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Background Neuromuscular blocking agents are crucial for anesthesia but can cause reversible paralysis, leading to risks like postoperative residual dysfunction. Undetected paralysis in the post-anesthesia care unit (PACU) jeopardizes patient safety by impairing airway function and increasing complications. Effective reversal, assessed clinically or via nerve stimulation, is critical to prevent residual postoperative curarization (RPOC), which is linked to significant morbidity and mortality. Evaluating agents like rocuronium and cisatracurium helps optimize anesthesia outcomes and patient recovery. Methodology The study included 100 American Society of Anaesthesiologists (ASA) I and II patients approved by the Institutional Review Board of Kasturba Medical College, Mangalore, India. Patients were briefed about the study, provided written informed consent, and underwent pre-anesthetic evaluations, including discussions on anesthetic procedures and associated risks. They were instructed to fast overnight after consenting. Results The study compared 100 ASA I and II patients receiving rocuronium or cisatracurium during anesthesia, analyzing age distribution (p=0.429), gender (p=0.839), ASA status (p=0.228), and physical characteristics (height, weight, BMI, p>0.05). Recovery parameters such as hand grip, sustained head lift, and double burst stimulation (DBS) twitch response showed no significant differences between groups (p=0.538 for hand grip and sustained head lift; p=0.220 for DBS. Late recovery rates at 15 minutes were observed with 16% for hand grip, 14% for sustained head lift, and 26% for DBS in the rocuronium group; compared to 14%, 10%, and 16%, respectively, in the cisatracurium group. Conclusion The study found significant postoperative residual curarization in both groups, emphasizing the need for intraoperative and PACU peripheral nerve stimulation for effective assessment. Further research on intraoperative variables could improve understanding of residual paralysis in PACU, guiding better anesthesia management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Kasturba Medical College, Mangaluru issued approval IEC KMC MLR 09-18/340. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rani M et al.)

Background: Shivering is often encountered in patients undergoing targeted temperature management (TTM) after cardiac arrest. The most efficient, safe way to prevent shivering during TTM is not clearly defined. Objective: The purpose of this study was to evaluate the impact of shivering management using a stepwise shivering protocol on time to target temperature (TT), medication utilization and nursing confidence. Methods: Single-center, retrospective chart review of all post-cardiac arrest patients who underwent TTM between 2016 and 2021. The primary outcome is a comparison of time to TT pre- and post-protocol implementation. Secondary objectives compared nursing confidence and medication utilization pre- and post-shivering protocol implementation. Results: Fifty-seven patients were included in the pre-protocol group and thirty-seven were in the post-protocol group. The median (IQR) time to TT was 195 (250) minutes and 165 (170), respectively (p = 0.190). The average doses of acetaminophen was 285 mg pre- vs 1994 mg post- (p <0.001, buspirone 47 mg pre- vs 127 mg post- (p < 0.001), magnesium 0.9 g pre-vs 2.8 g post- (p < 0.001), and fentanyl 1564 mcg pre- vs 2286 mcg post- (p=0.023). No difference was seen for midazolam and cisatracurium. Nurses reported feeling confident with his/her ability to manage shivering during TTM 38.5% of the time pre-protocol compared to 60% post-protocol (p = 0.306). Conclusion: Implementation of a stepwise approach to prevent and treat shivering improved time to TT in our institution, although this finding was not statistically significant. The stepwise protocol supported a reduced amount of high-risk medication use and increased nursing confidence in shivering management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background General anaesthesia (GA) is predominantly important for conducting tracheal intubation; it should be quick and precise, having a prudent performance. It is preferable to use a neuromuscular blocking drug, which ideally should be highly potent, with a rapid onset and a short duration clinical effect in order to prevent the development of hypoxia during laryngoscopy and tracheal intubation and also avoid any changes in haemodynamics caused by the release of histamine, ganglion block, and anti-muscarinic actions. The non-depolarizing muscle relaxants rocuronium and cisatracurium don't have any noticeable independent side effects when used within the recommended dosage levels. Aim The aim was to compare the clinical efficacy of rocuronium bromide and cisatracurium besylate with respect to their property as muscle relaxants in producing favourable intubating conditions and to assess their haemodynamic stability. The objectives of the study were to evaluate the onset of action and any undesirable effects. Methods Between the ages of 20 to 60 years, 60 patients of either gender, divided randomly into groups of 30 each, of American Society of Anesthesiologists (ASA) physical status classification I and II, were put for elective surgical procedures to be done under general anaesthesia. Patients were given 0.6 mg kg-1 IV of rocuronium in Group R and 0.15 mg kg-1 IV of cisatracurium in Group C. After injecting the muscle relaxants, parameters were measured 60, 90, 120, 150, 180, 240, and 300 seconds later. Result Demographical variables like age, gender, and ASA physical status of the two groups were analogous. Group R had good to excellent/favourable intubating conditions by 90 seconds, and Group C by 240 seconds with comparable haemodynamic stability. The onset of action was significantly faster in Group R (92 ± 7.61 seconds) than in Group C (188 ± 40.88 seconds). Conclusion Rocuronium produced favourable intubating conditions having good haemodynamic stability and a statistically significant (p < 0.00001) faster onset of action in comparison to cisatracurium., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, S et al.)

Background and Aims: The present study was conducted to determine the optimal dose of cisatracurium for intubating conditions and onset and offset of neuromuscular blockade. Data in Indian population are scarce, and hence, the present study was planned to evaluate different doses of cisatracurium., Material and Methods: The prospective randomized double-blind study was conducted on 180 patients of either sex in the age group of 20-60 yrs., having physical status class I to III, scheduled for surgery under general anesthesia. After exclusion 154 patients were randomly divided into three groups comprising 52, 51, and 51, respectively, in Group A, Group B, and group C. They received 0.1 mgkg -1 , 0.2 mgkg -1 , and 0.3 mgkg -1 of cisatracurium, respectively, to facilitate endotracheal intubation. Time of onset, intubating conditions, hemodynamic parameters, signs of histamine release, and recovery time were noted., Results: Mean time to onset was maximum in group A (4.37 ± 0.48 minutes) and minimum in group C (2.33 ± 0.43 minutes). Intubating conditions were found excellent in 88% patients in group. Change in HR was found to be non-significant at all time periods, but decrease in MAP was found between 2 and 10 minutes in group C. Duration of action was longest in group C., Conclusion: We conclude that cisatracurium in dose of 0.2 mgkg -1 and 0.3 mgkg -1 provides good-to-excellent intubating conditions within less than 3 minutes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Anaesthesiology Clinical Pharmacology.)

