Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals.

Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product N-nitrosamines without published AI information from animal carcinogenicity testing. Finally, a novel risk evaluation strategy for predicting and investigating the possible nitrosation of amine precursors and amine pharmaceuticals as powerful prevention of nitrosamine contamination is addressed.

Atracurium Versus Cisatracurium in the Treatment of Acute Respiratory Distress Syndrome.

Background: Neuromuscular blocking agents are one of the few medication classes that have demonstrated a clinical benefit in patients with severe acute respiratory distress syndrome (ARDS). However, most literature utilized cisatracurium, and utilization of atracurium is limited to 1 small study. Objective: The purpose of this study was to provide further evidence comparing the safety and efficacy of atracurium versus cisatracurium for the treatment of ARDS. Methods: This multicenter, retrospective, observational cohort noninferiority study was conducted at 3 hospitals within a tertiary health care system. We included subjects diagnosed with ARDS who received either atracurium or cisatracurium for at least 12 hours. The primary outcome measured the change in PaO2/FiO2 (P/F) ratio from baseline to 48 hours after initiation. Results: Baseline characteristics were similar between groups except for a higher median age and a higher proportion of subjects who were COVID-positive in the atracurium group. There were also some noted differences in the baseline P/F ratios. In a multivariable model adjusting for baseline characteristics, the change in the P/F ratio for atracurium was noninferior to cisatracurium at 24, 48, and 72 hours. A significant cost reduction, measured as cost per patient per day, was seen with the use of atracurium ($14.81-$25.16 vs $33.86-$41.91). Conclusion: Atracurium appears to be a safe and cheaper alternative agent in the management of ARDS.

Metabolomic transition trajectory and potential mechanisms of N-nitrosomethylbenzylamine induced esophageal squamous cell carcinoma in rats.

Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD+ in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.

Validation of neuromuscular blocking agent use in acute respiratory distress syndrome: a meta-analysis of randomized trials.

BACKGROUND: We aimed to synthesize up-to-date trials to validate the effects of neuromuscular blocking agent (NMBA) use in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). METHODS: Several databases including PubMed, EMBASE, Web of Science, and Cochrane Central Register were searched up to November 14, 2019. All randomized trials investigating the use of NMBAs in patients with moderate-to-severe ARDS and reporting mortality data were included in the meta-analysis. The primary outcome was mortality, and the secondary outcomes were clinical outcomes, including respiratory physiological parameters, incidence of barotrauma, ICU-free days, and ventilation-free days. RESULTS: A total of 7 trials enrolling 1598 patients were finally included in this meta-analysis. The results revealed that the use of NMBAs in moderate-to-severe ARDS could significantly decrease the mortality truncated to day 28 (RR 0.74, 95% CI 0.56 to 0.98, P = 0.03) and day 90 (RR 0.77, 95% CI 0.60 to 0.99, P = 0.04). NMBA use could significantly decrease the incidence of barotrauma (RR 0.56, 95% CI 0.36 to 0.87, P = 0.009). No significant difference was observed in ICU-free days or ventilation-free days between the NMBA and control groups. CONCLUSION: The use of NMBAs could significantly decrease mortality in moderate-to-severe ARDS patients and decrease the incidence of barotrauma during mechanical ventilation. However, more large-scale randomized trials are needed to further validate the effect of NMBA use in ARDS.

Recovery and prediction of postoperative muscle power - is it still a problem?

