Abstract
All work was performed at the Barrow Neurological Institute at Phoenix Children's Hospital.Objective: Investigate injury severity, neuroimaging, physiology, and outcomes with bolus hyperosmolar therapy (HT) of 3% hypertonic saline or mannitol.Methods: Retrospective cohort analysis was performed. Physiologic variables included intracranial pressure (ICP), arterial blood pressure (ABP), and heart rate (HR). Volume-pressure compensation (PVC) indices included ICP pulse amplitude (AMP) and correlation of AMP and ICP (RAP). Cerebrovascular pressure reactivity (CVPR) indices included pressure reactivity index (PRx), pulse amplitude index (PAx), wavelet PRx (wPRx), and correlation of AMP and cerebral perfusion pressure (RAC). Heart rate variability (HRV) indices included heart rate standard deviation (HRsd), heart rate root mean square of successive differences (HRrmssd) and low-high frequency ratio (LHF). Outcome was assessed using Glasgow Outcomes Scale Extended Pediatrics, 12-months post-injury. Generalized estimating equations was applied to investigate associations of physiologic changes and pre-treatment indices with HT efficacy. Repeated measures analysis of variance was applied to investigate changes after HT without intracranial hypertension (ICH). Wilcoxon rank-sum was applied to investigate HT responsiveness with age, injury severity, neuroimaging, and outcomes.Results: Thirty children received bolus HT. ICH reduction after HT was associated with reduced ICP (p = 0.0064), ABP (p = 0.0126), PRx (p = 0.0063), increased HRsd (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wPRx (p = 0.0072). HT-responsive patients were older and had improved outcomes (p = 0.0394). HT without ICH was associated with increased ICP (P < 0.0001) and ABP (P < 0.0001), increases in all HRV indices and decreases in all PVC indices.Conclusion: After pediatric TBI, efficacious HT is associated with decreased ICP and ABP, pre-treatment indices suggesting efficient CVPR, and potentially improved outcomes.
Highlights
Traumatic brain injury (TBI) represents a leading cause of pediatric morbidity and mortality, affecting an estimated 280 per 100,000 children in the United States [1]
intracranial hypertension (ICH) reduction after hyperosmolar therapy (HT) was associated with reduced intracranial pressure (ICP) (p = 0.0064), arterial blood pressure (ABP) (p = 0.0126), pressure reactivity index (PRx) (p = 0.0063), increased heart rate standard deviation (HRsd) (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wavelet PRx (wPRx) (p = 0.0072)
HT without ICH was associated with increased ICP (P < 0.0001) and ABP (P < 0.0001), increases in all Heart rate variability (HRV) indices and decreases in all pressure-volume compensation (PVC) indices
Summary
Traumatic brain injury (TBI) represents a leading cause of pediatric morbidity and mortality, affecting an estimated 280 per 100,000 children in the United States [1]. Mannitol is available as a hyperosmolar agent, but it has not been subjected to rigorous controlled clinical trials vs placebo or other therapy in children. While use of hyperosmolar therapy (HT) has been shown to reduce ICH, its putative pharmacological mechanisms focus on reduction of cerebral edema, yet this would make it potentially ineffective when ICH arises from other etiologies. Concern has arisen that in patients with intact cerebrovascular pressure reactivity (CVPR), hypertonic saline may impair cerebral hemodynamics [3]. For these reasons, further study and understanding of the mechanisms of actions of HT and real time responses to treatment are necessary
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