CLINICAL ARTICLE

J Neurosurg Pediatr 30:239–249, 2022

Invasive brain tissue oxygen and intracranial pressure

(ICP) monitoring versus ICP-only monitoring in pediatric
severe traumatic brain injury
*Shih-Shan Lang, MD,1,2 Nankee K. Kumar,1 Chao Zhao, MS,1,2 David Y. Zhang,1
Alexander M. Tucker, MD,1,2 Phillip B. Storm, MD,1,2 Gregory G. Heuer, MD,1,2 Avi A. Gajjar,1,3
Chong Tae Kim, MD,4 Ian Yuan, MD,5 Susan Sotardi, MD,6 Todd J. Kilbaugh, MD,5 and
Jimmy W. Huh, MD5
1
Division of Neurosurgery, Children’s Hospital of Philadelphia, Department of Neurosurgery, University of Pennsylvania
Perelman School of Medicine, Philadelphia, Pennsylvania; 2Center for Data Driven Discovery in Biomedicine, Children’s
Hospital of Philadelphia, Pennsylvania; 3Department of Chemistry, Union College, Schenectady, New York; 4Department of
Physical Medicine and Rehabilitation and Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman
School of Medicine, Philadelphia, Pennsylvania; 5Department of Anesthesiology and Critical Care Medicine, Children’s Hospital
of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and 6Department
of Radiology and Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine,
Philadelphia, Pennsylvania

OBJECTIVE Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population.
While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe
TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes.
The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have
better outcomes than those who underwent ICP-only monitoring and treatment.
METHODS Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children’s
hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements
of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between
patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay
(LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow
Outcome Score–Extended (GOS-E) scale at 6 months postinjury.
RESULTS Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak
negative association between ICP and PbtO2 (β = −0.04). Conversely, there was a strong positive correlation between
CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (β = 0.30 and β = 0.29, p < 0.001, respectively). An increased
number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p =
0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation
(p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively).
An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p =
0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and
average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring
experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E
score difference between groups (p = 0.733).
CONCLUSIONS An increased number of cerebral hypoxic episodes and an increased number of intracranial hyper-
tension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased
number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum

ABBREVIATIONS BOOST-II = Brain Tissue Oxygen Monitoring and Management in Severe Traumatic Brain Injury; CPP = cerebral perfusion pressure; FiO2 = fraction of
inspired oxygen; GCS = Glasgow Coma Scale; GOS-E = Glasgow Outcome Score–Extended; ICP = intracranial pressure; LOS = length of stay; MAP = mean arterial pres-
sure; PbtO2 = brain tissue oxygen tension; PEEP = positive end-expiratory pressure; PICU = pediatric intensive care unit; PILOT = Pediatric Intensity Level of Therapy; TBI
= traumatic brain injury.
SUBMITTED December 11, 2021. ACCEPTED April 7, 2022.
INCLUDE WHEN CITING Published online May 27, 2022; DOI: 10.3171/2022.4.PEDS21568.
* S.S.L. and N.K.K. contributed equally to this work.

©AANS 2022, except where prohibited by US copyright law J Neurosurg Pediatr Volume 30 • August 2022 239

