Johanna Savilampi

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.

The Reliability of Pharyngeal High Resolution Manometry with Impedance for Derivation of Measures of Swallowing Function in Healthy Volunteers

Purpose. We evaluated the intra- and interrater agreement and test-retest reliability of analyst derivation of swallow function variables based on repeated high resolution manometry with impedance measurements. Methods. Five subjects swallowed 10 × 10 mL saline on two occasions one week apart producing a database of 100 swallows. Swallows were repeat-analysed by six observers using software. Swallow variables were indicative of contractility, intrabolus pressure, and flow timing. Results. The average intraclass correlation coefficients (ICC) for intra- and interrater comparisons of all variable means showed substantial to excellent agreement (intrarater ICC 0.85–1.00; mean interrater ICC 0.77–1.00). Test-retest results were less reliable. ICC for test-retest comparisons ranged from slight to excellent depending on the class of variable. Contractility variables differed most in terms of test-retest reliability. Amongst contractility variables, UES basal pressure showed excellent test-retest agreement (mean ICC 0.94), measures of UES postrelaxation contractile pressure showed moderate to substantial test-retest agreement (mean Interrater ICC 0.47–0.67), and test-retest agreement of pharyngeal contractile pressure ranged from slight to substantial (mean Interrater ICC 0.15–0.61). Conclusions. Test-retest reliability of HRIM measures depends on the class of variable. Measures of bolus distension pressure and flow timing appear to be more test-retest reliable than measures of contractility.

Effects of remifentanil on the esophagogastric junction and swallowing

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.

Effects of cricoid pressure and remifentanil on the esophageal sphincters using high-resolution solid-state manometry.

Background: Cricoid pressure has been shown to decrease the pressure in the lower esophageal sphincter (LES), increasing the risk of aspiration. Whether this reaction is due to pain associated with the application of cricoid pressure has not been studied. The aim of this study was to compare the effects of cricoid pressure with those of peripheral pain on pressures in the LES, and to study whether remifentanil influences these effects. Data from the upper esophageal sphincter (UES) are also described.

Effects of remifentanil on pharyngeal swallowing: A double blind randomised cross-over study in healthy volunteers.

BACKGROUND Exposure to remifentanil increases the incidence of pulmonary aspiration in healthy volunteers. This effect may be explained by impairment of airway defence mechanisms and/or altered swallowing function. Pressure-flow analysis is a technique that allows objective assessment of swallowing based on pressure-impedance patterns recorded during bolus swallowing. OBJECTIVES The aim of this study was to use pressure-flow analysis to quantify the effect of remifentanil on healthy pharyngeal swallowing and to compare these effects with morphine. DESIGN A double-blind, randomised, cross-over study. SETTING A tertiary care teaching hospital. VOLUNTEERS Eleven young volunteers (mean age, 23 years) and seven older volunteers (mean age, 73 years). INTERVENTIONS Volunteers were studied twice and received either a target-controlled remifentanil infusion (target concentrations: young, 3 ng ml−1; old, 2 ng ml−1) or a bolus injection of morphine (dose: young, 0.1 mg kg−1; old, 0.07 mg kg−1). Pharyngeal pressure and impedance were recorded with an indwelling catheter while swallowing 10 boluses of liquid during each measuring phase. Variables defining swallowing function were calculated and compared to determine drug effects. MAIN OUTCOME MEASURES Pharyngeal pressure-flow variables following remifentanil exposure. RESULTS Changes produced by remifentanil in the measured variables were consistent with greater dysfunction of swallowing. Both the strength of the pharyngeal contractions and pharyngeal bolus propulsion were reduced, whereas flow resistance was increased. The swallow risk index, a global index of swallowing dysfunction, increased overall. At the experimental doses tested, morphine produced similar, but less extensive effects on swallowing. CONCLUSION Remifentanil induced dysfunction of the pharyngeal swallowing mechanism. This may contribute to an increased risk of aspiration. TRIAL REGISTRATION NCT01924234 (www.clinicaltrials.gov).

Remifentanil alters sensory neuromodulation of swallowing in healthy volunteers: quantification by a novel pressure-impedance analysis

Exposure to remifentanil contributes to an increased risk of pulmonary aspiration, likely through reduced pharyngeal contractile vigor and diminished bolus propulsion during swallowing. We employed a novel high-resolution pressure-flow analysis to quantify the biomechanical changes across the upper esophageal sphincter (UES). Eleven healthy young (23.3 ± 3.1 yr old) participants (7 men and 4 women) received remifentanil via intravenous target-controlled infusion with an effect-site concentration of 3 ng/ml. Before and 30 min following commencement of remifentanil administration, participants performed ten 10-ml saline swallows while pharyngoesophageal manometry and electrical impedance data were recorded using a 4.2-mm-diameter catheter housing 36 circumferential pressure sensors. Remifentanil significantly shortened the duration of UES opening (P < 0.001) and increased residual UES pressure (P = 0.003). At the level of the hypopharynx, remifentanil significantly shortened the latency from maximum bolus distension to peak contraction (P = 0.004) and significantly increased intrabolus distension pressure (P = 0.024). Novel mechanical states analysis revealed that the latencies between the different phases of the stereotypical UES relaxation sequence were shortened by remifentanil. Reduced duration of bolus flow during shortened UES opening, in concert with increased hypopharyngeal distension pressures, is mechanically consistent with increased flow resistance due to a more rapid bolus flow rate. These biomechanical changes are congruent with modification of the physiological neuroregulatory mechanism governing accommodation to bolus volume.

Effects of remifentanil on esophageal motility: a double‐blind, randomized, cross‐over study in healthy volunteers

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.

Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis

Remifentanil is associated with subjective dysphagia and an objective increase in aspiration risk. Studies of opioid effects have shown decreased lower esophageal sphincter relaxation. We assessed bolus transit through the esophagus and esophagogastric junction (EGJ) during remifentanil administration using objective pressure‐flow analysis.