Background and Aims: Cancer chemotherapeutic agents cause alteration in the response to neuromuscular blocking drugs, which can have serious perioperative implications. Magnesium, commonly found to be deficient in these patients, plays an indispensable role in neuromuscular transmission. This study aimed to understand the effect of neoadjuvant chemotherapy on the neuromuscular blocking properties of cisatracurium., Material and Methods: One hundred female patients scheduled for breast cancer surgery were divided into two groups ( n = 50 each). Group B received neoadjuvant chemotherapy with taxane, adriamycin, and cyclophosphamide, and Group A did not receive neoadjuvant chemotherapy. Neuromuscular block following cisatracurium 0.15 mg/kg was measured using peripheral nerve stimulator at the ulnar nerve. Onset time, duration of intense block, clinical duration of action, time to TOF4 after the last dose of cisatracurium, along with preoperative serum magnesium concentration were measured. Correlation and multiple regression were run to analyze the relationship between history of neoadjuvant chemotherapy, preoperative magnesium, and the abovementioned time points. Mediation analysis was done to ascertain if magnesium was mediating the observed effects., Results: Onset time was prolonged by nearly 18% in Group B compared to Group A ( P = 0.001). The duration of intense block was 35.27 ± 8.9 min in Group B and 42.07 ± 10.99 min in Group A ( P < 0.001). The clinical duration of action of cisatracurium was significantly shorter in Group B (46.06 ± 8.68 min) compared to Group A (55.87 ± 11.04 min, P < 0.001). The time to TOF4 was 32.86 ± 5.66 min in Group B and 36.57 ± 8.49 min in Group A ( P < 0.05). Preoperative serum magnesium levels were significantly lower in Group B ( P < 0.001)., Conclusion: Patients who had received neoadjuvant chemotherapy had a delayed onset, shorter duration of action, and faster recovery for cisatracurium. Although preoperative magnesium levels were lower in Group B, it was found to be an independent predictor rather than a mediator of these effects., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

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 PaO 2 /FiO 2 (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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: To compare the intubating conditions at 60 seconds between 4*ED95 dose of cisatracurium and 2*ED95 dose of cisatracurium in combination with priming and low dose ketamine., Primary Objective: jaw relaxation for laryngoscopy, vocal cord position on laryngoscopy, and coughing or bucking response to intubation., Secondary Objective: To compare the hemodynamic changes up 10 minutes after intubation in the two groups. In this prospective study, a total of 68 patients were undergoing general anesthesia for surgery with placement of endotracheal tube placement. Patients will be divided into two groups comprising 34 patients each. The patients were allocated one of the two groups by computerized randomization. *Group A received bolus dose of cisatracurium which is 0.2 mg/kg (4*ED95). **Group B received cisatracurium in dose of 0.1 mg/kg (2*ED95) with priming (which is 10% of the bolus dose) and low dose ketamine of about 0.5 mg/kg. It was possible to achieve acceptable laryngoscopy and intubating condition in both the groups within 90 seconds. When grades of laryngoscopy and ease of intubation were compared, 2*ED95 dose along with priming plus low dose ketamine produced superior results than 4*ED95 group. When the mean arterial pressure and pulse rate were compared between the two groups, it was observed that mean arterial pressure and pulse rate were only slightly higher in the 2*ED95 along with priming and ketamine., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Aim: To evaluate the antifungal activity of cisatracurium against Candida spp. resistant to fluconazole strains in planktonic and biofilm forms, in addition to determining its mechanism of action. Materials & methods: Antifungal activity and pharmacological interactions were determined using broth microdilution methods and the mechanism of action was evaluated by flow cytometry and molecular docking. Results: Cisatracurium presented antifungal activity against Candida spp. planktonic cells due to alterations of mitochondrial transmembrane potential leading to cellular apoptosis in addition to interacting with important targets related to cellular respiration, membrane and cell wall evidenced by molecular docking. Furthermore, the drug both prevented biofilm formation and impaired mature biofilms. Conclusion: Cisatracurium exhibits potential antifungal activity against Candida spp.

Background: Stability study of a 10 mg/mL injectable cisatracurium solution stored refrigerated in amber glass ampoules for 18 months (M18)., Methods: 4000 ampoules were aseptically compounded using European Pharmacopoeia (EP)-grade cisatracurium besylate, sterile water for injection, and benzenesulfonic acid. We developed and validated a stability-indicating HPLC-UV method for cisatracurium and laudanosine. At each stability study time point, we recorded the visual aspect, cisatracurium and laudanosine levels, pH, and osmolality. Sterility, bacterial endotoxin content, and non-visible particles in solution were checked after compounding (T0) and after M12 and M18 of storage. We used HPLC-MS/MS to identify the degradation products (DPs)., Results: During the study, osmolality remained stable, pH decreased slightly, and the organoleptic properties did not change. The number of non-visible particles remained below the EP's threshold. Sterility was preserved, and bacterial endotoxin level remained below the calculated threshold. Cisatracurium concentration remained within the ±10% acceptance interval for 15 months and then decreased to 88.7% of C0 after M18. The laudanosine generated accounted for less than a fifth of the cisatracurium degradation, and three DPs were generated-identified as EP impurity A, impurities E/F, and impurities N/O., Conclusion: Compounded 10 mg/mL cisatracurium injectable solution is stable for at least 15 months.

Background: Nutrition support is an essential part of critical care medicine. It is commonly accepted that for the critically ill patient, enteral nutrition (EN) is favored. For the patient who receives neuromuscular blockades, EN may be held, or initiation delayed, because of concerns for EN intolerance. We hypothesized there would be no difference in EN tolerance between groups receiving cisatracurium while receiving EN compared with those not receiving cisatracurium., Methods: This was a retrospective study that included 459 patients from a combined medical and surgical intensive care unit. There were 44 patients who received cisatracurium with EN and 415 who received EN alone. Data collected included gastric residual volume (GRV) and emesis occurrences, new-onset abdominal pain, new or worsening abdominal distention, and bowel ischemia., Results: There were more patients with new or worsening abdominal distention in the group receiving cisatracurium (31.82% vs 14.94%; P < 0.01) as well as occurrences of GRV > 300 ml (P < 0.01). There was no statistically significant difference between the groups regarding emesis, new-onset abdominal pain, or bowel ischemia., Conclusion: Our findings suggest that it is acceptable to provide patients with EN who are receiving cisatracurium., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Purpose: Previous studies analyzing neuromuscular blocking agents (NMBAs) in acute respiratory distress syndrome (ARDS) have evaluated the benefit of cisatracurium with conflicting results, and data evaluating other NMBAs remains limited. The objective of this study was to compare the efficacy and safety of cisatracurium to vecuronium in ARDS., Materials and Methods: A single-center, retrospective, propensity matched review of patients who received cisatracurium or vecuronium continuous infusions between October 1, 2017 and June 30, 2020 for ARDS was conducted. The primary endpoint was duration of mechanical ventilation. Secondary endpoints included change in PaO 2 /FiO 2 ratio at 48 h, intensive care unit (ICU) and hospital mortality, and ICU and hospital length of stay (LOS). Safety endpoints included newly developed myopathy, presence of bradycardia or hypotension, and newly developed barotrauma or volutrauma., Results: Twenty-nine patients were included in each group. There was no statistically significant difference in the primary endpoint of ventilator days between cisatracurium and vecuronium groups (mean 15.9 vs. 20.5 days respectively; p  = .2). No statistically significant differences were found in secondary endpoints of ICU mortality (51.7% vs. 51.7%) or length of stay (18.7 vs. 23.9 days, p   =   .19 ), hospital mortality (51.7% vs. 55.2%, p   =   .79 ) or length of stay (22 vs. 30.6 days, p   =   .08 ), or mean change in PaO 2 /FiO 2 (29.8 vs. 36.6; p   =   .74 ). Statistically significant differences were not observed in safety endpoints of myopathy (37.9% vs. 37.9%), barotrauma or volutrauma (13.8% vs. 3.5%; p  = .16), bradycardia (31% vs. 13.8%; p  = .12), or hypotension (96.6% vs. 82.8%; p  = .08)., Conclusions: No significant differences were seen in efficacy or safety endpoints between cisatracurium or vecuronium groups, suggesting that vecuronium may be a safe alternative agent for neuromuscular blockade in ARDS. Results of this analysis warrant confirmation in a larger, randomized study.

