Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes?

PLOS ONE, Dec 2019

Although opioid-induced nausea and vomiting (OINV) is common and debilitating, its mechanism is still unclear. Recently, we suggested that opioids affect semicircular canal function and that this leads to a mismatch between canal input and other sensory information during head motion, which triggers OINV. Here, we assess if visual input is relevant for this mismatch. In a randomized-controlled crossover study 14 healthy men (26.9±3.4 years, mean±SD) were tested twice, once blindfolded and once with eyes open, with at least one-day washout. The opioid remifentanil was administered intravenously (0.15 μg/kg/min) for 60 minutes. After a thirty-minutes resting period, subjects’ head and trunk were passively moved. Nausea was rated before remifentanil start (T0), before the movement intervention (T30) and after 60 minutes (T60) of administration. At rest (T0, T30), median nausea ratings were zero whether subjects were blindfolded or not. Movement triggered nausea independently of visual input (nausea rating 1.5/3.0 (median/interquartile range) in the blindfolded, 2.5/6 in the eyes-open condition, χ2(1) = 1.3, p = 0.25). As movement exacerbates OINV independently of visual input, a clash between visual and semicircular canal information is not the relevant trigger for OINV. To prevent OINV, emphasis should be put on head-rest, eye-closure is less important.

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Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes?

March Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes? Fabian Heuser 0 1 Christian Schulz 0 1 Murat Sağlam 1 Cecilia Ramaioli 1 Maria Heuberger 1 Klaus J. Wagner 0 1 Klaus Jahn 1 Erich Schneider 1 Thomas Brandt 1 Stefan Glasauer 1 Nadine Lehnen 1 0 Department of Anaesthesiology, Klinikum rechts der Isar, Technische UniversitaÈ t MuÈ nchen , Munich, Germany , 2 German Centre for Vertigo and Balance Disorders, Klinikum der Universit aÈt M uÈnchen , Munich, Germany , 3 Department of Neurology, Klinikum der Universit aÈt M uÈnchen , Munich, Germany, 4 Sch oÈn Klinik, Bad Aibling, Germany , 5 Brandenburg University of Technology , Cottbus-Senftenberg, Germany , 6 Institute for Clinical Neurosciences, Klinikum der Universit aÈt MuÈnchen , Munich, Germany , 7 Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technische Universit aÈt MuÈnchen , Munich , Germany 1 Editor: Manabu Sakakibara, Tokai University , JAPAN Although opioid-induced nausea and vomiting (OINV) is common and debilitating, its mechanism is still unclear. Recently, we suggested that opioids affect semicircular canal function and that this leads to a mismatch between canal input and other sensory information during head motion, which triggers OINV. Here, we assess if visual input is relevant for this mismatch. In a randomized-controlled crossover study 14 healthy men (26.9±3.4 years, mean ±SD) were tested twice, once blindfolded and once with eyes open, with at least one-day washout. The opioid remifentanil was administered intravenously (0.15 μg/kg/min) for 60 minutes. After a thirty-minutes resting period, subjects' head and trunk were passively moved. Nausea was rated before remifentanil start (T0), before the movement intervention (T30) and after 60 minutes (T60) of administration. At rest (T0, T30), median nausea ratings were zero whether subjects were blindfolded or not. Movement triggered nausea independently of visual input (nausea rating 1.5/3.0 (median/interquartile range) in the blindfolded, 2.5/6 in the eyes-open condition, χ2(1) = 1.3, p = 0.25). As movement exacerbates OINV independently of visual input, a clash between visual and semicircular canal information is not the relevant trigger for OINV. To prevent OINV, emphasis should be put on head-rest, eye-closure is less important. - Data Availability Statement: All relevant data are within the paper. Funding: This work was supported by the German Federal Ministry of Education and Research (Grants 01 EO 0901 and 01 EO 0914). The funder "SchoÈn Klinik Bad Aibling" provided support in the form of salaries for author KJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the `author contributions' section. Introduction Opioids are essential in the treatment of moderate to severe pain [1], but also induce debilitat ing nausea and vomiting. Opioid-induced nausea and vomiting (OINV) occurs in a third of all patients treated with morphine-equivalents [ 2 ] and is one of the main reasons for post-operative nausea and vomiting (PONV) [ 3 ]. PONV is a significant factor in complications such as pulmonary aspiration, dehydration, and electrolyte imbalance, delaying discharge and leading Competing interests: FH, CS, MS, CR, MH, KJW, and KJ report no disclosures. ES is general manager and a shareholder of EyeSeeTec GmbH. TB and SG are shareholders of EyeSeeTec GmbH. NL is a shareholder and consultant to EyeSeeTec GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials. to hospital admission after ambulatory surgery, which greatly increases health care cost [ 4 ]. PONV negatively impacts patient satisfaction [5] and patients even rank it amongst the most distressing non-life-threatening side effects [ 1 ]. The exact mechanism of OINV is still not clear. Opioids affect vestibular function, as demonstrated by a decrease in caloric response with morphine [ 6 ], a diminished active vestibuloocular reflex (VOR) with pethidine and fentanyl administration [ 7 ], vestibular dysfunction with heroin abuse [ 8 ], and decreased semicircular canal function, measured by the VOR gain, during administration of the short-acting μ-agonist remifentanil [ 9,10 ]. Opioid receptors are present within the VOR-three-neuron arc [ 11,12 ] and in the cerebellum [ 13 ], and could mediate the changes in vestibular-ocular motor function (VOR gain). Additional oculomotor findings during opioid administration, such as gaze-evoked nystagmus, saccadic smooth pursuit and, in particular, downbeat-nystagmus, point to cerebellar involvement [ 7,9 ]. Importantly, we demonstrated that head movement greatly exacerbates nausea during administration of the opioid remifentanil, while resting protects from it [ 9,14 ]. We suggested that the change in (...truncated)


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Fabian Heuser, Christian Schulz, Murat Sağlam, Cecilia Ramaioli, Maria Heuberger, Klaus J. Wagner, Klaus Jahn, Erich Schneider, Thomas Brandt, Stefan Glasauer, Nadine Lehnen. Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes?, PLOS ONE, 2017, Volume 12, Issue 3, DOI: 10.1371/journal.pone.0173925