| Home | E-Submission | Sitemap | Editorial Office |  
Journal of Korean Neurosurgical Society > Volume 65(3); 2022 > Article
Ha: Pediatric Severe Traumatic Brain Injury : Updated Management


Traumatic brain injury (TBI) is the leading cause of death and disability in children. Survivors of severe TBI are more susceptible to functional deficits, resulting in disability, poor quality of life, cognitive decline, and mental health problems. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Internationally, efforts are being made to expand knowledge of pathophysiology and develop practical clinical treatment recommendations to improve outcomes. Here we discuss recently updated evidence and management of severe pediatric TBI.


Traumatic brain injury (TBI) is the leading cause of death or severe disability in children older than 1 year. From 1997 to 2007, the United States Centers for Disease Control and Prevention reported that 73276 children died from TBI [10]. Another study analyzing the discharge data from more than 3000 hospitals in 30 states found that more than 29000 cases of hospitalized children with TBI and 4907 with severe TBI had a combined mortality rate of 24.2% [17]. Internationally, the impact of TBI on childhood mortality and disability is similar [12]. Moreover, the long-term effect of severe TBI on children’s health is enormous. Approximately 61% of children with moderate-to-severe TBI experience disability. Estimates conclude that at least 145000 children aged 0-19 years are currently living with long-term symptoms of TBI [29].
The morbidity associated with TBI is significantly higher in children than in adults. Because children exhibit more neuroplasticity than adults, they are expected to recover better, but the opposite seems true for severe TBI. This is due to the physical characteristics of children, who have weak neck muscles and relatively large heads, which increase the risk of brain damage during trauma. In addition, children’s brains have higher water content due to incomplete myelination, which renders the brain more vulnerable to traumatic forces [4,16]. In addition, since high energy expenditure is required for neural network formation and synaptic branching development, it is susceptible to ischemic damage due to increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF) [31].
Therefore, understanding the mechanisms of severe pediatric TBI is necessary to improve the quality of management. This article reviews the literature on the appropriate management of severe pediatric TBI.


Several methods have been used to define severe TBI, most of which rely on the Glasgow coma scale (GCS). Specifically, TBI is considered severe with a GCS score of ≤8 [23]. The primary damage in TBI is mechanical contusion after direct impact. The consequent inflammatory responses and apoptotic cascade activation result in secondary brain damage. This contributes to the propagation of the injury and the development of cerebral edema. Cerebral edema is a frequent complication of pediatric TBI and can arise from a combination of cytotoxic and osmolar swelling, and vasogenic edema. Cerebral edema peaks 24-72 hours after TBI and exacerbates neuronal damage by limiting CBF. It is essential to anticipate the worsening of cerebral edema in patients with severe TBI, which, if not prevented, can ultimately lead to refractory increased ICP, brain herniation, and death [15,21].


Rapid imaging is important for identifying the extent of the primary damage and triaging those patients who might require early surgical intervention. Due to its fast results and availability, computed tomography (CT) is the primary modality used for this purpose. However, routine, repeated head CT after initial imaging without clinical changes is not recommended [22]. Magnetic resonance imaging (MRI) is more sensitive than CT in evaluating intracranial pathologies such as diffuse axonal injury. However, there is no evidence to support the efficacy of routine MRI in immediate management. After the patient is stabilized, MRI can be performed to further delineate the extent of intracranial injuries and aid in prognostication.


In 2019, the third edition of the Guidelines for the Management of Pediatric Severe TBI was updated (Table 1) [22-24,26]. ICP monitoring is recommended to improve the clinical outcomes of all patients with severe pediatric TBI. Although the evidence for the efficacy of this method is only correlative and achieves class III for long-term outcomes related to ICP monitoring, a few studies support the association of successful ICP-guided management with improved survival and neurologic outcomes [3,6].
An association between sustained increased ICP (generally >20 mmHg) and poor neurologic outcome or death has been demonstrated in pediatric patients in previous studies. Therefore, the therapeutic target threshold for ICP is suggested to be less than 20 mmHg [2,13]. However, individual reports do support lower ICP thresholds (15 mmHg) [9], while other pediatric studies suggest higher values (40 mmHg) [11]. Thus, although an ICP threshold of 20 mmHg is generally used as reference, the optimal threshold for ICP-guided therapy should be individualized according to age, severity of the damage, and clinical findings.