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Lang et al.
hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with
more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance
of multimodal invasive neuromonitoring in pediatric severe TBI.
https://thejns.org/doi/abs/10.3171/2022.4.PEDS21568
KEYWORDS traumatic brain injury; brain tissue oxygen monitoring; intracranial pressure monitoring; multimodality
neuromonitoring; intracranial hypertension; pediatric intensive care unit; outcome; safety; trauma
T
raumatic brain injury (TBI) is a leading cause of
morbidity and death in the worldwide pediatric
population.1 More than 600,000 children require
medical attention due to TBI each year in the United
States.2 Patients with severe TBI are especially at risk for
developing intracranial hypertension. Prior studies have
shown that treating elevated intracranial pressure (ICP)
is associated with improved outcomes, making invasive
ICP monitoring and ICP-guided therapy a standard of
care in adult and pediatric populations with severe TBI.3–8
Despite this standard, cerebral ischemia as determined
by low brain oxygen values may still occur despite ICP-
directed treatment.9–13
Because brain hypoxia may have a more direct impact
on tissue viability compared to intracranial hypertension,
brain tissue oxygen tension (PbtO2) monitoring has been
introduced and evaluated as an additional form of patient-
specific therapy, primarily in the adult population with
severe TBI. The Brain Tissue Oxygen Monitoring and
Management in Severe Traumatic Brain Injury (BOOST-
II) randomized control trial, in addition to other studies,
has examined primarily adult patients with severe TBI
using ICP and PbtO2 monitoring and revealed improved
outcomes and reduced mortality rates.14–18 The current
BOOST-III trial enrolls patients 14 years of age and older
(ClinicalTrials.gov identifier: NCT03754114). Similar
randomized controlled trials evaluating the addition of
PbtO2 on patient outcomes have not been conducted in
the pediatric TBI population. Most pediatric studies have
evaluated the safety of PbtO2 monitoring and the relation-
ship between PbtO2 and conventional parameters, such as
ICP and cerebral perfusion pressure (CPP).19–22 One of the
goals of the Approaches and Decisions for Acute Pediatric
TBI (ADAPT) trial, a multinational cohort study of 1000
children with severe TBI, was to evaluate the efficacy of
PbtO2 monitoring.23 Almost all of the studies that have
been conducted in the pediatric population have found
that direct brain oxygen monitoring in children was a safe
and useful adjunct to ICP monitoring, as PbtO2 values re-
vealed additional information about the viability of brain
tissue.19–22,​24,25 Single-institution studies have also shown
that reduced PbtO2 was strongly associated with poorer
functional and neuropsychological outcomes after pediat-
ric severe TBI.21,26,27
Given the inconsistent use of PbtO2 monitoring across
institutions, there is a need to better understand the risks
and benefits of PbtO2 monitoring in the treatment of pedi-
atric severe TBI.28–30 The primary objective of the current
study was to analyze two cohorts of a pediatric severe TBI
population at a single quaternary children’s hospital, one
group with invasive ICP + PbtO2 monitoring and treatment
and the other with invasive ICP-only monitoring and treat-
ment, to evaluate whether there was a difference in out-
240 J Neurosurg Pediatr Volume 30 • August 2022
come at 6 months postinjury using the Glasgow Outcome
Scale–Extended (GOS-E).31 Our secondary objective was
to analyze whether cerebral hypoxic episodes and intra-
cranial hypertension episodes correlated with this GOS-
E outcome. The third objective was to determine if there
were differences between these two groups in hospital
length of stay (LOS), pediatric intensive care unit (PICU)
LOS, duration of mechanical ventilation (intubation), and
extent of ICP-directed therapy, as calculated by the Pe-
diatric Intensity Level of Therapy (PILOT) scale score.32
Our main hypothesis was that the cohort of pediatric pa-
tients who received ICP + PbtO2 monitoring and treatment
would have more favorable GOS-E scores. Our secondary
hypothesis was that lower overall PbtO2 levels, increased
number of cerebral hypoxic episodes, higher overall ICP
values, and increased number of intracranial hypertension
episodes would correlate with less favorable outcomes.
Our third hypothesis was that those who received ICP +
PbtO2 monitoring and treatment would have a decreased
hospital and PICU LOS, decreased duration of mechani-
cal ventilation, and decreased extent of ICP-directed ther-
apy compared to patients who received ICP-only monitor-
ing and treatment.
Methods
Patient Population
Pediatric patients were retrospectively reviewed in a
single-center quaternary pediatric hospital between 1998
and 2021. Inclusion criteria included age ≤ 18 years, acci-
dental severe TBI with Glasgow Coma Scale (GCS) score
≤ 8, and the presence of a Camino intraparenchymal ICP
monitoring device (Camino, Integra NeuroSciences) and/
or a Licox PbtO2 dual-lumen monitoring system (Integra
NeuroSciences). Exclusion criteria included penetrating or
abusive head trauma, fixed and dilated pupils upon admis-
sion, and cardiac arrest before or during the hospital ad-
mission. The IRB of Children’s Hospital of Philadelphia
approved the study.
Management of Pediatric Severe TBI
Initial neurocritical care management included placing
the patient supine with the head of the bed elevated at 30°
and providing adequate oxygenation from intubation and
mechanical ventilation with a goal of normocarbia. An in-
tracranial hypertension episode was defined as sustained
ICP ≥ 20 mm Hg for ≥ 5 minutes. To achieve an ICP goal
< 20 mm Hg, patients received sedation and/or analgesia
medications, hyperosmolar therapy, and a neuromuscu-
lar blockade as needed. Phenylephrine, epinephrine, and
dopamine were used as needed to increase mean arterial
pressure (MAP) to maintain minimum age–dependent
CPP at 40–65 mm Hg. Decompressive hemicraniectomy
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was considered for refractory elevated ICP despite maxi-
mal medical management. PILOT scores were calculated
