eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Critical Care

Neurointensive Care for Traumatic Brain Injury in Children

Author: Felice Su, MD, FAAP, Instructor of Pediatrics, Division of Critical Care Medicine, Stanford University; Attending Physician, Department of Pediatrics, Division of Critical Care Medicine, Lucile Packard Children's Hospital
Coauthor(s): Ramesh Raghupathi, PhD, Associate Professor, Department of Neurobiology and Anatomy, Drexel University College of Medicine; Jimmy Huh, MD, Assistant Professor of Anesthesiology and Pediatrics, Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Jun 26, 2009

Introduction

Pediatric traumatic brain injury (TBI) affects infants and children of all ages and is caused by various mechanisms, such as falls, motor vehicle collisions, child abuse, and gunshot wounds (GSWs).
 
From 1989-1998, 84,792 children aged 0-19 years died as a result of traumatic brain injury in the United States, with a male-to-female ratio of 2.5:1.¹ Although traumatic brain injury is one of the leading causes of acquired disability and death in infants and children, relatively little research has been done on traumatic brain injury compared with research efforts directed at other pediatric diseases, such as cancer.

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center, Public Health Center, and Children's Health Center and Medscape's Trauma Resource Center. Also, see eMedicine's patient education articles Head Injury, Concussion, Bicycle and Motorcycle Helmets, Child Abuse, Normal Pressure Hydrocephalus, and Dementia in Head Injury.

Pathophysiology

Following primary brain injury, a cascade of cellular and biochemical events occur in the initial minutes and extend into the weeks following the primary injury, leading to secondary neuronal cell degeneration (secondary brain injury) and, ultimately, neuronal impairment or cell death. Much of the research on traumatic brain injury (TBI) is directed at affecting secondary brain injury mechanisms in an effort to reduce the sequelae of traumatic brain injury; some of these mechanisms are outlined below.

Cerebrovascular dysregulation

After traumatic brain injury, alterations in cerebral blood flow are thought to contribute to secondary brain ischemia. In a study of infants and young children, decreased cerebral blood flow (<20 mL/100 g/min) in the initial 24-hour period following injury was associated with poor outcome.² In newborn piglets following traumatic brain injury, reduced levels of vasodilators, including nitric oxide, cyclic guanosine 3',5'-monophosphate (cGMP), cyclic adenosine 3',5'-monophosphate (cAMP), and prostanoids, are thought to contribute to decreased cerebral blood flow.³ Similarly, increased levels of vasoconstrictors, such as endothelin-1, are also implicated in cerebral vascular dysregulation.⁴  Increases in the cerebrospinal fluid (CSF) levels of endothelin-1 have been observed early after severe traumatic brain injury in infants and children.⁴

Cerebral swelling

Diffuse cerebral swelling following pediatric traumatic brain injury may be a significant contributor to increased intracranial pressure (ICP), which can result in further ischemia and herniation. This swelling is thought to result from blood-brain barrier disruption (vasogenic edema), osmolar changes, and edema at the cellular level (cytotoxic or cellular edema). Furthermore, hypoxia, hypoperfusion, inflammation, and oxidative stress can also contribute to cerebral swelling.

Osmolar shifts primarily occur in areas of necrosis where the osmolar load increases with the degradation of neurons. As reperfusion and recovery occurs, water is drawn into the area secondary to the high osmolar load, and the surrounding neurons become edematous.

Traumatic axonal injury

A common pathology observed in infants and young children, in both unintentional and inflicted traumatic brain injury, is diffuse or traumatic axonal injury (TAI). TAI involves widespread damage to axons in the white matter of the brain, primarily in regions such as the corpus callosum, basal ganglia, and periventricular white matter.⁵ Hypoxic-ischemic injury, calcium and ionic flux dysregulation, and mitochondrial and cytoskeletal dysfunction are thought to play important roles in axonal damage.

Following head trauma, excitotoxicity occurs with the release of excessive amounts of excitatory amino acids such as glutamate, resulting in neuronal injury. This occurs in 2 phases: (1) sodium-dependent neuronal swelling followed by (2) delayed, calcium-dependent neuronal degeneration.⁶  These effects are mediated through activation N -methyl-D-aspartate (NMDA) and glutamate receptors, leading to a rise in the intracellular calcium-mediated activation of proteases and lipases, which facilitates neuronal degeneration and necrotic cell death. 

