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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Prehosp Emerg Care. 2020 Jul 7;25(3):341–346. doi: 10.1080/10903127.2020.1778823

Inferior Vena Cava Diameter is an Early Marker of Central Hypovolemia during Simulated Blood Loss

Blair D Johnson 1, Zachary J Schlader 2, Michael W Schaake 1, Moragn C O'Leary 1, David Hostler 1,3, Howard Lin 3, Erika St James 3, Penelope C Lema 4, Aaron Bola 3, Brian M Clemency 3,1
PMCID: PMC8672380  NIHMSID: NIHMS1618344  PMID: 32628063

Abstract

Introduction

Inferior vena cava (IVC) diameter decreases under conditions of hypovolemia. Point-of-care ultrasound (POCUS) may be useful to emergently assess IVC diameter. This study tested the hypothesis that ultrasound measurements of IVC diameter decreases during severe simulated blood loss.

Methods

Blood loss was simulated in 14 healthy men (22±2 years) using lower body negative pressure (LBNP). Pressure within the LBNP chamber was reduced 10 mmHg of LBNP every four minutes until participants experienced pre-syncopal symptoms or until 80 mmHg of LBNP was completed. IVC diameter was imaged with POCUS using B-mode in the long and short axis views between minutes two and four of each stage.

Results

Maximum IVC diameter in the long axis view was lower than baseline (1.5±0.4 cm) starting at −20 mmHg of LBNP (1.0±0.3 cm; p<0.01) and throughout LBNP (p<0.01). The minimum IVC diameter in the long axis view was lower than baseline (0.9±0.3 cm) at −20 mmHg of LBNP (0.5±0.3 cm; p<0.01) and throughout LBNP (p<0.01). Maximum IVC diameter in the short axis view was lower than baseline (0.9±0.2 cm) at 40 mmHg of LBNP (0.6±0.2; p=0.01) and the final LBNP stage (0.6±0.2 cm; p<0.01). IVC minimum diameter in the short axis view was lower than baseline (0.5±0.2 cm) at the final LBNP stage (0.3±0.2 cm; p=0.01).

Conclusion

These data demonstrate that IVC diameter decreases prior to changes in traditional vital signs during simulated blood loss. Further study is needed to determine the view and diameter threshold that most accurate for identifying hemorrhage requiring emergent intervention.

Keywords: hemorrhage, ultrasound, lower body negative pressure, shock, POCUS

INTRODUCTION

Hemorrhage is one of the leading causes of deaths from trauma, but many of these deaths can be prevented with timely interventions (1–3). Despite severe blood loss, heart rate and blood pressure may demonstrate little or no change during the prehospital interval, making traditional vital signs inadequate indicators of impending cardiovascular decompensation (4).

Inferior vena cava (IVC) diameter has been proposed as a useful tool to identify central hypovolemia and blood loss in humans. This method has shown some promise for the indication of central hypovolemia in studies that examined low volumes (450 – 500 ml) of blood loss (5, 6). However, it is unclear if ultrasound measurements of the IVC are able to reliably detect more severe hemorrhage.

Lower body negative pressure (LBNP) is a validated, non-invasive surrogate of progressive blood loss in humans that can be used to study a variety of physiological responses to hemorrhage (7–10). During LBNP, the lower half of a participant’s body is sealed to an airtight chamber (Figure 1). The pressure within the LBNP chamber is controlled using a voltage-regulated vacuum. When suction is applied. LBNP sequesters circulating blood volume in the lower extremities to induce central hypovolemia that can be quickly restored when the technique is terminated. In this regard, LBNP can safely elicit cardiovascular decompensation in human participants (11), whereas the amount of blood volume that can be safely removed from human volunteers in the laboratory is limited. The objective of this study was to test the hypothesis that ultrasound measurements of IVC diameter would decrease during simulated severe hemorrhage using LBNP.

Figure 1.

Figure 1.

