Despite the increased amount of education and research on the prevention of head injury, acute TBI in children remain a serious concern. A brain injury is often discussed in two phases, the primary injury and the secondary injury. The primary injury is defined as “mechanical damage sustained immediately at the time of trauma from direct impact, or from shear forces when the gray matter and white matter move at different speeds during deceleration or acceleration” (Schunk & Schutzman 2012 pg 400). A secondary injury is defined as the “ongoing derangement to neuronal cells not initially injured during the traumatic event. This ongoing injury results from “processes initiated by the trauma: hypoxia, hypofusion, metabolic derangements, expanding mass and increased pressure and edema.” (Schunk & Schutzman 2012 pg 400). Surviving a TBI requires a very rapid response in the acute phase (Gazzellini et al. 2012). This first section will discuss the treatments that may be used in the acute stages of TBI in a pediatric population.
In the acute phase post-TBI, prevention of increased ICP is necessary to mitigate secondary injury. Elevated ICP or intracranial hypertension (ICH) is not only difficult to diagnose, as invasive techniques must be used (Kukreti et al. 2014), but is associated with death and poor neurological outcomes (Kochanek et al. 2012). ICP>20mmHg and each additional hour with elevated ICP were associated with poor outcomes (Miller Ferguson et al. 2016). Additionally, children with a severe TBI (GSC score ≤8) are at a higher risk for ICH (Dixon et al. 2016). It is therefore important to be able to monitor ICP and alleviate ICH before such outcomes can manifest. Cerebral perfusion pressure (CPP), the pressure gradient that drives cerebral blood flow, also needs to be maintained following a TBI (Kochanek et al. 2012). According to clinical guidelines, CPP should be no lower than 40mmHg and ICP no higher than 20mmHg for children post-TBI in order to prevent detrimental effects (Kochanek et al. 2012).
It is important to prevent ICH and CPP in order to reduced secondary damage. Hospitals that have increased ICP monitoring have lower rates of mortality and severe disability compared to those that do not (Bennett et al. 2012). According to the current guidelines, monitoring ICP may be effective at early detection and reducing poor outcomes (Kochanek et al. 2012). However, ICP monitoring recommendations are for children with severe TBI, as it is not routinely common for moderate TBI (Kochanek et al. 2012). In practice, children with a severe TBI and older children are more commonly monitored (Sigurta et al. 2013). Once it is identified that a child has elevated ICP, procedures such as regulating the angle of the child’s head while bedridden, hypertonic saline treatment, and decompressive craniectomies have been explored to reduce ICP to normal levels.
For children who are critically ill as a result of a TBI, tumor infections or hydrocephalus, the position of the child’s head is important. It is believed that by elevating the head of the bed 15 to 30° jugular venous drainage is encouraged (Bhalla et al. 2012; Marcoux 2005). The literature suggests placing the head of the bed at 30° is optimal to prevent any impairment in drainage from the jugular veins. Ensuring the child is “euvolemic prior to placing him or her in this position is important to avoid orthostatic hypotension” (Marcoux 2005 pg 222). However, during elevation of the head of the bed, it is important to vigilantly maintain CPP (Bhalla et al. 2012). Despite the amount of research looking at effects of elevating the head of the bed in adults little is known of its efficacy with children.
Agbeko and colleagues (2012) examined the impact head of bed elevation on ICP by randomly altering its position. Results suggest that ICP decreased when the head of the bed was elevated by a minimum of 10cm. If it was lower, ICP was found to increase. It is important to note that this effect occurred in most children, but not all (Agbeko et al. 2012). CPP was not found to change significantly as a result of adjusting the head of the bed, which contradicts the aforementioned concerns of decreased CPP after head elevation (Bhalla et al. 2012). The height and age of each individual should be accounted for before changing the head of bed, as a decrease in ICP was associated with the change in vertical distance, from the base of the skull to the heart. Therefore, the effect size from the change in head of the bed would depend on height of the child (Agbeko et al. 2012).