to assess the extent of therapeutic intensity required for
ICP management. Our treatment protocol was consistent
with the “Guidelines for the Acute Medical Management
of Severe Traumatic Brain Injury in Infants, Children, and
Adolescents.”7,33
For patients with PbtO2 monitoring, the PbtO2 goal was
≥ 15 mm Hg based on a small number of pediatric TBI
studies and a larger number of adult TBI studies that dem-
onstrated unfavorable outcomes with lower PbtO2.10,17,​21,​22,29
PbtO2 < 15 mm Hg was treated with an initial increase in
fraction of inspired oxygen (FiO2) and other maneuvers to
promote oxygen delivery, such as an increase in positive
end-expiratory pressure (PEEP), intravenous isotonic fluid
bolus or vasopressor support to augment CPP, packed red
blood cell transfusion for anemia, and increases in arterial
CO2, with adjustments of mechanical ventilator support
as long as there was no intracranial hypertension. Mecha-
nisms to decrease metabolic demand for oxygen consump-
tion, such as sedation, analgesia, neuromuscular blockade,
or seizure treatment and prophylaxis, were also used to
increase PbtO2.
Of note, many of the treatments used to decrease ICP
are also indicated in the setting of low PbtO2, such as seda-
tion, analgesia, and neuromuscular blockade. Thus, in the
scenario with high ICP and low PbtO2, the same therapies
helped improve both measures. In situations of ICP and
PbtO2 discordance (i.e., high ICP and high PbtO2 or low
ICP and low PbtO2), treatments were provided to either
lower the ICP or increase the PbtO2, while monitoring and
addressing changes in the other modality if they arose. In
one case, a 15-year-old female presenting with loss of con-
sciousness after a motor vehicle accident initially experi-
enced increased ICP in the range of 30–40 mm Hg, which
prompted clinicians to focus their treatment on sedation,
analgesia, neuromuscular blockade, and hyperosmolar
therapy to reduce the elevated ICP. Even during episodes
when ICP was refractory to medical management, PbtO2
values remained within the appropriate range. This metric
and the patient’s stable imaging findings over time pro-
vided objective evidence for the clinicians to appropri-
ately discontinue hyperosmolar therapy with hypertonic
saline due to severe hypernatremia, knowing there were
no signs of cerebral ischemia. The patient’s ICP eventu-
ally normalized. In another case, an 8-year-old male pre-
senting after a pedestrian versus motor vehicle collision
initially had low PbtO2 and normal ICP. Thus, treatment
centered on increasing cerebral oxygenation. While the
patient was on mechanical ventilator support, FiO2 was in-
creased and packed red blood cells were administered to
increase oxygen-carrying capacity and delivery. However,
the ICP eventually increased into the range of 40–50 mm
Hg. Hypertonic saline, sedation, analgesia, a neuromuscu-
lar blockade, and pentobarbital were administered to help
decrease ICP. Because of the continued poor PbtO2, FiO2
was kept at a higher percentage of 55% with an increase in
PEEP on mechanical ventilator support. An epinephrine
infusion was needed to maintain adequate MAP and CPP
due to the increase in ICP. This increase in CPP improved
PbtO2 and eventually decreased ICP.
Lang et al.
Our institution has a protocol for pediatric severe TBI,
including the recommendation to place an invasive moni-
tor for GCS scores ≤ 8. Children were selected to receive
dual ICP + PbtO2 monitoring versus ICP-only monitor-
ing based on pediatric neurosurgeon familiarity with the
PbtO2 monitoring device. Increased injury severity was not
an indication for PbtO2 monitoring. Prior to 2005, PbtO2
monitoring was not available at this institution; therefore,
pediatric patients admitted prior to this time frame would
have only ICP data.
Data Variables
Hourly ICP, CPP, and PbtO2 were analyzed to calcu-
late the minimum hourly and average hourly values over
a 24-hour period, which is equivalent to weighted aver-
age daily values. To account for some missing data and
be inclusive of all patients’ average daily measurements,
we used weighted mean values. The number of intracra-
nial hypertension episodes (ICP ≥ 20 mm Hg, > 25 mm
Hg, and > 30 mm Hg lasting for ≥ 5 minutes), the num-
ber of episodes of low CPP < 40 mm Hg, and the number
of brain hypoxic episodes (PbtO2 < 15 mm Hg and < 20
mm Hg) were calculated. The first 2 hours of ICP, CPP,
and PbtO2 recordings were excluded from analysis, due to
potential inaccuracy innate to initial probe placement. A
Marshall score, which categorizes brain injury by severity
based on the admission CT scan, was analyzed by a pe-
diatric neuroradiologist (S.S.) who was blinded to patient
history and outcomes.34
Outcome Variables
The Glasgow Outcome Score–Extended (GOS-E),
which categorizes patient outcome after TBI according
to level of function, was calculated by a blinded pediat-
ric rehabilitation physician (C.T.K.) at 6 months posthos-
pital admission.31 This scale ranges in score from 1 to 8,
in which 1 represents death and 8 indicates normal or
near-normal function without disabling deficits. GOS-E
scores of 7–8 were categorized as favorable outcomes and
scores of 1–6 as unfavorable. We also calculated hospital
and PICU LOS, duration of mechanical ventilation, and
PILOT scores, a measure of the use of ICP-directed thera-
pies, for the first 6 days after TBI.32
Statistical Analysis
In the group that received both ICP + PbtO2 monitoring,
a partial Spearman’s correlation with sex and age adjust-
ment was used to analyze the relationship between PbtO2
and clinical outcomes. Longitudinally, average daily PbtO2
change over time was assessed by a linear mixed-effects
model with subject-specific random intercepts and ran-
dom slopes. The relationship between physiological vari-
ables of ICP + PbtO2 was analyzed using linear regression.
To compare outcomes between the ICP-only group and
the ICP + PbtO2 group, a Student t-test, Wilcoxon rank-
sum test, or Fisher’s exact test was used. ICP was analyzed
in relation to outcomes using partial Pearson’s correlation
with sex and age adjustment. The weighted daily ICP and/
or PbtO2 mean is calculated by multiplying the weight (the
