Abstract

The management of trauma and hemorrhagic shock (T/HS) is a critical aspect of emergency medicine and trauma care. The use of whole blood for fluid resuscitation is considered the gold standard when available because it provides a balanced combination of red blood cells, plasma, and clotting factors. However, whole blood is not always readily available, and alternative options must be considered. In such cases, various fluid replacements and vasoactive drugs can be used to help stabilize patients with T/HS. The goal of our study was to compare several fluid therapies and vasoactive drugs for blood pressure stabilization after T/HS. Male Wistar rats (±400g) were subjected to laparotomy and hypotension (a mean arterial blood pressure (MAP) of 35-40mmHg) was induced by blood withdrawal for 90 min. Following the hypotensive period, animals were resuscitated with candidate solutions and/or vasoactive drugs in an effort to increase MAP to at least 60mmHg for 120min. Lactated Ringers (LR) with 5% dextrose was used as control fluid and in combination with vasopressors; whole blood resuscitation was considered the positive control. Among the studied medications, only vasopressin (60.0mmHg*) and resveratrol (60.2mmHg*) were able to achieve the target MAP. (Packed) red blood cells (70.4mmHg***), polymerized hemoglobin (74.4mmHg***), and whole blood (84.4mmHg****) increased MAP closer to baseline levels. While all of the groups studied were capable of restoring systolic pressure not significantly different from to baseline (SHAM =108.5mmHg), the inability to recover MAP was almost exclusively due to low diastolic arterial pressure (DAP). Using the SHAM DAP as reference (65.2mmHg) and the LR-reperfusion group as control (31.7mmHg), there was no increase in effcacy upon addition of angiotensin II (25.4mmHg), phenylephrine (27.9mmHg), vasopressin (37.8mmHg), L-NAME (35.7mmHg), resveratrol (41.1mmHg), sphingosine-1-phosphate (33.0mmHg), or naloxone (31.8mmHg). There was a similar lack of effcacy found using different fluid therapies: Hetastarch increased DAP to only 33.9mmHg, and 10% Albumin (41.0mmHg), and plasma (38.6mmHg) were only slightly superior to control. Only oxygen-carrying solutions were able to increase DAP: polymerized hemoglobin (55.7mmHg***), red blood cells (55.5mmHg***), and whole blood (67.8mmHg***). These findings underscore the complexity of T/HS management and the challenges in restoring and maintaining perfusing blood pressure, e.g. MAP, in these situations. This study provides valuable insights into the comparative effectiveness of various resuscitative approaches, shedding light on potential strategies to enhance outcomes after T/HS. Many shock studies often concentrate only on mean arterial pressure, potentially overlooking a crucial aspect of hemorrhage resuscitation—low diastolic pressure. Our study emphasizes that low diastolic pressure constitutes the primary component contributing to low MAP after reperfusion in T/HS. This result is likely associated with inadequate oxygen availability to the tissues, as only oxygen carriers, such as polymerized hemoglobin, red blood cells, and whole blood were capable of improving DAP. Future therapies should be directed towards preferentially improving DBP as an approach to achieving optimal hemodynamics after T/HS.(*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 compared to LR control). Department of Defense Award W81XWH-17-2-0047. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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