Sugammadex and neuromuscular disease: a systematic review with assessment of reporting quality and content validity.

BACKGROUND: Efficacy and safety of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) in patients with neuromuscular diseases remains unclear. We summarised the available evidence and evaluated the quality of data reporting and the validity of published reports. METHODS: We searched for reports (any design) on the usage of sugammadex (any regimen) for the reversal of an NMBA in patients (any age) with any neuromuscular disease. We used a modified CARE checklist (maximum score 23) to assess the quality of data reporting and an original specific validity checklist (maximum score 41) that was developed through a Delphi process. RESULTS: We retrieved 126 observational reports (386 patients). Most dealt with myasthenia gravis patients receiving rocuronium. The train-of-four ratio returned to ≥0.9 in 258 of 265 (97.4%) patients in whom neuromonitoring was used. Adverse events occurred in 14 of 332 (4.2%) patients in whom adverse events were reported as present or absent. In 90 case reports, the median score of the 23-point CARE checklist was 13.5 (inter-quartile range [IQR] 11-16). In all 126 reports, the median score of the 41-point validity checklist was 23 (IQR 20-27). Scores were positively correlated. CONCLUSIONS: These uncontrolled observations (of mainly low to moderate quality and validity) do not allow confident assessment of the efficacy and safety of sugammadex for the reversal of NMBAs in patients with neuromuscular diseases. Reporting of observational data should follow established guidelines, include specific information to ensure validity, and emphasise what the new data add to current knowledge. SYSTEMATIC REVIEW PROTOCOL: PROSPERO 2019 (CRD42019119924).

Area under the curve and amplitude of the compound motor action potential are clinically interchangeable quantitative measures of neuromuscular block: a method comparison study.

Background: Current guidelines recommend quantitative neuromuscular block monitoring during neuromuscular blocking agent administration. Monitors using surface electromyography (EMG) determine compound motor action potential (cMAP) amplitude or area under the curve (AUC). Rigorous evaluation of the interchangeability of these methods is lacking but necessary for clinical and research assurance that EMG interpretations of the depth of neuromuscular block are not affected by the methodology. Methods: Digitised EMG waveforms were studied from 48 patients given rocuronium during two published studies. The EMG amplitudes and AUCs were calculated pairwise from all cMAPs classified as valid by visual inspection. Ratios of the first twitch (T1) to the control T1 before administration of rocuronium (T1c) and train-of-four ratios (TOFRs) were compared using repeated measures Bland-Altman analysis. Results: Among the 2419 paired T1/T1c differences where the average T1/T1c was ≤0.2, eight (0.33%) were outside prespecified clinical limits of agreement (-0.148 to 0.164). Among the 1781 paired TOFR differences where the average TOFR was ≥0.8, 70 (3.93%) were outside the prespecified clinical limits of agreement ((-0.109 to 0.134). Among all 7286 T1/T1c paired differences, the mean bias was 0.32 (95% confidence interval 0.202-0.043), and among all 5559 paired TOFR differences, the mean bias was 0.011 (95% confidence interval 0.0050-0.017). Among paired T1/T1c and TOFR differences, Lin's concordance correlation coefficients were 0.98 and 0.995, respectively. Repeatability coefficients for T1/T1c and TOFR were <0.08, with no differences between methods. Conclusions: Quantitative assessment neuromuscular block depth is clinically interchangeable when calculated using cMAP amplitude or the AUC.

A new pharmacological approach for tracheal intubation?

Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation.

Impact of neuromuscular block on myocardial injury after non-cardiac surgery (MINS) incidence in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection: a randomized controlled study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. METHODS: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. RESULTS: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg-1·h-1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), µg·kg-1·min-1, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant. CONCLUSIONS: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).

Effect of coadministration of 10 mg/kg calcium chloride and neostigmine on extubation time: A randomized controlled trial.

INTRODUCTION AND OBJECTIVES: Some studies investigating the effect of calcium on neostigmine-induced recovery of neuromuscular blockade have shown that this combination promotes neuromuscular recovery, but does not significantly affect the incidence of postoperative residual curarization and time to extubation. This study aimed to evaluate the effects of 10 mg/kg calcium chloride co-administered with neostigmine on early recovery and time to extubation. PATIENTS AND METHODS: This prospective, randomized, double-blinded, placebo-controlled study included 88 ASA I-II patients aged between 18 and 65 years who were scheduled for elective surgery lasting at least 1 h under general anaesthesia in which 10 mg/kg of calcium chloride or the same volume of normal saline was co-administered with 5 µg/kg of neostigmine at the end of surgery. Time to extubation (time from neostigmine administration to extubation), time from neostigmine administration to TOF ratio (TOFr) 0.9 (neuromuscular recovery), and the incidence of residual neuromuscular blockade (RNMB) and other adverse effects were recorded. RESULTS: Median (Q1, Q3) extubation time was significantly shorter in the calcium group vs. the placebo group (6.5 min [5.52-7.43] vs. 9.78 min [8.35-11]), P < .001. Median neuromuscular recovery time in the calcium group was 5 min vs. 7.1 min in the placebo group, P < .001. Patients in the calcium group had significantly higher TOFr and lower incidence of RNMB at 5 and 10 min vs. the placebo group, and no significant side effects. CONCLUSION: Calcium chloride at a dose of 10 mg/kg co-administered with neostigmine promotes early neuromuscular recovery and reduces time to extubation by about 32%.

