Neurocritical Care for Severe Pediatric Traumatic Brain Injury

Neurocritical Care for Severe Pediatric Traumatic Brain Injury

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Traumatic brain injury (TBI) is one of the leading causes of acquired disability and death in infants and children. Falls and motor vehicle collisions are common unintentional causes, whereas abuse in infants and young children and assaults in adolescents are unfortunate inflicted causes of TBI. Management of these injuries focuses on limiting the progression of the primary brain injury and minimizing secondary brain injury(ies). Research has revealed important age-dependent responses following pediatric TBI.

For patient education information, see the Brain & Nervous System Center and Trauma Resource Center, as well as Head Injury (Brain Injury)ConcussionBicycle and Motorcycle HelmetsChild AbuseNormal Pressure Hydrocephalus, and Dementia in Head Injury.

See Pediatric Concussion and Other Traumatic Brain Injuries7 Potentially Devastating Traumatic Brain Injuries, as well as Recognizing Physical Child Abuse, Critical Images slideshows, to help identify the signs and symptoms of TBI, determine the type and severity of injury, and initiate appropriate treatment.

Primary injury to the brain occurs as an immediate consequence of the force of the trauma. Linear forces as a result of direct blows to the head generate focal injuries such as intracranial hemorrhages and contusions. Intracranial hemorrhage resulting from trauma typically occurs in 4 locations: epidural, subdural, subarachnoid, and intraparenchymal (see the chart of features below).

Contusions are bruises of the brain parenchyma as a result of blunt head injury that causes the brain surface to impact the bony ridges of the skull. Injury patterns include acceleration-deceleration injuries, where the brain strikes the skull in a “coup-contracoup” fashion, with the “coup” contusion occurring at the site of impact and the “contracoup” contusion located directly opposite the site of impact.

Clinical symptoms of traumatic brain injury (TBI) relate to the severity and location of the injury. Contusions may lead to local edema, and ischemia will result in neurologic deterioration, increased intracranial pressure (ICP) and intracranial hypertension (ICH), and brain herniation.

Acceleration-deceleration injuries can also generate inertial, angular forces, resulting in the physical shearing or tearing of axons (termed primary axotomy). Rotational forces on the brain during acceleration-deceleration injuries cause widespread damage to axons in the white matter of the brain, and this should be suspected in a child when the degree of neurologic deterioration is out of proportion to a relatively unremarkable cranial computed tomography (CT) scan.

Secondary brain injury develops in the initial minutes to weeks following primary brain injury and occurs in two forms. The first form of secondary brain injury is potentiated by a myriad of physiologic and metabolic alterations, including but not limited to, the following:

This form of secondary brain injury is potentially avoidable and is amenable to treatment. Currently, the primary focus in the acute management of TBI is to prevent or ameliorate these events that promote secondary brain injury.

The other form of secondary brain injury includes a cascade of cellular events that occur in the initial minutes and extend into the weeks following the primary injury, leading to neuronal cell degeneration, ongoing or secondary traumatic axonal injury (TAI), and, ultimately, neuronal cell death. [1] Some of these mechanisms include cerebrovascular dysregulation, cerebral swelling, TAI, necrosis and apoptosis, and inflammation. Although vigorous research continues in these areas, no treatment for this type of secondary brain injury is available.

Cerebrovascular response

Hyperemia (cerebrovascular engorgement) does not seem to play a large role in the pathology of pediatric TBI. [2] Instead, a decrease in cerebral blood flow (CBF) of 20 mL/100 g/min in the initial 24 hours following severe TBI in infants and young children has been associated with poor outcome. [3] Furthermore, impairment of cerebral autoregulation following TBI in children as demonstrated by transcranial Doppler ultrasonographic measurements is associated with poor outcome. [4, 5]

Mechanisms of cerebrovascular dysregulation include direct vessel wall injury and reduced levels of vasodilators, including nitric oxide, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). [6] Similarly, increased levels of vasoconstrictors, such as endothelin-1 (ET-1), are also implicated in cerebrovascular dysregulation. [7]