In contrast to necrotic cell death, apoptosis or programmed cell death, is not marked by swelling and dissolution of cell membranes but rather is marked by DNA fragmentation and the formation of apoptotic cell bodies associated with neuronal cell shrinkage. Apoptosis is a cellular event that is triggered by intrinsic mechanisms (initiated in the mitochondria) or extrinsic mechanisms (tumor necrosis factor superfamily of cell-surface death receptors), which activate a cascade of enzymes called caspases that lead to cell termination. Apoptosis is felt to contribute to secondary neuronal injury after a traumatic brain injury event.

Animal studies have shown that developing neurons are more susceptible to excitotoxic injury than mature neurons, probably because more calcium is transmitted via the NMDA-mediated calcium channel in the immature brain.⁷ However, although the administration of NMDA antagonists following traumatic brain injury in immature rats decreased excitotoxic-mediated neuronal death, apoptotic cell death increased. Further research is needed to address the role of excitotoxicity and apoptosis following trauma to the developing brain.

Inflammatory mediator release

Studies of CSF support a role for inflammation following pediatric traumatic brain injury.⁸ Interleukin-6 and interleukin-8 and soluble adhesion molecules (sP-selectin and intercellular adhesion molecule [sICAM-1]) were increased in the CSF of infants and children following traumatic brain injury. Whether these inflammatory mediators contribute to neurodegeneration or neuroprotection remains to be determined.

Treatment

Despite ongoing research targeting the previously mentioned mechanisms of secondary brain injury (see Pathophysiology), treatment for the pediatric patient with traumatic brain injury (TBI) remains mainly supportive.

Other causes of secondary brain injury, such as hypoxemia, hypotension, elevated intracranial pressure (ICP) or intracranial hypertension, hypercarbia, hyperglycemia or hypoglycemia, electrolyte abnormalities, enlarging hematomas, coagulopathy, seizures, and hyperthermia, are potentially avoidable or treatable. 

The primary goal in the acute management of pediatric patients with severe head injuries is to prevent or ameliorate factors that promote secondary brain injury. The Society of Critical Care Medicine has recently published guidelines for the acute management of severe traumatic brain injury for the pediatric population based on a review of the pediatric traumatic brain injury literature and previously established adult guidelines (see Media file 1-2).⁹

Primary interventions

Treatment of severe traumatic brain injury (Glasgow Coma Scale 3-8) begins with the ABCs. This includes initial stabilization, including securing the airway, achieving sufficient oxygenation and ventilation, and avoiding or rapidly treating hypotension. Furthermore, maneuvers to prevent or limit intracranial hypertension should also be instituted.

• Early airway management involves providing proper airway position and clearance of debris while keeping C-spine precautions in place until the C-spine has been evaluated and cleared. Appropriate bag-mask ventilation and endotracheal intubation should be used as needed.
• Hypercarbia and hypoxia are both potent cerebral vasodilators that result in increased cerebral blood flow and volume and, potentially, increased ICP; thus, they must be avoided. Orotracheal intubation allows for airway protection in patients who are severely obtunded and allows for better control of oxygenation and ventilation.
• In the initial resuscitation period, efforts should be made to maintain eucapnia at the low end of the reference range (PaCO₂ of 35-40 mm Hg) and prevent hypoxia (PaO₂ <100 mm Hg) to prevent or to limit secondary brain injury. Nasotracheal intubation should be avoided because of the risk of direct intracranial injury, especially in patients with basilar skull fractures.
• Special neuroprotective considerations must be given to the choice of medications used to facilitate endotracheal intubation (prevent elevated ICP, minimize cerebral metabolic rate or oxygen consumption, and avoid hypotension). Common medications used in the intubation of patients with traumatic brain injury include etomidate, thiopental, and potentially lidocaine as an added agent. Ketamine is commonly avoided because of its potential for elevating ICP.
• Hypotension has been shown to significantly increase mortality rates in children with head injury, with or without the presence of hypoxia. Every effort should be made to avoid hypotension in patients with traumatic brain injury. These patients should undergo aggressive fluid resuscitation with isotonic fluids until euvolemia is achieved. Isolated traumatic brain injury rarely leads to severe hypotension. Other possible injuries (eg, spinal cord trauma), ongoing occult blood loss, and reasons for cardiac tamponade, including hemothorax or pneumothorax, should be identified and quickly treated.
• Manipulation of the head of the bed to optimal levels to decrease venous obstruction may help to control ICP. Traditionally, 30º elevation of the head in midline position is thought to be optimal, although this has not been confirmed by pediatric studies. Again, care of the C-spine must always be a consideration when moving patients with traumatic brain injury.
• Fever (ie, temperature >38°C or 100.4°F) or hyperthermia is not uncommon following traumatic brain injury.¹⁰ Temperature control through the treatment of fever can aid in decreasing systemic and cerebral metabolic requirements. Fever also decreases the seizure threshold. Efforts should be made to avoid hyperthermia using medications and cooling devices (see Hypothermia).
• Sedation and analgesia are also important adjuncts to minimize increases in ICP. Painful stimuli and stress increase metabolic demands and increase blood pressure and ICP; however, sedatives and analgesics must be judiciously chosen to prevent unwanted side effects (eg, hypotension). Short-acting and reversible medications, such as fentanyl, are commonly used. Short-acting benzodiazepines, such as midazolam, are also commonly used and have the added benefit of increasing the seizure threshold.
• Head CT scanning should be performed after initial resuscitation in patients with traumatic brain injury to establish a baseline and assess initial damage. Neurosurgeons evaluate the potential need for surgical intervention, such as evacuation of a hematoma that may lead to intracranial hypertension and herniation. Repeat CT scanning should be considered whenever neurologic deterioration or increased ICP persists despite interventions.

