Original Contribution
Non-Invasive Venous waveform Analysis (NIVA) for monitoring blood loss in human blood donors and validation in a porcine hemorrhage model

https://doi.org/10.1016/j.jclinane.2019.109664Get rights and content

Highlights

  • Non-Invasive Venous waveform Analysis (NIVA) detects 500 mL blood loss.

  • NIVA predicts 500 mL blood loss with a sensitivity of 92% and specificity of 84%.

  • In a porcine model, NIVA correlates with graded volume of blood removed.

  • In a porcine model, NIVA correlates with hemodynamic indices during hemorrhage.

Abstract

Study objective

There is an unmet need for a non-invasive approach to diagnose hemorrhage early, before changes in vital signs occur. Non-Invasive Venous waveform Analysis (NIVA) uses a unique physiological signal (the peripheral venous waveform) to assess intravascular volume. We hypothesized changes in the venous waveform would be observed with blood loss in healthy adult blood donors and characterized hemorrhage using invasive monitoring in a porcine model.

Design

Prospective observational study.

Setting

American Red Cross donation center.

Patients

50 human blood donors and 12 non-donating controls; 7 Yorkshire pigs.

Interventions

A venous waveform capturing prototype (NIVA device) was secured to the volar aspect of the wrist in human subjects. A central venous catheter was used to obtain hemodynamic indices and venous waveforms were obtained using the prototype NIVA device over the saphenous vein during 400 mL of graded hemorrhage in a porcine model.

Measurements

Venous waveforms were transformed from the time to the frequency domain. The ratiometric power contributions of the cardiac frequencies were used to calculate a NIVA value representative of volume status.

Main results

A significant decrease in NIVA value was observed after 500 mL of whole blood donation (p < .05). A ROC curve for the ability of the NIVA to detect 500 mL of blood loss demonstrated an area under the curve (AUC) of 0.94. In the porcine model, change in NIVA value correlated linearly with blood loss and with changes in hemodynamic indices.

Conclusions

This study provides proof-of-concept for a potential application of NIVA in detection of blood loss. NIVA represents a novel physiologic signal for detection of early blood loss that may be useful in early triage and perioperative management.

Introduction

Current clinical, laboratory and monitoring techniques for determining intravascular volume lack accuracy [[1], [2], [3]]. Clinicians often rely on heart rate (HR) and blood pressure (BP) for estimation of fluid status and as a surrogate for assessment of blood loss and fluid replacement therapy [[4], [5], [6], [7]]. However, HR and BP have routinely been shown to be unreliable at detecting reduced intravascular volume [7,8]. HR and BP were not reliable in detecting an acute 450 mL blood loss (~8% of total blood volume) in blood donors [9]. Typically, a blood loss of 25–35% is required before alterations in heart rate or blood pressure occur [7]. This maintenance of perfusion with normal vital signs is due to shifting of blood volume from the venous reservoir as well as the sympathetic response to hemorrhage. When these compensatory mechanisms fail, hypotension and shock ensue.

Monitoring modalities for volume assessment such as central venous pressure (CVP), pulmonary artery catheters (PAC), arterial waveform analysis, esophageal doppler, transesophageal echocardiography, and transthoracic echocardiography have been developed, but these techniques are invasive and require user expertise [5,10,11]. Central or peripheral venous pressures are not clinically accurate for determining intravascular volume status [12]. Dynamic non-invasive monitoring of pulse pressure variation is limited by the requirement for mechanical ventilation with large (>8 mL/kg) tidal volumes and sinus rhythm for accuracy [13,14]. Thus, most decisions regarding resuscitation in the setting of hemorrhage are made empirically [5,12,15,16]. Failure to appropriately diagnose hypovolemia secondary to hemorrhage can lead to reduced cardiac output, hypotension, shock, end-organ failure, and mortality [10,17].

Peripheral venous waveform analysis in the frequency domain has recently been developed as a novel, alternative approach to monitor intravascular volume status. When the venous waveform is converted into the frequency domain, it has been noted that the power contributions of the frequencies corresponding to the pulse rate (f0) and its higher harmonics (f12) are altered at different volume states (Fig. 1). Acquisition of venous waveforms through a transducer in a peripheral intravenous line (Peripheral IntraVenous waveform Analysis, PIVA) can detect blood loss due to hemorrhage before changes in vital signs occur in a porcine model and in humans [18,19]. PIVA is also accurate in detection of volume overload and changes in volume after diuresis or dialysis in heart and renal failure patients, respectively [20,21].

