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

In this randomized, double-blinded study, we compared the onset and recover y characteristics of an investigational benzodiazepine, Ro 48-6791 (when ad ministered alone or combined with meperidine), a midazolam-meperidine combi nation for sedation during gastrointestinal (GI) endoscopic procedures. Nin ety consenting outpatients scheduled for upper or lower GI procedures were randomly assigned as follows: Group I received midazolam 1 mg IV and meperi dine 50 mg; Group II received Po 48-6791 0.5 mgIV 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 o f 4 (where 5 = awake/alert to 1 = asleep) in less than or equal to 2 min, a second bolus dose, equal to half of the original dose of midazolam or Ro 4 8-6791, 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 t he total induction dose was given to maintain an OAA/S score of 4. The indu ction 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 48-6 791 than with midazolam. The Ro 48-6791 groups also experienced more dizzin ess 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 HT LW test to return to baseline values after the procedure was similar among the three groups. However, the Po 48-6791 groups had significantly reduced times to return to an OAA/S score of 5 and to achieve the baseline HTLW val ue after the last dose of the benzodiazepine. In conclusion, compared with midazolam, Po 48-6791 is more potent and may be associated with a more rapi d early recovery after endoscopic GI procedures. However, sedation with Ro 48-6791 required more supplemental bolus doses and "rescue" analgesic medic ation and was associated with a higher incidence of dizziness. Implications : The investigational water-soluble benzodiazepine, Ro 48-6791, is a more p otent sedative than midazolam, which appears to have a slightly shorter dur ation of action. Unfortunately, use of Po 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 af ter the procedure.