Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing

Abstract

Background: Chronic opioid therapy for pain management has increased dramatically without adequate study of potential deleterious effects on breathing during sleep.

Methods: A retrospective cohort study comparing 60 patients taking chronic opioids matched for age, sex, and body mass index with 60 patients not taking opioids was conducted to determine the effect of morphine dose equivalent on breathing patterns during sleep.

Results: The apnea-hypopnea index was greater in the opioid group (43.5/h vs 30.2/h, p < .05) due to increased central apneas (12.8/h vs 2.1/h; p < .001). Arterial oxygen saturation (SpO2) in the opioid group was significantly lower during both wakefulness (difference 2.1%, p < .001) and non-rapid eye movement (NREM) sleep (difference 2.2%, p < .001) but not during rapid eye movement (REM) sleep (difference 1.2%) than in the nonopioid group. Within the opioid group, and after controlling for body mass index, age, and sex, there was a dose-response relationship between morphine dose equivalent and apnea-hypopnea (p < .001), obstructive apnea (p < .001), hypopnea (p < .001), and central apnea indexes (p < .001). Body mass index was inversely related to apnea-hypopnea index severity in the opioid group. Ataxic or irregular breathing during NREM sleep was also more prevalent in patients who chronically used opioids (70% vs 5.0%, p < .001) and more frequent (92%) at a morphine dose equivalent of 200 mg or higher (odds ratio = 15.4, p = .017).

Conclusions: There is a dose-dependent relationship between chronic opioid use and the development of a peculiar pattern of respiration consisting of central sleep apneas and ataxic breathing. Although potentially significant, the clinical relevance of these observations remains to be established.

Figures

Figure 1

Rate ratio for morphine dose equivalent and obstructive apnea, central apnea, and hypopnea indexes; all adjusted for weight, sex, and age. REM refers to rapid eye movement sleep; NREM, non-rapid eye movement sleep.

Figure 2

Rate ratios from the Poisson regression analyses for apnea-hypopnea index for body mass index (kg/m2) (BMI) adjusted for age and sex, as well as morphine dose equivalent (mg), in the opioid group.

Figure 3

A 120-second period from a 32-year-old female (A) opioid patient, body mass index 22 kg/m2, morphine dose equivalent 375 mg, and apnea-hypopnea index 67/hour (A) compared with a 32-year-old female (B) control subject with a body mass index 23 kg/m2 and apnea-hypopnea index 5/hour.

Figure 4

Respiratory patterns during 300 seconds of non-rapid eye movement (NREM) stage 2 sleep in a 32-year-old woman with a body mass index of 22 kg/m2 and a morphine dose equivalent of 375 mg, breathing room air and 2 L/min oxygen. Note the ataxic respiration and brief respiratory pauses lasting less than 10 seconds under both breathing conditions.

Figure 5

Adaptation of part 1 and 2 of a pneumograph of the original depiction of Biot's respiration (Contribution a 1'ètude de phènomène respiratoire de Cheyne-Stokes. Lyon Mèd; 1876;). Note respiratory variability in frequency and depth.