The Incidence of Residual Neuromuscular Block in Pediatrics: A Prospective, Pragmatic, Multi-institutional Cohort Study.

Introduction Residual neuromuscular block, defined as a quantitatively measured train-of-four ratio (TOFr) <0.9, is common postoperatively. Using a pragmatic trial design, we hypothesized that qualitative and/or clinical assessment of neuromuscular block would inadequately detect residual block following antagonism with neostigmine or sugammadex. Method After IRB approval and written informed consent, 74 children (aged 2-17 years), undergoing elective surgery and receiving rocuronium, were prospectively enrolled in the study at Children's Hospital Colorado and Children's Healthcare of Atlanta. Routine clinical practice at both institutions consisted of clinical signs and/or qualitative assessment with peripheral nerve stimulators. Children at the Colorado hospital routinely received sugammadex antagonism; whereas children at the Atlanta hospital received neostigmine. Residual neuromuscular block was assessed postoperatively using quantitative electromyography. If TOFr was <0.9, patients received sugammadex until TOFr ≥0.9. Result Qualitative and clinical assessment failed to detect residual block in 29.7% of patients in the neostigmine reversal cohort (adjusted odds ratio (aOR) 29.8, 95% confidence interval (CI): 2.7 to 5,559.5, p-value = 0.002). No residual block was detected in the sugammadex reversal cohort. A correlation between increasing patient weight and incidence of postoperative residual block was observed in the neostigmine cohort (aOR 1.05, 95% CI: 1.02 to 1.10, p-value = 0.002). Conclusion Qualitative and/or clinical assessment of neuromuscular block inadequately detects residual block following neostigmine antagonism.

Practice Guidelines for Monitoring Neuromuscular Blockade-Elements to Change to Increase the Quality of Anesthesiological Procedures and How to Improve the Acceleromyographic Method.

Neuromuscular blocking agents are a crucial pharmacological element of general anesthesia. Decades of observations and scientific studies have resulted in the identification of many risks associated with the uncontrolled use of neuromuscular blocking agents during general anesthesia or an incomplete reversal of neuromuscular blockade in the postoperative period. Residual relaxation and acute postoperative respiratory depression are the most serious consequences. Cyclic recommendations have been developed by anesthesiology societies from many European countries as well as from the United States and New Zealand. The newest recommendations from the American Society of Anesthesiologists and the European Society of Anesthesiology were published in 2023. These publications contain very detailed recommendations for monitoring the dosage of skeletal muscle relaxants in the different stages of anesthesia-induction, maintenance and recovery, and the postoperative period. Additionally, there are recommendations for various special situations (for example, rapid sequence induction) and patient populations (for example, those with organ failure, obesity, etc.). The guidelines also refer to pharmacological drugs for reversing the neuromuscular transmission blockade. Despite the development of several editions of recommendations for monitoring neuromuscular blockade, observational and survey data indicate that their practical implementation is very limited. The aim of this review was to present the professional, technical, and technological factors that limit the implementation of these recommendations in order to improve the implementation of the guidelines and increase the quality of anesthesiological procedures and perioperative safety.

Quantitative Neuromuscular Monitoring Permits Early Diagnosis of Abnormal Butyrylcholinestrase: Two Case Studies Demonstrating Prevention of Awareness from Premature Awakening.

Administration of succinylcholine to patients with a variant in the butyrylcholinesterase (BChE) gene increases the risk of anesthesia emergence prior to recovery from neuromuscular blockade (NMB). Application of quantitative neuromuscular monitoring (NMM) can identify residual NMB. We present two patients with abnormal BChE gene variants. In the first case, quantitative monitoring was applied too late to prevent awareness, but allowed diagnosis and prevented admission to the intensive care unit. In the second case, monitoring was applied prior to NMB, which enabled early diagnosis and prevented premature awakening from anesthesia. These cases illustrate the importance of quantitative NMM, even in short cases and with short-acting depolarizing agents such as succinylcholine. The clinical implications of this report include a more consistent use of NMM to identify and manage patients with undiagnosed abnormal BChE and to prevent premature anesthesia emergence.

Effect of deep neuromuscular block on the quality of early recovery after sleeve gastrectomy in obese patients: a randomized controlled trial.

