23.4% Hypertonic Saline and Intracranial Pressure in Severe Traumatic Brain Injury Among Children: A 10-Year Retrospective Analysis

Abstract

Objective: To explore the effect of 23.4% hypertonic saline for management of elevated intracranial pressure in children admitted to our institution for severe traumatic brain injury. Design: Single-center, retrospective medical chart analysis. Setting: A PICU at a level 1 pediatric trauma center in the United States. Patients: Children admitted for severe traumatic brain injury from 2006 to 2016 who received 23.4% hypertonic saline and whose intracranial pressures were measured within 5 hours of receiving 23.4% hypertonic saline. Interventions: None. Measurements and Main Results: Over the 10-year period, 1,587 children were admitted for traumatic brain injury, 155 of whom were deemed severe per this study’s criteria. Forty of these children received at least one dose of hypertonic saline, but 14 were excluded for insufficient intracranial pressure data. Among the remaining 26 children, one hundred one 23.4% hypertonic saline boluses were used in the analysis. Use of 23.4% hypertonic saline was associated with a decrease in intracranial pressure of approximately 7 mm Hg at both within 1 hour after the bolus (p < 0.01) and 4 hours after the bolus (p < 0.01) when compared with the intracranial pressure measured within 1 hour before the hypertonic saline bolus. These effects remained significant after adjusting for Functional Status Scale score and CT Marshall scores. There was no statistically significant association between adjunctive therapies, such as antiepileptics and analgesics, and changes in intracranial pressure. There was no laboratory evidence of hyperkalemia or renal injury after use of 23.4% hypertonic saline. Across all hospitalizations, 65% of the study population demonstrated an abnormally elevated creatinine at least once, but only three episodes of acute kidney injury occurred in total, all before hypertonic saline administration. Eight of the 26 children in this analysis died during their hospitalization. The Functional Status Scale scores ranged from 6 to 26 with a mean of 12.2 and sd of 5.7. Conclusions: Use of 23.4% hypertonic saline with children admitted for severe traumatic brain injury is associated with a statistically significant decrease in intracranial pressure within 1 hour of use.

Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats

“…Following 10% HS treatment by intravenous injection, the IcP of the rats after MCAO was significantly reduced. This was consistent with the effects of HS on traumatic brain injury (30) and subarachnoid hemorrhage (31).…”

Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience

“…These authors hypothesized that the smaller reduction they observed could be a result of the fact that they only described severe TBI, which could be more refractory to HTS. 8 One possible explanation for any difference in ICP reduction in our study compared with previous studies could be that we enrolled pediatric patients who received 23.4% HTS regardless of indication. The much larger meta-analysis in the adult population, which included all those who were given 23.4% HTS for raised ICP, showed a 50% reduction in ICP comparable to the 37% reduction that we observed.…”

“…Because 3% HTS is 0.513 mEq/L and 23.4% HTS is 4 mEq/ L, it delivers equivalent solute at almost an eighth of the volume. 8 This can be useful because fluid overload is frequently cited as an independent risk factor for morbidity and mortality in critically ill pediatric patients. 12,13 A standardized dosing protocol such as ours may be easier for clinicians to remember and, in addition, requires less calculation than weight-based dosing; it also requires less storage space, is easily available because it is aligned with adult practice, and there is reduced variance in delivery of the drug, all helpful in these emergent critical situations.…”

NFAT5 and HIF-1α Coordinate to Regulate NKCC1 Expression in Hippocampal Neurons After Hypoxia-Ischemia

“…HS can be used to treat brain edema in clinical settings, which leads to inhibition of NKCC1 expression (Deng et al, 2016;Wu et al, 2019). HS also significantly stimulates NFAT5 expression, which is highly expressed in the fetal brain, and genetically knocking out NFAT5 resulted in an edematous stillborn fetus (Yang et al, 2018).…”

“…NFAT5 is a transcription factor that sensitive to extracellular osmolarity and its transcription activation is dramatically increased after HS stimulation (Yang et al, 2018). HS, which inhibits NKCC1 expression (Huang et al, 2014;Rasmussen et al, 2015) is an efficient way to treat brain edema in clinical settings (Bhardwaj and Ulatowski, 2004;Wu et al, 2019). Hence, we assumed that NFAT5 mediate NKCC1 expression in hippocampal neurons after OGD.…”