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.

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.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Sugammadex and oral contraceptives.

PURPOSE OF REVIEW: This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined. RECENT FINDINGS: Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex. SUMMARY: Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting.

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.

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

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

How robust are the STRONGER and STIL-STRONGER studies?

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.

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.

Postoperative Risk of Transfusion After Reversal of Residual Neuromuscular Block With Sugammadex Versus Neostigmine: A Retrospective Cohort Study.

BACKGROUND: Sugammadex and neostigmine are routinely used to reverse residual neuromuscular blocks at the end of surgery. Sugammadex has been linked with prolongation of laboratory coagulation markers, but clinical relevance on postoperative blood loss and transfusions remains unclear. METHODS: In this retrospective, single-center, cohort study, we analyzed medical records of adult patients having noncardiac surgery who were given sugammadex or neostigmine from May 2016 to December 2020. Our primary outcome was the incidence of any postoperative transfusion of red blood cells, and/or fresh-frozen plasma, and/or platelets. Secondary outcomes were duration of hospitalization, need for resurgery, and postoperative intensive care unit (ICU) admission. After propensity score weighting, the odds ratio (OR) for postoperative transfusion was assessed in both groups (sugammadex versus neostigmine) using a generalized estimation equation to count within-subject correlation weighted by the inverse propensity score. RESULTS: Out of 39,325 eligible surgeries, 33,903 surgeries in 29,062 patients were included in the analysis; with 4581 patients receiving sugammadex and 29,322 patients receiving neostigmine. The raw incidence of postoperative transfusion was 7.40% in sugammadex and 7.45% in the neostigmine group. After weighting by propensity score, the incidence of postoperative transfusion was 8.01% in the sugammadex and 7.38% in the neostigmine group (OR, 1.11 [95% confidence interval [CI], 0.97-1.26; P = .118]). There was no difference in duration of hospitalization and need for resurgery, but odds of postoperative ICU admission were significantly higher for patients receiving sugammadex than those receiving neostigmine (OR, 1.33 [98.33% CI, 1.17-1.52; P < .0001]). Our a priori planned analysis of coagulation laboratory parameters could not be completed because of a high amount of missing laboratory data. CONCLUSIONS: There is no statistically significant nor clinically important difference in the risk of postoperative transfusion in patients receiving sugammadex or neostigmine.

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.

Clarifying the grey space of sugammadex induced bradycardia.

PURPOSE OF REVIEW: This review describes recent prospective and retrospective work exploring the incidence and clinical consequence of sugammadex-induced bradycardia and an update of recent evidence and adverse event reports to the United States Food and Drug Administration regarding the incidence of sugammadex induced bradycardia. RECENT FINDINGS: This work suggests that the incidence of sugammadex-induced bradycardia can range from 1 to 7% depending on the definition to reverse moderate to deep neuromuscular blockade. For most instances, the bradycardia is inconsequential. For those instances that have hemodynamic instability, the adverse physiology is easily treated with appropriate vasoactive agents. One study demonstrated that the incidence of bradycardia from sugammadex is less than with neostigmine. There are several case reports that describe marked bradycardia with cardiac arrest from reversal with sugammadex. The incidence of this type of reaction to sugammadex appears to be very rare. Data from the United States Food and Drug Administration's Adverse Event Reporting System public dashboard corroborates this presence of this rare finding. SUMMARY: Sugammadex-induced bradycardia is common and, in most instances, of minimal clinical consequence. Nevertheless, anesthesia providers should maintain proper monitoring and vigilance to treat hemodynamical instability with each administration of sugammadex.

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.

Association of Sugammadex or Neostigmine With Major Postoperative Pulmonary Complications in Children.

BACKGROUND: Recent data in adult patients indicate that the use of sugammadex compared to neostigmine for reversal of neuromuscular block (NMB) was associated with a significant reduction in the risk of composite postoperative pulmonary complications. Despite the clinical significance of pulmonary complications in children, studies exploring the role of NMB reversal in the risk of these complications are currently unavailable. METHOD: We performed a propensity score-matched retrospective study using the Pediatric Health Information System (PHIS) dataset spanning the years 2016 and 2020. We studied children <18 years who underwent elective, inpatient, noncardiac surgical procedures and received either neostigmine or sugammadex for reversal of NMB. Our primary outcome was major postoperative pulmonary complication, which we defined as the occurrence of either postoperative pneumonia or respiratory failure. RESULTS: Our study included a study population of 33,819 children, of whom 23,312 (68.9%) received neostigmine and 10,507 (31.1%) received sugammadex. After propensity score matching (10,361 matched from each group), we found no evidence of a statistically significant association between the NMB reversal agent and the incidence of pulmonary complications (3.1% vs 3.1%; odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.05; P = .19). The components of pulmonary complications, including respiratory failure and pneumonia, were not statistically associated with the choice of NMB reversal agent. CONCLUSIONS: Choice of NMB reversal agent does not appear to impact the incidence of major postoperative pulmonary complications. Further research is needed to determine whether our results carry forth across subpopulations defined by surgical specialty, the presence of complex chronic conditions, and anesthesia technique.

Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

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.

Role of sugammadex in the treatment of anaphylaxis due to rocuronium in children: Extrapolation from adult and animal reports.

Allergic reactions are generalized hypersensitivity processes triggered by different antigenic stimuli, resulting in the end effect of mast cell degranulation and adverse physiologic effects. During the perioperative period, the most commonly identified agents include antibiotics, neuromuscular blocking agents (rocuronium and succinylcholine), chlorhexidine, and iodinated dyes for radiologic imaging. Sugammadex is a novel agent for the reversal of neuromuscular blockade achieved with rocuronium or vecuronium. Its unique mechanism of action, whereby it encapsulates and forms a one-to-one complex with rocuronium, has led to its anecdotal use as an adjunct in the treatment of anaphylactic and anaphylactoid reactions following rocuronium. The current manuscript discusses the potential use of sugammadex in the treatment of allergic reactions following the administration of rocuronium, reviews previous anecdotal reports of its use in these scenarios, and provides recommendations for future care.

Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study.

BACKGROUND: Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. AIM: To assess sugammadex for reversal of neuromuscular blockade in pediatric participants. METHODS: This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age. RESULTS: Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3). CONCLUSIONS: Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17 years. CLINICAL TRIAL REGISTRATION: NCT03351608/EudraCT 2017-000692-92.

Comment on Fierro et al. Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient. Medicina 2021, 57, 79.

We read with great interest the case report by Fierro et al. [...].

Reply to Sagliocco, O.; Betelli, M. Comment on "Fierro et al. Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient. Medicina 2021, 57, 79".

We thank Dr. Sagliocco and Dr. Betelli for their comments [...].