Comparison of the sedation and recovery profiles of Ro 48-6791, a new benzodiazepine, and midazolam in combination with meperidine for outpatient endoscopic procedures.

UNLABELLED: In this randomized, double-blinded study, we compared the onset and recovery characteristics of an investigational benzodiazepine, Ro 48-6791 (when administered alone or combined with meperidine), a midazolam-meperidine combination for sedation during gastrointestinal (GI) endoscopic procedures. Ninety consenting outpatients scheduled for upper or lower GI procedures were randomly assigned as follows: Group I received midazolam 1 mg IV and meperidine 50 mg; Group II received Ro 48-6791 0.5 mg IV and meperidine 50 mg; or Group III received Ro 48-6791 1.0 mg IV alone. If the level of sedation did not achieve an Observer's Assessment of Alertness/Sedation (OAA/S) score of 4 (where 5 = awake/alert to 1 = asleep) in < or = 2 min, a second bolus dose, equal to half of the original dose of midazolam or Ro 48-6791, was administered. The onset time was defined as the time to achieve an OAA/S score of 4. During the procedure, a bolus dose equal to half of the total induction dose was given to maintain an OAA/S score of 4. The induction and maintenance dosages, as well as recovery times to an OAA/S score of 5, were recorded. A heel-toe line walk (HTLW) test used to determine the time to "fitness for discharge." Although the onset times were similar in all three groups, the induction dosages were significantly reduced in Group II compared with Groups I and III. There were significantly more patients requiring supplemental sedative boluses and "rescue" analgesia with Ro 48-6791 than with midazolam. The Ro 48-6791 groups also experienced more dizziness after the procedures. Ro 48-6791 was associated with a higher incidence of inadequate sedation (18% vs 3%) without the opioid. The time for the HTLW test to return to baseline values after the procedure was similar among the three groups. However, the Ro 48-6791 groups had significantly reduced times to return to an OAA/S score of 5 and to achieve the baseline HTLW value after the last dose of the benzodiazepine. In conclusion, compared with midazolam, Ro 48-6791 is more potent and may be associated with a more rapid early recovery after endoscopic GI procedures. However, sedation with Ro 48-6791 required more supplemental bolus doses and "rescue" analgesic medication and was associated with a higher incidence of dizziness. IMPLICATIONS: The investigational water-soluble benzodiazepine, Ro 48-6791, is a more potent sedative than midazolam, which appears to have a slightly shorter duration of action. Unfortunately, use of Ro 48-6791 increased the requirement for supplemental doses of the sedative medication and the need for "rescue" analgesics during the procedure and was associated with more dizziness after the procedure.

RCT Entities:   Population Interventions Outcomes