There is Level 4 evidence to suggest head elevation reduces intracranial pressure in children post TBI.
Elevating the head of the bed post TBI is effective at lowering intracranial pressure in children.
Mannitol is the drug most widely used in the treatment of ICH; however, the research evidence in a pediatric population is lacking and hypertonic saline is used more frequently. “Hypertonic saline differs from normal saline, in the number of osmoles of sodium and chloride contained in the solution (Knapp 2005 pg 205). Hypertonic saline increases serum sodium levels and osmolarity, thereby establishing an osmotic gradient. Water can then diffuse passively from the cerebral intracellular and interstitial space into blood capillaries causing a reduction in water content and a subsequent reduction in ICP (Khanna, 2000). Hypertonic saline is used more frequently in older children, children with intracranial hemorrhages and skull fractures, and severe TBI (Bennett et al. 2012). According to guidelines of for acute medical management in children, there is insufficient evidence to either support or refute the use of mannitol, whereas the use of hypertonic saline (3%) has supporting evidence for children with severe TBI and ICH post-TBI (Kochanek et al. 2012).
Fluid resuscitation using hypotonic lactated Ringer’s solution was compared to fluid resuscitation using hypertonic saline in children with a severe TBI during the first three days post-injury (Simma et al. 1998). There was an inverse relationship between sodium concentration and ICP. Increased serum sodium concentration correlated with lower ICP and higher CPP. The children treated with hypertonic saline were reported to have a significantly lower frequency of acute respiratory distress syndrome, a lower frequency of two or more complications and significantly shorter ICU stay. Hypertonic saline is superior to lactated Ringer’s solution for early fluid resuscitation in children with TBI (Simma et al. 1998).
ICP was effectively reduced after a 7 day continuous injection of 3% saline (Khanna et al. 2000; Peterson et al. 2000), due to the maintenance of a hyperosmolar and hypernatremic state (Peterson, 2000). Despite increased serum sodium above normal physiological levels, there was no incidence of renal failure, subarachnoid hemorrhage, rebound of ICP, or central pontine myelinolysis, all which are potential detrimental side effects of increased sodium levels (Peterson et al. 2000). CPP had appreciable improvement throughout the 7 days (Khanna et al. 2000). There was no long term complications up to 6 months following the 7 day continuous administration (Khanna et al. 2000). When a single bolus of saline was used, it was determined that 3% saline with 5 mEg/kg was effective to reduce ICP in children within 2 hours, compared to a 0.9% normal saline bolus (Fisher et al. 1992). In conclusion, as serum sodium levels increased, ICP decreased (Khanna et al. 2000) and continuous administration of saline at 3% maintained stable serum sodium levels and prevented rebound hypernatremia (Peterson et al. 2000).
There is Level 1b evidence that use of hypertonic saline in the intensive care unit setting results in a lower frequency of multiple early complications and a shorter intensive care unit stay compared with lactated Ringer’s solution. Further, an increase in serum sodium concentrations significantly correlates with lower intracranial pressure and higher cerebral perfusion pressure.
There is Level 1b evidence that a single bolus of 3% saline reduces intracranial pressure and increases serum sodium levels, when compared to 0.9% saline.
There is Level 4 evidence that continuous infusion of 3% saline is effective at reducing intracranial pressure in children following a severe TBI.
Use of hypertonic saline in the intensive care unit setting results in a lower frequency of early complications and shorter intensive care unit stays.
An increase in serum sodium concentrations significantly correlates with lower intracranial pressure and higher cerebral perfusion pressure.
Continuous infusion of hypertonic saline reduces intracranial pressure and stabilizes serum sodium levels in children with severe TBI.
