To Örebro University

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 orebro, Sweden. They were studied on two different occasions, during which they were randomly assigned to receive either methylnaltrexone 0.15mg/kg or saline subcutaneously 30min before the target-controlled infusion of remifentanil of 3ng/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.

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 orebro, orebro, 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.

Background: Recent studies have shown that remifentanil increases the risk of aspiration and induces subjective swallowing difficulties. The mechanisms are not completely understood. Here, we investigated whether remifentanil impairs esophageal motility and hypothesized that this is one possible underlying mechanism. Naloxone was used to evaluate whether the effects of remifentanil are mediated through opioid receptors. We also examined subjective swallowing difficulties and the influence of metoclopramide on remifentanil-induced effects.

Methods: Fourteen healthy volunteers participated in a double-blind, randomized, cross-over trial at the University Hospital in orebro, Sweden. They were studied on two different occasions, during which they were randomly assigned to receive either naloxone given as a bolus of 6g/kg followed by an infusion of 0.1g/kg/min, or saline 5min before target-controlled infusions of remifentanil at three target-site concentrations: 1, 2, and 3 ng/ml. On both occasions, 0.2mg/kg metoclopramide was given before the final measurement. Five swallows were performed during each measuring condition, and the metrics defining esophageal motility were measured by high-resolution manometry. Outcomes were differences in the metrics at baseline vs. during remifentanil infusion, with naloxone vs. placebo, and with remifentanil before and after metoclopramide administration. Differences in swallowing difficulties were also recorded.

Results: Remifentanil decreased swallow-evoked esophagogastric junction relaxation and the latency time of esophageal peristalsis. There were no significant effects of naloxone or metoclopramide on remifentanil-induced effects, and we detected no differences in swallowing difficulties.

Conclusions: Remifentanil induces dysfunction of esophageal motility; this may contribute to the elevated risk of regurgitation and aspiration.