Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

BACKGROUND: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. METHODS: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 µg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. CONCLUSION: No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

A novel stimulating electrode attachment method designed to maintain electromyography-based neuromuscular monitoring detectability during laparoscopic surgery: a single-center randomized, double-blind, controlled pilot study.

PURPOSE: We evaluated the electromyography (EMG)-based neuromuscular monitoring detectability of our novel stimulating electrode attachment method compared to the original Nihon-Kohden (Tokyo, Japan) attachment method. METHODS: This single-center randomized, double-blind, controlled pilot study enrolled 32 patients aged ≥ 18 years, undergoing scheduled laparoscopic surgery. The EMG electrode NM-345Y™ was attached to one forearm using the Nihon-Kohden method (Pattern N-K) and the other forearm using our novel method (Pattern Cross). The allocation to each attachment method was determined post-randomization. In Pattern Cross, the NM-345Y™ was attached such that the line connecting the anode and cathode crosses the ulnar nerve. Patients received 0.9 mg/kg rocuronium after calibration with the forearm in 90-degree supination. Following tracheal intubation, the forearm was positioned in 0-degree pronation. Intraoperatively, 0.2 mg/kg rocuronium was administered if the train-of-four (TOF) count one persisted for 1 min on either side. Post-surgery, the forearm position was returned to 90-degree supination, and rocuronium was antagonized with sugammadex. TOF and post-tetanic count (PTC) were simultaneously measured bilaterally every 15 s and 5 min, respectively, from post-calibration to tracheal extubation. RESULTS: The time to first PTC appearance was significantly shorter by 33 min in the Pattern Cross group than in the Pattern N-K group (95% Confidence interval: 1-66, p = 0.043). Following sugammadex administration, TOF ratios ≥ 0.9 were achieved in 72% of patients in the Pattern N-K group and 97% of those in the Pattern Cross group (p = 0.025). CONCLUSIONS: Crossing the line connecting the anode and cathode with the ulnar nerve stabilizes EMG-based neuromuscular monitoring detectability.

Pholcodine, perioperative anaphylaxis, and the European Medicines Agency: finally the decision to remove pholcodine from the market in the European Union.

Two recent case-control studies, both published in the British Journal of Anaesthesia, have shown that intake of pholcodine-containing cough medicines during the year preceding general anaesthesia significantly increased the risk of anaphylaxis caused by neuromuscular blocking agents. Both a French multicentre study and a single-centre study from Western Australia offer strong support to the pholcodine hypothesis for IgE-sensitisation to neuromuscular blocking agents. The European Medicines Agency, criticised for not taking preventive action at its first assessment of pholcodine in 2011, finally recommended a stop to sales of all pholcodine-containing medicines throughout the EU on December 1, 2022. Time will tell whether this reduces the incidence of perioperative anaphylaxis in the EU, as in Scandinavia.

Comparison of the effects of sugammadex versus neostigmine for reversal of neuromuscular block on hospital costs of care.

BACKGROUND: Sugammadex reversal of neuromuscular block facilitates recovery of neuromuscular function after surgery, but the drug is expensive. We evaluated the effects of sugammadex on hospital costs of care. METHODS: We analysed 79 474 adult surgical patients who received neuromuscular blocking agents and reversal from two academic healthcare networks between 2016 and 2021 to calculate differences in direct costs. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to calculate differences in total costs in US dollars. Perioperative risk profiles were defined based on ASA physical status and admission status (ambulatory surgery vs hospitalisation). RESULTS: Based on our registry data analysis, administration of sugammadex vs neostigmine was associated with lower direct costs (-1.3% lower costs; 95% confidence interval [CI], -0.5 to -2.2%; P=0.002). In the HCUP-NIS matched cohort, sugammadex use was associated with US$232 lower total costs (95% CI, -US$376 to -US$88; P=0.002). Subgroup analysis revealed that sugammadex was associated with US$1042 lower total costs (95% CI, -US$1198 to -US$884; P<0.001) in patients with lower risk. In contrast, sugammadex was associated with US$620 higher total costs (95% CI, US$377 to US$865; P<0.001) in patients with a higher risk (American Society of Anesthesiologists physical status ≥3 and preoperative hospitalisation). CONCLUSIONS: The effects of using sugammadex on costs of care depend on patient risk, defined based on comorbidities and admission status. We observed lower costs of care in patients with lower risk and higher costs of care in hospitalised surgical patients with severe comorbidities.

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis. METHODS: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated. RESULTS: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions. CONCLUSIONS: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis. CLINICAL TRIAL REGISTRATION: NCT02250729.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Postoperative pulmonary complications after sugammadex reversal of neuromuscular blockade: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Sugammadex has been reported to lower the incidence of postoperative residual neuromuscular blockade. Despite the advantages, until recently the effects of sugammadex on postoperative pulmonary complications (PPCs) were controversial. We conducted a systematic review and meta-analysis to determine whether reversal with sugammadex was associated with a lower risk of PPCs compared with neostigmine. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to May 2022. Randomized controlled trials (RCTs) and observational studies comparing PPCs in patients receiving sugammadex or neostigmine as reversal agent at the end of surgery were included. The primary outcomes focused on PPCs including desaturation, pneumonia, atelectasis, noninvasive ventilation (NIV) and reintubation. Trial sequential analysis was performed on the primary outcomes to confirm whether firm evidence was reached. RESULTS: Meta-analysis of included studies showed that the rate of desaturation (43.2% vs 45.0%, RR = 0.82; 95% CI 0.63 to 1.05; p = 0.11) were comparable between the two groups. When looking at other primary outcomes, significantly lower risk of pneumonia (1.37% vs 2.45%, RR = 0.65; 95% CI 0.49 to 0.85; p = 0.002), atelectasis (24.6% vs 30.4%, RR = 0.64; 95% CI 0.42 to 0.98; p = 0.04), NIV (1.37% vs 2.33%, RR = 0.65; 95% CI 0.43 to 0.98; p = 0.04) and reintubation (0.99% vs 1.65%, RR = 0.62; 95% CI 0.43 to 0.91; p = 0.01) in the sugammadex group were detected compared with the neostigmine group. CONCLUSIONS: We concluded that sugammadex is more effective at reducing the incidence of PPCs including pneumonia, atelectasis, NIV and reintubation compared with neostigmine. Further evidence, preferably from RCTs, is required to confirm these findings.

Effective dose of remimazolam co-administered with remifentanil to facilitate I-gel insertion without neuromuscular blocking agents: an up-and-down sequential allocation trial.

BACKGROUND: Remimazolam is a new anesthetic drug developed and is an ultra-short-acting agent with rapid onset and offset. The pharmacology of this drug seems to be ideal for short surgeries eligible for I-gel insertion. Therefore, this study aimed to determine the optimal bolus dose of remimazolam for I-gel insertion when co-administered with remifentanil without neuromuscular blocking agents (NMBAs). METHODS: Patients aged 19-65 years with American Society of Anesthesiologists physical status I or II scheduled for general anesthesia were enrolled. The first dose of remimazolam was 0.15 mg/kg and remifentanil was co-administered at an effect-site concentration (Ce) of 3.0 ng/mL. The dose of remimazolam for the following patient was decreased or increased by 0.05 mg/kg depending on the success or failure of I-gel insertion in the previous patient. RESULTS: The remimazolam bolus dose required for successful I-gel insertion in 50% of adult patients using modified Dixon's up-and-down method with remifentanil Ce 3.0 ng/mL and no NMBAs was 0.280 ± 0.048 mg/kg. Isotonic regression analysis showed that the 50% and 95% effective doses were 0.244 (83% confidence interval [CI] 0.213-0.313) mg/kg and 0.444 (95% CI 0.436-0.448) mg/kg, respectively. The mean time to loss of consciousness (Modified Observer's Assessment of Alertness/Sedation score < 2) was 52.2 s. Three patients (12.0%) showed a reduction in systolic blood pressure of more than 30% from baseline. CONCLUSIONS: Selecting the appropriate dose of remimazolam/remifentanil without NMBAs makes it feasible to insert the I-gel. TRIAL REGISTRATION: This study protocol was registered at http://cris.nih.go.kr (KCT0007801, 12th, October, 2022).

An Assessment of the Practice of Neuromuscular Blockade and the Association Between Its Prophylactic Use and Outcomes Among Postoperative Pediatric Cardiac Patients.

