Decurarization After Thoracic Anesthesia using sugammadex compared to neostigmine (DATA trial): a multicenter randomized double-blinded controlled trial.

BACKGROUND: Thoracic surgery is a high-risk surgery especially for the risk of postoperative pulmonary complications. Postoperative residual paralysis has been shown to be a risk factor for pulmonary complications. Nevertheless, there are few data in the literature concerning the use of neuromuscular blocking agent antagonists in patients undergoing lung surgery. METHODS: Seventy patients were randomized in three Italian centers to receive sugammadex or neostigmine at the end of thoracic surgery according to the depth of the residual neuromuscular block. The primary outcome was the time from reversal administration to a train-of-four ratio (TOFR) of 0.9. Secondary outcomes were the time to TOFR of 1.0, to extubation, to postanesthesia unit (PACU) discharge, postoperative complications until 30 days after surgery, and length of hospital stay. RESULTS: Median time to recovery to a TOFR of 0.9 was significantly shorter in the sugammadex group compared to the neostigmine one (88 vs. 278 s - P < 0.001). The percentage of patients who recovered to a TOFR of 0.9 within 5 min from reversal administration was 94.4% and 58.8% in the sugammadex and neostigmine groups, respectively (P < 0.001). The time to extubation, but not the PACU stay time, was significantly shorter in the sugammadex group. No differences were found between the study groups as regards postoperative complications and length of hospital stay. The superiority of sugammadex in shortening the recovery time was confirmed for both deep/moderate and shallow/minimal neuromuscular block. CONCLUSIONS: Among patients undergoing thoracic surgery, sugammadex ensures a faster recovery from the neuromuscular block and earlier extubation compared to neostigmine.

One-Lung Ventilation and Postoperative Pulmonary Complications After Major Lung Resection Surgery. A Multicenter Randomized Controlled Trial.

OBJECTIVES: The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established. DESIGN: Multicenter, randomized, single-blind, controlled trial. SETTING: Sixteen Italian hospitals. PARTICIPANTS: A total of 880 patients undergoing elective major lung resection. INTERVENTIONS: Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay. MEASUREMENTS AND MAIN RESULTS: ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p = 0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p = 0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups. CONCLUSIONS: In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

Delayed Gastric Emptying After Multivisceral Resection for Retroperitoneal Sarcoma.

INTRODUCTION: Delayed gastric emptying (DGE) is a common complication in surgery, but incidence and relevance following multivisceral resection are unknown. METHODS: Data from 100 consecutive patients treated for primary retroperitoneal sarcoma (RPS) were analyzed from our institutional prospectively maintained database from January 2019 to April 2020. DGE severity was graded according to the International Study Group of Pancreatic Surgery and classified as primary or secondary to other complications. The primary outcome was incidence and grade of clinically relevant DGE (grades B-C). Secondary outcomes were correlation with patient, tumor, and treatment characteristics, and non-DGE morbidity [Clavien-Dindo (CD) grade ≥ 3]. RESULTS: Forty-two patients developed DGE and 28 had clinically relevant DGE. DGE was primary in 10 patients and secondary in 18 patients; the most common associated complications were: infections (11/18, 61.1%), pancreatic leak (7/18, 38.9%), bleeding (6/18, 33.3%), and bowel leak (6/18, 33.3%). DGE was related to longer length of hospital stay (P < 0.001), ICU admission (P = 0.004), ICU length of stay (P = 0.001), postoperative complications (CD [Formula: see text] 3 in 14/28 in DGE patients vs 11/72 in no-DGE; P = 0.04), and re-operation (P = 0.03). With multivariate analysis, the independent risk factors for DGE were patient comorbidities (OR 1.05; 95% CI 1.01-1.1; P = 0.04) and tumor size (OR 1.05; 95% CI 1.0-1.1; P = 0.02). DISCUSSION: Following multivisceral resection, DGE is a clinically relevant event that can be caused by an underlying complication. Prompt diagnosis and treatment of both DGE and any underlying complications led to full recovery in all cases.

The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial - EURO-RELAX TRIAL.

BACKGROUND: Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established. METHODS: Trial design: an international multicenter randomized controlled double-blind strategy trial. Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery. INTERVENTION: Patients will be randomized to a deep NMB (post-tetanic count 1-2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team). Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra® classification (i.e., ClassIntra® grade ≥ 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients' quality of recovery. DISCUSSION: This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04124757 (EURO-RELAX); registration URL: https://clinicaltrials.gov/ct2/show/NCT04124757 , registered on October 11th, 2019.

A comparison of accelerometric monitoring by TOF Watch® SX and electromyographic monitoring by Tetragraph® for recovery from neuromuscular blockade.