ratio of the number of measurement hours in 1 day to the
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Lang et al.
total number of measurement hours over all study days)
associated with the daily ICP and/or PbtO2 arithmetic
mean and then summing all the products together.
Results
Patient Characteristics
ICP ± PbtO2 measurements were recorded in a total of
73 pediatric patients, using either invasive fiber-optic ICP
± PbtO2 probes or external ventricular devices. Of these
73 patients, 62 received invasive intraparenchymal ICP ±
PbtO2 monitors, as opposed to external ventricular drains.
From these 62 patients, 13 were excluded based on their
mechanism of trauma (such as gunshot wound or abusive
head trauma) or cardiac arrest before or during treatment.
As a result, 49 of these patients were included in this study
(Table 1). Thirty patients with a mean age of 7.4 years
were analyzed in the ICP-only group. Nineteen patients
with a mean age of 12.2 years were analyzed in the ICP +
PbtO2 group.
There were no significant differences in ICP or CPP
measurements between the two groups, with an average
daily value of 18.79 mm Hg in the ICP-only group and
ICP of 13.35 mm Hg in the ICP + PbtO2 group (Table 1).
The average daily PbtO2 was 23.2 mm Hg, with an aver-
age of 8.84 hypoxic episodes for PbtO2 < 15 mm Hg and
15.42 episodes for PbtO2 < 20 mm Hg (Table 1). There was
a weak negative correlation between average daily and
hourly ICP and PbtO2 (Fig. 1) without adjusting for covari-
ates. Conversely, there was a strong positive correlation
between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm
Hg (β = 0.30 and β = 0.29, p < 0.001, respectively; Fig. 2).
Correlation Between ICP and Outcomes
Higher minimum hourly (r = −0.52, p < 0.001) and
higher average daily ICP values (r = −0.61, p < 0.001) were
significantly correlated with less favorable GOS-E scores
(Fig. 3). Minimum hourly ICP values and average daily
ICP values did not show strong or significant relationships
to hospital or PICU LOS or duration of mechanical venti-
lation. However, increased episodes of intracranial hyper-
tension (ICP ≥ 20 mm Hg) were associated with increased
LOS in the hospital (r = 0.39, p = 0.007) and PICU (r =
0.49, p < 0.001) and increased duration of mechanical ven-
tilation (r = 0.57, p < 0.001). Increased episodes of intra-
cranial hypertension (ICP > 25 mm Hg) were correlated
with increased LOS in the PICU (r = 0.36, p = 0.012) and
increased duration of mechanical ventilation (r = 0.42, p
= 0.003). There was an association between higher mini-
mum hourly (r = 0.3, p = 0.044) and average daily (r =
0.34, p = 0.019) ICP and higher average PILOT scores, but
a lack of association between the number of intracranial
hypertension episodes ≥ 20 mm Hg and PILOT scores
(Fig. 3).
Correlation Between PbtO2 and Outcomes
In the cohort that received ICP + PbtO2 monitoring,
more cerebral hypoxic episodes (< 15 mm Hg) were as-
sociated with more unfavorable GOS-E scores (ρ = −0.49,
p = 0.045) as well as increased hospital LOS (ρ = 0.61, p
= 0.01), PICU LOS (ρ = 0.58, p = 0.015), and duration of
242 J Neurosurg Pediatr Volume 30 • August 2022
mechanical ventilation (ρ = 0.58, p = 0.015; Fig. 4). This
was also true for number of PbtO2 episodes < 20 mm Hg,
except that the duration of mechanical ventilation was
positively correlated but not statistically significant (ρ =
0.46, p = 0.063). The number of PbtO2 episodes < 20 mm
Hg was strongly correlated with more unfavorable GOS-E
(ρ = −0.55, p = 0.022). More cerebral hypoxic episodes
(PbtO2 < 15 mm Hg and < 20 mm Hg) were significantly
associated with increased PILOT scores (ρ = 0.63, p =
0.006, and ρ = 0.5, p = 0.041, respectively; Fig. 4).
While the children with favorable GOS-E scores had
higher daily PbtO2 values, the average daily PbtO2 did
not differ significantly between patients with favorable
outcomes (GOS-E scores 7–8) and unfavorable outcomes
(GOS-E scores 1–6) during the first 6 days of admission
(p = 0.949; Fig. 5).
Difference in Outcomes Between the ICP + PbtO2 and
ICP-Only Groups
Long-term outcome as reflected by GOS-E score at 6
months, PILOT score, Marshall score, hospital LOS, du-
ration of mechanical ventilation, discharge location, and
mortality did not differ significantly between the two
groups (Table 2, Fig. 6). Mean LOS in the PICU was lon-
ger in the ICP + PbtO2 group compared to the ICP-only
group, but after adjusting for age and sex, this difference
became insignificant (Table 2, Fig. 6).
ICP and PbtO2 Burden
Supplemental Fig. 1 shows the correlations between
PbtO2 and clinical outcomes, independent of elevated ICP.
The cumulative and daily ICP burdens in both the ICP-
only and ICP + PbtO2 groups were calculated for ICP ≥ 20
mm Hg (representing elevated ICP), PbtO2 < 15 mm Hg,
and PbtO2 < 20 mm Hg (representing low PbtO2; Supple-
mental Figs. 2–7). The cumulative and daily hypoxic bur-
dens of PbtO2 < 15 mm Hg and < 20 mm Hg while ICP
remained ≥ 20 mm Hg were also calculated (Supplemen-
tal Figs. 8–11).
Discussion
Our study evaluated outcomes in pediatric patients
with severe TBI who received directed therapy of ICP
+ PbtO2 compared to those who received directed ther-
apy of ICP only. The additional analyses specific to ICP
+ PbtO2 measurements allowed us to evaluate the role of
cerebral oxygen levels influencing treatment course and
outcomes. We found that an increased number of cere-
bral hypoxic episodes were associated with less favorable
functional outcomes (i.e., lower GOS-E scores). An in-
creased number of cerebral hypoxic episodes also resulted
in longer hospital and PICU LOS and longer durations of
mechanical ventilator support. Regarding ICP, we found
that higher minimum hourly ICP and average daily ICP
measurements were strongly correlated with less favorable
functional outcomes. These results are consistent with the
literature on pediatric severe TBI, which indicates that
lower average ICP measurements and reduced intracranial
hypertensive episodes correlate with improved functional
outcomes and reduced mortality rates.35–40 While we did
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TABLE 1. Patient demographic, invasive monitoring, and imaging findings

