The Effect of Opioid Dose and Route on Risk for Respiratory Depression

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The researchers’ goals were to evaluate the geographic differences of opioid administration and to examine how opioid administration was associated with respiratory depression.

Despite geographic variations in opioid dose and route, opioid-induced respiratory depression (OIRD) remains a common problem in medical and surgical units, according to a post hoc analysis of Prediction of Opioid-Induced Respiratory Depression in Patients Monitored by Capnography (PRODIGY) data, published in the Journal of Clinical Anesthesia.

Opioid treatment is commonly used to address pain in hospitalized patients, and it is the most common pharmacologic treatment for postoperative pain. However, this treatment modality may result in significant adverse events, including respiratory depression, which was reported in almost half of patients treated with parenteral opioids in the PRODIGY trial.

The objective of the current post hoc analysis was to assess the geographic variations in opioid dosing and route and to determine the association between opioid administration characteristics and the risk for OIRD.

The prospective observational study included 1335 patients treated with parenteral opioids in 16 general care medical (76 patients) and surgical (1259 patients) units in Asia, Europe, and the United States during the PRODIGY trial. Alarm-silenced continuous capnography and pulse oximetry monitoring were used to identify respiratory compromise events, defined as a respiratory rate of 5 breaths or less per minute, oxygen saturation of 85% or less, or end-tidal carbon dioxide of 15 or less or 60 mmHg or more for at least 3 minutes.

In addition, apnea episodes lasting more than 30 seconds and respiratory opioid-related adverse events were recorded.

Of all study participants, 220 (16%) patients received only short-acting opioids, 779 (58%) received only long-acting opioids, and 286 (21%) patients received a combination of short- and long-acting opioids following the medical procedure. The researchers observed significant geographical differences in opioid administration characteristics, including opioid types, dose, and delivery.

Of the 220 patients treated with short-acting opioids only, 119 patients (54%) experienced at least 1 episode of OIRD, as did 347 of the 779 (45%) patients receiving only long-acting opioids.

On multivariable analysis, several factors were associated with a significant reduction in OIRD, including postprocedure tramadol (odds ratio [OR], 0.62; 95% CI, 0.424-0.905; P =.0133) and postprocedure epidural opioids (OR, 0.485; 95% CI, 0.322-0.731; P =.0005).

Interestingly, OIRD did not change when patients were administered other drugs, such as benzodiazepines or gabapentinoids, concomitant with the opioids.

The study had several limitations, including an observational design, missing data on opioid administration times, the study cohort being limited to parenteral opioids, and heterogeneity in the opioid and concomitant medicine dataset.

“Our study demonstrates that there are varying opioid administration characteristics between Asia, Europe, and the United States, and OIRD remains a common problem on general care medical and surgical wards. Globally, OIRD still remains a common, often underreported problem on general care medical and surgical wards,” concluded the researchers.

Disclosure: This clinical trial was supported by Medtronic. Please see the original reference for a full list of authors’ disclosures.


Urman RD, Khanna AK, Bergese SD, et al. Postoperative opioid administration characteristics associated with opioid-induced respiratory depression: results from the PRODIGY trial. J Clin Anesth. Published online January 22, 2021. doi:10.1016/j.jclinane.2021.110167