Kevin Ahern, MD, a chief hospitalist for Sound Physicians, has never before experienced the kind of drug shortages as have occurred in the last year or so.
They have involved mainstay treatment drugs, like the anesthetic propofol, for which access has become so limited at times that other drugs were prescribed for patients on mechanical ventilators, said Dr. Ahern, who practices at Springfield Regional Medical Center and Mercy Memorial Hospital in western central Ohio.
For now, the propofol crisis has eased, said Dr. Ahern, speaking in early August. But that shortage has been replaced by other worries, including difficulties in obtaining acetylcysteine—key to treating acetaminophen overdoses—and intravenous trimethoprim-sulfamethoxazole (Bactrim), relied upon to treat pneumocystis pneumonia in patients with HIV. The ongoing series of shortages “make me a little bit nervous,” he said.
The drugs in limited or non-existent supply can vary from week to week, and even across regions of the country. But the number of medications affected—many of them injectable drugs vital to hospital treatment—has steadily increased, in some cases undermining patient care, according to hospital physicians and pharmacists.
The scope of the problem
Last year, 211 shortages were reported compared with 166 in 2009 and 149 in 2008, according to data compiled by the University of Utah Drug Information Service.
As of August 25th of this year, 194 shortages had been identified, on pace to surpass last year's record.
“The duration of a lot of these shortages also has been longer than it has been in the past,” said Cynthia Reilly, director of the practice development division of the American Society of Health-System Pharmacists (ASHP).
In response, clinicians have set up alternate treatment protocols, programmed alerts into their electronic health systems, and restricted drugs to patients with the greatest need. Hospitals that are part of larger systems sometimes share supplies across facilities. Clinicians also admit to some internal drug hoarding, with 58% reporting having taken that step, according to a 2010 survey of more than 1,800 clinicians conducted by the nonprofit Institute for Safe Medication Practices in Horsham, Pa.
A more recent survey, conducted by the University of Michigan Health System and ASHP in late 2010, found that many of the unavailable drugs were frequently used on hospital floors. The three most often cited included epinephrine injections, dextrose syringes, and succinylcholine, according to the survey results, published online in July in the American Journal of Health-System Pharmacy.
“What's most concerning is that the drugs we are talking about are medications that are used for acute life-threatening situations,” said Burgunda Sweet, PharmD, senior author of the survey results and director of drug information and medication use policy at the University of Michigan Health System. “They are not your run-of-the-mill product, where you can potentially have an easy substitute or you have time necessarily to identify a substitute.”
When the succinylcholine supply became tight at University of Michigan, steps were taken to restrict its use to a few categories of patients, including trauma patients who required urgent intubation, Dr. Sweet said. Other neuromuscular blockers can be used, but they might not work as quickly and thus aren't ideal during crises, she said. “Even if it takes just a couple of minutes longer to act, that's a couple of minutes that you don't have airway access to that patient.”
Dr. Sweet was monitoring about 40 drugs that required some type of action plan to cope with an ongoing shortage. Development of a plan, though, can sometimes be complicated by uncertainties. The drug supplier may provide a “squishy time frame or a time frame that you don't have confidence in,” she said. In those cases, clinicians adopt a particularly conservative approach, designed to reserve remaining drugs for those with the greatest clinical need for as long as possible.
Nearly every U.S. hospital has been affected by the shortages, with 99.5% reporting at least one shortage during the prior six months, according to a June survey of 820 facilities conducted by the American Hospital Association. More than four out of five hospitals (82%) reported that treatment was delayed as a result and 17% said those delays occurred frequently.
In Camden, N.J., Cooper University Hospital ran out of norepinephrine this spring, something that Phil Dellinger, MD, an intensivist and sepsis expert, could never have envisioned prior to this year. The drug is the optimal one for patients in septic shock, said Dr. Dellinger, director of the hospital's critical care division. “It's the only drug we have in our armamentarium that increases the pump function in septic shock and that is very unlikely to be associated with [heart] arrhythmias,” he said.
Cooper clinicians learned in May that they couldn't order any more of the drug, at which point they had roughly a week's supply, said Quinn Czosnowski, PharmD, a clinical pharmacist at the hospital who works primarily in the intensive care unit.
Clinicians developed alternate treatment protocols and immediately took steps to drastically restrict the remaining norepinephrine supply to stretch it, Dr. Czosnowski said. The worst stretch lasted about a month, he said. As of late summer, the drug was available but still in limited supply.
