Long-Term Detection of Propofol Glucuronide in Urine Following Anesthetic Induction and Maintenance with Propofol

Joseph Salerno,Joseph Jones,Charles Plate,Mary Jones,Douglas Lewis

doi:10.4236/pp.2013.47076

Abstract

Propofol is the most commonly used compound for the intravenous induction and maintenance of anesthesia. Propofol addiction and abuse have become causes for concern in the healthcare community, especially among anesthesia and surgical professionals. The US Drug Enforcement Administration does not list propofol on any Schedules and most hospitals do not have inventory controls in place to prevent its misuse. Propofol is detectable in blood plasma as the parent compound for as much as 15 hours post-anesthesia. The metabolite propofol glucuronide (PPFG) has been detected in blood and urine as far out as 60 hours. Here we report the long-term renal excretion of PPFG in specimens from A) four participants following a 14-day course of orally ingested propofol dosing, and B) a female patient following anesthetic induction and 15 minutes’ maintenance with propofol. Urinary PPFG was measurable well above limits of quantitation up to 6 days following oral ingestion and 28 days post-anesthesia. We also present a third set of data evaluating the likelihood of passive exposure to aerosolized propofol in the surgical environment by analyzing the levels of urinary PPFG of healthcare workers following operating room work shifts. The results presented here demonstrate that quantitation of PPFG in urinary samples is an efficient method of long-term screening for propofol misuse and abuse.

Highlights

Propofol (2,6-diisopropylphenol; Diprivan®, AstraZeneca Pharmaceuticals) is a fast-acting, short-duration, hypnotic agent that is administered intravenously for the induction and maintenance of general anesthesia [1]
Creatinine secretion from muscles is relatively constant in an individual, and Propofol glucuronide (PPFG) concentrations were normalized to 100 mg/dL creatinine levels to correct for differences in urinary production and flow-rate by the patient resulting from fluctuations in hydration levels [16]
Bleeker et al (2008) hypothesized that renal reuptake, presumably following release from sequestration in deep tissues, and subsequent renal glucuronidation play a major role in terminal elimination of propofol, and the results presented here suggest their hypothesis is worth closer pharmacokinetic investigation [8], though glucuronidation may just as likely occur by the hepatic pathway after rerelease

Summary

Introduction

Propofol (2,6-diisopropylphenol; Diprivan®, AstraZeneca Pharmaceuticals) is a fast-acting, short-duration, hypnotic agent that is administered intravenously for the induction and maintenance of general anesthesia [1]. With a quick recovery time following induction and minimal side effects [2], propofol has become the most widely used compound for intravenously administered general anesthesia [3]. Not traditionally seen as a drug of abuse, non-procedural misuse of propofol by anesthesiology and surgical healthcare professionals with direct access to the compound has become a cause for concern [6]. The fatality hazard of propofol abuse owes in great part to the compound’s extremely narrow window of safety resulting from the rapid onset of unconsciousness during administration. Propofol is not scheduled with the US Drug Enforcement Administration and 71% of surveyed anesthesia programs have no control system in place to secure and account for propofol supplies [6]

Results

Discussion

Conclusion