Key-words:
Head injury - outcomes - pediatric population - traumatic brain injury
Introduction
Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide.[[1]] In the United States, approximately 600,000 pediatric patients are admitted to
the Emergency Department due to TBI.[[2]] In Singapore, TBI is the leading cause of trauma among pediatric patients.[[3]] Pediatric TBI is a crippling condition which extends not only to oneself but also
to the society. However, significant variations of clinical data and management strategies
exist in the literature.[[2]]
Adult and pediatric TBI have different pathophysiology and outcomes.[[4]],[[5]] An infant skull being less rigid with higher plasticity allows more movement in
response to mechanical stress. In neonates, the cerebral white matter contains less
myelin. These factors result in different absorption of forces in adults and pediatric
patients.[[4]] Furthermore, neonates having a larger head to body ratio are more susceptible to
head injury. This corroborates with many studies that reported worse outcomes following
TBI in infants.[[6]],[[7]],[[8]] Moreover, Bruce et al. found cerebral edema twice more common in pediatric patients
after TBI due to cerebral hyperemia.[[5]],[[9]]
A review of the literature revealed multiple factors which were associated with poor
outcomes in pediatric TBI. Age, Glasgow coma scale (GCS) scores, clinical features
(vomiting, pupil size, etc.,), and injury mechanisms have been reported in various
studies.[[5]],[[10]],[[11]],[[12]] Radiological studies also attempted to examine the relationship between computed
tomography (CT) findings and outcomes. The presence of subarachnoid hemorrhage (SAH),
diffuse axonal injury, and brain swelling has been reported to predict poor outcomes
in pediatric TBI.[[13]] However, the few studies that investigated predictive factors of TBI outcomes have
revealed variable results. For instance, pupil size was only a significant predictor
only in certain studies.[[13]] Postresuscitation GCS score was a significant predictor [[14]] in some studies but not in others.[[15]] The same issue applies for age, duration of loss of consciousness, the presence
of hypothermia, and the presence of injury severity scores.[[2]],[[5]],[[10]] Much debate exists between clinicians regarding the priority of management of clinical
parameters on presentation of a pediatric TBI.
Surgery for pediatric patients with TBI remains a controversial topic of discussion.
Commonly practiced procedures such as intracranial pressure (ICP) monitoring have
conflicting evidence of utility.[[16]] Although many clinicians still edge on the conservative side of management, there
is growing evidence that decompressive surgery could improve outcomes of pediatric
TBI patients.[[5]],[[17]] Minimal data exist in the literature that identifies risk factors which predict
outcomes in pediatric TBI patients who underwent surgery.
The objective of this study was to identify pertinent clinical parameters and radiological
factors that could predict outcomes in pediatric TBI patients who underwent surgery.
Materials and Methods
This Institutional Review Board approved study was conducted in the National University
Hospital of Singapore. Pediatric patients aged 18 and under were retrospectively collected
from June 2011 to January 2017. Inclusion criteria were any pediatric patient who
suffered a TBI and was referred to the neurosurgical unit for any form of the neurosurgical
procedure, including decompressive craniectomy, craniotomy, and external ventricular
drain insertion. Pediatric TBI patients who did not undergo surgery, patients with
preinjury neurological or psychiatric conditions, patients who had no follow-up after
initial hospitalization and patients who did not survive before any surgery performed
were excluded from the study.
Demographic data collected include age, gender, mechanism of injury, and type of hemorrhage.
Patients were grouped into three groups based on their age as follows: 0–6 years,
7–12 years, and 13–18 years. Predictor variables collected for analysis include: GCS
score, mechanism of injury, the presence of loss of consciousness, vomiting, palpable
skull fracture, signs of basilar skull fracture, presence of a nonfrontal scalp hematoma,
pupil size and reactivity, CT findings of type of hemorrhage, CT findings of severity
of injury (midline shift, mass effect), presence of hypotension (age adjusted), ICP,
need for blood transfusion, and use of inotrope prior or during surgery. Hypotension
was defined as systolic blood pressure (SBP) <90 mmHg for patients over 10 years,
SBP <70 + (2 × age in years) mmHg for patients aged 1–10 years old and SBP <70 mmHg
for infants (1 month to 12 months). Mass effect was defined as the presence of effacement
or compression of basal cisterns with midline shift <0.5 cm. Midline shift is defined
as a measured perpendicular distance >5 mm between the septum pellucidum and the midline.
