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Effects of fentanyl on gastric myoelectrical activity: a possible association with polymorphisms of the mu-opioid receptor gene?
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
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2008 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 5, p. 708-715Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Opioids have inhibitory effects on gastric motility, but the mechanism is far from clear. Electrical slow waves in the stomach determine the frequency and the peristaltic nature of gastric contractions. The primary aim of this study was to investigate the effects of the opioid fentanyl on gastric myoelectric activity. As there were large variations between the subjects, we investigated whether the variation was correlated to single nucleotide polymorphisms (SNP) of the mu-opioid receptor (MOR) gene. METHODS: We used cutaneous multichannel electrogastrography (EGG) to study myoelectrical activity in 20 patients scheduled for elective surgery. Fasting EGG was recorded for 30 min, followed by intravenous administration of fentanyl 1 microg/kg and subsequent EGG recording for 30 min. Spectral analysis of the two recording periods was performed and the variables assessed were dominant frequency (DF) of the EGG and its power (DP). Genetic analysis of the SNP A118G and G691C of the MOR gene was performed with the polymerase chain reaction technique. RESULTS: There was a significant reduction in DF and DP after intravenous fentanyl. However, there was a large variation between the patients. In eight subjects EGG was unaffected, five subjects had a slower DF (bradygastria) and in six subjects the slow waves disappeared. We found no correlation between the EGG outcome and the presence of A118G or G691C in the MOR gene. CONCLUSIONS: Fentanyl inhibited gastric myoelectrical activity in about half of the subjects. The variation could not be explained by SNP in the MOR gene. Because of small sample size, the results must be regarded as preliminary observations.

Place, publisher, year, edition, pages
2008. Vol. 52, no 5, p. 708-715
Keywords [en]
Adult, Aged, Analgesics, Opioid/metabolism/*pharmacology, Electrophysiology, Female, Fentanyl/metabolism/*pharmacology, Gastrointestinal Motility/*drug effects/*genetics/physiology, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction/methods, Polymorphism, Single Nucleotide, Postoperative Nausea and Vomiting/physiopathology/prevention & control, Receptors, Opioid; mu/*genetics, Stomach/physiology
National Category
Medical and Health Sciences Anesthesiology and Intensive Care Surgery
Research subject
Anaesthesiology; Surgery
Identifiers
URN: urn:nbn:se:oru:diva-3395DOI: 10.1111/j.1399-6576.2008.01624.xPubMedID: 18419726OAI: oai:DiVA.org:oru-3395DiVA, id: diva2:137692
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2017-12-14Bibliographically approved
In thesis
1. The influence of opioids on gastric function: experimental and clinical studies
Open this publication in new window or tab >>The influence of opioids on gastric function: experimental and clinical studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Efter operation och anestesi får patienter ofta en negativ påverkan på magsäck och tarmar. Illamående och kräkningar är ett stort problem och många har svårt att komma igång med intag av föda och normal tarmfunktion då magsäcken och tarmarna ”står stilla”. Flera faktorer bidrar- bl.a. smärtan, det kirurgiska traumat och de läkemedel vi ger i samband med anestesin. Av de senare är opioider, d.v.s morfin och morfinliknande läkemedel, starkt bidragande. I detta avhandlings- arbete har opioiders effekter på magsäckens motilitet studerats.

Med ett absorptionstest (paracetamolmetoden) studerades hos frivilliga hur opioiden remifentanil påverkar magsäckstömning och om kroppspositionen har betydelse för tömningshastigheten ut i tarmen. Remifentanil fördröjde magsäcks-tömningen och under pågående opioid behandling hade kroppspositionen ingen större betydelse, vilket det däremot hade under kontrollförsöken. Med samma metod jämförde vi hos patienter två anestesimetoder och studerade magsäcks-tömning direkt efter en operation. Ingen skillnad kunde påvisas mellan en opioidbaserad och en opioidfri anestesi, men inom respektive grupp var det en stor variation i magsäckstömning mellan individerna.

Med en barostat studerades tonus i övre delen av magsäcken. Hos hälften av de frivilliga orsakade remifentanil en ökning av tonus och hos den andra hälften en minskning av tonus. Vidare undersöktes hos en grupp patienter opioiden fentanyls påverkan på den elektriska aktiviteten i magsäcken. Med en elekroga-strograf (EGG) registrerades de långsamma elektriska vågor som koordinerar muskelrörelserna i magsäcken. Hos hälften av de undersökta påverkades aktiviteten av fentanyl med en sänkt vågfrekvens eller upphörande av vågor, medan aktiviteten var opåverkad hos den övriga hälften. För att finna en förklaring till variationen gjordes genetiska analyser av genen för opioidreceptorn hos de undersökta i barostat och EGG studierna. Variationer i genomet, s.k. polymorfism, var inte associerad till utfallen i studierna.

Studierna har visat på att opioider har en uttalad effekt på magsäckens motilitet och att den varierar kraftigt mellan individer. Polymorfism i genen för opioid- receptorn förklarade inte skillnaden mellan individer. Direkt efter operation bidrar sannolikt andra faktorer än anestesimetod till det variabla utfallet i magsäckstömning.

Abstract [en]

After anesthesia and/or surgical procedures, gastrointestinal motility is commonly impaired. The causes are multifactorial, with surgical trauma, pain and perioperative drugs playing a major role. This thesis explores opioid effects on gastric motility in healthy volunteers and patients undergoing surgery.

Gastric emptying was studied by an absorption test (paracetamol method), and in healthy volunteers a remifentanil infusion delayed gastric emptying. Body position altered emptying during the control situations, but not during the remifentanil infusion. Further, two anesthetic methods were compared and no differences were found in immediate postoperative gastric emptying between a remifentanil/propofol based intravenous anesthesia and an opioid free inhalational anesthesia, although the interindividual variability was high. Proximal gastric tone was studied using a gastric barostat. An infusion of remifentanil caused two patterns of reaction regarding gastric tone, with half of the subjects increasing and half decreasing in gastric tone. Gastric myoelectrical activity was evaluated with electrogastrography (EGG), and a bolus dose of fentanyl caused a decrease in frequency of the gastric slow waves or disrupted this activity. However, the activity was unaffected in half of the investigated subjects. Analysis of polymorphisms (A118G and G691C) in the µ-opioid receptor gene was performed to find an explanation for the great interindividual variations seen in the barostat and EGG studies, but no association could be found.

These studies have shown that opioids have pronounced effects on gastric motility with variable individual responses that are difficult to predict. Polymorphisms in the µ-opioid receptor gene could not explain the variations. Postoperatively, other factors might contribute more than opioids to the impairment in gastric motility.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2008. p. 66
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 14
Keywords
gastrointestinal motility, gastric emptying, gastric tone, electrogastrography, analgesics, opioids, µ-opioid receptor, polymorphism
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-1762 (URN)978-91-7668-583-9 (ISBN)
Public defence
2008-03-27, Wilandersalen, M-huset, Universitetssjukhuset Örebro, Örebro, 13:00 (English)
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Supervisors
Note
ISSN 1652-4063Available from: 2008-03-06 Created: 2008-03-06 Last updated: 2017-10-18Bibliographically approved

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Walldén, JakobThörn, Sven-EgronWattwil, Magnus

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