title: Opioid-Induced Nausea Involves a Vestibular Problem Preventable by Head-Rest.
abstract: OBJECTIVE
  Opioids are indispensable for pain treatment but may cause serious nausea and vomiting. The mechanism leading to these complications is not clear. We investigated whether an opioid effect on the vestibular system resulting in corrupt head motion sensation is causative and, consequently, whether head-rest prevents nausea.
  
  
  METHODS
  Thirty-six healthy men (26.6 ± 4.3 years) received an opioid remifentanil infusion (45 min, 0.15 μg/kg/min). Outcome measures were the vestibulo-ocular reflex (VOR) gain determined by video-head-impulse-testing, and nausea. The first experiment (n = 10) assessed outcome measures at rest and after a series of five 1-Hz forward and backward head-trunk movements during one-time remifentanil administration. The second experiment (n = 10) determined outcome measures on two days in a controlled crossover design: (1) without movement and (2) with a series of five 1-Hz forward and backward head-trunk bends 30 min after remifentanil start. Nausea was psychophysically quantified (scale from 0 to 10). The third controlled crossover experiment (n = 16) assessed nausea (1) without movement and (2) with head movement; isolated head movements consisting of the three axes of rotation (pitch, roll, yaw) were imposed 20 times at a frequency of 1 Hz in a random, unpredictable order of each of the three axes. All movements were applied manually, passively with amplitudes of about ± 45 degrees.
  
  
  RESULTS
  The VOR gain decreased during remifentanil administration (p<0.001), averaging 0.92 ± 0.05 (mean ± standard deviation) before, 0.60 ± 0.12 with, and 0.91 ± 0.05 after infusion. The average half-life of VOR recovery was 5.3 ± 2.4 min. 32/36 subjects had no nausea at rest (nausea scale 0.00/0.00 median/interquartile range). Head-trunk and isolated head movement triggered nausea in 64% (p<0.01) with no difference between head-trunk and isolated head movements (nausea scale 4.00/7.25 and 1.00/4.5, respectively).
  
  
  CONCLUSIONS
  Remifentanil reversibly decreases VOR gain at a half-life reflecting the drug's pharmacokinetics. We suggest that the decrease in VOR gain leads to a perceptual mismatch of multisensory input with the applied head movement, which results in nausea, and that, consequently, vigorous head movements should be avoided to prevent opioid-induced nausea.
authors: Centre for Sensorimotor Research, Munich University Hospital, Munich, Germany; German Centre for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany; Department of Neurology, Munich University Hospital, Munich, Germany.
authors: Nadine
authors: N
authors: Lehnen
authors: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Fabian
authors: F
authors: Heuser
authors: Department of Biomedical Engineering, Faculty of Engineering and Architecture, Gediz University, Izmir, Turkey.
authors: Murat
authors: M
authors: Sağlam
authors: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Christian M
authors: CM
authors: Schulz
authors: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Klaus J
authors: KJ
authors: Wagner
authors: Department of Otolaryngology-HNS, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Masakatsu
authors: M
authors: Taki
authors: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Eberhard F
authors: EF
authors: Kochs
authors: German Centre for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany; Schön Klinik Bad Aibling, Bad Aibling, Germany.
authors: Klaus
authors: K
authors: Jahn
authors: German Centre for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany; Institute for Clinical Neurosciences, Munich University Hospital, Munich, Germany.
authors: Thomas
authors: T
authors: Brandt
authors: Centre for Sensorimotor Research, Munich University Hospital, Munich, Germany; German Centre for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany; Department of Neurology, Munich University Hospital, Munich, Germany.
authors: Stefan
authors: S
authors: Glasauer
authors: German Centre for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany; Institute for Clinical Neurosciences, Munich University Hospital, Munich, Germany; Institute for Medical Technology, Brandenburg Institute of Technology, Cottbus-Senftenberg, Germany.
authors: Erich
authors: E
authors: Schneider
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D019416:Head Movements / Q000502:physiology; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced* / Q000517:prevention & control; D010880:Piperidines / Q000009:adverse effects*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects*; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil