Beruflich Dokumente
Kultur Dokumente
Abstract
Traumatic brain injury remains a leading cause of morbidity and mortality in children. Key pathophysiologic processes of
traumatic brain injury are initiated by mechanical forces at the time of trauma, followed by complex excitotoxic cascades
associated with compromised cerebral autoregulation and progressive edema. Acute care focuses on avoiding secondary
insults, including hypoxia, hypotension, and hyperthermia. Children with moderate or severe traumatic brain injury often
require intensive monitoring and treatment of multiple parameters, including intracranial pressure, blood pressure, metabolism, and seizures, to minimize secondary brain injury. Child neurologists can play an important role in acute and long-term
care. Acutely, as members of a multidisciplinary team in the intensive care unit, child neurologists monitor for early signs of
neurological change, guide neuroprotective therapies, and transition patients to long-term recovery. In the longer term, neurologists are uniquely positioned to treat complications of moderate and severe traumatic brain injury, including epilepsy and
cognitive and behavioral issues.
Keywords
pediatric brain trauma, closed head injury, pediatric neurocritical care, intracranial pressure
Received March 11, 2014. Received revised August 26, 2014. Accepted for publication October 14, 2014.
36
Physiologic Monitoring
Most children with severe traumatic brain injury will be
admitted to a pediatric intensive care unit for physiologic
monitoring to avoid secondary insults including hypoxia,
hypotension and hyperthermia. For children with a Glasgow
Coma Score 8, the guidelines recommend endotracheal
intubation. In addition to mechanical support, these patients
will typically also require arterial cannulation for continuous
blood pressure monitoring. While 90 mmHg or 5th percentile
for age (70 mmHg [2 age in years]) is commonly used as
a lower threshold for systolic blood pressure, maintaining
higher normal to mildly hypertensive blood pressures can be
beneficial. Allowing children to be mildly hypertensive with
systolic blood pressure measurements up to 30 mmHg above
age-corrected normal values has been correlated with lower
mortality rates.14 The main focus of blood pressure measurements in traumatic brain injury, however, is the mean arterial
pressure (MAP [2/3 diastolic] [1/3 systolic]), as it relates
to cerebral perfusion pressure. Cerebral perfusion pressure is
calculated by the difference between mean arterial pressure
and intracranial pressure (CPP MAP ICP). The 2012
guidelines recommend maintaining a minimum cerebral perfusion pressure of 40 mmHg in all patients, independent of
age.1 A number of studies have investigated age-specific
change in intracranial pressure, attempting to establish thresholds associated with good outcome.15,16 Others investigators
have proposed more sophisticated methods for quantifying
the burden of abnormal intracranial pressure or cerebral
perfusion pressure based on time and degree of deviation from
normal values.16,17 However, none of these approaches have
been applied in routine clinical practice.18 A recent multicenter observational cohort study investigated survival rates
following traumatic brain injury based on predefined agespecific cerebral perfusion pressure thresholds.19 Data from
these 2074 cases support a goal cerebral perfusion pressure
above 40 mm Hg in 0- to 5-year-olds and about 50 mm Hg
in 6- to 17-year-olds.
Cerebral autoregulation is often compromised after pediatric traumatic brain injury and is associated with poor outcome.20 In uninjured brains, local control tightly regulates
the cerebrovasculature to maintain a steady cerebral blood
flow over a range of mean arterial blood pressures. If the mean
arterial pressure is either lower or higher than the range of
autoregulation, the cerebral blood flow is dependent on mean
arterial pressure. In adults, the range of autoregulation is
estimated at mean arterial pressure of 50-170 mmHg, and
37
Patient Positioning
Basic maneuvers can help assist venous drainage from the
cranium and lower intracranial pressure with minimal risk.
Positioning head midline will prevent kinking and obstruction
of the jugular veins. Cervical collars should be appropriately
snug, but not so tight as to impede venous return. Elevating
the head of the bed 30 degrees by flexing the patient at the hip
(not the abdomen) promotes venous drainage. However, if
the patient is hypotensive or hypovolemic, the risk of exacerbating hypoperfusion and ischemia can outweigh benefits of
head elevation.
