Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

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.

Low-pressure pneumoperitoneum with deep neuromuscular blockade versus standard pressure pneumoperitoneum in patients undergoing laparoscopic cholecystectomy for gallstone disease: a non-inferiority randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt at improving laparoscopic surgery. However, it has the issue of poor working space for which deep neuromuscular blockade (NMB) may be a solution. There is a lack of literature comparing LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB. METHODOLOGY: This was a single institutional prospective non-inferiority RCT, with permuted block randomization of subjects into group A and B [Group A: LPP; 8-10 mmHg with deep NMB [ Train of Four count (TOF): 0, Post Tetanic Count (PTC): 1-2] and Group B: SPP; 12-14 mmHg with moderate NMB]. The level of NMB was monitored with neuromuscular monitor with TOF count and PTC. Cisatracurium infusion was used for continuous deep NMB in group A. Primary outcome measures were the surgeon satisfaction score and the time for completion of the procedure. Secondarily important clinical outcomes were also reported. RESULTS: Of the 222 patients screened, 181 participants were enrolled [F: 138 (76.2%); M: 43 (23.8%); Group A n = 90, Group B n = 91]. Statistically similar surgeon satisfaction scores (26.1 ± 3.7 vs 26.4 ± 3.4; p = 0.52) and time for completion (55.2 ± 23.4 vs 52.5 ± 24.9 min; p = 0.46) were noted respectively in groups A and B. On both intention-to-treat and per-protocol analysis it was found that group A was non-inferior to group B in terms of total surgeon satisfaction score, however, non-inferiority was not proven for time for completion of surgery. Mean pain scores and incidence of shoulder pain were statistically similar up-to 7 days of follow-up in both groups. 4 (4.4%) patients in group B and 2 (2.2%) in group A had bradycardia (p = 0.4). Four (4.4%) cases of group A were converted to group B. One case of group B converted to open surgery. Bile spills and gallbladder perforations were comparable. CONCLUSION: LPP with deep NMB is non-inferior to SPP with moderate NMB in terms of surgeon satisfaction score but not in terms of time required to complete the procedure. Clinical outcomes and safety profile are similar in both groups. However, it could be marginally costlier to use LPP with deep NMB.

Comparison of inflammatory markers in low-pressure pneumoperitoneum with deep neuromuscular block versus standard pressure pneumoperitoneum among patients undergoing laparoscopic cholecystectomy for gallstone disease: a randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

Sugammadex use in pediatric patients with stage IV-V chronic kidney disease in a quaternary referral hospital: a case series.

BACKGROUND: Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital. METHODS: After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room. RESULTS: The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified. CONCLUSION: No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population.

The use of sub-Tenon's anesthesia versus a low-dose neuromuscular blockade for canine cataract surgery: A comparative study of 224 eyes.

OBJECTIVE: Assess the utility of a Sub-Tenon's anesthesia (STA) protocol to provide suitable operating conditions for canine cataract surgery and compare it to an alternative low-dose neuromuscular blockade (LD-NMB) protocol used for canine cataract surgery. PROCEDURES: Clinical study of dog eyes undergoing cataract surgery with either an STA or LD-NMB protocol. While intraoperative vitreal expansion scores and intraoperative complications were collected prospectively, globe position, intraocular pressure, return of vision, and postoperative complications were collected retrospectively. Statistical testing was used to compare results between the STA and the LD-NMB groups for the data available. RESULTS: A total of 224 eyes from 126 dogs were assessed, with 133/224 (59.4%) eyes from 99/126 (78.6%) dogs receiving STA and 91/124 (40.6%) eyes from 72/126 (57.1%) dogs receiving LD-NMB. Forty-five of these dogs (45/126; 37.7%) received STA for one eye and LD-NMB for the other eye. There was no significant change in intraocular pressure measurements following STA administration. This was not measured for the LD-NMB group. The globe achieved a central position in 110/133 (82.7%) of eyes that received STA. This was not measured for the LD-NMB group. Intraoperative vitreal expansion scores were slightly higher in STA-treated eyes compared to LD-NMB-treated eyes. The intraoperative complication rate for STA-treated eyes was higher (73/133; 54.8%) compared to NMB-treated eyes (12/91; 13.2%). The most common intraoperative complication for STA was chemosis (64/133; 48.1%), the risk of which increased with an increase in the volume of local anesthetic injected. The post-operative complication rate was higher in STA-treated eyes (28/133; 21.1%) compared to NMB-treated eyes (16/91; 17.6%). Post-operative corneal ulceration was the most common postoperative complication in STA-treated eyes (6/133; 4.5%). CONCLUSION: The STA protocol described resulted in suitable operating conditions, but more intraoperative and postoperative complications compared to the LD-NMB protocol. Despite these complications, the STA protocol did not cause a significant deleterious impact on post-operative outcomes as defined in the present study.