The physiologic relevance of this type of analysis lies in the mechanical characteristics of the peripheral venous system, the most compliant vascular compartment of the body. [22,23] Because of this property, the peripheral venous system stores 60–70% of the total circulating blood volume, and hence serves as a volume reservoir whereby changes in overall volume status are reflected first in the venous system. Because the wave amplitude is low in veins, venous waveforms have not been rigorously examined until sensing and amplifying technologies became available [24]. In general, studies of venous hemodynamics have lagged behind studies of arterial hemodynamics.

There is a clear need for an accurate and easy-to-obtain measure for detection and quantification of early hemorrhage. Given the described limitations of current techniques, such data would greatly assist with resuscitation and triage of patients, including after traumatic injury or in the routine surgical setting. More recently, technology to capture venous waveforms non-invasively has been developed utilizing a piezoelectric sensor placed on the skin over the venous complex on the volar aspect of the wrist (Non-Invasive Venous waveform Analysis, NIVA; Fig. 1). This is different from previous peripheral venous waveform analysis in that acquisition of the waveform does not rely on the presence of a peripheral intravenous catheter and is completely non-invasive. In this study, validation of a prototype NIVA device was performed through assessment of its ability to detect changes in venous waveforms during blood loss in two controlled settings: human volunteers undergoing blood donation, and a porcine hemorrhage model. The porcine hemorrhage model allowed concurrent invasive hemodynamic monitoring that was not possible in human blood donors. The hypothesis of this investigation was that a quantifiable change in the venous waveform (NIVA value) would be associated with hypovolemia due to blood loss in healthy adult subjects and during controlled hemorrhage in the porcine model.

Section snippets

Healthy human hemorrhage

This prospective observational study was conducted with permission from the American Red Cross under a protocol reviewed and approved by the University of Alabama Birmingham Institutional Review Board through Vanderbilt University Medical Center Institutional Review Board . Informed consent was obtained from all study participants. To be included in the study, subjects were required to be deemed healthy enough to donate blood by the American Red Cross health history and medical examination

NIVA before and after blood donation in healthy human subjects

53 blood donors were enrolled, and three were excluded from final analysis (one subject was excluded due to poor signal quality, one subject due to data acquisition error, and one subject excluded as a repeat donor), providing a total of 50 subjects for analysis. Demographic information and NIVA values of healthy adult subjects donating whole blood are represented in Table 1. There was a significant decrease in mean NIVA value (mean difference −3.3, 95% CI −3.7 to −2.8) noted following donation

Discussion

The primary findings of this study are: 1) In healthy, spontaneously breathing adults, NIVA value obtained with the NIVA prototype (Fig. 1) accurately detected blood loss during 500 mL blood donation (Fig. 2); 2) In a porcine controlled hemorrhage model, NIVA value correlated with graded volume of blood removed (Fig. 3, Fig. 4); and with hemodynamic indices (PAD, CO and PCWP) during hemorrhage (Fig. 5). These data provide proof of concept for the use of NIVA in detection of early blood loss.

Conclusion

In both human subjects donating blood and in a controlled porcine hemorrhage model, a decrease in NIVA value was associated with low volume blood loss. With device optimization and additional clinical and experimental data, NIVA may ultimately assist clinicians in early identification and appropriate volume resuscitation of patients with hypovolemia due to hemorrhage.

Funding

The American Red Cross did not fund, sponsor, or participate in this study—we thank them for the permission to enroll subjects in their facility. This work was supported by the National Science Foundation grant number 1549576 to KH. This work was also supported by a grant from the National Institutes of Health to BA:R01HL148244.

Declaration of competing interest

Kyle Hocking, PhD, is Founder, CEO and President of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to Vanderbilt and licensed to VoluMetrix. Colleen Brophy, MD, is Founder and CMO of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to Vanderbilt and licensed to VoluMetrix. Bret Alvis, MD, owns stock in VoluMetrix and an inventor on intellectual property in the field of venous waveform

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