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Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been used for acute pain treatment and has dose-dependent analgesic effects, and therefore presents an alternative to intravenous (iv) opioids for postoperative pain relief. The aim of this meta-analysis was to compare high-frequency, high-intensity (HFHI or intense) TENS to iv opioids with regard to postoperative pain intensity, recovery time in the Post Anesthesia Care Unit (PACU) and opioid consumption after elective gynecological surgery. We searched Medline, Embase, Web of Science, Cochrane, Amed and Cinahl for RCTs and quasi-experimental studies (2010–2022), and WHO and ClinicalTrials.gov for ongoing/unpublished studies. Meta-analysis and subsequent Trial Sequential Analysis (TSA) was performed for all stated outcomes. Quality of evidence was assessed according to GRADE. Only three RCTs met the inclusion criteria (362 participants). The surgical procedures involved surgical abortion, gynecologic laparoscopy and hysteroscopy. The applied TENS frequency was 80 Hz and intensity 40–60 mA. There was no difference in pain intensity according to Visual Analogue Scale (VAS) at discharge from PACU between the TENS and opioid group (MD VAS −0.15, 95 % CI −0.38 to 0.09) (moderate level of evidence). Time in PACU was significantly shorter in the TENS group (MD −15.2, 95 % −22.75 to −7.67), and this finding was manifested by TSA (high-level of evidence). Opioid consumption in PACU was lower in the TENS group (MD Morphine equivalents per patient mg −3.42, 95 % −4.67 to −2.17) (high-level of evidence). There was no detectable difference in postoperative pain relief between HFHI TENS and iv opioids after gynecological surgery. Moreover, HFHI TENS decreases recovery time and opioid consumption in PACU. HFHI TENS may be considered an opioid-sparing alternative for postoperative pain relief after gynecological surgery. PROSPERO CRD42021231048. [ABSTRACT FROM AUTHOR]

Background and Objectives: Preeclampsia is a multisystem disorder that affects maternal endothelium. The glycocalyx lines and protects the endothelial surface. In severe systemic diseases, like sepsis, it is shed and glycocalyx degradation products can be detected in increased concentrations in plasma. The aim of this study was to compare circulating concentrations of glycocalyx degradation products in degrees of preeclampsia severity. Study design: In this observational study, we included women from the South African PROVE biobank. Women were divided into normotensive controls, women with preeclampsia without end-organ complications, women with a single end-organ complication and women with multiple end-organ complications. Plasma samples taken at inclusion after diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed with ELISA for syndecan-1, hyaluronic acid and thrombomodulin and compared between groups. Results: Women with preeclampsia (n = 47) had increased plasma concentrations of hyaluronic acid (100.3 ng/ml IQR 54.2--204 vs. 27.0 ng/ml IQR (13.5--66.6), p < 0,001) and thrombomodulin (4.22 ng/ml IQR 3.55--5.17 vs. 3.49 ng/ml IQR 3.01--3.68, p = 0.007) but not syndecan-1 compared with normotensive women (n = 10). There were no differences in plasma concentration in any of these biomarkers in women with preeclampsia with no end-organ complications (n = 10) compared with women with preeclampsia and one end-organ complication (n = 24). Women with preeclampsia with two or more end-organ complications (n = 13) had increased plasma concentrations of thrombomodulin (5.46 ng/ml, IQR 4.85--7.83 vs. 4.66 ng/ml, IQR 3.45--4.88, p = 0.042) compared with women with preeclampsia and no end-organ complications. Conclusion: Thrombomodulin was associated with disease severity and may be valuable for risk-stratifying women with preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Opioid‐based treatment is used to manage stress responses during surgery and postoperative pain. However, opioids have both acute and long‐term side effects, calling for opioid‐free anaesthetic strategies. This meta‐analysis compares adverse events, postoperative recovery, discharge time from post‐anaesthesia care unit, and postoperative pain, nausea, vomiting, and opioid consumption between strict opioid‐free and opioid‐based general anaesthesia. Methods: We conducted a systematic review and meta‐analysis. We searched PubMed, Embase, Cinahl, Cochrane Library, selected reference lists, and Google Scholar. We included randomised controlled trials (RCTs) published between January 2000 and February 2021 with at least one opioid‐free study arm, i.e. no opioids administered preoperatively, during anaesthesia induction, before skin closure, or before emergence from anaesthesia. Results: The study comprised 1934 patients from 26 RCTs. Common interventions included laparoscopic gynaecological surgery, upper gastrointestinal surgery, and breast surgery. There is firm evidence that opioid‐free anaesthesia significantly reduced adverse postoperative events (OR 0.32, 95% CI 0.22 to 0.46, I2 = 56%, p < 0.00001), mainly driven by decreased nausea (OR 0.27, (0.17 to 0.42), p < 0.00001) and vomiting (OR 0.22 (0.11 to 0.41), p < 0.00001). Postoperative opioid consumption was significantly lower in the opioid‐free group (−6.00 mg (−8.52 to −3.48), p < 0.00001). There was no significant difference in length of post‐anaesthesia care unit stay and overall postoperative pain between groups. Conclusions: Opioid‐free anaesthesia can improve postoperative outcomes in several surgical settings without evidence of adverse effects on patient safety and pain management. There is a need for more evidence‐based non‐opioid anaesthetic protocols for different types of surgery as well as postoperative phases. [ABSTRACT FROM AUTHOR]

Background: Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines.Methods: This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin.Results: Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations.Conclusion: In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans. [ABSTRACT FROM AUTHOR]

Background: Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma. Methods: CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum. Results: Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy. Conclusion: NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications. [ABSTRACT FROM AUTHOR]

Background/Aim: A number of patients continue to suffer from chronic abdominal pain of unknown origin, which may also lead to a prolonged use of opioid analgesics. Symptoms of abdominal pain, nausea and vomiting in this patient group resemble the characteristics of the Roux stasis Syndrome. The aim was to elucidate relationships between chronic abdominal pain, Roux limb motor activity and opioid analgesics. Methods: Roux limb high-resolution manometry and ratings of abdominal pain and quality of life were analysed in 15 gastric bypass patients reporting abdominal pain of unknown origin. Effect of acute opiate administration (morphine i.v.) on fasting Roux limb motor activity was assessed in asymptomatic and morphine-naïve gastric bypass patients (n = 9) and compared with an untreated control group (n = 11). Results: In the symptomatic patient group, we found disturbed Roux limb motor patterns in 10 out of 15 examinations, but no signs of Roux stasis syndrome. A high prevalence of prescribed opioid analgesics as well as a high number of reoperations in this group. The worst quality of life and the highest number of pain-killing medications were observed among the patients with distal pacemaker activity in Roux limb. In the morphine-naïve and asymptomatic patients, morphine increased the muscular tone in the Roux limb during phase III-like motor activity. Summary and Conclusions: A majority of the RYGBP patients with chronic abdominal pain had a disturbed Roux limb fasting motility, and there was a high prevalence of prescribed opioid analgesics. In opiate-naïve RYGBP patients, acute morphine intravenously increased the muscular tone of the Roux limb. [ABSTRACT FROM AUTHOR]

Background: Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer.Methods/design: We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis.Discussion: An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results.Trial Registration: ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

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 μg/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. [ABSTRACT FROM AUTHOR]

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. Fifty 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. 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·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. 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. [ABSTRACT FROM AUTHOR]

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