Evolution of a laboratory mechanomyograph.

Mechanomyography is currently the accepted laboratory reference standard for quantitative neuromuscular blockade monitoring. Mechanomyographs are not commercially available. Previously, a mechanomyograph was built by our laboratory and used in several clinical studies. It was subsequently redesigned to improve its usability and functionality and to accommodate a wider range of hand sizes and shapes using an iterative design process. Each version of the redesigned device was initially tested for usability and functionality in the lab with the investigators as subjects without electrical stimulation. The redesigned devices were then assessed on patients undergoing elective surgery under general anesthesia without neuromuscular blocking drugs. Since the patients were not paralyzed, the expected train-of-four ratio was 1.0. The device accuracy and precision were represented by the train-of-four ratio mean and standard deviation. If issues with the device's useability or functionality were discovered, changes were made, and the redesign processes repeated. The final mechanomyograph design was used to collect 2,362 train-of-four ratios from 21 patients. The mean and standard deviation of the train-of-four ratios were 0.99 ± 0.030. Additionally, the final mechanomyograph design was easier to use and adjust than the original design and fit a wider range of hand sizes. The final design also reduced the frequency of adjustments and the time needed for adjustments, facilitating data collection during a surgical procedure.

Comparative performance of stimpod electromyography with mechanomyography for quantitative neuromuscular blockade monitoring.

PURPOSE: The purpose of this study was to compare the Stimpod electromyograph neuromuscular blockade monitor to mechanomyography, which is widely considered to be the reference standard. METHODS: The Stimpod electromyograph was used with its designated electrode array on the same hand as the mechanomyograph. Pairs of train-of-four measurements were recorded every 0.5-2 min. When the train-of-four count was zero on the electromyograph monitor, pairs of post tetanic count measurements were recorded every 2.5 min, instead of train-of-four measurements. Measurements were recorded from immediately after induction of anesthesia until just before emergence. Stimulation current was set to 60 mA with a duration of 200 microsec. The mechanomyography recording system recorded each twitch waveform for analysis. High resolution electromyograph waveforms were also recorded using a datalogger accessory provided by the manufacturer, facilitating inspection of individual waveforms. The administration of neuromuscular blocking drugs was left up to the discretion of the anesthesia care team. RESULTS: Twenty-three patients contributed 1,088 data pairs suitable for analysis. Bland-Altman analysis of 415 pairs of train-of-four ratios showed a bias of 0.028 and limits of agreement of -0.18 and 0.24. Two hundred seventy-three train-of-four count data pairs were compared by Cohen's quadratically weighted kappa which was calculated to be 0.44, indicating moderate agreement. Three hundred thirty-eight post tetanic count data pairs were compared by Cohen's quadradically weighted kappa which was calculated to be 0.80, indicating substantial agreement. CONCLUSION: The electromyograph produced results that were comparable to the mechanomyograph.

Onset and duration of action of escalating doses of atracurium in anesthetized healthy goats.

