Remifentanil Inhibits Rapid Eye Movement Sleep but Not the Nocturnal Melatonin Surge in Humans

Bonafide, Christopher P.; Aucutt-Walter, Natalie; DiVittore, Nicole A.; King, Tonya S.; Bixler, Edward O.; Cronin, Arthur J.

doi:10.1097/aln.0b013e3181684bc3

Cited by 40 publications

(29 citation statements)

References 35 publications

(26 reference statements)

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“…To our knowledge, this is the first time melatonin secretion pattern is investigated under remifentanil infusion in critically ill patients. Nevertheless, our results are in line with the study by Bonafide et al, where melatonin secretion was investigated in healthy participants under sedation with remifentanil and found preserved [18]. The relatively small doses of remifentanil used in both studies may possibly explain the missing effect of remifentanil on melatonin secretion.…”

Section: Discussionsupporting

confidence: 92%

“…However, remifentanil was not found to have the same effect on acetylcholine as morphine and fentanyl in the study by Mortazavi et al [5]. Bonafide et al investigated the effect of remifentanil on sleep in healthy humans and found reduced REM sleep [18]. In line with this study, we only observed REM sleep in the epochs recorded under the period without remifentanil.…”

Section: Discussionsupporting

confidence: 81%

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Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study

Boyko

Holst

Jennum

et al. 2017

Critical Care Research and Practice

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Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin secretion and sleep patterns differed in these patients with and without remifentanil infusion. Eight patients were included. Blood-melatonin was taken every 4th hour, and polysomnography was carried out continually during a 48-hour period. American Academy of Sleep Medicine criteria were used for sleep scoring if sleep patterns were identified; otherwise, Watson's classification was applied. As remifentanil was periodically administered during the study, its effect on melatonin and sleep was assessed. Melatonin secretion in these patients followed a phase-delayed diurnal curve. We did not observe any effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p < 0.001) under remifentanil infusion. Rapid Eye Movement (REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 81%

Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study

Boyko

Holst

Jennum

et al. 2017

Critical Care Research and Practice

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“…Some believe that medications from the agonist/antagonist class, such as buprenorphine, may be less associated with the adverse effects of traditional μ-agonists; however, the present data indicate that the sleep-disrupting effects of buprenorphine are similar to those of other opioids. 26,30,37,53 The present results encourage studies designed to objectively quantify the effects of buprenorphine on sleep in humans.…”

Section: Discussionsupporting

confidence: 53%

“…52 The chronic effects of μ-opioid receptor agonists on sleep in pain patients are not completely understood. 39 Opioids cause sleep disturbance 4,37,53 and the present results demonstrate that buprenorphine increases wakefulness and disrupts the temporal organization of sleep (figs. 2-4).…”

Section: Discussionmentioning

confidence: 52%

“…There is good agreement between preclinical and clinical data that opioids disrupt sleep 37 , a finding confirmed by administering opioids to pain free humans. 53 The restorative effects of sleep require normal temporal organization of sleep. Unfortunately, morphine and fentanyl slow the electroencephalogram during wakefulness, increase lighter stage 2 NREM sleep, decrease stage 3 and 4 NREM sleep, and decrease or eliminate REM sleep.…”

Section: Discussionmentioning

confidence: 99%

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Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat

Gauthier¹,

Guzick²,

Brummett

et al. 2011

Anesthesiology

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Background Buprenorphine, a partial μ opioid receptor agonist and κ opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine levels in regions of the basal forebrain and pontine brain stem that regulate sleep. Methods Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep/wake states were recorded for 24 h. In additional rats buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while simultaneously measuring adenosine. Results An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in both nonrapid eye movement sleep (−22.1%) and rapid eye movement sleep (−3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative/hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine levels in the pontine reticular formation (−14.6%) and substantia innominata (−36.7%). Intravenous administration of buprenorphine significantly decreased (−20%) adenosine in the substantia innominata. Conclusions Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative/hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine levels in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.

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Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review

Iacovides

Kamerman

Baker

et al. 2021

Comprehensive Physiology

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We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep-wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pain-or drug-induced, negatively impacts quality of life, mental and physical health. In the context of chronic pain, poor sleep quality heightens pain sensitivity and may affect analgesic function, potentially resulting in further analgesic need. Clinicians already have to consider factors including efficacy, abuse potential, and likely side effects when making analgesic prescribing choices. We propose that analgesicrelated sleep disruption should also be considered. The neurochemical mechanisms underlying the reciprocal relationship between pain and sleep are poorly understood, and studies investigating sleep in those with specific chronic pain conditions (including those with comorbidities) are lacking. We emphasize the importance of further work to clarify the effects (intended and unintended) of each analgesic class to inform personalized treatment decisions in patients with chronic pain.

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Remifentanil Inhibits Rapid Eye Movement Sleep but Not the Nocturnal Melatonin Surge in Humans

Cited by 40 publications

References 35 publications

Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study

Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study

Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat

Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review

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