Background: Electromyography can be used for quantitative neuromuscular monitoring during general anesthesia, mostly using the stimulation train-of-four (TOF) pattern. Relaxometry measures the muscular response of the adductor pollicis muscle to electrical stimulation of the ulnar nerve, which is routinely used in clinical practices for monitoring the neuromuscular block. However, when it is not always possible to be used for all patients, the posterior tibial nerve is a suitable alternative., Objectives: Using electromyography, we compared the neuromuscular block between the ulnar and the posterior tibial nerves., Methods: In this study, the participants were 110 patients who met inclusion criteria and submitted their written consent. Following the administration of cisatracurium intravenously, the patients had relaxometry performed simultaneously on the ulnar and the posterior tibial nerves using electromyography., Results: Eighty-seven patients were included in the final analysis. The onset time was 296 ± 99 s at the ulnar nerve and 346 ± 146 s at the tibial nerve, with a mean difference of -50 s and a standard deviation of 164 s. The 95% limits of agreement ranged from -372 s to 272 s. The relaxation time was 105 ± 26 min at the ulnar nerve and 87 ± 25 min at the tibial nerve, with a mean difference of 18 min and a standard deviation of 20 min., Conclusions: Using electromyography, no statistically significant difference was noticed between the ulnar and the posterior tibial nerve during the neuromuscular block. The onset time and the relaxation time assessed with an electromyogram to compare the stimulation of the ulnar and posterior tibial nerves showed large limits of agreement., Competing Interests: Conflict of Interests: Funding or research support: None; employment: Hospitals; personal financial interests: None; stocks or shares in companies: None; consultation fees: None; patents: None; personal or professional relations with organizations and individuals (parents and children, wife and husband, family relationships, etc.): None; unpaid membership in a government or non-governmental organization: None; are you one of the editorial board members or a reviewer of this journal? No., (Copyright © 2023, Author(s).)

Background: Low-dose ephedrine and ketamine may accelerate the onset time of action of neuromuscular blocking agents. We studied the effect of ephedrine and ketamine and cisatracurium priming on endotracheal intubation conditions and the onset time of action of cisatracurium., Materials and Methods: The study was a double-blind clinical trial performed on American Society of Anesthesiologists (ASA) class 1 and 2 patients, who were candidates for general anesthesia. In total, 120 patients were entered into the study and were divided into 4 groups, E, K, E + K, and N. The first group was given 70 mcg/kg ephedrine (E group), the second group was given 0.5 ml/kg ketamine (K group), the third group was given the same amount of ketamine plus ephedrine (E + K group), and the fourth group was given the same volume of normal saline (control group); a single dose of 0.1 mg/kg cisatracurium was given, and intubating conditions were evaluated at 60 seconds after cisatracurium administration., Results: The mean Cooper score based on the response to laryngoscopy, the position of the vocal cords, and the movement of the diaphragm of patients in the control group with a mean of 2.53 ± 1.07 was significantly lower than in the three groups of E, K, and E + K with the means of 4.47. 1.17, 4.53 ± 1.14, and 7.63 ± 1.42, respectively ( P value < 0.001). In the (E + K) group, it was significantly higher than in the two other drugs alone ( P value < 0.001). The two groups of E and K alone were not significantly different from each other ( P value = 0.997). The means of hemodynamic parameters were not significantly different in any of the groups ( P value > 0.05)., Conclusion: According to the results of the present study, the use of low-dose ephedrine and ketamine alone can improve intubation conditions. In addition, the combined use of these drugs not only had any Positive effect on patients' hemodynamic parameters but also greatly improved intubation conditions., Competing Interests: The authors declare that they have no conflict of interest, (Copyright: © 2023 Advanced Biomedical Research.)

Background: We investigated the influence of different neuromuscular blocking agents and reversal agents during anaesthesia on early removal of chest tube drainage after video-assisted thoracoscopic surgery (VATS)., Methods: This retrospective single-centre study included patients who underwent VATS after tracheal intubation under general anaesthesia. Patients received either cisatracurium and neostigmine (n=547) or rocuronium and sugammadex (n=151). Quantitative neuromuscular monitoring was used and one chest tube (size 24 Fr) was inserted. To reduce potential bias, 140 patients from each group were matched by propensity score for sex, age, body mass index and indication for VATS. Primary outcome was duration of chest tube drainage after surgery., Results: Use of rocuronium and sugammadex was associated with a shorter duration of chest tube drainage (2 [1-2] vs 2 [1-3] days; P=0.049) and a 63% reduction in delayed chest tube removal (odds ratio 0.37; 95% confidence interval [CI]: 0.20-0.67; P=0.005). This group also had a lower incidence of postoperative atelectasis (P=0.047) and consolidation (P=0.008). Each 1 h increase in the duration of anaesthesia was associated with a 1.57-fold increase in the delayed removal of the chest tube (95% CI: 1.25-1.96; P=0.005)., Conclusions: During general anaesthesia for VATS, compared with cisatracurium and neostigmine, use of rocuronium and sugammadex was associated with a significant decrease in the incidence of postoperative delayed removal of the chest tube, atelectasis, and pulmonary consolidation., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There is a growing interest in minimally invasive left atrial appendage closure therapies. However, for successful catheter surgery, it is necessary to achieve high-quality postoperative recovery. The aim of the study is to comparison of neuromuscular blockade and reversal using cisatricurium and neostigmine with rocuronium and sugamadex on the quality of recovery from general anaesthesia for percutaneous closure of left atria appendage., Methods: Eighty-four patients who received percutaneous LAAC were randomly placed into two groups, general anesthesia and endotracheal intubation with either propofol-remifentanil-cisatracurium-neostigmine (group C) or propofol-remifentanil-rocuronium-sugammadex (group S). The QoR-40 questionnaire was used to assess recovery quality 6 h after surgery, and the time of spontaneous respiration, the time of consciousness recovery, the time of extubation, the duration in the postanaesthesia care unit (PACU), and the adverse events after awakening were collected., Results: Compared with the group C, the group S demonstrated significantly higher individual QoR-40 dimension scores, a significantly shorter recovery time for spontaneous respiration and consciousness, time of extubation, and duration in the PACU, and a lower incidence of transient hypoxemia, agitation, nausea and vomiting and urinary retention. There was a non-significant trend for the length of stay in the hospital in both groups., Conclusions: General anesthesia and endotracheal intubation with propofol-remifentanil-rocuronium-sugammadex provided better quality of recovery, shorter anaesthesia duration, and lower incidence of hypoxemia and agitation. Neuromuscular blockade and reversal using rocuronium and sugamadex is better than with cisatricurium and neostigmine on the quality of recovery from general anaesthesia for percutaneous closure of left atria appendage., Trial Registration: chictr.org, ChiCTR2000031857. Registered on April 12, 2020., (© 2022. The Author(s).)

Case Series Summary: This case series describes the neuromuscular blockade (NMB) following 0.15 mg/kg intravenous (IV) cisatracurium administration in 11 cats undergoing ophthalmological surgery and anaesthetised with isoflurane. Anaesthetic records were analysed retrospectively. Neuromuscular function was assessed by a calibrated train-of-four (TOF) monitor. Cats were 73 ± 53 months old, weighed 4 ± 1 kg and were of American Society of Anesthesiologists' physical classification 2. Duration of anaesthesia and surgery were 144 ± 27 and 94 ± 24 mins, respectively. The lowest TOF count was zero in four cats, four in six cats and for one cat the TOF ratio never decreased below 31%. The time of onset was between 1 and 6 mins after the administration of cisatracurium and the mean duration of action was 20.4 ± 10.1 mins., Relevance and Novel Information: Cisatracurium at a dose of 0.15 mg/kg IV did not consistently induce a TOF count of zero in all cats. The dose used in these cats did not produce any remarkable cardiovascular side effects. Although the NMB was not complete, the dose given was sufficient to produce central eyeball position, which was the goal of the ophthalmic surgeries.

