J Neurosurg Pediatrics (Suppl) 14:8–23, 2014
8 J Neurosurg: Pediatrics / Volume 14 / November 2014
©AANS, 2014
Although 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-
Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 2: Management of posthemorrhagic hydrocephalus in premature infantsCatherine 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
1Division 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 • ventricular dilation • ventricular index • head circumference • in utero • shunt • reservoir • endoscopic third ventriculostomy • ventriculoperitoneal shunt • practice guidelines
Abbreviations used in this paper: AANS = American Association of Neurological Surgeons; CDC = Centers for Disease Control and Prevention; CNS = Congress of Neurological Surgeons; ELBW = extremely low birth weight; ETV = endoscopic third ventriculos-tomy; EVD = external ventricular drain; HUS = head ultrasound; 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.
Part 2: Management of posthemorrhagic hydrocephalus in infants
9J Neurosurg: Pediatrics / Volume 14 / November 2014
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.
MethodsSearch Criteria
Both the US National Library of Medicine and the
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 “hydro ceph-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].
StrategyTwo 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 ResultsOf 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-
C. A. Mazzola et al.
10 J Neurosurg: Pediatrics / Volume 14 / November 2014
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,
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.
ResultsSurgical 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
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.
Part 2: Management of posthemorrhagic hydrocephalus in infants
11J Neurosurg: Pediatrics / Volume 14 / November 2014
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
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 PunctureRecommendAtion: 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 AgentsIntraventricular 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-
C. A. Mazzola et al.
12 J Neurosurg: Pediatrics / Volume 14 / November 2014
TABL
E 1:
Surg
ical
tem
poriz
ing
mea
sure
s: su
mm
ary o
f evid
ence
*
Auth
ors &
Yea
rSt
udy D
escr
iption
Data
Clas
s, Qu
ality,
& R
easo
nsRe
sults
& C
onclu
sions
Corn
ips et
al.,
1997
Retro
spec
tive r
eview
of 14
pts w
/ Gra
de II
I or G
rade
IV IV
H dia
gnos
ed on
HUS
stud
y & tr
eated
w/ E
VD.
14 pt
s wer
e com
pare
d w/ a
histo
rical
coho
rt of
15 in
fants
w/
simila
r Gra
de II
I/IV
IVH.
Clas
s II
Retro
spec
tive r
eview
of 2
coho
rts: p
rema
ture i
nfants
tre
ated w
/ EVD
vs th
ose t
reate
d med
ically
.
Ventr
icular
drain
age i
s a sa
fe op
tion f
or in
fants
w/ P
HH.
Gurtn
er et
al.,
1992
Retro
spec
tive c
onse
cutiv
ely en
rolle
d stu
dy of
736 L
BW in
fants
(<
1500
g).
After
exclu
sion o
f som
e infa
nts fo
r var
ious r
easo
ns, 5
47 in
fants
were
inclu
ded i
n the
retro
spec
tive c
onse
cutiv
e rev
iew.
Shun
ts we
re pl
aced
for p
rogr
essiv
e hyd
roce
phalu
s & O
FC >
95
perc
entile
.3 y
rs of
data
exam
ined b
y yr, b
y ana
lyses
of va
rianc
e, &
Dunc
an’s
mean
comp
ariso
n tes
ts.Ch
i-squ
are a
nalys
es on
disc
rete
varia
bles s
uch a
s rate
s of
comp
licati
on &
mor
tality
. Stu
dent
t-tes
t w/ B
onfer
roni
cor-
recti
ons.
Spea
rman
corre
lation
coef
ficien
ts we
re co
mpute
d wh
en ap
prop
riate.
Qua
ntita
tive d
ata a
re pr
esen
ted.
Clas
s II
Cons
ecut
ive, b
ut no
t a ra
ndom
ized c
ontro
lled s
tudy
.A
nonr
ando
mize
d hist
orica
l coh
ort, c
ompa
red b
y yr o
f tre
atmen
t & tr
eatm
ent t
ype.
1st y
r: EV
D.2n
d & 3
rd yr
: sub
cuta
neou
s res
ervo
ir was
used
.Ou
tcome
s eva
luated
: mor
bidity
, mor
tality
, & ne
ed fo
r sh
unt r
evisi
on.
Freq
uenc
y & m
orta
lity of
Gra
des I
II & IV
hemo
rrhag
e in
infan
ts we
ighing
btwn
500
& 70
0 g re
maine
d re
lative
ly co
nsta
nt ov
er th
e 3-y
r per
iod.
