Effects of Midazolam on Organ Dysfunction in Rats with Endotoxemia Induced by Lipopolysaccharide

Abstract

Sepsis is associated with high mortality and septic patients sometimes need sedation to attenuate anxiety and agitation. Recently, it has been suggested that midazolam, a benzodiazepine, modulates the responses to cytokines released from macrophages in vitro. The purpose of the present study was to evaluate the effect of midazolam on hemodynamics and organic function in rats with septic syndromes induced by intravenous endotoxin. Wistar rats were randomly allocated to three groups and treated intravenously as follows: (1) control group, in which the rats were given saline vehicle (1 mL/kg) at time 0; (2) LPS group, in which the rats were given Escherichia coli lipopolysaccharide (10 mg/kg) in an infusion over 10 minutes; (3) LPS+Midazolam group, in which the rats were given E. coli LPS infusion as in the LPS group followed immediately by infusion of midazolam, given at a rate of 1 microg/kg per hour. All hemodynamic and biochemical parameters were measured during the 4-hour observation period. The injection of LPS led to hypotension, tachycardia, and vascular hyporeactivity to vasoconstrictors. In addition, initial hyperglycemia, delayed hypoglycemia, hypoalbuminemia, elevated serum indicators of hepatic and renal injury and high mortality were also observed in rats treated with LPS. However, midazolam given in the designated dosage did not offer any modulatory effects on hemodynamic responses, multiple organic dysfunction and survival rate in rats with endotoxemia. No deleterious or beneficial effects on hemodynamics and organ dysfunction were observed in the endotoxemic rats treated with midazolam at the designated dosage. However, previous reports which showed substantial benefits from the inhibitory effects of midazolam on proinflammatory factors in vitro should be subjected to further elucidation.