TY - JOUR
T1 - Human dose confirmation for self-expanding intra-abdominal foam
T2 - A translational, adaptive, multicenter trial in recently deceased human subjects
AU - Mesar, Tomaz
AU - Martin, David
AU - Lawless, Ryan
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.
AU - Marini, John
AU - Sharma, Upma
AU - Rago, Adam P.
AU - King, David R.
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015/7/3
Y1 - 2015/7/3
N2 - 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.
AB - 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.
KW - Trauma
KW - dosing
KW - foam
KW - noncompressible hemorrhage
KW - translational
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U2 - 10.1097/TA.0000000000000696
DO - 10.1097/TA.0000000000000696
M3 - Article
C2 - 26091312
AN - SCOPUS:84935042414
SN - 2163-0755
VL - 79
SP - 39
EP - 47
JO - Journal of Trauma and Acute Care Surgery
JF - Journal of Trauma and Acute Care Surgery
IS - 1
ER -