title: Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans.
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 microg x kg x 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.
authors: The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Christopher P
authors: CP
authors: Bonafide
authors: Natalie
authors: N
authors: Aucutt-Walter
authors: Nicole
authors: N
authors: Divittore
authors: Tonya
authors: T
authors: King
authors: Edward O
authors: EO
authors: Bixler
authors: Arthur J
authors: AJ
authors: Cronin
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000097:blood*; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D017286:Polysomnography / Q000187:drug effects / Q000379:methods; D000077208:Remifentanil; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D010880:Piperidines; D008550:Melatonin; D000077208:Remifentanil