Immediate mobilization in post-anesthesia care unit does not increase overall postoperative physical activity after elective colorectal surgery: A randomized, double-blinded controlled trial within an enhanced recovery protocol.

BACKGROUND: The level of post-operative mobilization according to Enhanced Recovery After Surgery (ERAS) guidelines is not always achieved. We investigated whether immediate mobilization increases postoperative physical activity. The objective was to evaluate the effects of immediate postoperative mobilization in the post-anesthesia care unit (PACU) compared to standard care. METHODS: This randomized controlled trial, involved 144 patients, age ≥18 years, undergoing elective colorectal surgery. Patients were randomized to mobilization starting 30 min after arrival in the PACU, or to standard care. Standard care consisted of mobilization a few hours later at the ward according to ERAS guidelines. The primary outcome was physical activity, in terms of number of steps, measured with an accelerometer during postoperative days (PODs) 1-3. Secondary outcomes were physical capacity, functional mobility, time to readiness for discharge, complications, compliance with the ERAS protocol, and physical activity 1 month after surgery. RESULTS: With the intention-to-treat analysis of 144 participants (median age 71, 58% female) 47% underwent laparoscopic-or robotic-assisted surgery. No differences in physical activity during hospital stay were found between the participants in the intervention group compared to the standard care group (adjusted mean ratio 0.97 on POD 1 [95% CI, 0.75-1.27], p = 0.84; 0.89 on POD 2 [95% CI, 0.68-1.16], p = 0.39, and 0.90 on POD 3 [95% CI, 0.69-1.17], p = 0.44); no differences were found in any of the other outcome measures. CONCLUSIONS: Addition of the intervention of immediate mobilization to standard care did not make the patients more physically active during their hospital stay. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NTC 03357497.

Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane.

Background: Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods: From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings: Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation: No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Funding: Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.

Supervised Immediate Postoperative Mobilization After Elective Colorectal Surgery: A Feasibility Study.

BACKGROUND: Early mobilization is a significant part of the ERAS® Society guidelines, in which patients are recommended to spend 2 h out of bed on the day of surgery. However, it is not yet known how early patients can safely be mobilized after completion of colorectal surgery. The aim of this study was to evaluate the feasibility, and safety of providing almost immediate structured supervised mobilization starting 30 min post-surgery at the postoperative anesthesia care unit (PACU), and to describe reactions to this approach. METHODS: This feasibility study includes 42 patients aged ≥18 years who received elective colorectal surgery at Örebro University Hospital. They underwent a structured mobilization performed by a specialized physiotherapist using a modified Surgical ICU Optimal Mobilization Score (SOMS). SOMS determines the level of mobilization at four levels from no activity to ambulating. Mobilization was considered successful at SOMS ≥ 2, corresponding to sitting on the edge of the bed as a proxy of sitting in a chair due to lack of space. RESULTS: In all, 71% (n = 30) of the patients reached their highest level of mobilization between the second and third hour of arrival in the PACU. Before discharge to the ward, 43% (n = 18) could stand at the edge of the bed and 38% (n = 16) could ambulate. Symptoms that delayed advancement of mobilization were pain, somnolence, hypotension, nausea, and patient refusal. No serious adverse events occurred. CONCLUSIONS: Supervised mobilization is feasible and can safely be initiated in the immediate postoperative care after colorectal surgery. Trial registration Clinical trials.gov identifier: NTC03357497.

ASA classification and surgical severity grading used to identify a high-risk population, a multicenter prospective cohort study in Swedish tertiary hospitals.

