Of the 2.5 million patients seen in emergency departments with traumatic brain injury (TBI) in the United States in 2014, more than 800,000 were children, according to the Centers for Disease Control and Prevention.1 There are an estimated 37,200 cases of severe TBI among children, with 7000 resulting deaths each year.2 In addition, these injuries are associated with substantial morbidity, various cognitive sequelae, long-term disability, and financial burden to both patients and the healthcare system.3,4

These findings underscore the critical importance of timely and adequate treatment for pediatric patients with severe TBI. To that end, the 3rd edition of the Brain Trauma Foundation’s guidelines for managing pediatric severe TBI were published in March 2019 in Pediatric Critical Care Medicine.5 Neurology Advisor recently provided a thorough summary of the guidelines, which contain multiple updates since the previous edition was published in 2012.

To learn more about challenges of treating severe TBI in the pediatric population, and to hone in on specific aspects of the guidelines that physicians may find most beneficial, we interviewed lead author Patrick M. Kochanek, MD, MCCM, the Ake N. Grenvik Professor of Critical Care Medicine and vice chair of the department of critical care medicine at the University of Pittsburgh School of Medicine and the UPMC Children’s Hospital.

Neurology Advisor: What are some of the main challenges specific to treating pediatric severe TBI?

Dr Kochanek: Severe TBI is an extremely heterogeneous condition that produces a spectrum of endophenotypes as identified by [computed tomography] imaging. The key target in the [intensive care unit (ICU)] is, of course, intracranial hypertension, and although it is clear that inability to control brain swelling with marked increases in intracranial pressure (ICP) and/or herniation lead to poor outcomes, it appears that control of intracranial hypertension is necessary but not sufficient to ensure favorable outcome.

Other mechanisms — such as axonal injury, delayed neuronal death, vascular dysregulation, and inflammation — [have an] impact [on] the ultimate outcome but are not targeted with current treatment, which other than ICP-directed therapy, focuses largely on supportive care. As is evident from the 3rd edition of the guidelines, although progress has been made, high-level evidence is lacking for both the optimal approach to treat intracranial hypertension and supportive care. Indeed, we appear to know more about what is bad for the traumatically injured brain than strategies to mitigate the ongoing damage.

Neurology Advisor: Which of the new additions to the guidelines might clinicians find most helpful?

Dr Kochanek: Notably, regarding ICU-directed care, we were able to make stronger recommendations for the use of hypertonic saline, particularly for the use of bolus administration of 3% saline, now at a level II of evidence. Studies in infants and children with severe TBI for the first time included comparisons of the impact of various ICP-directed therapies in real-world use, such as bolus hypertonic saline, fentanyl, or barbiturates to treat ICP spikes, and 3% saline showed superiority as the only agent to simultaneously reduce ICP while increasing cerebral perfusion pressure.

We also now have level III evidence for the use of 23.4% saline for refractory intracranial hypertension, adding another tool to our armamentarium. Based on several high-quality studies, we are now also able to recommend against the use of prophylactic moderate hypothermia and have support only for hypothermia as a second-tier therapy for refractory intracranial hypertension.

We also have specific recommendations to avoid midazolam and/or fentanyl boluses for ICP crises, assuming that appropriate analgesia and sedation are part of appropriate background care. In addition, we have a new evidence-based recommendation to begin nutrition within the initial 72 hours after injury.

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It is also noteworthy that accompanying this new edition of the evidence-based guidelines, we have provided, in a separate linked article, a consensus plus evidenced-based algorithm6 for first- and second-tier approaches to care, which we believe will be very helpful to the caregiver at the bedside addressing topics such as an approach to treating herniation, dealing with different tempos of disease progression, weaning therapies, and other rarely discussed facets of care. Finally, there is also an executive summary of the guidelines document that is dually published in both Pediatric Critical Care Medicine and Neurosurgery.7

Neurology Advisor: What should be the focus of future studies regarding this topic?

Dr Kochanek: As indicated above, additional high-quality level II or I evidence is needed for almost all facets of pediatric ICU care of infants and children after severe TBI. Better evidence for age-related approaches to treatment is badly needed given the obvious differences in physiology and anatomy [among] infants, children, and adolescents. Studies addressing optimal approaches to second-tier therapy are needed, as are studies to define the role of surgical decompression.

Finally, in pediatrics, abusive head trauma (the shaken baby syndrome) represents a key contributor to the spectrum of injury and presents special and unique challenges to treatment. Endophenotype-based approaches to this condition, among other cases, may be essential to designing clinical trials and optimal therapy.

References

1. Centers for Disease Control and Prevention. TBI-related Emergency Department (ED) Visits. https://www.cdc.gov/traumaticbraininjury/data/tbi-ed-visits.html. Reviewed March 29, 2019. Accessed March 29, 2019.

2. Popernack ML, Gray N, Reuter-Rice K. Moderate-to-severe traumatic brain injury in children: complications and rehabilitation strategies. J Pediatr Health Care. 2014;29(3):e1-e7.

3. Rabinowitz AR, Levin HS. Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am. 2014;37(1):1-11.

4. Ovalle F, Xu L, Pearson WS, Spelke B, Sugerman DE. Outcomes of pediatric severe traumatic brain injury patients treated in adult trauma centers with and without added qualifications in pediatrics – United States, 2009. Inj Epidemiol. 2014;1(1):15.

5. Kochanek PM, Tasker RC, Carney N, 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. 2019;20(3S Suppl 1):S1-S82.

6. Kochanek PM, Tasker RC, Bell MJ, 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. 2019;20(3):269-279.

7. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition. Update of the Brain Trauma Foundation guidelines, executive summary. Pediatr Crit Care Med. 2019;20(3):280-289.