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Lower body negative pressure set up. Participants are sealed to the airtight chamber using a neoprene skirt. The chamber is connected to a voltage-regulated vacuum which creates a relative negative pressure within the chamber to sequester circulating blood within the lower body.

METHODS

Participants

Fourteen healthy men (age: 22±2 y, height: 179±6 cm, mass: 83±13 kg) participated in the study. All participants self-reported being free from cardiovascular, respiratory, metabolic, endocrine, or autonomic disease. None of the participants reported taking medications. All participants were fully informed of the experimental procedures and possible risks before providing informed, written consent. The study was approved by the Institutional Review Board at the [Blinded for Peer Review].

Experimental Design

Participants were asked to abstain from exercise, alcohol, and caffeine for at least 12 hours and food for at least two hours prior to the study. Participants were secured in the LBNP chamber in the supine position using a neoprene skirt that was sealed at the level of the iliac crest. Following a 10-minute rest period, baseline data were collected for an additional 10 minutes. Pressure within the LBNP chamber was then decreased by 10 mmHg of LBNP every four minutes until four minutes at 80 mmHg of LBNP were completed or until trial termination criteria were met. Trials were terminated if the participant syncopized, if systolic blood pressure fell below 80 mmHg of LBNP or mean arterial pressure fell by 30% from baseline accompanied by the participant reporting pre-syncopal symptoms (i.e. blurred vision, tunnel vision, sweating, and/or nausea), relative bradycardia accompanied by decreasing mean arterial pressure, or if the participant chose to end the protocol. Recovery data were collected for five minutes following the end of the protocol.

Ultrasound Image Acquisition

Long and short axis 3-second cine-loop ultrasound images of the IVC were obtained in B-mode (grayscale) with a broadband 1.5–3.6 MHz M4S phased array transducer (Vivid 7 Dimension, GE, Milwaukee, WI). Images were collected during minutes 2 to 4 of each stage. The anteroposterior (AP) diameter of the longitudinal axis view of the IVC was measured 2 cm caudal to the hepatic vein inlet in the subcostal transabdominal view. The short axis view of the IVC was measured at the level of the left renal vein. The order of IVC image acquisition (long axis first versus short axis first) was randomized for each participant. The maximum IVC diameter was measured during passive expiration. The minimum IVC diameter was measured during passive inspiration. IVC collapsibility is measure of the change in IVC size during inhalation. It has been validated as a non-invasive measure of volume status and has been shown to correlate with central venous pressure.(12–14) The IVC collapsibility index was calculated using the formula [(IVCmax diameter – IVCmin diameter)/IVCmax diameter] x 100. (12–14) Images were obtained by a board-eligible emergency medicine physician during his emergency ultrasound fellowship (HL) and reviewed by emergency ultrasound fellowship trained board-certified emergency medicine physicians (PCL, ESJ).

Vital Signs

Hemodynamic data were analyzed in 1-minute segments at the end of baseline, the end of each LBNP stage, and at the end of the 5-minute recovery period. Pulse pressure was calculated as the difference between systolic and diastolic blood pressure.

Statistical Analyses

A one-way repeated measures ANOVA followed by Dunnett’s post hoc procedure was used when a significant time effect was observed to determine when variables were different than baseline (version 6, GraphPad Software, La Jolla, CA). Six participants did not achieve or complete 80 mmHg of LBNP, however all participants completed 50 mmHg of LBNP. Therefore, the ANOVA analyses were performed using data up to 40 mmHg of LBNP and the last completed stage (70±10 mmHg) for each participant. Actual p values are reported when possible and statistical significance was set a priori at p ≤ 0.05. Data are reported as mean±SD.

RESULTS

The LBNP protocol was terminated early for six participants due to relative bradycardia that was accompanied by decreasing mean arterial pressure. The last completed stage for these participants were as follows: 50 mmHg (n = 1), 60 mmHg (n = 3), and 70 mmHg (n = 2) of LBNP.

