*3.1. Defining the Compensatory Reserve*

The compensatory reserve is a concept that represents the sum total of all physiological mechanisms that contribute to the maintenance of systemic DO<sup>2</sup> to the body's tissue. Conceptually, a compensatory reserve can be calculated as the difference between a baseline value at rest (100% reserve) and the value at the onset of hemodynamic instability (i.e., 0% reserve) [14,22–25,30,34–36]. In this regard, each individual has a finite 'reserve' consisting of physiological feedback mechanisms designed to compensate for low blood flow states. The complexity of this compensatory reserve is reflected by the reported observation that the physiology of integrated compensation is unique for each individual [37]. When this capacity to compensate becomes depleted, a state of decompensated shock occurs. Clinically, a compensatory reserve measurement (CRM) can be obtained from assessment of changing arterial pressure waveform morphology associated with changes in compensation [14,18,21,23,30,38–54]. Figure 2 illustrates that each arterial waveform consists of two primary waves: (1) an 'ejected' wave with features that are dictated by all compensatory mechanisms that influence myocardial function; and (2) a 'reflective' wave with features that are influenced by all compensatory mechanisms involved in the control of peripheral blood flow [14,22]. The LBNP model of hemorrhage has been used to generate a large reference database of more than 650,000 arterial pressure analog waveforms generated from noninvasive photoplethysmographic techniques and collected from more than 260 healthy men and women with age range of 18 to 55 years across various stages of reduced central blood volume to the point of decompensated shock (0% compensatory reserve) [22]. With application of advanced machine-learning technology to this large physiologically-diverse database, the CRM algorithm has 'learned' to provide rapid and continuous measures of changing arterial pressure waveform morphology to the clinical caregiver with the ability to gain an early and accurate assessment of the individual patient's medical status without the need for demographic data or measures of the patient's baseline physiology (as depicted in Figure 3) [21,24].

**Figure 2.** Illustration of changes in features of the ejected and reflected arterial waveforms progressing from a normal blood volume state to a state of reduced central blood volume (i.e., hypovolemia) such as that experienced during hemorrhage. The red line indicates the integrated waveform that is clinically observed. Modified from Convertino et al. [14,22,23].

**Figure 3.** Diagram illustrating the overall framework envisioned for using the compensatory reserve measurement (CRM) in pre-hospital care, including the details on the CRM machine learning algorithm for assessing beat-to-beat analog arterial pressure waveform features in an individual patient unknown to the algorithm. The unknown arterial waveform is compared to a large waveform "library" collected from a diversity of human subjects exposed to progressive reductions in central blood volume. The algorithm identifies the most similar waveform in the waveform library with the unknown sample to generate a CRM value. Modified from Convertino et al. [14,18,21–23,55].