BACKGROUND: In the postoperative period, immediate recovery of muscular power is essential for patient safety, but this can be affected by anaesthetic drugs, opioids and neuromuscular blocking agents (NMBA). In this cohort study, we evaluated anaesthetic and patient-related factors contributing to reduced postoperative muscle power and pulse oximetric saturation. METHODS: We prospectively observed 615 patients scheduled for minor surgery. Premedication, general anaesthesia and respiratory settings were standardized according to standard operating procedures (SOP). If NMBAs were administered, neuromuscular monitoring was applied to establish a Train of four (TOF)-Ratio of >0.9 before extubation. After achieving a modified fast track score > 10 at 4 time points up to 2 h postoperatively, we measured pulse oximetric saturation and also static and dynamic muscle power, using a high precision digital force gauge. Loss of muscle power in relation to the individual preoperative baseline value was analysed in relation to patient and anaesthesia-related factors using the T-test, simple and multiple stepwise regression analysis. RESULTS: Despite having achieved a TOF ratio of >0.9 a decrease in postoperative muscle power was detectable in most patients and correlated with reduced postoperative pulse oximetric saturation. Independent contributing factors were use of neuromuscular blocking agents (p < 0.001), female gender (p = 0.001), TIVA (p = 0.018) and duration of anaesthesia >120 min (p = 0.019). CONCLUSION: Significant loss of muscle power and reduced pulse oximetric saturation are often present despite a TOF-Ratio > 0.9. Gender differences are also significant. A modified fast track score > 10 failed to predict recovery of muscle power in most patients. TRIAL REGISTRATION: German Clinical Trial Register DRKS-ID DRKS00006032 ; Registered: 2014/04/03.

Predictive value of allergy tests for neuromuscular blocking agents: tackling an unmet need.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are a predominant cause of perioperative anaphylaxis in Europe. Diagnosis of NMBA allergy relies upon the careful review of the anaesthetic report complemented with skin tests. Additional diagnostic tests are quantification of specific IgE antibodies (sIgE) and basophil activation test (BAT). However, data on the predictive value of the skin tests, the BAT and the sIgE assays (drug-specific and substituted ammonium structures) are limited or not available, mainly because such exploration requires dangerous NMBA provocation tests. METHODS: In this study, the predictive value of skin test, BAT and measurement of sIgE to substituted ammonium structures is gathered from a review of anaesthetic records of subsequent surgical procedures with NMBA administration and/or occurrence of perioperative incidents. RESULTS: We investigated a series of 272 patients with perioperative anaphylaxis, of whom 100 had undergone second general anaesthesia. Negative skin test and negative BAT assisted the selection of alternative NMBA, which were well tolerated in all cases. Five patients with a positive sIgE to rocuronium but with negative skin testing and BAT safely received rocuronium during second anaesthesia. Twelve patients with sIgE reactivity to morphine, but negative skin test and BAT to benzylisoquinolines, tolerated administration of cisatracurium or atracurium. Alternatively, benzylisoquinoline allergy went undetected in the morphine solid-phase assay. CONCLUSIONS: Skin test and BAT have an excellent negative predictive value in our series. The uneventful re-exposure of rocuronium in patients with an isolated positive sIgE result to rocuronium calls into question the predictive value of this assay and suggests sIgE serology to be less clinically predictive than the functional investigations relying upon activation of mast cells or basophils. The presence of a positive sIgE to substituted ammonium structures such as morphine does not preclude further use of benzylisoquinolines.

Rocuronium-Induced Anaphylaxis in the Perioperative Period: A Clinical Review.

Rocuronium, a nondepolarizing neuromuscular blocking agent used for muscle relaxation especially during endotracheal intubation, can cause hypersensitivity reactions. This article provides an overview of anaphylactic reactions; risk factors; and the pathophysiology, presentation, diagnosis, treatment, and nursing implications associated with rocuronium-induced anaphylaxis. Life-threatening anaphylaxis can be immunoglobulin E-mediated or non-immunoglobulin E-mediated and usually occurs after the first dose. Anaphylaxis can present with hypotension and bronchospasm; cutaneal symptoms, such as erythema, may not be obvious. Diagnosis is initially presumptive and may require a transesophageal echocardiogram to rule out other causes of hypotension (eg, pulmonary embolus). Emergency treatment begins with epinephrine administration and fluid boluses; cardiac support devices may be needed. Definitive diagnosis requires early measurement of histamine and tryptase levels and skin testing after the patient recovers from the reaction. Perioperative nurses should be prepared to participate in emergency treatment of anaphylaxis and advocate for testing for a definitive diagnosis.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Multi-omics analysis revealed NMBA induced esophageal carcinoma tumorigenesis via regulating PPARα signaling pathway.

