SPECIAL ISSUE ARTICLE

Traumatic Brain Injury in the

Pediatric Intensive Care Unit
Elora Hussain, MD

CLINICAL INJURY SEVERITY

ABSTRACT TBI severity has classically been
Head trauma is a leading cause of brain injury in children, and it can have profound life- defined by using the Glasgow Coma
long physical, cognitive, and behavioral consequences. Optimal acute care of children with Scale (GCS)4 or Pediatric GCS on ad-
traumatic brain injury (TBI) requires rapid stabilization and early neurosurgical evaluation mission.5 A GCS of 13 to 15 is consid-
by a multidisciplinary team. Meticulous attention is required to limit secondary brain injury ered mild TBI; 9 to 12 is considered
after the initial trauma. This review discusses pathophysiology, acute stabilization, and mon- moderate; and GCS less than 9 is con-
itoring, as well as supportive and therapeutic measures to help minimize ongoing brain sidered severe. Frequent repeated as-
injury and optimize recovery in children with TBI. [Pediatr Ann. 2018;47(7):e274-e279.] sessments of the patient’s neurologic
examination and GCS are fundamental

T
raumatic brain injury (TBI) is a MECHANISMS OF BRAIN INJURY to understanding the severity and pro-
leading cause of morbidity and The distribution of damage after TBI gression of illness, and to guide clinical
mortality in children. In the may be focal or diffuse. Focal injury is management.6
United States, approximately 475,000 produced by direct impact forces act-
children younger than age 14 years ing on the skull, resulting in compres- PATHOPHYSIOLOGY
suffer from TBI annually.1 Financial sion of brain tissue at the site of impact Cerebral pathology from TBI occurs
burden can be significant, with pedi- (coup) or opposite the site of impact by two mechanisms: primary (or im-
atric inpatients accounting for over $1 (contrecoup). Focal injuries may cause mediate) brain injury and secondary (or
billion in total charges for TBI-associ- parenchymal contusions, intraparen- delayed) brain injury. Primary injury is
ated hospitalizations.2 chymal hemorrhage, subdural and epi- the immediate parenchymal injury that
Injury patterns due to TBI vary by dural hematomas, and subarachnoid occurs from the trauma itself. Preven-
age. In infants, inflicted or nonacci- hemorrhage. tion is the only measure that can affect
dental injury must always be consid- Diffuse injury is more widely dis- primary injury.
ered. Falls are the primary mechanism tributed, involving the axons and vas- In the minutes to days after primary
of TBI-related emergency department cular structures, and can be associated injury, the brain is particularly vulnera-
visits in children (age 0 to 4 years). with hypoxic ischemic injury and ce- ble to secondary injury due to increased
In school-age children, falls decrease rebral edema. It is typically caused by metabolic demands and compromised
with age, with a rise in bicycle acci- rapid acceleration-deceleration move- cerebral perfusion. A complex cascade
dents. In adolescents, there is a dra- ments of the head. Diffuse axonal in- of cellular, biochemical, and meta-
matic rise in TBI due to motor vehicle jury is caused by widespread insult to bolic processes is initiated, which can
accidents, sports-related injuries, and cerebral white matter and may result in lead to ongoing neuronal damage and
violence.1 extended loss of consciousness.3 cell death. Both cytotoxic and vaso-
genic edema may occur, with cytotoxic
Elora Hussain, MD, is the Medical Director of Neurocritical Care, Division of Pediatric Critical Care edema from cellular swelling, and va-
Medicine, Helen DeVos Children’s Hospital; and an Assistant Professor, Department of Pediatrics and sogenic edema from disruption of the
Human Development, Michigan State University College of Human Medicine. blood-brain barrier and vascular integ-
Address correspondence to Elora Hussain, MD, Helen DeVos Children’s Hospital, 100 Michigan Street rity.7 This phase of injury can be further
NE, MC 117, Grand Rapids, MI 49503; email: elora.hussain@helendevoschildrens.org. exacerbated by physiologic derange-
Disclosure: The author has no relevant financial relationships to disclose. ments including hypoxia, hypotension,
doi:10.3928/19382359-20180619-01 and hyperthermia.8,9 Management strat-

