Cytokines and endotoxin generation and the effects of dopexamine in patients undergoing abdominal aortic reconstruction (AAR)

Hypothesis

Colonic ischaemia may increase morbidity and mortality following AAR. Animal studies suggest ischaemic colon causes endotoxin and cytokines release, initiating the systemic inflammatory response and multiorgan dysfunction syndrome.

Aim of study

• (1) Study the effects of temporary ischaemia, caused by aortic cross clamping (AXC); (2) confirm ischaemic colon as source of endotoxin and cytokine release in humans; (3) investigate any modification of the degree of ischaemia and cytokine and endotoxin generation with dopexamine hydrochloride.

Study design

Placebo-controlled prospective trial, 15 patients undergoing AAR randomised to receive dopexamine hydrochloride (n = 8) or normal saline (n = 7). Inferior mesenteric vein (IMV) sampled for IL-6. TNFα, endotoxin, pH, P_CO2 and P_O2 prior to AXC and 30 min postreperfusion. Peripheral systemic cytokines and endotoxin measured 24 h preoperatively and postoperatively. Hepatic and renal functions studied perioperatively.

Results

A statistically significant rise occurred in IMV IL-6 (P = 0.001) between pre-clamping and postreperfusion hut not in TNF-α and endotoxin. IL-6 and endotoxin levels showed negative correlation with IMV pH (r = -0.49 and -0.47 respectively). Patients with IMV pH <7.3 had higher levels of endotoxin (P = 0.04).

Dopexamine (1 μg/kg/min) produced an improvement in colonic pH without statistical significance between groups. Dopexamine produced statistical difference in postoperative creatinine clearance (P = 0.02), serum albumin (P = 0.02) and INR (P = 0.05).

Conclusion

Results confirm hypoperfused colon generates cytokines which, with endotoxin, are related to the IMV pH. Pharmacological modification of this response was not statistically significant. Dopexamine could improve renal and hepatic functions during AAR.