Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared with a conventional total intravenous anesthesia (TIVA) group of 11 patients (4 females and 7 males). The endpoints used to assess inflammatory and biochemical responses to mini-CPB were plasma interleukin (IL)-1, IL-6, IL-10, interferon (INF)-γ, tumor necrosis factor (TNF)-α, C-reactive protein, creatine phosphokinase, creatine phosphokinase-MB, cardiac troponin I, cortisol, and glucose levels. These variables were determined before anesthesia, 90 min after beginning CPB, 5 h after beginning CPB, and 24 h after the end of surgery. Endpoints of oxidative stress, including thiobarbituric acid reactive species and delta-aminolevulinate dehydratase activity in erythrocytes were also determined. DEX+TIVA use was associated with a significant reduction in IL-1, IL-6, TNF-α, and INF-γ (P<0.0001) levels compared with TIVA (two-way ANOVA). In contrast, the surgery-induced increase in thiobarbituric acid reactive species was higher in the DEX+TIVA group than in the TIVA group (P<0.01; two-way ANOVA). Delta-aminolevulinate dehydratase activity was decreased after CPB (P<0.001), but there was no difference between the two groups. DEX as an adjuvant in anesthesia reduced circulating IL-1, IL-6, TNF-α, and INF-γ levels after mini-CPB. These findings indicate an interesting anti-inflammatory effect of DEX, which should be studied in different types of surgical interventions.

Figure 1. Interleukin (IL)-1 (A,B), IL-6 (C,D), and IL-10 (E,F) levels were measured in patients who underwent coronary arterial bypass graft surgery under mini-cardiopulmonary bypass, using two different types of anesthesia (conventional total intravenous anesthesia [TIVA; n=11] and TIVA+DEX [n=12]). Two-way ANOVA showed a significant interaction between type of anesthesia and sampling time for IL-1 and IL-6 levels (P<0.0001). This finding indicated that the increase in IL-1 and IL-6 levels as a function of time after surgery was attenuated in patients who were anesthetized with TIVA+DEX compared with those who received only TIVA. Two-way ANOVA of IL-10 levels only showed a significant main effect of sampling time (P<0.0001) with a similar and progressive decrease of IL-10 in both anesthetic groups.

Figure 2. A, B, Plasma γ-interferon (INF-γ) and C, D, tumor necrosis factor-α (TNF-α) levels in patients who underwent coronary arterial bypass graft surgery under mini-cardiopulmonary bypass, using two different types of anesthesia (conventional total intravenous anesthesia [TIVA; n=11] and TIVA+DEX [n=12]). Two-way ANOVA showed a significant type of anesthesia versus sampling time interaction for INF-γ and TNF-α levels (P<0.0001). This finding indicated that the increase in INF-γ and TNF-α levels after surgery was lower in patients who were anesthetized with TIVA+DEX than in patients who received only TIVA.

Figure 3. A, B, Thiobarbituric reactive substances (TBARS) and C, D, δ-aminolevulinate dehydratase (ALA-D) enzyme activity of erythrocytes in patients who underwent coronary arterial bypass graft surgery under mini-cardiopulmonary bypass, using two different types of anesthesia (conventional total intravenous anesthesia [TIVA; n=11] and TIVA+DEX [n=12]). For TBARS, two-way ANOVA showed a significant sampling time versus type or anesthesia interaction (P<0.001). For ALA-D activity, two-way ANOVA showed only a significant main effect of time (P<0.0001).