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Propofol Thriller Or Killer Lewis Mccarver, MS, CRNA Marcia Spear, ACNP-BC, CPSN, CWS

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Propofol Thriller Or Killer Lewis Mccarver, MS, CRNA Marcia Spear, ACNP-BC, CPSN, CWS PSN200050.qxd 2/15/10 11:33 PM Page 29 CE Propofol Thriller or Killer Lewis McCarver, MS, CRNA Marcia Spear, ACNP-BC, CPSN, CWS nown by the proprietary name Diprivan or its generic court documents, Murray gave Jackson only 25 mg K name propofol, this anesthetic drug is among the of propofol on the night of the star’s death. But 25 most widely used sedatives in the United States. Propofol mg is less than the dosage required to anesthetize has a unique pharmacologic profile, making it an ideal someone and keep him or her asleep, several drug for use in plastic surgery nursing. Propofol is utilized experts have said (Yoshino, 2009). This article will discuss the indications, adverse effects, and actions as an anesthetic induction agent and sedative during of propofol. many plastic surgeries. This article explores indications, pharmacokinetics, adverse effects, and potential abuse of propofol. PROPOFOL ABUSE Six months ago most lay people had no idea what Propofol is not a controlled substance and is main- propofol was, what it was used for, or even if it was ly used in operating rooms, procedure rooms, and a drug. However, since Michael Jackson’s untimely intensive care units. Propofol abuse was originally death a few short months ago, the notoriety of limited to anesthesia professionals who have ready propofol has climaxed. If Michael Jackson’s death access to the drug. With a self-administered intra- was related to the administration of the powerful venous dose, propofol offers effects ranging from a anesthetic propofol, then he must have been inject- brief sense of well-being to unconsciousness with- ed with more propofol than his personal physician out any “hangover.” Propofol’s brief effects, quick reportedly told police he gave to Jackson, medical metabolism, and no “hangover” offer specific experts have said. According to court records advantages for use in operating rooms, yet propofol unsealed in Houston on August 24, 2009, Dr. Conrad poses a narrow therapeutic index for abusers. Murray told police that he had given Jackson 50 mg Propofol’s potency and narrow dose range leave lit- of propofol each night over a 6-week period. In a tle margin for error and provide effects ranging 3-hr interview with police, Murray said on the night from euphoria to unconsciousness and apnea. of Jackson’s death, the physician gave him a com- Abusers of propofol are powerless to fight effects of bination of benzodiazepines before yielding to the drug and may injure themselves immediately Jackson’s demands for more propofol. According to after self-administration by falling. In 1989, the Food and Drug Administration approved propofol Lewis McCarver, MS, CRNA, Nurse Anesthetist, Vanderbilt University Medical Center, and Monroe Carroll Children’s Hospital, with little thought of its potential abuse. Yet even Nashville, Tennessee, and Assistant Program Administrator, Middle before the Michael Jackson media coverage, the Tennessee School of Anesthesia, Madison. Food and Drug Administration was petitioned to Marcia Spear, ACNP-BC, CPSN, CWS, Nurse Practitioner and make propofol a controlled substance. Propofol has Certified Wound Specialist, Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. addictive potential and may cause intense dreams, amorous behavior, and hallucinations. The authors have no conflict of interest. Propofol is supplied in a 1% solution, providing Address correspondence to Lewis McCarver, MS, CRNA, Vanderbilt University Medical Center, D-4207 Medical Center North, Nashville, 10 mg of drug in an aqueous solution of 10% soy- TN 37232 (e-mail: [email protected]). bean oil, 2.25% glycerol, and 1.2% egg phosphatide. Plastic Surgical Nursing ❙ January-March 2010 ❙ Volume 30 ❙ Number 1 29 PSN200050.qxd 2/15/10 11:33 PM Page 30 Propofol is a substituted isopropylphenol with the INDICATIONS FOR PROPOFOL chemical name of 2,6-diisopropylphenol. Why has propofol become a popular drug for Appropriate use of propofol is as an induction anesthesia? Propofol has the most rapid and com- drug for anesthesia, especially in outpatient plastic plete awakening of any induction drug, rendering it surgery settings, when rapid wakeup is desirable. ideal for use in plastic surgery. The most important Propofol doses for anesthesia induction are 1.5–2.5 advantage of propofol is the rapid return of con- mg/kg. Induction doses are often given incremen- sciousness with minimal residual central nervous tally to avoid hypotension. For induction of anes- system effects. thesia, a dose of 1.5–2.5 mg/kg produces blood lev- els of 2–6 ␮g/ml, which produce unconsciousness. Children need greater doses up to 2.5–3.5 