As widespread environmental carcinogens causing esophageal carcinoma (EC), the effects of N-nitrosamines on human health hazards and accurate toxicity mechanisms have not been well-elucidated. In this study, we explored the tumorigenic mechanism of N-nitrosomethylbenzylamine (NMBA) exposure using both cell and rat models. It was found that NMBA (2 µM) exposure for 26 weeks induced malignant transformation of normal esophageal epithelial (Het-1A) cells. After then proteomics analysis showed that lipid metabolism disorder predominantly participated in the process of NMBA-induced cell malignant transformation. Further the integrated proteomics and lipidomics analysis revealed that the enhancement of fatty acid metabolism promoted the EC tumorigenesis induced by NMBA through facilitating the fatty acid-associated PPARα signaling pathway. The animal studies also revealed that accelerated fatty acid decomposition in the progression of NMBA-induced EC models of rats was accompanied by the activation of the PPARα pathway. Overall, our findings depicted the key dynamic molecular alteration triggered by N-nitrosamines, and provided comprehensive biological perspectives into the carcinogenic risk assessment of N-nitrosamines.

Effects of pH and Crosslinking Agent in the Evaluation of Hydrogels as Potential Nitrate-Controlled Release Systems.

Water scarcity and the loss of fertilizer from agricultural soils through runoff, which also leads to contamination of other areas, are increasingly common problems in agriculture. To mitigate nitrate water pollution, the technology of controlled release formulations (CRFs) provides a promising alternative for improving the management of nutrient supply and decreasing environmental pollution while maintaining good quality and high crop yields. This study describes the influence of pH and crosslinking agent, ethylene glycol dimethacrylate (EGDMA) or N,N'-methylenebis (acrylamide) (NMBA), on the behavior of polymeric materials in swelling and nitrate release kinetics. The characterization of hydrogels and CRFs was performed by FTIR, SEM, and swelling properties. Kinetic results were adjusted to Fick, Schott, and a novel equation proposed by the authors. Fixed-bed experiments were carried out by using the NMBA systems, coconut fiber, and commercial KNO3. Results showed that on the one hand, no significant differences were observed in nitrate release kinetics for any system in the selected pH range, this fact allowing to apply these hydrogels to any type of soil. On the other hand, nitrate release from SLC-NMBA was found to be a slower and longer process versus commercial potassium nitrate. These features indicate that the NMBA polymeric system could potentially be applied as a controlled release fertilizer suitable for a wide variety of soil typologies.

REVersal of nEuromusculAr bLocking Agents in Patients Undergoing General Anaesthesia (REVEAL Study).

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

DNA polymerase ß deficiency promotes the occurrence of esophageal precancerous lesions in mice.

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase ß (Polß), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polß is related to the occurrence of esophageal cancer, but the role of Polß deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polß-knockout mice were used to explore the relationship of Polß deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polß-KO mice were more serious than those in Polß-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polß increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polß-KO mice. We also found that deletion of Polß promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polß knockout promotes the occurrence of esophageal precancerous lesions.

Fixed dilated pupils in Covid-19 ARDS patients under rocuronium, reversed after discontinuation.

Neuromuscular Blockade Agents (NMBA) are used in the management of moderate and severe Acute Respiratory Distress Syndrome (ARDS) patients. They have never been reported to present Central Nervous System adverse reactions. Shortage of cis-atracurium during the pandemic, led to the use of rocuronium. We report three patients with Covid-19 ARDS, who presented bilateral dilated, non-reactive pupils, after continuous rocuronium infusion. Brain CT findings were unremarkable and transcranial doppler tracings did not suggest brain edema or hemorrhage. NMBA's discontinuation led to reversal of the pupillary dilation. We believe that impairment of Blood-Brain-Barrier, due to Covid-19, led rocuronium access into the Central Nervous System, leading to this adverse effect. Clinicians should be aware of this adverse reaction when managing patients with Covid-19 ARDS warranting NMBA use.