Long Axis View of the Inferior Vena Cava

Maximum IVC diameter was lower than baseline (1.5±0.4 cm) at 20 mmHg of LBNP (1.3±0.4 cm; p<0.001), 30 mmHg of LBNP (0.9±0.3 cm; p<0.001), 40 mmHg of LBNP (0.8±0.2 cm; p<0.001), and the final LBNP stage (0.8±0.3 cm; p<0.001) (Figure 2A). Minimum IVC diameter was lower than baseline (0.9±0.3 cm) at 20 mmHg of LBNP (0.5±0.3 cm; p=0.002), 30 mmHg of LBNP (0.5±0.3 cm; p<0.001), 40 mmHg of LBNP (0.4±0.2 cm; p<0.001), and the final LBNP stage (0.3±0.2 cm; p<0.001) (Figure 2B). The collapsibility index of the IVC in the long axis view did not differ throughout the LBNP protocol (p=0.11) (Figure 2C).

Figure 2.

Figure 2.

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Maximum IVC diameter (A), minimum IVC diameter (B), and IVC collapsibility index obtained from the long axis view throughout the protocol. Data are presented as means ± SD. B = different from baseline (P < 0.05).

Short Axis View of the Inferior Vena Cava

Maximum IVC diameter was lower than baseline (0.9±0.2 cm) at 40 mmHg of LBNP (0.6±0.2 cm; p=0.011) and the final LBNP stage (0.6±0.2 cm; p=0.001) (Figure 3A). Minimum IVC diameter was lower than baseline (0.5±0.2 cm) at the final LBNP stage (0.3±0.2; p=0.01) (Figure 3B). The collapsibility index of the IVC in the short axis view did not differ throughout the LBNP protocol (p=0.36) (Figure 3C).

Figure 3.

Figure 3.

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Maximum IVC diameter (A), minimum IVC diameter (B), and IVC collapsibility index obtained from the short axis view throughout the protocol. Data are presented as means ± SD. B = different from baseline (P < 0.05).

Hemodynamics

Heart rate was greater than baseline (70±16 bpm) only at the final LBNP stage (94±19 bpm; p<0.001) (Figure 4A). Mean arterial pressure was lower than baseline (91±7 mmHg) only at the final LBNP stage (78±17 mmHg; p<0.001). Systolic blood pressure was lower than baseline (129±11 mmHg) at 40 mmHg of LBNP (119±12; p=0.01) and the final LBNP stage (102±21; p<0.001) (Figure 4B). Despite a significant time effect (p=0.03), diastolic blood pressure was not lower than baseline (70±5.1 mmHg) at any time point (p>0.05 for all LBNP pressures) (Figure 4C). Pulse pressure was lower than baseline (58±8 mmHg) at 40 mmHg of LBNP (51±8 mmHg; p<0.001) and the final LBNP stage (36±8 mmHg; p<0.001) (Figure 4D).

Figure 4.

Figure 4.

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Heart rate (A), systolic blood pressure (B), diastolic blood pressure (C), and pulse pressure (D) obtained throughout the protocol. Data are presented as means ± SD. B = different from baseline (p < 0.05).

DISCUSSION

Maximum IVC diameter measured in the long and short axis views were lower than baseline starting at 20 mmHg of LBNP and 40 mmHg of LBNP respectively and remained lower throughout the LBNP protocol. Changes in IVC diameter preceded changes in heart rate and blood pressure. LBNP is able to safely simulate much greater decreases in central blood volume compared to prior blood donation studies, which are limited to no more than 500 ml of blood loss. (6, 12, 15) This study examined IVC diameter and collapsibility changes throughout a wide range of central blood volumes, and in some cases, to the point of cardiovascular decompensation.

This study used LBNP as an experimental surrogate to study the effects of blood loss on IVC diameter. Prior studies have demonstrated that LBNP mimics the hemodynamic (7, 9), coagulation (8), and white blood cell (10) responses observed during actual blood loss. This study supports the use of LBNP as a surrogate to study the effects of blood loss on IVC diameter.

