Resuscitation from Hemorrhagic Shock after Traumatic Brain Injury with Polymerized Hemoglobin

AbstractTraumatic 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.

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Traumatic brain injury may worsen clinical outcomes after prolonged partial resuscitative endovascular balloon occlusion of the aorta in severe hemorrhagic shock model

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000002149 ◽

2019 ◽

Vol 86 (3) ◽

pp. 415-423 ◽

Cited By ~ 5

Author(s):

Aaron M. Williams ◽

Umar F. Bhatti ◽

Isabel S. Dennahy ◽

Nathan J. Graham ◽

Vahagn C. Nikolian ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Clinical Outcomes ◽

Balloon Occlusion ◽

Shock Model ◽

Endovascular Balloon Occlusion ◽

Hemorrhagic Shock Model

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Abstract WP276: Drag Reducing Polymers Based Resuscitation Fluid Improves Cerebral Microcirculation After Mild Traumatic Brain Injury and Hemorrhagic Shock

Stroke ◽

10.1161/str.47.suppl_1.wp276 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Devon Lara ◽

Gloria Statom ◽

Olga A Bragina ◽

Marina V Kameneva ◽

Edwin M Nemoto ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Arterial Pressure ◽

Hemorrhagic Shock ◽

Hospital Care ◽

Microvascular Perfusion ◽

Arterial Hypotension ◽

Cerebral Microcirculation ◽

Neuronal Necrosis ◽

Resuscitation Fluid

Introduction: Hemorrhagic shock (HS), causing arterial hypotension, often occurs after traumatic brain injury (TBI). Current resuscitation fluids do not ameliorate the impaired cerebral microvascular perfusion leading to hypoxia, neuronal death, increased mortality and poor neurological outcome. Nanomolar concentrations of intravascular blood soluble drag reducing polymers (DRP) were shown to increase tissue perfusion and oxygenation and decrease peripheral vascular resistance by rheological modulation of hemodynamics. We hypothesized that the resuscitation fluid with DRP would improve cerebral microcirculation, oxygenation and neuronal recovery after TBI combined with HS (TBI+HS). Methods: Mild TBI was induced in rats by fluid percussion pulse (1.5 ATA, 50 ms duration) followed by induced by phlebotomy arterial hypotension (40 mmHg). Resuscitation fluid (lactated Ringers, LR) with DRP (DRP/LR) or without (LR) was infused to restore mean arterial pressure (MAP) to 60 mmHg for one hour (pre-hospital care), followed by re-infusion of blood to a MAP of 100 mmHg (hospital care). Using in vivo 2-photon laser scanning microscopy over the parietal cortex we monitored changes in microvascular blood flow, tissue oxygenation (NADH) and neuronal necrosis (i.v. propidium Iodide) for 5 hr after TBI+HS. Doppler cortical flow, rectal and cranial temperatures, arterial pressure, blood gases and electrolytes were monitored. Results: TBI+HS compromised brain microvascular flow leading to tissue hypoxia followed by neuronal necrosis. Resuscitation with DRP/LR compared to LR better improved cerebral microvascular perfusion (82 ± 9.7% vs. 62 ± 9.7%, respectively from pre-TBI baseline, p<0.05, n=7), attenuated capillary microtrombi formation and re-recruited collapsed during HS capillaries. Improved microvascular perfusion increased cortical oxygenation reducing hypoxia (77 ± 8.2% vs. 60 ± 10.5%, by DRP-LR vs. LR, respectively from baseline, p<0.05) and decreased neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively as a percentage of total neurons, p<0.05). Conclusions: DRP/LR resuscitation fluid is superior in the restoration of the cerebral microcirculation and neuroprotection following TBI + HS compared to volume expansion with LR.

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A systematic review of large animal models of combined traumatic brain injury and hemorrhagic shock

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2019.06.024 ◽

2019 ◽

Vol 104 ◽

pp. 160-177 ◽

Cited By ~ 2

Author(s):

Andrew R. Mayer ◽

Andrew B. Dodd ◽

Meghan S. Vermillion ◽

David D. Stephenson ◽

Irshad H. Chaudry ◽

...

Keyword(s):

Systematic Review ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Animal Models ◽

Hemorrhagic Shock ◽

Large Animal ◽

Large Animal Models

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HEMODYNAMIC AND OXYGENATION RESPONSES TO EXPERIMENTAL HEMORRHAGIC SHOCK (HS) WITH AND WITHOUT TRAUMATIC BRAIN INJURY (TBI).

Shock ◽

10.1097/00024382-200406002-00120 ◽

2004 ◽

Vol 21 ◽

pp. 41

Author(s):

Capone A. Neto ◽

F. G. Pinto ◽

R. Prist ◽

E. C. S. Ramos ◽

M. Rocha e Silva

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Experimental Hemorrhagic Shock

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Resuscitation Fluid with Drag Reducing Polymer Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock

Advances in Experimental Medicine and Biology - Oxygen Transport to Tissue XL ◽

10.1007/978-3-319-91287-5_7 ◽

2018 ◽

pp. 39-43 ◽

Cited By ~ 1

Author(s):

D. E. Bragin ◽

D. A. Lara ◽

O. A. Bragina ◽

M. V. Kameneva ◽

E. M. Nemoto

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Tissue Oxygenation ◽

Cerebral Microcirculation ◽

Resuscitation Fluid ◽

Drag Reducing Polymer

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Concomitant Traumatic Brain Injury and Hemorrhagic Shock: Outcomes Using the Spanish Trauma ICU Registry (RETRAUCI)

The American Surgeon ◽

10.1177/0003134820949990 ◽

2020 ◽

pp. 000313482094999

Author(s):

Mario Chico-Fernández ◽

Jesús A. Barea-Mendoza ◽

Jon Pérez-Bárcena ◽

Iker García-Sáez ◽

Manuel Quintana-Díaz ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Hemorrhagic Shock ◽

Fresh Frozen Plasma ◽

Categorical Variables ◽

P Value ◽

Trauma Patients ◽

Chi Square ◽

Exact Test ◽

Fresh Frozen

Background To compare the main outcomes of trauma patients with and without traumatic brain injury (TBI), hemorrhagic shock, and the combination of both using data from the Spanish trauma intensive care unit (ICU) registry (RETRAUCI). Methods Patients admitted to the participating ICUs from March 2015 to May 2019 were included in the study. The main outcomes were analyzed according to the presence of TBI, hemorrhagic shock, and/or both. Comparison of groups with quantitative variables was performed using the Kruskal-Wallis test, and differences between groups with categorical variables were compared using the Chi-square test or Fisher’s exact test as appropriate. A P value <.05 was considered significant. Results Overall, 310 patients (3.98%) were presented with TBI and hemorrhagic shock. Patients with TBI and hemorrhagic shock received more red blood cell (RBC) concentrates, fresh frozen plasma (FFP), a higher ratio FFP/RBC, and had a higher incidence of trauma-induced coagulopathy (60%) ( P < .001). These patients had higher mortality ( P < .001). Intracranial hypertension was the leading cause of death (50.4%). Conclusions Concomitant TBI and hemorrhagic shock occur in nearly 4% of trauma ICU patients. These patients required a higher amount of RBC concentrates and FFP and had an increased mortality.

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