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The influence of opioids on gastric function: experimental and clinical studies
Örebro University, School of Health and Medical Sciences.
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. , 66 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 14
Keyword [en]
gastrointestinal motility, gastric emptying, gastric tone, electrogastrography, analgesics, opioids, µ-opioid receptor, polymorphism
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-1762ISBN: 978-91-7668-583-9 (print)OAI: oai:DiVA.org:oru-1762DiVA: diva2:135443
Public defence
2008-03-27, Wilandersalen, M-huset, Universitetssjukhuset Örebro, Örebro, 13:00 (English)
Opponent
Supervisors
Note
ISSN 1652-4063Available from: 2008-03-06 Created: 2008-03-06 Last updated: 2011-05-17Bibliographically approved
List of papers
1. The delay of gastric emptying induced by remifentanil is not influenced by posture
Open this publication in new window or tab >>The delay of gastric emptying induced by remifentanil is not influenced by posture
2004 (English)In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 99, no 2, 429-434 p.Article in journal (Refereed) Published
Abstract [en]

Posture has an effect on gastric emptying. In this study, we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics. Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method. On two occasions the subjects were given a continuous infusion of remifentanil (0.2 microg. kg(-1). min(-1)) while lying either on the right lateral side in a 20 degrees head-up position or on the left lateral side in a 20 degrees head-down position. On two other occasions no infusion was given, and the subjects were studied lying in the two positions. When remifentanil was given, there were no significant differences between the two postures in maximal acetaminophen concentration (right side, 34 micromol. L(-1); versus left side, 16 micromol. L(-1)), time taken to reach the maximal concentration (94 versus 109 min), or area under the serum acetaminophen concentration time curve from 0 to 60 min (962 versus 197 min. micromol. L(-1)). In the control situation, there were differences between the postures in maximal acetaminophen concentration (138 versus 94 micromol. L(-1); P < 0.0001) and area under the serum acetaminophen concentration time curves from 0 to 60 min (5092 versus 3793 min. micromol. L(-1); P < 0.0001), but there was no significant difference in time taken to reach the maximal concentration (25 versus 47 min). Compared with the control situation, remifentanil delayed gastric emptying in both postures. We conclude that remifentanil delays gastric emptying and that this delay is not influenced by posture.

National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-2896 (URN)10.1213/​01.ANE.0000121345.58835.93 (DOI)
Available from: 2008-03-06 Created: 2008-03-06 Last updated: 2011-05-17Bibliographically approved
2. The effect of anesthetic technique on early postoperative gastric emptying: comparison of propofol-remifentanil and opioid-free sevoflurane anesthesia
Open this publication in new window or tab >>The effect of anesthetic technique on early postoperative gastric emptying: comparison of propofol-remifentanil and opioid-free sevoflurane anesthesia
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2006 (English)In: Journal of Anesthesia, ISSN 0913-8668, E-ISSN 1438-8359, Vol. 20, no 4, 261-267 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: A postoperative decrease in the gastric emptying (GE) rate may delay the early start of oral feeding and alter the bioavailability of orally administered drugs. The aim of this study was to compare the effect on early gastric emptying between two anesthetic techniques.

METHODS: Fifty patients (age, 19-69 years) undergoing day-case laparoscopic cholecystectomy were randomly assigned to received either total intravenous anesthesia with propofol/remifentanil/rocuronium (TIVA; n = 25) or inhalational opioid-free anesthesia with sevoflurane/rocuronium (mask induction; GAS; n = 25). Postoperative gastric emptying was evaluated by the acetaminophen method. After arrival in the recovery unit, acetaminophen (paracetamol) 1.5 g was given through a nasogastric tube, and blood samples were drawn during a 2-h period. The area under the serum-acetaminophen concentration curve from 0-60 min (AUC60), the maximal concentration (Cmax), and the time to reach C-max (Tmax) were calculated.