ICP + PbtO2 ICP-Only p
Characteristic Group, n = 19 Group, n = 30 Value
Demographic variables
Sex, n (%)
  Male 15 (78.95) 24 (80.00)
  Female 4 (21.05) 6 (20.00) 1.000
Mean age at PICU admission (SD), yrs 12.21 (4.81) 7.37 (4.73) <0.001
Mean body weight (SD), kg 45.24 (20.47) 28.82 (20.03) 0.006
Race, n (%)
  White 8 (42.11) 14 (46.67)
  Asian 2 (10.53) 1 (3.33)
  Black 6 (31.58) 8 (26.67)
  Other 3 (15.79) 7 (23.33) 0.713
Clinical/CT variables at baseline
Median GCS score (IQR) 3 (3–3) 3 (3–3) 0.457
CT categorization, n (%)
  Subdural 2 (10.53) 7 (23.33)
  Intraparenchymal 11 (57.89) 8 (26.67)
   Subdural + intraparenchymal 1 (5.26) 7 (23.33)
   Subdural + epidural + intraparenchymal 2 (10.53) 0 (0.00)
   All other combinations 3 (15.79) 8 (26.67) 0.041
Mean duration of monitoring (SD), days 8.16 (3.59) 7.80 (2.83) 0.698
Mean PbtO2 measurements over course (SD), mm Hg
   Minimum hourly PbtO2 12.41 (6.28) — —
   Average daily PbtO2* 23.20 (8.33) — —
   No. of episodes PbtO2 <15 8.84 (21.98) — —
   No. of episodes PbtO2 <20 15.42 (23.94) — —
Mean ICP measurements over course (SD), mm Hg
   Minimum hourly ICP 5.37 (3.64) 7.63 (10.35) 0.360
   Average daily ICP* 13.35 (4.54) 18.79 (14.77) 0.120
   No. of episodes of ICP >20 18.21 (37.9) 15.07 (20.17) 0.705
Mean CPP measurements over course (SD), mm Hg
   Minimum hourly CPP 46.96 (9.64) 40.18 (15.17) 0.083
   Average daily CPP* 68.24 (8.13) 64.11 (14.78) 0.265
   No. of episodes of CPP <40 0.63 (1.5) 5.4 (15.15) 0.173
Surgery, n (%)
  No surgery 12 (63.16) 26 (86.67)
  EVD 2 (10.53) 1 (3.33)
  DHC 2 (10.53) 2 (6.67)
   DHC & hematoma evacuation 2 (10.53) 1 (3.33)
   EVD, DHC, & hematoma evacuation 1 (5.26) 0 (0.00) 0.332
DHC = decompressive hemicraniectomy; EVD = external ventricular drain.
Boldface type indicates statistical significance.
* Weighted mean values.