Precision Neuromuscular Block Management for Neural Monitoring During Thyroid Surgery.

INTRODUCTION: Titration of neuromuscular block (NMB) plays a key role in intraoperative recurrent laryngeal nerve monitoring during thyroid surgery. The combination of neuromuscular blocking agent and timely partial reversal of NMB was investigated in both animal experiments and clinical neuro-monitored thyroidectomy. METHODS: In animal experiments, 8 piglets received sugammadex to assess the laryngeal EMG recovery after rocuronium-induced NMB. In clinical monitored thyroidectomy, 40 patients each were allocated to conventional group and sugammadex group. Conventional group received rocuronium 0.3 mg/kg at anesthesia induction, while sugammadex group received partial NMB recovery protocol- 0.6 mg/kg of rocuronium at anesthesia induction and 0.5 mg/kg of sugammadex. Main outcome was assessed by first (V1) and final (V2) EMG signal induced by vagal stimulation. RESULTS: In the porcine model, 50% recovery of laryngeal EMG amplitude was achieved at 16.8 ± 1.9 and 6 ± 2.7 minutes respectively after 0.5 and 1 mg/kg of sugammadex (p < 0.01). In monitored thyroidectomy, EMG amplitudes at V1 in group S and group C were 1214 ± 623 and 915 ± 476 µV, respectively (p = 0.02). Positive and adequately high EMG amplitudes were observed at the early surgical stage for all patients. Sugammadex groups were superior to conventional group in EMG tube placement (p < 0.001). CONCLUSION: Both porcine model and clinical application showed that precise NMB management by low-dose sugammadex was effective for intraoperative neural monitoring (IONM). The regimen ensured optimal conditions for tracheal intubation and timely neuromuscular function restoration for high-quality EMG signal.

An appraisal of allergic disorders in India and an urgent call for action.

India is the second most populous country in the world with a population of nearly 1.3 billion, comprising 20% of the global population. There are an estimated 37.5 million cases of asthma in India, and recent studies have reported a rise in prevalence of allergic rhinitis and asthma. Overall, 40-50% of paediatric asthma cases in India are uncontrolled or severe. Treatment of allergic rhinitis and asthma is sub-optimal in a significant proportion of cases due to multiple factors relating to unaffordability to buy medications, low national gross domestic product, religious beliefs, myths and stigma regarding chronic ailment, illiteracy, lack of allergy specialists, and lack of access to allergen-specific immunotherapy for allergic rhinitis and biologics for severe asthma. High quality allergen extracts for skin tests and adrenaline auto-injectors are currently not available in India. Higher postgraduate specialist training programmes in Allergy and Immunology are also not available. Another major challenge for the vast majority of the Indian population is an unacceptably high level of exposure to particulate matter (PM)2.5 generated from traffic pollution and use of fossil fuel and biomass fuel and burning of incense sticks and mosquito coils. This review provides an overview of the burden of allergic disorders in India. It appraises current evidence and justifies an urgent need for a strategic multipronged approach to enhance quality of care for allergic disorders. This may include creating an infrastructure for education and training of healthcare professionals and patients and involving regulatory authorities for making essential treatments accessible at subsidised prices. It calls for research into better phenotypic characterisation of allergic disorders, as evidence generated from high income western countries are not directly applicable to India, due to important confounders such as ethnicity, air pollution, high rates of parasitic infestation, and other infections.

Effects of Sugammadex on Time of First Postoperative Bowel Movement: A Retrospective Analysis.