BACKGROUND: Identification of surgical populations at high risk for negative outcomes is needed for clinical and research purposes. We hypothesized that combining two classification systems, ASA (American Society of Anesthesiology physical status) and surgical severity, we could identify a high-risk population before surgery. We aimed to describe postoperative outcomes in a population selected by these two classifications system. METHODS: Data were collected in a Swedish multicentre, time-interrupted prospective, consecutive cohort study. Eligibility criteria were age ≥18 years, ASA ≥3, elective or emergent, major to Xmajor/complex (Specialist Procedure Codes used in United Kingdom), gastrointestinal, urogenital or orthopaedic procedures. Postoperative morbidity was identified by the Postoperative Morbidity Survey on postoperative days 3 ± 1, 7 ± 1, 10 + 5 and graded for severity by the Clavien-Dindo system. Mortality was assessed at 30, 180 and 360 days. RESULTS: Postoperative morbidity was 78/48/47 per cent on postoperative days 3/7/10. Majority of morbidities (67.5 per cent) were graded as >1 by Clavien-Dindo. Any type of postoperative morbidity graded >1 was associated with increased risk for death up to one year. The mortality was 5.7 per cent (61/1063) at 30 days, 13.3 per cent (142/1063) at 6 months and 19.1 per cent (160/1063) at 12 months. CONCLUSION: Severity classification as major to Xmajor/complex and ASA ≥3 could be used to identify a high-risk surgical population concerning postoperative morbidity and mortality before surgery. Combining the two systems future electronic data extraction is possible of a high-risk population in tertiary hospitals.

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients.

BACKGROUND: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. METHODS: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. RESULTS: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). CONCLUSIONS: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.

Detailed measurements of oesophageal pressure during mechanical ventilation with an advanced high-resolution manometry catheter.

BACKGROUND: Oesophageal pressure (PES) is used for calculation of lung and chest wall mechanics and transpulmonary pressure during mechanical ventilation. Measurements performed with a balloon catheter are suggested as a basis for setting the ventilator; however, measurements are affected by several factors. High-resolution manometry (HRM) simultaneously measures pressures at every centimetre in the whole oesophagus and thereby provides extended information about oesophageal pressure. The aim of the present study was to evaluate the factors affecting oesophageal pressure using HRM. METHODS: Oesophageal pressure was measured using a high-resolution manometry catheter in 20 mechanically ventilated patients (15 in the ICU and 5 in the OR). Different PEEP levels and different sizes of tidal volume were applied while pressures were measured continuously. In 10 patients, oesophageal pressure was also measured using a conventional balloon catheter for comparison. A retrospective analysis of oesophageal pressure measured with HRM in supine and sitting positions in 17 awake spontaneously breathing patients is also included. RESULTS: HRM showed large variations in end-expiratory PES (PESEE) and tidal changes in PES (ΔPES) along the oesophagus. Mean intra-individual difference between the minimum and maximum end-expiratory oesophageal pressure (PESEE at baseline PEEP) and tidal variations in oesophageal pressure (ΔPES at tidal volume 6 ml/kg) recorded by HRM in the different sections of the oesophagus was 23.7 (7.9) cmH2O and 7.6 (3.9) cmH2O respectively. Oesophageal pressures were affected by tidal volume, level of PEEP, part of the oesophagus included and patient positioning. HRM identified simultaneous increases and decreases in PES within a majority of individual patients. Compared to sitting position, supine position increased PESEE (mean difference 12.3 cmH2O), pressure variation within individual patients and cardiac artefacts. The pressure measured with a balloon catheter did not correspond to the average pressure measured with HRM within the same part of the oesophagus. CONCLUSIONS: The intra-individual variability in PESEE and ΔPES is substantial, and as a result, the balloon on the conventional catheter is affected by many different pressures along its length. Oesophageal pressures are not only affected by lung and chest wall mechanics but are a complex product of many factors, which is not obvious during conventional measurements. For correct calculations of transpulmonary pressure, factors influencing oesophageal pressures need to be known. HRM, which is available at many hospitals, can be used to increase the knowledge concerning these factors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02901158.

Effect of positive end-expiratory pressure on gastric insufflation during induction of anaesthesia when using pressure-controlled ventilation via a face mask: A randomised controlled trial.