e274 Copyright © SLACK Incorporated


egies in the acute period after TBI are
primarily focused on minimizing and
preventing secondary brain injury.
EVALUATION
Details of the patient’s medical his-
tory, timing and mechanism of the trau-
ma, and resuscitation efforts prior to
presentation are essential. On physical
examination, adequacy of the patient’s
respiratory and cardiovascular status,
as well as neurologic examination, must
be rapidly assessed. Cervical spine sta-
bilization should be maintained to avoid
cervical spine injury. GCS should be
determined, and life-threatening signs
of impending herniation rapidly identi-
fied. These may include altered level of
consciousness, pupillary dysfunction,
lateralizing extremity weakness, or
Cushing’s triad (systemic hypertension,
bradycardia, irregular respirations).
The presence of Cushing’s triad is a late
and ominous sign of herniation.7
INITIAL STABILIZATION
If a child has normal mentation, re-
spiratory effort, and favorable hemody-
namics, advanced airway management
may not be required. However, in pa-
tients with signs of airway obstruction,
inadequate oxygenation or ventilation,
or shock, rapid stabilization and resus-
citation by a multidisciplinary team is
required.
In patients with decreasing level
of consciousness (and/or GCS ≤8),
advanced airway support with endo-
tracheal intubation is indicated while
maintaining stabilization of the cervical
spine. Strict avoidance of hypotension,
hypoxemia, and intracranial hyperten-
sion are necessary during intubation.
Fluid resuscitation with isotonic so-
lutions to reverse hypovolemic shock
may be necessary and to replenish in-
travascular volume. Hypotonic fluid is
contraindicated in the initial resusci-
tation as this may exacerbate cerebral
edema and cell death.7
PEDIATRIC ANNALS • Vol. 47, No. 7, 2018
SPECIAL ISSUE ARTICLE
After initial stabilization, patients
with moderate or severe TBI warrant
emergent neuroimaging with computed
tomography without contrast to assess
for lesions requiring emergent neuro-
surgical intervention. A full trauma as-
sessment by a multidisciplinary trauma
team is also necessary to evaluate for
and treat extracranial insults.
INVASIVE NEUROMONITORING
An intracranial pressure (ICP)
monitor is often placed by a neuro-
surgeon after stabilization in children
with severe injury (GCS ≤8) for ICP
monitoring and potential treatment of
intracranial hypertension. This can al-
low for early detection of patients at
risk for cerebral herniation and may
allow for therapeutic drainage of cere-
brospinal fluid (CSF) if needed. Cur-
rent recommendations in pediatrics are
for treatment of intracranial pressure
≥20 mm Hg.10
Invasive ICP monitoring is the cur-
rent standard of care for children with
concern for intracranial hypertension.
However robust evidence supporting
this practice is lacking, with only class
III evidence available.10 The BEST
TRIP trial published in 2012 is the
only large-scale, high-quality random-
ized multicenter controlled trial on this
subject to date, and created significant
controversy regarding ICP monitoring
in severe TBI.11 This trial randomized
pediatric and adult patients in South
America to receive either invasive ICP
monitoring or treatment based on im-
aging and clinical examination alone.11
There was no significant difference be-
tween groups in morbidity or mortal-
ity measured at 6 months postinjury.
The degree to which these results can
be generalized to clinical practice in
North America is controversial, due to
potential differences in prehospital care
and resuscitation. Although the BEST
TRIP trial may not warrant a change in
the current clinical practice of invasive
ICP monitoring, it does highlight the
need for additional investigation re-
garding the role of ICP monitoring in
the management of severe TBI.12
Invasive and noninvasive tissue
oximeters may be used in combina-
tion with ICP monitors, with studies
suggesting that reduced brain tissue
oxygen tension is associated with poor
outcomes in severe pediatric TBI.13
Oxygenation parameters and manage-
ment targets, however, are largely ex-
trapolated from adult data.
ONGOING MANAGEMENT
After initial stabilization and resus-
citation, ongoing physiologic monitor-
ing and management should continue
in a pediatric intensive care unit (ICU)
to avoid secondary insults such as hy-
poxia, hypotension, and hyperthermia.
In 2012, the revised Guidelines for the
Acute Medical Management of Severe
Traumatic Brain Injury in Infants, Chil-
dren, and Adolescents were published
by the Brain Trauma Foundation.10
These guidelines focus on minimizing
secondary brain injury after pediatric
TBI and are based on best-available
current evidence. Figure 1 shows an
example of a clinical management
pathway for severe pediatric TBI. It
should be noted, however, that high
quality evidence in this field remains
lacking; these consensus guidelines
include no level I recommendations,
and most recommendations are level
III evidence.9
INTRACRANIAL PRESSURE AND
CEREBRAL AUTOREGULATION
One of the most severe consequenc-
es of TBI is intracranial hypertension
reflected by an elevated ICP. With a
space-occupying lesion, such as an ex-
panding hematoma or cerebral edema,
initial compensatory mechanisms can
prevent elevated ICP to a limited ex-
tent. Once these mechanisms are ex-
hausted, even small increases in intra-
e275
 SPECIAL ISSUE ARTICLE

