Anesthesia drug shortage shrinks margin of safety

Anesthesiologists are concerned about the shortage of key drugs needed for patients during surgery

March 29, 2001 Web posted at: 2:27 PM EST (1927 GMT) In this story: Close calls Drugs without substitutes Shortages are national What's causing the shortages? RELATED STORIES, SITES

By Rhonda Rowland CNN Medical Unit ATLANTA, Georgia (CNN) -- Patients may not be getting preferred anesthetic drugs when they're being put to sleep for surgical procedures. Anesthesiologists say supplies of some key drugs have dried up without warning, raising concerns about patient safety.

The supply of anesthesia took another hit Thursday, when an injectable anesthesia drug was voluntarily recalled, following reports of five deaths.

The manufacturer of Raplon received reports that the drug may be associated with bronchospasm, an inability to breathe normally, and notified anesthesiologists and hospital pharmacies, the U.S. Food and Drug Administration said in a statement.

Organon Inc., based in West Orange, New Jersey, voluntarily withdrew the drug, rapacuronium chloride, which was used as a muscle relaxant during the placement of breathing tubes for surgery.

However, the FDA said Raplon was already in short supply and was being used by very few doctors. Also, other drugs are available to replace it, so the withdrawal "does not affect the overall availability of anesthesiology drugs," the agency said.

But physicians remain concerned about the shortage.

"It was inconceivable that this could happen," said Dr. John Neeld, chairman of anesthesiology at Atlanta's Northside Hospital and past president of the American Society of Anesthesiologists. "In November I was told we had a 3-day supply of the drug fentanyl. We had to discontinue use immediately and reserve the drug for our obstetric patients needing epidurals and for the treatment of postoperative pain."

Four months later the hospital continues to ration fentanyl. The drug is used routinely in surgery, but is also useful for epidurals.

RESOURCES For more information on drug shortages:

FDA: Center for Drug Evaluation and Research American Society of Health-System Pharmacists "Since we had to reserve fentanyl for our obstetric patients, we had to use older drugs such as narcotics like morphine," said Dr. David Birnbach, director of obstetrical anesthesia at St. Luke's-Roosevelt Hospital in New York. "These older drugs are safe, but not as desirable, since patients must stay in recovery longer."

As a result, some hospitals are experiencing overcrowding in surgical recovery rooms, causing logistical problems.

"It's diminished our safety margin," said Neeld. "Patients are staying in the recovery room for long periods of time; they're taking longer to wake up. When the recovery room is full, we can't bring in more patients. With some of these alternative drugs our recovery nurses have to be more attuned for respiratory problems."

Close calls One in ten pharmacists who responded to a survey conducted by the Institute for Safe Medication Practices (ISMP) reported problems related to the use of various fentanyl alternatives. They included six reports of over-sedation or overdoses, three of which required CPR. There were two reports each of phlebitis, hypotension, itching and hallucinations. There were also 14 reports of an overall increase in patients' recovery time, length of stay, and nausea and vomiting.

The ISMP, a non-profit group representing pharmacists, also reported two serious dosing errors that occurred when a particular drug called sufentanil was used as a substitute for fentanyl. In both cases the errors were due to look-alike packaging and nurses' mistaken belief that the two drugs were the same product. One patient developed respiratory arrest and a second patient became unresponsive and required drug treatment.

Fentanyl, commonly used in surgery, is in short supply in some parts of the U.S.

"Sufentanil has a bit shorter duration of action and is more potent than fentanyl," said Dr. William Lanier, an anesthesiologist at the Mayo Clinic and editor-in-chief of Mayo Clinic Proceedings. "There can be medication errors because some providers may not be as familiar with the drug. There is also a lot of art involved in figuring out the right dose for individual patients."

Lanier said more experienced anesthesia providers will find it easier to transition to drug substitutes, but there's concern about those who have not had extensive training with older drugs.

There's also been a close call with succinylcholine, according to the ISMP. A pharmacy expecting a specific dose of the drug from Abbott Laboratories received a strength not commonly used in hospitals. The two vials and labels look very similar. If the more concentrated dose had been dispensed unnoticed, there could have been serious harm to the patient, experts said. The hospital is unsure if the drug was incorrectly ordered or if Abbott sent the only strength available.

Drugs without substitutes When a patient must be put to sleep quickly, there's no better drug than succinylcholine.

"This is 'the' drug for emergency situations," said Birnbach, "and it's in short supply."

Thirty seconds after administration of the drug, which works as a muscle relaxant, a thin breathing tube can be inserted down a patient's throat, allowing the anesthesiologist to breathe for the patient. The fast action of the drug prevents patients from aspirating, which can cause dangerous complications including pneumonia.

"Without succinylcholine a patient's life could be in jeopardy," said Birnbach. "I'm talking death."

Anesthesiologists said alternatives to succinylcholine are inferior since they may be slower acting and more expensive. At the Mayo Clinic in Rochester, Minnesota, pharmacologists have been forced to develop alternatives or repackage drugs to the lowest tolerable dose.

"At Mayo we have great laboratory support and can work around the shortage pharmacologically," said Lanier, "but I wonder what other hospitals across the country are doing."

Cost is another consideration. While succinylcholine costs about $1.00 a dose, some alternatives cost as much as $30.00 a dose.

Shortages are national There are no precise figures on how many hospitals are feeling the pinch with the anesthesia shortage, but doctors said it's been felt across the country. Earlier this month, the fentanyl shortage reached a crisis level in Seattle and New York, but has since eased. In Atlanta, doctors are experiencing overcrowded recovery rooms. The Mayo Clinic in Rochester, Minnesota has found succinylcholine to be in short supply, but Northside Hospital in Atlanta has not felt the squeeze.