[[Table 1]] summarizes all the predictor variables included for analysis. The verbal and motor
component of the GCS scale was modified for pediatric patients below the age of 2
according to local institutional guidelines. For the verbal component, 5 describes
an infant that coos and babbles. Four corresponds to an infant who is irritable and
crying, 3 describes crying in response to pain, 2 moaning in response to pain, and
1 has no response. For the motor component: 6 describes an infant moving spontaneously
and purposely, 5 corresponds to withdrawing in response to touch, 4 for withdrawing
in response to pain, 3 for abnormal flexion, 2 for abnormal extension, and 1 for no
response. The severity of TBI was categorized into mild (GCS 13–15), moderate (GCS
9–12), and severe (GCS ≤8). Raised ICP was defined as ICP >20 mmHg. At our center,
The CODMAN ICP intraoperative monitor was used to measure ICP intraoperatively at
the parenchymal level. The highest reading intraoperatively was chosen. All data were
extracted from electronic medical records.
Table 1: Patient demographics and variables
Table 1: Contd...
Outcomes were measured using the Glasgow outcome score (GOS). The GOS scale was modified
for it to be applicable to pediatric patients based on Prasad's et al. report.[[5]] Good recovery (GOS 5) referred to patients who returned to age appropriate levels
of functioning or returned to normal classes without special assistance. Moderate
disability (GOS 4) referred to patients with reduced cognitive function from premorbid
levels, neurological deficits affecting daily activities or patients who were enrolled
in classes with special needs. Severe disability (GOS 3) referred to patients who
were deficient in cognitive function or patients who were unable to carry out age-appropriate
motor tasks. Vegetative state (GOS 2) referred to patients who required full dependence
on daily activities. GOS 1 represented the death of the patient. Patients were divided
into two groups based on their GOS scores. Patients with a GOS score of 1–3 represented
the unfavorable outcome group while patients with a GOS score of 4–5 represented the
favorable outcome group. Outcomes of the patients were taken at their latest follow-up
appointment. The mean follow-up period was 31 weeks postdischarge. Neurological, psychological,
and social assessments were reviewed by study investigators before awarding a GOS
score to the patient.
Statistical analysis was carried out using IBM SPSS 22.0 Armonk, New York, United
States of America. Continuous variables were represented as mean ± standard deviation
if normally distributed. For skewed distribution, data were presented as median and
interquartile ranges. Chi-square, Fisher's exact, and paired t-test were used for
univariate analysis. Binary logistic regression was used to examine variables that
were significant on univariate analysis. A value of P < 0.05 was considered to be
significant.
Results
A total of 43 pediatric patients were included in this study. Thirty-three were male
and 10 were female. The mean age was 9.6 ± 4.9 years. 14 (33%) patients were aged
0–6 years, 15 (35%) patients were 7–12 years old, and 14 (32%) patients were 13–18
years old. Mean GCS score was 10.3 ± 4.3. Majority of the patients (17, 39.5%) presented
with a mild GCS score of 13–15. The most common type of injury was an extradural hemorrhage
(19, 44%), followed by a sub-dural hemorrhage (10, 23%), SAH (7, 16%), and intraparenchymal
hemorrhage (4, 8%). 30 (70%) patients had favorable outcomes whereas 13 (30%) patients
had unfavorable outcomes. The basic characteristics of the patients are summarized
in [[Table 1]].
[[Table 2]] summarizes the factors that were analyzed for univariate analysis. On univariate
analysis, the following factors were found to be significantly associated with outcomes
following pediatric TBI: GCS scores (P = 0.001), mechanism of injury (P = 0.043),
presence of vomiting (P = 0.004), pupil size >3 mm (P = 0.001), bilaterally nonreactive
pupils (P < 0.001), use of inotropes (P < 0.001), presence of hypotension (P < 0.001),
raised ICP (P < 0.001), and blood transfusion required during operation (P = 0.007).
For the severity of TBI based on GCS scores, 15 patients had severe, 11 patients had
moderate and 17 patients had mild TBI. Among the 15 patients with severe TBI, 9 (60%)
had unfavorable outcomes. Among the 11 patients with moderate TBI, 4 (36.4%) had unfavorable
outcomes. None of the 17 patients with mild TBI had unfavorable outcomes. Vomiting
was seen in 13 patients. None of the patients who vomited had unfavorable outcomes.
