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. / 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. / ISSN 1652-4063

<p>Postoperative nausea and vomiting (PONV) is still a clinical problem and its incidence is unacceptably high. After the introduction of propofol as an agent for induction and maintenance of anesthesia, it was reported that the incidence of PONV was lower. It was also proposed that propofol possesses antiemetic effects. Dopamine, serotonin and opioids may contribute to PONV. Therefore the purpose of these investigations was to evaluate if propofol has dopamine, serotonin or opioid antagonistic effects and if a subhypnotic infusion of propofol decreases the incidence of PONV. </p><p>Nausea and vomiting were induced in volunteers by a dopamine agonist, apomorphine, and by ipecacuanha which releases serotonin from the enterochromaffin cells in the gut. The effects of propofol on gastric emptying and orocecal transit time were evaluated in volunteers with the paracetamol method and by measuring the endtidal hydrogen concentration after ingestion of the trisaccharide raffinose. The effects of morphine on gastric emptying and gastric tone were studied in patients before surgery with the paracetamol method and with an electronic barostat, respectively. The effects of low dose propofol for prophylaxis of PONV were studied in 172 patients undergoing breast and abdominal surgery. Propofol prophylaxis was compared with a multidrug regimen consisting of dexamethasone and three antiemetic drugs, ondansetron, droperidol and metoclopramide. </p><p>Propofol did not abolish apomorphine-induced vomiting but reduced the number of retchings induced by ipecacuanha. Propofol sedation did not influence gastric emptying of liquids but it slightly prolonged orocecal transit time. Gastric relaxation induced by morphine was abolished by propofol but propofol did not abolish morphine-induced delay of gastric emptying. Propofol in a low dose infusion reduced the incidence of PONV but nausea and especially vomiting increased significantly after termination of the infusion. Pro- phylaxis with the multidrug regimen was very effective in preventing PONV. </p><p>These studies have shown that propofol does not have any dopamine antagonistic effect but may have a weak serotonin antagonistic effect. Propofol cannot abolish morphine-induced delay of gastric emptying. Low dose propofol infusion was effective in preventing PONV as long as the infusion was ongoing but after termination of the infusion nausea and especially vomiting substantially increased. The multidrug regimen (dexamethasone, ondansetron, droperidol, metoclopramide) was very effective in preventing PONV and can be recommended as prophylaxis in patient groups with a known high risk for PONV. </p>

Postoperative nausea and vomiting (PONV) is still a clinical problem and its incidence is unacceptably high. After the introduction of propofol as an agent for induction and maintenance of anesthesia, it was reported that the incidence of PONV was lower. It was also proposed that propofol possesses antiemetic effects. Dopamine, serotonin and opioids may contribute to PONV. Therefore the purpose of these investigations was to evaluate if propofol has dopamine, serotonin or opioid antagonistic effects and if a subhypnotic infusion of propofol decreases the incidence of PONV. Nausea and vomiting were induced in volunteers by a dopamine agonist, apomorphine, and by ipecacuanha which releases serotonin from the enterochromaffin cells in the gut. The effects of propofol on gastric emptying and orocecal transit time were evaluated in volunteers with the paracetamol method and by measuring the endtidal hydrogen concentration after ingestion of the trisaccharide raffinose. The effects of morphine on gastric emptying and gastric tone were studied in patients before surgery with the paracetamol method and with an electronic barostat, respectively. The effects of low dose propofol for prophylaxis of PONV were studied in 172 patients undergoing breast and abdominal surgery. Propofol prophylaxis was compared with a multidrug regimen consisting of dexamethasone and three antiemetic drugs, ondansetron, droperidol and metoclopramide. Propofol did not abolish apomorphine-induced vomiting but reduced the number of retchings induced by ipecacuanha. Propofol sedation did not influence gastric emptying of liquids but it slightly prolonged orocecal transit time. Gastric relaxation induced by morphine was abolished by propofol but propofol did not abolish morphine-induced delay of gastric emptying. Propofol in a low dose infusion reduced the incidence of PONV but nausea and especially vomiting increased significantly after termination of the infusion. Pro- phylaxis with the multidrug regimen was very effective in preventing PONV. These studies have shown that propofol does not have any dopamine antagonistic effect but may have a weak serotonin antagonistic effect. Propofol cannot abolish morphine-induced delay of gastric emptying. Low dose propofol infusion was effective in preventing PONV as long as the infusion was ongoing but after termination of the infusion nausea and especially vomiting substantially increased. The multidrug regimen (dexamethasone, ondansetron, droperidol, metoclopramide) was very effective in preventing PONV and can be recommended as prophylaxis in patient groups with a known high risk for PONV.