Fentanyl-Associated Overdose Deaths Outside the Hospital

TO THE EDITOR:

In March 2022, 12-month drug-overdose fatalities reached their highest recorded level in the United States, with an estimated 110,360 deaths.¹ Changes in the illicit drug supply during the pandemic have resulted in more fentanyl-associated overdose deaths.² The potency of fentanyl and the rapidity of onset of its effect have the potential to increase overdose mortality, especially among people who are unable to receive timely medical care.

We used cause-of-death data from the National Center for Health Statistics³ to evaluate drug-overdose deaths that occurred outside the hospital before the Covid-19 pandemic as compared with deaths that occurred during the early years of the pandemic (2016 through 2021). Overdose deaths were categorized according to whether they involved a synthetic opioid other than methadone (primarily fentanyl),⁴ another opioid without fentanyl, or no opioid. The place of death was categorized as outside a hospital or in a hospital or other medical setting, and we calculated the annual incidence of death per million U.S. population. Poisson regression models were used to calculate changes in mortality. We used Joinpoint statistical software to perform regression analysis to identify changes in trends in the percentage of out-of-hospital overdose deaths in each drug category.⁵ Details regarding the methods and data analysis used in the study are available in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

We found that overdose deaths increased during the early pandemic period and were driven primarily by out-of-hospital deaths that were associated with fentanyl, which increased from 46.6 per million in 2016 to 178.0 per million in 2021, a 282% increase (95% confidence interval [CI], 275 to 289) (Fig. 1). In 2016, 74.1% of all overdose deaths occurred outside the hospital, a percentage that increased to 78.0% in 2020 and 78.6% in 2021. Deaths occurred outside the hospital in 83.0% of fentanyl overdoses in 2021, as compared with 76.1% of opioid-overdose deaths without fentanyl involvement and 67.8% of overdose deaths that did not include opioids. The proportion of out-of-hospital deaths increased for fentanyl overdoses (annual percent change, 1.6%; 95% CI, 1.1 to 2.0) at the same time that the proportions remained similar for other opioid overdoses (annual percent change, 0.1%; 95% CI, −0.2 to 0.3) and nonopioid overdoses (annual percent change, −0.3%; 95% CI, −1.1 to 0.5). Additional data regarding yearly overdose deaths, changes in incidence, and place of death are provided in Tables S1 through S4 in the Supplementary Appendix.

Figure 1. Trends in Drug-Overdose Deaths, According to Location and Drug Type.

Shown are the number of deaths from drug overdoses per 1 million U.S. population from 2016 through 2021, a period that encompassed the years immediately before and after the start of the Covid-19 pandemic.

Joinpoint regression analysis identified changes in trend in the proportion of overdose deaths that occurred outside the hospital for each drug category during the first and second years of the pandemic. The increase in out-of-hospital overdose deaths during the early years of the Covid-19 pandemic suggests that drug overdoses had increased in severity because of the increasing involvement of fentanyl.