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).

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.

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.

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).

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.

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 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.

Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.

Safety of sugammadex for reversal of neuromuscular block: A postmarketing study based on the World Health Organization pharmacovigilance database.

AIM: Residual neuromuscular blockade is a common complication after general anaesthesia. Sugammadex can reverse the action of aminosteroid neuromuscular blockers. This study aimed to explore sugammadex safety issues in the real world and determine the spectrum of adverse reactions. METHODS: All sugammadex-related adverse events reported in VigiBase between 2010 and 2019 were classified by group queries according to the Medical Dictionary for Regulatory Activities. A disproportionality analysis of data was performed using the information component (IC); positive IC values were deemed significant. RESULTS: Overall, 16 219 410 adverse events were reported and 2032 were associated with sugammadex. The frequent reactions were recurrence of neuromuscular blockade (n = 54, IC 6.74, IC025 6.33), laryngospasm (n = 53, IC 6.05, IC025 5.64), bronchospasm (n = 119, IC 5.63, IC025 5.36) and bradycardia (n = 169, IC 5.13, IC025 4.90). Fatal cases were more likely among patients with cardiac disorders, especially those over 65 years. In addition, the common adverse drug reactions (ADRs) differed between different age groups (P < .01). ADRs were higher in the 0-17 years age group than in other age groups. The onset time of common ADRs was typically within 1 day and 68.9% occurred within half an hour after sugammadex administration. CONCLUSIONS: Anaesthesiologists should carefully monitor the anaesthesia recovery period to correct the ADRs caused by sugammadex and recommend monitoring neuromuscular function throughout the anaesthesia process. Sugammadex should be used carefully in patients with cardiovascular diseases, and electrocardiography and hemodynamic changes should be monitored after medication.

An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

BACKGROUND: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it. METHODS: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models. RESULTS: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001). CONCLUSIONS: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03128151.

Association of sugammadex reversal of neuromuscular block and postoperative length of stay in the ambulatory care facility: a multicentre hospital registry study.

BACKGROUND: Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ambulatory surgery. METHODS: We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs. RESULTS: Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: -9.5 min; 95% confidence interval [95% CI], -10.5 to -8.5 min; adjusted difference in direct hospital costs: -US$77; 95% CI, -$88 to -$66; respectively; P<0.001). The association was magnified in patients over age 65 yr, with ASA physical status >2 undergoing short procedures (<2 h) (adjusted difference in PLOS-ACF: -18.2 min; 95% CI, -23.8 to -12.4 min; adjusted difference in direct hospital costs: -$176; 95% CI, -$220 to -$128; P<0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P<0.001), which mediated its effects on length of stay. CONCLUSIONS: Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.

Association between choice of reversal agent for neuromuscular block and postoperative pulmonary complications in patients at increased risk undergoing non-emergency surgery: STIL-STRONGER, a multicentre matched cohort study.

BACKGROUND: Postoperative pulmonary complications are a source of morbidity after major surgery. In patients at increased risk of postoperative pulmonary complications we sought to assess the association between neuromuscular blocking agent reversal agent and development of postoperative pulmonary complications. METHODS: We conducted a retrospective matched cohort study, a secondary analysis of data collected in the prior STRONGER study. Data were obtained from the Multicenter Perioperative Outcomes Group. Included patients were aged 18 yr and older undergoing non-emergency surgery under general anaesthesia with tracheal intubation with neuromuscular block and reversal, who were predicted to be at elevated risk of postoperative pulmonary complications. This risk was defined as American Society of Anesthesiologists Physical Status 3 or 4 in patients undergoing either intrathoracic or intra-abdominal surgery who were either aged >80 yr or underwent a procedure lasting >2 h. Cohorts were defined by reversal with neostigmine or sugammadex. The primary composite outcome was the occurrence of pneumonia or respiratory failure. RESULTS: After matching by institution, sex, age (within 5 yr), body mass index, anatomic region of surgery, comorbidities, and neuromuscular blocking agent, 3817 matched pairs remained. The primary postoperative pulmonary complications outcome occurred in 224 neostigmine cases vs 100 sugammadex cases (5.9% vs 2.6%, odds ratio 0.41, P<0.01). After adjustment for unbalanced covariates, the adjusted odds ratio for the association between sugammadex use and the primary outcome was 0.39 (P<0.0001). CONCLUSIONS: In a cohort of patients at increased risk for pulmonary complications compared with neostigmine, use of sugammadex was independently associated with reduced risk of subsequent development of pneumonia or respiratory failure.

Rate of residual neuromuscular block using single-dose rocuronium in general anesthesia for ENT surgery: a retrospective cohort study.