Background: The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation., Methods: A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications., Results: No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] μmol/L, p = 0.0128) and serum urea (14.9 [10.8-21.6] vs 17.1 [13.1-22.0] mmol/L, p = 0.0486) were lower, while eGFR (8.0 [6.0-11.0] vs 8.0 [6.0-10.0], p = 0.0473) was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia (0.6% vs 6.3%, p = 0.006), shorter PACU stay (70 [60-90] min vs 90 [60-105] min, p < 0.001), and reduced ICU admissions (0.6% vs 8.0%, p = 0.001)., Conclusions: Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation., (© 2022. The Author(s).)

As a common muscle relaxant, cisatracurium has shown good antitumor effect on some tumors. Recent studies reported that cisatracurium could inhibit the progression of colon cancer by upregulating tumor suppressor gene p53. However, its role in ovarian cancer and its regulatory effect on p53 and p53 downstream targeting gene long intergenic noncoding RNA p21 (lincRNA-p21) is still unknown. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to assess the expression of p53, lincRNA-p21 and miR-181b. Cell viability and proliferation were detected by CCK-8 assay and Edu staining, respectively. Wound-healing and Transwell assays were performed to determine the abilities of cell migration and invasion. Apoptosis was evaluated by TUNEL staining. Luciferase reporter assay was conducted to detect the relationship between lincRNA-p21 and miR-181b. As a result, cisatracurium could increase the expressions of p53 and lincRNA-p21 of ovarian cancer cell line (OVCAR-3) in a dose-dependent manner. In addition, cisatracurium significantly inhibited the proliferation, migration and invasion of OVACR-3 cells, and induced apoptosis. However, these above changes in biological function can be attenuated by lincRNA-p21 knockdown. Next, lincRNA-p21 could directly target miR-181b and negatively regulate its expression by luciferase reporter assay. In conclusion, cisatracurium inhibited the progression of OVCAR-3 cells through upregulation of lincRNA-p21 expression activated by p53 inhibiting miR-181b expression. The experimental results provide a new research idea for the application of cisatracurium in ovarian cancer.

Purpose: Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy., Methods: We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO 2 /FiO 2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h., Results: A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318-528] compared to both the TOF: 665 [IQR 472-927] and the FD arms: 1730 [IQR 1695-1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points., Conclusion: Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anesthetics are extensively used during cancer surgeries. The progression of cancer can be influenced by perioperative events such as exposure to general or local anesthesia. However, whether they inhibit cancer or act as a causative factor for metastasis and exert deleterious effects on cancer growth differs based on the type of cancer and the therapy administration. Recent experimental data suggested that many of the most commonly used anesthetics in surgical oncology, whether general or local agents, can alter gene expression and cause epigenetic changes via modulating miRNAs. miRNAs are single-stranded non-coding RNAs that regulate gene expression at various levels, and their dysregulation contributes to the pathogenesis of cancers. However, anesthetics via regulating miRNAs can concurrently target several effectors of cellular signaling pathways involved in cell differentiation, proliferation, and viability. This review summarized the current research about the effects of different anesthetics in regulating cancer, with a particular emphasis on the role of miRNAs. A significant number of studies conducted in this area of research illuminate the effects of anesthetics on the regulation of miRNA expression; therefore, we hope that a thorough understanding of the underlying mechanisms involved in the regulation of miRNA in the context of anesthesia-induced cancer regulation could help to define optimal anesthetic regimens and provide better perspectives for further studies., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Electroconvulsive therapy (ECT) is nowadays used commonly as one the most effective treatment methods in psychiatric disorders. In patients undergoing ECT, succinylcholine is usually used. In addition, cisatracurium is occasionally used on a case report basis globally. In this study, we compared the hemodynamic changes and serum potassium levels in the use of succinylcholine and cisatracurium in ECT., Materials and Methods: The current crossover clinical trial was performed on 45 patients who were candidates for ECT between 2017 and 2018. The patients were given succinylcholine or cisatracurium randomly on two separate occasions of ECT. The independent t -test and Chi square Test were used to compare the data., Results: Comparison of mean systolic blood pressure ( P = 0.14), diastolic blood pressure ( P = 0.33), and mean arterial pressure ( P = 0.23) did not show any significant difference between the two groups. The induced seizure duration ( P = 0.002), return of spontaneous respiratory from seizure ending ( P = 0.001), and apnea duration ( P = 0.01) were significantly higher in the cisatracurium group compared to the succinylcholine group. However, the frequency of tachycardia in cisatracurium group was lower than the succinylcholine group ( P < 0.001). In addition, the serum potassium level had a significant difference ( P < 0.001) between the two groups., Conclusion: Using cisatracurium can be an alternative to succinylcholine during ECT since it causes less elevation in serum potassium and creates a longer duration of induced seizure, more rapid re emergence of spontaneous breathing at the end of seizure ( P = 0.001), and a lower prevalence of tachycardia compared to succinylcholine ( P < 0.001)., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

The benefit of continuous infusion neuromuscular blockade concurrently with venovenous (VV) extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome who are receiving mechanical ventilation remains unclear. Adult patients with severe acute respiratory distress syndrome requiring VV ECMO were analyzed in 2 groups: continuous infusion neuromuscular blockade with cisatracurium vs no neuromuscular blockade. Similar mechanical ventilation strategies were used. The primary end point was duration of VV ECMO. This single-center, retrospective observational cohort included a total of 47 patients, 28 of whom received continuous infusion cisatracurium and 19 patients who did not receive neuromuscular blockade. There was no difference in the duration of VV ECMO in patients who received cisatracurium, 226.5 hours (interquartile range, 119-362.3) vs 187.0 hours (interquartile range, 108-374) in the group who did not receive a paralytic (P = .64). There were no differences in secondary outcomes of days in the hospital, days free of organ dysfunction, ECMO survival, or discharged alive. Among patients with severe ARDS who were managed with VV ECMO, patients who received continuous infusion cisatracurium had no difference in the duration of VV ECMO compared to the nonparalytic comparator group., (© 2021, The American College of Clinical Pharmacology.)

