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.
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.
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.
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.
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.
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.
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.
Despite recent evidence supporting the adoption of opioid-free anaesthetic and analgesic alternatives in the perioperative context, opioid-based regimens remain standard of care. There is limited ...knowledge about the patients’ perioperative experiences of bariatric surgery, with no study yet investigating their experiences within an opioid-free care pathway.
We aimed to describe similarities and differences in patients’ perioperative experiences of undergoing bariatric surgery with either an opioid-free or opioid-based care pathway.
A qualitative interview study
A strategic sample of patients enrolled in an ongoing randomized controlled trial investigating the effects of opioid-free anaesthesia for bariatric surgery were recruited. In the randomized controlled trial, participants were randomized to either opioid-based anaesthesia or opioid-free anaesthesia, including transcutaneous electrical nerve stimulation as primary postoperative pain management.
Twenty patients were interviewed 3 months after surgery: 10 participants in the opioid-free group versus 10 in the opioid-based group.
Semi-structured interviews were conducted between December 2020 and February 2022 and analysed with qualitative content analysis.
The analysis yielded four categories and 12 subcategories. In Category 1, participants shared diverse emotions before surgery, including anticipation of a healthier life, but also apprehensions and feelings of failure. In Category 2, describing liminality of general anaesthesia, there were similar descriptions of struggling to remember the anaesthesia induction and struggling to surface when recovering from anaesthesia. However, some participants in the opioid-free group shared descriptions of struggling to keep control, describing accentuated memories of the anaesthesia induction. Category 3, managing your pain, showed similar experiences and strategies but different narrations of pain management, with the opioid-free group stating that transcutaneous electrical nerve stimulation works but not when it really hurts, and the opioid-based group describing confidence in but awareness of opioids. Throughout the overall perioperative time period, participants acknowledged Category 4, a patient-professional presence, stating that preparations boost the feeling of confidence before surgery and that they felt confidence in a vulnerable situation although vulnerability challenges communication.
We highlighted the overall similarities in perioperative experiences of patients undergoing bariatric surgery. However, the differences in experiences during opioid-free anaesthesia induction need to be addressed in further implementation and research studies investigating strategies to reduce the sense of loss of control. More research is needed to facilitate the implementation of opioid-free treatment strategies into clinical practice and improve the patient care experience.
Patients with obesity are prescribed more opioids than the general population.
To compare opioid consumption in patients with obesity who underwent Roux-en-Y bariatric surgery (RYGB) with population ...controls with and without obesity, not undergoing bariatric surgery, and to identify characteristics associated with opioid use.
This study included all patients with a principal diagnosis of obesity, aged 18–72 years, with a RYGB surgical code in the Swedish Patient Register between 2007 and 2013.
RYGB patients (n = 23,898) were age- and sex-matched with 1 control patient with obesity (n = 23,898) and 2 population controls without obesity (n = 46,064). Participants were classified as nonconsumers and consumers based on their opioid dispensations during the 12 months before baseline. Opioid consumption was assessed for 24 months.
Nonconsumers. Within 24 months, a significantly higher proportion of RYGB patients (16.6%) started using opioids compared with the controls with obesity (14.3%, P < .0001) and population controls (5.4%, P < .0001). RYGB patients and controls with obesity had higher median daily intake of opioid morphine equivalent (MEQ) (2.8 mg/d) than population controls (2.5 mg/d, P < .0001). Consumers. Within 24 months, the proportion of RYGB patients and controls with obesity that was using opioids were similar (53.1% and 53.4%), but higher compared to population controls (38.0%, P < .0001). The median daily opioid MEQ was higher among RYGB patients than in population controls (10.5 versus 7.8 mg/d, P < .0001). RYGB patients, overall, had higher incidence of bowel surgery and cholecystectomy compared with controls with obesity and population controls, leading to prolonged opioid use in this group. Opioid consumption in general was associated with chronic pain and psychiatric disorder, which were more common in patients with obesity than in the population controls.
RYGB surgery increased the risk of prolonged opioid use in patients with obesity who were nonconsumers before surgery but had no effect on overall opioid use among prior consumers. RYGB-associated complications requiring surgery influenced opioid use for both nonconsumers and consumers. Regular reassessments of pain mechanisms and specific treatment owing to type of pain could prevent unnecessary opioid use in this patient group.