Auth
ors c
onclu
ded t
hat th
ere w
as a
signifi
cant
redu
c-tio
n in m
orbid
ity &
mor
tality
asso
ciated
w/ L
BW
infan
ts wh
en th
ey be
gan u
sing r
eser
voirs
inste
ad of
EV
Ds.
Hudg
ins et
al.,
1997
Use o
f uro
kinas
e via
rese
rvoir
to tr
eat P
HH in
18 pt
s. 4 d
iffer-
ent d
oses
of ur
okina
se; u
ltimate
ly gr
oupe
d into
“high
” (n =
9)
& “l
ow” d
ose (
ever
yone
else
, n =
9).
Both
grou
ps co
mpar
ed to
histo
rical
contr
ol gr
oup w
/ res
pect
to ou
tcome
& ne
ed fo
r shu
nt. P
rosp
ectiv
e, ca
se co
ntrol.
Clas
s II
Pros
pecti
ve, n
onra
ndom
ized,
case
-con
trol s
eries
.Di
vision
of 9
pts in
to “lo
w” do
se gr
oup w
ould
appe
ar to
dil
ute st
atisti
cal p
ower
desp
ite st
atisti
cal s
ignific
ance
ob
taine
d.
“Low
dose
” uro
kinas
e red
uced
shun
t rate
(71%
vs 92
%)
comp
ared
to hi
storic
al co
ntrols
. Few
er sh
unt r
evi-
sions
in bo
th gr
oups
comp
ared
to co
ntrol
grou
p.
Lam
& He
il-ma
n, 20
09Si
ngle-
institu
tion,
retro
spec
tive h
istor
ical c
ohor
t stu
dy of
32
prete
rm in
fants
w/ P
HH. T
his st
udy c
ompa
red 2
coho
rts of
inf
ants:
thos
e tre
ated w
/ VAD
/Omm
aya p
lacem
ent v
s tho
se
treate
d w/ V
SG sh
unts.
Ther
e wer
e no s
tatis
tical
differ
ence
s in a
ge or
birth
weig
ht of
the i
nfants
in th
e 2 gr
oups
. The
grou
ps w
ere s
tudie
d for
IVH
grad
e, ne
ed fo
r dail
y CSF
with
draw
al, C
SF le
ak fr
om th
e sc
alp, C
SF in
fectio
n, &
need
for a
VP
shun
t.
Clas
s II
A ch
i-squ
are t
est w
as pe
rform
ed (c
2 = 19
.2, d
f = 1,
p =
0.000
016,
p < 0.
05),
which
show
ed th
at VS
G sh
unts
signifi
cantl
y red
uced
the n
eed f
or da
ily C
SF as
pira-
tion c
ompa
red t
o VAD
s.Th
e high
er ra
te of
comp
licati
ons o
f VSG
shun
ts wa
s not
statis
ticall
y sign
ifican
t com
pare
d w/ th
e VAD
grou
p (p
= 0.
17).
93.75
% (1
5 of 1
6 pts)
in th
e VAD
grou
p req
uired
VP
shun
ts wh
ile 71
.42%
(10 o
f 14 p
ts) in
the V
SG sh
unt
grou
p nee
ded V
P sh
unts.
Ther
e was
a tre
nd to
ward
VP
shun
t inde
pend
ence
in
the V
SG sh
unt g
roup
, as c
ompa
red t
o the
VAD
gr
oup,
but it
did n
ot re
ach s
ignific
ance
.VS
G sh
unts
decr
ease
d the
need
for d
aily t
aps.
Ther
e wa
s a sl
ightly
high
er ra
te of
comp
licati
ons i
n the
VS
G sh
unt g
roup
, but
it was
not s
ignific
ant.
Anwa
r et a
l., 19
86Co
nsec
utive
, non
rand
omize
d stu
dy of
19 pr
eterm
infa
nts w
/ PH
H wh
o und
erwe
nt pla
ceme
nt of
rese
rvoir
s for
symp
tom-
atic h
ydro
ceph
alus.
Symp
tomati
c hyd
roce
phalu
s was
defin
ed as
infa
nts w
/ rap
idly
incre
asing
OFC
, ven
tricu
lomeg
aly, &
sign
s of in
crea
sed I
CP
pres
ent, s
uch a
s ten
se fo
ntan
elle,
splay
ed su
tures
, apn
ea,
brad
ycar
dia, s
eizur
e, fe
eding
diffic
ulties
, or le
thar
gy.