ICP monitoring

Intracranial hypertension is associated with poor neurologic outcome. In the neurointensive care unit, continuous ICP monitoring is predominantly used to help target therapies to maintain adequate cerebral perfusion pressure (CPP), which is equal to the mean arterial blood pressure minus ICP. Continuous ICP monitoring is also used to minimize intracranial hypertension and to monitor trends in ICP. Although no randomized controlled trials have been conducted to assess the use of ICP monitoring, it is generally widely accepted as an essential tool in major pediatric centers to guide therapies for the treatment of severe traumatic brain injury.

The exact upper limit of pathological ICP for a given age has not been established, but the general consensus is that treatment efforts should, at a minimum, attempt to keep ICP less than 20 mm Hg. ICP can be measured using an external strain gauge transducer, a catheter tip pressure transducer, or a catheter tip fiberoptic transducer. External strain gauge devices measure ICP via transduction through fluid-filled lines. The external device must be placed with reference to the head for accurate measurements. Complications in measurement most commonly arise from line obstruction. Catheter tip devices are calibrated and then placed in the parenchyma or are coupled to a ventricular catheter. They are susceptible to measurement drift after several days of use if not replaced. Choice of measurement device is made on the basis of the mechanism and the severity of injury and accessibility of the ventricles. Ventricular devices have the added benefit of cerebrospinal fluid (CSF) drainage.

As secondary brain injury occurs, brain edema increases and cerebral blood flow decreases with ensuing ischemia. Goals of ICP monitoring revolve around adjusting therapies to maintain a CPP greater than 40 mm Hg (and higher for older children) and an ICP less than 20 mm Hg, based on studies that reported increased mortality rates in patients with lower CPP and higher ICP. Maintaining normal blood pressure, adequate oxygenation, and ventilation during this time is necessary in patients with traumatic brain injury to prevent further ischemic damage.

CSF drainage

Ventricular drains have long been used for the drainage of CSF in patients with hydrocephalus. With the advent of ventricular ICP monitoring, ventricular drainage for patients with increased ICP has also been commonly used. With removal of CSF, total intracranial volume is reduced, which may lead to decreased ICP and improvement of CPP.

Paralysis

If initial maneuvers are unsuccessful in controlling elevated ICP, neuromuscular blockade should be considered. Paralysis can be facilitated through intermittent boluses as opposed to continuous infusion. Benefits of paralysis include the prevention of shivering, which decreases the metabolic demands and oxygen consumption; improved cerebral venous drainage through decreased intrathoracic pressure; and ease of ventilation and oxygenation by elimination of ventilator-patient asynchrony. Specific concerns regarding neuromuscular blockade in patients with traumatic brain injury include masking of seizure activity, secondary complications due to ineffective pulmonary toilet, increased stress and ICP related to inadequate sedation and analgesia, and the inability to perform a clinical neurologic examination to monitor the patient's course.

Hyperosmolar therapy

Mannitol has long been successfully used to treat increased ICP, especially following traumatic brain injury in adults.

