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Validation of a noninvasive monitor to continuously trend individual responses to hypovolemia

Moulton, Steven L. MD; Mulligan, Jane PhD; Santoro, Maria Antoinette; Bui, Khanh; Grudic, Gregory Z. PhD; MacLeod, David

Journal of Trauma and Acute Care Surgery: July 2017 - Volume 83 - Issue 1 - p S104–S111
doi: 10.1097/TA.0000000000001511
Clinical Study and Performance Improvement

BACKGROUND Humans are able to compensate for significant blood loss with little change in traditional vital signs, limiting early detection and intervention. We hypothesized that the Compensatory Reserve Index (CRI), a new hemodynamic parameter that trends changes in intravascular volume relative to the individual patient’s response to hypovolemia, would accurately trend each subject’s progression from normovolemia to decompensation (systolic blood pressure < 80) and back to normovolemia in humans.

METHODS Men and women, ages 19 years to 36 years, underwent stepwise (~333 mL aliquot) removal and replacement of 20% blood volume (men, 15 mL/kg; women, 13 mL/kg) via a large bore intravenous (i.v.) line. During each experiment, subjects were monitored with four CipherOx CRI Tablets. Withdrawn blood was reinfused at the end of each experiment.

RESULTS Forty-two subjects (24 men; 18 women) were enrolled in the study, of which 32 completed the protocol. Seven subjects became symptomatic and collapsed (systolic blood pressure < 80), six never achieving maximum blood loss; each was rescued with a saline infusion followed by reinfusion of their stored blood. The mean CRI at baseline for all 42 subjects was 0.9 ± 0.04. The mean CRI for the 32 subjects while asymptomatic at maximum blood loss was 0.611 ± 0.028. For the asymptomatic subjects, the average blood loss volume was 1018 mL ± 286 mL. In comparison, the mean CRI at maximum blood loss for the seven subjects who collapsed was 0.15 ± 0.007 and their average blood loss volume was 860 ± 183 mL. Mean CRI after reinfusion of blood was 0.89 ± 0.02. In addition symptomatic subjects demonstrated three times larger average decrease in CRI per liter of blood removed, 0.85 versus 0.28 for asymptomatic subjects.

CONCLUSION CRI trends change in intravascular volume relative to an individual’s response to hypovolemia and is sensitive to the differing risks associated with individuals’ differing tolerance to volume loss.

LEVEL OF EVIDENCE Prognostic study, level II.

From the Department of Surgery (S.L.M.), University of Colorado School of Medicine, Aurora; Flashback Technologies (S.L.M., J.M.), Inc., Boulder, Colorado; Department of Anesthesiology (M.A.S., K.B., G.Z.G., D.M.L.), Duke University School of Medicine, Durham, North Carolina.

Submitted: November 1, 2016, Revised: March 14, 2017, Accepted: April 1, 2017, Published online: May 1, 2017.

This study was presented at the 2016 European Society of Trauma and Emergency Surgery and 2016 Military Health Services Research Symposium. Results describing the first 20 subjects, specifically excluding those who collapsed early, were previously published as: Convertino VA, Howard JT, Hinojosa-Laborde C, Cardin S, Batchelder P, Mulligan J, Grudic GZ, Moulton SL, MacLeod DB. Individual-specific, beat-to-beat trending of significant human blood loss: the compensatory reserve. Shock 2015;44 Suppl 1:27–32. PMID 25565640.

IRB Approval: This study was conducted under a protocol reviewed and approved by The Institutional Review Board at Duke University, School of Medicine and the Institutional Review Board of the Office of Human Research Protection under the US Army Medical Research and Materiel Command.

This study was registered with NCT02980471.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Address for reprints: Steven L. Moulton, MD, Pediatric Surgery, B-323 Children’s Hospital Colorado 13123 E. 16th Ave. Aurora, CO 80045; email:

© 2017 Lippincott Williams & Wilkins, Inc.