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1.
Front Endocrinol (Lausanne) ; 13: 875597, 2022.
Article in English | MEDLINE | ID: mdl-36004347

ABSTRACT

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.


Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , Androstanols/pharmacology , Animals , Atracurium/analogs & derivatives , Electromyography , Neostigmine/pharmacology , Neuromuscular Blockade/methods , Neuromuscular Nondepolarizing Agents/pharmacology , Rocuronium , Swine
3.
Zhonghua Yi Xue Za Zhi ; 102(21): 1574-1578, 2022 Jun 07.
Article in Chinese | MEDLINE | ID: mdl-35644957

ABSTRACT

Objective: To compare the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery, and to provide clinical evidence and reference for further optimization of muscle relaxation application. Methods: From October 2021 to January 2022, fifty-six patients of Beijing Tongren Hospital, Capital Medical University, scheduled for laser laryngeal microsurgery with general anesthesia, were enrolled. These patients, aged 18-65 years old, 25 males and 31 females, were divided into two groups (n=28) by random number table method. Cisatracurium besylate group (group C): cisatracurium besylate was injected at 0.1 mg/kg. Normal saline was continuously infused during operation. Mivacurium group (group M):Mivacurium was injected at 0.25 mg/kg and continuously infused at 0.3 mg·kg-1·h-1 during operation.The intubation time, the extubation time, recovery index, Cooper's score, Cormack-Lehane grade, surgical condition grade, postoperative residual neuromuscular block and allergic related adverse events were compared between the two groups. Results: The intubation time and the extubation time of group M were (3.7±1.1) and (16.2±5.0) min, which were statistically significant shorter than those of group C (4.9±0.7) and (26.4±8.6) min (all P<0.05). The recovery indexes of the patients in group M and group C were (4.5±3.4) and (6.2±5.0) min. The Cooper's scores of the two groups were both 9(9, 9). The Cormack-Lehane grades of the two groups were all grade Ⅰ. The number of cases with good/excellent surgical condition grades in group M and group C were 5/23 and 0/28. There were no significant differences in recovery index, Cooper's score, Cormack-Lehane grades and surgical condition grades between the two groups (all P>0.05). The TOF ratio of group M in the post anesthesia care unit (PACU) was (95.7±2.6) %, which was significantly higher than (92.9±3.9) % of group C(P=0.015). There were no significant differences in MAP and HR between the two groups at different time points (all P>0.05). The incidence of skin flushing in group M and group C was 10.7% (3/28) and 0, and the difference was not statistically significant (P=0.074). There were no cases of severe hypotension, significantly elevated airway pressure or airway spasm in both groups. Conclusion: In laser laryngeal microsurgery, compared with cisatracurium besylate, mivacurium has shorter intubation time and extubation time, stable hemodynamics, no significant increase in allergic related adverse events. mivacurium is safe and effective.


Subject(s)
Anesthetics , Neuromuscular Nondepolarizing Agents , Adolescent , Adult , Aged , Atracurium/analogs & derivatives , Female , Humans , Isoquinolines/pharmacology , Lasers , Male , Microsurgery , Middle Aged , Mivacurium , Neuromuscular Nondepolarizing Agents/adverse effects , Young Adult
4.
BMC Anesthesiol ; 22(1): 32, 2022 01 22.
Article in English | MEDLINE | ID: mdl-35065599