Objective: To investigate the role of cisatracurium in diaphragm atrophy in mechanically ventilated (MV) rats and its possible mechanism., Methods: 30 adult male Sprague-Dawley (SD) rats were randomly assigned to 5 groups: Rats in the control (CON) group ( n =6) were fasted for 30 h without any other intervention; rats in the MV group ( n =6) were fasted for 6 h, and then mechanically ventilated for 24 h while receiving continuous infusion of sodium pentobarbital and 0.9% NaCl; rats in the MV+cisatracurium (MVC) group ( n =6) were fasted for 6 h, and then mechanically ventilated for 24 h while receiving continuous infusion of sodium pentobarbital and cisatracurium; rats in the MV+chloroquine (QMV) group ( n =6) and rats in the MV+cisatracurium+chloroquine (QMVC) group ( n =6) received intraperitoneal injection of chloroquine (30 mg/kg), an autophagy inhibitor, at 24 h and 30 min prior to MV in addition to the treatments given to the MV group and the MVC group, respectively. The rats in each group were sacrificed 30 hours later, and costal diaphragm muscle specimens were collected. The cross-sectional area (CSA) of the diaphragm fibers was observed through HE staining, and the colocalizations of TOM20 and LC3 were assessed by immunofluorescence staining. The expression levels of PINK1, Parkin, P62 and LC3, the mitophagy-related proteins, and the expression levels of MAFbx and MURF-1, muscular-atrophy-related proteins, were evaluated by Western blot., Results: Respective comparisons of the MV group with the CON group and the MVC group with the MV group showed that the CSA decreased ( P <0.05), the expression of MURF-1, MAFbx, PINK1, Parkin and LC3Ⅱ/Ⅰproteins increased ( P <0.05), the number of co-expressed mitochondria of TOM20 and LC3 and the expression of LC3 increased and the expression of P62 protein decreased ( P <0.05) in the MV and MVC groups. Respective comparisons of the QMV group with the MV group and the QMVC group with the MVC group showed that the CSA increased ( P <0.05), the expression of MURF-1, MAFbx, PINK1, Parkin and LC3Ⅱ/Ⅰ proteins increased ( P <0.05), the number of co-expressed mitochondria of TOM20 and LC3 and the expression of LC3 decreased and the expression of P62 protein decreased ( P <0.05) in the QMV and QMVC group., Conclusion: Mechanical ventilation for 24 h caused diaphragm atrophy in SD rats. Cisatracurium may aggravate diaphragm atrophy in mechanically ventilated rats through the autophagy-lysosome (AL) pathway, a process that may be related to the PINK1/Parkin-mediated mitophagy, and chloroquine may reduce diaphragmatic atrophy induced by cisatracurium by blocking the AL pathway., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Purpose: To compare the ventilatory and clinical outcomes associated with a fixed-dose cisatracurium infusion versus a titrated infusion strategy in patients with Acute Respiratory Distress Syndrome (ARDS)., Materials and Methods: Single-center, retrospective, cohort study in a medical ICU of a tertiary care academic medical center. Adult patients ≥18 years old with a continuous infusion of cisatracurium for ≥12 h for treatment of ARDS were included. The primary outcome was the PaO2 /FiO2 ratio assessed at 24 and 48 h following cisatracurium initiation. Secondary outcomes included amount of average dose of drug administered, 28-day ventilator-free days, LOS, and hospital mortality., Results: 167 patients were included; median baseline PaO2/FiO2 was 97 (76-146), median SOFA score of 9 (7-11), and ICU mortality was 71/167 (43%). In a mixed-effects model, fixed dose and titrated cisatracurium associated with similar changes in PaO2/FiO2 assessed at 24 and 48 h (p = 0.316). Fixed-dose was associated with a >3-fold increase in drug exposure (average dose 6.4 (5.4-8.0) vs. 2.0 (1.5-2.8) mcg/kg/min; p < 0.001, respectively). No differences were observed in secondary clinical endpoints., Conclusion: Fixed-dose cisatracurium was associated with similar ventilatory and clinical outcomes compared to titrated strategy, yet it was associated with a 3-fold increase in dose administered., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neuromuscular blockade (NMB) with cisatracurium may improve outcomes in the acute respiratory distress syndrome (ARDS) population; however, optimal dosing strategy remains unknown. Factors affecting pharmacokinetics and pharmacodynamics of cisatracurium may impact the dose required to achieve adequate train-of-four (TOF) response. The aims of this study were to determine cisatracurium dose requirements in a critically ill ARDS population and to identify clinical factors that affect dosing. This was a single-center, retrospective cohort study of medical intensive care patients who received cisatracurium infusion for treatment of ARDS. "Stable dose" was defined as the infusion rate producing 2 consecutive TOFs of 1/4 to 2/4. Factors examined for association with dose were temperature, pH, age, and the presence of acute kidney injury (AKI). The analysis included 39 patients. The median stable dose of cisatracurium was 2.8 (2.0, 3.1) μg/kg/min. Multivariable linear regression model for weight-normalized dose identified AKI as a factor independently associated with steady-state dose requirements (% change -31.4, 95% confidence interval [CI]: -51.9, -2.3). Our study provides information on cisatracurium doses required in patients with ARDS to reduce time required to reach goal TOF. Further studies are needed to determine effect of AKI on cisatracurium dose requirements and clinical outcomes.

Background: Intraoperative neuromonitoring (IONM) reduces the risk of recurrent laryngeal nerve (RLN) injury during thyroid surgery. However, the use of neuromuscular blocking agents (NMBAs), which are essential to improve intubation conditions, may hinder the electromyographic response during IONM. The aim of this prospective, double-blind, randomized controlled trial was to explore the optimal dosage of cisatracurium to produce adequate muscle relaxation for tracheal intubation without significantly affecting evoked potentials of IONM during thyroidectomy., Methods: Patients undergoing thyroidectomy with IONM in our institution, with an American Society of Anesthesiologists grade of I-II, aged 18-75 years, and with a body mass index below 32 kg/m 2 were enrolled and randomly assigned (by random numbers) to receive 1× (group C1) or 2× (group C2) the effective dose (ED 95 ) of cisatracurium for tracheal intubation. The patients, surgeons, and anesthesiologists in charge were blinded to group assignment. Anesthesia was induced with sufentanil, propofol, and cisatracurium (0.05 mg/kgin group C1, 0.1 mg/kg in group C2). Ease of intubation was evaluated with the intubation condition score (Cooper score) and the intubation difficulty scale (IDS). Amplitudes of evoked potentials during intermittent IONM were compared between groups. The primary outcomes were the Cooper score, the IDS score, and the evoked potentials of IONM., Results: Fifty-three patients were randomized from October 2019 to November 2020, and 52 were analyzed (with 26 patients in each group). The Cooper score was significantly lower in group C1 [median, 8.0 (interquartile range, 7.0-8.3)] than in group C2 [9.0 (9.0-9.0), P<0.001]. The rate of difficult laryngoscopy without external laryngeal pressure was significantly higher in group C1 than in group C2 (61.5% vs. 11.5%, P<0.001). More patients in group C1 required assistance to complete tracheal intubation (16 vs. 4, P=0.001). The IDS score was significantly higher in group C1 [3.0 (0.0-4.0) vs. 1.0 (0.0-1.0), P=0.045]. There were no significant differences between groups in amplitudes of evoked potentials. No serious adverse events were observed., Conclusions: A dose of 2× ED 95 of cisatracurium provided better intubation conditions and easier tracheal intubation than 1× ED 95 , without disturbing IONM., Trial Protocol: Chinese Clinical Trial Registry (No. ChiCTR1900022884)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-109). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Objective: To reveal the effects and related mechanism of cisatracurium on colorectal cancer (CRC) development., Methods: HCT116 and SW480 cells were treated with various concentrations of cisatracurium or transforming growth factor-β (TGF-β). Chemokine C-X-C-Motif Receptor 4 (CXCR4) was overexpressed and let-7a-5p was silenced in cells by transfection with pcDNA3.1-CXCR4 or let-7a-5p inhibitor. Cell Counting Kit-8 (CCK-8) assay measured cell viability, and transwell and wound healing assays evaluated cell invasion and migration, respectively. The expression levels of let-7a-5p and CXCR4 were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was conducted to test the levels of CXCR4, TGF-β/SMAD2/3 signalling and metastasis-related proteins. A tumour xenograft assay was performed to assess tumour growth., Results: Cisatracurium treatment suppressed the viability and metastasis of HCT116 and SW480 cells in a concentration-dependent manner, whereas activating TGF-β/SMAD2/3 signalling significantly reversed these effects. Cisatracurium treatment markedly reduced CXCR4 expression by inhibiting TGF-β/SMAD2/3 signalling. Besides, let-7a-5p was identified as a target of CXCR4 and could be upregulated by cisatracurium. Both CXCR4 overexpression and let-7a-5p knockdown alleviated the biological roles of cisatracurium in CRC cells. Moreover, a tumour xenograft assay further confirmed that cisatracurium inhibited tumour growth and metastasis by increasing let-7a-5p expression., Conclusion: Cisatracurium suppressed the viability, metastasis and tumour growth of CRC by regulating the CXCR4/let-7a-5p axis via inhibiting TGF-β/SMAD2/3 signalling. These findings provide a theoretical basis for the role of cisatracurium in the prognosis of CRC patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI) associated with hypoxemic lung damage and inflammation. Matrix metalloproteinase protein-3 (MMP3 or Stromelysin-1) is known to promote vascular injury in ALI/ARDS. Cisatracurium, a nicotinic neuromuscular blocker, is used in ARDS patients to decrease mechanical ventilator dyssynchrony, increase oxygenation, and improve mortality. However, the magnitude and the underlying mechanisms of these potential benefits of cisatracurium remains unclear. We investigated the effect of cisatracurium on lipopolysaccharide-induced MMP3 expression in human microvascular endothelial cells. In our results, cisatracurium treatment significantly decreased LPS-induced MMP3 expression and increased expression of cell junction proteins such as vascular endothelial cadherin (VE-cadherin) and claudin-5.

