Safety evaluation of fospropofol for sedation during minor surgical procedures.

STUDY OBJECTIVE

To evaluate the safety of intravenous (IV) fospropofol when used to provide minimal to moderate sedation in patients undergoing minor surgical procedures.

DESIGN

Phase 3, open-label, single-arm study.

SETTING

Multi-center.

PATIENTS

123 ASA physical status I, II, III, and IV patients, aged>or=18 years.

INTERVENTIONS

Patients were pretreated with fentanyl 50 microg before receiving an initial dose of IV fospropofol 6.5 mg/kg. Patients could receive up to 5 supplemental doses of fospropofol 1.63 mg/kg to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score<or=4 to allow the start of the procedure and to maintain adequate sedation levels during the procedure.

MEASUREMENTS

Study endpoints included measures of sedation depth, requirement for supplemental sedative doses, use of alternative sedatives, and the frequency and nature of treatment-emergent and sedative-related adverse events.

MAIN RESULTS

A mean of 2.4 supplemental doses of fospropofol was administered, and in 60% of patients, two or fewer supplemental doses of fospropofol were sufficient to initiate and complete the procedure. Alternative sedative medication was administered in 6 of 123 patients (4.9%). Mean (SD) MOAA/S score during the procedure was 3.8 (0.5). Sixty-one percent (61%) of patients had a MOAA/S score of 5 (fully alert) within two minutes after the end of the procedure. Few patients (7 of 123; 5.7%) had MOAA/S scores of 0 to 1 (deep sedation) during the procedure, and all 7 were either ASA physical status I (n=1) or II (n=6). The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62.6%) and pruritus (27.6%). Five patients experienced sedation-related adverse events, including hypotension (n=4), bradycardia (concurrently with hypotension and managed with atropine; n=1), or hypoxemia (less than one min and managed with chin lift and verbal stimulation; n=1). Twenty patients with previous or existing hepatic disease (ranging from minimal to severe) and 5 patients with severe renal impairment had adverse events similar to the overall population. No deaths were reported, and no patient discontinued the study due to adverse events.

CONCLUSION

An initial dose of IV fospropofol 6.5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures.