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Association Between US Norepinephrine Shortage and Mortality Among Patients With Septic Shock

Educational Objective
To learn whether a national shortage of a vasopressor used for patients with septic shock was associated with an increase in mortality.
1 Credit CME
Key Points

Question  Was there an association between the 2011 US norepinephrine shortage and mortality among adults with septic shock?

Findings  In this cohort study of 27 835 patients with septic shock admitted to 26 hospitals, phenylephrine use significantly increased during 3-month periods of active norepinephrine shortage. Compared with hospital admission with septic shock during periods of normal use, admission during hospital periods of shortage was associated with an increased rate of in-hospital mortality (35.9% vs 39.6%, respectively).

Meaning  The US norepinephrine shortage was significantly associated with increased mortality among patients with septic shock.


Importance  Drug shortages in the United States are common, but their effect on patient care and outcomes has rarely been reported.

Objective  To assess changes to patient care and outcomes associated with a 2011 national shortage of norepinephrine, the first-line vasopressor for septic shock.

Design, Setting, and Participants  Retrospective cohort study of 26 US hospitals in the Premier Healthcare Database with a baseline rate of norepinephrine use of at least 60% for patients with septic shock. The cohort included adults with septic shock admitted to study hospitals between July 1, 2008, and June 30, 2013 (n = 27 835).

Exposures  Hospital-level norepinephrine shortage was defined as any quarterly (3-month) interval in 2011 during which the hospital rate of norepinephrine use decreased by more than 20% from baseline.

Main Outcomes and Measures  Use of alternative vasopressors was assessed and a multilevel mixed-effects logistic regression model was used to evaluate the association between admission to a hospital during a norepinephrine shortage quarter and in-hospital mortality.

Results  Among 27 835 patients (median age, 69 years [interquartile range, 57-79 years]; 47.0% women) with septic shock in 26 hospitals that demonstrated at least 1 quarter of norepinephrine shortage in 2011, norepinephrine use among cohort patients declined from 77.0% (95% CI, 76.2%-77.8%) of patients before the shortage to a low of 55.7% (95% CI, 52.0%-58.4%) in the second quarter of 2011; phenylephrine was the most frequently used alternative vasopressor during this time (baseline, 36.2% [95% CI, 35.3%-37.1%]; maximum, 54.4% [95% CI, 51.8%-57.2%]). Compared with hospital admission with septic shock during quarters of normal use, hospital admission during quarters of shortage was associated with an increased rate of in-hospital mortality (9283 of 25 874 patients [35.9%] vs 777 of 1961 patients [39.6%], respectively; absolute risk increase = 3.7% [95% CI, 1.5%-6.0%]; adjusted odds ratio = 1.15 [95% CI, 1.01-1.30]; P = .03).

Conclusions and Relevance  Among patients with septic shock in US hospitals affected by the 2011 norepinephrine shortage, the most commonly administered alternative vasopressor was phenylephrine. Patients admitted to these hospitals during times of shortage had higher in-hospital mortality.

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Article Information

Corresponding Author: Hannah Wunsch, MD, MSc, Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Ave, Room D1.08, Toronto, ON M4N 3M5, Canada (hannah.wunsch@sunnybrook.ca).

Published Online: March 21, 2017. doi:10.1001/jama.2017.2841

Author Contributions: Dr Gershengorn had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Vail and Gershengorn are co–first authors.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Vail, Gershengorn, Hua, Walkey, Wunsch.

Drafting of the manuscript: Vail, Rubenfeld, Wunsch.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Vail, Gershengorn, Hua, Rubenfeld, Wunsch.

Supervision: Wunsch.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Walkey reported receiving a grant from the National Institutes of Health and personal fees from UpToDate. Dr Hua reported receiving grants from the National Institute on Aging and the American Federation for Aging Research. No other disclosures were reported.

Funding/Support: This study was supported by funds from the Herbert and Florence Irving Scholars Program at Columbia University (Dr Wunsch).

Role of the Funder/Sponsor: The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentation: This article was presented at the 37th International Symposium on Intensive Care and Emergency Medicine; March 21, 2017; Brussels, Belgium; and was presented as an abstract at the 46th Critical Care Congress of the Society of Critical Care Medicine; January 23, 2017; Honolulu, Hawaii.

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