Perspectives on the Role of Fospropofol in the Monitored Anesthesia Care Setting

Abstract

Monitored anesthesia care (MAC) is a safe, effective, and appropriate form of anesthesia for many minor surgical procedures. The proliferation of outpatient procedures has heightened interest in MAC sedation agents. Among the most commonly used MAC sedation agents today are benzodiazepines, including midazolam, and propofol. Recently approved in the United States is fospropofol, a prodrug of propofol which hydrolyzes in the body by alkaline phosphatase to liberate propofol. Propofol liberated from fospropofol has unique pharmacological properties, but recently retracted pharmacokinetic (PK) and pharmacodynamic (PD) evaluations make it difficult to formulate clear conclusions with respect to fospropofol's PK/PD properties. In safety and efficacy clinical studies, fospropofol demonstrated dose-dependent sedation with good rates of success at doses of 6.5 mg/kg along with good levels of patient and physician acceptance. Fospropofol has been associated with less pain at injection site than propofol. The most commonly reported side effects with fospropofol are paresthesia and pruritus. Fospropofol is a promising new sedation agent that appears to be well suited for MAC sedation, but further studies are needed to better understand its PK/PD properties as well its appropriate clinical role in outpatient procedures.

A Comparison of Fospropofol to Midazolam for Moderate Sedation During Outpatient Dental Procedures

“…[8][9][10][11] Sedation success rates of 87 to 89% for fospropofol have been cited, versus approximately 69% for midazolam. 5,9 Patient satisfaction was found to be 92.3% with fospropofol compared to 69.2% with midazolam, and physician satisfaction was almost 3 times higher with fospropofol. 5,9 To date, published studies have focused on comparing the 2 sedative agents during either colonoscopy or bronchoscopy procedures; the use of such drugs in dentistry has yet to be studied.…”

“…Due to the necessary enzymatic conversion, the blood concentration of propofol liberated from fospropofol increases at a slower rate, exhibits a longer duration, and does not reach the same peaks as direct injections of propofol. 1,5,6 The rate of increase of the liberated propofol depends more on the rate-limited metabolism of fospropofol than on the rate of the injection of the prodrug itself. 7 These pharmacokinetic properties retard the negative side effects of propofol and potentially create a wider margin of safety.…”

Medical, Political, and Economic Considerations for the Use of MAC for Endoscopic Sedation: Big Price, Little Justification?

“…Although sedation produced with fospropofol was dose-dependent and acceptable in the performance of GI endoscopy, its cardiac and respiratory side effects were largely similar. Further, even though the drug was devoid of any local pain on injection, it caused unacceptable perineal pain and pruritus [ 32 ]. The last hurdle was the same as with propofol.…”

A Double-Blind, Randomized, Multicenter, Dose-Ranging Study to Evaluate the Safety and Efficacy of Fospropofol Disodium as an Intravenous Sedative for Colonoscopy in High-Risk Populations

“…[1][2][3][4] During these procedures, the level of sedation should be titrated to minimize patient anxiety and risk of complications while maintaining a verbally responsive patient to allow for active cooperation during the procedure when needed. According to the American Society of Anesthesiologists (ASA) guidelines, moderate sedation requires that the patient be capable of a purposeful response to verbal or light tactile stimulation while maintaining ventilatory and cardiovascular function.…”