CPP, defined as the difference between mean arterial pressure (MAP) and mean ICP, is the pressure gradient that drives blood flow to the brain. A continuously low CPP is associated with poor outcomes in patients with severe TBI. In children, the healthy CPP range may vary depending on the age. A recent study reported age specific CPP thresholds associated with poor outcomes [20]. However, the Guidelines for the Management of Pediatric Severe TBI only recommend keeping the minimum CPP >40 mmHg [24].
Recent research of adult patients has attempted to determine the optimal individual CPP value by calculating the autoregulatory status index based on real-time ICP and MAP. This method has been proposed as an optional strategy in the fourth edition of the Guidelines for the Management of Severe TBI [8]. For pediatric patients, small-scale studies have been undertaken [25,30]. Optimal individualized CPP-directed therapy is expected to play an important role in improving the outcomes of pediatric TBI.


Baseline care comprises several therapies that should be administered to achieve better outcomes and ICP control at the stage of initial management. It consists of the following nine components : proper sedation, euvolemic status achievement, fever treatment, coagulopathy correction, minimum hemoglobin (7.0 g/dL) maintenance, neutral head positioning with 30° head-of-bed elevation, and antiepileptic drug therapy [24]. As the occurrence of electrographic seizures after severe TBI is higher in children than in adults, occurring in up to 70% of cases, seizure prophylaxis for these patients is recommended. The prophylactic use of antiepileptic drugs prevents early post-traumatic seizures [26].


Elevated ICP may be caused by pain or anxiety. Therefore, the use of analgesics and sedatives has become an important routine treatment for ICP control. However, due to a lack of evidence and specific guidelines, the choice of the type of medication and its dosage is entirely at the discretion of clinicians [24]. The use of bolus midazolam or fentanyl should be avoided, as it exacerbates the increase in ICP. In addition, prolonged continuous infusion of propofol for increased ICP regulation and sedation is not recommended, as per the guidelines of the Food and Drug Administration [24].


Intravenous osmotic therapy is widely used to control ICP, with mannitol being routinely employed for increased ICP in children with severe TBI. Usually, 20% mannitol is administered at a dose ranging between 0.5 and 1.0 g/kg, and administration is repeated according to the ICP value. However, mannitol increases the risk of hypovolemia and hypotension, which must be avoided in severe TBI [24].
Therefore, hypertonic saline (HTS) is the most popular treatment option for increased ICP. HTS has been rapidly replacing mannitol in North America, as it is associated with the more favorable cerebral hemodynamics and fastest resolution of increased ICP in children with severe TBI and was the only medication that improved CPP [28]. In a pediatric double-blinded study, 3% saline resulted in a more significant reduction in ICP than 0.9% saline. The suggested dosage for continuous infusion of 3% saline ranges between 0.1 and 1.0 mL/kg per hour and is administered on a sliding scale [14]. The minimum dose required to maintain ICP <20 mmHg should be used.
Intravenous bolus administration of 23.4% HTS can be used to treat refractory increased ICP, which is defined as an ICP >20 mmHg lasting longer than 5 minutes that is unresponsive to a stepwise therapeutic protocol including sedation, analgesia, head elevation, mild hyperventilation, mild hypothermia (35-36°C), neuromuscular blocker, and inotropic support to achieve age-appropriate CPP. The suggested dose is 0.5 mL/kg, with a maximum of 30 mL [22].
To minimize complications, it is recommended that, during hyperosmolar therapy, serum sodium levels exceeding 160 mEq/L be avoided.


High-dose barbiturate therapy is recommended for hemodynamically stable patients with refractory increased ICP. Pentobarbital has been found to be effective in lowering ICP in children with severe TBI. During phenobarbital infusion, continuous electroencephalogram (EEG) monitoring to confirm burst-suppression EEG patterns is beneficial for phenobarbital dose titration. Because hypotension is frequent, careful monitoring is necessary. In addition, ventilator-associated pneumonia is common; therefore, preemptive surveillance is required. During coma therapy, if ICP remains stable below 20 mmHg for 24 hours, phenobarbital can be gradually discontinued over 24-96 hours [22].


Maintaining normothermia is essential for pediatric patients with severe TBI, as fever exacerbates secondary brain injury [27]. Therefore, therapeutic hypothermia reduces cerebral edema, prevents the progression of secondary brain injury, and reduces ICP. Its effectiveness has been proven in animal studies of TBI [32]. However, clinical studies have shown that, compared to normothermia (36.5-37°C), early moderate hypothermia (32-33°C) did not lead to improved outcomes [1,5,19]. Therefore, prophylactic moderate hypothermia is not recommended. Despite these results, the Guidelines for the Management of Pediatric Severe TBI recommend moderate hypothermia in cases of refractory increased ICP based on studies that showed significant effects of lowered ICP in patients who were subjected to therapeutic hypothermia [7].