ABSTRACT

BACKGROUND: Previous studies reported a slow neuromuscular response with the currently recommended dose of cisatracurium in critically ill patients. Pharmacokinetic and pharmacodynamic studies of cisatracurium in critically ill patients are still limited. To our knowledge, this is the first study performed to better understand the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a loading dose of cisatracurium and to identify factors that affect PK and PD changes in critically ill patients. METHODS: A prospective PKs and PDs study was designed. Arterial blood samples of 10 critically ill patients with respiratory failure were collected after administering a loading dose of 0.2 mg/kg of cisatracurium. Plasma cisatracurium and laudanosine concentrations were determined using liquid chromatography-tandem mass spectrometry. The achievement of the desired pharmacodynamic response was evaluated by both 1) clinical assessment and 2) train-of-four monitoring. The PK/PD indices were analyzed for their correlation with patient'characteristics and other factors. RESULTS: The one-compartment model best described the plasma pharmacokinetic parameters of cisatracurium. The volume of distribution at steady state and total clearance were 0.11 ± 0.04 L/kg and 2.74 ± 0.87 ml/minute/kg, respectively. The mean time to train-of-four 0/4 was 6 ± 3.86 minutes. A time to the desired pharmacodynamic response of less than 5 minutes was found in 10% of the patients. A positive correlation was found between cisatracurium concentration and albumin levels and between pharmacokinetics data and patient factors [partial pressure of carbon dioxide and respiratory alkalosis]. CONCLUSION: The currently recommended loading dose of cisatracurium might not lead to the desired pharmacodynamic response in critically ill patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03337373. Registered on 9 November 2017.


Subject(s)
Atracurium/analogs & derivatives , Critical Care/methods , Neuromuscular Blocking Agents/pharmacology , Respiration, Artificial/methods , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Adult , Aged , Aged, 80 and over , Atracurium/blood , Atracurium/pharmacokinetics , Atracurium/pharmacology , Critical Illness , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Neuromuscular Blocking Agents/blood , Neuromuscular Blocking Agents/pharmacokinetics , Prospective Studies
5.
BMC Anesthesiol ; 22(1): 29, 2022 01 21.
Article in English | MEDLINE | ID: mdl-35062872

ABSTRACT

BACKGROUND: It is debatable whether opioid-free anaesthesia (OFA) is better suited than multimodal analgesia (MMA) to achieve the goals of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic sleeve gastrectomy. METHODS: In all patients, anaesthesia was conducted with an i.v. induction with propofol (2 mg. kg-1), myorelaxation with cisatracurium (0.15 mg.kg-1), in addition to an ultrasound-guided bilateral oblique subcostal transverse abdominis plane block. In addition, patients in the OFA group (n = 51) received i.v. dexmedetomidine 0.1 µg.kg-1 and ketamine (0.5 mg. kg-1) at induction, then dexmedetomidine 0.5 µg. kg-1.h-1, ketamine 0.5 mg.kg-1.h-1, and lidocaine 1 mg. kg-1.h-1 for maintenance, while patients in the MMA group (n = 52) had only i.v. fentanyl (1 µg. kg-1) at induction. The primary outcome was the quality of recovery assessed by QoR-40, at the 6th and the 24th postoperative hour. Secondary outcomes were postoperative opioid consumption, time to ambulate, time to tolerate oral fluid, and time to readiness for discharge. RESULTS: At the 6th hour, the QoR-40 was higher in the OFA than in the MMA group (respective median [IQR] values: 180 [173-195] vs. 185 [173-191], p < 0.0001), but no longer difference was found at the 24th hour (median values = 191 in both groups). OFA also significantly reduced postoperative pain and morphine consumption (20 mg [1-21] vs. 10 mg [1-11], p = 0.005), as well as time to oral fluid tolerance (238 [151-346] vs. 175 min [98-275], p = 0.022), and readiness for discharge (505 [439-626] vs. 444 min [356-529], p = 0.001), but did not influence time to ambulate. CONCLUSION: While regional anaesthesia achieved most of the intraoperative analgesia, avoiding intraoperative opioids with the help of this OFA protocol was able to improve several sensible parameters of postoperative functional recovery, thus improving our knowledge on the OFA effects. CLINICAL TRIAL NUMBER: Registration number NCT04285255.


Subject(s)
Anesthesia, Conduction/methods , Anesthesia, Local/methods , Enhanced Recovery After Surgery , Gastrectomy/methods , Nerve Block/methods , Pain, Postoperative/drug therapy , Adult , Anesthetics, Dissociative , Anesthetics, Intravenous , Anesthetics, Local , Atracurium/analogs & derivatives , Dexmedetomidine , Female , Fentanyl , Humans , Hypnotics and Sedatives , Ketamine , Lidocaine , Male , Neuromuscular Blocking Agents , Pain Management/methods , Propofol , Young Adult
6.
J Feline Med Surg ; 24(4): 402-406, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34152242

ABSTRACT

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.


