Aspiration induced by remifentanil: a double-blind, randomized, crossover study in healthy volunteers.

BACKGROUND: Remifentanil is widely used for monitored anesthesia care in spontaneously breathing patients. However, the authors' previous studies have shown that remifentanil induces subjective swallowing difficulties, which may increase the risk of aspiration. METHODS: Twenty-five healthy volunteers participated in a double-blind, randomized, crossover trial at the University Hospital in Örebro, Örebro, Sweden. The volunteers were studied on two different occasions during which they received either remifentanil with an effect-site target concentration of 3 ng/ml or saline over 1 h. A radionuclide tracer was infused simultaneously into the nasopharynx at a rate of 0.1 ml/min. Aspiration was determined by lung scans, and subjective swallowing difficulties and grip strength were evaluated. The primary outcome was the difference in occurrence of aspiration between remifentanil and placebo treatments. The secondary outcomes were differences in swallowing difficulty and grip strength and the association between aspiration and swallowing difficulty. RESULTS: During remifentanil and placebo infusion, 48 and 12% of the volunteers aspirated, respectively, difference: 36% (95% CI, 10 to 62%). A similar significant difference was found for swallowing difficulties but not for the association between aspiration and swallowing. No difference was found in grip strength between the two treatments. CONCLUSIONS: Remifentanil infusion at concentrations used in monitored anesthesia care increases the incidence of aspiration. However, the subjective swallowing difficulty induced by remifentanil is not indicative of the aspiration risk.

Effects of remifentanil on the esophagogastric junction and swallowing.

BACKGROUND: A recent study demonstrated that reflux is associated with impaired pressure augmentation in the esophagogastric junction (EGJ), caused by diaphragmal contractions during inspiration. It is unknown whether this augmentation is influenced by opioids. Swallowing difficulties can be a poorly recognised side effect of remifentanil. Here, we investigated whether remifentanil influences inspiratory EGJ augmentation and evaluated subjective swallowing difficulties induced by remifentanil. We also used the peripheral opioid receptor antagonist methylnaltrexone to evaluate whether these effects are centrally or peripherally mediated. METHODS: Ten healthy volunteers participated in a double-blind, randomised, cross-over trial at the University Hospital in Örebro, Sweden. They were studied on two different occasions, during which they were randomly assigned to receive either methylnaltrexone 0.15 mg/kg or saline subcutaneously 30 min before the target-controlled infusion of remifentanil of 3 ng/mL. EGJ pressures were measured by high-resolution manometry. Swallowing difficulties were assessed when volunteers performed dry swallows. The outcomes were the differences in EGJ pressures at baseline and during remifentanil infusion and with methylnaltrexone vs. placebo. Differences in swallowing difficulties before and during remifentanil, and with methylnaltrexone vs. placebo were also recorded. RESULTS: Remifentanil decreased the inspiratory EGJ augmentation and induced swallowing difficulties. No statistically significant differences between methylnaltrexone and placebo occasions were found. CONCLUSIONS: Remifentanil may increase risk for gastroesophageal reflux by decreasing the inspiratory EGJ augmentation. The clinical significance of remifentanil-induced swallowing difficulties is to be studied further. Given the limited sample size, it cannot be concluded whether these effects are centrally or peripherally mediated.

Barrier pressure of the oesophagogastric junction during propofol induction with and without alfentanil: a double-blind, randomised, crossover study in volunteers.

CONTEXT: Practice varies regarding the use of opioids during rapid sequence induction. Controversy exists as to whether opioids may increase the risk of pulmonary aspiration by decreasing the barrier pressure (lower oesophageal sphincter-intragastric pressure). OBJECTIVES: To evaluate the effects of adding alfentanil during anaesthesia induction with propofol with respect to the barrier pressure in the oesophagogastric junction. PARTICIPANTS AND SETTING: Seventeen healthy volunteers (11 men and six women) participated in a double-blind, randomised, crossover trial at the University Hospital in Orebro, Sweden. INTERVENTIONS AND OUTCOME MEASURES: The volunteers were anaesthetised on two different occasions, randomly assigned to receive either alfentanil 20 µg kg(-1) or an equivalent amount of isotonic saline, administered intravenously, 1 min before induction with propofol 2 mg kg(-1). One minute after propofol administration, a cricoid pressure of 30 N was applied. The primary outcome was the difference in the change in barrier pressure between the alfentanil and the placebo occasion 1 min after propofol administration. The secondary outcomes were differences in the changes in barrier pressure 1 min after alfentanil or placebo administration and during ongoing cricoid pressure application. RESULTS: There were no statistically significant differences in barrier pressure, at any time point, between anaesthesia induction with alfentanil and propofol compared with induction with placebo and propofol. The barrier pressure never decreased to less than 2.4 mmHg in any volunteer. CONCLUSION: Our study showed no increased risk regarding the integrity of the gastro-oesophageal junction when alfentanil is added during an induction with propofol in volunteers. This supports the practice of adding opioids as adjuvants during rapid sequence induction.