"Based on our survey, the shortages have been experienced in multiple locations," said Dr. Bruce Cullen with the American Society of Anesthesiologists. "In some cases, hospitals can get the drugs, but they're not able to obtain the sizes and strengths they typically use, which increases the risk of dosing errors." Anesthesiologists are not the only doctors grappling with shortages. There's a shortage of tetanus vaccine, and last year there were delays in production of flu vaccine. A drug used to induce labor and reduce bleeding during childbirth, oxytocin, was in short supply.

Abbott Laboratories has exhausted its emergency supply of Isuprel, a drug used to treat cardiac arrest. According to the U.S. Food and Drug Administration's Web site, which lists drugs in short supply, the pharmaceutical company is cooperating with the federal agency to secure the ingredients needed to resume manufacturing.

Succinylcholine is the drug normally used in emergency situations as a muscle relaxant

There's also a growing problem with unavailability of certain injectable steroids.

"This is a concern since a lot of these medications are alternatives for each other," said Joe Deffenbaugh, with the American Society of Health-System Pharmacists (ASHP). The ASHP also operates a Web site listing drug shortages.

"I've been in anesthesia for 20 years and have seen one or two drugs in short supply," said Lanier, "but I've never seen anything like this. There have been more drugs in short supply in the last 10 weeks than in the last two decades."

What's causing the shortages? There's no single reason for the shortages or why some drugs become unavailable practically overnight, without warning.

"Who blew it?" asked Birnbach.

The reason for the fentanyl shortage was an unexpected increase in demand for the product, according to the FDA.

"How could that be? We haven't increased the number of operations we do overnight," said Birnbach. "Next time, patients could be in jeopardy. We need safeguards. This was a close call."

Abbott Laboratories blamed the increased demand for fentanyl on one of the suppliers leaving the market. The pharmaceutical company doubled its production, but some hospitals may still find the product on backorder.

"Manufacturers know when they're going to have shortages," said Deffenbaugh, "but they're not forthcoming with the information."

Deffenbaugh said the causes range from difficulties in getting raw materials, which often come from overseas, to consolidation in the pharmaceutical industry.

Abbott Laboratories said that's the case with its drug Isuprel. The bulk drug needed for the product is no longer being made by its supplier, so Abbott worked with the FDA to identify another supplier.

"We're concerned there's a trend toward critical drugs being made by just one company. When companies merge, some products are discontinued for a variety of reasons," explained Deffenbaugh.

Some anesthesiologists believe shortfalls may be driven by the need for profits. When drugs come off a patent, they might not produce enough revenue for the pharmaceutical company. Decisions are made to put those resources into more profitable drugs.

"When I see something not explainable, I have to look at the bigger picture," said Neeld. "Private industry (is) not interested in serving the larger public good."

Sometimes drugs are replaced by better ones. For instance, Novartis Pharmaceuticals stopped making Mesantoin, an anticonvulsant, because it said there were better alternatives on the market and it was no longer widely prescribed.

On March 5th, the American Society of Anesthesiologists requested a meeting with the FDA, Drug Enforcement Agency, Pharmaceutical Research and Manufacturers of American (PhRMA) and several drug manufacturers in an attempt to end the shortage.

"We'd like to know if something's changed," said Deffenbaugh. "Has the FDA increased inspections, have they increased in rigor, are new testing methods being used that are more sensitive in picking up problems?"

The PhRMA, a trade association representing large pharmaceutical companies, said it doesn't get involved with shortages. The unavailability of critical drugs is the result of individual decisions based on marketing or shortages of raw materials, it said.

The FDA's role in stopping the drug shortage is limited. The agency has tried to determine which critical drugs are at risk of being in short supply by finding alternative suppliers, and has encouraged smaller companies to take on the products that larger ones are no longer interested in manufacturing.

So far, the fact-finding meeting has not been scheduled.

"How did this happen?" asked Lanier. "How can it be resolved? If it's not, I'm very concerned about what could happen in the future." www.cnn.com/2001/HEALTH/0...index.html

-- Carl Jenkins (somewherepress@aol.com), March 30, 2001

Answers

A summary of observations by an engineer in January of 2001 may well shed light on the root causes of some of the problems that are becoming evident in the pharmaceutical industry, not to mention other sectors. The summary is a result of an exchange I had with an engineer who has direct knowledge of IT and embedded control system problems in the field. Here is a excerpt from the summary:

"I said that I have been hearing about shortages in the pharmaceutical industry and asked (the engineer) if he thought this might be related to (Y2K-related) problems (involving) manufacturing processes. He said that there are manufacturing problems and that too many bugs have slowed manufacturing processes. He added that there is a major shortage of computer components and that the parts that are available are often parts that have been put back in stock even though they do not work. He said he has found the same to be the case when it comes to other technology companies and parts vendors...."

~ From 1/30/2001 Summary of an Engineer's Observations Regarding the Status of Ongoing Y2K-Related Embedded Systems and Complex Integrated Systems Problems Compiled by Paula Gordon (With a minor revision made 2/1/2001)

[The Summary of an Engineer's Observations..." is now posted at http://www.gwu.edu/%7Ey2k/keypeople/gordon/EngObs.html The summary focuses on problems of the sort that were predicted prior to the January 1, 2000 rollover have been occurring in a wide range of sectors. This summary of observations of an engineer provides abundant clues concerning the possible causes of problems that are evident in the energy sector and in other sectors as well.]

-- Paula Gordon (pgordon@erols.com), March 30, 2001.