Experimental and clinical studies on the antiemetic effects of propofol

Sammanfattning: 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.