Effects of propofol on oesophageal sphincters: a study on young and elderly volunteers using high-resolution solid-state manometry.

BACKGROUND AND OBJECTIVE: The oesophageal sphincters play an important role in protecting the airway. During manometric studies, administration of an anxiolytic agent is often required to make insertion of the catheter acceptable for the patient. The anxiolytic should not affect the results of the measurements. This study evaluates the effects of two different doses of propofol on the pressures in the oesophageal sphincters. The effect of increased abdominal pressure was also studied. METHODS: Twenty healthy volunteers, 10 young (mean age 25 years) and 10 elderly (mean age 71 years), were recruited. The effects of a low dose of propofol [0.3 mg kg(-1) intravenously (i.v.)] and a high dose of propofol (young group 0.9 mg kg(-1) i.v. and elderly group 0.6 mg kg(-1) i.v.) were studied with and without external abdominal pressure. RESULTS: There were no statistically significant changes in lower oesophageal sphincter (LOS) pressure after the low dose of propofol. After the high dose, there was an increase in LOS pressure, which was statistically significant in the young group (P < 0.05). The upper oesophageal sphincter (UOS) pressure decreased after both doses of propofol (P < 0.01 for the higher dose and P < 0.05 for the lower dose). CONCLUSION: A low dose of propofol (0.3 mg kg(-1) i.v.) leaves the LOS unaffected in young and elderly volunteers and can be used safely as an anxiolytic agent during studies of the LOS without influencing the results. However, the UOS is more sensitive to the effects of propofol and we do not recommend the use of propofol as an anxiolytic agent during manometric studies of the UOS.

High-resolution solid-state manometry of the upper and lower esophageal sphincters during anesthesia induction: a comparison between obese and non-obese patients.

BACKGROUND: The prevalence of obesity has increased dramatically in recent decades. The gastrointestinal changes associated with obesity have clinical significance for the anesthesiologist in the perioperative period. The lower esophageal sphincter and the upper esophageal sphincter play a central role in preventing regurgitation and aspiration. The effects of increased intra-abdominal pressure during anesthesia on the lower esophageal sphincter and the upper esophageal sphincter in obese patients are unknown. In the present study we evaluated, with high-resolution solid-state manometry, the upper esophageal sphincter, lower esophageal sphincter, and barrier pressure (BrP) (lower esophageal pressure--gastric pressure) in obese patients during anesthesia induction and compared them with pressures in non-obese patients. METHODS: We studied 28 patients, ages 18 to 72 years, 14 with a body mass index > or = 35 kg/m(2), who were undergoing laparoscopic gastric bypass, and 14 with a body mass index < or = 30 kg/m(2), who were undergoing laparoscopic cholecystectomy, using high-resolution solid-state manometry. RESULTS: Upper esophageal sphincter pressure decreased during anesthesia induction in both groups. Lower esophageal sphincter pressure decreased in both groups during anesthesia induction, and it was significantly lower in obese patients than in non-obese patients. The BrP decreased in both groups and was significantly lower in the obese group than in the non-obese group. The BrP remained positive at all times in both groups. CONCLUSION: Lower esophageal sphincter and BrPs decreased in both obese and non-obese patients during anesthesia induction, but were significantly lower in obese patients. Although the BrP was significantly lower, it remained positive in all patients.

Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial.