Nine patients had pupils >3 mm. Of these 9 patients, 7 (77.8%) had unfavorable outcomes.
Two patients had unilaterally nonreactive pupils of which 1 had an unfavorable outcome.
Nine patients had bilaterally nonreactive pupils. Seven of these 9 patients had unfavorable
outcomes. Inotropes were used in 8 patients. 7 (87.5%) patients had unfavorable outcomes.
Hypotension was recorded in 12 patients. 10 (83.3%) patients had unfavorable outcomes.
ICP was raised intraoperatively in 17 patients. 12 (70.6%) had unfavorable outcomes.
Six patients required blood transfusion intraoperatively. Five (83.3%) patients had
unfavorable outcomes.
Table 2: Factors analyzed on univariate analysis
Table 2: Contd...
Factors that were statistically significant in univariate analysis were examined using
a backward stepwise binary logistic regression. [[Table 3]] shows the factors that were statistically significant after logistic regression.
On multivariate analysis, only patients who had raised ICP (odds ratio [OR] = 35.6,
P = 0.008, 95% confidence interval CI 2.6–493.5) and hypotension (OR = 26.1, P = 0.010,
95% CI 2.2–311.8) emerged to be statistically significant.
Table 3: Factors significant on multivariate analysis
Discussion
This study examined the relationship between different clinical parameters and the
outcomes of pediatric TBI patients who required surgery. In our cohort of 43 patients
who underwent surgery, it was found that raised ICP and hypotension were significant
independent predictors of unfavorable outcomes. Although multiple predictor variables
have been reported in the literature, there is no agreement as to which variable is
most predictive of outcome. The aim of this study was to find out pertinent clinical
parameters that would predict outcomes after TBI in a defined group of pediatric patients.
Ultimately, this would improve the focus of management in pediatric TBI patients undergoing
surgery.
Despite TBI being a common cause of mortality and morbidity, clinical management of
pediatric patients is not as well established as adults. Many authors have reported
different results over the past 20 years. An important point of discussion would be
the use of GCS scores in predicting outcomes due to its extensive use in daily clinical
practice. Initially, GCS was thought to be a significant predictor of outcome in pediatric
TBI patients.[[18]] Subsequently, there have been two sides to the story regarding the value of GCS
scores in predicting severity.[[14]],[[15]],[[19]] We believe this is due to a few reasons. First, different authors reported GCS
scores at different stages of clinical assessment. Ducrocq et al. reported that initial
GCS score at presentation was a significant predictor of unfavorable outcome.[[20]] However, Massagli et al. reported that GCS recorded only at 24 and 72 h were significant
predictors of outcome.[[18]] Furthermore, the sample population in different studies varied in terms of sample
size, age, and patient characteristics. Some studies included patients with only moderate-to-severe
GCS scores [[18]],[[21]] while others included all patients regardless of their GCS score.[[5]] The different range of GCS scores coupled with the different target age groups
and sample size could have well affected statistical significance. In this study,
different pediatric age groups were well represented at each age category had approximately
one-third of the sample population. Furthermore, our sample population was specific
to those who underwent surgery following TBI. Our results showed that GCS scores were
significantly associated with outcomes only on univariate analysis (P = 0.001). This
is in line with authors who reported the limited use of GCS scores to predict outcomes
of pediatric TBI patients.[[19]]
The same problem with GCS scores is encountered for other factors that have been reported
in the literature. A review of the literature showed that common predictor variables
investigated include: age, injury severity scores, mechanism of injury, pupil size,
vomiting, loss of consciousness, the base of skull fracture, CT findings, blood pressure,
and ICP.[[5]],[[11]],[[21]],[[22]] Prasad et al. and Wells et al. reported that age at injury was not a good predictor
of outcomes in pediatric TBI patients.[[5]],[[23]] However, Prigatano et al. found that age was the strongest predictor of post-TBI
performance in neuropsychological tests in school going children.[[24]] Similarly, pupil size was only found to be a significant predictor in certain studies.[[5]],[[25]] Kamal et al. reported that GCS score, brain CT findings, and hypotension were significant
predictors of outcome on univariate analysis in the pediatric population younger than
12 years old.[[26]] In a French trauma center with 585 patients of mean age 7 years, Ducrocq et al.
