TY - JOUR
T1 - Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format
AU - Cho, S. David
AU - Holcomb, John B.
AU - Tieu, Brandon
AU - Englehart, Michael S.
AU - Morris, Melanie S.
AU - Karahan, Z. Ayhan
AU - Underwood, Samantha A.
AU - Muller, Patrick J.
AU - Prince, M. Dale
AU - Medina, Leticia
AU - Sondeen, Jill
AU - Shults, Christian
AU - Duggan, Michael
AU - Tabbara, Malek
AU - Alam, Hasan B.
AU - Schreiber, Martin A.
PY - 2009/1
Y1 - 2009/1
N2 - We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. Yorkshire swine were anesthetized, intubated, and instrumented. They then underwent femur fracture, 60% total blood volume hemorrhage, a 30-min shock period, induced hypothermia to 33°C, and hemorrhage volume replacement with 3:1 isotonic sodium chloride solution (NS) at each of three centers. Hemodynamic parameters were measured continuously. Thromboelastography, arterial blood gas, and laboratory values were collected at baseline, after the shock period, and after NS replacement. Thirty-seven animals were used for model development. Eight (21%) died before completion of the study period. Twenty-nine survivors were included in the analysis. MAP (±SEM) after the shock period was 32 ± 2 mmHg and was similar between centers (P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 ± 0.02, 8.20 ± 0.65 mmol/L, and 5.29 ± 0.44 mmol/L, respectively, after NS replacement. These were similar between centers (P > 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy (P < 0.02). Thromboelastography maximum amplitude values were similar among centers (P > 0.05) and demonstrated progressively weakened platelet interaction overtime (P< 0.03). Hematocrit was similar after controlled hemorrhage (P= 0.15) and dilution (P = 0.9). The pH, lactate, base deficit, and coagulation tests reflect a severely injured state. A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model.
AB - We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. Yorkshire swine were anesthetized, intubated, and instrumented. They then underwent femur fracture, 60% total blood volume hemorrhage, a 30-min shock period, induced hypothermia to 33°C, and hemorrhage volume replacement with 3:1 isotonic sodium chloride solution (NS) at each of three centers. Hemodynamic parameters were measured continuously. Thromboelastography, arterial blood gas, and laboratory values were collected at baseline, after the shock period, and after NS replacement. Thirty-seven animals were used for model development. Eight (21%) died before completion of the study period. Twenty-nine survivors were included in the analysis. MAP (±SEM) after the shock period was 32 ± 2 mmHg and was similar between centers (P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 ± 0.02, 8.20 ± 0.65 mmol/L, and 5.29 ± 0.44 mmol/L, respectively, after NS replacement. These were similar between centers (P > 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy (P < 0.02). Thromboelastography maximum amplitude values were similar among centers (P > 0.05) and demonstrated progressively weakened platelet interaction overtime (P< 0.03). Hematocrit was similar after controlled hemorrhage (P= 0.15) and dilution (P = 0.9). The pH, lactate, base deficit, and coagulation tests reflect a severely injured state. A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model.
KW - Coagulopathy
KW - Femur fracture
KW - Multicenter
KW - Preclinical trial
KW - Resuscitation
KW - Shock
KW - Swine
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=58849134888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849134888&partnerID=8YFLogxK
U2 - 10.1097/SHK.0b013e3181777ffb
DO - 10.1097/SHK.0b013e3181777ffb
M3 - Article
C2 - 18497710
AN - SCOPUS:58849134888
SN - 1073-2322
VL - 31
SP - 87
EP - 96
JO - Shock
JF - Shock
IS - 1
ER -