Hypothermia for Traumatic Brain Injury in Children—A Phase II Randomized Controlled Trial*

Beca, John; McSharry, Brian P.; Erickson, Simon; Yung, Michael; Schibler, Andreas; Slater, Anthony; Wilkins, Barry; Singhal, Ash; Williams, Gary; Sherring, Claire; Butt, Warwick

doi:10.1097/ccm.0000000000000947

Cited by 69 publications

(39 citation statements)

References 30 publications

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“…Limitations to our study not mentioned previously include those inherent to the retrospective observational design. The population in this study was more heterogeneous than other published studies of children with severe TBI, as we did not exclude young infants(39, 40), patients with known or suspected child abuse(39–42), patients with isolated acute epidural hematoma(39, 40), or patients without abnormalities on the first CT scan(39, 40, 42). The median ICU length of stay that we found, 4 days, was longer than that reported in a single-center retrospective cohort study (2 days)(41) but shorter than investigators observed in a multi-center efficacy trial (11 days) with a more homogeneous study population and a temperature-control protocol that could lengthen the ICU stay.…”

Section: Discussionmentioning

confidence: 99%

Seizures in Children With Severe Traumatic Brain Injury*

Bennett

DeWitt

Harlaar

et al. 2017

Pediatric Critical Care Medicine

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Objective Traumatic brain injury (TBI) causes substantial morbidity and mortality in children. Post-traumatic seizures (PTS) may worsen outcomes after TBI. PTS risk factors are incompletely understood. Our objective was to clarify PTS risk factors in a large cohort of children with severe TBI. Design Retrospective cohort study of a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007–2010 Setting 29 U.S. children’s hospitals Patients 2,122 children (age < 18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] < 8) TBI, hospital length of stay > 24 hours, and non-missing disposition Interventions None Measurements and Main Results The outcome was PTS, identified using validated ICD-9-CM diagnosis codes. Pre-specified candidate predictors of PTS included age, injury mechanism, ED GCS, intracranial hemorrhage type, hypoxia, hypotension, and cardiac arrest. PTS were diagnosed in 25.2% of children with severe TBI. In those without abuse/assault or subdural hemorrhage (SDH), the PTS rate varied between 36.6% in those < 2 years old and 16.4% in those 14–17 years old. Age, abusive mechanism, and subdural hemorrhage (SDH) are each significant predictors of PTS. The risk of PTS has a complex relationship with these predictors. The estimated odds of PTS decrease with advancing age, OR = 0.929 (0.905, 0.954) per additional year of age with no abuse/assault and no SDH; OR = 0.820 (0.730, 0.922) per additional year of age when abuse and SDH are present. An infant with accidental TBI and SDH has approximately the same estimated probability of PTS as an abused infant without SDH, 47% (95% CI: 39%, 55%) versus 50% (95% CI: 41%, 58%), P = 0.69. The triad of young age, injury by abuse/assault, and SDH confers the greatest estimated probability for PTS, 60% (95% CI: 53%, 66%). Conclusions PTS risk in children with severe TBI is greatest with a triad of younger age, injury by abuse/assault, and SDH. However, PTS is common even in the absence of these factors.

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Section: Discussionmentioning

confidence: 99%

Seizures in Children With Severe Traumatic Brain Injury*

Bennett

DeWitt

Harlaar

et al. 2017

Pediatric Critical Care Medicine

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“…Similarly, TBI represents a significant cause of morbidity and mortality in children admitted to the PICU (31,36,42,100). As shown in other fields, protocolized care and adherence to guidelines, even if of low evidence level, can be associated with improved outcomes.…”

Section: Neurologic Outcomes Following Picu Carementioning

confidence: 99%

Neurologic Outcomes Following Care in the Pediatric Intensive Care Unit

Caprarola

Kudchadkar

Bembea

2017

Curr Treat Options Peds

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Purpose of review With increasing survival of children requiring admission to pediatric intensive care units (PICU), neurodevelopmental outcomes of these patients are an area of increased attention. Our goal was to systematically review recently published literature on neurologic outcomes of PICU patients. Recent Findings Decline in neurofunctional status occurs in 3%–20% of children requiring PICU care. This proportion varies based on primary diagnosis and severity of illness, with children admitted for primary neurologic diagnosis, children who suffer cardiac arrest or who require invasive interventions during the PICU admission, having worse outcomes. Recent research focuses on early identification and treatment of modifiable risk factors for unfavorable outcomes, and on long-term follow-up that moves beyond global cognitive outcomes and is increasingly including tests assessing multidimensional aspects of neurodevelopment. Summary The pediatric critical care research community has shifted focus from survival to survival with favorable neurologic outcomes of children admitted to the PICU.

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“…Unfortunately, although these studies provided encouraging support for a role of hypothermia in the clinic, when this experimental therapy was tested in several multicenter trials, no benefits on neurological outcome were seen in severe TBI patients (Adelson et al, 2013; Beca et al, 2015). Three multicenter studies found either no difference or worse mortality rates in the hypothermia group compared to normothermia (Clifton et al, 2001b; Clifton et al, 2011; Maekawa, 2015; Maekawa et al, 2015).…”

Section: Clinical Tbi Studies With Hypothermiamentioning

confidence: 99%

Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation

Dietrich

Bramlett

2016

Brain Research

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The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induce hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients.

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Hypothermia for Traumatic Brain Injury in Children—A Phase II Randomized Controlled Trial*

Cited by 69 publications

References 30 publications

Seizures in Children With Severe Traumatic Brain Injury*

Seizures in Children With Severe Traumatic Brain Injury*

Neurologic Outcomes Following Care in the Pediatric Intensive Care Unit

Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation

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