When interventions to manage elevated ICP fail, decompressive craniectomy may be an option but is often considered only as a last resort (Kochanek et al. 2012; Ruf et al. 2003). Management of individuals who sustain a severe TBI with refractory ICP and no evidence of a mass lesion, remains controversial (Kan et al. 2006). The research literature suggests decompressive craniectomies are effective in reducing ICP and are associated with positive outcomes in children following a severe TBI (Jagannathan et al. 2007; Weintraub et al. 2012). Figaji et al. (2008) noted that in children who had sustained a severe TBI, craniectomies performed to reduce diffuse brain swelling did improve ICP and cerebral oxygenation. Additionally, a systematic review revealed that favourable outcomes were observed after a decompressive craniectomy regardless of whether the acquired brain injury (ABI) was of a traumatic or non-traumatic cause (60% versus 69% respectively), or performed within 24 hours compared to after 24 hours (61% versus 69% respectively) (Guresir et al. 2012).
Refractory ICP levels were normalized or improvement significantly after a decompressive craniectomy in children (mean age 7.8-14.5yrs) who had sustained a severe TBI (Josan & Sgouros 2006; Ruf et al. 2003; Rutigliano et al. 2006). Children (mean age 10.1yrs) that underwent a craniectomy improved in ICP compared to children that received standard ICP management, although this difference was not statistically significant (Taylor et al. 2001). An early decompressive craniectomy within younger children (mean age 1.6yrs) had a survival advantage of 50%, where 70% of mortality occurred within the first week post-operation (Prasad et al. 2015).
Although ICP appears to improve for most children following a decompressive craniectomy, it is important to consider other complications that may arise. Two studies examined post-operative complications to highlight the potential detrimental effects of an emergency decompressive craniectomy (Pechmann et al. 2015; Prasad et al. 2015). The most common complications following decompressive craniectomy in toddlers and children are ventilator assisted pneumonia (31%), formation of hygroma (15-83%), and development of post-traumatic hydrocephalus (18-42%). Other potential complications were epilepsy, secondary infections from the surgery, and septicemia (Pechmann et al. 2015; Prasad et al. 2015). Seventy five percent of children required further surgery due to complications following the decompressive craniectomy (Pechmann et al. 2015).
Decompressive craniectomies performed later than 4 hours following admission and intraoperative blood exceeding 300 mL significantly predicted poorer outcomes (Khan et al. 2014). Additionally, young children that have experienced non-accidental head trauma had a higher odds of mortality (Oluigbo et al. 2012) and poorer outcomes (Adamo et al. 2009) than accidental traumas. The authors suggest that either decompressive craniectomies are not likely to change fatal outcomes or that the threshold requirement for decompression should be lower for children that have sustained a non-accidental head trauma (Oluigbo et al. 2012).
Based on a review of the literature from Weintraub et al. (2012) and the current paediatric guidelines (Kochanek et al. 2012), decompressive craniectomies are effective to manage ICP when ICP levels are hazardous to the child and cannot be alleviated non-surgically. However, the majority of studies are retrospectively conducted and further rigorous controlled trials are warranted to make definite conclusions of the effectiveness of decompressive craniectomies as an emergency treatment for ICP.
There is Level 1b evidence that in children, decompressive craniectomy reduces elevated intracranial pressure.
There is Level 3 evidence that children who sustain a severe TBI from non-accidental trauma have poorer outcomes and higher odds of mortality following a decompressive craniectomy, when compared to accidental trauma victims.
There is Level 4 evidence to suggest that children with a severe TBI have secondary complications following a decompressive craniectomy that may prolong rehabilitation.
A decompressive craniectomy reduces elevated intracranial pressure in children with TBI.
Despite the potential benefit of a decompressive craniectomy for reduction of intracranial pressure, there are numerous secondary complications that must be acknowledged when considering a decompressive craniectomy for children with severe TBI.
Predictors of poor outcomes after a decompressive craniectomy include non-accidental head trauma, delay (>4hrs) in surgery following admission, and intraoperative bleeding that exceeds 300mL.