RESULTS: Twelve patients were excluded due to surgical complications (e.g., conversion to open surgery) and difficulty in drawing blood samples (TIVA, n = 7; GAS, n = 5). Gastric emptying parameters were (mean +/- SD): TIVA, AUC60, 2458 +/- 2775 min.micromol.l(-1); Cmax, 71 +/- 61 micromol.l(-1); and Tmax, 81 +/- 37 min; and GAS, AUC60, 2059 +/- 2633 min.micromol.l(-1); Cmax, 53 +/- 53 micromol.l(-1); and Tmax, 83 +/- 41 min. There were no significant differences between groups.

CONCLUSION: There was no major difference in early postoperative gastric emptying between inhalation anesthesia with sevoflurane versus total intravenous anesthesia with propofol-remifentanil. Both groups showed a pattern of delayed gastric emptying, and the variability in gastric emptying was high. Perioperative factors other than anesthetic technique may have more influence on gastric emptying.

National Category
Medical and Health Sciences Surgery Anesthesiology and Intensive Care
Research subject
Anaesthesiology; Surgery
Identifiers
urn:nbn:se:oru:diva-2897 (URN)10.1007/s00540-006-0436-3 (DOI)
Available from: 2008-03-06 Created: 2008-03-06 Last updated: 2011-05-17Bibliographically approved
3. Effects of remifentanil on gastric tone
Open this publication in new window or tab >>Effects of remifentanil on gastric tone
2008 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 7, 969-976 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Opioids are well known for impairing gastric motility. The mechanism is far from clear and there is wide interindividual variability. The purpose of this study was to evaluate the effect of remifentanil on proximal gastric tone. MATERIALS AND METHODS: Healthy volunteers were studied on two occasions and proximal gastric tone was measured by a gastric barostat. On the first occasion (n=8), glucagon 1 mg IV was given as a reference for a maximal relaxation of the stomach. On the second occasion (n=9), remifentanil was given in incremental doses (0.1, 0.2 and 0.3 microg/kg/min) for 15 min each, followed by a washout period of 30 min. Thereafter, remifentanil was readministered, and 10 min later glucagon 1 mg was given. Mean intragastric bag volumes were calculated for each 5-min interval. RESULTS: Glucagon decreased gastric tone in all subjects. Remifentanil had a marked effect on gastric tone; we found two distinct patterns of reactions with both increases and decreases in gastric tone and, during the remifentanil infusion, glucagon did not affect gastric tone. CONCLUSIONS: Remifentanil induced changes in gastric tone with both increases and decreases. The effect of remifentanil on gastric tone is probably dependent on the current state of the systems involved.

Place, publisher, year, edition, pages
Copenhagen: Blackwell Munksgaard, 2008
Keyword
Adult, Analgesics, Opioid/*pharmacology, Dose-Response Relationship, Drug, Fasting, Gastrointestinal Agents/administration & dosage, Gastrointestinal Motility/*drug effects/physiology, Glucagon/administration & dosage, Humans, Male, Piperidines/*pharmacology, Reference Values, Stomach/*drug effects/physiology
National Category
Medical and Health Sciences Anesthesiology and Intensive Care Surgery
Research subject
Anaesthesiology; Surgery
Identifiers
urn:nbn:se:oru:diva-3397 (URN)10.1111/j.1399-6576.2008.01685.x (DOI)18494844 (PubMedID)
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2011-05-17Bibliographically approved
4. Effects of fentanyl on gastric myoelectrical activity: a possible association with polymorphisms of the mu-opioid receptor gene?
Open this publication in new window or tab >>Effects of fentanyl on gastric myoelectrical activity: a possible association with polymorphisms of the mu-opioid receptor gene?
Show others...
2008 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 5, 708-715 p.Article 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.

Keyword
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:nbn:se:oru:diva-3395 (URN)10.1111/j.1399-6576.2008.01624.x (DOI)18419726 (PubMedID)
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2011-05-17Bibliographically approved

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