Evidence for misleading decision support in characterizing differences in tolerance to reduced central blood volume using measurements of tissue oxygenation.

BACKGROUND: The physiological response to hemorrhage includes vasoconstriction in an effort to shunt blood to the heart and brain. Hemorrhaging patients can be classified as "good" compensators who demonstrate high tolerance (HT) or "poor" compensators who manifest low tolerance (LT) to central hypovolemia. Compensatory vasoconstriction is manifested by lower tissue oxygen saturation (StO2 ), which has propelled this measure as a possible early marker of shock. The compensatory reserve measurement (CRM) has also shown promise as an early indicator of decompensation. METHODS: Fifty-one healthy volunteers (37% LT) were subjected to progressive lower body negative pressure (LBNP) as a model of controlled hemorrhage designed to induce an onset of decompensation. During LBNP, CRM was determined by arterial waveform feature analysis. StO2 , muscle pH, and muscle H+ concentration were calculated from spectrum using near-infrared spectroscopy (NIRS) on the forearm. RESULTS: These values were statistically indistinguishable between HT and LT participants at baseline (p ≥ 0.25). HT participants exhibited lower (p = 0.01) StO2 at decompensation compared to LT participants. CONCLUSIONS: Lower StO2 measured in patients during low flow states associated with significant hemorrhage does not necessarily translate to a more compromised physiological state, but may reflect a greater resistance to the onset of shock. Only the CRM was able to distinguish between HT and LT participants early in the course of hemorrhage, supported by a significantly greater ROC AUC (0.90) compared with STO2 (0.68). These results support the notion that measures of StO2 could be misleading for triage and resuscitation decision support.

Predictors of hemodynamic decompensation in progressive hypovolemia: Compensatory reserve versus heart rate variability.

BACKGROUND: Hemorrhage remains the leading cause of death following traumatic injury in both civilian and military settings. Heart rate variability (HRV) and heart rate complexity (HRC) have been proposed as potential "new vital signs" for monitoring trauma patients; however, the added benefit of HRV or HRC for decision support remains unclear. Another new paradigm, the compensatory reserve measurement (CRM), represents the integration of all cardiopulmonary mechanisms responsible for compensation during relative blood loss and was developed to identify current physiologic status by estimating the progression toward hemodynamic decompensation. In the present study, we hypothesized that CRM would provide greater sensitivity and specificity to detect progressive reductions in central circulating blood volume and onset of decompensation as compared with measurements of HRV and HRC. METHODS: Continuous, noninvasive measurements of compensatory reserve and electrocardiogram signals were made on 101 healthy volunteers during lower-body negative pressure (LBNP) to the point of decompensation. Measures of HRV and HRC were taken from electrocardiogram signal data. RESULTS: Compensatory reserve measurement demonstrated a superior sensitivity and specificity (receiver operator characteristic area under the curve [ROC AUC] = 0.93) compared with all HRV measures (ROC AUC ≤ 0.84) and all HRC measures (ROC AUC ≤ 0.86). Sensitivity and specificity values at the ROC optimal thresholds were greater for CRM (sensitivity = 0.84; specificity = 0.84) than HRV (sensitivity, ≤0.78; specificity, ≤0.77), and HRC (sensitivity, ≤0.79; specificity, ≤0.77). With standardized values across all levels of LBNP, CRM had a steeper decline, less variability, and explained a greater proportion of the variation in the data than both HRV and HRC during progressive hypovolemia. CONCLUSION: These findings add to the growing body of literature describing the advantages of CRM for detecting reductions in central blood volume. Most importantly, these results provide further support for the potential use of CRM in the triage and monitoring of patients at highest risk for the onset of shock following blood loss.

Bridging the gap between military prolonged field care monitoring and exploration spaceflight: the compensatory reserve.

The concept of prolonged field care (PFC), or medical care applied beyond doctrinal planning timelines, is the top priority capability gap across the US Army. PFC is the idea that combat medics must be prepared to provide medical care to serious casualties in the field without the support of robust medical infrastructure or resources in the event of delayed medical evacuation. With limited resources, significant distances to travel before definitive care, and an inability to evacuate in a timely fashion, medical care during exploration spaceflight constitutes the ultimate example PFC. One of the main capability gaps for PFC in both military and spaceflight settings is the need for technologies for individualized monitoring of a patient's physiological status. A monitoring capability known as the compensatory reserve measurement (CRM) meets such a requirement. CRM is a small, portable, wearable technology that uses a machine learning and feature extraction-based algorithm to assess real-time changes in hundreds of specific features of arterial waveforms. Future development and advancement of CRM still faces engineering challenges to develop ruggedized wearable sensors that can measure waveforms for determining CRM from multiple sites on the body and account for less than optimal conditions (sweat, water, dirt, blood, movement, etc.). We show here the utility of a military wearable technology, CRM, which can be translated to space exploration.