Clas
s III
Stud
y was
a ca
se se
ries o
f infa
nts w
eighin
g <20
00 g,
w/
clea
r CSF
& tr
eated
w/ r
eser
voirs
.Th
ere w
as on
ly lim
ited p
rese
ntati
on of
quali
tativ
e &
quan
titativ
e dat
a. Da
ta in
clude
d: mo
rbidi
ty, m
orta
lity,
& ne
ed fo
r shu
nt pla
ceme
nt in
thes
e infa
nts.
Ther
e was
no co
mpar
ison w
/ a co
hort
of no
ntrea
ted
infan
ts or
infa
nts tr
eated
w/ v
entri
cular
drain
s.
The a
utho
rs co
nclud
ed th
at re
serv
oirs p
rovid
e safe
&
effec
tive t
reatm
ent fo
r infa
nts w
/ PHH
& sy
mptom
-ati
c hyd
roce
phalu
s.
(cont
inued
)
Part 2: Management of posthemorrhagic hydrocephalus in infants
13J Neurosurg: Pediatrics / Volume 14 / November 2014
TABL
E 1:
Surg
ical
tem
poriz
ing
mea
sure
s: su
mm
ary o
f evid
ence
* (co
ntin
ued)
Auth
ors &
Yea
rSt
udy D
escr
iption
Data
Clas
s, Qu
ality,
& R
easo
nsRe
sults
& C
onclu
sions
Benz
el et
al.,
1993
41 pt
s req
uiring
ventr
icular
drain
age f
or hy
droc
epha
lus/P
HH
were
evalu
ated r
etros
pecti
vely.
All d
raina
ge pr
oced
ures
wer
e per
form
ed on
pts w
/ IVH
& hy
-dr
ocep
halus
(Gra
de II
I [25 p
ts]) &
pts w
/ IVH
& IP
H (G
rade
IV
[16 p
ts]) in
who
m me
dical
mana
geme
nt ha
d fail
ed.
Clas
s III
Retro
spec
tive c
ase s
eries
of 41
cons
ecut
ive pr
ematu
re
infan
ts.26
ventr
icular
rese
rvoir
s (Ri
ckha
m or
McC
omb r
eser
-vo
irs) w
ere p
laced
in ne
onate
s weig
hing <
1500
g,
allow
ing fo
r safe
but in
termi
ttent
ventr
icular
acce
ss.
18 of
thes
e res
ervo
irs w
ere s
ubse
quen
tly co
nver
ted
to VP
shun
ts. 32
% of
pts d
evelo
ped a
VP
shun
t &/or
re
serv
oir in
fectio
n & 59
% re
quire
d a sh
unt r
evisi
on
durin
g the
1st y
r of li
fe.No
Gra
de IV
pts a
chiev
ed no
rmal
func
tiona
l leve
l, whil
e 10
Gra
de III
pts d
id. T
he in
ciden
ce of
seve
re de
vel-
opme
ntal
delay
(44%
vs 28
%) &
death
(38%
vs 12
%)
was g
reate
r in G
rade
IV th
an in
Gra
de II
I pts.
Auth
ors s
tate,
“The
plac
emen
t of v
entri
cular
rese
rvoir
s is
acce
ptab
le as
an al
terna
tive t
o ear
ly pla
ceme
nt of
ventr
iculo-
perit
onea
l shu
nts. T
his ap
proa
ch m
ay
redu
ce th
e inc
idenc
e of s
hunt
infec
tion a
s well
as
nonin
fectio
us sh
unt c
ompli
catio
ns.”
Berg
er et
al.,
2000
Retro
spec
tive r
eview
of ou
tcome
s afte
r plac
emen
t of E
VDs
in 37
prem
ature
infa
nts (5
1 dra
ins).
PHH
diagn
osed
by
ultra
soun
d.
Clas
s III
Sing
le-ins
titutio
n retr
ospe
ctive
revie
w.Ne
urod
evelo
pmen
tal o
utcom
e dep
ende
nt on
exten
t of
pare
nchy
mal in
jury.
Infec
tion r
ates:
5.4%
pts,
3.9%
drain
. 11 o
f 37 p
ts did
no
t req
uire s
hunt
place
ment.
Brou
wer e
t al.,
2007
Sing
le-ce
nter r
etros
pecti
ve re
view
of 76
prete
rm in
fants
tre
ated f
or P
HVD
w/ ve
ntricu
lar re
serv
oirs.
Infec
tion r
ates w
ere m
easu
red i
n 2 su
cces
sive 6
-yr in
terva
ls.
No. o
f res
ervo
ir pun
cture
s also
exam
ined.
Clas
s III
Sing
le-ce
nter r
etros
pecti
ve re
view.
