate degree of clinical certainty.
The evidence demonstrates that VADs reduce mor-
bidity and mortality compared with EVDs.
Routine Use of Serial Lumbar Punctures
Recommendation: The routine use of serial lumbar
puncture (LP) is not recommended to reduce the need for
shunt placement or to avoid the progression of hydroceph-
alus in premature infants. Strength of Recommendation:
Level I, high clinical certainty.
Nonsurgical Temporizing Measures
Recommendation: Intraventricular thrombolytic agents
including tissue plasminogen activator (tPA), urokinase,
or streptokinase are not recommended as methods to re-
duce the need for shunt placement in premature infants
with PHH. Strength of Recommendation: Level I, high
clinical certainty.
Recommendation: Acetazolamide and furosemide are
not recommended as methods to reduce the need for shunt
placement in premature infants with PHH. Strength of
Recommendation: Level I, high clinical certainty.
Timing of Shunt Placement
Recommendation: There is insufficient evidence to
recommend a specific weight or CSF parameter to direct
the timing of shunt placement in premature infants with
PHH. Clinical judgment is required. Strength of Recom-
mendation: Level III, unclear clinical certainty.
Endoscopic Third Ventriculostomy
Recommendation: There is insufficient evidence to
recommend the use of endoscopic third ventriculostomy
(ETV) in premature infants with PHH. Strength of Rec-
ommendation: Level III, unclear clinical certainty.
Acknowledgments
We acknowledge the American Association of Neurologi-
cal Surgeons (AANS)/Congress of Neurological Surgeons (CNS)
J Neurosurg: Pediatrics / Volume 14 / November 2014
Joint Guidelines Committee for the members’ reviews, comments,
and suggestions; the Hydrocephalus Association and Debby Buffa,
patient advocate representative, for participation and input through-
out the guidelines development; Pamela Shaw, research librarian,
for her assistance with the literature searches; Kevin Boyer for his
assistance with data analysis; and Sue Ann Kawecki for her assis-
tance with editing.
We acknowledge the following individuals for their contribu-
tions throughout the review process: Timothy Ryken, M.D.; Kevin
Cockroft, M.D.; Sepideh Amin-Hanjani, M.D.; Steven N. Kalkanis,
M.D.; David P. Adelson, M.D.; Brian L. Hoh, M.D.; Mark D. Krieg-
er, M.D.; Mark E. Linskey, M.D.; Jeffrey J. Olson, M.D.; Patricia
Raskin, M.D.; Krystal L. Tomei, M.D.; and Monica Wehby, M.D.
Disclosure
Dr. Limbrick receives research funding from the National
Institute of Neurological Disorders and Stroke. The systematic
review and evidence-based guidelines were funded exclusively by
the CNS and AANS Pediatric Section, which received no funding
from outside commercial sources to support the development of this
document.
Conflict(s) of Interest: None. All Pediatric Hydrocephalus
Systematic Review and Evidence-Based Guidelines Task Force
members declared any potential conflicts of interest prior to begin-
ning work on this systematic review and evidence-based guidelines.
Author contributions to the study and manuscript preparation
include the following. Conception and design: AANS/CNS Joint
Section on Pediatrics. Acquisition of data: all authors. Analysis and
interpretation of data: all authors. Drafting the article: Mazzola. Crit-
ically revising the article: all authors. Reviewed submitted version of
manuscript: all authors. Approved the final version of the manuscript
on behalf of all authors: Flannery. Administrative/technical/material
support: all authors. Study supervision: Flannery.
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Manuscript submitted June 25, 2014.
Accepted July 7, 2014.
Please include this information when citing this paper: DOI:
10.3171/2014.7.PEDS14322.
Address correspondence to: Ann Marie Flannery, M.D., Depart-
ment of Neurological Surgery, Saint Louis University, 3565 Vista
Ave., St. Louis, MO 63110. email: flanneam@slu.edu.
23