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Sleep, Pain, and Breathing

Hillman, David R. MB

doi: 10.1213/ANE.0000000000000666
Editorials: Editorial

From the Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Australia.

Accepted for publication January 13, 2015.

Funding: No external funding.

Conflicts of Interest: See Disclosures at the end of the article.

Reprints will not be available from the author.

Address correspondence to David R. Hillman, MB,, Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Australia. Address e-mail to

Sleep and pain have a difficult, multidimensional relationship. Pain disturbs sleep.1–4 Disturbed sleep aggravates pain.5–8 Treatment of sleep disorders can reduce pain.9 Relieving pain can improve sleep although, as shown by Correa and colleagues10 in this issue of Anesthesia & Analgesia, where opioids are involved this is not uniformly the case.

Sleep is a vulnerable state for breathing. Ventilatory drive is reduced because of loss of the stimulatory effects of wakefulness, accompanied by reduction in hypercapnic and hypoxic responsiveness. Sleep depresses muscle activation, reflex gain, and arousal responses. These changes are more prominent in rapid eye movement than non-rapid eye movement sleep. Upper airway obstruction and/or hypoventilation occur in predisposed subjects.11 This makes sleep of enormous relevance to anesthesiologists, as these state-related physiological changes are also present during anesthesia. Knowledge of breathing behavior during sleep is helpful in predicting likely behavior under drug-induced sedation. Furthermore, it is important to appreciate the potential for sleep to potentiate the effects on breathing of drugs that depress ventilatory drive.12

It is only now that these relationships are becoming widely appreciated. In a 1997 consensus statement, the American Academy of Pain Medicine and American Pain Society took it upon themselves to announce that “withholding the appropriate use of opioids from a patient who is experiencing pain on the basis of respiratory concerns is unwarranted.”13 They did so because they contended “it is now accepted by practitioners of the specialty of pain medicine that respiratory depression induced by opioids tends to be a short-lived phenomenon, generally only occurs in the opioid-naive patient and is antagonized by pain.” Predictably, the number of opioid prescriptions written exploded in the years that followed. Sadly, so did the number of opioid-related deaths. The compounding effects of sleep on the ventilatory depressant effects of opioids were not considered at the time of the statement. This appears to have been a fatal flaw in the guidance.12

The review of Correa et al.10 helps make this clear. As they point out, adequate breathing during wakefulness does not provide any assurance that it will be adequate during sleep. This wake-sleep dichotomy in breathing behavior is self-evident in the case of snoring and obstructive sleep apnea (OSA). While more subtle, it is also evident with sleep hypoventilation and central sleep apnea, the particular focus of the article by Correa et al..10 The stimulatory effect of wakefulness on ventilation and muscle activation acts both to ensure a patent upper airway and to augment ventilatory drive and dampen oscillations in it. It has long been understood that the breathing periodicity (Cheyne-Stokes ventilation) associated with heart failure is more prominent during sleep than wakefulness. So, it appears, is breathing periodicity from other causes including those associated with neurologic disease, high altitude, and opioid use.14–17

Opioids have complex effects on breathing that are particularly prominent (and may only be clinically evident) during sleep. They reduce upper airway muscle activation, predisposing to snoring and upper airway obstruction (i.e., OSA).18 They depress hypoxic and hypercapnic ventilatory drive, particularly in opioid-naive subjects, leading to hypoventilation.19 With chronic opioid use, breathing periodicity becomes evident, particularly if doses are high.16,17 This breathing periodicity can take the form of regular waxing and waning of ventilatory drive or more ataxic breathing patterns with irregularly placed central apneas and hypopneas. While common among chronic opioid users, the mechanism of this periodicity is not well understood. Teichtahl et al.20 present some evidence to suggest that the mechanism may relate to chronic opioid use changing the balance between hypoxic and hypercapnic ventilatory drive. With chronic opioid use, hypoxic ventilatory drive may recover, or even be augmented, while the opioids still depress hypercapnic ventilatory drive. If so, this would help explain recurrent periods of under-breathing terminated by augmentation of ventilation once stimulated by sufficient hypoxemia.

The review of Correa et al.10 is a timely reminder that the relationships among sleep, anesthesia, and breathing go well beyond consideration of OSA and its perioperative implications. Awareness of sleep-related breathing disorders and their physiologic basis helps inform anesthesiology practice. The presence of such disorders indicates increased vulnerability to breathing disturbances when under the influence of opioids and sedative drugs. Conversely, observation of these disturbances in patients not previously known to have a sleep-related breathing disorder should alert anesthesiologists in their role as perioperative physicians to that possibility.

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Name: David R. Hillman, MB.

Contribution: This author wrote the manuscript.

Attestation: David R. Hillman approved the final manuscript.

Conflicts of Interest: David R. Hillman received honoraria from ResMed, received research funding from ResMed, received honoraria from Philips Healthcare, and received honoraria from SomnoMed.

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Dr. David R. Hillman is the Section Editor for Respiration and Sleep Medicine for Anesthesia & Analgesia. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. Hillman was not involved in any way with the editorial process or decision.

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