OBJECTIVES: The authors investigated the management of neuromuscular blocking agents (NMBAs) for pediatric patients after cardiac surgery, and compared the outcomes of patients who received prophylactic NMBA (pNMBA) infusions and patients without pNMBA infusions. DESIGN: A retrospective cohort study. SETTING: At a tertiary teaching hospital. PARTICIPANTS: Patients younger than 18, with congenital heart disease, who underwent cardiac surgery. INTERVENTIONS: Commencement of NMBA infusion in the first 2 hours after surgery MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a composite of one or more of the following major adverse events (MAEs) that occurred within 7 days after surgery: death from any cause, a circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. The secondary endpoints included the total duration of mechanical ventilation for the first 30 days after surgery. A total of 566 patients were included in this study. The MAEs occurred in 13 patients (2.3%). An NMBA was commenced within 2 hours after surgery in 207 patients (36.6%). There were significant differences in the incidence of postoperative MAEs between the pNMBA group and the non-pNMBA group (5.3% v 0.6%; p < 0.001). In multivariate regression models, pNMBA infusion was not significantly associated with the incidence of MAEs (odds ratio: 1.79, 95% CI: 0.23-13.93, p = 0.58), but was significantly associated with prolonged mechanical ventilation by 3.85 days (p < 0.001). CONCLUSIONS: Postoperative prophylactic neuromuscular blockade after cardiac surgery can be associated with prolonged mechanical ventilation, but has no association with MAEs among pediatric patients with congenital heart disease.

Tracheal intubating conditions in elderly patients when train-of-four count is zero after rocuronium 0.6 or 0.9 mg/kg. A secondary analysis.

PURPOSE: The neuromuscular blocking agent rocuronium can be administered to facilitate tracheal intubation. We hypothesized that rocuronium 0.9 mg/kg provided a larger proportion of patients with vocal cords in abducted position compared to rocuronium 0.6 mg/kg at train-of-four (TOF) 0. METHODS: This secondary analysis was based on 52 elderly surgical patients of which 36 patients received rocuronium 0.6 mg/kg and 16 patients received rocuronium 0.9 mg/kg. Neuromuscular block was monitored with acceleromyography with TOF stimulation at the ulnar nerve. The primary outcome was the proportion of patients with vocal cords in abducted position at TOF 0. Secondary outcomes were intubating conditions evaluated by the Fuchs-Buder scale, the Intubating Difficulty Score (IDS), onset time, and duration of action of rocuronium. RESULTS: At TOF 0, a significantly larger proportion of patients had vocal cords in abducted position in the rocuronium 0.9 mg/kg group (81%) compared with the rocuronium 0.6 mg/kg group (53%); difference (%) 28, 95% Cl 3-53, P = 0.05. Excellent intubating conditions (Fuchs-Buder) were more common in the rocuronium 0.9 mg/kg group (62.5%); difference (%) 32.5, 95% Cl 4-61), P = 0.03. No significant difference was found in IDS or onset time of rocuronium (difference 19 s, 95% Cl: -5-43). Duration of action was significantly longer (difference 29 min, 95% Cl: 10-47) in the 0.9 mg/kg group. CONCLUSION: The proportion of patients with vocal cords in abducted position was significantly larger after rocuronium 0.9 mg/kg compared to rocuronium 0.6 mg/kg at TOF 0 monitored at the ulnar nerve.

Effects of the attachment method of the stimulating electrodes Nihon-Kohden NM-345Y™ and changes in forearm position on stimulus current values during calibration in electromyography-based neuromuscular monitoring: a single-center experimental study.

PURPOSE: The traditionally recommended method for attaching electromyography (EMG) electrodes (NM-345Y™) during EMG-based neuromuscular monitoring developed by Nihon-Kohden may decrease the monitoring accuracy when forearm limb position changes. This study investigated methods for attaching stimulating electrodes that maintained stable EMG-based neuromuscular monitoring accuracy, regardless of forearm limb position changes. METHODS: This single-center experimental study recruited 28 healthy adults from October 2022 to December 2022. The NM-345Y™ was attached to the forearm using three patterns: Pattern N, electrodes attached according to the attachment pattern recommended by Nihon-Kohden; Pattern U, electrodes attached along the ulnar nerve identified using an ultrasound device; Pattern C, electrodes attached where the ulnar nerve crosses the line connecting the centers of the anode and cathode of the stimulating electrodes. The stimulus current values during calibration were measured at three forearm positions for each attachment pattern: supination 90 degrees; pronation 0 degrees; pronation 90 degrees. The differences in stimulus current values caused by forearm position changes were calculated as the difference between values at supination 90 degrees and pronation 0 degrees and between values at supination 90 degrees and pronation 90 degrees. RESULTS: Pattern C showed significantly smaller differences than Pattern N between the stimulus current values at supination 90 degrees and pronation 0 degrees (p = 0.018) and between the stimulus current values at supination 90 degrees and pronation 90 degrees (p = 0.008). CONCLUSION: Crossing the ulnar nerve with the line connecting the anode and cathode of the stimulating electrodes may stabilize EMG-based neuromuscular monitoring accuracy.