OBJECTIVE: To determine whether time to first postoperative bowel movement after intraperitoneal surgery differs among neuromuscular blockade reversal with either anticholinesterase/anticholinergic combination vs sugammadex. PATIENTS AND METHODS: Sugammadex was introduced to our practice in October 2016. Patients were identified who underwent intraperitoneal surgery between January 1, through June 30, 2016, and January 1 through June 30, 2017, and received aminosteroid neuromuscular blockade for paralysis. Reversal was initiated with neostigmine, coadministered with glycopyrrolate (neostigmine/glycopyrrolate) for control participants and sugammadex for patients. Time to first bowel movement was determined from nursing documentation for study cohorts (2016 and 2017). We compared times to first bowel movement between cases and controls using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the 2016 cohort, 2583 received neostigmine/glycopyrrolate. Of 2750 patients in 2017, sugammadex reversal technique was administered to 1500 patients and neostigmine/glycopyrrolate to 1250 participants. Without weighting, the groups were relatively balanced for most baseline characteristics, and after IPTW, all standardized differences were <0.035. In comparison with the 2016 and 2017 controls, sugammadex treatment was associated with faster occurrence of first bowel movement. For 2016, unweighted hazard ratio (HR) (95% confidence interval [CI]) was 1.35 (1.21-1.51) (P<.001). After IPTW, HR (95% CI) was 1.27 (1.12-1.43) (P<.001). For 2017, unweighted HR (95% CI) was 1.51 (1.31-1.72) (P<.001); after IPTW, it was 1.25 (1.08-1.45) (P =.003). CONCLUSION: Patients undergoing intraperitoneal surgery who had aminosteroid neuromuscular blockade reversal with sugammadex had earlier first postoperative bowel movement than patients with reversal through neostigmine/glycopyrrolate.

Preliminary Indications for the Use of Sugammadex After Its Addition to a Formulary at a Tertiary Care Children's Hospital.

OBJECTIVES: Neuromuscular blocking agents (NMBAs) are administered to facilitate endotracheal intubation and provide skeletal muscle relaxation in surgical procedures. Sugammadex (Bridion) recently received approval by the United States Food and Drug Administration for reversal of rocuronium and vecuronium-induced neuromuscular blockade thereby providing an alternative to acetylcholinesterase inhibitors such as neostigmine. This quality improvement analysis sought to investigate the clinical reasons and common clinical perceptions for choosing sugammadex over neostigmine to reverse NMBAs. METHODS: One hundred cases were reviewed where sugammadex was used for neuromuscular blockade reversal in the operating room. Cases were identified from electronic medical record reports. Anesthesia providers responsible for administering sugammadex were interviewed to obtain rationales for sugammadex use in the perioperative setting. Responses were reviewed to identify distinct reasons for using sugammadex. Two independent raters ranked the reasons according to prevalence. The study was exempt from Institutional Review Board approval as a quality improvement (QI) project. RESULTS: Forty-two anesthesia providers (15 Certified Registered Nurse Anesthetists, 5 anesthesiology trainees, and 22 attending anesthesiologists) were interviewed to identify reasons why sugammadex was administered intraoperatively in 100 surgical cases (69/31 male/female patients, age 9.4 ± 6.5 years). The author identified the top 19 common reasons respondents chose to use sugammadex for each case, and independent raters reviewed the response summaries for those 19 primary reasons sugammadex was used. The most common reasons for choosing sugammadex were: 1) beneficial pharmacokinetics of the agent; 2) sugammadex's perceived superior efficacy over neostigmine; and 3) concerns regarding adverse effects of neostigmine and/or the anticholinergic agent. CONCLUSIONS: Sugammadex has recently been introduced for clinical use to reverse NMBAs at our institution. Primary reasons and perceptions for its use over neostigmine included a limited adverse effect profile, a greater sense of control and predictability of patients' response, and a limited incidence of residual neuromuscular blockade.