Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery

Abstract

Objectives: Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3(+), CD4(+), CD8(+), CD11b(+), CD16(+)/56(+) T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients.

Methods: Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3(+) (mature T cells), CD4(+) (T helper cells), CD8(+) (suppressor cytotoxic T cells), CD16(+)/56(+) (natural killer lymphocytes), and CD11b(+) (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4(+):CD8(+) ratio was calculated.

Results: Between-group comparisons showed significantly higher levels of TNF-α at T1 (2 h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4(+):CD8(+) ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b(+) levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56(+) levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24 h after surgery in Group HES (347±207 mL) was not significantly different from that of Group GEL (272±177 mL) or Group ISO (247±109) (p>0.05).

Conclusion: Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4(+):CD8(+) ratio, suggesting less immunosuppression.

Keywords: Coronary surgery; Cytokine; Gelatin; Hydroxyethyl starch; Inflammation.