BACKGROUND: Face mask ventilation (FMV) during induction of anaesthesia is associated with risk of gastric insufflation that may lead to gastric regurgitation and pulmonary aspiration. A continuous positive airway pressure (CPAP) has been shown to reduce gastric regurgitation. We therefore hypothesised that CPAP followed by FMV with positive end-expiratory pressure (PEEP) during induction of anaesthesia would reduce the risk of gastric insufflation. OBJECTIVE: The primary aim was to compare the incidence of gastric insufflation during FMV with a fixed PEEP level or zero PEEP (ZEEP) after anaesthesia induction. A secondary aim was to investigate the effects of FMV with or without PEEP on upper oesophageal sphincter (UES), oesophageal body and lower oesophageal sphincter (LES) pressures. DESIGN: A randomised controlled trial. SETTING: Single centre, Department of Anaesthesia and Intensive Care, Örebro University Hospital, Sweden. PARTICIPANTS: Thirty healthy volunteers. INTERVENTIONS: Pre-oxygenation without or with CPAP 10 cmH2O, followed by pressure-controlled FMV with either ZEEP or PEEP 10 cmH2O after anaesthesia induction. MAIN OUTCOME MEASURES: A combined impedance/manometry catheter was used to detect the presence of gas and to measure oesophageal pressures. The primary outcome measure was the cumulative incidence of gastric insufflation, defined as a sudden anterograde increase in impedance of more than 1 kΩ over the LES. Secondary outcome measures were UES, oesophageal body and LES pressures. RESULTS: The cumulative incidence of gastric insufflation related to peak inspiratory pressure (PIP), was significantly higher in the PEEP group compared with the ZEEP group (log-rank test P < 0.01). When PIP reached 30 cmH2O, 13 out of 15 in the PEEP group compared with five out of 15 had shown gastric insufflation. There was a significant reduction of oesophageal sphincter pressures within groups comparing pre-oxygenation to after anaesthesia induction, but there were no significant differences in oesophageal sphincter pressures related to the level of PEEP. CONCLUSION: Contrary to the primary hypothesis, with increasing PIP the tested PEEP level did not protect against but facilitated gastric insufflation during FMV. This result suggests that PEEP should be used with caution after anaesthesia induction during FMV, whereas CPAP during pre-oxygenation seems to be safe. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02238691.

Pressure measurement in the upper esophagus during cricoid pressure: A high-resolution solid-state manometry study.

BACKGROUND: The use of cricoid pressure is controversial, and its ability to occlude the esophagus has been questioned. In this study, high-resolution solid-state manometry was used to analyze pressure changes in the upper esophagus from cricoid pressure during modified rapid sequence induction. This is a secondary analysis of data from a previous study. METHODS: Seventeen healthy volunteers participated in a double-blind, randomized, placebo-controlled, cross-over study with primary aim to compare differences in the barrier pressure on the lower esophageal sphincter during rapid sequence induction with or without alfentanil. Standardized cricoid pressure of 30 N was applied 2 minutes after propolipid injection and held for 15 seconds and pressures in the esophagus were measured. RESULTS: Cricoid pressure resulted in a pressure increase of 127 ± 98 mmHg (95% CI: 73-182) (placebo) and 123 ± 74 mmHg (95% CI: 84-162) (alfentanil) at the level of the upper esophageal sphincter (UES), compared to baseline. The pressure difference around the UES compared to the proximal esophagus during cricoid pressure application was 165 ± 100 mmHg (placebo) and 159 ± 87 mmHg (alfentanil) (mean ± 1 SD). CONCLUSION: This study using high-resolution solid-state manometry under clinically relevant conditions shows that 30 N cricoid pressure generates high pressure in the area of the UES, far exceeding the levels previously considered necessary to prevent regurgitation. Additional studies are needed to clarify the effectiveness of cricoid pressure in preventing passive regurgitation before it is rejected as a part of rapid sequence induction.