BACKGROUND: Sugammadex, a specifically designed gamma-cyclodextrin, is a selective relaxant binding drug that rapidly reverses rocuronium-induced and, to a lesser extent, vecuronium-induced neuromuscular blockade. In this study, we compared the efficacy of sugammadex and neostigmine for the reversal of vecuronium-induced neuromuscular blockade in patients scheduled for elective surgery. METHODS: Patients aged > or = 18 yr, ASA Class I-III, and scheduled for a surgical procedure under sevoflurane/opioid anesthesia received an intubating dose of vecuronium (0.1 mg/kg) and maintenance doses of 0.02-0.03 mg/kg at reappearance of the second twitch (T(2)) of train-of-four (TOF) if required. Neuromuscular blockade was monitored using acceleromyography (TOF-Watch SX, Schering-Plough Ireland, Dublin, Ireland). At end of surgery, at reappearance of T(2) after the last dose of vecuronium, patients were randomized to receive either sugammadex (2 mg/kg) or neostigmine (50 microg/kg) plus glycopyrrolate (10 microg/kg) i.v.. The primary efficacy end-point was time from start of administration of sugammadex or neostigmine to recovery of TOF ratio to 0.9. RESULTS: The geometric mean time to recovery of the TOF ratio to 0.9 was significantly faster with sugammadex compared with neostigmine (2.7 min [95% confidence interval {CI}]: 2.2-3.3) versus 17.9 min [95% CI: 13.1-24.3], respectively; P < 0.0001). The mean recovery times to a TOF ratio of 0.8 and 0.7 were also significantly shorter with sugammadex. No serious adverse events or unexpected side effects were reported with either drug. CONCLUSION: Sugammadex provided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine.

Effects of remifentanil on gastric tone.

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.

The effect of anesthetic technique on early postoperative gastric emptying: comparison of propofol-remifentanil and opioid-free sevoflurane anesthesia.

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.

Betamethasone does not prevent nausea and vomiting induced by the dopamine-agonist apomorphine.

PURPOSE: The mechanism of the antiemetic actions of corticosteroids is not known. The purpose of this study was to evaluate if betamethasone can prevent nausea, vomiting or increase of vasopressin induced by apomorphine. Metoclopramide, a dopamine antagonist, was used as a control substance. METHODS: Ten healthy volunteers were studied on three occasions. In a randomized order they were allocated to receive pretreatment with betamethasone 8 mg iv, metoclopramide 10 mg iv, and normal saline 2 mL as placebo on the three different occasions, 15 min before the administration of apomorphine 30 microg x kg(-1) s.c.. After administration of apomorphine, episodes of vomiting were recorded, and the intensity of nausea was estimated by the subject on a visual analogue scale (VAS 0-10 cm). Blood samples for analysis of plasma concentrations of vasopressin were analyzed. RESULTS: One volunteer decided to withdraw, as he experienced akathisia after receiving metoclopramide. During the first two hours after apomorphine, eight of nine volunteers vomited both after betamethasone and placebo. One volunteer did not vomit after betamethasone and placebo but he experienced nausea. None of the volunteers vomited after metoclopramide (P < 0.01 vs betamethasone and placebo). The maximum VAS for nausea was significantly higher after betamethasone and placebo compared to metoclopramide (P < 0.01). The vasopressin levels increased after betamethasone and placebo, but there was no increase in any volunteer after pretreatment with metoclopramide. CONCLUSION: This study demonstrates that betamethasone does not prevent nausea, vomiting and increase of vasopressin induced by apomorphine, whereas metoclopramide prevents apomorphine-induced emesis. Our work suggests that betamethasone does not have dopamine-antagonistic effects.

The effects of cricoid pressure, remifentanil, and propofol on esophageal motility and the lower esophageal sphincter.

Cricoid pressure is the gold standard during the induction of anesthesia when there is a risk of aspiration of gastric contents. However, the effect of cricoid pressure during the different steps of complete anesthesia induction has not been studied. The purpose of this study was to investigate the effects of cricoid pressure, remifentanil, and propofol on lower esophageal sphincter (LES) and esophageal motility. We recorded LES pressure (LESP) and calculated barrier pressure ([BrP] = LESP - gastric pressure) in 10 healthy volunteers using a Dent sleeve device. There was a significant decrease in LESP and BrP when a cricoid pressure of 30 N was performed in the awake volunteers (P < 0.05). However, this effect was not seen during the infusion of remifentanil 0.2 microg . kg(-1) . min(-1). Remifentanil per se or together with a bolus dose of propofol 1 mg/kg IV did not induce any statistical change in LESP or BrP. Remifentanil abolished spontaneous esophageal motility and completely eliminated the experience of discomfort induced by cricoid pressure. In conclusion, cricoid pressure of 30 N induced a decrease of LESP and BrP in awake volunteers. These effects were not seen during the remifentanil infusion. This shows the importance of when to apply cricoid pressure during rapid-sequence induction.

The delay of gastric emptying induced by remifentanil is not influenced by posture.

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.