Effects of neuromuscular block reversal with neostigmine/glycopyrrolate versus sugammadex on bowel motility recovery after laparoscopic colorectal surgery: A randomized controlled trial.

STUDY OBJECTIVE: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A single tertiary center. PATIENTS: 111 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 µg.kg-1 of neostigmine and 10 µg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg-1 of sugammadex (sugammadex group). MEASUREMENTS: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed. MAIN RESULTS: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001). CONCLUSIONS: The time to the first flatus was shorter using 2 mg.kg-1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate.

The safety and efficacy of sugammadex for reversing neuromuscular blockade in younger children and infants.

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.

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.

Impact of sugammadex and neostigmine on outcome after major orthopaedic surgery: A population-based analysis.

BACKGROUND: Residual neuromuscular blockade after surgery remains a major concern given its association with pulmonary complications. However, current clinical practices with and the comparative impact on perioperative risk of various reversal agents remain understudied. OBJECTIVE: We investigated the use of sugammadex and neostigmine in the USA, and their impact on postoperative complications by examining national data. DESIGN: This population-based retrospective study used national Premier Healthcare claims data. SETTING AND PARTICIPANTS: Patients undergoing total hip/knee arthroplasty (THA, TKA), or lumbar spine fusion surgery between 2016 and 2019 in the United States who received neuromuscular blocking agents. INTERVENTION: The effects of sugammadex and neostigmine for pharmacologically enhanced reversal were compared with each other and with controls who received no reversal agent. MAIN OUTCOMES: included pulmonary complications, cardiac complications, and a need for postoperative ventilation. Mixed-effects regression models compared the outcomes between neostigmine, sugammadex, and controls. We report odds ratios (OR) and 95% confidence intervals (CI). Bonferroni-adjusted P values of 0.008 were used to indicate significance. RESULTS: Among 361 553 patients, 74.5% received either sugammadex (20.7%) or neostigmine (53.8%). Sugammadex use increased from 4.4% in 2016 to 35.4% in 2019, whereas neostigmine use decreased from 64.5% in 2016 to 43.4% in 2019. Sugammadex versus neostigmine or controls was associated with significantly reduced odds for cardiac complications (OR 0.86, 95% CI, 0.80 to 0.92 and OR 0.83, 95% CI, 0.78 to 0.89, respectively). Both sugammadex and neostigmine versus controls were associated with reduced odds for pulmonary complications (OR 0.85, 95% CI, 0.77 to 0.94 and OR 0.91, CI 0.85 to 0.98, respectively). A similar pattern of sugammadex and neostigmine was observed for a reduction in severe pulmonary complications, including the requirement of invasive ventilation (OR 0.54, 95% CI, 0.45 to 0.64 and OR 0.53, 95% CI, 0.46 to 0.6, respectively). CONCLUSIONS: Population-based data indicate that sugammadex and neostigmine both appear highly effective in reducing the odds of severe life-threatening pulmonary complications. Sugammadex, especially, was associated with reduced odds of cardiac complications.

Combined administration of anisodamine and neostigmine alleviated colitis by inducing autophagy and inhibiting inflammation.

Our previous work demonstrated that the anisodamine (ANI) and neostigmine (NEO) combination produced an antiseptic shock effect and rescued acute lethal crush syndrome by activating the α7 nicotinic acetylcholine receptor (α7nAChR). This study documents the therapeutic effect and underlying mechanisms of the ANI/NEO combination in dextran sulfate sodium (DSS)-induced colitis. Treating mice with ANI and NEO at a ratio of 500:1 alleviated the DSS-induced colitis symptoms, reduced body weight loss, improved the disease activity index, enhanced colon length, and alleviated colon inflammation. The combination treatment also enhanced autophagy in the colon of mice with DSS-induced colitis and lipopolysaccharide/DSS-stimulated Caco-2 cells. Besides, the ANI/NEO treatment significantly reduced INF-γ, TNF-α, IL-6, and IL-22 expression in colon tissues and decreased TNF-α, IL-1ß, and IL-6 mRNA levels in Caco-2 cells. Meanwhile, the autophagy inhibitor 3-methyladenine and ATG5 siRNA attenuated these effects. Furthermore, 3-methyladenine (3-MA) and the α7nAChR antagonist methyllycaconitine (MLA) weakened the ANI/NEO-induced protection on DSS-induced colitis in mice. Overall, these results indicate that the ANI/NEO combination exerts therapeutic effects through autophagy and α7nAChR in a DSS-induced colitis mouse model.

Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment: A Randomized, Double-Blinded Study.

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study.

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects.

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.

Influence of Neostigmine on Early Postoperative Cognitive Dysfunction in Older Adult Patients Undergoing Noncardiac Surgery: A Double-Blind, Placebo-Controlled, Randomized Controlled Trial.

BACKGROUND: The goal of this study was to investigate the efficacy of neostigmine on postoperative cognitive dysfunction (POCD) and determine its effect on systematic markers of oxidative stress in older patients. METHODS: This double-blind placebo-controlled trial enrolled 118 elderly patients (≥65 years) undergoing noncardiac surgeries who were allocated to a neostigmine treatment group (0.04 mg/kg) or a placebo control group (normal saline) postoperatively. POCD was diagnosed if the Z -scores for the mini-mental state examination and the Montreal Cognitive Assessment were both ≤-1.96. Postoperative serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were also compared. Multivariable regression analysis with dose adjustment of atropine was used to demonstrate the influence of neostigmine on the incidence of POCD. RESULTS: Patients receiving neostigmine had a significantly reduced incidence of POCD compared to patients who were treated with placebo on the first day after surgery (-22%, 95% confidence interval [CI], -37 to -7), but not on the third (8%, 95% CI, -4 to 20) or seventh day after surgery (3%, 95% CI, -7 to 13). Postoperative plasma MDA levels were significantly lower ( P = .016), but SOD and BDNF levels were increased ( P = .036 and .013, respectively) in the neostigmine group compared to the control group on the first day after surgery. CONCLUSIONS: Neostigmine reduced POCD on the first day after noncardiac surgery in older patients. Neostigmine treatment inhibited oxidative stress and increased serum BDNF levels. There was no significant influence of neostigmine on POCD on the third or seventh day after surgery. The clinical influence of neostigmine on POCD should be further investigated.

[Effect of sugammadex on postoperative nausea and vomiting after surgery for intracranial aneurysm].

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ2 or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ2=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ2=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ2=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.

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.

Evaluation of a Protocol for the Management of Maintenance and Reversal of Rocuronium Block Using Neostigmine or Sugammadex.

BACKGROUND: Postoperative residual neuromuscular blockade (PRNB) is defined as an adductor pollicis train-of-four ratio (TOFR) <0.9. It is a common postoperative complication when nondepolarizing muscle relaxants are either not reversed or reversed with neostigmine. PRNB has been reported in 25% to 58% of patients who receive intermediate-acting nondepolarizing muscle relaxants, and it is associated with increased morbidity and decreased patient satisfaction. We conducted a prospective descriptive cohort study during the implementation of a practice guideline that included the selective use of sugammadex or neostigmine. The primary study aim of this pragmatic study was to estimate the incidence of PRNB at arrival to the postanesthesia care unit (PACU) when the practice guideline is followed. METHODS: We enrolled patients undergoing orthopedic or abdominal surgery requiring neuromuscular blockade. Rocuronium administration was guided by surgical requirements and based on ideal body weight, with dose reductions for women and/or age >55 years. Only qualitative monitoring was available to the anesthesia providers, and selection of sugammadex or neostigmine was guided by tactile assessments of the response to train-of-four (TOF) stimulation by a peripheral nerve stimulator. Neostigmine was administered if no fade was detected in the TOF response at the thumb. Deeper blocks were reversed with sugammadex. The prespecified primary and secondary end points were the incidence of PRNB at arrival to the PACU, defined as a normalized TOFR (nTOFR) < 0.9, and severe PRNB, defined as nTOFR <0.7 on arrival to the PACU. Anesthesia providers were blinded to all quantitative measurements made by research staff. RESULTS: Analysis included 163 patients, and 145 underwent orthopedic and 18 abdominal surgeries. Of the 163 patients, 92 (56%) were reversed with neostigmine and 71 (44%) with sugammadex. The overall incidence of PRNB at PACU arrival was 5 of 163 or 3% (95% confidence interval [CI], 1-7). The incidence of severe PRNB in PACU was 1% (95% CI, 0-4). Three of the 5 subjects with PRNB had TOFR <0.4 at time of reversal but were given neostigmine since anesthesia providers detected no fade by qualitative assessment. CONCLUSIONS: The use of a protocol that specifies rocuronium dosing and selective use of sugammadex versus neostigmine based on qualitative assessment of TOF count and fade allowed us to achieve an incidence of PRNB of 3% (95% CI, 1-7) at PACU arrival. Quantitative monitoring may be needed to further reduce this incidence.