There has been an interest in hypothermic treatment for children with acute brain injuries. Authors have cited physiological reasons suggesting that children, even more than adults, would benefit from this treatment (Biagas & Gaeta 1998). Moderate therapeutic hypothermia (32-33°C) is thought to reduce the onset of secondary injuries by preventing hyperthermia (body temperature >38-38.5°C) and decreasing cell death, excito-toxicity, metabolic demands and inflammation, to name a few (Kochanek et al. 2012). Clinical trials in adults have demonstrated a relationship between hypothermia and increased Glasgow Outcome Scale scores within the adult population (Clifton et al. 1993; Marion et al. 1997); however, in the pediatric population there appears to be a link between hypothermia and an elevated risk of dying post TBI (Sundberg et al. 2011). Hypothermic treatment may be administered for a duration of 24, 48 or 72 hours. Results from several studies looking at the efficacy of using hypothermia to improve outcomes in children are reviewed below.
Several RCTs investigated the efficacy of therapeutic hypothermia compared to normothermia treatment after a severe TBI in children. All treatments were initiated within 24 hours of TBI onset. Methods of delivering hypothermia included a blanket (Adelson et al. 2005; Adelson et al. 2013; Bayir et al. 2009; Beca et al. 2015; Hutchison et al. 2010; Hutchison et al. 2008) and a cooling cap (Li et al. 2009). The length of treatment differed between 24, 48 and 72 hours.
Hypothermic treatment that began a mean time of 6.3 hours post-admission and held for 24 hours did not improve the outcome of neurological status or risk of death in children with TBI (Hutchison et al. 2010; Hutchison et al. 2008). Children in the hypothermia group had a greater risk of unfavorable outcomes which was further amplified if under the age of 7, compared to normotherapy at 6 month follow-up (Hutchison et al. 2008). Additionally, the hypothermia group had lower systolic blood pressure, more episodes of hypotension and low CPP, and more unfavourable outcomes than in the normotherapy group (Hutchison et al. 2010).
Hypothermic treatment was most often delivered for 48 hours with onset within 24 hours (Adelson et al. 2005; Adelson et al. 2013; Bayir et al. 2009; Biswas et al. 2002). There was no significant difference between groups in mortality rates (Adelson et al. 2005; Adelson et al. 2013) or outcomes such as arrhythmias, infection, and coagulopathy (Adelson et al. 2005; Adelson et al. 2013; Biswas et al. 2002). Intracranial pressure was reported significantly lower in the hypothermia treatment group within 24 hours post-treatment (Adelson et al. 2005); however, ICP measurements taken after 24 hours did not show significant between group differences (Adelson et al. 2005; Biswas et al. 2002). Total antioxidant reserve and glutathione levels were significantly greater in the hypothermia group, highlighting the attenuated consumption of antioxidants due to hypothermia treatment (Bayir et al. 2009). The biomarker for oxidative stress, F2-isoprostane, had lower levels in both groups, but no significant differences between groups. Both aforementioned findings indicate that cerebrospinal fluid, where these measurements are extracted, may be a beneficial tool to monitor effects of hypothermia on oxidative stress, a large contributor to secondary damage post-TBI (Bayir et al. 2009).
The longest treatment time for hypothermia was 72 hours with an onset between 5-7 hours post-TBI (Beca et al. 2015; Li et al. 2009). There was no significant difference reported for infection, arrhythmias, bleeding, (Beca et al. 2015) or blood pressure levels (Li et al. 2009). A significant reduction in ICP was maintained by 72 hours when a cooling cap was used but no long-term follow-up was reported (Li et al. 2009). Levels of S-100 (Ca2+ binding protein), NSE (metabolic enzyme), and CK-BB (marker of brain damage) were all significantly lower in the hypothermia group, indicating that hypothermic treatment provided neuronal protection in children post-TBI (Li et al. 2009).
