Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin

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.

17α-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial

“…With the exception of glucose, current findings also partially replicate a previous swine model of severe hemorrhage, which reported that increased glucose/potassium/lactate and decreased bicarbonate/MAP were associated with survival [ 15 ]. In contrast to previous work in rodents [ 20 ], EE-3-SO 4 administration did not significantly affect either point-of-care markers or MAP relative to Placebo, suggesting the need for polytherapeutic approaches to further promote survival and more rapidly restore homeostasis following TBI + HS [ 7 ].…”

“…Hypovolemia also decreases arterial pressure and increases vasoconstriction, resulting in earlier and more severe cerebral dysautoregulation, reduced blood flow, hypoxia, increased contusion volume and a doubling of mortality rate in concurrent TBI + HS [ 5 , 6 ]. Although fluid resuscitation is recommended for HS, unless carefully managed it can also exacerbate brain edema and elevate intracranial pressure [ 7 ]. Similarly, hyperventilation helps to restore systemic acid–base balance following HS [ 8 ], whereas respiratory depression is the most common cause of death in preclinical models of moderate-to-severe TBI [ 9 ].…”

“…Respiratory complications are also more common in TBI + HS relative to HS alone in humans [ 10 ]. Thus, the optimal resuscitation approaches for concurrent TBI + HS remain actively debated [ 3 , 7 ].…”

Central nervous system injury–induced immune suppression

“…One possible explanation for these findings is increased sympathetic tone with release of circulatory catecholamines. 46 Clinically, in patients with severe trauma with a class III or IV hemorrhage, use of exogenous catecholamines was associated with an alteration in levels of serum cytokines with significant increases in serum IL-10 and significant decreases in TNFα in the first 24 hours compared with patients with traumatic injury who did not receive catecholamines. 47…”

CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock

“…Clinical outcomes after traumatic brain injury (TBI) are significantly worsened by concomitant hemorrhagic shock (HS) due to increased reduction of cerebral blood flow (CBF) leading to hypoxia, approximately doubling the mortality rate compared with TBI alone 1 – 3 . Despite advances in the management of TBI complicated by HS (TBI + HS), the current resuscitative approach to TBI + HS still entails immediate intravascular volume expansion, vasopressors, or oxygen supplementation 4 – 6 .…”