Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans

Christopher P. Bonafide, Natalie Marie Aucutt-Walter, Nicole Divittore, Tonya King, Edward Bixler, Arthur J. Cronin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

BACKGROUND: Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. METHODS: Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 μg · kg · min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. RESULTS: Remifentanil inhibited rapid eye movement sleep (14.1 ± 7.2% to 3.9 ± 6.9%). The amount of slow wave sleep decreased from 6.8 ± 7.6% to 3.2 ± 6.1%, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. CONCLUSIONS: An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.

Original languageEnglish (US)
Pages (from-to)627-633
Number of pages7
JournalAnesthesiology
Volume108
Issue number4
DOIs
StatePublished - Jan 1 2008

Fingerprint

REM Sleep
Melatonin
Sleep
Opioid Analgesics
Capsules
Placebos
remifentanil
Polysomnography
Sleep Stages
Postoperative Pain
Hydrocortisone
Volunteers
Analysis of Variance
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Bonafide, Christopher P. ; Aucutt-Walter, Natalie Marie ; Divittore, Nicole ; King, Tonya ; Bixler, Edward ; Cronin, Arthur J. / Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans. In: Anesthesiology. 2008 ; Vol. 108, No. 4. pp. 627-633.
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abstract = "BACKGROUND: Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. METHODS: Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 μg · kg · min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. RESULTS: Remifentanil inhibited rapid eye movement sleep (14.1 ± 7.2{\%} to 3.9 ± 6.9{\%}). The amount of slow wave sleep decreased from 6.8 ± 7.6{\%} to 3.2 ± 6.1{\%}, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. CONCLUSIONS: An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.",
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Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans. / Bonafide, Christopher P.; Aucutt-Walter, Natalie Marie; Divittore, Nicole; King, Tonya; Bixler, Edward; Cronin, Arthur J.

In: Anesthesiology, Vol. 108, No. 4, 01.01.2008, p. 627-633.

Research output: Contribution to journalArticle

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N2 - BACKGROUND: Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. METHODS: Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 μg · kg · min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. RESULTS: Remifentanil inhibited rapid eye movement sleep (14.1 ± 7.2% to 3.9 ± 6.9%). The amount of slow wave sleep decreased from 6.8 ± 7.6% to 3.2 ± 6.1%, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. CONCLUSIONS: An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.

AB - BACKGROUND: Postoperative patients are sleep deprived. Opioids, commonly administered for postoperative pain control, are often mistakenly considered inducers of naturally occurring sleep. This study describes the effect of the opioid remifentanil on nocturnal sleep in healthy volunteers. In addition, this study tests the hypothesis that opioid-induced sleep disturbance is caused by a circadian pacemaker disturbance, reflected by suppressed nocturnal plasma concentration of melatonin. METHODS: Polysomnography was performed in 10 volunteers from 11:00 pm to 7:00 am for four nights at 6-day intervals. On two nights, remifentanil (0.01-0.04 μg · kg · min) was infused from 10:30 pm to 7:00 am, and either a placebo capsule or 3.0 mg melatonin was administered at 10:30 pm. On two additional nights, saline was infused, and the placebo or melatonin capsules were administered at 10:30 pm. Blood was drawn at 12:00 am, 3:00 am, and 6:00 am to measure the plasma concentration of melatonin and cortisol. A repeated-measures analysis of variance model was used to determine the effect of remifentanil on sleep stages, the effect of remifentanil on the plasma concentration of melatonin, and the effect of exogenous melatonin on remifentanil-induced sleep disturbance. RESULTS: Remifentanil inhibited rapid eye movement sleep (14.1 ± 7.2% to 3.9 ± 6.9%). The amount of slow wave sleep decreased from 6.8 ± 7.6% to 3.2 ± 6.1%, but this decrease was not statistically significant. Remifentanil did not decrease melatonin concentration. Melatonin administration did not prevent remifentanil-induced sleep disturbance. CONCLUSIONS: An overnight constant infusion of remifentanil inhibits rapid eye movement sleep without suppressing the nocturnal melatonin surge.

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