Subject(s)
Anesthetics , Cat Diseases , Isoflurane , Neuromuscular Blockade , Neuromuscular Diseases , Animals , Atracurium/analogs & derivatives , Cat Diseases/drug therapy , Cat Diseases/surgery , Cats , Neuromuscular Blockade/veterinary , Neuromuscular Diseases/veterinary , Retrospective Studies
7.
Fundam Clin Pharmacol ; 36(1): 182-198, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34050969

ABSTRACT

A quick literature search using "sex/gender" vs. the commonly used hypnotic propofol or neuromuscular-blocking agent cisatracurium will reveal numerous contradictory sex difference publications depending on the ethnic-geographic location of where these studies were conducted. We induced anesthesia with cisatracurium besylate (GlaxoSmithKline) 100 µg kg-1 administered exactly 1 minute following propofol (AstraZeneca) 2 mg kg-1 . In 20 male and 20 female ethnic Han-Chinese test set patients (Xi'an China), and in similar ethnic white Austrian validation set patients (Graz Austria), we quantified propofol/cisatracurium pharmacodynamic parameters namely propofol onset time, lag time, plasma concentrations (Cp ) at loss-of-behavioral response (LOBR) using bispectral index (BIS); cisatracurium onset time, lag time, and Cp at T1 % (first twitch of train-of-four) complete twitch suppression using mechanomyography (MMG). Serial arterial blood samples were collected for population pharmacokinetic (PopPK) analysis of all demographic and biological covariates (region, sex, age, weight, and height) versus volumes of distribution and clearances pharmacokinetic parameters. In Chinese women (but not in white women), propofol Cp at LOBR was 33.60% lower than men and cisatracurium Cp at T1 % complete twitch suppression was 21.49% lower than men, a clear pharmacodynamic assertion. Region and weight were significant PopPK covariates. We demonstrated that sex differences are influenced by ethnic-geographic location as only in Chinese women (but not in white women) propofol Cp at LOBR and cisatracurium Cp at T1 % complete twitch suppression were lower than in men. When defining sex differences, ethnic-geographic location should be taken into consideration as a predictive factor for optimizing propofol/cisatracurium initial loading recommended dosages.


Subject(s)
Propofol , Transgender Persons , Anesthetics, Intravenous , Atracurium/analogs & derivatives , Austria , Female , Humans , Male , Sex Characteristics
8.
Bioengineered ; 12(2): 11213-11224, 2021 12.
Article in English | MEDLINE | ID: mdl-34845969

ABSTRACT

Cisatracurium besilate is the most commonly used non-depolarizing muscle relaxant in general anesthesia and in intensive care units. Studies have indicated that the proliferation of gastric cancer (GC) cells can be restrained by cisatracurium besilate. The present study aimed to investigate the mechanism underlying the role of cisatracurium besilate in TNF-related apoptosis-inducing ligand (TRAIL)-induced GC. The AGS cell line was exposed to cisatracurium besilate, and then cell viability, colony formation and apoptosis were assessed by performing Cell Counting Kit-8, colony formation, TUNEL and Western blot assays, respectively. Furthermore, the expression levels of p53 and p53 upregulated modulator of apoptosis (PUMA) were measured by Western blotting to determine the effect of cisatracurium besilate on p53/PUMA signaling. After co-treatment with p53 inhibitor, cisatracurium besilate and pifithrin-α/TRAIL, cell apoptosis was detected. Finally, cisatracurium besilate and pifithrin-α were used to co-treat TRAIL-induced AGS cells followed by apoptosis detection. Cisatracurium besilate treatment restrained the proliferation and promoted the apoptosis of AGS cells. Cisatracurium besilate also promoted the expression of p53 and PUMA in AGS cells. Furthermore, TRAIL induced the apoptosis of AGS cells, which was aggravated by cisatracurium besilate treatment. However, pifithrin-α reversed the synergistic effects of cisatracurium besilate and TRAIL on the activities of AGS cells. Therefore, the present study suggested that cisatracurium besilate enhanced the TRAIL-induced apoptosis of GC cells via p53 signaling, and the synergistic effects of cisatracurium besilate and TRAIL may achieve maximal therapeutic efficacy in GC management.


