Jakob Walldén

The influence of opioids on gastric function : experimental and clinical studies

BACKGROUND: Opioids have inhibitory effects on gastric motility, but the mechanism is far from clear. Electrical slow waves in the stomach determine the frequency and the peristaltic nature of gastric contractions. The primary aim of this study was to investigate the effects of the opioid fentanyl on gastric myoelectric activity. As there were large variations between the subjects, we investigated whether the variation was correlated to single nucleotide polymorphisms (SNP) of the mu-opioid receptor (MOR) gene. METHODS: We used cutaneous multichannel electrogastrography (EGG) to study myoelectrical activity in 20 patients scheduled for elective surgery. Fasting EGG was recorded for 30 min, followed by intravenous administration of fentanyl 1 microg/kg and subsequent EGG recording for 30 min. Spectral analysis of the two recording periods was performed and the variables assessed were dominant frequency (DF) of the EGG and its power (DP). Genetic analysis of the SNP A118G and G691C of the MOR gene was performed with the polymerase chain reaction technique. RESULTS: There was a significant reduction in DF and DP after intravenous fentanyl. However, there was a large variation between the patients. In eight subjects EGG was unaffected, five subjects had a slower DF (bradygastria) and in six subjects the slow waves disappeared. We found no correlation between the EGG outcome and the presence of A118G or G691C in the MOR gene. CONCLUSIONS: Fentanyl inhibited gastric myoelectrical activity in about half of the subjects. The variation could not be explained by SNP in the MOR gene. Because of small sample size, the results must be regarded as preliminary observations.

Supraventricular Tachycardia Induced by Datex Patient Monitoring System

We thank Dr. Spahn for his comments regarding our recent article. As he points out, there were several errors in the units of doses. We would like to correct the mistakes and also provide additional information conceming the study protocol. Prostaglandin E, and nitroglycerin were infused Iv at a rate of 0.3 pg * kg-l . mini and 5 pg . kg-i . mini, respectively. Anesthesia was induced by an IV dose of 30 pg/ kg of fentanyl, 0.2 mg / kg of midazolam and 0.2 mg/kg of vecuronium. Vecuronium was supplemented at a rate of 0.1 mg * kg-i .30 mir-’ by the end of operation. The study reported in this article was completed within 1 h after the induction. No other drug was given in this study. The administration protocol of the anesthetics and the muscular relaxant was exactly the same for each group. Considering the hemodynamic stabiIity of the patients, their anesthesia status was thought to be stable and sufficient for the stimulus in this study. Before the operation, the patients in this study had been under the same preoperative medication protocol at least for 1 wk. That pro-tocol was oral administration of 20 mg/d isosorbide dinitrate and 10 mg/d nitrendipine. Because the body weights of the patients were within the 40-60 kg range, the dose was not modified according to the body weight.

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 μg · kg−1 · min−1) while lying either on the right lateral side in a 20° head-up position or on the left lateral side in a 20° 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 μmol · L−1; versus left side, 16 μmol · 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 · μmol · L−1). In the control situation, there were differences between the postures in maximal acetaminophen concentration (138 versus 94 μmol · L−1; P <0.0001) and area under the serum acetaminophen concentration time curves from 0 to 60 min (5092 versus 3793 min · μmol · 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.

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

PurposeA 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.MethodsFifty patients (age, 19–69 years) undergoing day-case laparascopic 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.ResultsTwelve 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·µmol·l−1; Cmax, 71 ± 61 µmol·l−1; and Tmax, 81 ± 37 min; and GAS, AUC60, 2059 ± 2633 min·µmol·l−1; Cmax, 53 ± 53 µmol·l−1; and Tmax, 83 ± 41 min. There were no significant differences between groups.ConclusionThere 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.

Effects of fentanyl on gastric myoelectrical activity : a possible association with polymorphisms of the μ-opioid receptor gene?

Background: Opioids have inhibitory effects on gastric motility, but the mechanism is far from clear. Electrical slow waves in the stomach determine the frequency and the peristaltic nature of gastric contractions. The primary aim of this study was to investigate the effects of the opioid fentanyl on gastric myoelectric activity. As there were large variations between the subjects, we investigated whether the variation was correlated to single nucleotide polymorphisms (SNP) of the μ‐opioid receptor (MOR) gene.

Post-operative nausea and vomiting in bariatric surgery patients: an observational study

The risk of post‐operative nausea and vomiting (PONV) in patients undergoing bariatric surgery is unclear. The aim of the study was to investigate the risk of PONV and the use and effectiveness of PONV prophylaxis.

