# Opioid-associated modulation of respiratory-related cortical activity in dyspnoeic mechanically ventilated patients: An electroencephalographic study

## TL;DR

This study shows that opioids can reduce breathlessness in ICU patients and affect brain activity related to breathing.

## Contribution

The study demonstrates that opioids modulate respiratory-related cortical networks beyond general effects on brain activity.

## Key findings

- Opioids reduced dyspnoea without significant sedation in ventilated ICU patients.
- Opioids modulated low and high beta power bands in respiratory-related cortical activity.
- These effects were specific to breathing and not observed in random EEG segments.

## Abstract

Dyspnoea is frequent in mechanically ventilated patients and contributes to substantial distress and a heightened risk of post-traumatic stress disorder. It attests to respiratory-related brain suffering that must be actively managed. This is particularly challenging in noncommunicative patients, hence the interest of electroencephalographic surrogates. This study aims at characterizing the effects of opioids, proposed to relieve dyspnoea, on respiratory-related cortical activity in mechanically ventilated patients.

In a 16-bed intensive care unit (ICU) over a 4-month period, we consecutively included eighteen mechanically ventilated patients with self-reported dyspnoea (visual analog scale –VAS–, communicative patients) or an observation-derived suspicion of respiratory-related brain suffering (noncommunicative patients, respiratory distress observation scores –RDOS–) persisting despite ventilator settings optimisation. Participants underwent electroencephalographic (EEG) recordings before and after administration of intravenous opioids. Respiratory-related cortical activity was assessed using covariance-based connectivity analysis, preinspiratory potentials (PIPs), and time-frequency analysis (TFA) time-locked to inspiration. To disentangle respiratory-specific from general effects of opioids, TFA was also computed from randomly selected EEG segments.

Opioids reduced dyspnoea evaluated by VAS and RDOS without significant sedation. EEG covariance analysis showed changes in brain state in 15 of 18 patients. PIP occurrence was variable and not modulated by opioids. TFA revealed statistically significant opioid-induced modulations in low beta and high beta power bands time-locked to inspiration, not observed in randomly timed analyses hence a specific effect of opioids on respiratory-related cortical networks.

Opioids can relieve dyspnoea in mechanically ventilated ICU patients and modulate respiratory-related cortical activity beyond their general effects on cortical electrogenesis. This suggests that their effects on breathing control are not limited to brainstem mechanisms.