Lorazepam Sedation for Critically Ill Children
Lorazepam Sedation for Critically Ill Children
This clinical trial is being performed under the Best Pharmaceuticals for Children Act,
 signed into law in 2002 in order to improve pediatric labeling for off-patent drugs. The
 purpose of this study is to make sure that lorazepam, when given to children who are very
 sick in the Intensive Care Unit and who are on a breathing machine, is safe and works as well
 as a drug called midazolam. Midazolam is already approved by the FDA for this use, but
 lorazepam is not, even though both drugs are commonly used for sedation.
Lorazepam is used clinically for sedation of mechanically ventilated children, but has not
 been approved by the FDA for this indication in children. The purpose of this study, in
 response to the Written Request by FDA, is to determine the safety, efficacy, and dosage
 required for lorazepam compared with midazolam, which is approved by FDA for children for
 this indication.

 Study participants must be children who are critically ill and receiving mechanical
 ventilation who require sedation. Participants will be randomized to lorazepam (intermittent
 bolus or continuous infusion) or midazolam (continuous infusion). Sedation will be monitored
 using the COMFORT score. Blood will be drawn to measure lorazepam/midazolam plasma
 concentrations, and to measure the plasma concentrations of excipients (benzyl alcohol and
 glycols) in patients receiving lorazepam.
Inclusion Criteria:

 -  Males or females from full term birth (at least 38 weeks post conceptual age) through
 18 years

 -  Patients must be intubated and mechanically ventilated in the PICU less than or equal
 to 24 hr

 -  Patients in whom the use of neuromuscular blocking agents would normally NOT be
 expected to be used.

 -  Patient's parent or guardian has signed a consent form prior to initiation of study
 procedures

 -  Patients with cardiac, renal, or hepatic dysfunction will be actively sought

 Exclusion Criteria:

 -  Life expectancy < 48 hr

 -  Expected duration of sedation < 48 hr

 -  Patient with history of hypersensitivity to any component of lorazepam, midazolam,
 fentanyl, thiopental

 -  Females pregnant or breast feeding

 -  Patient requires sedatives or analgesics other than study drug