Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients.

Objectives: Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular trap (NETs) markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients. Methods: We examined the plasma levels of two NETs protein markers [myeloperoxidase (MPO) and neutrophil elastase (NE)], as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origin in 29 colon, prostate, and breast cancer patients and in 114 healthy individuals (HI). Results: The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer [r = 0.60 (P < 0.001) and r = 0.53 (P < 0.01), respectively], but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI. Conclusion: Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.

Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56;1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95%CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916.).

Teleconsultation compared with face-to-face consultation in the context of pre-anesthesia evaluation: TELANESTH, a randomized controlled single-blind non-inferiority study.

STUDY OBJECTIVE: During the COVID crisis, pre-anesthesia teleconsultations were widely used leading to savings in time and money. However, the non-inferiority of this system has not yet been evaluated. DESIGN: Prospective, randomized, controlled, single-blind non-inferiority study. SETTING: University hospital. PATIENTS: Patients scheduled for surgery requiring a single pre-anesthesia consultation (PAC). INTERVENTION: Pre-anesthesia teleconsultation (PATC) from patient's home. MEASUREMENTS: Primary outcome: concordance between the pre-anesthesia visit (PAV), performed on the day of surgery, and PAC or PATC on: Secondary outcomes: cancellation rate, immediate perioperative complications, patient satisfaction, organization, and economic and ecological costs. MAIN RESULTS: Out of 172 patients included, 149 were analyzed. PATC was no less effective than PAC in terms of the primary outcome or each of its components: the difference between groups was: - 0.044[90% CI: -0.135; 0.047] (p = 0.0002). There was no difference in cancellation rates (PAC 1.99% vs. PATC 1.27%, p = 0.6) or in immediate perioperative complications (none). Satisfaction was 9.48 (±1.45) in the PAC group and 8.96 (±1.68) in the PATC group (p = 0.0006). In the PATC group, the mean savings per patient were 30 km (± 29), 36 min (± 27), and 18 (± 18) euros, respectively. CONCLUSIONS: According to our criteria, PATC was not inferior to PAC for preoperative patient evaluation and may be an interesting economical, ecological alternative.

Management of patients suffering from mild traumatic brain injury 2023.

OBJECTIVE: To develop a multidisciplinary French reference that addresses initial pre- and in-hospital management of a mild traumatic brain injury patient. DESIGN: A panel of 22 experts was formed on request from the French Society of Emergency Medicine (SFMU) and the French Society of Anaesthesiology and Critical Care Medicine (SFAR). A policy of declaration and monitoring of links of interest was applied and respected throughout the process of producing the guidelines. Similarly, no funding was received from any company marketing a health product (drug or medical device). The expert panel had to respect and follow the Grade® (Grading of Recommendations Assessment, Development and Evaluation) methodology to evaluate the quality of the evidence on which the recommendations were based. Given the impossibility of obtaining a high level of evidence for most of the recommendations, it was decided to adopt a "Recommendations for Professional Practice" (RPP) format, rather than a Formalized Expert Recommendation (FER) format, and to formulate the recommendations using the terminology of the SFMU and SFAR Guidelines. METHODS: Three fields were defined: 1) pre-hospital assessment, 2) emergency room management, and 3) emergency room discharge modalities. The group assessed 11 questions related to mild traumatic brain injury. Each question was formulated using a PICO (Patients Intervention Comparison Outcome) format. RESULTS: The experts' synthesis work and the application of the GRADE® method resulted in the formulation of 14 recommendations. After two rounds of rating, strong agreement was obtained for all recommendations. For one question, no recommendation could be made. CONCLUSION: There was strong agreement among the experts on important, transdisciplinary recommendations, the purpose of which is to improve management practices for patients with mild head injury.

Telemedicine for Preanesthesia Consultations During the First COVID-19 Lockdown.

Introduction: In an effort to avoid travel and interpersonal contact, the COVID-19 health crisis was an opportunity to offer preanesthesia teleconsultation (TCs) to patients scheduled for surgery. Materials and Methods: We studied the technical feasibility and patient experiences of these TCs using a 4-point Likert scale questionnaire. Results: Eighty-six patients out of 139 responded. Technical difficulties (no connection, picture, or sound) occurred in 24% of cases. The patient's experience was considered very positive both in terms of feelings and understanding instructions: 4 (4-4). No deprogramming was required. Conclusion: TCs were approved by patients despite technical problems. Further studies are required to ensure that this type of consultation is not inferior to face-to-face consultations. NCT04920604.

A Pilot Study Assessing a Closed-Loop System for Goal-Directed Fluid Therapy in Abdominal Surgery Patients.