Intensive Care Unit- Acquired Weakness and Hospital Functional Mobility Outcomes Following Invasive Mechanical Ventilation in Patients with COVID-19: A Single-Centre Prospective Cohort Study.

Background: Acute physical function outcomes in ICU survivors of COVID-19 pneumonia has received little attention. Critically ill patients with COVID-19 infection who require invasive mechanical ventilation may undergo greater exposure to some risk factors for ICU-acquired weakness (ICUAW). Purpose: To determine incidence and factors associated with ICUAW at ICU discharge and gait dependence at hospital discharge in mechanically ventilated patients with COVID-19 pneumonia. Methods: Single-centre, prospective cohort study conducted at a tertiary hospital in Madrid, Spain. We evaluated ICUAW with the Medical Research Council Summary Score (MRC-SS). Gait dependence was assessed with the Functional Status Score for the ICU (FSS-ICU) walking subscale. Results: During the pandemic second wave, between 27 July and 15 December, 2020, 70 patients were enrolled. ICUAW incidence was 65.7% and 31.4% at ICU discharge and hospital discharge, respectively. Gait dependence at hospital discharge was observed in 66 (54.3%) patients, including 9 (37.5%) without weakness at ICU discharge. In univariate analysis, ICUAW was associated with the use of neuromuscular blockers (crude odds ratio [OR] 9.059; p = 0.01) and duration of mechanical ventilation (OR 1.201; p = 0.001), but not with the duration of neuromuscular blockade (OR 1.145, p = 0.052). There was no difference in corticosteroid use between patients with and without weakness. Associations with gait dependence were lower MRC-SS at ICU discharge (OR 0.943; p = 0.015), older age (OR 1.126; p = 0.001), greater Charlson Comorbidity Index (OR 1.606; p = 0.011), longer duration of mechanical ventilation (OR 1.128; p = 0.001) and longer duration of neuromuscular blockade (OR 1.150; p = 0.029). Conclusions: In critically ill COVID-19 patients, the incidence of ICUAW and acute gait dependence were high. Our study identifies factors influencing both outcomes. Future studies should investigate optimal COVID-19 ARDS management and impact of dyspnea on acute functional outcomes of COVID-19 ICU survivors.

Comparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15 mg/kg in young and elderly patients.

INTRODUCTION: Tracheal intubation during anesthesia can be facilitated by the neuromuscular blocking agent cisatracurium. However, limited data exists about onset time, duration of action and effect on intubating conditions in elderly patients above 80 years of age. We hypothesized that elderly patients would present a longer onset time and duration of action compared to younger adults. METHODS: This prospective observational study included 31 young (18-40 years) and 29 elderly (≥ 80 years) patients. Patients were given fentanyl 2 µg/kg and propofol 1.5-2.5 mg/kg for induction of anesthesia and maintained with remifentanil and propofol. Monitoring of neuromuscular function was performed with acceleromyography. Primary outcome was onset time defined as time from injection of cisatracurium 0.15 mg/kg (based on ideal body weight) to a train-of-four (TOF) count of 0. Other outcomes included duration of action (time to TOF ratio ≥ 0.9), intubation conditions using the Fuchs-Buder scale and the Intubating Difficulty Scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: Elderly patients had significantly longer onset time compared with younger patients; 297 seconds (SD 120) vs. 199 seconds (SD 59) (difference: 98 seconds (95% CI: 49-147), P < 0.001)). Duration of action was also significantly longer in elderly patients compared with younger patients; 89 minutes (SD 17) vs. 77 minutes (SD 14) (difference: 12 minutes (95% CI: 2.5-20.5) P = 0.01)). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 19/29 (66%) vs 21/31 (68%) (P = 0.86) or IDS score (P = 0.74). A larger proportion of elderly patients reported hoarseness 24 hours postoperatively; 62% vs 34% P = 0.04. CONCLUSION: In elderly patients cisatracurium 0.15 mg/kg had significantly longer onset time and duration of action compared with younger patients. No difference was found in intubating conditions at a TOF count of 0. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04921735, date of registration 10 June 2021).

