Protective Effects of Dexmedetomidine-Ketamine Combination Against Ventilator-Induced Lung Injury in Endotoxemia Rats

Background. Pulmonary inflammatory response is crucial in mediating the development of ventilator-induced lung injury (VILI) in animals experiencing endotoxemia. Dexmedetomidine and ketamine are two sedative agents with potent anti-inflammatory capacity. We sought to elucidate the anti-inflammatory effects of dexmedetomidine-ketamine combination against VILI in endotoxemia rats. Materials and Methods. Eighty-four adult male rats were allocated to receive normal saline, VILI, VILI plus dexmedetomidine-ketamine combination (DDK), lipopolysaccharide (LPS), LPS plus DDK, LPS plus VILI, or LPS plus VILI plus DDK (designated as the NS, V, V-DDK, LPS, LPS-DDK, LPS/V, and LPS/V-DDK group, respectively; n = 12 in each group). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 50 breath/min; FiO(2) 21%). After being mechanically ventilated for 4 h, rats were sacrificed and the levels of pulmonary inflammatory response were evaluated. Results. Histologic findings revealed severe, moderate, and mild inflammation in lung tissues of the LPS/V, LPS, and V groups, respectively, whereas those of the LPS/V-DDK, LPS-DDK, and V-DDK groups revealed moderate, mild, and normal to minimal inflammation, respectively. Moreover, the total cell number and the concentrations of macrophage inflammatory protein-2 and interleukin-1b in bronchoalveolar lavage fluid as well as the lung water content, leukocyte infiltration, myeloperoxidase activity, and the concentrations of inducible nitric oxide synthase/nitric oxide, and cyclooxygenase 2/prostaglandin E-2 in lung tissues of the LPS/V, LPS, and V groups were significantly higher than those of the LPS/V-DDK, LPS-DDK, and V-DDK groups, respectively. Conclusions. Dexmedetomidine-ketamine combination could mitigate pulmonary inflammatory response induced by VILI in endotoxemia rats. (C) 2011 Elsevier Inc. All rights reserved.