not notice an improvement in functional outcome in pa-
tients who received PbtO2 in addition to ICP monitoring
and treatment, the lack of a strong correlation between
ICP and PbtO2 values supports the importance of multi-
modal invasive neuromonitoring in pediatric severe TBI.
The weak correlation between the measurement mo-
dalities indicates that ICP and PbtO2 measurements may
not be related to the same injury processes occurring
within the pediatric brain. The independent analyses of
ICP and PbtO2 with functional outcomes support this con-
clusion, as the number of episodes of low PbtO2, versus
the minimum hourly or average daily PbtO2, correlates
most strongly with GOS-E scores. However, in terms of
ICP measurements, minimum hourly and average daily

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FIG. 1. Correlation between average daily (A; β = −0.03, p = 0.847) and hourly (B; β = −0.04, p < 0.001) ICP and PbtO2. *Weighted
daily ICP/PbtO2 means. Figure is available in color online only.

values, rather than the number of intracranial hypertensive
episodes, correlate most strongly with GOS-E scores. ICP
and PbtO2 might reflect brain injury (ischemia vs hyper-
emia) occurring at different timescales or with differing
severity. Our study shows that both low PbtO2 and high
ICP are correlated with worse GOS-E scores; therefore,
we believe it is valuable to monitor and treat both modali-
ties.
In the pediatric TBI literature, outcomes that are im-
portant markers of patient safety, such as hospital and
PICU LOS and duration of mechanical ventilation, have
been less studied compared with mortality, discharge lo-

FIG. 2. Correlation between CPP and PbtO2 ≥ 15 mm Hg (A) and CPP and PbtO2 ≥ 20 mm Hg (B). Figure is available in color
online only.

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FIG. 3. Correlation between ICP and clinical outcomes. Direction of ellipse, color, and circle shape indicate magnitude and direc-
tion of correlation. Direction of ellipse to the left or right indicates a negative or positive correlation, respectively. The darker the
blue or orange color indicates an increased negative or positive correlation, respectively. The rounder the shape of the circle, the
weaker the correlation; the more elliptical the shape, the stronger the correlation. The average daily ICP means are weighted. *p <
0.05, **p < 0.01, ***p < 0.001. Figure is available in color online only.

cation, or GOS-E score. In our study, we discovered that
more episodes of intracranial hypertension were associ-
ated with increased LOS in the hospital and PICU and in-
creased duration of mechanical ventilation. In a study us-
ing the National Trauma Data Bank, the authors evaluated
more than 3000 pediatric patients with TBI and found that
patients who received ICP monitoring and ICP-directed
therapy experienced increased hospital and PICU LOS as
well as duration of mechanical ventilation compared to pa-
tients who did not receive ICP monitoring.41 Although the
authors evaluated the correlation between safety outcomes
and the presence of ICP monitoring, as opposed to actual
ICP measurements, their findings suggest that increased
monitoring predicts worse safety outcomes. However, ICP
monitoring was also associated with a reduction in mor-
tality for patients with the most severe injury (i.e., GCS
score of 3).41 In another single-institution, severe pediat-
ric TBI study, ICP monitoring was not associated with a
significant increase in average hospital LOS and duration
of mechanical ventilation, but fewer intracranial hyperten-
sion episodes were associated with decreased mortality.42
Similarly, a study of severe TBI in adults found no sig-
nificant association between ICP monitoring and intensive
care unit LOS.43 In our institution, none of the patients
with invasive neuromonitoring developed clinically sig-
nificant or operative intracranial hemorrhage or infection.
In our study, an increased number of low PbtO2 events
were associated with longer hospital and PICU LOS and
longer duration of mechanical ventilation. These patients
may have experienced increased duration of intubation
because FiO2 and PEEP titrations were specific care treat-
ments used to increase PbtO2. Interestingly, patients with
lower PbtO2 values received more ICP-intensive therapy,
as demonstrated by the higher average PILOT scores. This
result may reflect the PbtO2 treatment protocol, which in-
cludes many of the therapies used to treat high ICP, such as
sedation, analgesia, and neuromuscular blockade. While
there was a weak correlation between ICP and PbtO2 in
this study, the increase in PILOT scores with cerebral
hypoxic episodes may also suggest that cerebral hypoxic
episodes foster ICP elevation in a subset of patients and
subsequently require more intensive ICP-directed therapy.
Within the ICP + PbtO2 group, an increased number of
cerebral hypoxic episodes were also associated with more
unfavorable GOS-E scores, consistent with our hypothesis.
One single-institution study of pediatric severe TBI found
a positive yet insignificant correlation between daily mean
PbtO2 values and GOS-E scores.21 Other pediatric studies
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Lang et al.

