Total resuscitative endovascular balloon occlusion of the aorta causes inflammatory activation and organ damage within 30 minutes of occlusion in normovolemic pigs

Abstract

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes physiological, metabolic, end-organ and inflammatory changes that need to be addressed for better management of severely injured patients. The aim of this study was to investigate occlusion time-dependent metabolic, end-organ and inflammatory effects of total REBOA in Zone I in a normovolemic animal model.

Methods: Twenty-four pigs (25-35 kg) were randomized to total occlusion REBOA in Zone I for either 15, 30, 60 min (REBOA15, REBOA30, and REBOA60, respectively) or to a control group, followed by 3-h reperfusion. Hemodynamic variables, metabolic and inflammatory response, intraperitoneal and intrahepatic microdialysis, and plasma markers of end-organ injuries were measured during intervention and reperfusion. Intestinal histopathology was performed.

Results: Mean arterial pressure and cardiac output increased significantly in all REBOA groups during occlusion and blood flow in the superior mesenteric artery and urinary production subsided during intervention. Metabolic acidosis with increased intraperitoneal and intrahepatic concentrations of lactate and glycerol was most pronounced in REBOA30 and REBOA60 during reperfusion and did not normalize at the end of reperfusion in REBOA60. Inflammatory response showed a significant and persistent increase of pro- and anti-inflammatory cytokines during reperfusion in REBOA30 and was most pronounced in REBOA60. Plasma concentrations of liver, kidney, pancreatic and skeletal muscle enzymes were significantly increased at the end of reperfusion in REBOA30 and REBOA60. Significant intestinal mucosal damage was present in REBOA30 and REBOA60.

Conclusion: Total REBOA caused severe systemic and intra-abdominal metabolic disturbances, organ damage and inflammatory activation already at 30 min of occlusion.

Keywords: Ischemia reperfusion injury; Occlusion time; Organ damage; REBOA.

Fig. 1

Mean systemic arterial blood pressure (MAP) in anesthetized pigs subjected to Zone I resuscitative endovascular balloon occlusion of the aorta for 15 min (REBOA15), 30 min (REBOA30), 60 min (REBOA60) and control conditions (no occlusion) and reperfusion for 3 h (n = 6 per group). Data are means and 95% confidence intervals. a Statistically significant difference compared to controls

Fig. 2

Systemic and mesenteric venous (MV) pH (panel a, b), lactate concentration (panel c, d) and potassium concentration (panel e, f) in anesthetized pigs subjected to zone I resuscitative endovascular balloon occlusion of the aorta for 15 (REBOA15), 30 (REBOA30), 60 min (REBOA60) and control conditions (no occlusion) and reperfusion for 3 h (n = 6 per group). Data are means and 95% confidence intervals. a Statistically significant difference compared to control, b Statistically significant difference compared to REBOA 15 min, c Statistically significant difference compared to REBOA 30 min, d Statistically significant difference compared to REBOA 60 min

Fig. 3

Intraperitoneal and intrahepatic concentrations of glucose (panel a, b), lactate (panel c, d) and glycerol (panel e, f) in anesthetized pigs subjected to Zone I resuscitative endovascular balloon occlusion of the aorta for 15 min (REBOA15), 30 min (REBOA30), 60 min (REBOA60) and control conditions (no occlusion) and reperfusion for 3 h (n = 6 per group). Data are means and 95% confidence intervals. a Statistically significant difference compared to controls, b Statistically significant difference compared to REBOA 15 min, c Statistically significant difference compared to REBOA 30 min, d Statistically significant difference compared to REBOA 60 min

Fig. 4

Plasma concentrations of interleukin-6 (IL-6, panel a), interleukin-8 (IL-8, panel b), interleukin-10 (IL-10, panel c) and tumor necrosis factor alpha (TNF-α, panel d) in anesthetized pigs subjected to Zone I resuscitative endovascular balloon occlusion of the aorta (I) for 15 min (REBOA15), 30 min (REBOA30), 60 min (REBOA60) and control conditions (no occlusion) and reperfusion for 3 h (n = 6 per group). Data are means and 95% confidence intervals. a Statistically significant difference compared to controls. b Statistically significant difference compared to REBOA 15 min. c Statistically significant difference compared to REBOA 30 min. d Statistically significant difference compared to REBOA 60 min

Fig. 5

Histological mucosal damage score in anesthetized pigs subjected to Zone I resuscitative endovascular balloon occlusion of the aorta for 15 min (REBOA15), 30 min (REBOA30), 60 min (REBOA60) and control conditions (no occlusion) and reperfusion for 3 h (n = 6 per group). Data are means and 95% confidence intervals. a Statistically significant difference compared to controls. b Statistically significant difference compared to REBOA 15 min. c Statistically significant difference compared to REBOA 30 min. d Statistically significant difference compared to REBOA 60 min