DC is recommended in pediatric severe TBI for treating neurological deterioration, herniation, or refractory increased ICP, achieving level III of recommendations. The timing of DC in pediatric patients with severe TBI is a matter of debate. Primary DC is usually undertaken as soon as possible, while secondary DC is performed according to the patient’s ICP. The optimal timing, most appropriate surgical technique, and specific benefits of DC for children are not well-studied.
Despite its effective results in lowering ICP, DC is associated with significant early and late complications, including expansion of contusion volume, hemorrhagic infarction, seizures, infection, hygroma, and hydrocephalus [18,33]. Thus, the decision to perform DC should be carefully assessed by a multidisciplinary team (neurosurgeons and neuro-intensivists), and parents should be appropriately informed of the surgical risks and clinical prognosis [23].


Recently, proper nutritional therapy has been found to be essential for critically ill patients, including those with severe TBI. Proper nutrition is expected to prevent the progression of secondary brain injury and improve prognosis. However, only a few studies have been conducted on patients with TBI. If patients are hemodynamically stable, enteral feeding should be started within 72 hours after injury [24].


An evidenced- and consensus-based algorithm for the management of severe TBI in pediatric patients was suggested in the Guidelines for the Management of Pediatric Severe TBI (Fig. 1) [22,26]. The algorithm includes the following components : an ICP-driven management pathway, a herniation-triggering pathway, a CPP pathway, and a brain tissue partial pressure of oxygen pathway. Treatment methods such as surgery, hyperosmotic treatment, barbiturate coma treatment, and target temperature management were applied, and their application order also followed the guidelines [26].
Treatment practitioners can create optimal treatment therapies by integrating all available information and implementing guidelines within the patient’s unique response to various treatments. In addition, this algorithm allows for changes in the timing and tempo of the treatment being implemented or withdrawn according to a given clinical context, leaving room for personalization according to the patient’s needs.


The updated ICP- and CPP-driven treatments show the possibility of goal-directed, tailored therapy that could lead to improved clinical outcomes. However, the updated guidelines are still limited, as they are based on the results of small studies, none of which achieve level I evidence. Future studies should be conducted to obtain higher-level evidence.
The implementation of the current guidelines might also present as an obstacle. In fact, ICP monitoring does not or cannot be performed in many countries or regions, as exemplified by the results of global prospective cohort studies, that showed that only 33-62% of patients underwent ICP monitoring [26]. For the full implementation of ICP monitoring in clinical practice, solid evidence must be presented that suggests that ICP-based monitoring and treatment are essential to improve prognosis. In addition, it is necessary to compile treatment guidelines that do not include ICP monitoring.


The Guidelines for the Management of Pediatric Severe TBI have been updated to include better treatment options even if the evidence remains insufficient. Future research is needed to confirm the effectiveness of the current recommendations. High variability in treatment algorithms, particularly for monitoring and targeting, still exists. The treatment algorithm should be adjusted according to individual needs and circumstances.


Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Informed consent

This type of study does not require informed consent.

Author contributions

Conceptualization : EJH; Visualization : EJH; Writing - original draft : EJH; Writing - review & editing : EJH

Data sharing




Fig. 1.
The evidence- and consensus-based algorithm of the management for the severe TBI in pediatric patients. The algorithm includes several components, such as baseline care (black), an ICP pathway (yellow), a herniation pathway (green), a CPP pathway (orange), and a PbrO2 pathway (purple). Solid lines identify the ICP and CPP pathways, reflecting their primary role. If baseline care is insufficient to control ICP, first-tier interventions progressing down the ICP pathway. The blue box indicates the need for second-tier therapy. TBI : traumatic brain injury, GCS : Glasgow coma scale, CT : computed tomography, ICP : intracranial pressure, PbrO2 : brain tissue partial pressure of oxygen, CPP : cerebral perfusion pressure
Table 1.
Summary of the updated 2019 Brain Trauma Foundation recommendations
Topic Recommendation Updated content
ICP monitoring To improve overall outcomes (level III) Use of ICP monitoring is suggested.
ICP threshold To improve overall outcomes (level III) Treatment of ICP for values <20 mmHg is suggested.
CPP threshold To improve overall outcomes (level III) 1. Treatment to maintain CPP at a minimum of 40 mmHg is suggested.
2. Treatment should be administered for CPP values between 40 and
Hyperosmolar therapy For ICP control (level II) Hypertonic saline (3%) is recommended at doses of 2-5 mL/kg over 10-20 minutes.
For ICP control (level III) Hypertonic saline (23.4%) is suggested for refractory ICP at doses of 0.5 mL/kg.
Sedation and analgesia For ICP control (level III) Avoid bolus of midazolam and/or fentanyl to control ICP due to the risk of cerebral hypoperfusion.
Temperature control To improve overall outcomes (level II) Prophylactic moderate hypothermia (32-33°C) is not recommended over normothermia.
To improve overall outcomes (level III) Moderate hypothermia (32-33°C) is suggested for the control of refractory ICP.
Decompressive craniectomy For ICP control (level III) Suggested to treat neurologic deterioration, herniation, or intracranial hypertension refractory to medical management.

