Identifying Critical DO2 with Compensatory Reserve during Simulated Hemorrhage in Humans

Abstract

BackgroundHemorrhage is a leading cause of potentially‐survivable death in trauma. The basic principle for treatment of ongoing bleeding prior to hemorrhage control is that early detection and intervention will improve outcome. However, current monitoring technologies that rely on standard vital signs are unreliable in assessing the clinical status of trauma patients because of variability in the capacity of individuals to compensate for hypovolemia. A monitoring capability designed to measure changes in systemic oxygen delivery (DO2) would provide an earlier indicator of clinical status in patients with life‐threatening blood loss. Maintaining DO2 above the level associated with the onset of shock (i.e., DO2crit) until bleeding is controlled should be the aim of any hemorrhage intervention. But DO2crit has not been identified in humans. Over the past decade, measuring the physiological phenomenon of compensatory reserve (CRM) based on interrogation of arterial waveform morphology has provided a capability to assess the reduction in the capacity to compensate for ongoing progressive central hypovolemia. Based on non‐human primate hemorrhage experiments, we hypothesized that humans would demonstrate a linear relationship between CRM and DO2, allowing for the identification of a DO2crit in humans of ~5 to 6 ml O2·kg‐1·min‐1. We also hypothesized that individuals with high (HT) and low (LT) tolerance to hypovolemia (i.e., ‘good’ versus ‘poor’ compensators) would have similar CRM‐DO2 relationships and DO2crit.Study Design and MethodsCRM and calculated DO2 were measured in 166 healthy subjects (97 males, 69 females) with a mean ± SD age of 23 ± 4 years, height of 171 ± 11 cm, and weight of 69 ± 11 kg. All subjects underwent progressive central hypovolemia induced by lower body negative pressure as a model of ongoing hemorrhage to a physiological state of hemodynamic decompensation. Subjects were classified as having either high tolerance (HT; N = 111) or low tolerance (LT; N = 55) to central hypovolemia based on whether they completed 5 minutes at ‐60 mmHg LBNP.ResultsHT and LT groups were matched for age, weight, BMI, and vital signs, DO2 and CRM at baseline. The CRM‐DO2 relationship was best fitted to a logarithmic model in HT subjects (R2 = 0.971) and a polynomial model in the LT group (R2 = 0.991). Average DO2crit for the entire subject cohort was estimated at 5.3 ml O2·Kg‐1·min‐1, but was ~14% lower in HT compared to LT subjects. The reduction in DO2 from 40% CRM to 20% CRM was 2‐fold greater in the LT compared to the HT group.ConclusionsAverage DO2crit in humans is 5.3 ml O2·Kg‐1·min‐1, but is ~14% lower in HT compared to LT subjects. The CRM‐DO2 relationship is curvilinear in humans, and different when comparing HT and LT individuals. A threshold for an emergent monitoring signal should be set to 40% CRM given that the decline in DO2 from 40% CRM to 20% CRM for LT subjects is located on the steepest part of the CRM‐DO2 relationship.