INTRODUCTION: NMB facilitates intubating conditions in general anesthesia. However, it is associated with significant residual postoperative paralysis and morbidity. OBJECTIVE: To investigate the rate of underdiagnosed residual NMB based on two TOFR criteria (< 0.91 and < 1.00). METHODS: We performed a retrospective study adhering to STROBE guidelines. We included patients undergoing ENT surgery using single-dose neuromuscular block for balanced general anesthesia from June to December 2018. We collected demographic and anthropometric data, ASA score, NMBA dose, TOFR recordings at 5, 30 and 60 min and end of the surgery, anesthesia and surgery time, and administration of reversal agent. Statistical analysis included descriptive and dispersion measures statistics, curve and cross tables for residual NMB on different TOFR criteria with sub-analysis for AR, RR, and OR in patients over 65 years old. RESULTS: We included 57 patients, mean age 41; 43 females and 14 males. Mean anesthetic and surgical time were 139.4 and 116.1 min, respectively. All the patients received rocuronium under a mean ponderal single-dose of 0.48 mg/kg. Residual NMB rates were 29.9 and 49.1% for a TOFR < 0.91 and < 1.00, respectively. Older adults had an OR of 6.08 for residual NMB. CONCLUSIONS: The rate of residual NMB was 29.9 to 49.1%, depending on the criteria used (TOFR < 0.91 and < 1.00, respectively). Patients above 65 years old had an increased risk of residual NMB (6.08 OR) and clinical symptoms related to residual NMB (11.75 OR). We recommend future research aiming to provide a specific surveillance protocol for patients above 65 years old, including shorter-action NMB, early reversal, and prolonged surveillance using the TOFR criteria of < 1.00 to identify patients at risk of residual NMB readily.

Postoperative recurarization after sugammadex administration in two patients who received neoadjuvant chemotherapy: case reports and literature review.

BACKGROUND: Preoperative neoadjuvant chemotherapy plays a critical role in multidisciplinary therapy for a variety of malignant tumours. Although oncologists consider myocardial injury to be the most concerning side effect of chemotherapy, unique chemotherapy-mediated skeletal muscular damage has received attention recently. CLINICAL FEATURES: We report two unusual cases of postoperative delayed respiratory failure following administration of the recommended sugammadex dosage for patients undergoing lengthy operations with deep neuromuscular blockade (NMB) after neoadjuvant chemotherapy. Based on clinical outcomes, especially the comparison of muscle imaging results in patients at different treatment time points, we concluded that NMB recurrence had a possible correlation with neoadjuvant chemotherapy-induced muscular damage. CONCLUSION: The early identification of neoadjuvant chemotherapeutic side effects on NMB could be instrumental for clinical safety, especially in cases of major surgery requiring deep NMB. Thus, the timing of NMB antagonism and the recommended dosage of sugammadex warrant special consideration in these patients. In addition to neuromuscular monitoring during the operation, a more extended and closer observation period in the postanesthesia care unit is warranted.

RéSUMé: CONTEXTE: La chimiothérapie néoadjuvante préopératoire joue un rôle crucial dans le traitement multidisciplinaire de diverses tumeurs malignes. Bien que les oncologues considèrent les lésions myocardiques comme l'effet secondaire le plus inquiétant de la chimiothérapie, des lésions musculosquelettiques spécifiques induites par la chimiothérapie ont récemment fait l'objet d'une attention plus précise. CARACTéRISTIQUES CLINIQUES: Nous signalons deux cas inhabituels d'insuffisance respiratoire postopératoire retardée suite à l'administration de la posologie recommandée de sugammadex chez des patient·es bénéficiant d'opérations prolongées avec blocage neuromusculaire (BNM) profond après une chimiothérapie néoadjuvante. Sur la base des résultats cliniques, en particulier de la comparaison des résultats d'imagerie musculaire chez les patient·es à différents moments du traitement, nous avons conclu que la récurrence du BNM avait une corrélation intéressante avec les lésions musculaires induites par la chimiothérapie néoadjuvante. CONCLUSION: L'identification précoce des effets secondaires de la chimiothérapie néoadjuvante sur le BNM pourrait jouer un rôle déterminant dans l'innocuité clinique, en particulier en cas de chirurgie majeure nécessitant un BNM profond. Ainsi, le moment de l'antagonisme du BNM et la posologie recommandée de sugammadex nécessitent une attention particulière chez ces patient·es. En plus du monitorage neuromusculaire pendant l'opération, une période d'observation plus longue et plus étroite en salle de réveil est justifiée.