Background: This prospective multicentre pilot study of patients scheduled for elective major abdominal surgery aimed to validate the fluid challenge (FC) proposed by the closed-loop (CL) system via anaesthesiologist assessment. Methods: This was a phase II trial consisting of two inclusion stages (SIMON method). Each FC (250 mL saline solution for 10 min) proposed by the CL was systematically validated by the anaesthesiologist who could either confirm or refuse the FC or give FC without the CL system. A ≥ 95% agreement between the CL and the anaesthesiologist was considered acceptable. Results: The study was interrupted after interim analysis of the first 19 patients (10 men, median age = 61 years, median body mass index = 26 kg/m2). The anaesthesiologists accepted 165/205 (80%) of fluid boluses proposed by the CL. Median cardiac index (CI) was 2.9 (interquartile: IQ (2.7; 3.4) L/min/m2) and the median coefficient of variation (CV) for CI was 13% (10; 17). Fifteen out of nineteen patients (79%) had a mean CI > 2.5 L/min/m2 or spent > 85% surgery time with pulse pressure variation < 13%. No adverse events related to the CL were reported. Conclusion: In this study of patients scheduled for elective major abdominal surgery, the agreement between CL and anaesthesiologist for giving fluid challenge was 80%, suggesting that CL cannot replace the physician but could help in decision making.

Considerations for the Use of Local Anesthesia in the Frail Elderly: Current Perspectives.

The frail, elderly population is at a high risk of postoperative complications. Besides perioperative rehabilitation techniques and management by geriatric teams, the least invasive techniques in anesthesia are required, making regional anesthesia very interesting in terms of benefit-risk ratio. Among them, local anesthesia is a simple, reproducible, inexpensive technique applied to many superficial or deep surgeries, which should make it a gold standard for the frail person. This review provides an update on the current possibilities for various surgeries and exclusion.

How traditional and digital analytics interventions can enhance lung-protective ventilation strategies during general anaesthesia: A two-year quality improvement project analysis.

PURPOSE: This quality improvement project evaluated interventions implemented to enhance individual adherence to a lung-protective ventilation strategy and its triad: low tidal volume, PEEP ≥ 5, recruitment manoeuvres. METHODS: For two years, nine anaesthesia workstations were connected to an automated cloud-based analytics software tool, which automatically recorded ventilation parameters as soon as a new patient case was opened. Four quality improvement periods were determined over the first year: baseline, intervention, no intervention, intervention + digital. In the second year, the digital strategy was continued for nine months, followed by a final "overtime" period. Baseline and no intervention periods included no training. The intervention period included both conventional and educational programs. The digital period included pop-up messages, which automatically appeared on the screen of the anaesthesia data management system when patients were intubated. The primary endpoint was provider adherence to the recommended triad. RESULTS: From October 2018 to December 2020, 12,883 procedures were performed. Data were available for 8968 procedures: baseline (n = 2361), intervention (n = 2423), no intervention (n = 1064), intervention + digital (n = 1862), overtime (n = 1258). Age, Predicted Body Weight, ASA score, type of surgery and airway management were similar between periods. At baseline, 75.2% of procedures reported low tidal volume but only 6.9% involved the complete triad. At over time, Triad was 22% (p < 0.001). Over study period, each parameter of the Triad (RM, Vt and Peep) increased (p < 0.001 vs. baseline), driving pressure decreased although EtCO2 and plateau pressure had not changed. CONCLUSION: Training with the help of digital apps improved LPV adherence over time.

Analgesic efficacy of erector spinae plane blocks for lumbar spine surgery: a randomized double-blind controlled clinical trial.

INTRODUCTION: Erector spinae plane block has been proposed to reduce opioid use and improve pain relief with controversial results. This randomized clinical study aimed to assess the efficacy of erector spinae plane block in major spine surgery including multimodal and 'Enhance Recovery After Surgery' programs. METHOD: After institutional review board approval, adult patients undergoing elective lumbar spine surgery with standardized general anesthesia, rehabilitation and multimodal analgesia protocols were randomly allocated to receive bilateral ultrasound-guided block with saline versus ropivacaine (3.75 mg/mL). Before surgery, a bilateral erector spinae plane block was performed at lumbar level (third vertebrae) with 20 mL of solution for each side. The primary outcome was morphine consumption after 24 hours. Secondary outcomes included pain scores and side effects, from postanesthesia care unit to discharge, and questionnaires at 3 months on pain and quality of life (EQ-5D). RESULTS: From November 2019 to July 2021, 50 patients were enrolled with similar characteristics and surgery for each group. After the first 24 hours, there was no statistical difference regarding cumulative intravenous morphine consumption between ropivacaine and saline groups: 7.3 mg (3.7-19) vs 12.5 mg (3.5-26) (p=0.51). Over the five postoperative days, opioid sparing, pain scores and side effects were similar between groups. At 3 months, pain relief, incidence of chronic pain and EQ-5D were similar between groups. DISCUSSION: Erector spinae plane block used in conjunction with 'Enhance Recovery After Surgery' and multimodal analgesia protocols provides limited reduction in opioid consumption and no long-term benefits. TRIAL REGISTRATION NUMBER: EudraCT 2019-001678-26.

