Sedation during Artificial Ventilation by Continuous Intravenous Infusion of Midazolam: Effects of Hepatocellular or Renal Damage

Abstract

To evaluate the effects of hepatocellular or renal damage on therapeutic doses of midazolam and emergence time after withdrawal of the drug, 87 patients under continuous sedation with midazolam on artificial ventilation were prospectively studied. They needed continuous sedation for 12 hours or more. They included 55 patients with normal hepatocellular and renal functions (C group), 21 patients with hepatocellular damage (II group), and 11 patients with hepatocellular and renal damage (HR group). Midazolam was initiated with an intravenous dose of 0.1 mg/kg followed by 0.05 mg/kg/hr. Dosage was regulated to maintain a state in which patients responded to verbal command and had bucking responses to endotracheal suctioning. The three groups were compared with respect to midazolam dosage, emergence time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels and urine volume. The mean doses of midazolam in the C, H, and HR groups were 0.083 ± 0.038 mg/kg/hr, (mean ± standard deviation) 0.073 ± 0.037 mg/kg/hr, and 0.088 ± 0.048 mg/kg/hr, respectively, showing no differences among these groups. Emergence time was significantly longer in the H group (333 ± 263 min; p < 0.005) and the HR group (305 ± 225 min; p < 0.025) than in the C group (171 ± 106 min). No effect of midazolam administration was seen on AST, ALT, BUN, Cr, and urine volume in all groups. In conclusion, presence of hepatocellular or renal damage did not alter required dosage of midazolam. Hepatocellular damage prolonged emergence time, but renal damage had no more additive effect. There was no evidence of hepatocellular and renal damages during treatment.