FIG. 4. Correlation between PbtO2 and clinical outcomes. Direction of ellipse, color, and circle shape indicate magnitude and direc-
tion of correlation. Direction of ellipse to the left or right indicates a negative or positive correlation, respectively. The darker the
blue or orange color indicates an increased negative or positive correlation, respectively. The rounder the shape of the circle, the
weaker the correlation; the more elliptical the shape, the stronger the correlation. The average daily PbtO2 means are weighted. *p
< 0.05, **p < 0.01, ***p < 0.001. Figure is available in color online only.

have demonstrated significant correlations between PbtO2
measurements and functional outcomes.24,26–28
The correlation between ICP and PbtO2 was small, re-
vealing that increased ICP did not always correspond to
decreased PbtO2. Conversely, during periods of normal
ICP, PbtO2 could be lower than normal. This finding dif-
fers from our initial pilot study of only 6 children, which
found that PbtO2 was significantly higher at an ICP < 20
mm Hg compared with an ICP ≥ 20 mm Hg.22 However,
our present study is consistent with findings from more re-
cent multimodal neuromonitoring studies, which suggest
that even though PbtO2 may be negatively correlated with
lower ICP, the association is weak because episodes of low
PbtO2 may occur during periods of normal ICP.20–22,25,44 At
the same time, we found that as CPP increases (CPP ≥
40 mm Hg), PbtO2 also increases for thresholds of both ≥
15 mm Hg and ≥ 20 mm Hg. These findings reiterate the
importance of multimodality neuromonitoring to inform
treatment.19,20,45
246 J Neurosurg Pediatr Volume 30 • August 2022
When evaluating differences between the ICP + PbtO2
versus the ICP-only group, we found that our primary
outcome of GOS-E scores at 6 months did not differ sig-
nificantly between groups. PICU LOS was significant-
ly higher in the ICP + PbtO2 compared to the ICP-only
group. While not statistically significant, hospital LOS and
length of mechanical ventilation were also longer in the
ICP + PbtO2 group. Although these correlations became
insignificant after controlling for age and sex, these trends
aligned with a recent study in the adult severe TBI pop-
ulation that found significantly increased ICU LOS and
duration of mechanical ventilation in patients receiving
ICP + PbtO2 monitoring, compared to patients receiving
only ICP monitoring.14 Despite the increased LOS and me-
chanical ventilation period, which could be due to adverse
effects from the treatments for cerebral hypoxia, the ICP +
PbtO2 group demonstrated lower mortality than the ICP-
only group.14 In a phase 2 safety and feasibility BOOST-II
trial for adult severe TBI, a reduction in cerebral hypoxia

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 Lang et al.