Despite the mentioned potential beneficial effects of hypothermia treatment for children, a meta-analysis conducted by Zhang et al. (2015) found that hypothermia increased the risk of mortality and arrhythmias. Additionally, therapeutic hypothermia was ineffective for improvement of outcomes according to the Glasgow Outcome Scale (Zhang et al. 2015). The lowering of core body temperature can be harmful and put a child at risk for further complications. It is therefore important to conduct more controlled trials to understand the proper onset, duration, and outcomes of hypothermia treatment to evaluate its safety and effectiveness within children who have sustained a severe TBI.
There is Level 1a evidence to suggest that therapeutic hypothermia (24, 48 and 72 hours) does not significantly improve mortality rates or outcomes, in relation to normothermia therapy.
There is Level 1a evidence that intracranial pressure is not improved long term (>24hrs) following hypothermia treatment in children following a TBI.
There is Level 1b evidence that hypothermia treatment maintained for 48 hours preserves antioxidant defenses in children following a severe TBI, when compared to normothermia.
There is Level 1b evidence that 72 hours of hypothermic treatment with a cooling cap improves short-term intracranial pressure levels and reduces biomarkers of brain damage (S-100, NSE, CK-BB), compared to normothermia therapy.
Long term intracranial pressure does not significantly improve following moderate hypothermia treatment compared to normothermia.
Induced hypothermia for 24, 48, and 72 hours has not yet been shown to reduce the risk of poor outcomes (death, severe disability etc.) in children post TBI.
Hypothermic treatment for 48 and 72 hours aids in the protection from secondary damage in children following a TBI.
Promoting Emergence from Disorders of Consciousness
Disorders of consciousness have been defined as residing in a comatose, vegetative, and minimally conscious state (Giacino & Whyte 2005). In theory, promoting arousal in children with reduced consciousness in the acute phase can facilitate participation in rehabilitation earlier to improve outcomes post-TBI (Evanson et al. 2016; Suskauer & Trovato 2013). Dopaminergic agents increase the amount of dopamine in the brain to facilitate arousal and responsiveness (McMahon et al. 2009). Potential dopaminergic agents include pramipexole, bromocriptine, methylphenidate, and amantadine which is the most commonly used (Suskauer & Trovato 2013). Although amantadine is a non-competitive N-methyl-D-aspartate receptor antagonist it is also thought to work pre- and post-synaptically by increasing the amount of dopamine in the brain (Napolitano et al. 2005). Given that children may respond differently to dopamine compared to adults due to ongoing development in the neurotransmitter systems (McMahon et al. 2009) additional research for a pediatric population is needed.
The results of the effects of dopaminergic agents to improve arousal and responsiveness post-ABI are conflicting and sparse. Patrick et al. (2003) initially conducted a retrospective review of children who were administered a variety of dopaminergic agents. Overall, there was a net increase in dopamine receptors and an increase in responsiveness in these children, despite the difference in mechanism of action for each drug (Patrick et al. 2003). This study lacked a comparative control group and studied a variety of drugs, but provided preliminary results for future RCTs.
Further studies were then conducted on the effects of amantadine on disorders of consciousness (McMahon et al. 2009; Patrick et al. 2006). One RCT found that standardized measures of arousal and consciousness did not significantly improve in children; however, blinded physicians’ ratings of consciousness, but not arousal, improved significantly (McMahon et al. 2009). Authors hypothesize that the effectiveness of amantadine may be determined by prognosis, but lacked a separate analysis for TBI, stroke, and anoxic injury (McMahon et al. 2009). Another RCT found that both amantadine and pramipexole improved physical arousal and disability in children (Patrick et al. 2006). It appeared that children were more responsive initially according to the Ranchos Los Amigos Scale. However, there was a lack of comparative placebo group and no difference between the two dopaminergic agents (Patrick et al. 2006). Additionally, recommendations cannot be made for younger children, as all three studies included older children.