ICP : intracranial pressure, CPP : cerebral perfusion pressure.


1. Adelson PD, Wisniewski SR, Beca J, Brown SD, Bell M, Muizelaar JP, et al : Comparison of hypothermia and normothermia after severe traumatic brain injury in children (cool kids): a phase 3, randomised controlled trial. Lancet Neurol 12 : 546-553, 2013
crossref pmid
2. Alberico AM, Ward JD, Choi SC, Marmarou A, Young HF : Outcome after severe head injury. Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients. J Neurosurg 67 : 648-656, 1987
3. Alkhoury F, Kyriakides TC : Intracranial pressure monitoring in children with severe traumatic brain injury: national trauma data bank-based review of outcomes. JAMA Surg 149 : 544-548, 2014
crossref pmid
4. Araki T, Yokota H, Morita A : Pediatric traumatic brain injury: characteristic features, diagnosis, and management. Neurol Med Chir (Tokyo) 57 : 82-93, 2017
crossref pmid pmc
5. Beca J, McSharry B, Erickson S, Yung M, Schibler A, Slater A, et al : Hypothermia for traumatic brain injury in children-a phase II randomized controlled trial. Crit Care Med 43 : 1458-1466, 2015
crossref pmid
6. Bennett TD, Riva-Cambrin J, Keenan HT, Korgenski EK, Bratton SL : Variation in intracranial pressure monitoring and outcomes in pediatric traumatic brain injury. Arch Pediatr Adolesc Med 166 : 641-647, 2012
crossref pmid pmc
7. Biswas AK, Bruce DA, Sklar FH, Bokovoy JL, Sommerauer JF : Treatment of acute traumatic brain injury in children with moderate hypothermia improves intracranial hypertension. Crit Care Med 30 : 2742-2751, 2002
crossref pmid
8. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al : Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 80 : 6-15, 2017
crossref pmid
9. Chambers IR, Treadwell L, Mendelow AD : Determination of threshold levels of cerebral perfusion pressure and intracranial pressure in severe head injury by using receiver-operating characteristic curves: an observational study in 291 patients. J Neurosurg 94 : 412-416, 2001
crossref pmid
10. Coronado VG, Xu L, Basavaraju SV, McGuire LC, Wald MM, Faul MD, et al : Surveillance for traumatic brain injury-related deaths--United States, 1997-2007. MMWR Surveill Summ 60 : 1-32, 2011

11. Cruz J, Nakayama P, Imamura JH, Rosenfeld KG, De Souza HS, Giorgetti GV : Cerebral extraction of oxygen and intracranial hypertension in severe, acute, pediatric brain trauma: preliminary novel management strategies. Neurosurgery 50 : 774-779, 2002
crossref pmid
12. Dewan MC, Mummareddy N, Wellons JC 3rd, Bonfield CM : Epidemiology of global pediatric traumatic brain injury: qualitative review. World Neurosurg 91 : 497-509, 2016
crossref pmid
13. Downard C, Hulka F, Mullins RJ, Piatt J, Chesnut R, Quint P, et al : Relationship of cerebral perfusion pressure and survival in pediatric braininjured patients. J Trauma 49 : 654-658, 2000
crossref pmid
14. Fisher B, Thomas D, Peterson B : Hypertonic saline lowers raised intracranial pressure in children after head trauma. J Neurosurg Anesthesiol 4 : 4-10, 1992
crossref pmid
15. Gardner MT, O’Meara AMI, Miller Ferguson N : Pediatric traumatic brain injury: an update on management. Current Pediatrics Reports 5 : 213-219, 2017
16. Gelineau-Morel RN, Zinkus TP, Le Pichon JB : Pediatric head trauma: a review and update. Pediatr Rev 40 : 468-481, 2019
crossref pmid
17. Haarbauer-Krupa JK, Glang A, Kurowski B, Breiding MJ : Report to congress : the management of traumatic brain injury in children. Available at : https://www.cdc.gov/traumaticbraininjury/pubs/congress-childrentbi.html

