Examining the Effect of Hypertonic Saline Administered for Reduction of Intracranial Hypertension on Coagulation

Abstract

Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation invitro and invivo in a murine model of traumatic brain injury (TBI). For the invitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the invivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n= 10 rats with TBI and 10 controls). For the invitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the invivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength invitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.