Figure 1. Clinical pathway for the management of severe pediatric traumatic brain injury. CPP, cerebral perfusion pressure; CSF, cerebrospinal fluid; CT, com-
puted tomography; EEG, electroencephalogram; EVD, external ventricular drain; ICP, intracranial pressure; IV, intravenous; GCS, Glasgow Coma Scale; MAP,
mean arterial pressure; TBI, traumatic brain injury.

e276 Copyright © SLACK Incorporated


cranial volume can lead to intracranial
hypertension, which can compromise
cerebral perfusion and lead to cerebral
ischemia, and even herniation.8
Under normal conditions, cerebral
autoregulation allows the cerebral
arterioles to vasodilate and vasocon-
strict to maintain constant cerebral
blood flow (CBF) over a wide range
of blood pressures. In the clini-
cal setting, cerebral perfusion pres-
sure (CPP) is used as a surrogate for
CBF.14 CPP is the difference between
mean arterial pressure (MAP) and ICP
(CPP = MAP – ICP). In healthy adults,
MAP between 50 and 170 mm Hg pro-
duces little to no change in CBF. In
healthy infants and children, there are
few studies on the physiologic range
of cerebral autoregulation.
In moderate and severe TBI, the
normal mechanisms for cerebral au-
toregulation are often compromised,
causing CBF to become dependent
on MAP. Decreased CPP and cere-
bral ischemia may occur due to ei-
ther decreased MAP or increased
ICP. Conversely, increased MAP and
decreased ICP may result in cerebral
hyperemia.7-9 Impaired cerebral au-
toregulation in children is associated
with worse outcomes.15 Thus, many
therapeutic interventions after TBI are
targeted at lowering ICP, augment-
ing MAP to ensure adequate CPP,
and maintaining euvolemia. Pediatric
guidelines recommend a minimum
CPP threshold of 40 to 50 mm Hg to
prevent cerebral hypoperfusion and
ischemia. However, the optimal CPP
in pediatric TBI is unknown.10,14
INTRACRANIAL PRESSURE
LOWERING THERAPIES
Patient Positioning
Maintaining the head in a neutral,
midline position and elevating the
head of the bed to 30 degrees has been
shown in adults to reduce ICP with-
out compromising CPP and cerebral
PEDIATRIC ANNALS • Vol. 47, No. 7, 2018
SPECIAL ISSUE ARTICLE
oxygenation.16 Data in pediatrics are
lacking; however, the same manage-
ment is applied to children. Internal
jugular catheterization is often avoided
in these patients to maintain venous
patency and optimize cerebral venous
drainage. Care should be taken to en-
sure that cervical collars do not impede
venous drainage.
Sedation, Analgesia, and
Neuromuscular Blockade
Moderate to deep sedation is of-
ten necessary to ensure comfort and
patient compliance with mechanical
ventilation and treatment goals after
TBI. Pain, agitation, and anxiety can
also increase ICP and cerebral meta-
bolic demand. Pediatric data on the
ideal medication regimen for sedation
and analgesia are lacking; however,