mg/kg PHARMACOKINETICS OF PROPOFOL due to larger central distribution volumes and greater clearance rates. The elderly need smaller Propofol interacts with ␥-aminobutyric acid doses due to smaller central distribution volumes (GABA), the principal inhibitory neurotransmitter. and smaller clearance rates. A 1.5–2.5 mg/kg dose GABA receptors are large macromolecules exclu- of propofol has equal potency to 4–5 mg/kg sively located in the central nervous system that thiopental or 1.5 mg/kg methohexital. contain physically separate receptor sites for a Propofol may be given by continuous infusion variety of drugs including propofol, benzodi- for conscious sedation during plastic surgery pro- azepines, and alcohol. Propofol exerts its pharma- cedures performed utilizing local anesthesia. Con- cologic effects by interaction with GABA receptors sciousness sedation doses range from 25 to 100 located in the reticular activating system, the ␮g/kg/min and produce minimal analgesia effects, chemoreceptor trigger zone, and the medullary and so time should be allowed for local anesthetics to pontine ventilatory centers. Other body systems are work before surgical incision when using propofol without GABA receptors, thus limiting propofol sedation. Significant amnesia effects and the reduc- activity to the central nervous system. Propofol tion of postoperative nausea and vomiting make causes a slower rate of dissociation of GABA from the use of propofol beneficial in plastic surgery. receptors, and an increased duration of GABA-acti- Propofol’s short context sensitive 1/2 time and vated opening of chloride channels resulting in effect site equilibration provide easy titration dur- hyperpolarization of cell membranes, resulting in ing plastic surgery procedures, allowing levels of sedation, unconsciousness, and centrally mediated sedation to be adjusted according to clinical ventilatory depression. demands. Clearance of propofol from plasma is due to rapid Propofol sedation may be supplemented with hepatic and extra-hepatic metabolism and tissue benzodiazepines or opioids necessitating a lower uptake by the vessel rich group. Hepatic metabolism dose of propofol. Propofol provides control of the of propofol is rapid and extensive with less than 0.3% stress response and possesses anticonvulsant and excreted unchanged in urine. The metabolism rate of amnesia properties. Postoperative nausea and propofol exceeds hepatic blood flow rates, confirm- vomiting is reduced when propofol is given any- ing extra-hepatic metabolism sites. Metabolites, time during an anesthetic induction. Small doses excreted in the urine, are all pharmacologically may be effectively used in the postanesthesia inactive, water-soluble sulfate and glucuronic acid care unit, especially if the nausea and vomiting is compounds. not vagal in origin. Propofol treats nausea and Propofol’s elimination 1/2 time is 0.5 to 1.5 hr. vomiting in doses that do not produce sedation, The context sensitive 1/2 time (time of a single com- that is, a 10-mg bolus followed by 10 ␮g/kg/min partment plasma concentration reduction by 50%) is infusion. Subhypnotic propofol doses are even less than 40 min for infusions. The length of a propo- effective against chemotherapy-induced nausea fol infusion does not significantly alter context sen- and vomiting. sitive 1/2 time. Propofol metabolism is so rapid that Propofol has a unique profile of central nervous as soon as propofol leaves tissue storage sites it is system depression. Propofol uniformly depresses broken down so plasma concentrations do not central nervous system structures including subcor- increase. tical areas where propofol’s anti-emetic actions may Propofol has a short effect-site equilibration, be exerted. Propofol has a direct depressant effect which means that a dose of propofol provides a on the vomiting center, although the mechanism is rapid onset of effects. There is no impairment of unclear. Propofol in 10-mg doses treats pruitis. The propofol elimination with cirrhosis or renal failure. mechanism by which propofol treats pruitis is Propofol crosses the placental barrier but is rapidly unclear, perhaps because of decreased segmental cleared from fetal circulation. spinal cord activity. 30 Plastic Surgical Nursing ❙ January-March 2010 ❙ Volume 30 ❙ Number 1 PSN200050.qxd 2/15/10 11:33 PM Page 31 SIDE EFFECTS OF PROPOFOL be avoided by using large veins for injection, opi- oids, and xylocaine. The incidence of phlebitis with Propofol has anti-convulsant properties due to propofol administration is less than 1%. GABA-mediated pre- and postsynaptic inhibition. Propofol decreases cerebral metabolic oxygen CONCLUSION requirements, cerebral blood flow, and intracranial pressures. Large propofol doses may reduce blood Could a 25-mg dose of propofol have caused the pressure enough to lower cerebral perfusion
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