Introduction: use of generic drugs is common. However, there is still concern among patients and physicians that brand name drugs are more efficient. The aim of the study was to compare efficacy and tolerance between two forms of cisatracurium: brand name versus generic name., Methods: it´s a crossover, randomized, double-blind physiological trial. Patients admitted for hypoxemic acute respiratory failure with PaO2/FIO2 < 200mmHg despite optimized ventilation and sedation thus requiring non-depolarizing neuromuscular blocking agents (NMBAs), were enrolled. Patients received consecutively, in a random order, cisatracurium brand name (Nimbex®) and generic (Cisatrex®) over two-hour period separated by one-hour washout period. Neuromuscular function was monitored by a calibrated train-of-four (TOF) stimulation device. Paralysis time delay to reach TOF of 2/4, recovery kinetics and tolerance were monitored. The number needed to demonstrate a significant difference in time delays to reach a TOF of 2/4 between the two forms of cisatracurium was estimated at 22 patients., Results: twenty-two patients were included. Eight (36.4%) had acute respiratory distress syndrome; 8(36.4%), acute exacerbation of chronic obstructive pulmonary disease and 3(13.6%), status asthmaticus. Median [IQR] SAPS II at admission, 28.5 [22, 41]. PaO2/FIO2, 121 [81, 156] mmHg. Paralysis time delays were respectively, 80 [50, 112] vs. 87 [65, 115] minutes, in Nimbex® group and Cisatrex® group; (p=0.579). Within the recovery period, the between two-studied drugs´ difference in TOF was at 0.25±0.96; p=0.64. There were no significant hemodynamic differences., Conclusion: the present study revealed no significant differences in efficacy nor in tolerance between cisatracurium brand name Nimbex® and generic name Cisatrex® in hypoxemic ventilated patients., Competing Interests: The authors declare no competing interests., (Copyright: Nesrine Fraj et al.)

As a cis-acting non-depolarizing neuromuscular blocker through a nicotinic acetylcholine receptor (nAChR), cisatracurium (CAC) is widely used in anaesthesia and intensive care units. nAChR may be present on Leydig cells to mediate the action of CAC. Here, by Western blotting, immunohistochemistry and immunofluorescence, we identified that CHRNA4 (a subunit of nAChR) exists only on rat adult Leydig cells. We studied the effect of CAC on the synthesis of testosterone in rat adult Leydig cells and mouse MLTC-1 tumour cells. Rat Leydig cells and MLTC-1 cells were treated with CAC (5, 10 and 50 μmol/L) or nAChR agonists (50 μmol/L nicotine or 50 μmol/L lobeline) for 12 hours, respectively. We found that CAC significantly increased testosterone output in rat Leydig cells and mouse MLTC-1 cells at 5 μmol/L and higher concentrations. However, nicotine and lobeline inhibited testosterone synthesis. CAC increased intracellular cAMP levels, and nicotine and lobeline reversed this change in rat Leydig cells. CAC may increase testosterone synthesis in rat Leydig cells and mouse MLTC-1 cells by up-regulating the expression of Lhcgr and Star. Up-regulation of Scarb1 and Hsd3b1 expression by CAC was also observed in rat Leydig cells. In addition to cAMP signal transduction, CAC can induce ERK1/2 phosphorylation in rat Leydig cells. In conclusion, CAC binds to nAChR on Leydig cells, and activates cAMP and ERK1/2 phosphorylation, thereby up-regulating the expression of key genes and proteins in the steroidogenic cascade, resulting in increased testosterone synthesis in Leydig cells., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Breast cancer is a type of cancer that begins in the breast tissue. Being a woman is the most important factor in the risk of breast cancer. Although men also get the cancer, women are much more likely to get it. This experiment was founded to investigate the effect and mechanism of Cisatracurium on breast cancer cell proliferation, migration and invasion. Breast cancer cells MDA-MB-231 were cultured in vitro. MDA-MB-231 cells were treated with cisatracurium of different concentrations for 48 h. CCK-8method detected cell proliferation, Transwell detected cell migration and invasion, Western Blot method detected the expression levels of CyclinD1, p21, MMP-2andMMP-9protein in cells, RT-qPCR) detected the expression level of miR-3174in cells. After miR-3174 inhibitor was transfected into MDA-MB-231 in order to down-regulate the expression of miR-3174, the same methods as above were used to observe the effect of the down-regulating miR-3174 expression on MDA-MB-231 cell proliferation, migration and invasion as well as the expression levels of CyclinD1, p21, MMP -2 andMMP-9 protein. After different concentrations of Cisatracurium acted on MDA-MB-231 cells, the cell inhibition rate and p21 protein expression were significantly increased (p&lt;0.05), the number of cell migration and invasion and the expression levels of CyclinD1, MMP-2 and MMP-9 were significantly reduced (p&lt;0.05), and the expression of miR-3174 in cells was significantly reduced (p&lt;0.05). After down-regulating the expression of miR-3174, the cell inhibition rate and p21 protein expression were significantly increased (p&lt;0.05), the number of cell migration and invasion and the expression levels of CyclinD1, MMP-2 and MMP-9 were significantly reduced (p&lt;0.05). Up-regulating miR-3174 expression could reverse the effect of Cisatracurium on the proliferation, migration and invasion of MDA-MB-231 cells. Cisatracurium can inhibit the proliferation, migration and invasion of breast cancer MDA-MB-231 cells, and its mechanism is related to the down-regulation of miR-3174 expression in cells.

