Since its introduction more than 20 years ago, propofol emulsion has become the sedative of choice for many ambulatory anesthesia providers. But recent manufacturing issues, recalls and legal woes have slowed production of the drug to a trickle. Let's take a look at the current state of the shortage, what you can do to deal with it and how to prepare for the possibility of life without propofol. First, here's a review of the drug's former and current manufacturers.

• Hospira. Baxter's propofol formulation (currently licensed to Hospira) was the first generic to hit the market. In the spring of 2009, Hospira announced an FDA recall of several lots that contained stainless steel shavings in some vials, which were blamed on production problems. The company temporarily shut down propofol production in early 2009, but manufacturing began again by the end of the year. Hospira announced a large recall again last May, citing the presence of microscopic metal particles in some batches. Currently, there is no word on when production will resume.
• Teva Pharmaceutical Industries. In the spring of 2009, microbial contamination led to the recall of several of Teva's propofol lots, which the company blamed on manufacturing problems. Teva shut down production and addressed the issues with the hope of resuming by the beginning of 2010. Unfortunately, the company discovered additional contaminated lots a few months later. Then in late May 2010, Teva announced the permanent end to its propofol production after being ordered to pay $500 million in damages to a patient who contracted hepatitis C in 2008 when vials of the drug were reused at a Las Vegas endoscopy center.
• APP Pharmaceuticals. Diprivan by AstraZeneca, the original propofol formulation, is currently manufactured by APP Pharmaceuticals. It is the only company producing and shipping propofol in the United States at this time. While APP Pharma was previously supplying an estimated 25% of the propofol consumed in the U.S., it is now producing the drug 24 hours a day and drop-shipping production runs to keep up with the current demand.

The alternatives
The days of inexpensive, plentiful supplies of propofol may be over. Options do exist, however, that will let us continue to provide safe, quality anesthetic care. Here are a few alternatives to a propofol-based sedation regimen.

• Intravenous agents. Without mentioning the various "cocktails" that many providers favor, most have embraced replacing the propofol component with other intravenous agents such as etomidate, pentothal or methohexitol, while leveraging the additive effects of benzodiazepines, opioids, low-dose ketamine (0.5mg/kg to 1.0mg/kg) and non-steroidals. This approach lets providers continue with total intravenous anesthesia in settings where volatile agents would be impractical. On the other hand, side effects and recovery profiles are not as favorable for these agents, meaning you'll have to anticipate dealing with decreased case throughput and decreased patient or surgeon satisfaction.
• Inhalation agents. The real propofol equivalent agents are the volatile anesthetics, led by the commonly used sevoflurane and desflurane — 2 effective, short-acting drugs. When used in conjunction with a propofol induction, the agents' resources are conserved and their benefits leveraged. However, they are known to cause a higher incidence of PONV, and environmental issues persist related to the difficulty in capturing waste gas in the OR.
• Alpha-2 agonists. Clonidine has long been recognized as an effective adjunct to general anesthesia. Some providers embrace its sedative- and blood-pressure-stabilizing effects, while others find the oral dosing imprecise and inconvenient and complain of hypotension and prolonged recoveries.

Dexmedetomidine is a promising new intravenous sedative that has been used in the ICU for years. Recently, the FDA approved its use during invasive procedures. It's a very effective sedative, especially in conjunction with varying doses of the other intravenous agents. Also, it has an opioid-sparing effect and is an effective option for use on patients at higher risk for PONV. Disadvantages include its prolonged recovery profile and relatively high cost.

• Fospropofol disodium. Lusedra by Eisai Pharmaceuticals is the newest intravenous sedative-hypnotic agent to receive FDA approval for intravenous sedation. Fospropofol is literally propofol phosphate. The addition of the phosphate group renders this a water-soluble molecule. As a result, fospropofol does not need to be suspended in a lipid emulsion, which avoids the production issues propofol manufacturers are currently experiencing.

Fospropofol has a delayed onset (3 to 5 minutes) and a prolonged duration (10 to 15 minutes). The drug's respiratory and cardiovascular profiles are very favorable to propofol, but there's limited data on the utility of this drug in the hands of qualified anesthesia providers.

Fospropofol appears to be much more expensive than propofol. In the current marketplace, a 20cc vial of propofol emulsion costs between $7 and $8, while a 30cc vial of fospropofol costs approximately $25. It appears that 30cc of Lusedra is approximately equivalent to 60cc of propofol emulsion. Studies examining the drug's use in various patients during various procedures are underway.

• Regional anesthesia and awareness monitoring. Leveraging nerve blocks provides effective anesthesia and post-operative pain relief while helping to spare intravenous agents. Brain monitoring devices designed and FDA-approved to monitor depth of sedation have also been shown to reduce drug use and speed recovery.