Drug Shortages and Septic Shock: Not a Good Mix

Greg Martin, MD


June 28, 2017

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

Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H
JAMA. 2017;317:1433-1442

Septic Shock Management During the 2011 Norepinephrine Shortage

In the United States, septic shock occurs in over 200,000 people and leads to over 40,000 deaths each year.[1] Drug shortages have become more common in the past decade, but the consequences are rarely examined.

Vail and colleagues sought to determine whether shortages of the common vasopressor norepinephrine in 2011 led to changes in patient care and clinical outcomes. Their retrospective cohort study used data from 26 US hospitals with a baseline rate of norepinephrine use of at least 60% for patients with septic shock. Shortage was defined as any 3-month interval in 2011 when norepinephrine use declined by at least 20%. The cohort included adults with septic shock admitted to study hospitals between July 1, 2008, and June 30, 2013.

Among 27,835 critically ill patients with septic shock, norepinephrine use declined from 77% before the shortage to a low of 55.7% during the shortage. Phenylephrine was the most frequently substituted vasopressor (baseline, 36.2%; peak, 54.4%). Hospital admissions for septic shock during quarters of shortage were associated with increased in-hospital mortality compared with admissions during quarters of normal use (39.6% vs 35.9%, respectively; adjusted odds ratio, 1.15; P = .03).

The authors concluded that patients with septic shock in US hospitals affected by the 2011 norepinephrine shortage had higher in-hospital mortality.


Drug shortages are an increasing problem and may be particularly problematic in the intensive care unit and critically ill patients because of the acuity of appropriate treatment.[2] The authors took the opportunity associated with the severe shortage of norepinephrine in 2011 to see whether shortages of this common and critical drug had implications for patients who needed it to treat septic shock. As the authors appropriately conclude, the norepinephrine shortage observed in 17% of hospitals may have contributed to at least hundreds of excess deaths in a short period.

It's interesting to speculate why patients were more likely to die during this shortage. For example, is the next most commonly used drug, phenylephrine, sufficiently less effective that patients died of shock? Or is phenylephrine use associated with other adverse effects that led to more deaths? The authors were unable to determine why the excess deaths occurred, and without that knowledge, we can only guess as to what may be the cause. Regardless, this reminds us as clinicians to be vigilant for drug shortages and mindful of what we choose as substitute drugs when shortages occur.



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