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Original Investigation
Caring for the Critically Ill Patient
April 11, 2017

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

Author Affiliations
  • 1Department of Anesthesiology, Columbia University, New York, New York
  • 2Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
  • 3Department of Neurology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
  • 4Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
  • 5Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts
  • 6Evans Center for Implementation and Improvement Sciences, Boston University School of Medicine, Boston, Massachusetts
  • 7Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 8Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
  • 9Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 10Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada
JAMA. 2017;317(14):1433-1442. doi:10.1001/jama.2017.2841
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.

Abstract

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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