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.

Heparin-binding protein as a biomarker of acute kidney injury in critical illness

There is no biomarker with high sensitivity and specificity for the development of acute kidney injury (AKI) in a mixed intensive care unit (ICU) population. Heparin‐binding protein (HBP) is released from granulocytes and causes increased vascular permeability which plays a role in the development of AKI in sepsis and ischemia. The aim of this study was to investigate whether plasma levels of HBP on admission can predict the development of AKI in a mixed ICU population and in the subgroup with sepsis.

Validation of a prediction model for post-discharge nausea and vomiting after general anaesthesia in a cohort of Swedish ambulatory surgery patients.

BACKGROUNDIn ambulatory surgery, post-discharge nausea and vomiting (PDNV) has been identified as a significant problem occurring in more than one-third of patients. OBJECTIVETo validate a simplified PDNV score in a Swedish population. DESIGNProspective observational study. SETTINGTwo county hospitals in Sweden: Sundsvall from June 2012 to May 2013 and Sunderbyn from January to October 2014. PATIENTSAdult patients undergoing ambulatory surgery under general anaesthesia. MAIN OUTCOME MEASURESPostoperative outcomes with a focus on nausea and vomiting were collected at 2, 4, and 6 h after surgery and on the first three postoperative days. The simplified PDNV score, calculated before discharge, included the factors: female sex, age less than 50 years, history of postoperative nausea and vomiting, postoperative nausea and opioids given postoperatively. The prediction performance of the simplified PDNV score was evaluated in terms of discrimination (area under receiver-operating characteristics curve) and calibration plots and was compared with that of the original development study. RESULTSA total of 559 patients were asked to participate, of which 431 were included in the final study cohort. The overall risk of postoperative nausea and vomiting and PDNV were 18.8 [95% confidence interval (CI), 15.4–22.8]% and 28.1 (95% CI, 24.0–32.5)%, respectively. The discrimination capacity of the simplified PDNV score in our study was similar to that of the original dataset [area under the curve 0.693 (95% CI, 0.638–0.748) vs. 0.706 (0.681–0.731), absolute difference 0.013]. The slope of the calibration curve was 0.893, with a constant of 0.021 (R-square 0.884). CONCLUSIONIn a Swedish cohort of patients, the simplified PDNV score performs well in discriminating between patients who will experience post-discharge nausea and/or vomiting after ambulatory surgery. Our results indicate that the simplified PDNV score is as valid in other cohorts as it was in the original development cohort.

Reply to : Sorbello et al., PONV in bariatric surgery: time for opioid-free anaesthesia

Sir, We thank Sorbello et al. for the comments and interesting views of our recent publication in Acta Anaesthesiologica Scandinavica regarding PONV in patients undergoing bariatric surgery. We totally agree that our results indicate that even a liberal PONV-prophylactic regime is not enough to minimize the risk of PONV. As Sorbello et al. points out, all our patients received opioids – remifentanil as part of the total intravenous anaesthesia and intravenous ketobemidone at the end of surgery. Furthermore, opioids were part of the rescue analgesic regime and given as needed at the recovery unit and at the ward. Our use of total intravenous anaesthesia with the administration of propofol and remifentanil was following a standard protocol and the dose given is primarily related to the size of the patient, adequate depth of anaesthesia and the length of the procedure. Studies have shown that the perioperative dose level of remifentanil do not have an association with PONV outcome. However, the fact that all patients received remifentanil with the addition of ketobemidone before the end of surgery might have major impact on PONV. The dose ketobemidone given was 5–10 mg and we found no association between the dose given and PONV outcome. Our patients represented an ordinary flow of patients. A total of 124 patients underwent bariatric surgery at our hospital during the study period, we managed to screen 88 patients and included 74. Main reasons for not screening patients were lack of research resources and we do not consider that selection bias contributes to the study results. Furthermore, no major conclusions can be drawn in comparing the surgical techniques in our cohort as the number of patients with gastric sleeve was low. Opioids are one of the main contributors to PONV and by minimizing, or even omit opioids, there are great potential to further reduce PONV. Sorbello et al. suggest the use of an opioid-free anaesthesia (OFA) in bariatric surgery. Their preliminary results are very interesting and we look forward to see more studies evaluating the OFA approach. Future anaesthetic/analgesic strategies must be balanced with perfect analgesia and PONVfreedom – today it is difficult to get them both!