# Prediction and early recognition of opioid-induced respiratory depression

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2022 · $238,500

## Abstract

ABSTRACT
Opioids are the most commonly-used and effective drugs in the management of moderate to severe
postoperative pain, but they have numerous adverse effects, the most serious being opioid-induced respiratory
depression. An important and consistent finding in studies of opioid-induced respiratory depression is the
highly variable risk across patient age, gender and co-morbidity profile. Identifying patients at highest risk of
opioid-induced respiratory depression in the perioperative setting may help target enhanced monitoring
(including hospital admission) and preventative strategies aimed at reducing adverse outcomes including
respiratory complications and death. Changes in the central drive to respiratory muscles including the
diaphragm are expected to impact the full range of ventilatory behaviors accomplished. It is essential to
recognize that respiratory muscles are important in both sustaining ventilation and performing higher-force
behaviors necessary for maintaining airway patency. Respiratory muscles accomplish a range of motor
behaviors with forces generated for ventilatory behaviors comprising only a small fraction of their maximal
force generating capacity. Thus, impairments in respiratory muscle function may not become clinically manifest
despite substantial loss of functional reserve until ventilation is impaired. Monitoring for opioid effects on higher
force behaviors may reveal patients with greater susceptibility to opioid-induced respiratory depression. Our
working hypotheses are that opioid-induced respiratory depression limits the generation of higher forces by
the diaphragm muscle, and that the early recognition of an individual patient’s response to opioids will help
identify those at greatest risk for respiratory complications. Exciting recent studies support the utility of
ultrasound-based shear wave elastography for measurements of diaphragm muscle function, but there is
limited information available about their utility in healthy (not critically-ill) patient populations, or opioid effects.
Two specific aims are proposed: 1) To test the hypothesis that shear wave elastography (SWE) reliably
measures the range of forces generated by the diaphragm muscle, in relation to state-of-the-art respiratory
function testing; and 2) To test the hypothesis that opioid-induced respiratory depression limits the range of
forces generated by the diaphragm muscle, identifying a sub-population of patients potentially at greater risk
for respiratory complications. We expect that the proposed studies in this novel application will determine the
dose-dependent effect of opioids across a range of ventilatory and higher-force behaviors and the utility of
SWE-based measurements of diaphragm muscle activity in the early recognition of patients displaying opioid-
induced respiratory depression. Ultimately, the proposed work will help predict patients at greater risk for
opioid-induced respiratory depression and permit assessment of the impact...

## Key facts

- **NIH application ID:** 10426828
- **Project number:** 1R21DA055848-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Carlos B Mantilla
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,500
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426828

## Citation

> US National Institutes of Health, RePORTER application 10426828, Prediction and early recognition of opioid-induced respiratory depression (1R21DA055848-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426828. Licensed CC0.

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