Subject(s)
Apoptosis , Atracurium/analogs & derivatives , Signal Transduction , Stomach Neoplasms/pathology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Tumor Suppressor Protein p53/metabolism , Apoptosis/drug effects , Atracurium/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Fluorouracil/pharmacology , Humans , Signal Transduction/drug effects
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(6): 975-980, 2021 Nov.
Article in Chinese | MEDLINE | ID: mdl-34841764

ABSTRACT

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.


Subject(s)
Diaphragm , Respiration, Artificial , Animals , Atracurium/analogs & derivatives , Diaphragm/pathology , Male , Muscular Atrophy/etiology , Muscular Atrophy/pathology , Rats , Rats, Sprague-Dawley , Respiration, Artificial/adverse effects
10.
Medicine (Baltimore) ; 100(38): e27333, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34559155

ABSTRACT

RATIONALE: Lipid storage myopathies (LSMs) are a series of genetic disorders of lipid metabolism predominantly affecting muscle. The low incidence and lethal properties of this disease make anesthesia experience limited in such patients. Among all etiologies of LSMs, primary carnitine deficiency (PCD) is now considered highly treatable by early administration of L-carnitine, though it remains unclear whether L-carnitine is effective enough to protect diseased muscle against conventionally used neuromuscular blocking agents (NMBAs) during general anesthesia. Currently, no data are available concerning possible prolonged muscle weakness in these cases. PATIENT CONCERNS: This case presents a 43-year-old female who was diagnosed with a PCD-induced LSM 3 years ago due to fatigability and exertional myalgias and has been treated with L-carnitine ever since. At the time of this report, she was admitted for uterine fibroids and scheduled for selective open gynecologic surgery under general anesthesia. DIAGNOSIS: The patient's diagnosis of PCD-induced LSM was based on the clinical features, muscle biopsy, and diminished organic cation/carnitine transporter 2 (OCTN2) transporter activity in the patient's skin fibroblasts. INTERVENTIONS: L-carnitine was taken by the patient until the morning of surgery. General anesthesia with cisatracurium and sevoflurane was selected as the anesthetic plan during the operation. The train-of-four (TOF) test was adopted as additional monitoring, particularly to track the recovery of neuromuscular function. OUTCOMES: The patient was extubated successfully following a spontaneously restored TOF ratio (TOFR) of 0.9. Nonetheless, we recorded a prolonged efficacy of cisatracurium in the clinical duration and the recovery time with TOFRs of 0.7 and 0.9, respectively. LESSONS: The conventional dose of cisatracurium combined with a low dose of sevoflurane can be safely used in patients with LSMs without additional anesthetic risks. Meanwhile, continuous TOF monitoring is recommended to perform high-quality anesthesia.


Subject(s)
Anesthesia, General/methods , Cardiomyopathies , Carnitine/deficiency , Carnitine/therapeutic use , Hyperammonemia , Muscular Diseases , Adult , Anesthetics, Inhalation , Atracurium/analogs & derivatives , Female , Humans , Neuromuscular Blocking Agents , Sevoflurane
11.
Biomed Res Int ; 2021: 5655061, 2021.
Article in English | MEDLINE | ID: mdl-34337032