OBJECTIVE: The aim of this study was to describe the onset and duration of action of escalating doses of atracurium in healthy, anesthetized goats. STUDY DESIGN: Randomized, blinded, triple crossover study. Animals A total of eight (five males and three females) healthy goats weighing 42.7-123.5 kg and aged from 11 months to 8 years. METHODS: Goats were anesthetized three times with propofol and anesthesia was maintained with isoflurane. One of three doses of atracurium was administered intravenously 30 minutes after induction: 0.25 mg kg-1 (AT25), 0.5 mg kg-1 (AT50) or 0.75 mg kg-1 (AT75). Acceleromyographic train-of-four ratio (TOFR) followed by train-of-four counts (TOFC) were recorded at 30 second intervals after atracurium administration to determine blockade onset (TOFC = 0). The TOFR followed by TOFC were recorded at 5 minute intervals until return to pre-atracurium baseline (TOFR = 1.0). Normally distributed data were analyzed with repeated measures anova and a Tukey multiple comparison test. Data not normally distributed were analyzed with a Friedman test and a Dunn's multiple comparison test. RESULTS: For AT50 and AT75, 100% of goats achieved TOFC = 0 after atracurium administration. For AT25, however, 87.5% of goats achieved TOFC = 0 after atracurium administration. The onset time was shorter for AT75 [1.5 (0.5-1.5) minutes; median (range)] than for AT25 [2 (1-4) minutes] (p = 0.048). The duration of action [from onset time to complete reversal (TOFR = 1.0)] was significantly shorter for AT25 (52 ± 12 minutes, mean ± SD) than for AT50 (77 ± 18 minutes) (p < 0.001) and AT75 (85 ± 16 minutes) (p < 0.001). There was no significant difference in duration between AT50 and AT75 (p = 0.238). CONCLUSIONS AND CLINICAL RELEVANCE: Doses of 0.5 and 0.75 mg kg-1 atracurium may produce complete neuromuscular blockade in healthy, anesthetized goats.

Updated review on the use of neuromuscular blockade during intraoperative motor-evoked potential monitoring in the modern anesthesia era.

Transcranial electrical stimulation motor-evoked potentials (Tc-MEP) monitoring is a common practice in neurosurgery to prevent postoperative neurological damage. However, the use of neuromuscular blocking agents (NMBAs) during Tc-MEP monitoring is a subject of controversy. In addition, the effectiveness of sugammadex, a selective reversal agent, in the context of Tc-MEP monitoring requires further investigation. This review aimed to clarify the considerations involved in achieving optimal Tc-MEP monitoring while ensuring patient safety. Preoperative patient selection, comorbidity assessment, motor power evaluation, and the nature of the planned surgery are critical factors. Accurate paralysis assessment, continuous NMBA infusion, and post-tetanic stimulation techniques are essential for achieving optimal partial NMB. The decision to administer an NMB during Tc-MEP monitoring necessitates a careful evaluation of the balance between accuracy and potential complications. This review emphasizes the challenges associated with NMB administration during Tc-MEP monitoring and highlights the need for personalized patient assessment.

Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Comparison of visual and electromyographic assessments with train-of-four stimulation of the ulnar nerve: a prospective cohort study.

PURPOSE: The use of a peripheral nerve stimulator to assess the level of neuromuscular blockade tasks the anesthesia clinician with subjectively assessing the response to neurostimulation. In contrast, objective neuromuscular monitors provide quantitative information. The purpose of this study was to compare subjective evaluations from a peripheral nerve stimulator with objective measurements of neurostimulation responses from a quantitative monitor. METHODS: Patients were enrolled preoperatively, and intraoperative neuromuscular blockade management was at the discretion of the anesthesiologist. Electromyography electrodes were placed over the dominant or nondominant arm in a randomized fashion. Following onset of nondepolarizing neuromuscular blockade, the ulnar nerve was stimulated, the response was measured with electromyography, and anesthesia clinicians, who were blinded to the objective measurements, subjectively (visually) evaluated the response to neurostimulation. RESULTS: Fifty patients were enrolled and 666 neurostimulations were performed at 333 different time points. Anesthesia clinicians subjectively overestimated the response of the adductor pollicis muscle following neurostimulation of the ulnar nerve 155/333 (47%) of the time when compared with objective electromyographic measurements. When subjective evaluations and objective measurements differed to any degree, subjective evaluations were higher than objective measurements 155/166 (92%) of the time (95% CI, 87 to 95; P < 0.001), representing significant evidence that subjective evaluation overestimates the response to train-of-four stimulation. CONCLUSIONS: Subjective observations of a "twitch" do not consistently correspond to objective measurements of neuromuscular blockade with electromyography. Subjective evaluation overestimates the response to neurostimulation and may be unreliable for determining the depth of block or confirming adequate recovery.

