UNLABELLED: Most intensive care (ICU) patients need pharmacological sedation during ventilatory support. The short-acting drug midazolam might be preferable to neuroleptic agents and opiates because of its anxiolytic and sedative properties. The dosage of a drug given in a continuous infusion is based upon knowledge of its clearance and of the function of concentration and effect. METHOD: A midazolam infusion (7.5 or 15 mg/h) was given to 16 patients receiving ventilatory support for 24 h. Clearance was estimated using the rule Cl = R/C (R = rate of infusion, C = concentration in steady state). To estimate the concentration of midazolam necessary for good sedation, the amount of supplementary injected neuroleptic during midazolam infusion was compared with that of the day before. Plasma cortisol and parameters of energy metabolism, electrolytes, and liver and kidney function were measured. RESULTS: Patients with disease of abdominal organs showed the lowest values for clearance (1.0-2.92 ml/min/kg). Some of the injured patients showed elevated values for clearance (3.0-21.36 ml/min/kg). Elimination half-life ranged from 1.5-50 h. Changes in intestinal perfusion or cardiac output might be responsible for the wide range. For good sedation, plasma midazolam concentrations had to be above 600 ng/ml. Plasma cortisol levels were not affected by midazolam, nor were metabolism, electrolytes, or liver and kidney function. CONCLUSION: Continuous infusion of midazolam is a useful way of sedation for ICU patients, but the wide range of clearance values must be considered.
UNLABELLED: Most intensive care (ICU) patients need pharmacological sedation during ventilatory support. The short-acting drug midazolam might be preferable to neuroleptic agents and opiates because of its anxiolytic and sedative properties. The dosage of a drug given in a continuous infusion is based upon knowledge of its clearance and of the function of concentration and effect. METHOD: A midazolam infusion (7.5 or 15 mg/h) was given to 16 patients receiving ventilatory support for 24 h. Clearance was estimated using the rule Cl = R/C (R = rate of infusion, C = concentration in steady state). To estimate the concentration of midazolam necessary for good sedation, the amount of supplementary injected neuroleptic during midazolam infusion was compared with that of the day before. Plasma cortisol and parameters of energy metabolism, electrolytes, and liver and kidney function were measured. RESULTS:Patients with disease of abdominal organs showed the lowest values for clearance (1.0-2.92 ml/min/kg). Some of the injured patients showed elevated values for clearance (3.0-21.36 ml/min/kg). Elimination half-life ranged from 1.5-50 h. Changes in intestinal perfusion or cardiac output might be responsible for the wide range. For good sedation, plasma midazolam concentrations had to be above 600 ng/ml. Plasma cortisol levels were not affected by midazolam, nor were metabolism, electrolytes, or liver and kidney function. CONCLUSION: Continuous infusion of midazolam is a useful way of sedation for ICU patients, but the wide range of clearance values must be considered.