Whil
e the
no. o
f res
ervo
ir pun
cture
s did
not c
hang
e, th
e infe
ction
rate
was l
ower
in th
e 2nd
, mor
e rec
ent
inter
val (2
of 5
0 pts
[4%] v
s 5 of
26 pt
s [19
.2%
]).Co
nclus
ion: R
isks a
ssoc
iated
w/ v
entri
cular
rese
rvoir
s ar
e w/in
acce
ptab
le lim
its.
de V
ries e
t al.,
2002
Retro
spec
tive r
eview
of co
nsec
utive
prete
rm in
fants
(EGA
≤3
4 wks
) w/ G
rade
III I
VH tr
eated
for p
osth
emor
rhag
ic ve
ntricu
lar di
latati
on in
5 co
llabo
ratin
g NIC
Us (n
= 9
5). P
ts we
re su
bdivi
ded i
nto ea
rly in
terve
ntion
or la
te int
erve
ntion
gr
oups
, dep
endin
g on t
heir v
entri
cular
inde
x at th
e tim
e of
initia
l trea
tmen
t.
Clas
s III
Mult
icente
r stu
dy, r
etros
pecti
ve ca
se se
ries.
Trea
tmen
ts we
re no
t sta
ndar
dized
trea
tmen
ts.LP
s, re
serv
oir, &
shun
t.
Early
trea
tmen
t was
asso
ciated
w/ a
redu
ced r
equir
e-me
nt fo
r VP
shun
t (OR
= 0.
22) &
redu
ced r
isk of
mo
dera
te-to
-sev
ere d
isabil
ity.
Gask
ill et
al.,
1988
The u
se of
a su
bcut
aneo
us re
serv
oir w
as st
udied
in a
con-
secu
tive,
nonr
ando
mize
d ser
ies of
38 i
nfants
w/ p
reter
m IV
H &
PHH.
In al
l infa
nts LP
& m
edica
l trea
tmen
t had
faile
d.
Clas
s III
Retro
spec
tive s
tudy
of a
serie
s of p
rema
ture i
nfants
wh
o req
uired
temp
orizi
ng m
easu
res (
rese
rvoir
plac
e-me
nt) af
ter m
edica
l trea
tmen
t/LP
for P
HH ha
d fail
ed.
Ther
e wer
e 28 s
urviv
ors o
vera
ll (8 d
ied be
fore
a sh
unt
could
be pl
aced
, 2 di
ed af
ter sh
unt p
lacem
ent).
4 su
rvivo
rs (1
5%) d
id no
t req
uire a
shun
t.
The a
utho
rs co
nclud
ed th
at ea
rly re
serv
oir pl
acem
ent
is a f
easib
le, sa
fe, &
effe
ctive
trea
tmen
t for P
HH
asso
ciated
w/ p
reter
m IV
H.
Harb
augh
et
al., 1
981
Retro
spec
tive r
eview
of 11
prem
ature
infa
nts w
/ IVH
& P
HH
who w
ere t
reate
d w/ tu
nnele
d EVD
. The
mea
n dur
ation
of
drain
age f
or th
is gr
oup w
as 20
.7 da
ys.
No m
orbid
ity or
mor
tality
occu
rred a
s a re
sult.
7 of 1
1 pts
requ
ired a
shun
t. 2 of
11 di
d not
requ
ire a
VP sh
unt.
Clas
s III
Small
retro
spec
tive c
ase r
eview
.EV
D via
a su
bcut
aneo
usly
tunne
led ca
thete
r was
fo
und t
o be a
safe
& re
liable
initia
l meth
od of
trea
t-ing
PHH
in pr
ematu
re in
fants
.
(cont
inued
)
C. A. Mazzola et al.
14 J Neurosurg: Pediatrics / Volume 14 / November 2014
TABL
E 1:
Surg
ical
tem
poriz
ing
mea
sure
s: su
mm
ary o
f evid
ence
* (co
ntin
ued)
Auth
ors &
Yea
rSt
udy D
escr
iption
Data
Clas
s, Qu
ality,
& R
easo
nsRe
sults
& C
onclu
sions
Heep
et al
., 20
01Sa
fety/e
fficac
y of R
ickha
m re
serv
oir pl
acem
ent fo
r pts
w/
PHH.
Clas
s III
Retro
spec
tive r
eview
. Bro
ad in
clusio
n crit
eria
for
rese
rvoir
plac
emen
t.No
comp
ariso
n w/ p
ts ma
nage
d w/ o
ther
meth
ods.
