Opioid-Induced Nausea Involves a Vestibular Problem Preventable by Head-RestReport as inadecuate

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Background and Aims

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.


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.


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.


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.

Author: Nadine Lehnen , Fabian Heuser , Murat Sağlam, Christian M. Schulz, Klaus J. Wagner, Masakatsu Taki, Eberhard F. Kochs, Klaus Jah

Source: http://plos.srce.hr/


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