An age-dependent response following experimental pediatric TBI has been noted in animal studies, with younger animals demonstrating a more sustained decrease in cerebral blood flow (CBF) and hypotension than older animals following diffuse TBI. [8, 9] Endogenous opioids and N-methyl-D-aspartate (NMDA) have also been found to participate in age-dependent impairment of cerebral autoregulation in the youngest animals following diffuse TBI. [10] In contrast, focal (contusive) injuries in older animals produced the most pronounced decrease in CBF. Thus, both age-at-injury and the type of injury may determine alterations in CBF. [11]

Diffuse cerebral swelling

Diffuse cerebral swelling following pediatric TBI may be a significant contributor to ICH, 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). Hypoxia and hypoperfusion can also contribute to cerebral swelling, and clinical studies suggest that cellular edema plays a prominent role. [2, 12]

Osmolar shifts

Osmolar shifts primarily occur in areas of necrosis, where the osmolar load increases with the degeneration of neurons. As reperfusion occurs, water is drawn into the area by the high osmolar load, and the surrounding neurons become edematous. Cellular swelling independent of osmolar load also occurs in astrocyte foot processes and is thought to be due to excitotoxicity-mediated uptake of glutamate. Glutamate uptake is coupled to sodium-potassium adenosine triphosphatase (ATPase), with sodium and water accumulating in astrocytes. [13] Endogenous water channels known as aquaporins present in astrocytes have also been implicated in the evolution of cerebral edema. [14]

Traumatic axonal injury

A common source of significant morbidity in infants and young children, in both unintentional (accidental) and inflicted (abusive) TBI, is TAI. [15, 16, 17] Widespread damage to axons may occur in the white matter of the brain, primarily in the corpus callosum, basal ganglia, and periventricular white matter. [18] Calcium and ionic flux alterations, hypoxic-ischemic injury, and mitochondrial and cytoskeletal dysfunction are thought to play important roles in axonal damage. [19]

In contrast to the immediate physical tearing of an axon (primary axotomy), TAI is thought to mainly occur by a delayed process involving ongoing axonal degeneration (secondary axotomy). [20] Animal models suggest that the younger brain may be more vulnerable to diffuse TBI than the adult brain following TBI of equivalent severity, with survivors exhibiting significant chronic cognitive disability. [21, 22]

Excitotoxicity and apoptosis

Following TBI, excitotoxicity occurs with the release of excessive amounts of excitatory amino acids such as glutamate, which results in neuronal injury. This occurs in two phases: (1) sodium-dependent neuronal swelling, followed by (2) delayed, calcium-dependent neuronal degeneration. [23] These effects are mediated through the activation of glutamate receptors, such as NMDA, and metabotropic receptors (linked to second-messenger systems), which lead to a rise in the intracellular calcium-mediated activation of proteases and lipases. This facilitates neuronal degeneration and necrotic cell death. Calcium-activated protease activation, such as with calpains, has been observed in areas that exhibited neuronal cell loss following TBI in the immature rat. [24]

In contrast to the cell swelling and dissolution of cell membranes that is observed following necrotic cell death, apoptosis (programmed cell death) is marked by DNA fragmentation and the formation of apoptotic cell bodies associated with neuronal cell shrinkage. Apoptosis may be triggered by intrinsic mechanisms (initiated in the mitochondria) or extrinsic mechanisms (tumor necrosis factor [TNF]–mediated cell-surface death receptors), which activate a cascade of enzymes (caspases) that lead to apoptotic cell death.

The response to excitotoxicity and apoptosis appears to be age dependent. Experimental studies have shown that immature 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. [25] Following TBI, however, calcium accumulation in the injured brain was more extensive and remained longer in the mature brain. [26] This difference may be due to the less severely injured immature brain, as no neuronal cell death was observed in contrast to the mature traumatized brain. This suggests that both age and injury severity may play an important role in the extent of excitotoxicity.

The administration of excitotoxic antagonists following TBI in immature and mature rats has been shown to decrease excitotoxic-mediated neuronal death. Nevertheless, apoptotic cell death increased in the immature rat. [27, 28] To date, no antiexcitotoxic agents have been successful in clinical TBI trials.

Inflammation

Studies of cerebrospinal fluid (CSF) support a role for inflammation following pediatric TBI. For example, interleukin (IL)-6 and IL-10 were increased in the CSF of infants and children following severe TBI. Furthermore, there was an age-dependent production of IL-1; higher concentrations were observed in children younger than 4 years. [29]

Age-dependent injury patterns exist. [30]  Abusive or intentional injury is a major cause of morbidity and mortality in infants and young children. [31, 32]  Unintentional injuries in this age group occur as a result of falls and motor vehicle collisions. Falls become the predominant mechanism of injury by the toddler age. Among motor vehicle–related injuries in this age group, motor-pedestrian injuries are more common than motor-vehicle occupant injuries. [33, 34]  School-aged children exhibit a rise in bicycle-related injuries. Adolescents experience a rise in motor vehicle injuries, sports-related injuries, and assaults. [35]

Children appear to experience age-dependent pathology following pediatric traumatic brain injury (TBI). In infants and young children, subdural hematomas and diffuse injury (eg, diffuse cerebral swelling) are more common than focal injuries (eg, contusions). [36, 37]  Hypoxic-ischemic injuries seem to be less common in unintentional TBI. [38, 39]

Traumatic brain injury (TBI) in children is a leading cause of morbidity and mortality in the United States, with an estimated cost of $1 billion per year. [40] ​ In the United States, at least 1.4 million TBI occur annually—1.1 million are treated in emergency departments (EDs), with more than 50,000 associated deaths. [41, 42]  An estimated 3.2 million US civilians live with disability following a TBI. [41] The highest combined rates of TBI-associated ED visits, hospitalizations, and deaths occur in the youngest children (aged 43</ref> 

The Monro-Kellie doctrine states that the intracranial vault is incompressible and holds a fixed volume of brain, cerebrospinal fluid (CSF), and blood; thus, any increase in volume of one of the cranial constituents must be compensated by a decrease in volume of another. This doctrine has critical consequences for patients with TBI.

As noted earlier, secondary brain injury results in cerebral edema. The initial compensatory mechanisms for this increase in intracranial volume are displacement of the CSF to the spinal canal and displacement of venous blood to the jugular veins; these reactions prevent elevation of intracranial pressure (ICP). Once these compensatory mechanisms are exhausted, even small increases in cerebral edema and intracranial volume lead to profound increases in ICP, which compromises cerebral perfusion. This then causes cerebral ischemia and further worsening of cerebral edema, which may culminate in brain herniation and death.

Patients with intracranial injuries resulting in increased intracranial pressure (ICP) and intracranial hypertension (ICH) may initially present with headache and vomiting, but they may rapidly progress to altered mental status and obtundation. The Glasgow Coma Scale (GCS) is classically used to evaluate injury severity. A GCS score of less than 9 suggests severe brain injury [44] :

As the ICP continues to rise with subsequent ICH, herniation syndromes may develop, with classic clinical findings of the Cushing triad: irregular respirations, bradycardia, and systemic hypertension. Neurogenic posturing and seizures may also occur, in addition to changes in cranial nerve examination due to brainstem compression.

Signs of occult TBI in patients with no history of trauma include retinal hemorrhages on ophthalmologic examination. The presence of these signs suggest abusive or intentional head trauma, and they are commonly associated with subdural hematomas. [31] Additionally, papilledema following unintentional or intentional trauma signifies ICH, necessitating emergent further evaluation.

Computed tomography (CT) scanning provides rapid images of the skull and brain, and it is the first imaging modality used to diagnose skull fractures and intracranial pathology, such as an epidural hematoma with mass effect. Evidence of elevated intracranial pressure (ICP) may include a midline shift due to mass effect and the loss of ventricular space, which are some of the features that herald impending herniation.

Magnetic resonance imaging (MRI) provides more detailed imaging than CT scanning and is used to confirm the diagnosis of traumatic brain injury. MRI also provides better visualization of posterior fossa lesions. However, MRI is not feasible in the initial stabilization and management of the patient in the emergency department and intensive care unit due to its lengthly time requirement, but it may provide useful information about the injury severity once the patient is stable.

The Society of Critical Care Medicine and World Federation of Pediatric Intensive and Critical Care Societies published the second edition of the Guidelines for the Acute Management of Severe Traumatic Brain Injury for Infants, Children, and Adolescents in 2012 (the most recent edition to date), based on a review of the pediatric traumatic brain injury (TBI) literature. [45]  A brief synopsis of the guidelines is discussed below, but the reader is urged to read the actual guidelines for complete details.