Omma
ya/R
ickha
m re
serv
oir is
a sa
fe, ef
fectiv
e opti
on
for m
anag
ing P
HH un
til pt
is re
ady f
or a
shun
t. 5%
inf
ectio
n rate
, 85%
of pt
s nee
ded a
shun
t.
Hudg
ins et
al.,
1998
Use o
f VAD
in 14
9 pts
w/ P
HH. D
aily t
aps f
or 1s
t “se
vera
l” da
ys (1
0–15
cm3 /k
g).Cl
ass I
IISi
ngle-
institu
tion r
etros
pecti
ve ca
se se
ries.
Shun
ts pla
ced a
t 2 kg
if pt
was s
till sy
mptom
atic,
but
crite
ria no
t oth
erwi
se cl
ear o
n whe
n to s
top V
AD
aspir
ation
s.
8% in
fectio
n & 20
% re
vision
rates
. 88%
shun
t impla
nta-
tion r
ate.
Kaza
n et a
l., 20
05Re
trosp
ectiv
e rev
iew of
prete
rm &
LBW
infa
nts di
agno
sed w
/ IV
H by
ultra
soun
d (n =
42).
11 in
fants
who
requ
ired V
P sh
unts
were
comp
ared
w/ 3
1 who
did
not. A
ll pts
rece
ived a
ceta
zolam
ide &
furo
semi
de as
an
initia
l med
ical tr
eatm
ent.
Clas
s III
Small
, sing
le-ce
nter r
etros
pecti
ve ca
se se
ries w
/ gr
oupin
g of p
ts de
spite
varia
ble tr
eatm
ents.
Risk
facto
rs fo
r VP
shun
t inclu
ded I
VH gr
ade,
later
EG
A at
birth,
& ag
e (da
ys) a
t time
of IV
H, bu
t not
treatm
ent fo
r IVH
/PHH
(ace
tazo
lamide
, fur
osem
ide,
LP, &
exter
nal v
entri
cular
drain
age).
Korm
anik
et al.
, 201
0Re
trosp
ectiv
e rev
iew of
the o
utcom
e of in
fants
rece
iving
a ve
ntricu
lar re
serv
oir fo
r PHH
.Cl
ass I
IIRe
trosp
ectiv
e obs
erva
tiona
l stu
dy: a
revie
w of
medic
al re
cord
s of a
ll infa
nts w
ho re
ceive
d a ve
ntricu
lar
rese
rvoir
in 1
cente
r bet
ween
2000
& 20
07.
35 ve
ntricu
lar re
serv
oirs w
ere p
laced
. 6 pt
s (17
%) w
ere
exclu
ded.
29 pt
s had
a tot
al of
681 t
aps.
Ther
e was
no
incr
ease
d risk
of in
fecti
on fr
om re
peate
d or d
aily
aspir
ation
.On
ly 1 C
SF cu
lture
-pro
ven r
eser
voir i
nfecti
on: C
andid
a alb
icans
.Kr
euss
er et
al.,
1984
Stud
y of 1
9 con
secu
tive i
nfants
w/ P
HH do
cume
nted b
y CT
or cr
anial
ultra
soun
d, &
ICP
meas
urem
ent b
y an i
ndwe
lling
ICP
monit
or.5 o
f 19 p
ts we
re in
itially
trea
ted w
/ LP,
30–4
0 ml C
SF dr
ained
da
ily fo
r 5–7
days
.Su
rvivi
ng pt
s wer
e eva
luated
w/ th
e Bay
ley S
cale
of Inf
ant
Deve
lopme
nt, th
e Car
tell In
fant
Intell
igenc
e Sca
le, or
the
Stan
ford
-Bine
t Intel
ligen
ce Te
st, ba
sed o
n the
child
’s ag
e at
evalu
ation
. Dev
elopm
enta
l quo
tient
(DQ)
was
deter
mine
d us
ing th
e Den
ver D
evelo
pmen
tal S
cree
ning T
est.
Clas
s III
Case
serie
s of a
grou
p of 1
9 con
secu
tive i
nfants
tre
ated w
/ exte
rnal
ventr
icular
drain
age.
Ther
e wa
s no r
ando
miza
tion t
o tre
at or
not tr
eat, &
no
rand
omiza
tion o
f typ
e of tr
eatm
ent. T
here
was
no
case
-con
trolle
d com
para
tive c
ohor
t or g
roup
.