38
Neuromuscular Blockade
No trials have specifically examined the role of neuromuscular
blockade in pediatric traumatic brain injury for intracranial
pressure control, but neuromuscular blockade can be considered for refractory intracranial hypertension. Potential benefits
include reducing intrathoracic pressure leading to improved
cerebral venous outflow, reducing shivering and posturing, and
decreasing metabolic demand. An adult study examining
potential early use of neuromuscular blockade found that prophylactic use did not add benefit to intracranial pressure control
and added to risk of pneumonia and length of stay in the intensive care unit.43
Osmotic Therapy
Mannitol and hypertonic saline are hyperosmolar agents often
used to lower intracranial pressure. Mannitol gained early
acceptance and establishment in clinical protocols (typically
39
Hyperventilation
Prophylactic, or chronic hyperventilation should be avoided.1,54
Hyperventilation induces hypocarbia (PaCO2 < 35 mmHg),
which leads to cerebral vasoconstriction and a reduction
in cerebral blood flow. As there is rarely excessive cerebral
blood flow in pediatric traumatic brain injury, hyperventilationinduced reduction in cerebral blood flow often leads to
ischemia.55,56 One retrospective study found that children
with 3 or more documented episodes of hypocarbia had an
increased odds ratio of 3.93 for mortality compared to children who remained normocarbic.57 As a temporizing rescue
to counteract impending herniation, hyperventilation can
be used, but only for a brief time until other therapies can
be enacted to control elevated intracranial pressure. The
2012 guidelines recommend advanced neuromonitoring to
specifically investigate possible cerebral ischemia if hyperventilation is used.1
Temperature Control
The adverse effects of fever58,59 and promising results from
animal and early adult studies created optimism for therapeutic hypothermia in the pediatric neurotrauma. However, 3
major clinical trials of hypothermia for pediatric traumatic
brain injury have not demonstrated improvement in outcomes.
The first study of therapeutic moderate hypothermia (32-33 C),
started within 8 hours, failed to demonstrate benefit in longterm outcomes.60 A second large trial, also using moderate
hypothermia within 8 hours, suggested worsened outcomes
and a trend toward increased mortality.61 More recently, the
third major trial was terminated early for futility after interim
analysis.62 Therefore, hypothermia should not be used for
prophylactic management of severe traumatic brain injury.
Brief moderate hypothermia (32-33 C) can be considered to
control elevated intracranial pressures,1 but preferably at a
center with significant experience with cooling and rewarming children.
Corticosteroids
There is no evidence to support steroid use in pediatric traumatic brain injury. In one study, children who received dexamethasone had no benefit in intracranial pressure or 6-month
outcomes compared to children who received placebo.63 The
treatment group also had a trend toward increased incidence
of bacterial pneumonia. The 2012 guidelines specifically recommend against corticosteroid use in severe traumatic brain
injury.1
Decompressive Craniectomy
A decompressive craniectomy with duraplasty is often considered for pediatric traumatic brain injury patients with
medically refractory intracranial hypertension or signs of
herniation.1 Research on decompressive craniectomies in
both children and adults is heterogenous with regard to type
(eg, unilateral, bilateral, subtemporal, frontotemporoparietal)
and timing. This creates difficulty in drawing conclusions
about effectiveness or benefit. One small pilot study of very
early surgery reported lower intracranial pressures and
improved 6-month outcomes in children.64 However, other
studies have not found quite as robust results. A randomized
controlled trial in adults with diffuse injury and refractory
intracranial hypertension found early decompressive craniectomy to lower pressure but have worse 6-month outcomes
compared to controls.65 Further research is needed to clarify
patient selection, timing, and long-term outcomes.
40
higher incidence of convulsive and nonconvulsive status epilepticus, which require continuous EEG monitoring to guide
effective treatment.81 A recent prospective study of 87 children with mild to severe traumatic brain injury with continuous EEG monitoring identified seizures in 43%, and 16% of
all cases had subclinical seizures.82 Subclinical seizures were
more likely to be found in younger children and children with
abusive head trauma. While there is at present no accepted
standard for its use, the collective results of these studies support the use of continuous EEG in young children following
traumatic brain injury, and particularly in victims of abusive
head trauma.