BACKGROUND: Deep neuromuscular block (NMB) has been shown to improve surgical conditions and alleviate post-operative pain in bariatric surgery compared with moderate NMB. We hypothesized that deep NMB could also improve the quality of early recovery after laparoscopic sleeve gastrectomy (LSG). METHODS: Eighty patients were randomized to receive either deep (post-tetanic count 1-3) or moderate (train-of-four count 1-3) NMB. The QoR-15 questionnaire was used to evaluate the quality of early recovery at 1 day before surgery (T0), 24 and 48 h after surgery (T2, T3). Additionally, we recorded diaphragm excursion (DE), postoperative pain, surgical condition, cumulative dose of analgesics, time of first flatus and ambulation, post-operative nausea and vomiting, time of tracheal tube removal and hospitalization time. MAIN RESULTS: The quality of recovery was significantly better 24 h after surgery in patients who received a deep versus moderate block (114.4 ± 12.9 versus 102.1 ± 18.1). Diaphragm excursion was significantly greater in the deep NMB group when patients performed maximal inspiration at T2 and T3 (P < 0.05). Patients who underwent deep NMB reported lower visceral pain scores 40 min after surgery; additionally, these patients experienced lower pain during movement at T3 (P < 0.05). Optimal surgical conditions were rated in 87.5% and 64.6% of all measurements during deep and moderate NMB respectively (P < 0.001). The time to tracheal tube removal was significantly longer in the deep NMB group (P = 0.001). There were no differences in other outcomes. CONCLUSION: In obese patients receiving deep NMB during LSG, we observed improved QoR-15 scores, greater diaphragmatic excursions, improved surgical conditions, and visceral pain scores were lower. More evidence is needed to determine the effects of deep NMB on these outcomes. TRIAL REGISTRATION: ChiCTR2200065919. Date of retrospectively registered: 18/11/2022.

Anesthetic Management of a Patient With Central Core Disease Undergoing Thoracoscopic Lung Resection: The Importance of Neuromuscular Monitoring at the Masseter Muscle.

Central core disease is a rare muscular disorder in which anesthetic considerations for the prevention of malignant hyperthermia and for avoidance of residual neuromuscular block are required. A 63-year-old woman with central core disease underwent thoracoscopic sublobar lung resection under total IV anesthesia with a prepared anesthetic workstation. The rocuronium-induced neuromuscular block was monitored by using acceleromyography at the left adductor pollicis muscle and the right masseter muscle. The recovery of neuromuscular block at the masseter was slower than that at the adductor pollicis. The patient showed no symptoms of malignant hyperthermia and residual neuromuscular block and had an uneventful postoperative course. In the present case, malignant hyperthermia was successfully prevented with general anesthesia that is free of triggering agents using a prepared anesthetic machine. The authors speculate that the masseter may be an auxiliary site for neuromuscular monitoring to ensure recovery from neuromuscular block in patients with central core disease.

Residual Neuromuscular Block Remains a Safety Concern for Perioperative Healthcare Professionals: A Comprehensive Review.

Residual neuromuscular block (RNMB) remains a significant safety concern for patients throughout the perioperative period and is still widely under-recognized by perioperative healthcare professionals. Current literature suggests an association between RNMB and an increased risk of postoperative pulmonary complications, a prolonged length of stay in the post anesthesia care unit (PACU), and decreased patient satisfaction. The 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade provide guidance for the use of quantitative neuromuscular monitoring coupled with neuromuscular reversal to recognize and reduce the incidence of RNMB. Using sugammadex for the reversal of neuromuscular block as well as quantitative neuromuscular monitoring to quantify the degree of neuromuscular block may significantly reduce the risk of RNMB among patients undergoing general anesthesia. Studies are forthcoming to investigate how using neuromuscular blocking agent reversal with quantitative monitoring of the neuromuscular block may further improve perioperative patient safety.

Laparoscopic vs. ultrasound-guided transversus abdominis plane (TAP) block in colorectal surgery: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The transversus abdominis plane block (TAPB) is effective for postoperative pain management in patients undergoing colorectal surgery. However, evidence regarding the optimal delivery method, either laparoscopic (L-TAPB) or ultrasound-guided (U-TAPB) is lacking. Our study aimed to compare the effectiveness of these delivery methods. METHODS: We carried out a literature search of PubMed, Cochrane Library, Web of Science, and Google Scholar databases to include randomized studies comparing patients receiving either L-TAPB or U-TAPB during minimally invasive colorectal surgery. The primary endpoint was opioid consumption in the first 24 h after surgery. Risk of bias was assessed with the RoB-2 tool. Effect size was estimated for each study with 95% confidence interval and overall effect measure was estimated with a random effect model. RESULTS: The literature search revealed 294 articles, of which four randomized trials were eligible. A total of 359 patients were included, 176 received a L-TAPB and 183 received a U-TAPB. We established the non-inferiority of L-TAPB, as the absolute difference of - 2.6 morphine-mg (95%CI - 8.3 to 3.0) was below the pooled non-inferiority threshold of 8.1 morphine-mg (low certainty level). No difference in opioid consumption was noted at 2, 6, 12, and 48 h (low to very low certainty level). Postoperative pain, nausea and vomiting were similar between groups at different timepoints (low to very low certainty level). No TAPB-related complications were recorded. Finally, the length of hospital stay was similar between groups. CONCLUSION: For postoperative multimodal analgesia both L-TAPB and U-TAPB may result in little to no difference in outcome in patients undergoing colorectal surgery. Registration Prospero CRD42023421141.

Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting.

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.