Objective: To compare the neuromuscular blocking effects of cisatracurium during isoflurane versus propofol anesthesia in dogs., Study Design: Prospective, randomized study., Animals: A total of 20 healthy, client-owned dogs (16 females, four males) weighing 12.5-22 kg and aged 1-8 years., Methods: Dogs undergoing elective surgery were randomized in equal numbers to an isoflurane (ISO) or propofol (PPF) group. Other drugs used during anesthesia were equal between groups. Single-twitch (ST) stimulation was used to monitor neuromuscular response. After recording the baseline ST (T0), cumulative doses of cisatracurium (0.05 mg kg -1 ) were administered intravenously until ST/T0 ≤5%. Effective doses 50 (ED 50 ) and 95 (ED 95 ) of cisatracurium in each group were calculated from group dose-response curves. Recovery of ST (TR) was defined as spontaneous recovery of ST to 80-120% of T0 remaining stable for 2 minutes. The ST after each dose of cisatracurium, duration 25% (time after the last dose until 25% recovery of TR), recovery index (time to recovery from 25% to 75% of TR) and duration to TR (time after the last dose until recovery of TR) were recorded., Results: Incremental doses of cisatracurium, median (range), were 2 (1-3) in ISO and 4 (2-5) in PPF to achieve ≥95% depression of ST/T0 (p < 0.01). ED 50 and ED 95 were 20 μg kg -1 and 117 μg kg -1 in ISO and 128 μg kg -1 and 167 μg kg -1 in PPF, respectively. The duration 25%, recovery index and duration to TR, median (range), were longer in ISO [22.6 (10.3-24.3), 5.3 (3.0-7.8) and 36.1 (20.1-49.7) minutes, respectively] than in PPF [10.2 (6.8-16.5), 3.0 (2.0-3.8) and 17.7 (14.2-28.7) minutes, respectively] (p < 0.01)., Conclusions and Clinical Relevance: Cisatracurium-induced neuromuscular blockade was significantly enhanced and prolonged by isoflurane compared with propofol., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Maintaining intraocular pressure (IOP) is important in preventing ocular complications in patients undergoing ophthalmic surgery for general anesthesia. The effects of non-depolarizing neuromuscular blockers on IOP remain unclear. The present study compared the effects of cisatracurium, rocuronium, and mivacurium on IOP during induction of general anesthesia in vitreous retinal surgery., Materials and Methods: In this prospective randomized double-blinded study, 133 patients undergoing vitreous retinal surgery were randomized into one of the three groups: Group cisatracurium (n=45), Group rocuronium (n=44), or Group mivacurium (n=44). Each drug (cisatracurium 0.1 mg kg -1 in Group cisatracurium, rocuronium 0.6 mg kg -1 in Group rocuronium, and mivacurium 0.2 mg kg -1 in Group mivacurium) was administered during induction of anesthesia. IOP and hemodynamic parameters were measured at 1 min before anesthesia induction (T0). Bispectral index (BIS) was maintained between 45 and 55 after propofol administration (T1). Train-of-four stimulation (TOF) was below 0 after muscle relaxant administration (T2) and after laryngeal mask implantation (T3)., Results: Both ipsi-operative and control-operative IOP at T1, T2, and T3 significantly decreased from the baseline values (T0) in all three groups ( P <0.05). The IOP changes between T1 and T2 among three groups were similar ( P >0.05). The values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at T1 and T2 significantly decreased in all three groups compared to T0 ( P <0.05)., Conclusion: Bilateral IOP significantly decreased from the baseline values in all three groups during the induction phase. Cisatracurium, rocuronium, and mivacurium did not induce significant changes in bilateral IOP., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Li et al.)

Cisatracurium besylate has been determined by fast and highly sensitive spectrofluorimetric method based on measuring the fluorescence intensity of its methanolic solution at 312 nm after excitation at 230 nm (Method I). The linearity occurred over the concentration range of 10.0-130.0 ng/mL with detection limit of 1.07 ng/mL. The method was further extended for the determination of the studied drug in spiked human plasma with good percentage recoveries (97.43-103.50%). Cisatracurium is co-administered with nalbuphine during surgery. The simultaneous determination of both drugs was based on synchronous spectrofluorimetric technique. First derivative synchronous spectrofluorimetric amplitude was measured in methanol at Δ λ = 60 nm and each drug could be estimated at the zero crossing point of the other. Hence, cisatracurium could be measured at 284.6 nm while nalbuphine at 276.3 nm (Method II). The method was linear over the ranges of 50.0-750.0 ng/mL and 0.5-7.0 μg/mL with the detection limits of 2.16 ng/mL and 0.04 μg/mL for cisatracurium and nalbuphine, respectively. The method was further extended for the simultaneous determination of both drugs in spiked human urine with mean percentage recoveries of 99.99 ± 2.06 and 99.53 ± 6.17 for cisatracurium and nalbuphine, respectively. Both methods were validated in agreement with Guidelines adopted by International Council of Harmonization (ICH)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits. However, new studies have provided evidence contradicting these results., Method: A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48 h. An English language restriction was applied. Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model. Sensitivity and meta-regression analysis were performed., Results: From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO 2 /FIO 2 of 104 ± 35 mmHg. The cisatracurium group had the same risk of death at 28 days (RR, 0.90; 95% CI, 0.78-1.03; I 2  = 50%, p  = 0.12) and 90 days (RR, 0.81; 95% CI, 0.62-1.06; I  = 0.06) as the control group (no cisatracurium). The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups. Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)-induced weakness. The PaO 2  = 56%, p ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO 2 /FIO 2 ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO 2 /FIO 2 ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity. Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes., Conclusion: NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness. However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Background: This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction., Methods: A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography., Results: The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K 12  = 0.19 ± 0.02 and K 21  = 0.11 ± 0.01 in the AR group vs. K 12= 0.26 ± 0.01 and K 21  = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group., Conclusion: Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction., Registration: Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction., Trial Registration Number: ChiCTR1800019654. Date of registration: November 20th 2018.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of cancer worldwide, with a poor prognosis. The aim of the present study was to investigate the effect of cisatracurium (Cis) on epithelial-to-mesenchymal transition (EMT) in ESCC and its potential mechanism of action. In the present study, Cis was used to treat ECA-109 cells, with cell proliferation measured by a Cell Counting Kit-8 assay and the expression of TGF-β and phospho-Smad2/3 detected by western blotting. TGF-β was then applied to induce EMT. Flow cytometry, wound healing and Transwell assays were used to evaluate cell proliferation, apoptosis, invasion and migration. In addition, cell cycle-related proteins, including cyclin D1, p53 and p21, and EMT-associated proteins, including E-cadherin (E-cad), N-cadherin (N-cad), Vimentin and Slug, were examined by western blot analysis. The results revealed that Cis inhibited the proliferation and promoted apoptosis of ESCC cells. Following treatment with Cis, the expression of TGF-β and phosphorylation of Smad2/3 were downregulated. Cis also suppressed cancer cell invasion and migration induced by TGF-β. In addition, the expression levels of cyclin D1 were decreased, accompanied by increased p53 and p21 expression. In addition, the expression level of E-cad was increased, whereas N-cad, Vimentin and Slug were significantly reduced. Taken together, the results of the present study revealed that exposure of ESCC cells to Cis inhibited EMT and reduced cell invasion and metastasis through the TGF-β/Smad signaling pathway., (Copyright: © Lv et al.)

