The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage

Abstract

Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss. AbstractThe ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflexmediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock).

The compensatory reserve: potential for accurate individualized goal‐directed whole blood resuscitation

“…The CRM has proven to be an earlier as well as more sensitive and specific indicator of compromised physiological status under conditions of reduced central blood volume than blood pressure, SpO 2 , heart rate, shock index, radial pulse character, end‐tidal CO 2 , respiratory rate, Glasgow Coma Score, blood pH, blood lactate, peripheral perfusion index, pulse pressure variability, and tissue oxygen, in both human experimentation and trauma patients . The superior sensitivity of the CRM is reflected by earlier changes in CRM when compared to various standard vital signs while its specificity emerges from the capability that the algorithm has “learned” to distinguish individuals who compensate well to hemorrhage from those who do not . Among other labels, these populations can be defined as “Good Compensators” who make up about two‐thirds of individuals while the remaining one‐third comprises “Poor Compensators” (Fig.…”

Neuromodulation as a new avenue for resuscitation in hemorrhagic shock

“…Severe blood loss leading to systemic hypoxia results in irreversible lethal damage of tissues and organs. The systemic response to blood loss acts to maintain levels of arterial pressure (AP) necessary to provide adequate perfusion pressure (PP) for sufficient oxygen delivery (Gutierrez et al 2004;Moore 2014;Schiller et al 2017). At early stages of hemorrhage, decreased AP and blood volume activate peripheral and central baro-and volumo-receptors and trigger compensatory sympathetic and endocrine mechanisms (Bonnano 2011).…”

Measurement of mean systemic filling pressure after severe hemorrhagic shock in swine anesthetized with propofol-based total intravenous anesthesia: implications for vasopressor-free resuscitation

“…During hemorrhage, physiological compensation may maintain tissue perfusion [4], but the compensatory response to blood loss and time course for development of shock is largely affected by the individual characteristics of the patient. Adjustments within the venous system are critical for maintaining venous pressure during hemorrhage, and mobilization of unstressed blood volume has been characterized as the predominant and most effective mechanism in preserving venous return and thus cardiac output (CO) [5].…”