There are very limited data to guide the use of or selection
of anticonvulsants for the treatment of posttraumatic seizures.
Retrospective and observational studies suggest a benefit of
decreased posttraumatic seizures and survival among patients
treated with phenytoin in the acute phase of injury.83,84 A randomized, double-blinded study of adults with severe injury
showed a benefit of phenytoin for early (<7 days) seizures,
but no benefit for seizure prevention between 8 days and
24 months85 or 90-day mortality.86 A randomized, doubleblinded study compared phenytoin to placebo for the prevention of early posttraumatic seizures in children with moderate
to severe head injury,87 comprising 62% severe traumatic
brain injury cases. In this study, subjects younger than 16
years who had suffered blunt head trauma were randomized
to either IV phenytoin or placebo within 60 minutes of arrival
to the emergency room. Surprisingly, there were no differences between group in the primary endpoint (seizures within
48 hours of drug administration), occurring in 7% of the phenytoin group and 5% of the placebo controls. The study was
limited by the low rate of early posttraumatic seizures, which
was lower than reported in other series. The distinction
between early and late posttraumatic seizures is arbitrary, and
the application of a 7-day window to different ages and
mechanisms of head trauma in children is not based on data.
Routine seizure prophylaxis for 7 days after severe traumatic
brain injury with phenytoin is reasonable. After 7 days, there
is no evidence for benefit. The effects of prolonged treatment
of the mechanisms of epileptogenesis are not known, and
there is the potential for adverse drug reaction. There are no
data to guide the selection of newer anticonvulsants for the
management of posttraumatic seizures or to address the
mechanisms of epileptogenesis.
Near-Infrared Spectroscopy. Light is absorbed at different wavelengths in oxygenated and deoxygenated hemoglobin. This
allows infrared electrodes and sensors to estimate percentage
of deoxygenated blood within a capillary bed. When placed
on the forehead, the probe provides an estimation of global cerebral tissue oxygen saturation. A downward trend can suggest
an inability to supply needed oxygen demands, whereas an
upward trend can suggest either luxury perfusion or a cellular
dysfunction and inability to utilize supplied oxygen. Normal
value ranges have been validated in normal children.88 Recent
correlations of near infrared spectroscopy with CT perfusion
41
intensive care unit.3 Acute management should include meticulous control of physiology with goal-directed intracranial
pressure and cerebral perfusion pressure therapies. During
this period the child neurologist can help integrate the results
of noninvasive cerebral monitoring, such as EEG, nearinfrared spectroscopy, and transcranial Doppler, with changes
in the neurologic exam and the pathophysiologic processes
leading to tissue injury. Understanding the pathophysiology
of secondary injury is essential to providing an effective
approach to neuroprotection. Finally, the child neurologist
has a unique long-term perspective within the multidisciplinary team caring for these patients in the intensive care unit
by continuing to provide care and guidance to the patient
and his or her family during the long process of recovery
with its attendant complications of epilepsy, cognitive, and
motor deficits.
Author Contributions
KPG and MSW drafted and edited the manuscript.
Funding
The author(s) received no financial support for the research, authorship,
and/or publication of this article.
Future Directions
The dearth of new data available to support new recommendations in the revised 2012 Brain Trauma Foundation guidelines highlights the difficulty of studies of severe traumatic
brain injury in children. It is clear that more sophisticated
approaches are needed to integrate intracranial pressure and
cerebral perfusion pressure data with other measures of
cerebral metabolism, as well as other physiologic and biochemical parameters.105,106 The availability of transcranial
Doppler, near infrared spectroscopy, and brain tissue oxygen
monitoring will allow care to be directed at maintaining optimum cerebral metabolism and autoregulation, not solely targeting a specific intracranial pressure value. Although the
prospects for new neuroprotective therapies for pediatric
traumatic brain injury are bleak,107 the advent of comparative
effective research approaches for research has the potential to
advance research in this field without development of new
drugs.108 Many important questions remain, including the
type and timing of neurosurgical interventions, and the optimal use of continuous EEG monitoring and antiseizure
medications. An international, multicenter comparative effectiveness study for severe pediatric traumatic brain injury is
currently in progress (http://www.adapttrial.org/).
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