Distal organ inflammation and injury after resuscitative endovascular balloon occlusion of the aorta in a porcine model of severe hemorrhagic shock

Abstract

Background and objective: Resuscitative Endovascular Balloon Occlusion of Aorta (REBOA) has emerged as a potential life-saving maneuver for the management of non-compressible torso hemorrhage in trauma patients. Complete REBOA (cREBOA) is inherently associated with the burden of ischemia reperfusion injury (IRI) and organ dysfunction. However, the distal organ inflammation and its association with organ injury have been little investigated. This study was conducted to assess these adverse effects of cREBOA following massive hemorrhage in swine.

Methods: Spontaneously breathing and consciously sedated Sinclair pigs were subjected to exponential hemorrhage of 65% total blood volume over 60 minutes. Animals were randomized into 3 groups (n = 7): (1) Positive control (PC) received immediate transfusion of shed blood after hemorrhage, (2) 30min-cREBOA (A30) received Zone 1 cREBOA for 30 minutes, and (3) 60min-cREBOA (A60) given Zone 1 cREBOA for 60 minutes. The A30 and A60 groups were followed by resuscitation with shed blood post-cREBOA and observed for 4h. Metabolic and hemodynamic effects, coagulation parameters, inflammatory and end organ consequences were monitored and assessed.

Results: Compared with 30min-cREBOA, 60min-cREBOA resulted in (1) increased IL-6, TNF-α, and IL-1β in distal organs (kidney, jejunum, and liver) (p < 0.05) and decreased reduced glutathione in kidney and liver (p < 0.05), (2) leukopenia, neutropenia, and coagulopathy (p < 0.05), (3) blood pressure decline (p < 0.05), (4) metabolic acidosis and hyperkalemia (p < 0.05), and (5) histological injury of kidney and jejunum (p < 0.05) as well as higher levels of creatinine, AST, and ALT (p < 0.05).

Conclusion: 30min-cREBOA seems to be a feasible and effective adjunct in supporting central perfusion during severe hemorrhage. However, prolonged cREBOA (60min) adverse effects such as distal organ inflammation and injury must be taken into serious consideration.

Fig 1. Overview of experimental design.

BL, baseline; EBV, estimated blood volume; EH, end of hemorrhage; EOS, end of study; R90, R150, R210 and R240 are 90-, 150-, 210-, and 240-min post-resuscitation, respectively; cREBOA, complete resuscitative endovascular balloon occlusion of the aorta.

Fig 2. The hemodynamic and metabolic performance of swine undergoing cREBOA.

Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. ^# p<0.05, A30 vs. PC group; * p<0.05, PC vs. A60 group; † p<0.05, A60 vs. A30 group. A30, cREBOA for 30 minutes; A60, cREBOA for 60 minutes; DBP, diastolic blood pressure; PC, positive control. BE, base excess; EOS, end of study; HR, heart rate; SBP, systolic blood pressure.

Fig 3. White blood cell counts in swine undergoing cREBOA.

Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. * p<0.05, PC vs. A60 group; † p<0.05, A60 vs. A30 group. WBC, white blood cells; Neu, neutrophils; Lym, lymphocytes.

Fig 4. Blood clotting measures in swine undergoing cREBOA.

Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. * p<0.05, PC vs. A60 group; † p<0.05, A60 vs. A30 group. INR, international normalized ratio; PT, prothrombin time; PTT, partial thromboplastin time.

Fig 5. Local tissue inflammatory response and oxidative stress in swine undergoing cREBOA.

Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. ^# p<0.05, A30 vs. PC; * p<0.05, A60 vs. PC; † p<0.05, A60 vs. A30.

Fig 6. Changes of end-organ damage in plasma from swine undergoing cREBOA.

Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. * p<0.05, PC vs. A60 group; † p<0.05, A60 vs. A30 group. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Fig 7. Histological alterations of end-organs in swine undergoing cREBOA.

A, representative histological photos of kidney (top panel), jejunum (middle panel) and liver (low panel). B, semiquantitative evaluation of the pathological features. Data are presented as mean ± SEM and were statistically analyzed using two-tailed Mann-Whitney test. * p<0.05, PC vs. A60 group; † p<0.05, A60 vs. A30 group.