Septic shock-related deaths at U.S. hospitals increased during a 2011 shortage of a drug used to treat the condition, according to a study published in JAMA.
Drug shortage details
FDA in February 2011 announced a severe shortage of the drug, norepinephrine, used to treat septic shock. The agency said production issues at three manufacturing centers caused the shortage, which lasted a year.
For the study, the researchers looked at data on 27,835 adults with septic shock who were admitted to one of 26 U.S. hospitals affected by the shortage between 2008 and 2013. Before the shortage, the 26 hospitals treated at least 60 percent of septic shock patients with norepinephrine.
A hospital was classified as experiencing a shortage if its use of the drug decreased by more than 20 percent over three months. The study also excluded hospitals that had similar decreases before or after the shortage and included those that rebounded to near-baseline use after the shortage ended. Based on those standards, the researchers determined all 26 hospitals experienced a norepinephrine shortage for at least one quarter in 2011.
The researchers found a strong association between the drug shortage and increased mortality rates among patients with septic shock.
During times of shortage, the researchers found the risk of death among septic shock patients was 39.6 percent, compared with about 36 percent when hospitals were not experiencing a shortage. Moreover, the study used statistical techniques to compare mortality at shortage hospitals to non-shortage hospitals and found a similar association. The researchers said the difference likely represents hundreds of additional deaths.
The researchers could not determine why the risk of death increased. However, according to Reuters, the trend might be explained in part by the drug doctors' used as a replacement. The researchers found that while use of norepinephrine for septic shock patients decreased, use of the drug phenylephrine increased from about 36 percent to about 54 percent.
Senior author Hannah Wunsch of Sunnybrook Health Sciences Center in Toronto said though guidelines suggest use of dopamine to raise blood pressure if norepinephrine is not available, doctors might have used phenylephrine because it is not tied to rapid heartbeats. However, researchers have not studied phenylephrine as a replacement for norepinephrine when treating septic shock, Reuters reports.
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The researchers said longer wait times for patients who did receive norepinephrine for septic shock also might have influenced the mortality rate.
Wunsch said she hopes the findings draw attention to the topic of drug shortages and encourage people to address questions about sustaining drug pipelines.
Separately, Julie Donohue and Derek Angus, both of the University of Pittsburgh, in an accompanying editorial wrote that drug shortages commonly affect generic, sterile, injectable drugs like norepinephrine. "Put another way," they wrote, "shortages occur for drugs with low profit margins that require specialized production operations and high storage costs."
Donohue and Angus suggested several solutions for addressing drug shortages, including:
- Boosting stockpiles;
- Early warning systems;
- Having FDA provide information to purchasers about quality differences among manufacturers;
- Quick changes in professional guidelines about alternatives; and
- Setting production requirements for drugmakers (Boyles, MedPage Today, 3/21; Seaman, Reuters, 3/21; Vail et al., JAMA, 3/21; Bean, Becker's Hospital Review, 3/22; Donohue/Angus, JAMA, 3/21).
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