Postoperative oxygenation assessed by SpO2/FiO2 ratio and respiratory complications after reversal of neuromuscular block with Sugammadex or neostigmine: A retrospective cohort study.

STUDY OBJECTIVE: Residual neuromuscular block may lead to postoperative muscle weakness, inadequate oxygenation, and other pulmonary complications. Sugammadex may provide more rapid and effective restoration of neuromuscular function than neostigmine. We therefore tested the primary hypothesis that noncardiac surgical patients given sugammadex oxygenate better during initial recovery than those given neostigmine. Secondarily, we tested the hypothesis that patients given sugammadex have fewer pulmonary complications during hospitalization. DESIGN: Retrospective cohort analysis. SETTING: Postoperative recovery area of a tertiary care hospital. PATIENTS: Adults who had non-cardiothoracic surgery and were given either neostigmine or sugammadex. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the lowest SpO2/FiO2 ratio in the post-anesthesia care unit. The secondary outcome was a composite of pulmonary complications. MAIN RESULTS: Among 71,457 cases, 10,708 (15%) were given sugammadex and 60,749 (85%) received neostigmine. After propensity weighting, the mean minimum SpO2/FiO2 ratio was 301 ± 77 (SD) in patients given sugammadex and 303 ± 71 in those given neostigmine, yielding an estimated difference in means of -3.5 (95% confidence interval: -5.3, -1.7; P = 0.0002). 4.4% of patients given sugammadex and 3.6% of patients given neostigmine had postoperative pulmonary complications (P = 0.0005, number-needed-to-be-exposed =136; 95% CI: 83, 330), with the main contributing components being new bronchospasm or exacerbation of obstructive pulmonary disease. CONCLUSIONS: Postoperative minimum SpO2/FiO2 ratio during PACU admission was similar after reversal of neuromuscular block by sugammadex and neostigmine. Reversal with sugammadex was associated with more pulmonary complications, but most were minor and of little consequence.

Nodal Tachycardia Induced By Neostigmine Administration During Off-Pump Coronary Artery Bypass Graft Surgery: What Makes the Difference? A Case Report.

Controlling the heart rate (HR) to a proper level is an important part during off-pump coronary artery bypass graft (CABG) surgery, particularly in two aspects. First, the oxygen consumption during cardiac work could be decreased, which is obviously beneficial for the myocardium suffering from inadequate blood supply. Second, slow heart action makes it easy for surgeons to perform. There are some treatments for lowering HR, where neostigmine is not commonly used but usually effective, which had been discussed more than 50 years ago. However, there are adverse responses that cannot be ignored and are even dangerous, for example, severe bradyarrhythmia and overload of secretion in the trachea. Here, we report a nodal tachycardia case after neostigmine infusion.

Efficacy and safety of neostigmine on treating gastrointestinal dysmotility in severe acute pancreatitis patients: study protocol for a randomized controlled trial.

BACKGROUND: Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed feeding, oral feeding intolerance, paralytic ileus, and abdominal compartment syndrome. Currently, there are limited treatment for this complication. Neostigmine is known to increase gastrointestinal motility and has been used to treat gastrointestinal dysmotility after surgery. However, research in treating acute pancreatitis with neostigmine is currently limited. METHODS: This trial is a randomized, placebo-controlled, double-blinded, mono-centric trial that will test the hypothesis that neostigmine can improve gastrointestinal motility in patients with severe acute pancreatitis. Up to 56 patients will be randomized in this study receiving 0.5 mg/1 ml of neostigmine methylsulfate injection twice per day or 1 ml of saline injection twice per day. Defection time (aim 1), mortality and organ failure (aim 2), borborygmus, starting of enteral nutrition and intra-abdominal pressure (aim 3), and length of ICU and hospital stay (aim 4) will be assessed. DISCUSSION: Findings from this study will provide data supporting the usage of neostigmine for treating severe acute pancreatitis patients with gastrointestinal dysmotility. TRIAL REGISTRATION: This study is registered on chictr.org.cn with the identifier as ChiCTR2200058305. Registered on April 5, 2022.