18. Honeybul S, Ho KM, Gillett GR : Long-term outcome following decompressive craniectomy: an inconvenient truth? Curr Opin Crit Care 24 : 97-104, 2018
19. Hutchison JS, Frndova H, Lo TY, Guerguerian AM : Impact of hypotension and low cerebral perfusion pressure on outcomes in children treated with hypothermia therapy following severe traumatic brain injury: a post hoc analysis of the Hypothermia pediatric head injury trial. Dev Neurosci 32 : 406-412, 2010
crossref pmid
20. Kapapa T, König K, Pfister U, Sasse M, Woischneck D, Heissler H, et al : Head trauma in children, part 2: course and discharge with outcome. J Child Neurol 25 : 274-283, 2010
crossref pmid
21. Kochanek PM, Clark RS, Ruppel RA, Adelson PD, Bell MJ, Whalen MJ, et al : Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med 1 : 4-19, 2000
crossref pmid
22. Kochanek PM, Tasker RC, Bell MJ, Adelson PD, Carney N, Vavilala MS, et al : Management of pediatric severe traumatic brain injury: 2019 consensus and guidelines-based algorithm for first and second tier therapies. Pediatr Crit Care Med 20 : 269-279, 2019
23. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al : Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guidelines, executive summary. Neurosurgery 84 : 1169-1178, 2019
crossref pmid
24. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al : Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guidelines. Pediatr Crit Care Med 20 : S1-S82, 2019
crossref pmid
25. Lewis PM, Czosnyka M, Carter BG, Rosenfeld JV, Paul E, Singhal N, et al : Cerebrovascular pressure reactivity in children with traumatic brain injury. Pediatr Crit Care Med 16 : 739-749, 2015
crossref pmid
26. Nacoti M, Fazzi F, Biroli F, Zangari R, Barbui T, Kochanek PM, et al : Addressing key clinical care and clinical research needs in severe pediatric traumatic brain injury: perspectives from a focused international conference. Front Pediatr 8 : 594425, 2021
pmid pmc
27. Natale JE, Joseph JG, Helfaer MA, Shaffner DH : Early hyperthermia after traumatic brain injury in children: risk factors, influence on length of stay, and effect on short-term neurologic status. Crit Care Med 28 : 2608-2615, 2000
crossref pmid
28. Shein SL, Ferguson NM, Kochanek PM, Bayir H, Clark RS, Fink EL, et al : Effectiveness of pharmacological therapies for intracranial hypertension in children with severe traumatic brain injury--results from an automated data collection system time-synched to drug administration. Pediatr Crit Care Med 17 : 236-245, 2016
crossref pmid pmc
29. Shi J, Xiang H, Wheeler K, Smith GA, Stallones L, Groner J, et al : Costs, mortality likelihood and outcomes of hospitalized US children with traumatic brain injuries. Brain Inj 23 : 602-611, 2009
crossref pmid
30. Tremlett W, Kanthimathinathan HK : Cerebral autoregulation monitoring in children with mild traumatic brain injury. Pediatr Crit Care Med 20 : 694-695, 2019
crossref pmid
31. Wahlström MR, Olivecrona M, Koskinen LO, Rydenhag B, Naredi S : Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy--the lund concept. Intensive Care Med 31 : 832-839, 2005
crossref pmid
32. Wang CF, Zhao CC, Jiang G, Gu X, Feng JF, Jiang JY : The role of posttraumatic hypothermia in preventing dendrite degeneration and spine loss after severe traumatic brain injury. Sci Rep 6 : 37063, 2016
crossref pmid pmc
33. Yue JK, Rick JW, Deng H, Feldman MJ, Winkler EA : Efficacy of decompressive craniectomy in the management of intracranial pressure in severe traumatic brain injury. J Neurosurg Sci 425-440, 2019
Editorial Office
1F, 18, Heolleung-ro 569-gil, Gangnam-gu, Seoul, Republic of Korea
TEL: +82-2-525-7552   FAX: +82-2-525-7554   E-mail: kns61@neurosurgery.or.kr
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © Korean Neurosurgical Society.                 Developed in M2PI
Close layer
prev next