Vargus-Adams et al. (2010) analyzed the pharmacokinetic properties of amantadine and determined that a dosage of 6mg/kg per day was an effective and safe dose for an ABI (N=7) population. Although, at high concentrations, amantadine caused nausea and vomiting. Therefore, authors recommend beginning with a dose of 4mg/kg per day and then increase to 6mg/kg per day after a week, to ensure reduction in side effects (Vargus-Adams et al. 2010).
There is Level 1b evidence that amantadine improves the level of consciousness in children post ABI compared to placebo but not level of arousal.
There is Level 2 evidence that amantadine and pramipexole improve the levels of consciousness in children and adolescents with TBI.
Dopamine enhancing drugs may facilitate rate of recovery post acquired brain injury in children; however, due to the small sample sizes more definitive research is needed.
Pharmacological Therapies for Prevention of Secondary Insults
Narcotics (fentanyl and morphine), barbiturates (pentobarbital), and midazolam are used for pediatric brain injury for sedation and analgesic effects and have been studied for the potential to reduce ICP levels (Guilliams & Wainwright 2016). Magnesium sulfate is a potential pharmacological agent that may be used to prevent secondary injuries post-TBI, as the additional magnesium targets several mechanisms that are involved in the onset of secondary injuries (Natale et al. 2007). Corticosteroids (dexamethasone) provide exogenous steroids to reduce vasogenic cerebral edema and thereby ICP (Fanconi et al. 1988), however there is a lack of evidence to support its use in pediatric brain injury. The aim of this section is to determine the effects of these pharmacological agents on secondary injury following TBI within the pediatric population.
Within the sedatives and analgesics category, Shein et al. (2016) found that 3% hypertonic saline administration was the most rapid medication to reduce ICP and improve CPP, which is critical due to the detrimental effects of a transient period of ICH. Pentobarbital reduced ICP more gradually without an effect on CPP and fentanyl decreased ICP but actually worsened CPP levels (Shein et al. 2016). Welch et al (2016) found that fentanyl and midazolam were not effective to treatment episodic ICH either alone or in combination and even increased ICH. There was no effect on CPP levels following treatment (Welch et al. 2016).
Pentobarbital administration in older children (mean age range 6-10 years) with refractory ICH was effective to reduce and control ICP in 28% of children (Mellion et al. 2013). When refractory ICH was unable to be controlled with pentobarbital, there was a reduction in time to death and increase in risk of death (Mellion et al. 2013). However, there was at least one episode of low CPP in 81% of children with severe TBI treated with pentobarbital, which is contradictory to the findings from Shein et al. (2016). Almost all participants required vasoactive medications, and together with low CPP episodes, these results suggest that cardiovascular compromise is associated with pentobarbital treatment (Mellion et al. 2013). The current pediatric guidelines suggest that pentobarbital therapy may be considered for children that are hemodynamically stable with refractory ICH, after other standard therapies and managements have been attempted (Kochanek et al. 2012).
Magnesium sulfate administration post-TBI does not compromise hemodynamics, such as mean arterial pressure, ICP, and CPP, in children (Natale et al. 2007). The importance of these findings resides in the fact that magnesium sulfate may work to target the pathophysiologic mechanisms involved in secondary injuries, without compromising systemic hemodynamics in children (Natale et al. 2007). However, long-term neurological outcomes of magnesium were not reported and future RCTs are needed on the effects of magnesium sulfate on the aforementioned pathophysiologic mechanism in secondary injury.
The pediatric data highlights that dexamethasone suppresses endogenous production of glucocorticoids, compared to controls (Fanconi et al. 1988; Kloti et al. 1987). Therefore, additional exogenous glucocorticoids from dexamethasone does not provide a beneficial effect to children. In addition to the suppression of endogenous glucocorticoids, excessive steroid present may lead to more severe side effects. For example, children on dexamethasone had a higher rate of bacterial pneumonia (Fanconi et al. 1988; Kloti et al. 1987). Authors suggest that the adrenal cortex can produce enough glucocorticoids on its own to elicit the maximum therapeutic effect on reduction of edema and membrane stabilization (Kloti et al. 1987). Therefore, dexamethasone is not superior to no steroid treatment and may even have additional detrimental side effects. The current pediatric guidelines recommend against dexamethasone administration for severe TBI (Kochanek et al. 2012).