Purpose: A case report involving varying cisatracurium dosing requirements in a hyperthermic patient undergoing prone ventilation who subsequently received active cooling as part of targeted temperature management is presented., Summary: Cisatracurium is known to be primarily metabolized via pH- and temperature-dependent Hofmann elimination. Previous reports in the literature described cases of decreased dosing requirements for both cisatracurium and its parent compound, atracurium, for patients in hypothermic states. While augmented atracurium dosing requirements in hyperthermic states have been reported, a literature search found no such reports concerning cisatracurium administration. In the case described here, a patient was initiated on cisatracurium for treatment of symptoms suggestive of acute respiratory distress syndrome (ARDS) and septic shock. An initial dosing requirement of 12 µg/kg/min (adjusted to a goal of 2-4 twitches per train-of-four monitoring) was needed to achieve adequate paralysis while the patient remained hyperthermic (a bladder temperature of 40.1°C). This cisatracurium infusion rate exceeded maximum reported and maximum institutional infusion rates (10 µg/kg/min). After initiation of cooling and lowering of the bladder temperature to 37.8°C, the cisatracurium rate requirement decreased to 5 µg/kg/min., Conclusion: A hyperthermic patient thought to have ARDS and septic shock required a high rate of cisatracurium infusion for adequate paralysis during mechanical ventilation. The cisatracurium did not appear to cause prolonged neuromuscular blockade., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions., Design: Prospective, randomized clinical trial with blinded outcomes assessment., Setting: University hospital, single institution., Participants: Adult patients having cardiac surgery requiring cardiopulmonary bypass., Interventions: One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire., Measurements and Main Results: The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02)., Conclusion: Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Neuromuscular blockade (NMB) is often utilized in the treatment of acute respiratory distress syndrome (ARDS). Its use for a period of 48 h has been shown to improve mortality in randomized control trials. We aimed to characterize outcomes associated with a prolonged NMB. We hypothesized that the duration of NMB would not be associated with increased mortality., Materials and Methods: This was a retrospective review from June 2014 to October 2016 of patients admitted to the surgical intensive care unit and receiving cisatracurium for ARDS. Patients paralyzed for ≤ 48 h (SHORT) were compared to those paralyzed for longer durations (LONG). Primary outcome was mortality. Parametric and nonparametric tests were utilized for the purposes of the comparison. A multivariate logistic regression model was utilized to adjust for differences., Results: Of 73 patients meeting inclusion criteria, 32 (44%) were SHORT and 41 (56%) LONG. Compared to the LONG cohort, those in SHORT were older (60 versus 52 years, P = 0.04) but were comparable with respect to sex, acute physiology and chronic health evaluation IV scores, presence of concurrent pneumonia, and the use of vasopressors. SHORT patients were less likely to require rescue therapy with inhaled nitric oxide (28% versus 66%, P < 0.01). Overall mortality was 60%. There was no difference in the adjusted odds for mortality (adjusted odds ratio: 0.57, P = 0.33). Secondary outcomes including deep venous thrombosis and pneumonia did not differ between the two groups., Conclusions: Extended NMB for ARDS was not associated with increased mortality. Discontinuation of this modality should not be based solely on the duration of therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pseudo-allergic reactions occur when patients receive muscle relaxants during perioperative anesthesia. These reactions may result in a serious threat to the patient's life, particularly to a child's life. Cisatracurium, a relatively new NMBA, has resulted in bronchospasms and cardiovascular collapse. However, the mechanisms underlying the anaphylactoid reactions caused by cisatracurium have not been fully elucidated., Methods: In the present study, the MRGPRX2-related pseudo-allergic reactions induced by cisatracurium were investigated using hindpaw swelling and extravasation assays in vivo and mast cell degranulation assays., Results: Cisatracurium caused anaphylactoid reactions in wild-type mice. However, cisatracurium did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, mast cell-related G protein-coupled receptor B2-knockout mice did not display an inflammatory response upon treatment with cisatracurium. Cisatracurium induced LAD2 cell degranulation, leading to the dose-dependent release of β-hexosaminidase, histamine and TNF-α. However, cisatracurium only induced the release of low levels of these mediator LAD2 cells transfected with MRGPRX2 siRNA. Cisatracurium also stimulated intracellular Ca 2+ influx in MRGPRX2-HEK293 cells compared with that in NC-HKE293 cells. Interestingly, cytokine release was not observed in LAD2 cells even with high dose of cisatracurium., Conclusions: Cisatracurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. Therefore, strategies targeting MRGPRX2 might potentially block cisatracurium-induced pseudo-allergic reactions., (Copyright © 2018. Published by Elsevier B.V.)

Colorectal cancer (CRC) is reported to be the third and fourth, most diagnosed and cause of cancer associated deaths respectively. In 2012 for instance, about 1.4 million new cases were reported, and approximately 700,000 deaths recorded. Survival from CRC is dependent on the stage at which it is diagnosed coupled with appropriate surgical and medical intervention. Cisatracurium is widely used for skeletal muscle relaxation during abdominal surgeries, including bowel and colon surgeries. Recent studies reported that cisatracurium inhibits progression of human cancer cells, however, the mechanisms leading to the inhibition are yet to be completely understood. To elucidate mechanisms resulting particularly in tumor cell growth and metastasis, we developed ex vivo and in in vivo xenograft models of CRC. Cisatracurium caused upregulation of p53 and its down-stream genes and proteins known to regulate proliferation and metastasis in vitro and in vivo . Genomic analyses of CRC following cisatracurium treatment revealed moderate to high DNA damage, while functional analyses demonstrated significant tumor cells growth regression, as well as repression of migration and invasion. Importantly, cisatracurium increased E-Cadherin and CALD-1 but decreased SNAI-1 and SLUG levels in vitro and in vivo . Together, the findings demonstrate that elevation of p53 upon cisatracurium-induced genomic injury, represent a potential mechanism by which cisatracurium result in the suppression of CRC progression and metastasis.

The effects of cisatracurium in combination with ventilation on inflammatory factors and immune variations in sepsis rats were investigated. A total of 54 male Sprague-Dawley rats were selected and divided randomly into three groups: Sham group (n=6), model group (n=24) and experiment group (n=24). Rats in the model and experiment groups underwent cecal ligation and puncture (CLP) for establishment of sepsis model. Rats in experiment group additionally received cisatracurium medication in combination with ventilation for treatment. At 6, 12 and 24 h after CLP, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and procalcitonin (PCT) in serum and the ratio of leukocyte to neutrophil in peripheral blood was also detected. Twenty-four hours later, the expression of high mobility group box 1 (HMGB1) in lung tissues and cluster of differentiation (CD) 4 + and CD8 + in T-lymphocyte subsets were also detected, and the wet/dry (W/D) ratio of lung was measured. Compared with that in model group, the levels of inflammatory factors in the experiment group were significantly decreased, while the indicators in assays of cellular immunity were obviously elevated. Ratio of leukocyte to neutrophil in peripheral blood was significantly decreased after treatment. Cisatracurium in combination with ventilation can alleviate the inflammatory injury to organs in sepsis rats through inhibiting the inflammatory responses and regulating the immune functions, which manifests a new significance in guiding the clinical diagnosis and treatment.

Objective This study was performed to observe the occurrence of corrected QT (QTc) interval prolongation during anesthetic induction for laryngeal mask airway insertion and the effects of cisatracurium administration on the QTc interval. Methods Eighty-eight patients were assigned to two groups: the cisatracurium administration group (n = 45) and non-cisatracurium administration group (n = 43). The QTc interval was continuously recorded by a 12-lead Holter electrocardiogram beginning in the hospital ward and continuing until after anesthetic induction. Results In the cisatracurium administration group, the QTc interval significantly increased from 417.9 ± 27.9 to 451.6 ± 32.5 ms after arrival in the operating room and significantly decreased to 432.4 ± 32.5 ms after a 15-minute rest; it significantly increased to 459.7 ± 23.8 ms again after propofol and fentanyl injection. However, the QTc interval decreased after cisatracurium injection. In the non-cisatracurium administration group, the QTc interval initially showed changes similar to those in the cisatracurium group until fentanyl and propofol were injected. Conclusions The QTc interval was significantly prolonged on arrival in the operating room and after propofol and fentanyl injection. The QTc interval did not significantly change by laryngeal mask airway insertion regardless of the administration of cisatracurium.