Exter
nal v
entri
cular
drain
age d
ecre
ased
ventr
icular
siz
e.3 i
nfants
did n
ot de
velop
recu
rrent
hydr
ocep
halus
& di
d no
t req
uire a
shun
t. 16 i
nfants
suffe
red r
ecur
rent
hy-
droc
epha
lus, w
/in 1
wk af
ter dr
ain re
mova
l. Ano
ther
EV
D wa
s plac
ed in
10 pt
s.Fo
llowi
ng re
peate
d EVD
s, 9 o
f the 1
0 infa
nts w
ere
stable
enou
gh fo
r a sh
unt. T
he au
thor
s con
clude
th
at EV
D is
a safe
& ef
fectiv
e tre
atmen
t for P
HH.
Limbr
ick et
al.,
2010
Larg
e sing
le-ce
nter r
etros
pecti
ve re
view
of 32
5 pre
term
infan
ts w/
Gra
de II
I or I
V IV
H. T
he de
velop
ment
of PH
H &
the n
eed f
or a
tempo
rizing
devic
e (VA
D or
VSG
shun
t) we
re
studie
d. Inf
ectio
ns, c
ompli
catio
ns, &
need
for V
P sh
unt
were
analy
zed,
as w
as th
e mor
tality
rate.
Clas
s III
Retro
spec
tive a
nalys
is sh
owed
75.4%
of th
e 65 i
nfants
tre
ated w
/ VAD
need
ed a
shun
t; 66.7
% of
the 3
0 tre
ated w
/ VSG
shun
ts re
quire
d a sh
unt.
Ther
e was
no si
gnific
ant d
iffere
nce i
n the
infe
ction
rate
betw
een V
AD &
VSG
shun
ts, re
vision
rate,
or V
P sh
unt in
fectio
n afte
rwar
ds.
Ther
e was
no si
gnific
ant d
iffere
nce i
n outc
ome b
e-tw
een i
nfants
trea
ted w
/ VAD
or V
SG sh
unts. (co
ntinu
ed)
Part 2: Management of posthemorrhagic hydrocephalus in infants
15J Neurosurg: Pediatrics / Volume 14 / November 2014
TABL
E 1:
Surg
ical
tem
poriz
ing
mea
sure
s: su
mm
ary o
f evid
ence
* (co
ntin
ued)
Auth
ors &
Yea
rSt
udy D
escr
iption
Data
Clas
s, Qu
ality,
& R
easo
nsRe
sults
& C
onclu
sions
Rahm
an et
al.,
1993
Sing
le-ins
titutio
n, sm
all re
trosp
ectiv
e rev
iew of
37 pt
s w/ P
HH,
31 of
who
m re
quire
d VP
shun
t.Cl
ass I
IIOb
serv
ation
al stu
dy of
outco
mes.
LP, E
VD, V
SG
shun
ts, &
Omm
aya r
eser
voirs
wer
e use
d.No
stati
stica
l dat
a ava
ilable
.
Sugg
ested
LP, V
SG, O
mmay
a res
ervo
ir, &
VP sh
unts
are s
afe &
effec
tive.
Of 26
infa
nts w
/ PHH
trea
ted w
/ EV
D, 20
did r
equir
e shu
nts. 6
did n
ot re
quire
furth
er
treatm
ent.
Rhod
es et
al.,
1987
37 pr
ematu
re in
fants
w/ P
HH w
ere t
reate
d w/ a
n EVD
. Com
pli-
catio
ns, in
cludin
g mor
bidity
, are
pres
ented
.32
pts d
id no
t req
uire a
perm
anen
t shu
nt. N
euro
deve
lopme
n-ta
l & ne
urom
uscu
lar ou
tcome
s are
pres
ented
.
Clas
s III
Retro
spec
tive,
cons
ecut
ive ca
se se
ries.
Leve
l III
Ventr
icular
drain
age i
s a sa
fe &
effec
tive m
echa
nism
for t
reati
ng in
fants
w/ P
HH &
may
obvia
te th
e nee
d fo
r a sh
unt.
Wen
inger
et
al., 1
992
Stud
y of 2
7 con
secu
tive i
nfants
w/ a
n ave
rage
gesta
tiona
l age
of
31 w
ks, w
ho ha
d PHH
& in
crea
sed I
CP &
wer
e tre
ated w
/ a t
unne
led E
VD.
PHH
was d
efine
d as v
entri
cular
dilat
ion, p
rogr
essiv
ely in
cr
eas in
g OFC
, bulg
ing fo
ntan
elle,
wide
ning o
f the s
uture
s, ap
nea,
or br
adyc
ardia
.
Clas
s III
The s
tudy
is a
case
serie
s rep
ort.