ABSTRACT

BACKGROUND: Anaesthesia can alter neuronal excitability and vascular reactivity and ultimately lead to neurovascular coupling. Precise control of the skeletal muscle relaxant doses is the key in reducing anaesthetic damage. METHODS: A total of 102 patients with the normal functioning preoperative facial nerve who required parotid tumour resection were included in this study. Facial nerve monitoring was conducted intraoperatively. The surgeon stimulated the facial nerve at different myorelaxation intervals at TOF% (T4/T1) and T1% (T1/T0) and recorded the responses and the amplitude of electromyogram (EMG). Body movements (BM) or patient-ventilator asynchrony (PVA) was recorded intraoperatively. RESULTS: In parotid tumour resection, T1% should be maintained at a range of 30 to 60% while TOF% should be maintained at a range of 20 to 30%. Analysis of the decision tree model for facial nerve monitoring suggests a partial muscle relaxation level of 30% < T1% ≤ 50% and TOF ≤ 60%. A nomogram prediction model, while incorporating factors such as sex, age, BMI, TOF%, and T1%, was constructed to predict the risk of BM/PVA during surgery, showing good predictive performance. CONCLUSIONS: This study revealed an adequate level of neuromuscular blockade in intraoperative parotid tumour resection while conducting facial nerve monitoring. A visual nomogram prediction model was constructed to guide anaesthetists in improving the anaesthetic plan.


Subject(s)
Atracurium/analogs & derivatives , Facial Nerve/pathology , Monitoring, Intraoperative , Neuromuscular Blockade , Parotid Neoplasms/surgery , Adult , Anesthesia , Atracurium/pharmacology , Decision Trees , Female , Humans , Male , Muscle Relaxation , Nomograms , ROC Curve
13.
J Crit Care ; 66: 166-172, 2021 12.
Article in English | MEDLINE | ID: mdl-34301439

ABSTRACT

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 PaO2/FiO2 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.


Subject(s)
Respiratory Distress Syndrome , Atracurium/analogs & derivatives , Drug Utilization , Humans , Respiratory Distress Syndrome/drug therapy , Retrospective Studies
14.
J Clin Pharmacol ; 61(11): 1415-1420, 2021 11.
Article in English | MEDLINE | ID: mdl-34180067

ABSTRACT

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.


Subject(s)
Atracurium/analogs & derivatives , Extracorporeal Membrane Oxygenation/methods , Neuromuscular Blockade/methods , Respiration, Artificial/methods , Respiratory Distress Syndrome/therapy , Adult , Aged , Atracurium/administration & dosage , Atracurium/therapeutic use , Body Mass Index , Female , Hospital Mortality , Humans , Infusions, Intravenous , Length of Stay , Male , Middle Aged , Organ Dysfunction Scores , Respiratory Distress Syndrome/mortality , Retrospective Studies
15.
J Crit Care ; 65: 86-90, 2021 10.
Article in English | MEDLINE | ID: mdl-34118504

ABSTRACT

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.


Subject(s)
Neuromuscular Blocking Agents , Respiratory Distress Syndrome , Adolescent , Adult , Atracurium/analogs & derivatives , Cohort Studies , Humans , Neuromuscular Blocking Agents/adverse effects , Respiratory Distress Syndrome/drug therapy , Retrospective Studies
17.
Bioengineered ; 12(1): 1505-1516, 2021 12.
Article in English | MEDLINE | ID: mdl-33944652

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Atracurium/analogs & derivatives , Ovarian Neoplasms/metabolism , RNA, Long Noncoding/metabolism , Atracurium/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Ovarian Neoplasms/genetics , RNA, Long Noncoding/genetics
18.
Medicine (Baltimore) ; 100(15): e25516, 2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33847670

