Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea.

BACKGROUND: Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. METHODS: Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. RESULTS: Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. CONCLUSIONS: Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.

Double-blind, randomized comparison of ondansetron and intraoperative propofol to prevent postoperative nausea and vomiting.

BACKGROUND: Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens. METHODS: Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide-oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Group PIP received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Thirty minutes before expected skin closure, isoflurane was discontinued and 50 to 150 micrograms.kg-1.min-1 propofol was given intravenously to maintain anesthesia. Group PP received propofol for induction and maintenance of anesthesia, nitrous oxide-oxygen, and fentanyl. Postoperative pain relief was provided with morphine administered by a patient-controlled analgesia pump. The incidence of nausea and vomiting, requests for rescue antiemetic and sedation, pain scores, and hemodynamic data were recorded for 24 h. RESULTS: Within 6 h of surgery, groups O and PP had a lower incidence of nausea compared with groups PI and PIP (P < 0.05). Fewer patients in group PP (19%) vomited during the 24-h period compared with groups O (48%), PI (64%), and PIP (52%) (P < 0.05). The incidence of antiemetic use was also less in group PP (P < 0.05). Patients in group PP had lower sedation scores at 30 min and at 1 h (P < 0.05). There were no differences among the groups in pain scores, blood pressure, heart rate, respiratory rate, and incidence of pruritus. CONCLUSIONS: Propofol administered to induce and maintain anesthesia is more effective than ondansetron (with thiopental-isoflurane anesthesia) in preventing postoperative vomiting and is associated with fewer requests for rescue antiemetic and sedation in the early phase of recovery. It is equally effective in preventing postoperative nausea as ondansetron in the first 6 h after operation. Propofol used only as an induction agent or for induction and at the end of surgery were not as protective against postoperative nausea and vomiting.

Gastric mucosal damage induced by 2-deoxy-D-glucose involves medullary TRH in the rat.

These studies examined the effect of 2-deoxy-D-glucose (2-DG) on gastric mucosal integrity. Intravenous administration of 2-DG in doses of 100 and 125 mg/kg dose-dependently produced multiple, hemorrhagic gastric mucosal lesions while 75 mg/kg of 2-DG failed to induce gastric lesions. Intracisternal injection of 2-DG in doses of 10 and 20 mg/kg also induced gastric mucosal damage in a dose-dependent manner whereas the injection of 5 mg/kg of 2-DG intracisternally did not induce the development of gastric lesions. Gastric mucosal damage by intravenous 2-DG was completely blocked by bilateral gastric branch vagotomy. Intracisternal but not intraperitoneal injection of anti-TRH antibody 8964 significantly reduced the severity of gastric mucosal lesions evoked by intravenous administration of 2-DG. These results suggest that 2-DG acts in the brain to induce gastric mucosal damage through vagal dependent pathways. Endogenous TRH in the central nervous system may be involved in the production of gastric mucosal damage by 2-DG.

Effects of enteral feeding products on survival from Escherichia coli peritonitis.

Male Fischer 344 rats were orally fed one of four diets (Osmolite HN, Alitraq, Impact, and Purina rodent chow). After 6 days, jejunal mucosal nitrogen content and thickness were normal in all groups. After 7 days, challenge with Escherichia coli intraperitoneally demonstrated no difference in survival for any dietary group. In a second study, acute protein-calorie malnutrition was induced by administering 5% dextrose orally for 10 days. Animals were refed for 7 days with one of the four diets. Serum albumin concentrations and intestinal mucosal nitrogen content and thickness returned to normal with each refeeding program. Challenge with E. coli after 7 days of refeeding, however, again demonstrated no difference in survival for any dietary group. Specialized enteral feeding products, containing additional amounts of arginine, glutamine, glutamate, RNA, and omega-3 fatty acids, are no more effective than a standard enteral feeding product or rat chow in maintaining intestinal anatomy or restoring anatomy following fasting. Furthermore, we found no survival advantage for the specialized products following E. coli peritonitis.

The effect of glibenclamide treatment on the insulin and glucagon responses to oral glucose and galactose in maturity onset diabetics.

Glibenclamide has been shown to stimulate an insulin releasing factor in the duodenum. The possibility that this effect is of importance in its hypoglycaemic action was investigated by studying the effect of galactose on insulin release before and after treatment with glibenclamide; galactose stimulates insulin release when given orally but has no effect when given parenterally; thus its ability to release insulin appears to reside in an action on a gut factor. Measurements of plasma glucose, insulin and glucagon were made on twelve maturity onset diabetic patients following an oral glucose tolerance test and an oral galactose tolerance test before and after one week of treatment with glibenclamide. Glibenclamide significantly reduced the blood glucose levels. Both basal insulin and basal glucagon levels were unchanged. The insulin response to oral glucose was enhanced. Glucagon levels before treatment did not suppression of glucagon levels. Galactose stimulated insulin release but insulin levels before and after treatment were identical. An effect of glibenclamide on gut insulin releasing activity was not demonstrated but the galactose tolerance test provides a useful technique by which to examine the enteroinsular axis.