Routine administration of neostigmine after recovery of spontaneous breathing versus neuromuscular monitor-guided administration of neostigmine in pediatric patients: a parallel, randomized, controlled study.

BACKGROUND: Neostigmine used to reverse the muscle relaxants should be guided by neuromuscular monitoring, as the degree of spontaneous pre-reversal recovery is the key to success to reverse the neuromuscular block. But neuromuscular monitoring is not always available for some patients during anesthesia and, in consequence, we need to use other clinical judgment to guide the use of neostigmine to reverse the neuromuscular block. In this trial, we aimed to evaluate the incidence of residual neuromuscular blockade (rNMB) in pediatric patients with routine use of neostigmine after recovery of spontaneous breathing compared with the patients with the use of neostigmine guided by neuromuscular monitoring. METHODS: A parallel, randomized, controlled noninferiority study was conducted. We enrolled aged 3 months to 12 years old patients who underwent inguinal hernia repair under general anesthesia. The enrolled patients were randomly divided into experimental and control groups. After surgery, children in the experimental group were given 0.02 mg/kg neostigmine after recovery of spontaneous breathing. Children in the control group were given 0.02 mg/kg neostigmine when the train-of-four (TOF) ratio was between 0.4 and 0.9. However, no neostigmine was administered if the TOF ratio was higher than 0.9. The primary outcome was the incidence of rNMB after extubation (TOF ratio < 0.9). Secondary outcomes included the incidence of neostigmine-induced muscle paralysis, end of surgery - extubation interval, end of surgery - exit OR interval, the length of stay in the PACU, the incidence of hypoxia in the PACU, the number of children who required assisted ventilation during the PACU stay, and neostigmine-related adverse events. RESULTS: A total of 120 children were included in this study, with 60 in the experimental group and 60 in the control group. There was no significant difference in the incidence of rNMB after extubation between the groups (45/60 vs 44/60, RR 1.02 [95% CI, 0.83 to 1.26], p = 0.84). There was no neostigmine-induced muscle paralysis in either group. Adverse events were similar occurred in both groups. However, time from end of the surgery to leaving the operating room was earlier in the experimental group than in the control group (13.6 ± 5.2 vs 15.7 ± 5.6 min, MD -2.10 min [95% CI, -3.70 to -0.50], p = 0.04). The risk ratio of the incidence of TOF ratio < 0.3 for the experimental group was 31.12 (95%CI, 1.89 to 512.61) compared with the control group (12/60 vs 0/60, p = 0.00) in exploratory analysis. CONCLUSIONS: Recovery of spontaneous breathing could be used as a substitute of neuromuscular monitoring to guide neostigmine use in pediatric patients following minor surgeries. However, care should be taken for the residual neuromuscular block. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012890. Registered on 5 October 2017.

Fetal outcomes with and without the use of sugammadex in pregnant patients undergoing non-obstetric surgery: a multicenter retrospective study.

BACKGROUND: The influence of sugammadex exposure during pregnancy on progesterone withdrawal and miscarriage is unknown. We aimed to compare the fetal outcomes in pregnant patients who had undergone non-obstetric surgery with and without sugammadex. METHODS: We retrospectively reviewed the medical charts of pregnant women who underwent non-obstetric surgery at three tertiary perinatal care centers in Japan from January 2013 to December 2020. The women were divided into those who received general anesthesia with sugammadex (GA with SGX) and those who received general anesthesia without sugammadex (GA without SGX). We compared miscarriages and preterm births within four weeks after surgery. RESULTS: Among the 124 women, 73 and 51 were included in the GA with SGX and GA without SGX groups, respectively. The two groups showed no differences in the rate of miscarriages or preterm births (3.0 % vs 4.3 %; odds ratio 1.42, 95 % confidence interval 0.19 to 10.47; P = 1.00). The SGX and no SGX groups were missing outcomes for 8.2 % and 7.8 % of cases, respectively. CONCLUSIONS: Having GA with SGX or GA without SGX did not result in different rates of miscarriage or preterm birth within four weeks after the procedure. These findings do not exclude a potential association between sugammadex exposure during pregnancy and adverse pregnancy outcomes. Missing data may have obscured possible adverse outcomes from sugammadex exposure.

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.