There was a 33% reduction (~0.5 cm) in the long axis view maximal IVC diameter and a 40% reduction (~0.5 cm) in minimum IVC diameter during 20 mmHg of LBNP, which represents approximately 333 to 500 ml of blood loss (7, 11). Lyon and colleagues imaged the IVC in the long axis view using B-mode in healthy adults before and after 450 ml of blood donation and found that IVC maximum and minimum diameters both decreased by ~0.5 cm (5). Furthermore, IVC diameters obtained in the long axis view using B-mode has been shown to be correlated with central venous pressure (16) and right atrial pressure (17) such that lower pressures were related to smaller diameters, similar to the decreases we found during LBNP. However, Resnick et al. found that IVC maximum diameter decreased by only 12% in the short axis view and 20% in the long axis view using M-mode following 500 ml of blood donation (6). The smaller percentage reductions that were found by Resnick et al. versus these data and others (5) can most likely be attributed to the larger baseline measurements that were obtained from M-mode images (6). IVC diameters can be overestimated when the IVC and M-mode line are not properly aligned. Previous studies have advocated for B-mode acquisition of IVC measurements due to inaccuracies that may occur in M-mode owing to respiratory displacement of the IVC (13, 18).

This study did not find any changes in IVC collapsibility index using the short axis or long axis views during LBNP. This finding is similar to those found by Moore et al. (19) and Resnick et al. (6), but differs from that of Nagdev (16) and Kircher (17). It is possible that changes in respiratory rate or tidal volume during LBNP or following blood donation may have also influenced IVC collapsibility.

The ability to easily track real time estimations of central blood volume is important in reducing the risk of overcompensating for fluid loss, as excessive administration of intravenous fluids is associated with a greater risk of complications (20). Using IVC diameters to assist with determining volume status and guiding resuscitation strategies might be beneficial for patients who have experienced blood loss. In this context, reductions in IVC diameter were found prior to changes in heart rate or blood pressure (4).

Previous studies have reported that EMS providers can effectively use ultrasound to identify esophageal intubation (21, 22), long bone fractures (23), and cardiac movement during resuscitation (24). It has also been shown to be feasible for paramedics to perform the Focused Assessment Sonography in Trauma (FAST) and abdominal aortic exams in the prehospital care environment (25). While many studies have reported that prehospital use of ultrasound is feasible, others have been less optimistic. One study of lung ultrasound imaging in the field with remote physician interpretation reported barriers to the implementation of prehospital ultrasound (26). The future of prehospital ultrasound for this technique, and others, likely depends on the training program and continuing education process (27, 28).

Limitations

This preclinical study has a number of important limitations. While LBNP does create a condition of relative upper body hypovolemia, it does not reproduce other conditions such as pain and psychological stress which are present in true traumatic hemorrhage. The opening of the LBNP unit limits our ability to include obese patents in our study design. The IVC is also more technically challenging to image in obese patients which might limit is utility for these patients. Our subjects were a cohort of young healthy males. While young healthy males are over represented in civilian and military trauma, they do not represent the totality of these populations. Finally, images were obtained by a single physician experienced in ultrasonography. Future studies should focus on interrater reliability, especially among providers with more limited ultrasound experience.

Conclusion

These data demonstrate IVC diameter decreases prior to changes in traditional vital signs during simulated blood loss. However, IVC collapsibility index remained stable. Further studies are needed to determine which view and which diameter threshold is most accurate for identifying hemorrhage requiring emergency intervention. Given the expanding literature on prehospital ultrasound, future studies should also determine the feasibility of prehospital providers performing this technique.

Acknowledgments

The authors wish to thank Dr. Heather Lindstrom and the study participants for their time and commitment to this research.

Footnotes

Dr. St. James and Dr. Lema are consultants for Mindray North America (Mahwah, NJ). Dr. Clemency is a speaker for Stryker (Kalamazoo, MI). No conflicts of interest, financial or otherwise, are declared by the other authors.

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