• Mannitol is an osmolar agent with rapid onset of action via 2 distinct mechanisms.
• Initial effects of mannitol result from reduction of blood viscosity and a reflex decrease in vessel diameter to maintain cerebral blood flow through autoregulation. This decrease in vessel diameter contributes to decreasing total cerebral fluid volume and pressure. This mechanism of action is transient (lasting about 75 min) and requires repeated dosing for prolonged effect.
• Mannitol exhibits its second mechanism of action through osmotic effects. It increases serum osmolality; thus, water is shifted from intracellular compartments to the intravascular space, and cellular edema is decreased. Although slower in onset, this mechanism lasts up to 6 hours in duration.
• Pitfalls of mannitol include its potential to accumulate in regions of cerebral vascular interruption and cause a reverse osmotic shift, therefore increasing brain edema and increasing ICP; this risk is reported with continuous infusions. For this reason, intermittent mannitol boluses are recommended. Also, mannitol has been linked to acute tubular necrosis and renal failure at serum osmol levels greater than 320 mOsm/L.
• Because mannitol is a potent diuretic, hypovolemia can also occur, leading to decreased cardiac output and a resulting decrease in cerebral perfusion. 
• More recently, hypertonic saline has been shown to be an effective therapy for intracranial hypertension following pediatric traumatic brain injury. Hypertonic saline, typically 3% saline, has an osmolar mechanism of action similar to that of mannitol, without the diuretic effects.
• Added theoretical benefits of hypertonic saline include improved vasoregulation, cardiac output, immune modulation, and plasma volume expansion.
• Pediatric patients with traumatic brain injury appear to tolerate a higher osmolar load with the use of hypertonic saline rather than mannitol. Patients using hypertonic saline have tolerated serum osmolalities of as much as 360 mOsm/L. However, in the author's institution, reversible renal insufficiency has been noted with the use of hypertonic saline when serum osmolality approached 320 mOsm/L; thus, caution should be used.
• Risks of hypertonic saline administration include rebound intracranial hypertension after withdrawal of therapy, central pontine myelinolysis with rapidly increasing serum sodium levels, subarachnoid hemorrhage due to rapid shrinkage of the cerebrum and tearing of bridging veins, and renal failure. 
• More research in the area of hyperosmolar therapy is needed to compare the effects of mannitol and hypertonic saline in pediatric patients with intracranial hypertension.

Hyperventilation

Although ventilation at the lower end of eucapnia may be beneficial in decreasing ICP, whether further reduction in PaCO₂ yields additional benefit and improves outcome is unclear. Hyperventilation has the potential to reduce ICP via reflex vasoconstriction in the presence of hypocapnia. The vasoconstriction leads to decreased cerebral blood flow, decreased overall cerebral fluid volume, and, therefore, decreased ICP. In addition, hyperventilation is thought to limit cerebral acidosis and improve metabolism. In cases of refractory intracranial hypertension, mild hyperventilation (PaCO₂ of 30-35 mm Hg) may be beneficial in decreasing ICP.

The potential dangers associated with inducing hypocapnia are related to the vasoconstriction that it produces. Individual autoregulation of cerebral blood flow with respect to hypocapnia widely varies and is difficult to predict. Excessive hypocapnia may lead to ischemia secondary to insufficient cerebral blood flow. Ensuing respiratory alkalosis also shifts the hemoglobin-oxygenation dissociation curve to the left, making release of oxygen to tissues more difficult. Although aggressive hyperventilation (PaCO₂ <30 mm Hg) may be necessary in emergency situations such as impending herniation (eg) in a patient with Cushing's triad (hypertension, bradycardia, and irregular respirations), it is not commonly used as a prolonged therapy for the reduction of ICP due to its association with worse long term neurologic outcomes.

Barbiturates

The use of high-dose barbiturate therapy, such as pentobarbital, has been successful in the management of increased ICP. This class of medication suppresses cerebral metabolism, thus decreasing oxygen demand. Barbiturates also have the added benefit of neuroprotection through mechanisms such as inhibition of free radical lipid peroxidation and neuronal membrane disruption.

Barbiturate therapy in the patient with traumatic brain injury requires continuous electroencephalographic monitoring. Clearance of barbiturate from the body varies among patients, and titration of therapy based on serum levels is difficult. With EEG monitoring, barbiturate infusions may be titrated to achieve burst suppression.

Despite the potential benefits of barbiturates, their adverse affects on the cardiovascular system limit their use to refractory intracranial hypotension. Barbiturates may cause both myocardial depression and hypotension that requires fluid resuscitation and inotropic support; ability to perform neurological examination is also lost when barbiturates are used to control ICP. Additionally, barbiturate therapy may result in immune suppression, leading to sepsis and ileus with subsequent feeding intolerance. The practice of obtaining daily surveillance cultures should be considered when using barbiturate therapy.