Evaluation of a three-axial acceleromyography monitor in dogs compared with mechanomyography.

OBJECTIVE: To compare the ratio of the train-of-four (TOF) and double burst stimulation (DBS) obtained with three-axial acceleromyography (AMG) and mechanomyography (MMG) in dogs during recovery from a rocuronium-induced neuromuscular block. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A total of six intact healthy adult male Beagle dogs, weighing 9.1 ± 1.9 kg and aged 3-5 years. METHODS: Dogs were anesthetized with intravenous (IV) dexmedetomidine and propofol, and isoflurane in oxygen. Neuromuscular function was measured with AMG and MMG in the contralateral thoracic limbs. Rocuronium (0.5 mg kg-1) was administered IV, and the TOF and DBS ratios measured. During neuromuscular block offset, MMG values were recorded when AMG first reached ratios of 0.9 and 1.0. True recovery from neuromuscular block was determined as MMG ratio ≥ 0.9. The false-positive (AMG ≥ 0.9 or 1.0, and MMG ratio < 0.9) rate was determined. Paired values were compared, and bias and limits of agreement were calculated. Receiver operating characteristic (ROC) curves were created. RESULTS: When AMG first reached 0.9 and 1.0 during recovery, MMG values were lower (p < 0.040). When AMG reached 0.9, the false-positive rate was 29% with TOF and 27% with DBS. It decreased to 12% (TOF) and 11% (DBS) when a ratio of 1.0 was used. AMG values were higher than paired MMG values (p < 0.001). The AMG overestimated MMG by 24% and 22% for TOF and DBS, respectively. Areas under the ROC curves (95% confidence interval) were 0.91 (0.89, 0.94) and 0.86 (0.81, 0.94) for TOF and DBS, respectively. CONCLUSIONS: and clinical relevance The three-axial AMG monitor overestimated neuromuscular function and, in some cases, indicated adequate recovery despite the MMG ratio being < 0.9. A TOF or DBS ratio of at least 1.0 should be considered when monitoring recovery of neuromuscular block with this AMG device.

Influence of the Pringle maneuver during partial hepatectomy on the neuromuscular block induced by intermittent and continuous dosing of rocuronium.

PURPOSE: The Pringle maneuver (PM) is a common procedure in hepatectomy that is known to interrupt drug elimination. The purpose of this study was to examine the influence of PM on the duration of action of rocuronium administered by intermittent bolus dosing, the continuous rocuronium infusion dose required for maintenance of a moderate neuromuscular block, and changes in plasma concentrations of rocuronium. METHODS: Twenty-seven adult patients undergoing partial hepatectomy with PM were enrolled in this study. The duration of action of 0.2 mg/kg rocuronium boluses (DUR), and the continuous rocuronium infusion dose required for maintenance of the height of the first twitch of the train-of-four (T1) at 10-20% of the control value (%T1), respectively, were electromyographically monitored on the adductor digiti minimi muscle. The effects of PM on DUR, %T1, and the plasma concentration of rocuronium were measured. RESULTS: The DUR was significantly prolonged during PM [mean: 42.2 (SD: 8.0) min, P < 0.001] compared to baseline [29.7 (6.3) min]. It was prolonged even after completion of the PM [46.2 (10.5) min, P < 0.001]. The plasma concentration of rocuronium measured at every reappearance of T1 was comparable between before and during PM. %T1 [15.5 (5.6)%] was significantly depressed after the start of PM [6.5 (3.9)%, P < 0.001], with persistence of the depression even after completion of PM. However, there were no significant changes in the plasma concentration of rocuronium. CONCLUSIONS: Rocuronium-induced neuromuscular block is significantly augmented during PM. However, the augmentation is not associated with an increase in plasma rocuronium concentration.

Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.

BACKGROUND: Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PK-pharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. METHODS: In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. RESULTS: Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Post-tetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. CONCLUSIONS: Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.

Sugammadex Versus Neostigmine for Neuromuscular Block Reversal and Postoperative Pulmonary Complications in Patients Undergoing Resection of Lung Cancer.

