The effect of acute exposure to morphine on breathing variability and cardiopulmonary coupling in men with obstructive sleep apnea: A randomized controlled trial

Abstract

Opioid‐related deaths from respiratory depression are increasing but there is only limited information on the effect of morphine on breathing during sleep. This study aimed to detect and quantify opioid‐induced cardiorespiratory pattern changes during sleep in obstructive sleep apnea (OSA) patients using novel automated methods and correlate these with conventional polysomnography (PSG) measures. Under a randomized double‐blind placebo‐controlled crossover design, 60 male OSA patients attended two one‐night visits to the sleep laboratory, at least a week apart. Either a 40‐mg controlled‐release oral morphine dose or placebo was administered. Breathing during sleep was measured by standard in‐laboratory PSG. We analysed the inter‐breath interval (IBI) from the PSG flow channel to quantify breathing irregularity. Cardiopulmonary coupling (CPC) was analysed using the PSG electrocardiogram (ECG) channel. Following the consumption of morphine, the 60 OSA patients had fewer breaths (p = .0006), a longer inter‐breath interval (p < .0001) and more irregular breathing with increased IBI coefficient of variation (CV) (p = .0015) compared to the placebo night. A higher CPC sleep quality index was found with morphine use. The change of key IBI and CPC parameters was significantly correlated with the change of key PSG sleep‐disordered breathing parameters. In conclusion, 40 mg controlled‐release morphine resulted in a longer breathing cycle and increased breathing irregularity but generally more stable sleep in OSA patients. The significant links between the IBI and CPC techniques and a range of PSG sleep‐disordered breathing parameters may suggest a practical value as surrogate overnight cardiorespiratory measurements, because both respiratory flow and ECG can be detected by small portable devices.

Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

“…Thus, OIRD involves reduced spiking during the percolation phase due, in part, to suppression of intrinsically driven pre-inspiratory spiking of Oprm1+ neurons and de-recruitment of neurons with synaptically driven, pre-inspiratory spiking activity. Thus, we predict that opioidinduced suppression of preBötC activity during the percolation phase underlies the prolonged and irregular durations between inspiratory efforts that are characteristic of OIRD in both mice and humans (Walker et al, 2007, Wu et al, 2020, Varga et al, 2020.…”

The influence of acute morphine use on obstructive sleep apnea: A systematic review and meta‐analysis

“…A total of 201 studies published before May 24, 2021, were identified through literature searching. Seven studies were retained for review after preliminary screening (Blake, Yew, Donnan, & Williams, 2009; Martins et al,2020; Rowsell et al, 2019, 2020; Tomazini Martins, Carberry, Gandevia, Butler, & Eckert, 2018; Wang et al, 2013; Wu et al, 2020), and three studies ( n = 132 patients) were deemed suitable for meta‐analysis (Blake et al, 2009; Rowsell et al, 2019; Wang et al, 2013; Figure 1).…”

“…Of the seven articles, two studies examined respiratory load detection, load magnitude perception, tactile sensation, and OSA phenotypes but not the outcome variables of interest (Martins et al,2020; Tomazini Martins et al, 2018,). Of the other five studies, two studied the same population (Rowsell et al, 2020; Wu et al, 2020) and examined breathing variability, cardiopulmonary coupling, and genetic variance but not the outcomes of interest.…”

Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

“…Thus, OIRD involves reduced spiking during the percolation phase due, in part, to suppression of intrinsically driven pre-inspiratory spiking of Oprm1+ neurons and de-recruitment of neurons with synaptically driven, pre-inspiratory spiking activity. Thus, we predict that opioid-induced suppression of preBötC activity during the percolation phase underlies the prolonged and irregular durations between inspiratory efforts that are characteristic of OIRD in both mice and humans (Walker et al, 2007, Wu et al, 2020, Varga et al, 2020).…”