Hypothermia

Hyperthermia has long been correlated with poor outcome in patients with traumatic brain injury, and control of fever is an important initial intervention to limit secondary brain injury. More recently, induced moderate hypothermia (32-34°C, 89.6-93.2°F) has emerged as a potentially useful strategy. Experimentally, temperature reduction has been associated with decreases in inflammatory response, excitotoxicity, metabolic demands, and oxidative stress. A recent phase II clinical trial demonstrated that 48 hours of moderate hypothermia initiated within 6-24 hours of acute traumatic brain injury in pediatric patients reduces ICP and was "safe," although a higher incidence of arrhythmias (reversed with fluid administration or rewarming) and rebound ICP elevation after rewarming were reported.¹¹  Until further clinical studies are performed, moderate hypothermia is reserved for patients with persistent intracranial hypertension refractory to other medical interventions. Problems associated with hypothermia include increased bleeding risk, arrhythmias, and increased susceptibility to infection and sepsis.

Decompressive craniectomy

When medical therapies for treatment of intracranial hypertension remains refractory, decompressive craniectomy is a surgical option. Decompressive craniectomy typically involves either unilateral frontal-temporal-parietal or bilateral frontal craniectomy. Patients typically undergo this procedure within the first 48 hours of initial injury. Potential complications from decompressive craniectomy include hemorrhage and exacerbation of cerebral edema.

Conclusion

Although various interventions are being investigated and developed to maintain adequate cerebral perfusion pressure (CPP) and limit intracranial hypertension in children with traumatic brain injury (TBI), the hallmark of an effective therapy is improved outcome. Most interventions have not specifically been targeted for outcome studies. A handful of studies have shown hypertonic saline to be associated with improved outcome.^12,13 Hypertonic saline has been shown to correlate with fewer complications, requiring fewer medical interventions and shorter ICU stays if initiated early. Likewise, barbiturates have also been associated with improved outcome.

In a study of 7 children in a single institution treated with pentobarbital for refractory intracranial hypertension, 3 patients had good recovery, 2 were moderately disabled, and 2 were severely disabled.¹⁴ The length of barbiturate therapy did not correlate with outcome in this study. Finally, some studies have also supported trends of improved outcome with use of decompressive craniectomy combined with medical therapy when compared with maximal medical therapy alone.¹⁵ Most patients had undergone decompressive craniectomy within 48 hours of injury.

Although further studies need to be performed to confirm the use of various medical therapies with respect to long-term outcome, other factors have been shown to have predictive value in determining morbidity and mortality. The factors most predictive of poor neurologic outcome include hypotension, ICP greater than 20 mm Hg, and hypoxia. Other studies have correlated poor outcome with low Glasgow Coma Scale scores and bilateral cerebral swelling and mass lesions upon initial presentation. A recent study concluded that traumatic brain injuries are more likely than orthopedic injuries to result in increases in long-term postconcussive symptoms.¹⁶

In a study of neurologic outcome in patients aged 0-16 years at 6 and 12 months postinjury, patients aged 0-4 years showed the poorest survival rate, with a 62% mortality rate at one year postinjury.¹⁷ This patient age group was notable for a higher percentage of subdural hematomas requiring evacuation (20% of patients) and hypotension (32% of patients). Patients aged 5-10 years had the most favorable outcome, with 66% having good recovery at one year postinjury.

In summary, severe pediatric traumatic brain injury causes a significant burden on our population and deserves further investigation in the hopes of improving outcomes.

Multimedia

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Media file 1: Critical pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury, according to the Society of Critical Care Medicine guidelines. GCS = Glasgow Coma Scale; ICP = Intracranial pressure; CPP = Cerebral perfusion pressure; HOB = Head of bed; CSF = Cerebrospinal fluid; PRN = As needed.

(Enlarge Image)

Media file 2: Second tier therapy for the treatment of established intracranial hypertension in pediatric traumatic brain injury, according to the Society of Critical Care Medicine guidelines. ICP = Intracranial pressure; CBF = Cerebral blood flow; SjO2 = Jugular venous oxygen saturation; AJDO2 = Arterial-jugular venous difference in oxygen content.

Keywords

neurointensive care for traumatic brain injury in children, fall, motor vehicle collision, auto accident, child abuse, child physical abuse, gunshot wound, GSW, head trauma, head injury, secondary brain injury, brain ischemia, brain trauma, closed-head injury, diffuse axonal injury, DAI, increased intracranial pressure, increased ICP, pediatric, traumatic brain injury, TBI, cerebrovascular dysregulation, cerebral swelling, vasogenic edema, traumatic axonal injury, hypoxic-ischemic injury, excitotoxicity, apoptosis, hypoxemia, hypotension, intracranial hypertension, hypercarbia, hypoglycemia, hyperglycemia, electrolyte abnormalities, hematomas, hyperthermia, treatment, diagnosis

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