continuous infusions of narcotics and
benzodiazepines are often used in the
pediatric ICU. These medications may
cause further respiratory depression
and hypotension, so the lowest pos-
sible doses needed for comfort and
ICP management should be used. Pre-
medication with lidocaine may be used
prior to potentially noxious therapies
such as suctioning of the endotracheal
tube; however, whether lidocaine use
effects clinical outcomes is unclear.17
The use of ketamine has been de-
bated in the setting of TBI due to early
studies demonstrating an association
with increased ICP. More recent stud-
ies suggest that when administered
in conjunction with other anesthetic
agents, ICP does not increase and may
even improve.18 Further studies of ket-
amine are needed to determine safety
in the setting of pediatric TBI. Propo-
fol is often used in adult TBI for con-
tinuous sedation; however, it is not rec-
ommended in children due to reports
of metabolic acidosis, organ failure,
and death, leading to safety warnings
from the US Food and Drug Admin-
istration.19 Single-dose administration
of etomidate may be considered for
control of severe intracranial hyper-
tension; however, the risk of adrenal
suppression must be considered. Bar-
biturates may also be used for control
of intracranial hypertension but may
cause myocardial depression and sys-
temic hypotension.10
Neuromuscular blockade is some-
times used to prevent cough, shivering,
and patient-ventilator dysynchrony.
Paralytics reduce metabolic demand
and may result in improved chest-wall
compliance, causing reduction in intra-
thoracic pressure to promote improved
cerebral venous drainage. However,
routine use of neuromuscular blockade
does not improve overall outcome and
is associated with prolonged ICU stay
and nosocomial pneumonia and should
therefore only be reserved for limited
clinical situations.20
Cerebrospinal Fluid Drainage
If an external ventricular drain is
placed, CSF removal may be used as a
therapeutic maneuver to decrease ICP
in patients with intracranial hyperten-
sion. Placement of such catheters may
be technically difficult in patients with
diffuse cerebral edema and compres-
sion of the lateral ventricles.8
Hyperosmolar Therapy
Mannitol and hypertonic saline are
used as hyperosmolar therapies for de-
creasing ICP. Insufficient evidence cur-
rently exists to support the use of one
therapy over the other. Mannitol has
had longstanding clinical acceptance
and is commonly used in both pedi-
atric and adult TBI cases. However,
there are no controlled clinical trials of
mannitol use in children. Hypertonic
saline, however, is gaining more ac-
ceptance and is currently supported by
class II evidence for acute treatment of
intracranial hypertension in children,
and class III evidence to support its use
as a continuous infusion.10
e277