PHH
was s
ucce
ssfu
lly tr
eated
in al
l pts;
the E
VD w
as
left in
situ
for a
n ave
rage
of 23
± 9
days
. 4 pt
s died
of
unre
lated
caus
es, &
23 pt
s sur
vived
. 16 r
equir
ed
shun
ts.Ne
urolo
gical
outco
me co
rrelat
ed w
/ sev
erity
of th
e Gr
ade o
f IVH
. Gra
de IV
IVH
infan
ts ha
d the
wor
st ne
urolo
gical
outco
mes,
desp
ite tr
eatm
ent.
The a
utho
rs co
nclud
e tha
t EVD
is a
safe
& ef
fectiv
e tre
atmen
t for P
HH in
prem
ature
infa
nts.
Willi
s et a
l., 20
0932
prem
ature
infa
nts w
/ PHH
wer
e tre
ated w
/ shu
nts or
re
serv
oirs.
Clas
s III
Retro
spec
tive,
cons
ecut
ive ca
se se
ries o
f 32 i
nfants
wh
o nee
ded t
reatm
ent fo
r PHH
. Mult
ivaria
te an
alysis
&
time s
eries
wer
e use
d to i
denti
fy fac
tors t
hat in
flu-
ence
the o
utcom
e in t
erms
of sh
unt r
evisi
ons.
Initia
lly re
serv
oirs w
ere p
laced
in 4
6.8%
of pt
s & sh
unts
in 53
% of
pts.
The g
roup
s wer
e not
comp
arab
le.Pe
rman
ent s
hunts
wer
e nee
ded i
n 90.6
% of
case
s.Inf
ants
who w
ere t
reate
d w/ a
shun
t initia
lly ha
d mor
e re
vision
s. p =
0.00
27.
CSF
rese
rvoir
s are
a sa
fe &
effec
tive m
ethod
of tr
eat-
ment
in inf
ants
cons
idere
d too
small
for V
P sh
unt
place
ment,
but th
is do
es no
t obv
iate t
he ne
ed fo
r a
shun
t.Yu
et al
., 200
9Th
e aut
hors
perfo
rmed
a re
trosp
ectiv
e cas
e stu
dy of
11 pr
e-ma
ture i
nfants
w/ P
HH w
ho w
ere a
ll tre
ated w
/ a su
bcut
ane-
ous r
eser
voir f
or C
SF as
pirati
on.
Clas
s III
Retro
spec
tive c
ase s
eries
.Th
e aut
hors
conc
luded
that
CSF
rese
rvoir
trea
tmen
t is
safe
& ef
fectiv
e for
infa
nts w
/ PHH
.
* EG
A =
estim
ated g
esta
tiona
l age
; ICP
= in
tracr
anial
pres
sure
; IPH
= in
trapa
renc
hyma
l hem
orrh
age;
NICU
= ne
onat
al int
ensiv
e car
e unit
; pts
= pa
tients
.
C. A. Mazzola et al.
16 J Neurosurg: Pediatrics / Volume 14 / November 2014
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-
TABLE 2: Serial lumbar punctures: summary of evidence
Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
Anwar et al., 1986
Randomized controlled study of 47 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.
Class IConsecutively 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.
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.
Behjati et al., 2011
Case series study that investigated risk factors for VP shunts in infants w/ hydro-cephalus following IVH in 97 consecu-tive preterm infants w/ IVH.
Class IIICase series of 97 infants w/ IVH associated
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.
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.
Chaplin et al., 1980
Retrospective review of 22 consecutive 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.
Class IIIRetrospective review of 22 infants w/ PHH.
There were 2 cohorts: 12 pts treated w/ VP shunt, & 10 pts treated w/ LP & diuretics.
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.
Kazan et al., 2005
Single-center retrospective review of pre-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.
Class IIISmall, retrospective case series w/ grouping of
pts despite variable treatments.
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).
Müller et al., 1998
Effect of aggressive LP schedule on PHH.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.
Class IIISingle-institution nonrandomized prospective
study.16% complete resolution, 65% ventriculomega-
ly but no shunts, 19% w/ shunts.
Serial LP should be started early for treatment of hydrocephalus.
Part 2: Management of posthemorrhagic hydrocephalus in infants
17J Neurosurg: Pediatrics / Volume 14 / November 2014
TABLE 3: Intraventricular thrombolytic agents: summary of evidence
Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
Whitelaw et al., 2007
Randomized multicenter clinical trial com-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.
Class IMulticenter randomized controlled trial.
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.
Hudgins et al., 1997
Use of urokinase via reservoir to treat 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.
Class IIProspective nonrandomized case-
control series.Division of 9 pts into “low” dose group
would appear to dilute statistical power, despite statistical significance obtained.
