Original ContributionNon-Invasive Venous waveform Analysis (NIVA) for monitoring blood loss in human blood donors and validation in a porcine hemorrhage model
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 (f1–2) 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
References (32)
- et al.
Vital signs in hospital patients: a systematic review
Int J Nurs Stud
(2001) - et al.
Orthostatic vital signs: variation with age, specificity, and sensitivity in detecting a 450-mL blood loss
Am J Emerg Med
(1992) - et al.
Arterial waveform analysis
Best Pract Res Clin Anaesthesiol
(2014) - et al.
Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares
Chest
(2008) - et al.
Alternative methods to central venous pressure for assessing volume status in critically ill patients
J Emerg Nurs
(2014) - et al.
Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis
Br J Anaesth
(2017) - et al.
Monitoring volume and fluid responsiveness: from static to dynamic indicators
Best Pract Res Clin Anaesthesiol
(2013) - et al.
Hemodynamic monitoring in shock and implications for management. International consensus conference, Paris, France, 27–28 April 2006
Intensive Care Med
(2007) - et al.
Comparing the air medical prehospital triage score with current practice for triage of injured patients to helicopter emergency medical services: a cost-effectiveness analysis
JAMA Surg
(2018) - et al.
Undertriage remains a vexing problem for even the most highly developed trauma systems: the need for innovations in field triage
JAMA Surg
(2018)
Perioperative hemodynamic instability and fluid overload are associated with increasing acute kidney injury severity and worse outcome after cardiac surgery
Blood Purif
Goal-directed fluid management reduces vasopressor and catecholamine use in cardiac surgery patients
Intensive Care Med
Bedside assessment of intravascular volume status in patients undergoing coronary bypass surgery
Anesthesiology
A systematic review of the relationship between blood loss and clinical signs
PLoS One
Intensivist bedside ultrasound (INBU) for volume assessment in the intensive care unit: a pilot study
J Trauma
Pulse pressure variations to predict fluid responsiveness: influence of tidal volume
Intensive Care Med
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