The Base Deficit, International Normalized Ratio, and Glasgow Coma Scale (BIG) Score, and Functional Outcome at Hospital Discharge in Children With Traumatic Brain Injury.

OBJECTIVES: To examine the association of the base deficit, international normalized ratio, and Glasgow Coma Scale (BIG) score on emergency department arrival with functional dependence at hospital discharge (Pediatric Cerebral Performance Category ≥ 4) in pediatric multiple trauma patients with traumatic brain injury. DESIGN: A retrospective cohort study of a pediatric trauma database from 2001 to 2018. SETTING: Level 1 trauma program at a university-affiliated pediatric institution. PATIENTS: Two to 17 years old children sustaining major blunt trauma including a traumatic brain injury and meeting trauma team activation criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two investigators, blinded to the BIG score, determined discharge Pediatric Cerebral Performance Category scores. The BIG score was measured on emergency department arrival. The 609 study patients were 9.7 ± 4.4 years old with a median Injury Severity Score 22 (interquartile range, 12). One-hundred seventy-one of 609 (28%) had Pediatric Cerebral Performance Category greater than or equal to 4 (primary outcome). The BIG constituted a multivariable predictor of Pediatric Cerebral Performance Category greater than or equal to 4 (odds ratio, 2.39; 95% CI, 1.81-3.15) after adjustment for neurosurgery requirement (odds ratio, 2.83; 95% CI, 1.69-4.74), pupils fixed and dilated (odds ratio, 3.1; 95% CI, 1.49-6.38), and intubation at the scene or referral hospital (odds ratio, 2.82; 95% CI, 1.35-5.87) and other postulated predictors of poor outcome. The area under the BIG receiver operating characteristic curve was 0.87 (0.84-0.90). Using an optimal BIG cutoff less than or equal to 8, sensitivity and negative predictive value for functional dependence at discharge were 93% and 96%, respectively, compared with a sensitivity of 79% and negative predictive value of 91% with Glasgow Coma Scale less than or equal to 8. In children with Glasgow Coma Scale 3, the BIG score was associated with brain death (odds ratio, 2.13; 95% CI, 1.58-2.36). The BIG also predicted disposition to inpatient rehabilitation (odds ratio, 2.26; 95% CI, 2.17-2.35). CONCLUSIONS: The BIG score is a simple, rapidly obtainable severity of illness score that constitutes an independent predictor of functional dependence at hospital discharge in pediatric trauma patients with traumatic brain injury. The BIG score may benefit Trauma and Neurocritical care programs in identifying ideal candidates for traumatic brain injury trials within the therapeutic window of treatment.

Differential effect of clomipramine on habituation and prepulse inhibition in dominant versus subordinate rats.

Many patients with depression have comorbidities associated with an impairment of sensorimotor gating, such as e.g. schizophrenia, Parkinson Disease, or Alzheimer disease. Anti-depressants like clomipramine that modulate serotonergic or norepinephrinergic neurotransmission have been shown to impact sensorimotor gating, it is therefore important to study potential effects of clomipramine in order to rule out an exacerbation of sensorimotor gating impairment. Prior studies in animals and humans have been inconclusive. Since serotonin and norepinephrine levels are closely related to anxiety and stress levels and therefore to the social status of an animal, we tested the hypothesis that acute and chronic effects of clomipramine on sensorimotor gating are different in dominant versus subordinate rats, which might be responsible for conflicting results in past animal studies. We used habituation and prepulse inhibition (PPI) of the acoustic startle response as operational measures of sensorimotor gating. After establishing the dominant animal in pair-housed male rats, we injected clomipramine for two weeks and measured acute effects on baseline startle, habituation and PPI after the first injection and chronic effects at the end of the two weeks. Chronic treatment with clomipramine significantly increased habituation in subordinate rats, but had no effect on habituation in dominant animals. Furthermore, PPI was slightly enhanced in subordinate rats upon chronic treatment while no changes occurred in dominant animals. We conclude that the social status of an animal, and therefore the basic anxiety/stress level determines whether or not clomipramine has a beneficial effect on sensorimotor gating and discuss possible underlying mechanisms.