At the University of New Mexico Health Sciences Center, hospitalist Peggy Beeley, ACP Member, has been closely watching deteriorating access to key electrolytes, such as calcium chloride. “I think that may get to a point of crisis,” said Dr. Beeley, who chairs the hospital's medication safety committee. “At least in our institution, we have not gotten to that point yet. We all have concerns that it will happen.”
Along with potentially being less effective, a substitute drug can impact patient treatment in other ways, according to the Institute for Safe Medication Practices. Clinicians may be less familiar with the new drug, including its dosage strength and side effects, raising the risk of errors. In the institute's survey of 1800-plus clinicians last year, about one in four reported medication errors related to a drug shortage and one in five reported some type of related harm to the patient.
According to an analysis of 2010 shortages, one of the primary causes has been problems identified with drug quality or manufacturing processes, a pattern that persists into 2011, said Valerie Jensen, RPh, associate director of the FDA's Drug Shortage Program. Meanwhile, the number of companies making these drugs has declined, she said. So there aren't necessarily other manufacturers to fill the gap while quality concerns are being addressed.
Manufacturers do sometimes provide FDA officials with advance warning regarding a potential shortage, providing the federal agency the opportunity to take steps in the hope of avoiding one, Ms. Jensen said. Last year, 38 potential shortages were averted in that way.
In some cases, when it's feasible, FDA officials have located an overseas supplier to provide some drug, once they verify that the quality meets FDA standards, Ms. Jensen said. Propofol was thus imported from November 2009 through August 2010. As of mid-August, seven drugs were being imported, including leucovorin and norepinephrine injections.
Whether they're notified by the FDA or in-house colleagues, as soon as hospital clinicians learn of supply problems, they quickly convene to develop alternate treatment plans and related strategies. Sometimes an alert is programmed into the electronic medical record system, with an automatic drug substitution suggested, Dr. Beeley said. “We can't do that for all of them because it would just be too time consuming for our pharmacy IT person, because they [the drugs in short supply] change so frequently,” she said.
When propofol became scarce, the hospitals where Dr. Ahern practices decided to conserve it for short-term sedation during surgical procedures rather than expending the limited supply on more prolonged use, such as for patients needing mechanical ventilation.
For patients on ventilation, one alternative was to use fentanyl infusions in combination with lorazepam (Ativan), Dr. Ahern said. That combination had some drawbacks, though, including the longer duration of lorazepam. The drug also can have a cumulative effect, potentially causing a drowsiness hangover feeling for patients with prolonged use, Dr. Ahern said.
With septic shock patients at Cooper University Hospital, the alternate treatment approach depended upon the individual patient's risk factors, Dr. Dellinger said.
For example, dopamine became one of the go-to drugs, he said. But if patients had excessive tachycardia or developed arrhythmias related to the dopamine, clinicians instead might have tried a low dose of vasopressin or a standard dose of phenylephrine, he said.
Dr. Dellinger said that he doesn't know of any patient care effects directly related to the lack of norepinephrine, such as a sepsis patient developing tachycardia from an alternate drug. Still, it's difficult to know for sure, given how sick the patients already are, with some dying despite the best treatment efforts, he said.
Norepinephrine wasn't the only example in recent months of the absence of an equivalent alternative drug, said Dr. Czosnowski. By mid-August, he was particularly concerned about the lack of intravenous trimethoprim-sulfamethoxazole. “It's a drug of choice and we don't have any,” he said. “We can't get any.”
Clinicians can prescribe the oral version of the antibiotic, but it's not typically absorbed as well if a patient is critically ill, according to Dr. Czosnowski. Other alternatives are second-line intravenous antibiotics, which are not believed to be as effective or may cause more toxic effects.
Currently, manufacturers are not required to notify FDA officials about pending shortages. Ms. Jensen encourages physicians to contact the agency if they see a drug access problem developing that's not listed on the website. “Unfortunately sometimes that's the first report that we see,” she said.
Congressional legislation also has been introduced this year that includes a notification requirement. But the heads up, albeit helpful for planning purposes, doesn't ease the problem itself, clinicians point out.
Will adapting to drug shortages become a chronic part of their job description? “This is a really bad week to ask me that question,” said Dr. Sweet with a weak laugh. At least, she said, the public is now more aware of the extent and severity of the problem.
The FDA is doing everything it can, but is limited in its authority, Ms. Jensen said. “We are very hopeful that we will see some light at the end of the tunnel, but we're not seeing it yet,” she said. “We are still seeing severe shortages.”