OBJECTIVES: This study aimed to compare the effect of sugammadex and neostigmine on neuromuscular block reversal and the incidence of postoperative pulmonary complications in patients undergoing lung cancer resection. DESIGN: A double-blind, randomized, prospective study. SETTING: A single major urban teaching and university hospital. PARTICIPANTS: One hundred adult patients underwent elective radical resection of lung cancer under general anesthesia. INTERVENTIONS: Patients were assigned into neostigmine (0.05 mg/kg) + atropine 0.02 mg/kg group and sugammadex (2 mg/kg) group. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of any postoperative pulmonary complications, and the time to achieve 90% of train-of-four (TOF) after the administration of sugammadex or neostigmine. The secondary endpoints were the number of patients with TOF ratio (TOFr) <0.9 at the time of tracheal extubation, the incidence of readmission 30 days after discharge, and specific postoperative pulmonary complications. Results showed that the average time of recovery to TOFr ≥0.9 with sugammadex was 164.5 ± 27.7 seconds versus 562.9 ± 59.7 seconds with neostigmine + atropine treatment. Fewer sugammadex-treated patients did not achieve TOFr of 0.9 at the time of tracheal extubation than did neostigmine-treated participants. Patients in the sugammadex group had lower incidence of postoperative lung complications, and shorter durations of postanesthesia care unit stay and postoperative hospital stay than those in the neostigmine group. There was no significant difference in the incidence of readmission between the 2 groups. CONCLUSIONS: Administration of sugammadex provided faster recovery of rocuronium-induced neuromuscular block when compared with neostigmine. Moreover, for patients undergoing lung cancer resection, administration of sugammadex could reduce the incidence of postoperative pulmonary complications and duration of postoperative hospital stay.

Evaluation of the impact of deep neuromuscular blockade on surgical conditions for laryngeal microsurgery with High Frequency Jet Ventilation. A comparison with no block during intravenous general anesthesia with topical lidocaine.

OBJECTIVE: Laryngeal transoral surgery classically requires a neuromuscular block (NMB) to facilitate tracheal intubation and to improve surgical conditions. However, the short duration of most procedures and the potential complications of residual NMB lead to consider a no block approach. The hypothesis that intravenous anesthesia (remifentanil and propofol infusions) without NMB but including glottis topical lidocaine anesthesia would allow clinically acceptable laryngeal exposure and good surgical conditions was tested in the specific context of procedures undergone with High Frequency Jet Ventilation (HFJV). STUDY DESIGN: A prospective randomized clinical comparison. METHODS: 66 consenting patients were planned to receive 0.6 mg·kg-1 rocuronium or saline at random. The outcome measurements included the time and conditions to complete suspended laryngoscopy, and the surgical conditions rated by the surgeon. Any vocal cord movement or coughing was recorded. Data were compared using a Wilcoxon rank-sum test for numerical variables and chi-square test for categorical ones. Treatment failure was defined as an impossible laryngoscopy or a grade 4 surgical field occurring at any time during surgery and was compared to its null theoretical value by a general z-test. An interim analysis after completion of 50% patients was performed using Pocock boundaries at 0.0294 significance levels. RESULTS: A significant failure rate occurred in the non paralysed group (27%, p < 0.001). No coughing and no vocal cords movement occurred in the NMB group. Poorer surgical conditions were obtained without NMB (p = 0.011). CONCLUSION: Inducing a deep NMB ensured improved conditions during direct laryngeal microsurgery with HFJV.

Comparison of a new EMG module, AF-201P, with acceleromyography using the post-tetanic counts during rocuronium-induced deep neuromuscular block: a prospective, multicenter study.

Recent advances in neuromuscular monitors have facilitated the development of a new electromyographic module, AF-201P™. The purpose of this study was to investigate the relationship between post-tetanic counts (PTCs) assessed using the AF-201P™ and the acceleromyographic TOF Watch SX™ during rocuronium-induced deep neuromuscular block. Forty adult patients consented to participate in this study. The integrated AF-201P™ stimulating and sensing electrode was placed over the ulnar nerve on the distal volar forearm and the belly of the abductor digiti minimi muscle of one arm. The TOF Watch SX™ was applied with the provided hand adaptor on the opposite arm, to observe twitch responses of the adductor pollicis muscle. After stabilization of train-of-four (TOF) responses, rocuronium 0.9 mg kg-1 was administered intravenously. Then, PTCs were observed every 3 min using both monitors. Whenever the TOF count was detected with the TOF Watch SX™, rocuronium 0.2 mg kg-1 was administered, and successive PTC measurements were continued. A total of 1732 paired PTC data points were obtained and analyzed. Regression analysis showed no significant difference in PTCs between the two monitors (PTCs measured by the TOF Watch SX™ = 0.78·PTCs measured by AF-201P™ + 0.21, R = 0.56). Bland-Altman analysis also showed acceptable ranges of bias [95% CI] and limits of agreement (0.3 [0.2 to 0.5] and - 4.6 to 5.3) for the PTCs. The new EMG module, AF-201P™, showed reliable PTCs during deep neuromuscular block, as well as the TOF Watch SX™.