Initial intervention for patients with TBI focuses on the detection of the primary injury and prevention or treatment of secondary brain injury. The following treatable conditions can exacerbate secondary brain injury:

Treatment of severe TBI (Glasgow coma scale [GCS] score, 3-8) follows current trauma life-support guidelines. Stabilization begins with applying the basic elements of resuscitation: securing the airway, achieving adequate oxygenation and ventilation, and avoiding or rapidly treating hypotension.

Early airway management involves providing proper airway position, clearance of debris while maintaining cervical spine precautions, and orotracheal intubation. Hypercarbia and hypoxia must be avoided, because they are both potent cerebral vasodilators that result in increased cerebral blood flow and volume and, potentially, increased ICP and ICH. Orotracheal intubation allows for not only airway protection in patients who are severely obtunded but also 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 normal reference range (partial pressure of carbon dioxide [PaCO2] of 35-39 mm Hg) and prevent hypoxia (partial pressure of oxygen [PaO2] <60-65 mm Hg) to prevent or to limit secondary brain injury. Nasotracheal intubation should be avoided because of the risk of cervical spine injury and 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. These considerations are as follows:

Common medications used in the intubation of patients with TBI include midazolam, fentanyl, etomidate, and/or lidocaine, along with neuromuscular blockade. Potential specific side effects of these medications include (but are not limited to) hypotension, chest wall rigidity, adrenal suppression, and myoclonus.

Other medications used to facilitate intubation include propofol and ketamine. Propofol increases the depth of sedation in a dose-dependent manner. Propofol reduces ICP and decreases the metabolic rate of cerebral oxygen consumption, but this agent is not recommended in hemodynamically compromised trauma patients as it can cause hypotension through myocardial depression and vasodilation. [46] ​Also, it should not be used for prolonged sedation in children with TBI because of the risk of propofol infusion syndrome, which consists of cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure. [45]  

Ketamine is thought to have the potential for elevating ICP. However, a prospective, controlled, clinical trial of ketamine administration in intubated and mechanically ventilated children with elevated ICP from severe TBI revealed that ketamine effectively decreased ICP and prevented untoward elevation of ICP during potentially distressing interventions, without lowering the blood pressure and the cerebral perfusion pressure (CPP). However, these patients were already on continuous infusions of intravenous (IV) sedative medications, and some patients received hyperosmolar therapy or decompressive craniectomy prior to the administration of ketamine. [47]  Although further studies are required to evaluate the isolated effect of ketamine on ICP, it is currently believed that the evidence for increased ICP due to ketamine is weak. A systematic review suggested that ketamine is unlikely to meaningfully elevate ICP. [48]

Every effort should be made to avoid hypotension in these patients, because hypotension has been shown to increase morbidity and mortality. Euvolemia should be maintained. Isolated TBI rarely leads to severe hypotension. Other causes of trauma-related hypotension include, but are not limited to:

Raising the head of the bed to decrease venous obstruction may help to control ICP. Traditionally, elevation of the head to 30° in the midline position is recommended, but titration of head elevation to achieve the lowest ICP would be optimal. Again, care of the cervical spine must always be a consideration when moving patients with TBI.

Posttraumatic hyperthermia (core body temperature ≥38.0°-38.5°C [100.4°-101.5°F]) is not uncommon in patients with TBI. [49]  Fever increases cerebral metabolic requirements and oxygen consumption, and it can promote ICH. Fever also decreases the seizure threshold. Consequently, efforts should be made to avoid hyperthermia. The patient should also be evaluated and treated for other etiologies of fever, such as infection and atelectasis.

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 selected to prevent unwanted side effects, such as hypotension. Short-acting and reversible analgesics, such as fentanyl, are commonly used. Short-acting benzodiazepines, such as midazolam, are also commonly used and they have the added benefit of increasing the seizure threshold.

Head computed tomography (CT) scanning should be performed after initial resuscitation in patients with severe TBI to establish a baseline and to assess the initial injury. Neurosurgeons will evaluate the potential need for surgical intervention, such as evacuation of a hematoma that could lead to ICH and herniation. Due to the potential for intracranial lesions to evolve, repeat CT scanning should be considered whenever neurologic deterioration or increased ICP persist despite medical interventions.

