Anesthesia & Clinical Research
Open Access

Abstract

Bolus-Dose Fospropofol Disodium (Lusedra^®): Is 10 mg/Kg Superior To 6.5 mg/Kg for Sedation in Patients Undergoing Regional Anesthesia Blocks Prior to Orthopedic Surgery?

John B Leslie, Terrence L Trentman, Lopa Misra, David M Rosenfeld, David P Seamans, Renee E Caswell, André R Watkins, Joseph G Hentz and Ryan Buckley

Objective: Fospropofol disodium (Lusedra®) is a pro-drug propofol for Monitored Anesthesia Care. The FDA-approved dose regimen is minimally effective with a slow onset often requiring supplemental doses at 4 minutes to achieve adequate sedation and frequently requires early re-dosing. This study was designed to assess if a larger initial bolus dose of 10 mg/kg could achieve successful sedation without supplemental doses and without an increase in sedation-related adverse events.

Methods: An IRB-approved trial enrolled 12 adults undergoing elective orthopedic surgery with regional block. After IV fentanyl 50-75 micrograms, patients were randomly assigned into three IV bolus groups: fospropofol 6.5 mg/kg, fospropofol 10 mg/kg, or placebo with midazolam for rescue sedation if needed. Following the initial bolus, the level of sedation was measured, and, if adequate, the block initiated or additional IV sedation injected before proceeding with the block.

Results: 100% of the 10 mg/kg fospropofol group achieved appropriate sedation in less than 4 minutes compared to 50% of the 6.5 mg/kg group (P=0.048) and 40% of the fentanyl only participants with average times to sedation of 2.0 ± 0.0 minutes, 5.0 ± 4.0 minutes, and 7.0 ± 6.0 minutes, respectively. All of the 10 mg/kg group experienced deep sedation (MOAA/S 1-2), 60% experienced paresthesia or pruritus on bolus injection, 40% experienced delayed recovery from sedation, and 20% (1 of 5 patients) experienced a short period of apnea without hypoxemia. Sedation with midazolam produced delayed recovery in 40% of patients and 20% experienced deep sedation (MOAA/S 1-2).

Conclusion: 10 mg/kg bolus-dose fospropofol was 100% successful in producing sedation in less than 4 minutes, but was accompanied by deep sedation (p+0.048) and delayed recovery from sedation and more frequent apnea that make this dose unsuitable for procedures requiring short or minimal-to-moderate sedation. Further randomized trials with adequate power are required including consideration of an 8 mg/kg dose of fospropofol for MAC sedation procedures.