Improved Hemodynamic Recovery and 72-Hour Survival Following Low-Volume Resuscitation with a PEGylated Carboxyhemoglobin in a Rat Model of Severe Hemorrhagic Shock

Abstract Introduction: Hemorrhage is a leading cause of death from potentially survivable civilian and military trauma. As projected conflicts move from settings of tactical and logistical supremacy to hyper-dynamic tactical zones against peer and near-peer adversaries, protracted medical evacuation times are expected. Treatment at the point-of-injury is critical. Although crystalloids like Lactated Ringer’s (LR) are ubiquitous, whole blood (WB) is the preferred resuscitation fluid following hemorrhage; however, logistical constraints limit the availability of WB in prehospital settings. Hemoglobin-based oxygen carriers (HBOCs) offer both hemodynamic support and oxygen-carrying capacity while avoiding logistical constraints of WB. We hypothesized that low-volume resuscitation of severe hemorrhagic shock with an HBOC (PEGylated carboxyhemoglobin, [PC]) would improve hemodynamic recovery and 72-hour survival; comparable to WB and superior to LR. Materials and Methods: A total of 21 anesthetized male Sprague-Dawley rats underwent severe hemorrhagic shock followed by randomly assigned low-volume resuscitation with LR, WB, or PC, and then recovered from anesthesia for up to 72-hour observation. Mean arterial pressure (MAP) was recorded continuously under anesthesia, and arterial blood gases were measured at baseline (BL), 60 minutes post-hemorrhage (HS1h), and 24 hours post-resuscitation (PR24h). Survival was presented on a Kaplan–Meier plot and significance determined with a log-rank test. Cardiovascular and blood gas data were assessed with one-way analysis of variance and post hoc analysis where appropriate. Results: All measured cardiovascular and blood chemistry parameters were equivalent between groups at BL and HS1h. BL MAP values were 90 ± 3, 86 ± 1, and 89 ± 2 mmHg for LR, PC, and WB, respectively. Immediately following resuscitation, MAP values were 57 ± 4, 74 ± 5, and 62 ± 3 mmHg, with PC equivalent to WB and higher than LR (P