For patients with severe TBI or a GCS score of 8 or less and suspected ICH, either an intraparenchymal or intraventricular ICP monitor is placed, with the latter being advantageous for draining cerebrospinal fluid (CSF) in the case of ICH.

Intracranial hypertension is associated with poor neurologic outcome. In the intensive care unit, continuous ICP monitoring is predominantly used to help target therapies to maintain adequate CPP, which is equal to the mean arterial blood pressure (MAP) minus either the ICP or the central venous pressure (CVP), whichever is greater.

Although no randomized controlled trials have been conducted to assess the use of ICP monitoring in pediatric patients with severe TBI, it is widely accepted as an essential tool in major pediatric centers to guide therapies for the treatment of severe TBI. The exact threshold of pathologic ICP or ICH 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 any of the following:

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. All of the devices have potential complications, such as infection and bleeding.

Goals of ICP monitoring revolve around adjusting therapies to maintain a minimum CPP greater than 40 mm Hg and a CPP threshold of 40-50 mm Hg, with infants at the lower end and adolescents at the upper end of this range.

Although data are very limited, some studies also suggest multimodality monitoring, such as the use of brain tissue oxygen monitoring in pediatric patients with severe TBI, because brain tissue hypoxia has been observed, even during periods when ICP is not elevated. [50, 51, 52, 53]  Further studies are clearly warranted to assess if treating brain tissue hypoxia improves outcome.

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 ICH has also been commonly used. Removal of CSF reduces total intracranial volume, which may lead to decreased ICP and improvement of CPP.

If initial maneuvers are unsuccessful in controlling ICH, neuromuscular blockade may be considered. Benefits of neuromuscular blockade include the following:

Concerns regarding neuromuscular blockade include, but are not limited to, the following:

Hypertonic saline has been shown to be an effective therapy for ICH in children with TBI. Hypertonic saline, typically 3% saline, increases serum osmolality, causing the shift of water from intracellular compartments to the intravascular space, with subsequent decrease in cellular edema. Additional theoretical benefits of hypertonic saline include improved vasoregulation, cardiac output, immune modulation, and plasma volume expansion.

Pediatric patients with severe TBI appear to tolerate a high osmolar load with the use of hypertonic saline, reaching serum osmolalities around 360 mOsm/L, although some of these patients developed reversible renal insufficiency. [54]  However, reversible renal insufficiency has been noted with the use of hypertonic saline when serum osmolality approached 320 mOsm/L; thus, caution should be used. [55]  Effective doses for acute use of 3% saline for ICH range from 6.5 to 10 mL/kg; continuous infusion of 3% saline ranges from 0.1 to 1 mL/kg/h administered on a sliding scale. The minimum dose needed to maintain an ICP of less than 20 mm Hg should be used. Serum osmolality should be maintained at less than 360 mOsm/L.

Risks of hypertonic saline administration include, but are not limited to, the following:

Hypertonic saline may have an advantage over mannitol in hypovolemic patients. In such situations, hypertonic saline may increase intravascular volume and thus increase blood pressure in addition to decreasing ICP. However, mannitol has long been successfully used to treat ICH, especially following TBI in adults. Mannitol is an osmolar agent with a rapid onset of action via two distinct mechanisms.

The initial effects of mannitol result from a 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 blood volume and ICP. Such a mechanism of action is transient (lasting about 75 min) and requires repeated dosing for prolonged effect. Mannitol exhibits its second mechanism of action through its osmotic effects. Although slower in onset, this mechanism lasts up to 6 hours.

Pitfalls of mannitol include the potential to accumulate in regions of injured brain if the blood-brain barrier is damaged, with subsequent reverse osmotic shift and worsening of ICP; this risk has been reported with continuous infusions. As a result, intermittent mannitol boluses are recommended. In addition, mannitol has been associated with renal failure at serum osmolality levels above 320 mOsm/L in adults. However, the literature supporting this finding is limited and was published at a time when dehydration therapy was common. A euvolemic hyperosmolar state generally is targeted with current care. Because mannitol is a potent diuretic, this effect is undesirable in hypotensive patients in whom the CPP is consequently decreased. Hypovolemia should be avoided by judicious fluid replacement.