Comparison of continuous with single-injection regional analgesia on patient experience after ambulatory orthopaedic surgery: a randomised multicentre trial.

BACKGROUND: The optimal approach to improving patient experience and analgesia after ambulatory orthopaedic surgery remains unclear. METHODS: This multicentre, randomised clinical trial compared single-injection nerve block analgesia with home delivery of continuous nerve block analgesia by remote-controlled electronic pump. The primary outcome was patient-reported satisfaction (Evaluation du Vecu de l'Anesthesie Generale [EVAN-G]; 0-100) assessed on postoperative Day 2. Secondary outcomes focused on pain, opioid consumption, quality of rehabilitation, activity tracking using a wearable electronic device, and 90-day quality of life. RESULTS: We randomly assigned 294 patients to continuous pump delivery or single injection. For subjects with normal level of pain catastrophising (Pain Catastrophizing Scale <30; n=211), median global EVAN-G was higher with the electronic pump compared with the single injection (78 [69-86] vs 72 [63-84]; P=0.03), as were pain satisfaction scores (P=0.01). For the maximum pain levels, the numerical rating scale score was 2.0 (1.0-5.0) in the electronic-pump group vs 5.0 (3.0-7.0) in the single-injection group on the first 2 days after surgery (P<0.0001). Total opioid consumption in morphine equivalent was higher with single injection (mean [standard deviation]): 70.5 [73.8] vs 31.9 [54.2] mg; P<0.01). The groups did not differ in early rehabilitation on Day 1 or quality of life on Day 45. Electronic activity tracking indicated higher activity in the electronic-pump group (P<0.01). CONCLUSIONS: Self-reported patient satisfaction at home was better with continuous nerve block analgesia via electronic pump vs single injection, without impairing early rehabilitation. Single-injection analgesia was associated with higher pain levels and opioid consumption and lower satisfaction. Patient catastrophising negatively affected the experience of pain. CLINICAL TRIAL REGISTRATION: NCT02720965.

Remote transmission monitoring for postoperative perineural analgesia after major orthopedic surgery: A multicenter, randomized, parallel-group, controlled trial.

STUDY OBJECTIVE: After surgery, patients reported the delay in receiving help as the primary factor for poorly controlled pain. This study aimed to compare the effectiveness of patient management through two communication modalities: remote transmission (RT) versus bedside control (BC). We hypothesized that using remote technology for pump programming may provide the best postoperative infusion regimen for the patient's self-assessment of pain and adverse events. DESIGN: A multicenter, randomized, parallel-group, controlled trial. SETTING: Anesthesiology department and orthopedic surgery ward at three university hospitals. PATIENTS: Eighty patients undergoing orthopedic surgery with postoperative perineural patient-controlled analgesia were included. INTERVENTIONS: Two groups (n = 40 for each group) were formed by randomization. In the postoperative period, perineural analgesia was followed up via an RT system or BC for 72 h. MEASUREMENTS: A nurse assessed daily pain, sensory and motor blocks and adverse events. Patients completed a questionnaire three times a day and alerted for any problem according to the group (RT system or nurses' follow-up). On the third postoperative day, the nurse removed the catheter, completed the final assessment, and collected the historical data from the pump. A physician's shorter response time to change the patient control analgesia (PCA) program was the primary endpoint. RESULTS: Of the 80 patients, 71 were analyzed (34 were randomized to the RT group and 37 to the BC group). Fifty-eight pump setting changes were noted. Analysis of repeated evaluations shows that mean time (SD) to change the PCA pump settings was significantly lower in the RT group (20 min (22.3 min)) than in the BC group (55.9 min (71.1 min)); mean difference [95% CI], -35.9 min [-74.3 to 2.4]); ß estimation [95% CI], -34 [-63 to -6], p = 0.011). Pain relief, sensory and motor blocks did not differ between the groups: ß estimation [95% CI], 0.1 [-0.4 to 0.6], p = 0.753; 0.5 [-0.4 to 1.4], p = 0.255; 0.9 [-0.04 to 1.8], p = 0.687, respectively. ß = -34 [-63 to -6], p = 0.011). The consumption of ropivacaine, nurse workload and the cost of the analgesia regimen decreased in the RT group. No differences were noted in satisfaction scores or complication rates. CONCLUSIONS: The response time for the physician to change the PCA program when necessary was shorter for patients using RT and alerts to the physician were more frequent compared with spot checks by nurses. RT helps to decrease nurses' workload, ropivacaine consumption, and costs but did not affect postoperative pain relief, complication rate, or patient-reported satisfaction score. IRB CONTACT INFORMATION: Comité de Protection des Personnes, Sud Méditerranée III, Montpellier-Nîmes, France, registration number EudraCT A01698-35. CLINICAL TRIAL NUMBER: ClinicalTrials.gov ID:NCT02018068 PROTOCOL: The full trial protocol can be accessed at Department of Anesthesiology and Critical Care Medicine, Medical Research and Statistics Unit, Lapeyronie University Hospital, Avenue Doten G Giraud, Montpellier, France. s-bringuierbranchereau@chu-montpellier.fr.