Interrelationship Between Sex, Age, Blood Volume, and Vo2max.

BACKGROUND: Circulating blood volume (BV) and maximal oxygen uptake (Vo2max) are physiological characteristics important for optimal human performance in aerospace and military operational environments. We tested the hypothesis that BV and Vo2max are lower in older people independent of sex.METHODS: To accomplish this, a "data mining" effort of an historic database generated from NASA and U.S. Air Force experiments was conducted. BV, red cell volume, plasma volume, hematocrit, and Vo2max were measured in 84 healthy individuals (24 women, 60 men) across an age range of 23 to 65 yr to assess the interrelationship between sex, age, BV, and Vo2max. Subjects were classified in age groups by < 40 yr and ≥ 40 yr; these groups identified women as pre- vs. postmenopausal.RESULTS: Consistent with our hypothesis, comparisons revealed that men had higher BV, red cell volume, hematocrit, and Vo2max than women when standardized for body mass. Against expectations, BV was not different in older compared with younger men and women. Vo2max was not different in older compared with younger women, while Vo2max was lower in older men.CONCLUSION: We conclude that physiological mechanisms other than BV associated with aging appear to be responsible for a decline in Vo2max of our older men. Furthermore, factors other than menopause may also influence the control of BV in the women. Our results provide evidence that aging may not compromise men or women in scenarios where BV can affect performance in aerospace and military environments.Koons NJ, Suresh MR, Schlotman TE, Convertino VA. Interrelationship between sex, age, blood volume, and Vo2max. Aerosp Med Hum Perform. 2019; 90(4):362-368.

Capacity to Compensate for Central Hypovolemia and Effects of Menstrual Cycle Phases.

BACKGROUND: Tolerance to central hypovolemia is dictated by exhaustion of the physiological capacity to compensate called the compensatory reserve. Such physiological compromise can have detrimental impact on performance in aerospace environments as well as survival from hemorrhage on the battlefield. We induced central hypovolemia using progressively stepwise lower body negative pressure (LBNP) in women during various phases of the menstrual cycle to test the hypothesis that similar tolerance across all menstrual cycle phases would be reflected by similar changes in compensatory reserve.METHODS: Based on self-reporting of the last menstrual period, 40 healthy women, matched by demographics, were classified into 1 of 5 menstrual cycle phases: early follicular (EF, Days 1-7; N = 10), late follicular and ovulatory (LF, Days 9-15, N = 6), early luteal (EL, Days 16-18, N = 6), midluteal (ML, Days 19-25, N = 8), and late luteal (LL, Days 26-30, N = 10). All subjects had a 28-30 d menstrual cycle and were not taking oral contraceptives. Tolerance to central hypovolemia was measured as time (seconds) from baseline to the onset of presyncopal symptoms induced by LBNP.RESULTS: Time to presyncope as well as hemodynamic and compensatory reserve responses were statistically indistinguishable across all menstrual cycle phases.DISCUSSION: Consistent with our hypothesis, compensatory reserve with associated hemodynamic responses and tolerance to central hypovolemia was not affected by menstrual cycle phases. Our findings indicate experimental comparisons of responses to central hypovolemia involving the participation of healthy women with normal menstrual cycles and not taking oral contraceptives can be conducted independent of menstrual cycle phase.Convertino VA, Schlotman TE, Stacey W, Hinojosa-Laborde C. Capacity to compensate for central hypovolemia and effects of menstrual cycle phases. Aerosp Med Hum Perform. 2019; 90(4):378-383.

1D Convolutional Neural Networks for Estimation of Compensatory Reserve from Blood Pressure Waveforms.

We propose a Deep Convolutional Neural Network (CNN) architecture for computing a Compensatory Reserve Metric (CRM) for trauma victims suffering from hypovolemia (decreased circulating blood volume). The CRM is a single health indicator value that ranges from 100% for healthy individuals, down to 0% at hemodynamic decompensation - when the body can no longer compensate for blood loss. The CNN is trained on 20 second blood pressure waveform segments obtained from a finger-cuff monitor of 194 subjects. The model accurately predicts CRM when tested on data from 22 additional human subjects obtained from Lower Body Negative Pressure (LBNP) emulation of hemorrhage, attaining a mean squared error (MSE) of 0.0238 over the full range of values, including those from subjects with both low and high tolerance to central hypovolemia.