Early Physiologic Numerical and Waveform Characteristics of Simulated Hemorrhagic Events With Healthy Volunteers Donating Blood

Abstract

OBJECTIVES: Early signs of bleeding are often masked by the physiologic compensatory responses delaying its identification. We sought to describe early physiologic signatures of bleeding during the blood donation process. SETTING: Waveform-level vital sign data including electrocardiography, photoplethysmography (PPG), continuous noninvasive arterial pressure, and respiratory waveforms were collected before, during, and after bleeding. SUBJECTS: Fifty-five healthy volunteers visited blood donation center to donate whole blood. INTERVENTION: After obtaining the informed consent, 3 minutes of resting time was given to each subject. Then 3 minutes of orthostasis was done, followed by another 3 minutes of resting before the blood donation. After the completion of donating blood, another 3 minutes of postbleeding resting time, followed by 3 minutes of orthostasis period again. MEASUREMENTS AND MAIN RESULTS: From 55 subjects, waveform signals as well as numerical vital signs (heart rate [HR], respiratory rate, blood pressure) and clinical characteristics were collected, and data from 51 subjects were analyzable. Any adverse events (AEs; dizziness, lightheadedness, nausea) were documented. Statistical and physiologic features including HR variability (HRV) metrics and other waveform morphologic parameters were modeled. Feature trends for all participants across the study protocol were analyzed. No significant changes in HR, blood pressure, or estimated cardiac output were seen during bleeding. Both orthostatic challenges and bleeding significantly decreased time domain and high-frequency domain HRV, and PPG amplitude, whereas increasing PPG amplitude variation. During bleeding, time-domain HRV feature trends were most sensitive to the first 100 mL of blood loss, and incremental changes of different HRV parameters (from 300 mL of blood loss), as well as a PPG morphologic feature (from 400 mL of blood loss), were shown with statistical significance. The AE group (n = 6) showed decreased sample entropy compared with the non-AE group during postbleed orthostatic challenge (p = 0.003). No significant other trend differences were observed during bleeding between AE and non-AE groups. CONCLUSIONS: Various HRV-related features were changed during rapid bleeding seen within the first minute. Subjects with AE during postbleeding orthostasis showed decreased sample entropy. These findings could be leveraged toward earlier identification of donors at risk for AE, and more broadly building a data-driven hemorrhage model for the early treatment of critical bleeding.