Pectoral Nerve Blocks for Breast Augmentation Surgery: A Randomized, Double-blind, Dual-centered Controlled Trial.

BACKGROUND: Pectoral nerve blocks have been proposed for analgesia during and after breast cancer surgery, but data are conflicted in aesthetic breast surgery. This trial tested the primary hypothesis that adding a preincisional pectoral nerve block is superior to systemic multimodal analgesic regimen alone for pain control after breast augmentation surgery. A second hypothesis is that rescue opioid consumption would be decreased with a long-lasting effect for both outcomes during the following days. METHODS: Seventy-three adult female patients undergoing aesthetic breast augmentation surgery under general anesthesia were randomly allocated to receive a pectoral nerve block versus no block. Both groups received standard care with protocolized multimodal analgesia alone including systematic acetaminophen and nonsteroidal anti-inflammatory drugs. The primary outcome measure was the maximal numerical rating scale in the first 6 h after extubation. Secondary outcomes included intraoperative remifentanil consumption and from extubation to day 5: maximal numerical rating scale, postoperative cumulative opioid consumption and postoperative opioid side effects, and patient satisfaction recorded at day 5. RESULTS: The maximal numerical rating scale score in the first 6 h was lower in the pectoral nerve block group compared with the control group (3.9 ± 2.5 vs. 5.2 ± 2.2; difference: -1.2 [95% CI, -2.3 to -0.1]; P = 0.036). The pectoral nerve block group had a lower maximal numerical rating scale between days 1 and 5 (2.2 ± 1.9 vs. 3.2 ± 1.7; P = 0.032). The cumulative amount of overall opioids consumption (oral morphine equivalent) was lower for the pectoral nerve block group from hour 6 to day 1 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 31.5] mg, P = 0.006) and from days 1 to 5 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 51] mg, P = 0.002). CONCLUSIONS: Pectoral nerve block in conjunction with multimodal analgesia provides effective perioperative pain relief after aesthetic breast surgery and is associated with reduced opioid consumption over the first 5 postoperative days.

Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery.

BACKGROUND: It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. METHODS: Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. RESULTS: The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. CONCLUSIONS: This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.

Characterisation of pragmatic postoperative PAin Trajectories over seven days and their association with CHronicity after 3 months: a prospective, pilot cohort study (PATCH study).

BACKGROUND: Reliable outcome measurement providing information both on early and late postoperative pain outcomes are still lacking. The purpose of this study was: 1) to characterise postoperative pain trajectories according to an innovative pragmatic concept: ideal pain trajectory (rapid and sustained pain relief) vs non-ideal pain trajectories (late, transient, or no pain relief); and 2) to assess the incidence of persistent post-surgical pain (PPSP) and the potential association between non-ideal pain trajectories and PPSP. METHODS: This prospective observational pilot cohort study was performed from March until June 2016. A total of 344 patients undergoing major general surgery were invited to complete a self-assessment of pain intensity using numerical rating scale (NRS; 0 = no pain to 10 = worst pain) from day 1 until day 7 after surgery, in order to establish their pain trajectory. Three months after surgery, patients were screened for PPSP. RESULTS: Rest pain score was analysed in 308 participants. Among them, 210 (68% - 95% CI: 63-73) had an "ideal" pain trajectory, while 98 (32% - 95% CI: 27-37) had "non-ideal" pain trajectories. Three months after surgery, 31% (95% CI: 26-37) reported PPSP. Multivariable analysis showed that "non-ideal" pain trajectories [OR 2.25; (95% CI: 1.26-4.01) P = 0.006] were significantly associated with PPSP. CONCLUSIONS: The present study proposes an innovative pragmatic concept of postoperative pain trajectories: ideal vs non-ideal pain trajectories, providing information both on acute postoperative pain resolution and early identification patients at risk for developing PPSP. TRIAL REGISTRATION: NCT02599233; November, 6, 2015, with clinicaltrials.gov.