Mannitol is typically given in bolus
doses of 0.25 to 1 g/kg and works via
rapid reduction of blood viscosity and
osmotic diuresis, thereby improving
CBF and decreasing cerebral blood vol-
ume. Risks of mannitol administration
include hypotension and renal failure,
particularly when serum osmolality is
>320 mOsm/L. Hypertonic saline is typ-
ically limited to 3% saline in children,
but higher concentrations are often used
in adults. Optimal dosing is not well
studied, but bolus dosing ranges between
6.5 and 10 mL/kg, with a higher serum
osmolar threshold of 360 mOsm/L. The
mechanisms of hypertonic saline also
include improved CBF and providing
an osmotic gradient to reduce ICP. It is
also thought to have theoretical benefits
of inhibiting inflammation, restoring
normal resting cellular membrane po-
tential, and enhancing cardiac output.10
Potential risks include rebound in ICP,
central pontine myelinolysis, and renal
impairment.21
Hyperventilation
Carbon dioxide (CO2) has a profound
and reversible effect on CBF, such that
hypercapnia causes dilation of cerebral
arteries and arterioles and increased
CBF, whereas hypocapnia causes vaso-
constriction and decreased CBF. Thus,
hyperventilation can rapidly reduce ICP.
It may be used as a brief temporizing
measure for acute impending herniation,
pending definitive therapy. However
prophylactic, chronic hyperventilation
in children should be avoided due to
risks of hypoperfusion and cerebral isch-
emia, and normocarbia with pCO2 of 35
to 40 mm Hg should be targeted.10,22
Temperature Control
Fever in the setting of neurologic
illness is associated with worse out-
comes.23 Animal models and early adult
studies have demonstrated benefit from
therapeutic hypothermia, making it a po-
tential neuroprotective therapy in pediat-
e278
SPECIAL ISSUE ARTICLE
ric TBI.9 However, pediatric clinical tri-
als have not demonstrated benefit, with
one trial showing a trend toward worse
outcomes.24,25 Therefore, prophylactic
therapeutic hypothermia is not currently
recommended for management of intra-
cranial hypertension. It may be reserved
only as a temporizing measure for pa-
tients with refractory intracranial hyper-
tension unresponsive to other medical
interventions.8
Seizure Control
Post-traumatic seizures have been
shown to cause persistent cerebral meta-
bolic crisis and increased ICP.26 In chil-
dren younger than age 2 years, abusive
head trauma, and presence of subdural
hemorrhage have been associated with
increased risk of post-traumatic sei-
zures.27 Seizures can be convulsive or
nonconvulsive, with nonconvulsive sei-
zures only detected by electroencepha-
logram monitoring. There is a paucity
of data to guide clinicians on treatment
of post-traumatic seizures; the current
pediatric guidelines suggest that routine
seizure prophylaxis for the first 7 days
after severe TBI is reasonable to reduce
the incidence of early post-traumatic
seizures.10
Decompressive Craniectomy
Surgical decompressive craniectomy
with duraplasty, leaving the bone flap
out, may be considered for pediatric
patients who have refractory intracra-
nial hypertension unresponsive to other
therapies.10 One randomized adult study,
the DECRA trial, showed that decom-
pressive craniectomy decreased ICP and
ICU length of stay, but was associated
with more unfavorable outcomes.28 An-
other recent adult study, the RESCUEicp
(Randomized Evaluation of Surgery
with Craniectomy for Uncontrollable
Elevation of Intracranial Pressure) trial,
resulted in lower mortality but higher
rates of severe disability and vegetative
state.29 Small studies in pediatrics have
shown there may be benefit in survival
and neurologic outcomes,30,31 but both
adult and pediatric trials have thus far
been heterogeneous in both trial design
and results, making it difficult to draw
definitive conclusions regarding benefit
from this procedure.9
OUTCOMES
Long-term outcomes of children with
TBI are quite heterogeneous, ranging
from near return to baseline to varying
degrees of disability or death. Many
children continue to have significant
neurologic impairment at the time of dis-
charge.9 In addition to physical disabili-
ties, neuropsychological sequelae from
TBI may influence vital development
in children, such as learning, emotional
awareness, and social functioning.2 On-
going management, rehabilitation, and
anticipatory guidance for a potentially
new seizure disorder, or newly acquired
physical, behavioral, and/or cognitive
disability are important for follow-up
care.
CONCLUSIONS
Care of children with TBI should
focus on rapid stabilization and early
neurosurgical evaluation, with ongo-
ing management focused on prevention
of secondary cerebral insults. Careful
physiologic monitoring, with optimiza-
tion of CPP and treatment of intracranial
hypertension are critical. The paucity of
high-quality literature in pediatric TBI
highlights the need for further research
to advance our understanding of patho-
physiology and to aid in the neurologic
recovery of children with TBI.
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