Does the ß-receptor antagonist esmolol have analgesic effects?: A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test.

BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo. DESIGN: Randomised, placebo-controlled cross-over study. SETTING: Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014. PARTICIPANTS: Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials. INTERVENTIONS: At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 µg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 µg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min. MAIN OUTCOME MEASURES: Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively. RESULTS: Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol. CONCLUSION: No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs. TRIAL REGISTRATION: European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.

Effects of Esmolol on the Esophagogastric Junction: A Double-Blind, Randomized, Crossover Study on 14 Healthy Volunteers.

BACKGROUND: Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia. Like remifentanil, the ß-1-adrenoreceptor antagonist may be used to attenuate the stress reaction to tracheal intubation and to modify perioperative anesthetic requirements. It may also reduce the need for opioids in the postoperative period. Its action on the EGJ is however unknown.The aim of this trial was to compare the effects of esmolol and remifentanil on EGJ pressures in healthy volunteers, when administrated as single drugs. METHODS: Measurements of EGJ pressures were made in 14 healthy volunteers using high-resolution solid-state manometry. Interventions were administered in a randomized sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg followed by an infusion of 10 µg·kg·minute over 15 minutes, and remifentanil with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were separated by a 20-minute washout period. Analyses of EGJ pressures were performed at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The primary outcome was the inspiratory EGJ augmentation, while the inspiratory and expiratory EGJ pressures were secondary outcomes. RESULTS: There was no effect on inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean difference -4.0 mm Hg [-9.7 to 1.7]; P= .15). In contrast, remifentanil significantly decreased both inspiratory and expiratory pressures compared to esmolol (-12.2 [-18.6 to -5.7]; P= .003 and -8.0 [-13.3 to -2.8]; P= .006). CONCLUSIONS: Esmolol, compared with remifentanil, does not affect EGJ function. This may be an advantage regarding passive regurgitation and esmolol may thus have a role to play in anesthesia where maintenance of EGJ barrier function is of outmost importance.

Time-to-intubation in obese patients. A randomized study comparing direct laryngoscopy and videolaryngoscopy in experienced anesthetists.

BACKGROUND: Airway management may be difficult in obese patients. Moreover, during prolonged intubation, oxygen desaturation develops rapidly. Videolaryngoscopy improves the view of the larynx, and the Storz® C-MAC™ has been shown to be superior to other videolaryngoscopes in terms of intubation time in obese patients. However, no effort has been made to compare the Storz® C-MAC™ with direct laryngoscopy. The aim of the study was to evaluate if the use of Storz® C-MAC™ may reduce intubation time when compared to direct laryngoscopy (classic Macintosh® blade). METHODS: Eighty patients with Body Mass Index >35 kg/m2 were randomized to orotracheal intubation using either Macintosh® laryngoscope, or the Storz® C-MAC™ with the standard Macintosh blade. Patients had no previous history of a difficult airway. Time-to-intubation (TTI) was defined as the time from the moment anesthetist took the laryngoscope until end-tidal carbon dioxide was detected. RESULTS: No significant difference in TTI could be demonstrated between the two devices tested (mean difference -1.7 s (95% CI:-6.9 to 3.5 s). All patients in the videolaryngoscopy group were successfully intubated with the allocated device, whereas five patients in the direct laryngoscopy group required an alternative device for successful intubation. No significant difference regarding the subjective difficulty of intubation and postoperative sore throat between groups was demonstrated. CONCLUSIONS: In obese patients the airway may be secured equally fast using direct laryngoscopy (Macintosh®) and with videolaryngoscopy using the Stortz® C-MAC™. The risk for failed intubation, however, appears to be greater with direct laryngoscopy, especially in male obese patients.

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; old, 2 ng ml) or a bolus injection of morphine (dose: young, 0.1 mg kg; old, 0.07 mg kg). 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).

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.