BACKGROUND: Neuromuscular monitoring has become a standard of care for management of anesthesia. While acceleromyography (AMG) is the most common technology used in clinical practice, guidelines suggest that electromyographic (EMG) devices are ideal for quantitative neuromuscular monitoring. The Tetragraph® is an EMG monitor that has recently been marketed. STUDY OBJECTIVE: The aim of this study is to assess the agreement during recovery from neuromuscular blockade of this new monitor with the TOF Watch® SX, and to compare intraobserver variability for the two devices. DESIGN: Single-center, prospective, observational clinical study. SETTING: Operating room. PATIENTS: Twenty-three patients were enrolled and twenty patients were included in the analysis. INTERVENTION: A comparison of TOF-ratios measured sequentially from the same hand with the Tetragraph and TOF Watch SX was conducted during spontaneous recovery of neuromuscular function from patients that received rocuronium during surgery. MAIN OUTCOME MEASURES: We used Bland-Altman plots for repeated measures to compare TOF-ratios obtained sequentially by the two devices. Subsequent measures with the same device were used to calculate intraobserver variability for each monitor. MAIN RESULTS: The bias between AMG and EMG for TOF-ratios range between 0.2 and 1.0 was 0.13 (95% CI 0.08 to 0.18) and the limits of agreement (LoA) were - 0.11 (95% CI -0.20 to -0.06) and 0.37 (95% CI 0.32 to 0.46), respectively. Agreement slightly improved for TOF-ratios higher than 0.8 compared with lower TOF-ratios: the bias was 0.12 (95% CI 0.08 to 0.17) and 0.13 (95% CI 0.08 to 0.19), respectively. EMG relative intraobserver variability was lower compared with AMG (2.0%, IQR 0.0% to 4.5% vs. 3.2%, IQR 1.2% to 6.0%, P = 0.001). CONCLUSIONS: Bias between the TOF Watch SX and the Tetragraph TOF-ratios is in line with previous results for AMG and EMG monitors.

Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial.

BACKGROUND: Over the past number of years, N-methyl-D-aspartate (NMDA) inhibitory drugs, like ketamine, have been introduced as adjuvant treatments for postoperative acute pain, within a multimodal approach. A further extension of this strategy could be the use of opioids with NMDA receptor (NMDAr) antagonism activity for control of postoperative pain. Methadone has a unique pharmacodynamic profile: it is both a µ-agonist and an NMDAr-blocker. OBJECTIVE: We designed this study to investigate the precise contribution of NMDAr antagonism in methadone-induced analgesia. DESIGN: Single-centre, prospective, randomised, double-blind study. SETTING: National Cancer Center - Fondazione IRCCS Istituto Nazionale Tumori Milano; patients were recruited between March 2010 and June 2012. PATIENTS: Ninety-six patients scheduled for an open laparotomy for anterior resection of the rectum. INTERVENTIONS: We randomly assigned patients to four groups: 0-Mo (placebo and morphine), K-Mo [S(+)-ketamine and morphine], 0-Me (placebo and methadone), K-Me [S(+)-ketamine and methadone]. MAIN OUTCOME MEASURES: The primary end-point was the extent of mechanical static (punctuate) hyperalgesia to von Frey hair stimulation lateral to the surgical incision. RESULTS: Peri-incisional hyperalgesia was 8.4 cm (95% confidence interval, 1.5 to 15.41) lower in the treatment group (K-Me) compared with the control group (0-Mo) at 24 h after surgery (P = 0.02). No significant differences were observed between the groups at 48 h after surgery (P = 0.88). Both groups treated with methadone had significantly lower pain during rest and movement, as measured with a Numerical Rating Scale at 24 h. At 48 h, only the movement Numerical Rating Scale was significantly lower. No difference occurred in opioid consumption. CONCLUSION: Methadone provides effective control of acute postoperative pain, independently, by modulation of the hyperalgesia mechanism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, no.: NCT01594047.

ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.

Although erythropoietin ameliorates experimental type 2 diabetes with neuropathy, serious side effects limit its potential clinical use. ARA 290, a nonhematopoietic peptide designed from the structure of erythropoietin, interacts selectively with the innate repair receptor that mediates tissue protection. ARA 290 has shown efficacy in preclinical and clinical studies of metabolic control and neuropathy. To evaluate the potential activity of ARA 290 in type 2 diabetes and painful neuropathy, subjects were enrolled in this phase 2 study. ARA 290 (4 mg) or placebo were self-administered subcutaneously daily for 28 d and the subjects followed for an additional month without further treatment. No potential safety issues were identified. Subjects receiving ARA 290 exhibited an improvement in hemoglobin A(1c) (Hb A(1c)) and lipid profiles throughout the 56 d observation period. Neuropathic symptoms as assessed by the PainDetect questionnaire improved significantly in the ARA 290 group. Mean corneal nerve fiber density (CNFD) was reduced significantly compared with normal controls and subjects with a mean CNFD >1 standard deviation from normal showed a significant increase in CNFD compared with no change in the placebo group. These observations suggest that ARA 290 may benefit both metabolic control and neuropathy in subjects with type 2 diabetes and deserves continued clinical evaluation.

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.