“Low dose” urokinase reduced shunt rate (71% vs 92%) compared to historical controls.
Fewer shunt revisions in both groups compared to control group.
Whitelaw & Odd, 2007
Review & meta-analysis of 2 prospective 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.
Class IIBoth sources’ studies were Class II
(both were small randomized, pro-spective case-control studies).
No difference in mortality or VP shunt rate was observed w/ intraventricular streptokinase.
Intraventricular fibrinolytic therapy cannot be recommended for infants following IVH.
Yapicioğlu et al., 2003
Single-blind prospective study.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.
Class IISmall randomized, prospective study
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.
Richard et al., 2001
Single-institution experience w/ Ommaya reservoir in 64 pts.
17 pts received fibrinolytic therapy through Ommaya reservoir.
Class IIIRetrospective 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.
Fibrinolytic therapy led to statistically sig-nificant lower rate of shunt placement (31% vs 87%).
Whitelaw et al., 2003
Prospective Phase I trial of new treatment 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.
Class IIIProspective Phase I trial in 24 pts &
compared w/ historical controls.
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)
C. A. Mazzola et al.
18 J Neurosurg: Pediatrics / Volume 14 / November 2014
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 3: Intraventricular thrombolytic agents: summary of evidence (continued)
Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
Whitelaw et al., 1992
Prospective study of 9 preterm infants 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.
Class IIISmall, prospective, nonrandomized
cohort study (Phase I trial).
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.
Whitelaw et al., 1996
Phase I study to evaluate safety of tPA in 22 preterm infants w/ posthemorrhagic ventricular dilation.
Dosefinding data reported.Outcome measures: death & need for
shunt prior to discharge & secondary IVH.
Class IIISmall, prospective, nonrandomized
cohort study (Phase I trial).
Dosefinding & 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.
TABLE 4: Acetazolamide/furosemide: summary of evidence*
Authors & Year Study Description Data Class, Quality, & Reasons Results & Conclusions
International PHVD Drug Trial Group, 1998
Use of acetazolamide & furosemide in pts w/ PHH.
Comparison w/ standard therapy for shunt placement & neurological outcome.
Class IRandomized controlled multicenter, well
designed.
Acetazolamide & furosemide led to higher rates of shunt placement (RR 1.42) & higher morbidity (84% vs 60%) com-pared w/ standard therapy
Kennedy et al., 2001
Multicenter randomized controlled trial 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.
Class IMulticenter 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.
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.”
Kazan et al., 2005
Single-center retrospective review of 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.
Class IIISmall retrospective case series w/ group-
ing of pts despite variable treatments.
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.
Part 2: Management of posthemorrhagic hydrocephalus in infants
19J Neurosurg: Pediatrics / Volume 14 / November 2014
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 Data Class, Quality, & Reasons Results & Conclusions
Anwar et al., 1986
Consecutive, nonrandomized study of 19 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.
Class IIICase 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.
Authors concluded that reservoirs provide safe & effective treatment for infants w/ PHH & symptomatic hydrocephalus.
Benzel et al., 1992
41 pts requiring ventricular drainage for 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.
Class IIIRetrospective case series of 41 con-
secutive premature infants.
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.
Fulkerson et al., 2011
Premature infants w/ PHH have a high 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.
Class IIIRetrospective 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.”
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.
C. A. Mazzola et al.
20 J Neurosurg: Pediatrics / Volume 14 / November 2014
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 StudiesWe 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 Data Class, Quality, & Reasons Results & Conclusions
Elgamal et al., 2011
Review of 52 consecutive ETV procedures 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.
Class IIICase 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.
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.
Lipina et al., 2008
Retrospective consecutive case series of 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.
Class IIIThis study included a small number of
pts w/ very different etiologies for hydrocephalus.
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.
Peretta et al., 2007
Single-institution retrospective review of 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).
Class IIISmall 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.
Recommended combining Ommaya placement w/ ETV. It reduces shunt dependency in this condition.
Siomin et al., 2002
Multicenter retrospective case series of 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.
Class IIIMulticenter study w/ a minority of pts
(25%) w/ PHH of prematurity.
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 firstline treatment.
ETV was not successful in pts w/ both hemorrhage & infection.
Part 2: Management of posthemorrhagic hydrocephalus in infants
21J Neurosurg: Pediatrics / Volume 14 / November 2014
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
ConclusionsSurgical 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 RecommendAtion: 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 PuncturesRecommendAtion: 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 MeasuresRecommendAtion: 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 PlacementRecommendAtion: 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)
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: [email protected].