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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.

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Amed and Cinahl for RCTs and quasi-experimental studies (2010–2022), and WHO and ClinicalTrials.gov for ongoing/unpublished studies.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]

Introduction: Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women's and their partners' experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care., Methods and Analysis: This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women's and partner's experiences are distributed at follow-up., Ethics and Dissemination: By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women's personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals., Trial Registration Number: ISRCTN13060768., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To compare the time spent in the Post-Anesthesia Care Unit (PACU) and the pain-relieving effects of treatment with high-frequency, high-intensity transcutaneous electrical nerve stimulation (TENS) or intravenous (IV) opioids after hysteroscopy., Methods: All patients who postoperatively reported a visual analogue scale (VAS) pain score of ≥3 were included in the study. TENS treatment was given with a stimulus intensity between 40 and 60 mA for 1 minute and repeated once if there was insufficient pain relief. In the opioid group, a fractionated dose of 5 mg morphine was administered. If the patient reported insufficient pain relief after the assigned treatment, the patient was reassigned to the other treatment group., Results: Seventy-four women were randomized to TENS (n=38) or IV opioids (n=36) for treatment. Both groups reported significant pain relief after discharge from the PACU, with a decrease of VAS scores from 5.6 to 1.4 in the TENS group (P<0.001) and 5.1 to 1.3 in the opioid group (P<0.001). There were no significant differences between the groups. When only the responders in both groups, i.e., patients with VAS scores of <3 on respectively assigned treatments, were compared, the TENS responders (n=22) were found to have spent a significantly shorter time in the PACU (91 vs. 69 minutes, P=0.013) compared to the opioid responders (n=20)., Conclusion: Using TENS as first line of pain relief may reduce the need for postoperative opioids. In addition, TENS appears preferable as the first line of treatment due to its association with a shorter time spent in the PACU if the patient responds to the treatment., Trial Registration: Västra Götalandsregionen Identifier: 211261.

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.

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.

Background and Objective: We investigated the relationship between acceleromyography and a peripheral nerve stimulator for measuring reversal in patients administered sugammadex following rocuronium., Methods: In this randomized, active and within-participant controlled study, patients received rocuronium 0.6 mg kg for intubation with 0.15 mg kg maintenance doses as required. Single-dose sugammadex 4.0 or 1.0 mg kg was given 15 min after the last rocuronium dose. Neuromuscular monitoring was performed simultaneously: acceleromyography on one forearm and a peripheral nerve stimulator on the other. The peripheral nerve stimulator assessor was blinded to acceleromyography results. The primary efficacy end point was the difference between time from start of sugammadex 4.0 mg kg administration to recovery of the train-of-four ratio to 0.9 (acceleromyography) and time to reappearance of the fourth twitch (T4) (peripheral nerve stimulator)., Results: Sixty-one patients received sugammadex 4.0 mg kg. With acceleromyography, mean (SD) recovery time to a train-of-four ratio of at least 0.9 was 1.5 (0.7) min. With both the peripheral nerve stimulator and acceleromyography, mean (SD) time to T4 reappearance was 0.8 (0.3) min. Mean (95% confidence interval) difference between time to T4 reappearance (peripheral nerve stimulator) and recovery to a train-of-four ratio of at least 0.9 (acceleromyography) was 0.8 (0.6-0.9) min., Conclusion: T4 is detected at similar times when measured by a peripheral nerve stimulator or acceleromyography following sugammadex 4.0 mg kg administration 15 min after rocuronium. The mean interval between T4 reappearance (peripheral nerve stimulator) and recovery to a train-of-four ratio of at least 0.9 (acceleromyography) was 0.8 min. These findings provide guidance for evaluating the reversal effect of sugammadex in clinical situations.

Background: The prevalence of obesity has increased dramatically in recent decades. The gastrointestinal changes associated with obesity have clinical significance for the anesthesiologist in the perioperative period. The lower esophageal sphincter and the upper esophageal sphincter play a central role in preventing regurgitation and aspiration. The effects of increased intra-abdominal pressure during anesthesia on the lower esophageal sphincter and the upper esophageal sphincter in obese patients are unknown. In the present study we evaluated, with high-resolution solid-state manometry, the upper esophageal sphincter, lower esophageal sphincter, and barrier pressure (BrP) (lower esophageal pressure--gastric pressure) in obese patients during anesthesia induction and compared them with pressures in non-obese patients., Methods: We studied 28 patients, ages 18 to 72 years, 14 with a body mass index > or = 35 kg/m(2), who were undergoing laparoscopic gastric bypass, and 14 with a body mass index < or = 30 kg/m(2), who were undergoing laparoscopic cholecystectomy, using high-resolution solid-state manometry., Results: Upper esophageal sphincter pressure decreased during anesthesia induction in both groups. Lower esophageal sphincter pressure decreased in both groups during anesthesia induction, and it was significantly lower in obese patients than in non-obese patients. The BrP decreased in both groups and was significantly lower in the obese group than in the non-obese group. The BrP remained positive at all times in both groups., Conclusion: Lower esophageal sphincter and BrPs decreased in both obese and non-obese patients during anesthesia induction, but were significantly lower in obese patients. Although the BrP was significantly lower, it remained positive in all patients.

Purpose: The mechanism of the antiemetic actions of corticosteroids is not known. The purpose of this study was to evaluate if betamethasone can prevent nausea, vomiting or increase of vasopressin induced by apomorphine. Metoclopramide, a dopamine antagonist, was used as a control substance., Methods: Ten healthy volunteers were studied on three occasions. In a randomized order they were allocated to receive pretreatment with betamethasone 8 mg iv, metoclopramide 10 mg iv, and normal saline 2 mL as placebo on the three different occasions, 15 min before the administration of apomorphine 30 microg x kg(-1) s.c.. After administration of apomorphine, episodes of vomiting were recorded, and the intensity of nausea was estimated by the subject on a visual analogue scale (VAS 0-10 cm). Blood samples for analysis of plasma concentrations of vasopressin were analyzed., Results: One volunteer decided to withdraw, as he experienced akathisia after receiving metoclopramide. During the first two hours after apomorphine, eight of nine volunteers vomited both after betamethasone and placebo. One volunteer did not vomit after betamethasone and placebo but he experienced nausea. None of the volunteers vomited after metoclopramide (P < 0.01 vs betamethasone and placebo). The maximum VAS for nausea was significantly higher after betamethasone and placebo compared to metoclopramide (P < 0.01). The vasopressin levels increased after betamethasone and placebo, but there was no increase in any volunteer after pretreatment with metoclopramide., Conclusion: This study demonstrates that betamethasone does not prevent nausea, vomiting and increase of vasopressin induced by apomorphine, whereas metoclopramide prevents apomorphine-induced emesis. Our work suggests that betamethasone does not have dopamine-antagonistic effects.

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