Although opioids exert immunomodulatory effects, which are beneficial in many instances, they may be harmful in others, especially when sepsis is involved.

In a recent study, reported at the annual meeting of the American Society of Anesthesiologists in New Orleans in 2022, Heyman et al extracted index hospitalizations from 2009 to 2015 meeting any of 3 validated International Classification of Diseases, Ninth Revision sepsis criteria from the MarketScan Research Databases.

The primary outcome of the study was in-hospital mortality, including discharge to hospice, in patients who had chronically consumed large amounts of opioids (morphine milligram equivalents, or MME, in excess of 20).

The final analytical data set comprised 883,358 encounters. The majority of patients (53.2%) were male, with a median age of 45 years. Baseline morphine milligram equivalents were categorized as either 20 to 49, 50 to 89, or 62 to 90+, in accordance with the Centers for Disease Control and Prevention (CDC) guidance regarding risk strata.

Patients with 180 days of continuous insurance coverage before admission were included in the analysis. Outpatient opioid prescriptions were summarized by MME values. Daily oral MME values were calculated from prescription drug claim information and summed into a maximum 90-day rolling average over a 180-day period. Patients with no baseline opioid use were compared with those who consumed a daily average of at least 20 MME before admission.

Compared with patients who had no prescribed baseline MME (n = 775,212), those who were prescribed at least 20 MME before admission (n = 108,146) had more severe comorbid illness with an overall unadjusted mortality rate for the entire cohort of 3.7%. Among individuals who were prescribed at least 20 MME before admission (6.9%), it was even higher than for those not taking any opioids at baseline (3.2%).

Logistic regression was adjusted for possible confounding variables, including age, sex, known drug abuse, comorbidities, explicit coding for sepsis, intensive care unit admissions, respiratory failure, and major surgery. After adjusting for such covariates, all 3 examined strata of outpatient MME were independently associated with escalating odds of in-hospital mortality.

The researchers noted that each baseline MME group was associated with an approximately 50% increased risk of mortality from sepsis relative to those patients who were not taking opioids at baseline. Although the 3 MME groups were not statistically significantly different in terms of in-hospital mortality from sepsis, there appeared to be a dose-dependent relationship in those taking the highest doses who had the greatest risk of mortality.

Commenting on the research, T. Anthony Anderson, PhD, MD, professor of anesthesiology, perioperative and pain medicine at Stanford University School of Medicine in California, noted that the results are not surprising as the long-term effects of opioids are poorly understood. He remarked that it is an extremely important topic, especially in light of the changes that the CDC has made to opioid-prescribing guidelines, part of relaxing restrictions on opioid prescribing.

Health care professionals should continue to minimize the risk of chronic opioid use by optimizing acute pain management, adding nonopioid analgesics in a multimodal fashion, researching technologies and therapeutics for pain management with widespread dissemination of relevant findings, and further investigation of additional adverse outcomes from chronic opioid use. (See Heyman et al. ASA Annual Meeting, New Orleans 2022, Abstract A 2001. Adapted from a report by Michael Vlessides, Anesthesiology News, February 28, 2023.)