Hyperventilation has the potential to reduce ICH via reflex vasoconstriction in the presence of hypocapnia. The vasoconstriction leads to decreased cerebral blood flow, decreased cerebral blood volume, and a subsequent decrease in ICP.

Hyperventilation is one of the fastest methods to lower ICP in a child with impending herniation. However, hyperventilation should only be considered as a temporizing measure for the reduction of ICP. In cases of refractory ICH despite all of the above treatments (sedation, analgesia, head elevation, CSF drainage, neuromuscular blockade, and hyperosmolar therapy), persistent mild hyperventilation (PaCO2 of 30-35 mm Hg) may be beneficial in decreasing ICP.

The potential dangers associated with hyperventilation are related to the cerebral vasoconstriction and the subsequent risk for cerebral ischemia. 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. As a result, avoidance of prophylactic severe hyperventilation to a PaCO2 below 30 mm Hg may be considered in the initial 48 hours after injury.

Severe hyperventilation (PaCO2 <30 mm Hg) may be necessary in emergencies such as impending herniation (eg, a patient with the Cushing triad), but it should not be commonly used for prolonged therapy unless there is refractory ICH. If aggressive hyperventilation is used for an extended period, advanced neuromonitoring for cerebral ischemia (eg, cerebral blood flow, brain tissue oxygen monitoring, jugular venous oxygen saturation, transcranial Doppler, near-infrared spectroscopy) is suggested.

High-dose barbiturate therapy (eg, with pentobarbital) is used for refractory ICH. This class of medications suppresses the cerebral metabolic rate, improves regional blood flow to metabolic demands, decreases cerebral blood volume, and inhibits excitotoxicity. With continuous electroencephalographic (EEG) monitoring, barbiturate infusions may be titrated to achieve burst suppression.

The minimum dose required to control refractory ICH is recommended, as barbiturates may cause myocardial depression, decreased systemic vascular resistance, and hypotension. Furthermore, the ability to perform neurologic examination is lost when barbiturates are used to control ICP. Prolonged barbiturate therapy may result in immune suppression, leading to sepsis and ileus with subsequent feeding intolerance. When administering high-dose barbiturate therapy, continuous blood pressure monitoring and adequate cardiovascular support are required to maintain adequate CPP.

Experimentally, hyperthermia (core body temperature ≥38.0°-38.5°C [100.4°-101.3°F]) has been shown to exacerbate neuronal cell damage, whereas therapeutic hypothermia (core body temperature <35°C) has been shown to decrease many of the mechanisms associated with secondary brain damage, such as decreased inflammation, excitotoxicity, and cerebral metabolism. The impact of hypothermia on TBI has been studied in several clinical trials.

In 2005, a phase II clinical trial demonstrated that 48 hours of induced moderate hypothermia (32°-34°C [89.6°-93.2°F]) initiated within 6-24 hours of acute severe TBI in pediatric patients reduced ICP. These researchers concluded that induced hypothermia was safe, although a higher incidence of arrhythmias (reversed with fluid administration or rewarming) and rebound ICP elevation after rewarming were reported. [57]  Rebound ICP elevation after rewarming was also observed in another pediatric TBI study. [58]

In 2008, a multicenter, international study of children with severe TBI randomized to induced moderate hypothermia (32.5°C [90.5°F]) for 24 hours initiated within 8 hours after injury or to normothermia (37°C [98.6°F]) found a worsening trend in morbidity and mortality in the hypothermia group. [59]

Tasker and colleagues evaluated clinical trials of hypothermia management on outcome in pediatric severe TBI using conventional and Bayesian meta-analyses and reported that in seven randomized controlled trials (n = 472), they found no difference in mortality (hypothermia vs. normothermia) with a pooled estimate of 1.42 (credible-interval [CI], 0.77-2.61; P = 0.26). However, Bayesian meta-analysis showed that the chance of relative risk reduction of death greater than 20% with hypothermia versus normothermia is 1 in 3. [60]

In a comprehensive meta-analysis that included eight studies in children (n = 454), Crompton et al concluded that therapeutic hypothermia cannot be recommended for the treatment of TBI in children. They observed adverse outcomes in children with TBI who underwent hypothermic treatment, with a 66% increase in mortality (risk ratio, 1.66; 95% CI, 1.06-2.59; P = 0.03) and a marginal deterioration of neurologic outcome (risk ratio, 0.90; 95% CI, 0.80-1.01; p = 0.06). [61]

