Human dose confirmation for self-expanding intra-abdominal foam: A translational, adaptive, multicenter trial in recently deceased human subjects

Tomaz Mesar, David Martin, Ryan Lawless, Jeanette Podbielski, Mackenzie Cook, Sam Underwood, Andreas Larentzakis, Bryan Cotton, Peter Fagenholz, Martin Schreiber, John B. Holcomb, John Marini, Upma Sharma, Adam P. Rago, David R. King

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    BACKGROUND: Noncompressible abdominal bleeding accounts for significant mortality in both military and civilian populations. There is an emergent need for a temporary hemostatic intervention whenever surgical care is not immediately available. Our team previously described a self-expanding polyurethane foam for the treatment of exsanguinating abdominal hemorrhage. The objective of this study was to translate a safe and effective swine dose into an appropriate human dose through foam administration in recently deceased humans with representative tissue compliance. METHODS: With institutional review board oversight and informed consent at three centers, terminal patients were identified. Within 3 hours of death, the abdomen was accessed, and fluid was added to simulate hemorrhage. Foam was percutaneously administered using a prototype delivery system at multiple doses (45, 55, 65, 75, and 100 mL). Intra-abdominal pressure was monitored for 15 minutes, and then, foam was removed via laparotomy to assess abdominal tissue contact. RESULTS: Twenty-one recently deceased patients ranging in age from 20 years to 92 years and body mass index from 18 kg/m2 to 39 kg/m2 were enrolled in the study. Foam was administered at a mean (SD) of 146 (34) minutes after death. Three subjects were screen failures, and three subjects were excluded from the analysis because of experimental errors. Change in intra-abdominal pressure and semiquantitative organ contact were used as surrogates to compare findings between humans and swine. Doses of 45, 55, and 65 mL resulted in peak pressures of 37 (20), 28 (8.1), and 33 (20) mmHg, respectively, within the acceptable range established in swine studies. Foam deployments of 75 mL and 100 mL exceeded acceptable pressures defined in swine. Higher foam doses tended to improve contact with the diaphragm, paracolic gutters, and liver. CONCLUSION: The use of recently deceased humans demonstrates a novel approach to device evaluation in representative human anatomy, particularly when tissue compliance is critical. Sixty-five milliliters was determined to be the clinically appropriate dose for foam treatment in bleeding human patients.

    Original languageEnglish (US)
    Pages (from-to)39-47
    Number of pages9
    JournalJournal of Trauma and Acute Care Surgery
    Volume79
    Issue number1
    DOIs
    StatePublished - Jul 3 2015

    Fingerprint

    Multicenter Studies
    Swine
    Pressure
    Hemorrhage
    Compliance
    Exsanguination
    Research Ethics Committees
    Hemostatics
    Diaphragm
    Informed Consent
    Abdomen
    Laparotomy
    Anatomy
    Body Mass Index
    Equipment and Supplies
    Mortality
    Liver
    Therapeutics
    Population

    Keywords

    • dosing
    • foam
    • noncompressible hemorrhage
    • translational
    • Trauma

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine
    • Surgery
    • Medicine(all)

    Cite this

    Human dose confirmation for self-expanding intra-abdominal foam : A translational, adaptive, multicenter trial in recently deceased human subjects. / Mesar, Tomaz; Martin, David; Lawless, Ryan; Podbielski, Jeanette; Cook, Mackenzie; Underwood, Sam; Larentzakis, Andreas; Cotton, Bryan; Fagenholz, Peter; Schreiber, Martin; Holcomb, John B.; Marini, John; Sharma, Upma; Rago, Adam P.; King, David R.

    In: Journal of Trauma and Acute Care Surgery, Vol. 79, No. 1, 03.07.2015, p. 39-47.

    Research output: Contribution to journalArticle

    Mesar, T, Martin, D, Lawless, R, Podbielski, J, Cook, M, Underwood, S, Larentzakis, A, Cotton, B, Fagenholz, P, Schreiber, M, Holcomb, JB, Marini, J, Sharma, U, Rago, AP & King, DR 2015, 'Human dose confirmation for self-expanding intra-abdominal foam: A translational, adaptive, multicenter trial in recently deceased human subjects', Journal of Trauma and Acute Care Surgery, vol. 79, no. 1, pp. 39-47. https://doi.org/10.1097/TA.0000000000000696
    Mesar, Tomaz ; Martin, David ; Lawless, Ryan ; Podbielski, Jeanette ; Cook, Mackenzie ; Underwood, Sam ; Larentzakis, Andreas ; Cotton, Bryan ; Fagenholz, Peter ; Schreiber, Martin ; Holcomb, John B. ; Marini, John ; Sharma, Upma ; Rago, Adam P. ; King, David R. / Human dose confirmation for self-expanding intra-abdominal foam : A translational, adaptive, multicenter trial in recently deceased human subjects. In: Journal of Trauma and Acute Care Surgery. 2015 ; Vol. 79, No. 1. pp. 39-47.
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    abstract = "BACKGROUND: Noncompressible abdominal bleeding accounts for significant mortality in both military and civilian populations. There is an emergent need for a temporary hemostatic intervention whenever surgical care is not immediately available. Our team previously described a self-expanding polyurethane foam for the treatment of exsanguinating abdominal hemorrhage. The objective of this study was to translate a safe and effective swine dose into an appropriate human dose through foam administration in recently deceased humans with representative tissue compliance. METHODS: With institutional review board oversight and informed consent at three centers, terminal patients were identified. Within 3 hours of death, the abdomen was accessed, and fluid was added to simulate hemorrhage. Foam was percutaneously administered using a prototype delivery system at multiple doses (45, 55, 65, 75, and 100 mL). Intra-abdominal pressure was monitored for 15 minutes, and then, foam was removed via laparotomy to assess abdominal tissue contact. RESULTS: Twenty-one recently deceased patients ranging in age from 20 years to 92 years and body mass index from 18 kg/m2 to 39 kg/m2 were enrolled in the study. Foam was administered at a mean (SD) of 146 (34) minutes after death. Three subjects were screen failures, and three subjects were excluded from the analysis because of experimental errors. Change in intra-abdominal pressure and semiquantitative organ contact were used as surrogates to compare findings between humans and swine. Doses of 45, 55, and 65 mL resulted in peak pressures of 37 (20), 28 (8.1), and 33 (20) mmHg, respectively, within the acceptable range established in swine studies. Foam deployments of 75 mL and 100 mL exceeded acceptable pressures defined in swine. Higher foam doses tended to improve contact with the diaphragm, paracolic gutters, and liver. CONCLUSION: The use of recently deceased humans demonstrates a novel approach to device evaluation in representative human anatomy, particularly when tissue compliance is critical. Sixty-five milliliters was determined to be the clinically appropriate dose for foam treatment in bleeding human patients.",
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    AU - Podbielski, Jeanette

    AU - Cook, Mackenzie

    AU - Underwood, Sam

    AU - Larentzakis, Andreas

    AU - Cotton, Bryan

    AU - Fagenholz, Peter

    AU - Schreiber, Martin

    AU - Holcomb, John B.

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