RéSUMé: OBJECTIF: Lors de l'utilisation d'un stimulateur nerveux périphérique pour évaluer le niveau de bloc neuromusculaire, le clinicien en anesthésie doit évaluer de manière subjective la réponse à la neurostimulation. Les moniteurs neuromusculaires objectifs fournissent quant à eux des informations quantitatives. L'objectif de cette étude était de comparer les évaluations subjectives d'un stimulateur nerveux périphérique avec des mesures objectives des réponses de neurostimulation provenant d'un moniteur quantitatif. MéTHODE: Les patients ont été recrutés avant leur opération, et la gestion du bloc neuromusculaire peropératoire était à la discrétion de l'anesthésiologiste. Des électrodes d'électromyographie ont été placées sur le bras dominant ou non dominant de manière aléatoire. Après l'amorce du bloc neuromusculaire non dépolarisant, le nerf cubital a été stimulé, la réponse a été mesurée par électromyographie, et les cliniciens en anesthésie, qui n'avaient pas accès aux mesures objectives, ont évalué subjectivement (visuellement) la réponse à la neurostimulation. RéSULTATS: Cinquante patients ont été recrutés et 666 neurostimulations ont été réalisées à 333 moments différents. Les cliniciens en anesthésie ont subjectivement surestimé la réponse du muscle adducteur du pouce après neurostimulation du nerf cubital 155/333 (47 %) fois par rapport aux mesures électromyographiques objectives. Lorsque les évaluations subjectives et les mesures objectives différaient à quelque degré que ce soit, les évaluations subjectives étaient plus élevées que les mesures objectives 155/166 (92 %) du temps (IC 95 %, 87 à 95; P < 0,001), ce qui représente une preuve significative que l'évaluation subjective surestime la réponse à la stimulation par train-de-quatre. CONCLUSION: Les observations subjectives d'une « contraction ¼ ne correspondent pas systématiquement aux mesures objectives d'un bloc neuromusculaire telles qu'obtenues par électromyographie. L'évaluation subjective surestime la réponse à la neurostimulation et pourrait ne pas être fiable pour déterminer la profondeur du bloc ou confirmer une récupération adéquate.

Analysis of the association of sugammadex with the length of hospital stay in patients undergoing abdominal surgery: a retrospective study.

BACKGROUND: Sugammadex is a newer medication used for rapid and reliable reversal of neuromuscular blockade. This study evaluated whether sugammadex could reduce the length of postoperative hospital stay in patients undergoing abdominal surgery. METHODS: This single center retrospective cohort study included patients who underwent major abdominal surgery between January 2015 and October 2019. Patients were randomized according to reversal with sugammadex or spontaneous recovery. The primary outcome was length of postoperative hospital stay. The secondary outcomes were length of post-anesthetic care unit (PACU) stay, postoperative ambulation time, time-to-first-defecation, and incidence of pulmonary complications. After 1:1 propensity score matching, univariate and multiple linear regression analyses estimated the differences in outcomes. RESULTS: Of the 1614 patients, 517 received sugammadex and 645 spontaneously recovered. After adjusting for potential confounders, non-linear relationship was detected between administration of sugammadex and the length of postoperative hospital stay (ß = 0.29 95% confidence interval {CI}: [- 1.13, - 0.54], P = 0.4912). However, it was associated with shorter PACU stay (ß = - 20.30 95% CI: [- 24.48, - 17.11], P < 0.0001), shorter time to postoperative ambulation movement (ß = - 0.43 95% CI: [- 0.62, - 0.23], P < 0.0001), and reduced time-to-first-defecation (ß = - 2.25 95% CI: [- 0.45, - 0.05], P = 0.0129), when compared to the spontaneously recovered group. The incidence of pneumonia in the sugammadex group was significantly lower than that in the spontaneously recovered group (18.6% [44/237] vs. 39.2% [93/237] P < 0.05). CONCLUSIONS: Neuromuscular blockade reversal with sugammadex after abdominal surgery demonstrated an excellent recovery profile and was associated with decreased risk of pneumonia, although it did not affect the length of postoperative hospital stay.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

MRI measurement of the effects of moderate and deep neuromuscular blockade on the abdominal working space during laparoscopic surgery, a clinical study.