The Cool Kids Trial involving a multicenter international study of children to determine if hypothermia (32°-33°C [89.6°-91.4°]) initiated earlier and for a longer duration following injury, with a slower rewarming period, improves neurologic outcome following TBI was terminated due to futility. [45]  In the revised guidelines, the authors suggested that moderate hypothermia (32°-33°C [89.6°-91.4°F]) beginning within 8 hours after severe TBI for up to 48 hours’ duration should be considered to reduce ICH. If hypothermia is induced, rewarming at a rate faster than 0.5°C/h should be avoided. However, the authors stated that “the implications of this development (Cool Kids Trial) on the recommendations may need to be considered by the treating physician when details of the study are published. [45]

Potential complications associated with hypothermia include, but are not limited to, increased arrhythmias, electrolyte abnormalities, bleeding risk, and increased susceptibility to infection or sepsis.

Decompressive craniectomy with duraplasty, leaving the bone flap out, may be considered for pediatric patients with TBI who show early signs of neurologic deterioration or herniation, or are developingICH refractory to medical management during the early stages of their injury. Potential complications from decompressive craniectomy include, but are not limited to, hemorrhage and exacerbation of cerebral edema.

It is generally agreed that posttraumatic seizures should be aggressively treated, because they may contribute to hyperthermia and ICH. Prophylactic anticonvulsant administration of phenytoin may be a treatment option to prevent early posttraumatic seizures (occurring within 1 wk following injury) in infants and young children with severe TBI. [45]

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Lindsey K Rasmussen, MD, FAAP Assistant Professor of Pediatrics, Division of Pediatric Critical Care Medicine, Assistant Professor, Department of Neurology and Neurological Sciences, Division of Child Neurology, Lucile Packard Children’s Hospital, Stanford University School of Medicine

Lindsey K Rasmussen, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Burn Association, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), Pediatric Neurocritical Care Research Group (PNCRG), Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Ramesh Raghupathi, PhD Associate Professor, Department of Neurobiology and Anatomy, Drexel University College of Medicine

Ramesh Raghupathi, PhD is a member of the following medical societies: American Association for the Advancement of Science, Society for Neuroscience

Disclosure: Nothing to disclose.

Shih-Shan Lang Chen, MD Assistant Professor of Neurosurgery, University of Pennsylvania School of Medicine; Attending Physician in Neurological Surgery, Children’s Hospital of Pennsylvania

Shih-Shan Lang Chen, MD is a member of the following medical societies: American Academy of Neurological Surgery, Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Jimmy W Huh, MD Associate Professor of Anesthesiology, Critical Care and Pediatrics, Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania and Children’s Hospital of Philadelphia

Jimmy W Huh, MD is a member of the following medical societies: American Academy of Pediatrics, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Felice Su, MD, FAAP Clinical Associate Professor of Pediatrics, Department of Pediatrics, Stanford University School of Medicine; Attending Physician, Department of Pediatrics, Division of Critical Care Medicine, Lucile Packard Children’s Hospital

Felice Su, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA Professor of Emergency Medicine in Clinical Pediatrics, Weill Cornell Medical College; Attending Physician, Departments of Emergency Medicine and Pediatrics, Lincoln Medical and Mental Health Center; Adjunct Professor of Emergency Medicine, Adjunct Professor of Pediatrics, St George’s University School of Medicine, Grenada

Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA is a member of the following medical societies: American Academy of Pediatrics, American Academy of Urgent Care Medicine, American College of Emergency Physicians, American Heart Association, American Medical Association, Association of Clinical Research Professionals, Public Responsibility in Medicine and Research, Society for Academic Emergency Medicine, Society for Simulation in Healthcare

Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children’s Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society

Disclosure: Nothing to disclose.

G Patricia Cantwell, MD Clinical Professor, Department of Pediatrics, Miller School of Medicine, University of Miami; Director of Pediatric Critical Care Medicine, Holtz Children’s Hospital/Jackson Memorial Hospital

G Patricia Cantwell, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children’s Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

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