reported that initial hypotension, GCS and injury severity score were significant
predictor variables on multivariate analysis.[[20]] Results from this study on univariate analysis were not entirely different from
those published. We found that only bilaterally nonreactive pupils were significantly
associated with unfavorable outcomes. The presence of unilaterally nonreactive pupils
was not a significant factor. Furthermore, the use of inotrope and patients requiring
blood transfusion are variables that have not been reported before. It is to the best
of our knowledge that the present study included the most number of predictor variables
for analysis. Essentially, in the few studies that investigated predictor variables
of outcome in pediatric TBI, no consensus has been reached by authors. This presents
as a clinical problem as doctors are unaware of important clinical parameters to pay
close attention to when managing pediatric TBI patients. Although all clinical parameters
should be monitored, there are some that require closer attention.
Perhaps another reason for the dissimilarity in predictor variables is the measure
of outcome in pediatric patients post-TBI. Authors reported different follow-up periods
as well as different outcome measures. Anderson et al. utilized intellectual measures
such as verbal and nonverbal skills, attention and processing speed to examine outcome
5 years postinjury in preschool pediatric TBI patients.[[27]] Prigatano et al. measured outcome based on performance cerebral functioning tests.[[24]] A recent study by Hale et al. measured outcome by the presence of postdischarge
seizures.[[28]] The GOS scale is the most commonly used measure of outcome in the literature.[[20]],[[21]] However, it has been reported that the GOS scale underestimates the impact of brain
injury in young children [[5]] as it was developed for use in adults.[[29]] In 1981, the GOS scale was modified to the GOS-Extended (GOS-E)[[30]] and a pediatric revision, GOS-E Peds was created and validated by Beers et al.[[31]] However, to the best of our knowledge, very few studies reported the use of GOS-E
Peds to measure outcomes.[[32]] The GOS-E Peds has a maximum score of 8 which is more time consuming to conduct
than the original GOS scale. In this study, we used a GOS scale modified by Prasad
et al. for pediatric patients.[[5]] Although further validation is required, the modifications appeared to have increased
the sensitivity of GOS in pediatric TBI outcomes.[[5]] The study shows that the majority of the patients had favorable outcomes (70%)
after undergoing a neurosurgical procedure. This result is similar to most of the
data published in the literature.[[5]],[[13]],[[20]],[[33]]
Several authors have used stepwise logistic regression to identify variables most
predictive of outcome.[[5]],[[18]],[[20]],[[21]] We adopted the same method for our study. The results from the present study found
that raised ICP and hypotension were variables most predictive of outcomes. This is
similar to the findings of a French trauma center reported by Ducrocq et al. on multivariate
analysis.[[20]] White et al. also reported that supra-normal blood pressures and mannitol administration
were associated with improved outcomes on multivariate analysis.[[21]] However, both studies only focused on pediatric patients with GCS ≤8. This present
study included all patients regardless of GCS scores that underwent any form of neurosurgical
procedure. Reduced blood pressure would result in a decrease in cerebral perfusion
leading to ischemic brain damage. This increases secondary brain damage which worsens
outcome. Furthermore, raised ICP would cause a decrease in cerebral perfusion pressure
which has been reported by Carter et al.[[34]] to be an accurate cause of the unfavorable outcome in pediatric TBI patients. Our
results show that priority must be given to manage these two clinical parameters in
a pediatric TBI patient. Further work needs to be done to accurately identify blood
pressure and ICP targets which are more precise in preventing unfavorable outcomes.
There were several limitations in this study. Being a retrospective review in a single-center
neurosurgical unit, the sample size was smaller compared to multicenter studies. Larger
sample size and multi-center studies should be undertaken to validate the current
findings. However, our targeted sample population is the first of its kind which will
be beneficial to neurosurgeons. Since our study only included patients who underwent
surgery, the results might not apply to pediatric TBI patients managed conservatively.
Third, it is also important to recognize that the GOS scale measures neurological
and psychiatric disorders.[[35]] Other outcome measures such as quality of life, education level, and social function
were not clearly defined in the GOS scale.
Conclusion
This study is the first of its kind to quantify that raised ICP and hypotension were
variables most predictive of unfavorable outcomes in a targeted population of pediatric
TBI patients who underwent neurosurgery. Our results also suggest that the majority
of pediatric TBI patients who required surgery have favorable outcomes. Neurosurgeons
should play closer attention to ICP and blood pressure when managing pediatric TBI
patients.
