Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin

Cynthia R Muller,Alfredo Lucas,Savannah R Moses,Vasiliki Courelli,Andre F Palmer,Clayton T Cuddington,Alexander T Williams,Fernando Dos Santos,Joyce B Li,Erik B Kistler,Pedro Cabrales

doi:10.1038/s41598-021-81717-3

Cynthia R Muller, Alfredo Lucas + Show 9 more

Open Access

https://doi.org/10.1038/s41598-021-81717-3

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Abstract

Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer’s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35–40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.

Highlights

Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is challenging because the two therapeutic treatment strategies for TBI and HS often conflict
This study evaluated the efficacy of large molecular weight polymerized human hemoglobin (PolyhHb) to restore blood pressure after resuscitation from hemorrhagic shock post-TBI compared to lactated Ringer’s solution (LR, electrolyte solution used to restore the loss of blood volume), and fresh whole blood (Blood, autologous blood drawn during hemorrhage)
The systolic blood pressure (SBP) was significantly higher for the Blood and PolyhHb groups compared to the LR group 30 min into resuscitation and remained significantly higher in the Blood group at the end of the resuscitation period

Summary

Introduction

Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Treatment of HS after TBI is challenging as the therapeutic regimens for the two individual conditions may conflict, since ischemia/reperfusion injury associated with resuscitation from HS can be exaggerated due to a loss of local and systemic autoregulatory mechanisms following T BI3. Cerebral edema is one of the most prominent pathophysiological factors associated with death and unfavorable outcomes after T BI9–11 While neurotraumas affect both systemic and cerebrovascular hemodynamic regulatory mechanisms, TBI exacerbates the cardiovascular instability observed during H S12. The systemic pathophysiological changes attributed to HS exacerbate the inflammatory response induced by TBI, negatively affecting the control of inflammatory mediators and oxidative stress, which in turn affects all organs[16] These pathways contribute to organ failure through microvascular shunting, coagulopathy, blood stasis, capillary occlusion, and a cidosis[17,18]. The optimal treatment goal for HS after TBI is ambiguous, especially since various strategies have been proposed without clear consensus[3]

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