OBJECTIVE: To determine the minimal effective dose (MED) of intravenous midazolam, required for appropriate sedation in 95% of patients, 1 h after drug administration. METHODS: A double-blind dose-finding study using the continual reassessment method, a Bayesian sequential design. Twenty-three newborn infants hospitalized in intensive care unit participated. Inclusion criteria were: (i) post-natal age <28 days, (ii) gestational age >33 weeks, (iii) intubation and ventilatory support required for respiratory distress syndrome, (iv) need for sedation (i.e. one of the six following criteria: agitation or grimacing or crying facial expression before tracheal suctioning, agitation or grimacing or crying facial expression during tracheal suctioning). Each neonate was allocated to a loading dose, ranging from 75 to 200 microg/kg, and a maintenance dose ranging from 37.5 to 100 microg/kg/h. RESULTS: The primary endpoint was the level of sedation 1 h after the onset of infusion. The sedation procedure was classified as a success if all the following clinical criteria were met: no agitation, no grimacing and no crying facial expression before as well as during tracheal suctioning. Based on the 23 patients, the final estimated probability of success was 76.9% (95% credibility interval: 56.6-91.4%) for the 200 microg/kg loading dose. no significant adverse effect was observed. CONCLUSIONS: Continual reassessment is a new approach, suitable for dose-finding study in neonates. this method overcomes some of the ethical, statistical and practical problems associated with this population. Using this method, the MED was estimated to be the 200 mug/kg loading dose of midazolam.
RCT Entities:
OBJECTIVE: To determine the minimal effective dose (MED) of intravenous midazolam, required for appropriate sedation in 95% of patients, 1 h after drug administration. METHODS: A double-blind dose-finding study using the continual reassessment method, a Bayesian sequential design. Twenty-three newborn infants hospitalized in intensive care unit participated. Inclusion criteria were: (i) post-natal age <28 days, (ii) gestational age >33 weeks, (iii) intubation and ventilatory support required for respiratory distress syndrome, (iv) need for sedation (i.e. one of the six following criteria: agitation or grimacing or crying facial expression before tracheal suctioning, agitation or grimacing or crying facial expression during tracheal suctioning). Each neonate was allocated to a loading dose, ranging from 75 to 200 microg/kg, and a maintenance dose ranging from 37.5 to 100 microg/kg/h. RESULTS: The primary endpoint was the level of sedation 1 h after the onset of infusion. The sedation procedure was classified as a success if all the following clinical criteria were met: no agitation, no grimacing and no crying facial expression before as well as during tracheal suctioning. Based on the 23 patients, the final estimated probability of success was 76.9% (95% credibility interval: 56.6-91.4%) for the 200 microg/kg loading dose. no significant adverse effect was observed. CONCLUSIONS: Continual reassessment is a new approach, suitable for dose-finding study in neonates. this method overcomes some of the ethical, statistical and practical problems associated with this population. Using this method, the MED was estimated to be the 200 mug/kg loading dose of midazolam.
Authors: Eric Vermeulen; John N van den Anker; Oscar Della Pasqua; Kalle Hoppu; Johanna H van der Lee Journal: J Pharm Pharmacol Date: 2016-09-27 Impact factor: 3.765