Jacqz-Aigrain E, Daoud P, Burtin P, Desplanques L, Beaufils F
Department of Clinical Pharmacology, Hôpital Robert Debré, Paris, France.
Lancet. 1994 Sep 3;344(8923):646-50. doi: 10.1016/s0140-6736(94)92085-0.
Although midazolam is used for sedation of mechanically ventilated newborn babies, this treatment has not been evaluated in a randomised trial. We have done a prospective placebo-controlled study of the effects of midazolam on haemodynamic variables and sedation as judged by a five-item behaviour score. 46 newborn babies on mechanical ventilation for respiratory distress syndrome were randomly assigned to receive midazolam (n = 24) or placebo (n = 22) as a continuous infusion. Doses of midazolam were calculated to obtain plasma concentrations between 200 and 1000 ng/mL within 24 h of starting treatment and to maintain these values throughout the study. Haemodynamic and ventilatory variables were noted every hour, as were complications and possible side-effects of treatment. Mean (SD) duration of inclusion was 78.7 (30.9) h. 1 patient in the treatment group and 7 in the placebo group were withdrawn because of inadequate sedation (p < 0.05). Midazolam gave a significantly better sedative effect than placebo, as estimated by the behaviour score (p < 0.05). Heart rate and blood pressure were reduced by treatment but remained within the normal range for gestational age and there was no effect on ventilatory indices. The incidence of complications was similar in the two groups. No midazolam-related side-effects were noted. Continuous infusion of midazolam at doses adapted to gestational age induces effective sedation in newborn babies on mechanical ventilation, with positive effects on haemodynamic variables. The course of the respiratory distress syndrome was not influenced by this treatment. Midazolam was given over only a few days and the limited effects on heart rate and blood pressure that we report should not encourage long-term administration.
尽管咪达唑仑用于机械通气新生儿的镇静，但该治疗方法尚未在随机试验中进行评估。我们进行了一项前瞻性安慰剂对照研究，以观察咪达唑仑对血流动力学变量及根据五项行为评分判断的镇静效果的影响。46例因呼吸窘迫综合征接受机械通气的新生儿被随机分配接受咪达唑仑（n = 24）或安慰剂（n = 22）持续输注。计算咪达唑仑的剂量，以便在开始治疗后24小时内获得200至1000 ng/mL的血浆浓度，并在整个研究过程中维持这些值。每小时记录血流动力学和通气变量，以及治疗的并发症和可能的副作用。纳入研究的平均（标准差）持续时间为78.7（30.9）小时。治疗组有1例患者和安慰剂组有7例患者因镇静不足而退出研究（p < 0.05）。根据行为评分估计，咪达唑仑的镇静效果明显优于安慰剂（p < 0.05）。治疗使心率和血压降低，但仍在胎龄的正常范围内，且对通气指标无影响。两组并发症的发生率相似。未观察到与咪达唑仑相关的副作用。根据胎龄调整剂量持续输注咪达唑仑可使接受机械通气的新生儿有效镇静，对血流动力学变量有积极影响。该治疗方法未影响呼吸窘迫综合征的病程。咪达唑仑仅给药数天，我们报告的对心率和血压的有限影响不应鼓励长期给药。
