Treatment Holds Promise for Decreasing Secondary Brain Injury in TBI Patients
Effective resuscitation in patients with traumatic brain injury (TBI) and hemorrhage is a challenging problem. While blood is the optimal resuscitation fluid, it is typically not available in the out-of-hospital setting, and its use is associated with certain risks, including infection and transfusion reactions. Large volumes of crystalloid solution, such as lactated Ringer’s (LR), are typically used to resuscitate patients with hemorrhage. However, crystalloid solutions do not contain hemoglobin, limiting their ability to carry oxygen to tissue. This fundamental problem has generated interest in developing a resuscitation fluid that contains hemoglobin, allowing effective restoration of the oxygen-carrying capacity that is compromised when an injury leads to profuse blood loss. Restoring oxygen-carrying capacity is even more important when a patient has experienced TBI because the injured brain is critically dependent on oxygen.
Neurosurgeons recently studied the use of Hemoglobin Oxygen-carrying Solution HBOC-201 in animal model trials utilizing 20 Yorkshire swine. The results of this study, Hemoglobin Oxygen-carrying Solution, HBOC-201, Improves Resuscitation Parameters and Prevents Secondary Brain Injury in a Swine Model of Traumatic Brain Injury and Hemorrhage, will be presented by Guy Rosenthal, MD, 4:45 to 5:00 p.m. on Tuesday, April 25, 2006, during the 74th Annual Meeting of the American Association of Neurological Surgeons in San Francisco. Co-authors are Mitchell Cohen, MD, Diane Morabito RN, MPH, Annina Roeytenberg MD, Nikita Derugin MA, Scott Panter, PhD, M. Margaret Knudson, MD, and Geoffrey T. Manley, MD, PhD.
HBOCs are balanced salt solutions containing chemically stabilized bovine or human hemoglobin that may increase oxygen delivery to tissue and are compatible with all blood types. HBOC-201 (Hemopure®, Biopure Corporation) is a hemoglobin-based oxygen carrying solution that carries as much oxygen on a gram-per-gram basis as the hemoglobin in human red blood cells and is stable at room temperature for up to three years. Previous studies have shown that HBOC-201 is more effective than LR in restoring mean arterial pressure (MAP) after hemorrhage. Because HBOC holds promise for resuscitation of the head-injured patient, the effects of HBOC-201 vs. LR in a translational and clinically relevant large animal model of brain injury and hemorrhage were studied. Both systemic and brain physiological parameters were monitored in a blinded, prospective, randomized study.
The 20 Yorkshire swine underwent brain impact injury and hemorrhage and were randomized to resuscitation with HBOC-201 (6 mL/kg), or LR solution (12 mL/kg) and observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, MRI was performed, the animals were sacrificed, and their brains removed for histological studies with Fluoro-Jade B, an early marker of neuronal degeneration.
Swine resuscitated with HBOC (n=10) had higher MAP, Cerebral Perfusion Pressure (CPP), improved base deficit, and higher brain tissue oxygen than animals resuscitated with LR (n=10). No significant difference in total injury volume on T2-weighted MRI was seen between animals resuscitated with HBOC-201 (270 + 87 mm3) and LR (292 + 65 mm3, p=0.55). On the side of impact injury, no significant difference in mean number of Fluoro-Jade positive cells was seen between HBOC and LR (61.47 + 14.66 and 48.91 + 17.66, respectively, p=0.13). Surprisingly, on the side opposite injury, a significant increase in Fluoro-Jade positive cells was seen in animals resuscitated with LR (42.8 + 28.3) compared to those resuscitated with HBOC (5.64 + 8.07, p<0.05), implying greater neuronal injury in LR-treated swine.
The improved MAP, CPP, and brain tissue oxygen seen with HBOC-201 in comparison with LR indicate that HBOC may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. Although HBOC did not ameliorate primary brain injury following impact injury and hemorrhage, it did appear to reduce the amount of secondary brain injury on the side opposite impact. The higher MAP and CPP values observed in HBOC-treated swine may lead to improved cerebral blood flow. In addition, HBOC may also improve oxygen delivery following impact injury and hemorrhage by increasing the oxygen-carrying capacity of the blood, mitigating a second insult to the injured brain and decreasing cellular injury.
“If resuscitation with HBOC-201 can decrease secondary brain injury in TBI patients with hemorrhage, it holds promise for improving outcome,” stated Dr. Rosenthal. “The use of HBOC for small-volume resuscitation may potentially be of greatest benefit in rural settings and combat situations where banked blood is not available and transport times are long,” added Dr. Rosenthal.
