Behne M, Asskali F, Steuer A, Förster H
Anaesthesist. 1987 May;36(5):228-32.
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.
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.
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.
Continuous infusion of midazolam is a useful way of sedation for ICU patients, but the wide range of clearance values must be considered.
大多数重症监护病房（ICU）患者在机械通气支持期间需要药物镇静。短效药物咪达唑仑因其抗焦虑和镇静特性，可能比抗精神病药物和阿片类药物更可取。持续输注给药的剂量基于对其清除率以及浓度和效应功能的了解。
对16例接受24小时机械通气支持的患者给予咪达唑仑输注（7.5或15毫克/小时）。使用公式Cl = R/C（R =输注速率，C =稳态浓度）估算清除率。为了估算达到良好镇静效果所需的咪达唑仑浓度，将咪达唑仑输注期间追加注射的抗精神病药物量与前一天的量进行比较。测量血浆皮质醇以及能量代谢、电解质、肝肾功能参数。
腹部器官疾病患者的清除率最低（1.0 - 2.92毫升/分钟/千克）。一些受伤患者的清除率升高（3.0 - 21.36毫升/分钟/千克）。消除半衰期为1.5 - 50小时。肠道灌注或心输出量的变化可能是造成这种广泛差异的原因。为达到良好镇静效果，血浆咪达唑仑浓度必须高于600纳克/毫升。血浆皮质醇水平不受咪达唑仑影响，代谢、电解质、肝肾功能也不受影响。
持续输注咪达唑仑是ICU患者镇静的一种有效方法，但必须考虑清除率值的广泛差异。