BACKGROUND: Conflicting data exist regarding the effects of deep neuromuscular blockade (NMB) on abdominal dimensions during laparoscopic procedures. We performed a clinical study to establish the influence of moderate and deep neuromuscular blockade (NMB) on the abdominal working space, measured by Magnetic Resonance Imaging (MRI), during laparoscopic donor nephrectomy with standard pressure (12 mmHg) pneumoperitoneum under sevoflurane anaesthesia. METHODS: Ten patients were intraoperatively scanned three times in the lateral decubitus position, with pneumoperitoneum maintained by a mobile insufflator. The first scan without NMB (T1) was followed by scans with moderate (T2) and deep NMB (T3). The skin-sacral promontory (S-SP) distance was measured, and 3D pneumoperitoneum volumes were reconstructed. RESULTS: The mean difference in the S-SP distance was -0.32 cm between T2 and T3 (95% CI -1.06 - 0.42 cm; p = 0.344) and + 2.1 cm between T1 and T2 (95% CI 0.81 - 3.39 cm; p = 0.006). The mean differences in pneumoperitoneum volume were 166 mL between T2 and T3 (95% CI, 5 - 327 mL; p = 0.044) and 108 mL between T1 and T2 (95% CI, -273 - 488 mL; p = 0.525). The pneumoperitoneum volume showed high inter-individual variability and no increase in three patients with a high volume at T1. CONCLUSIONS: During laparoscopic surgery in the lateral decubitus position with standard pressure under sevoflurane anaesthesia, deep NMB did not increase the S-SP distance compared to moderate NMB. Moderate NMB increased the S-SP distance by a mean of 2.1 cm (15.2%) compared with no NMB. The mean pneumoperitoneum volume increased slightly from moderate to deep NMB, with high inter-individual variability. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03287388.

Quantification of muscle tone by using shear wave velocity during an anaesthetic induction: a prospective observational study.

OBJECTIVES: The quantitative assessment of muscle stiffness or weakness is essential for medical care. Shear wave elastography is non-invasive ultrasound method and provides quantitative information on the elasticity of soft tissue. However, the universal velocity scale for quantification has not been developed. The aim of the study is to determine the shear wave velocities of abdominal muscle during anesthetic induction and to identify methods to cancel the effects of confounders for future development in the quantitative assessment of muscle tone using the universal scale. METHODS: We enrolled 75 adult patients undergoing elective surgery with ASA-PS I - III in the period between December 2018 and March 2021. We measured and calculated the shear wave velocity (SWV) before and after opioid administration (i.e., the baseline at rest and opioid-induced rigidity condition), and after muscle relaxant administration (i.e., zero reference condition). The SWV value was adjusted for the subcutaneous fat thickness by our proposed corrections. The SWVs after the adjustment were compared among the values in baseline, rigidity, and relaxation using one-way repeated-measures ANOVA and post hoc Tukey-Kramer test. A p-value of < 0.05 was considered to be statistically significant. UMIN Clinical Trials Registry identifier UMIN000034692, registered on October 30, 2018. RESULTS: The SWVs in the baseline, opioid-induced rigidity, and muscle relaxation conditions after the adjustment were 2.08 ± 0.48, 2.41 ± 0.60, and 1.79 ± 0.30 m/s, respectively (p < 0.001 at all comparisons). CONCLUSION: The present study suggested that the SWV as reference was 1.79 m/s and that the SWVs at rest and opioid-induced rigidity were ~ 10% and ~ 30% increase from the reference, respectively. The SWV adjusted for the subcutaneous fat thickness may be scale points for the assessment of muscle tone.