There is conflicting evidence regarding fentanyl use for reduction of intracranial pressure and improvement of cerebral perfusion pressure for children following a severe TBI.
There is Level 3 evidence that pentobarbital administration is effective for reduction of intracranial pressure, but may cause cardiovascular compromise.
There is Level 2 evidence that magnesium sulfate does not affect hemodynamics (intracranial pressure, cerebral perfusion pressure, mean arterial pressure) in children post-TBI.
There is Level 1a evidence that administration of dexamethasone inhibits endogenous production of glucocorticoids and has no proven impact on recovery post brain injury.
The effect of fentanyl administration on intracranial pressure and cerebral perfusion pressureis inconclusive.
Pentobarbital is effective at reducing intracranial pressure and improving refractory intracranial hypertension levels but has cardiovascular compromise as a side effect; additional studies are needed.
Magnesium sulfate does not affect intracranial pressure, cerebral perfusion pressure, or mean arterial pressure in children post-TBI.
Administration of dexamethasone inhibits endogenous production of glucocorticoids in children and has no proven impact on recovery post brain injury.
Post Traumatic Seizures
Post Traumatic Seizures (PTS) may contribute to secondary injury following head injury through the increase of metabolic demands and elevation of ICP (Chung & O'Brien 2016). The incidence of early PTS (onset <1 week post-injury) in children has been reported at 12-18% (Liesemer et al. 2011; Thapa et al. 2010), but can be upwards of 42.5% with continuous electroencephalography monitoring (Arndt et al. 2013). Risk factors of PTS include severe TBI, abusive head trauma, and younger age (<2 years) (Arndt et al. 2013; Liesemer et al. 2011; O'Neill et al. 2015). Children are different from adults in terms of mechanism of injury and likely the pathophysiology leading to the development of PTS. Children have been reported to react differently to a brain injury than adults, particularly with an increased amount of significant edema (Aldrich et al. 1992). This may affect the development of PTS as intracerebral heme deposition has been postulated to be an important mediator in the pathogenesis of both early and late PTS (Willmore 1990). Prophylactic anticonvulsants have proved effective in reducing early PTS in adults and thus it is important to investigate their efficacy in the pediatric population.
Phenytoin prophylaxis was ineffective at preventing both early PTS (<1wk of injury) (Young et al. 2004) and late PTS (>1wk of injury) (Young et al. 1983) compared to controls. However, there was an overall low occurrence of PTS (6%) that is not reported consistently with previous studies, according to the authors, which may have confounded the results (Young et al. 2004). There was also no difference in survival outcomes between phenytoin and placebo groups (Young et al. 2004).
PTS occurred at a rate of 17.6-25% under levetiracetam prophylaxis (Chung & O'Brien 2016; Vaewpanich & Reuter-Rice 2016). Children that developed early PTS after levetiracetam prophylaxis were younger and had experienced abusive head trauma, compared to those that did not develop PTS (Chung & O'Brien 2016; Vaewpanich & Reuter-Rice 2016). Although lacking a comparison group Chung and O’Brien (2016) report the prevalence of PTS (17.6%) post-levetiracetam administration is similar to prior studies without any seizure prophylaxis. Future RCTs are needed.
There is Level 1b evidence that phenytoin does not reduce the occurrence of early seizures in children.
There is Level 1b evidence from a second study that phenytoin is ineffective in reducing late seizures in children.
There is Level 4 evidence that children that develop early post-traumatic seizure under levetiracetam prophylaxis are younger and have experienced abusive head trauma, compared to those that did not develop post-traumatic seizure.
Phenytoin does not reduce early or late seizures in children post ABI.
The rate of early post-traumatic seizure is high among children that receive levetiracetam prophylaxis.