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A shortage several years ago of a drug used to treat a deadly infection known as septic shock was tied to an increase in deaths among patients with the condition, a new study shows.

The likelihood that hospitalized patients in septic shock would die was nearly 4 percentage points higher during the 2011 shortage of norepinephrine, compared to when hospitals had an adequate supply, researchers found.

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Norepinephrine, a so-called vasoconstrictor, raises blood pressure by causing blood vessels to constrict.

"There are a lot of things that happen for a shortage to occur," said senior author Dr. Hannah Wunsch, of Sunnybrook Health Sciences Center in Toronto. "They end up happening frequently."

Wunsch and colleagues write in JAMA that the U.S. Food and Drug Administration announced a severe shortage of norepinephrine in February 2011 due to production issues at three manufacturing centers. The shortage lasted a year.

For the study, the researchers analyzed data on 27,835 septic shock patients treated at 26 U.S. hospitals between 2008 and 2013. All of the hospitals treated at least 60 percent of their septic shock patients with norepinephrine before the shortage.

Hospitals were deemed to be experiencing a shortage of norepinephrine if their use of the drug dropped more than 20 percent over a three-month period.

Before the shortage, the drug was used in about 77 percent of septic shock patients at the 26 hospitals. Use fell to about 56 percent during the second quarter of 2011.

During times of shortage, the risk of death among septic shock patients was about 40 percent, compared to about 36 percent when hospitals weren't experiencing a shortage.

The researchers say the 4 percentage point difference likely represents hundreds of excess deaths among septic shock patients.

They can't explain why the risk of death increased during the drug shortage, but it may be due to the drugs doctors chose to use in place of norepinephrine.

For example, as norepinephrine use in patients with septic shock was decreasing, use of the vasoconstrictor drug known as phenylephrine rose from about 36 percent to about 54 percent.

Wunsch said that while guidelines suggest using dopamine to raise blood pressure if norepinephrine is not available, doctors may have used phenylephrine since it isn't tied to rapid heartbeats. Unfortunately, however, its use as a replacement for norepinephrine in septic shock hasn't been studied.

Her team says other issues, too, could explain the link between the drug shortage and the higher mortality. For example, patients who did receive the drug may have had to wait longer for it.

"You can't come to the firm conclusion that the alternative vasopressor was the problem, but it does point to problems in the system when there are shortages of medications like that," Wunsch said.

She hopes the new findings push the subject of drug shortages to the forefront and encourage people to revisit questions about sustaining drug pipelines.

In an editorial accompanying the new study, Julie Donohue and Dr. Derek Angus, both of the University of Pittsburgh, suggest five broad solutions to drug shortages, including early warning systems, rapid changes to professional guidelines about drug alternatives and expanded stockpiles of drugs.

Some of these approaches would "require major restructuring of the industry and its regulation," they write.

The new research was published to coincide with a presentation at the 37th International Symposium on Intensive Care and Emergency Medicine in Brussels.