2021 Acute Respiratory Distress Syndrome Update, With Coronavirus Disease 2019 Focus.

Acute respiratory distress syndrome (ARDS) is a heterogeneous lung disease responsible for significant morbidity and mortality among critically ill patients, including those infected with severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019. Despite recent advances in pathophysiology, diagnostics, and therapeutics, ARDS is dangerously underdiagnosed, and supportive lung protective ventilation and prone positioning remain the mainstay interventions. Rescue therapies, including neuromuscular blockade and venovenous extracorporeal membrane oxygenation, remain a key component of clinical practice, although benefits are unclear. Even though coronavirus disease 2019 ARDS has some distinguishing features from traditional ARDS, including delayed onset, hyperinflammatory response, and pulmonary microthrombi, it clinically is similar to traditional ARDS and should be treated with established supportive therapies.

Vigilance: the behavioral impact of quantitative monitoring on administration and antagonism of neuromuscular blocking agents.

PURPOSE: The aim of this study was to determine whether use of acceleromyography (1) changes dosing of neuromuscular blocking agents (NMBAs), and (2) increases the time between neostigmine administration and extubation, when compared with subjective assessment of neuromuscular blockade. METHODS: For this retrospective study, data were collected from patient electronic medical records. Patients were included if they had received an NMBA as part of a general anesthetic in 2013 and 2014. Data were analyzed by category of monitoring device: quantitative monitor (acceleromyograph [AMG]) or subjective device (peripheral nerve stimulator [PNS]). Outcomes measured were the total dose of NMBA administered and, the timing of the last dose of NMBA and anticholinesterase relative to tracheal extubation. RESULTS: Results from multivariate models showed that use of acceleromyography was not associated with a change in the total dose of NMBA administered. In contrast, the number of times any monitor was used, as determined by the frequency with which the train-of-four count (TOFC) was recorded, correlated with the administration of greater amounts of rocuronium (P < 0.01) and vecuronium (P < 0.01). The use of acceleromyography did not prolong the time interval between neostigmine administration and tracheal extubation. The number of times any monitor was used during an anesthetic was associated with a decrease in this time interval. The interval decreased an average of 2.7 min each successive time the TOFC was recorded (P < 0.01). CONCLUSIONS: The data presented provides insight about the behavioral engineering inherent to the practice of anesthesiology. Introduction of neuromuscular blockade assessment appeared to increase provider vigilance in dosing of NMBAs-regardless of assessment method. The frequency of intraoperative monitoring (quantitative or subjective) was associated with an increased total dose of NMBA administered and decreased time interval between the last dose of neostigmine and extubation.

Low-Dose of Rocuronium During Thyroid Surgery: Effects on Intraoperative Nerve-Monitoring and Intubation.

BACKGROUND: Intraoperative Neurophysiological Monitoring (IONM) reduces the incidence of Recurrent Laryngeal Nerve (RLN) injuries during thyroid surgery. To preserve nerve function, long acting neuromuscular blocking agents (NMBA) should be avoided. However, NMBA are necessary for laryngoscopy and endotracheal intubation. We designed this double-blinded, randomized, placebo-controlled trial to assess if a low-dose of rocuronium given at intubation would affect the IONM data recorded before the thyroid dissection. METHODS: Hundred patients undergoing elective thyroid surgery were randomized to receive either 0.3 mg kg-1 of low dose rocuronium (intervention) or no-NMBA (control). Intubation was performed with video-laryngoscopy. IONM was placed on RLN and nerve stimulation was performed before and after thyroid dissection. The presence of a valid amplitude prior to dissection was defined when the IONM signal was >100 µV. Occurrence of difficult laryngoscopy was reported together with intubation details including time, difficulty and failure. The lowest peripheral saturation (SpO2) and the number of desaturation episodes during the intubation were also registered. RESULTS: No patients showed impaired IONM signal before dissection in both groups. Cormack-Lehane grade was higher in the intervention group (11;2) compared to control one (11;1; P = 0.046). No-NMBA patients had increased number of difficult laryngoscopies (21% versus 6%, P = 0.041) and intubations (34% versus 8%; P = 0.003) as well as a longer time to intubation (78 [55; 175] versus 55 [31; 110] sec; P = 0.006). Lower values of peripheral SpO2 during intubation attempt were registered in the no NMBA group (99 [97; 100] versus 99 [99; 100] %; P = 0.020). However, the number of intubation failure was similar between groups (p=0.495). CONCLUSIONS: Low-dose of rocuronium does not compromise pre-dissection IONM signal and improves intubation condition when compared to a relaxant free strategy.