ABSTRACT

RATIONALE: Cis-atracurium as an intermediate-acting non-depolarizing neuromuscular blocker is widely used clinically with less causing cyclic fluctuations and less histamine release. As the use rate increases, allergic reactions and anaphylactoid reactions caused by cis-atracurium increase. PATIENT CONCERNS: A 23-year-old woman underwent laparoscopic bariatric surgery. Airway spasm occurred after anesthesia induction and the operation was suspended. After adjustment, the anesthesia was performed with the same anesthetic scheme again. After induction, skin flushing and airway resistance increased, then the symptoms were relieved. When the cis-atracurium was given again, the symptoms of airway spasm reappeared immediately, and after communicating with the family, the operation was successfully completed with rocuronium. DIAGNOSES: Serious bronchospasm induced by cisatracurium besylate. INTERVENTIONS: The patient was undergone assisted ventilation with continuous positive airway pressure (CPAP) and aminophylline 250 mg, methylprednisolone 80 mg were given intravenously. OUTCOMES: There was no any obvious discomfort in the patient's self-report during the next day's visit. The patient was discharged 7 days later. No abnormalities were observed during following 4 weeks. LESSONS: Although the anaphylactoid reactions caused by cis-atracurium are rare, the bronchospasm and anaphylactic shock caused by it greatly increase the risk of anesthesia, which should be taken seriously by clinicians. Increased vigilance in diagnosis, and treatment are essential to prevent aggravation and further complication.


Subject(s)
Anaphylaxis/chemically induced , Anesthesia, General/adverse effects , Atracurium/analogs & derivatives , Bronchial Spasm/chemically induced , Neuromuscular Blocking Agents/adverse effects , Atracurium/adverse effects , Bariatric Surgery , Female , Humans , Laparoscopy , Young Adult
19.
BMC Anesthesiol ; 21(1): 91, 2021 03 27.
Article in English | MEDLINE | ID: mdl-33773580

ABSTRACT

BACKGROUND: Lidocaine and magnesium sulfate have become increasingly utilized in general anesthesia. The present study evaluated the effects of these drugs, isolated or combined, on hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB). METHODS: At a university hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimuli were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation as follows: 3 mg.kg- 1 and 3 mg.kg- 1.h- 1 (lidocaine - L group), 40 mg.kg- 1 and 20 mg.kg- 1.h- 1 (magnesium - M group), equal doses of both drugs (magnesium plus lidocaine - ML group), and an equivalent volume of isotonic solution (control - C group). Hemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the train of four (TOF) ratio (TOFR > 0.9). RESULTS: The magnesium sulfate significantly prolonged all NMB recovery features, without changing the speed of onset of cisatracurium. The addition of lidocaine to Magnesium Sulfate did not influence the cisatracurium neuromuscular blockade. A similar finding was observed when this drug was used alone, with a significantly smaller fluctuation of mean arterial pressure (MAP) and heart rate (HR) measures during anesthesia induction and maintenance. Interestingly, the percentage of patients who achieved a TOFR of 90% without reaching T1-95% was higher in the M and ML groups. Than in the C and L groups. There were no adverse events reported in this study. CONCLUSION: Intravenous lidocaine plays a significant role in the hemodynamic stability of patients under general anesthesia without exerting any additional impact on the NMB, even combined with magnesium sulfate. Aside from prolonging all NMB recovery characteristics without altering the onset speed, magnesium sulfate enhances the TOF recovery rate without T1 recovery. Our findings may aid clinical decisions involving the use of these drugs by encouraging their association in multimodal anesthesia or other therapeutic purposes. TRIAL REGISTRATION: NCT02483611 (registration date: 06-29-2015).


Subject(s)
Anesthesia, General , Lidocaine/administration & dosage , Magnesium Sulfate/administration & dosage , Adult , Analgesics/administration & dosage , Anesthetics, Local/administration & dosage , Arterial Pressure/drug effects , Atracurium/administration & dosage , Atracurium/analogs & derivatives , Double-Blind Method , Drug Combinations , Female , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Neuromuscular Blockade , Neuromuscular Blocking Agents/administration & dosage , Prospective Studies
20.
Biosci Trends ; 15(1): 50-54, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33627570

ABSTRACT

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.


Subject(s)
Antigens, CD/metabolism , Atracurium/analogs & derivatives , Cadherins/metabolism , Claudin-5/metabolism , Endothelium, Vascular/metabolism , Lipopolysaccharides/pharmacology , Matrix Metalloproteinase 3/metabolism , Microvessels/metabolism , Atracurium/pharmacology , Cells, Cultured , Endothelium, Vascular/cytology , Humans , Microvessels/cytology
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