safety and efficacy of PbtO2 monitoring and treatment are

warranted.
Our study has several limitations. Our analysis is ret-
rospective in nature and is a single-institution study with
a small sample size. Our data are also limited by hourly
collection of data, because this is a retrospective study
and continuous data were not available for all modalities.
In the future, our PICU will have a more continuous and
rigorous data-capturing capability that will provide more
granular analysis of PbtO2 and other clinical physiological
variables. Despite the limitations of our study, our results
highlight the importance of weighing the risks and ben-
efits when introducing invasive multimodality neuromoni-
toring in pediatric patients with severe TBI.
FIG. 5. Graph of average daily PbtO2 (mm Hg) change over time
To our knowledge, this is the first study that has ex-
grouped by outcome. Figure is available in color online only. amined the difference in safety and functional outcomes
between invasive ICP + PbtO2 versus ICP-only groups in
the severe pediatric TBI population in a single institution.
These outcomes are especially important to consider in
time and a trend toward lower mortality and improved the pediatric population, as longer LOS may impact ab-
GOS-E outcome at 6 months were demonstrated in the sences from school and family life, which may influence
ICP + PbtO2 treatment group compared with the ICP-only
children’s social, emotional, and cognitive development.
treatment group.18 The ongoing BOOST-III adult study is
a multi-institutional randomized clinical trial to determine Our pediatric study is also unique as it analyzes multiple
the comparative effectiveness of guided treatment with aspects of PbtO2 data in relation to functional outcomes to
ICP + PbtO2 versus that with only ICP (ClinicalTrials.gov help guide clinicians’ interpretation of data and manage-
identifier: NCT03754114). Collectively, these studies dem- ment decisions. It is valuable for clinicians to note that the
onstrate that further adult and pediatric TBI studies on the number of low PbtO2 episodes is more significantly cor-
related with poorer outcomes than average daily PbtO2. In
addition, the number of low PbtO2 episodes, more so than
the minimum hourly or average daily PbtO2 values, indi-
TABLE 2. Patient characteristics by clinical outcomes
cates greater complexity of care in terms of longer hospital
Clinical ICP + PbtO2 ICP-Only p Adjusted and PICU LOS, duration of mechanical ventilation, and
Outcome Group, n = 19 Group, n = 30 Value p Value* increased PILOT score.
While we observed significant correlations between
Median GOS-E 8 (6–8) 8 (5.25–8.00) 0.733 0.623
PbtO2, ICP, and CPP values and functional outcomes, we
score (IQR)
did not observe an improvement in the primary functional
Average PILOT 9.72 (2.02) 10.15 (3.31) 0.609 0.685 outcome of GOS-E score with the addition of PbtO2 com-
score (SD) pared to ICP-only monitoring and treatment. Although the
Median Marshall 3 (2.5–4.5) 3 (2.00–4.25) 0.614 0.588 GOS-E score was higher in the ICP + PbtO2 group than in
score (IQR) the ICP-only group, the small size of each group may have
Mean hospital 632.47 (392.65) 466.48 (274.27) 0.084 0.354 prevented this difference from being statistically signifi-
LOS (SD), hrs cant, although clearly further studies with a larger pediat-
Mean PICU 401.17 (238.24) 258.85 (181.3) 0.018 0.112 ric population need to be conducted. The BOOST-II adult
LOS (SD), hrs study that demonstrated an improved trend in morbidity
Mean hrs of 234.52 (153.23) 170.25 (120.29) 0.102 0.238 and mortality was a higher-powered, multi-institutional
mechanical study with a much larger sample size.18 In addition, many
ventilation (SD) adult studies measure outcome by examining mortal-
Deceased, n (%) ity rate or discharge location.14,16,18 These outcomes were
No 19 (100.00) 27 (90.00)
not as apparent in our study: for example, there were only
3 deaths and only 2 patients were discharged to another
Yes 0 (0.00) 3 (10.00) 0.417 0.996 institution. Another difference between our results and
Discharge findings compared to the adult population is the inherent
location, n (%) difference in children recovery patterns. Nonetheless, our
Expired 0 (0.00) 3 (10.00) study has demonstrated that ICP or cerebral brain tissue
Home 5 (26.32) 5 (16.67) oxygen levels can independently influence outcome.
Inpatient 13 (68.42) 21 (70.00)
rehab facility Conclusions
Other 1 (5.26) 1 (3.33) 0.468 — We demonstrated that ICP and PbtO2 are weakly cor-
Boldface type indicates statistical significance. related to one another, while ICP or PbtO2 independently
* Adjusted by sex and age. affected functional outcome, supporting the use of both
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Lang et al.
FIG. 6. Box-and-whisker plots showing clinical outcome comparisons between ICP-only and ICP + PbtO2 groups. Red dots repre-
sent means. Figure is available in color online only.
invasive neuromonitoring techniques to complement each
other and help guide therapy in the pediatric severe TBI
population. Future research with larger, multicenter stud-
ies may seek to understand whether certain subpopula-
tions, based on the type of injury and/or age, would benefit
more from PbtO2 monitoring and treatment.
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Disclosures
The authors report no conflict of interest concerning the materi-
als or methods used in this study or the findings specified in this
paper.
Author Contributions
Conception and design: Lang, Huh. Acquisition of data: Lang,
Zhang, Gajjar, Sotardi. Analysis and interpretation of data:
Lang, Kumar, Zhao, Zhang, Sotardi, Huh. Drafting the article:
Lang, Kumar, Zhao, Zhang, Huh. Critically revising the article:
all authors. Reviewed submitted version of manuscript: Lang,
Kumar, Zhao, Tucker, Storm, Heuer, Kim, Yuan, Sotardi,
Kilbaugh, Huh. Approved the final version of the manuscript on
behalf of all authors: Lang. Statistical analysis: Lang, Zhao, Huh.
Administrative/technical/material support: Lang, Huh. Study
supervision: Lang, Huh.
Supplemental Information
Online-Only Content
Supplemental material is available with the online version of the
article.
Supplemental Figs. 1–11. https://thejns.org/doi/suppl/10.3171/​
2022.4.PEDS21568.
Correspondence
Shih-Shan Lang: Children’s Hospital of Philadelphia, PA.
chens4@chop.edu.
J Neurosurg Pediatr Volume 30 • August 2022 249
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