FDA Rejects ACG Petition: Propofol Remains in Realm of Anesthesia
If the FDA has anything to say about it, the black box warning on the labeling for propofol, indicating that the agent should be administered only by those who are trained in the administration of general anesthesia and not involved in the procedure, will remain intact.
In mid-August, the FDA sent a letter of denial to Richard M. Cooper, Esq., the lawyer who filed a petition on behalf of the American College of Gastroenterology (ACG) requesting that propofol’s warning label be removed.
The ACG’s petition, which was submitted to the FDA in June 2005, stated that the warning was neither warranted nor appropriate, and included 31 publications in support of the ACG’s claim that gastroenterologists and supervised nurses can safely administer propofol without training in general anesthesia administration.
The FDA did not find the ACG’s argument compelling, and concluded that the warning label is appropriate in light of the risks associated with propofol. The agency stated that it will not seek to have the label removed or amended in any way.
“I was pleased that the FDA talked about the nature of the drug, and about the level of skill required to use it safely, given the high variability in patient response,” said Alexander A. Hannenberg, MD, immediate past president of the American Society of Anesthesiologists (ASA), Newton-Wellesley Hospital, in Newton, Mass. “But they placed at least as much emphasis on the inherent problems with operator-administered sedation.”
Three Main Concerns
The FDA’s 12-page letter goes to great lengths in rebutting the ACG’s petition, but the agency’s arguments against removing the black box can be broken down into three main issues of concern, explained Lawrence B. Cohen, MD, associate professor of medicine, Mount Sinai School of Medicine, in New York City.
“Their first point pertains to the continuum of sedation,” Dr. Cohen said. “While conceding that some upper endoscopies and colonoscopies can be performed with moderate sedation, they claim that many patients require deep sedation, at least transiently, during the course of an endoscopic examination,” he explained. “That simply is untrue.”
The FDA’s second concern is the risk that a deeply sedated patient may slip into general anesthesia due to propofol’s narrow therapeutic window.
“While this is a theoretical concern, a vast amount of data indicates that trained endoscopists, assisted by experienced nursing personnel, can safely administer propofol to patients undergoing routine endoscopic procedures,” Dr. Cohen said. “The clinical outcome data are supported by three studies demonstrating that propofol, when combined with an opioid and a benzodiazepine, can be reliably titrated to moderate sedation with little risk of deeper levels of sedation.”
The third concern is that practitioners administering propofol should be appropriately trained in the management and rescue of patients at all levels of anesthesia, “and that individuals administering propofol not be involved in the conduct of the procedure,” Dr. Cohen said. It is this third issue that prompted the Centers for Medicare & Medicaid Services (CMS) last year to refuse reimbursement to providers in Medicare settings—hospitals and Medicare-approved ambulatory care centers—who do not comply with their position on who should deliver propofol—that is, a qualified anesthesia provider.
“More than anything else, that is at the heart of the issue—who is administering sedation and monitoring the patient,” Dr. Hannenberg commented. “Medicare’s conclusion, though not explicitly stated, was that the gastroenterologist who performs the endoscopy cannot be administering the anesthesia—meaning that the endoscopy nurse’s role becomes critical, and the FDA decision placed enormous emphasis on that point.”
As Dr. Cohen interprets the situation, however, the problem centers on how the target level of endoscopic sedation is defined.
“I believe that the vast majority of endoscopists target moderate sedation, not deep sedation. Therefore, FDA’s concerns about the risks of deep sedation and general anesthesia are unwarranted,” Dr. Cohen said.
“The thing [that the FDA doesn’t] recognize here is that you don’t need to produce deep sedation or anesthesia to provide a patient undergoing endoscopy with a satisfactory endoscopic experience,” Dr. Cohen said. “There is good amnesia at moderate levels of sedation, so that a patient can be responsive during a procedure, but have no recollection of the procedure or of pain.”
FDA Ruling May Carry Less Weight Than CMS Decree
The FDA’s decision should not be much of a surprise. The agency has made it clear over the past three years that it considers deep sedation to be exclusively the domain of anesthesiologists.
Although cost containment is currently one of the hottest concerns among all parties in health care, “the FDA is not concerned with health care economics,” Dr. Cohen remarked. “Their responsibility is to examine all of the scientific evidence available, and to base their decisions upon data with no consideration for the cost implications.”
The cost of employing an anesthesiologist for endoscopic procedures varies regionally, but Dr. Cohen estimates it adds about $500 to the cost of a procedure, on average.
At this point, it is not clear whether the FDA’s regulatory position will have much of an impact on practice. In contrast, the CMS policy, which influences payer policies, does seem to have had an effect.
“I’ve spoken to about 15 colleagues around the country who were practicing endoscopist-directed propofol [sedation], and 11 have changed their sedation practice since the CMS’s policy was achieved in December 2009,” Dr. Cohen said, noting that his office-based endoscopy program has been phasing out endoscopist-directed propofol in order to remain in compliance with state and federal guidelines and to avoid jeopardizing its accreditation.
But the battle is not over yet—16 states have opted out of federal policy mandating that an anesthesiologist be present to oversee propofol administration by a certified registered nurse anesthetist (CRNA).
“If you practice in an opt-out state, instead of needing an anesthesiologist present for each case, you can use a CRNA,” Dr. Cohen explained.
According to Dr. Hannenberg, the controversy surrounding propofol administration will remain unresolved until the gastroenterology community addresses the key issues behind the CMS policy, the FDA’s stance, the Institute for Safe Medication Practices’ position, “and on down the line, including the ASA,” he said. “The problem is there is no attention being paid to what the training and qualifications of a gastroenterologist are for this kind of practice, or of the nurse who is supporting the gastroenterologist.
“My feeling is that [gastroenterologists] shouldn’t expect anything to change until those issues are addressed in a rigorous way that addresses the need for a safe framework for the use of the drug and the administration of sedation,” Dr. Hannenberg said.