•More RYGB patients than controls with obesity started using opioids during the study period.•Proportions of prior consumers that remained consumers were similar in RYGB patients and controls with obesity during the study period.•Median daily opioid intake was similar in RYGB patients and controls with obesity, which was higher than for population controls.•Bowel surgery and cholecystectomy were associated with prolonged opioid use, and more common in RYGB patients compared to controls with obesity and populations controls.•Prior chronic pain and psychiatric disorders were associated with continuous opioid use during follow-up, and more common in RYGB patients and controls with obesity compared with population controls.•controls.
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.
Advanced-stage ovarian cancer has a poor prognosis; surgical resection with the intent to leave no residual tumour followed by adjuvant chemotherapy is the standard treatment. Local anaesthetics (LA) ...have anti-inflammatory and analgesic effects. We hypothesised that intraperitoneal LA (IPLA) would lead to improved postoperative recovery, better pain relief, and earlier start of chemotherapy.
This was a prospective, randomised, double-blind, placebo-controlled pilot study in 40 women undergoing open abdominal cytoreductive surgery. Patients were randomised to receive either intraperitoneal ropivacaine (Group IPLA) or saline (Group Placebo) perioperatively. Except for study drug, patients were treated similarly. Intraoperatively, ropivacaine 2 mg ml−1 or 0.9% saline was injected thrice intraperitoneally, and after operation via a catheter and analgesic pump into the peritoneal cavity for 72 h. Postoperative pain, time to recovery, home discharge, time to start of chemotherapy, and postoperative complications were recorded.
No complications from LA administration were recorded. Pain intensity and rescue analgesic consumption were similar between groups. Time to initiation of chemotherapy was significantly shorter in Group IPLA (median 21 inter-quartile range 21–29 vs 29 inter-quartile range 21–40 days; P=0.021). Other parameters including time to home readiness, home discharge and incidence, and complexity of postoperative complications were similar between the groups.
Intraperitoneal ropivacaine during and for 72 h after operation after cytoreductive surgery for ovarian cancer is safe and reduces the time interval to initiation of chemotherapy. Larger studies are warranted to confirm these initial findings.
NCT02256228.
We report results from a subgroup within the ongoing PHYSSURG-C trial with the aim to examine effects of exercise on IGF-1 and IGFBP-3 in patients undergoing colorectal cancer surgery.
Randomised ...controlled trial.
A Swedish university hospital.
Between 2015 and 2016, 217 patients were enrolled (I = 106, C = 111), with 122 patients that had given blood samples at baseline and at least at one follow-up (I = 51, C = 71). Patients 20 year or older with colorectal cancer were eligible. Exclusion criteria were emergency surgery, local surgery, language problems or inability to perform intervention.
Patients were computer-randomised to either a daily home-based aerobic exercise intervention (I), or to usual care (C). The intervention lasted two weeks before surgery and four weeks after discharge from hospital and consisted of medium-intensity aerobic exercise and inspiratory muscle training. Circulating concentrations of IGF-1 and IGFBP-3 were determined by blinded personnel at baseline, time of surgery and 4–6 weeks postoperatively.
The outcome of this subpopulation report was change in IGF-1/IGFBP-3 ratio, IGF-1 and IGFBP-3 concentrations from baseline to surgery, and 4–6 weeks postoperatively.
The IGF-1/IGFBP-3 ratio increased from baseline to surgery by 11% in I and 8% in C with no difference between groups (I vs. C: 1.04, 95%CI: 0.97–1.11; p = 1.000). Postoperative change was 5% in I and 3% in C with no difference between groups (I vs. C:1.03, 95%CI: 0.96–1.10; p = 1.000). Results concerning IGF-1 and IGFBP-3 also showed statistically significant dynamics over time with no difference between groups. No adverse events were reported.
The home-based exercise program in our trial did not have any effect on IGF-1, or IGFBP-3.
Trial registration: The study was registered at ClinicalTrials.gov with identifier NCT02299596. This work was funded externally.
•Randomised controlled study with large sample size, examining exercise before and after colorectal cancer surgery.•The first randomised controlled trial examining effect of exercise on IGF axis in patients with current cancer.•Pragmatic home-based intervention which increases external validity but reduces reliability of data on compliance.•We found no effect on IGF-1/IGFBP-3 ratio or concentrations of IGF-1, IGFBP-3, or HbA1c after exercise compared to control.
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.
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.
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.
ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014.
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