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Medicine Nov 2022Sevoflurane and desflurane are commonly used inhalation anesthetics in clinical practice. This study compared the synergistic effects of sevoflurane and desflurane on... (Randomized Controlled Trial)
Randomized Controlled Trial
Sevoflurane and desflurane are commonly used inhalation anesthetics in clinical practice. This study compared the synergistic effects of sevoflurane and desflurane on the muscarinic agent vecuronium in laparoscopic colon cancer surgery. The aim of this study was to compare sevoflurane and desflurane in a synergistic effect on the muscle relaxant vecuronium in laparoscopic colon cancer surgery. Sixty patients undergoing elective laparoscopic radical resection of colon cancer were randomly divided into sevoflurane (n = 30) and desflurane (n = 30) groups. After anesthesia and successful tracheal intubation, patients in both groups were maintained with combined remifentanil. Muscle relaxant effects were monitored in both groups using a muscle relaxant monitor (train of stimuli-Watch), the onset time, T1 and T2 recovery time, and muscle relaxant dosage of vecuronium were observed. Hemodynamic changes were observed in both groups, and the dosage of vasoactive drugs was recorded. The quality of recovery of the patients was evaluated using the Mini-Mental State Examination (MMSE) and the discharge from the Aldrete score criteria. There was no significant difference in the onset time of vecuronium between the two groups (P > .05). The desflurane group's T1 and T2 recovery times were later than that of the sevoflurane group. The dosage of vecuronium was statistically significantly less than that in the sevoflurane group (P < .05); the extubation time in the desflurane group was statistically significantly longer than that in the sevoflurane group (P < .05). There were no significant differences in preoperative and intraoperative mean arterial pressure, heart rate, ephedrine and atropine dosage, MMSE score, and Aldrete score between the 2 groups (P > .05). Compared with sevoflurane, desflurane has a stronger synergistic effect on the muscle relaxant of vecuronium without increasing the incidence of cardiovascular adverse reactions and affecting patient recovery.
Topics: Humans; Sevoflurane; Desflurane; Vecuronium Bromide; Isoflurane; Methyl Ethers; Anesthesia Recovery Period; Laparoscopy; Colonic Neoplasms; Muscles
PubMed: 36397349
DOI: 10.1097/MD.0000000000031569 -
Drug Design, Development and Therapy 2021High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the... (Review)
Review
High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.
Topics: Humans; Laparoscopy; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Robotic Surgical Procedures; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 34548781
DOI: 10.2147/DDDT.S328682 -
International Journal of General... 2023The incidence and severity of succinylcholine-induced fasciculation and postoperative myalgia have been shown to decrease when vecuronium bromide or preservative-free 2%...
The Effects of Prophylactic Intravenous Lignocaine vs Vecuronium on Succinylcholine-Induced Fasciculation and Postoperative Myalgia in Patients Undergoing Elective Surgery at Debre Markos Comprehensive Specialized Hospital, Ethiopia, 2022: Prospective Cohort Study.
BACKGROUND
The incidence and severity of succinylcholine-induced fasciculation and postoperative myalgia have been shown to decrease when vecuronium bromide or preservative-free 2% plain lignocaine hydrochloride is administered before induction. The aim of this study is to examine the effectiveness of defasciculation dosages of vecuronium bromide and 2% preservative-free plain lignocaine hydrochloride in decreasing succinylcholine-induced fasciculation and postoperative myalgia in patients undergoing elective surgery.
METHODS
A total of 110 participants were included in a prospective observational cohort study that was located in an institution. Patients were randomly assigned to (Group L) and (Group V) based on the prophylactic measures they received from the responsible anesthetist utilizing preservative-free 2% plain lignocaine and defasciculation dose of vecuronium bromide, respectively. We recorded, socio-demographic variables, fasciculation, postoperative myalgia, total number of analgesics administered following surgery in 48hrs, and kind of procedure. The descriptive data were compiled using descriptive statistics. Categorical and continuous data were evaluated, respectively, using chi-square statistics and the independent sample -test. To compare the prevalence of fasciculation and myalgia across the various groups, the Fischer exact test was performed. A 0.05 p-value was deemed statistically significant.
RESULTS
This study found that the incidence of fasciculation in the groups receiving the defasciculation doses of vecuronium bromide and preservative-free 2% plain lignocaine hydrochloride was 14.6% and 20% (p-value 0.007), respectively. The rate of mild-to-moderate postoperative myalgia in the vecuronium bromide group was 23.7%, 30.9%, and 16.4% in the first, 24th, and 48th hours, respectively (p-value 0.001), as opposed to 0%, 37.3%, and 9.1%, respectively (p-value 0.008) in the group receiving preservative-free 2% plain lignocaine hydrochloride.
CONCLUSION
Pretreatment with 2% plain lignocaine that is preservative-free is more efficient than vecuronium bromide at reducing the frequency and intensity of postoperative succinylcholine-induced myalgia, whereas defasciculation dose of vecuronium was more effective prevention of succinylcholine-induced fasciculation.
PubMed: 37388716
DOI: 10.2147/IJGM.S415854 -
Therapeutic Advances in Drug Safety 2019Sugammadex is used for the reversal of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide. As part of the post licensing phase of drug...
INTRODUCTION
Sugammadex is used for the reversal of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide. As part of the post licensing phase of drug development, adverse events related to the use of sugammadex are still being uncovered and being reported. The potential association between sugammadex and adverse events bronchospasm and coronary arteriospasm using a retrospective pharmacovigilance signal analysis was carried out.
METHODS
Food and Drug Administration's Adverse Event Reporting System database was used to run disproportionality analyses to investigate the potential association of sugammadex with bronchospasm or coronary arteriospasm. In this analysis we report the adverse event signal using frequentist methods of Relative reporting ratio (RRR), proportional reporting ratio (PRR), reporting odds ratio (ROR) and the Bayesian based Information Component metric.
RESULTS
A statistically significant disproportionality signal is found between sugammadex and bronchospasm ( = 44; chi-squared = 2993.87; PRR = 71.95 [95% CI: 54.00-95.85]) and sugammadex and coronary arteriospasm ( = 6; chi-squared = 209.39; PRR = 43.82 [95% CI: 19.73-97.33]) as per Evans criteria. Both statistically significant disproportionality signals persisted when stratified by gender. Based upon dynamic cumulative PRR graph, the PRR value has steadily increased and the 95% CI narrowed since December 2012.
CONCLUSION
The results of the pharmacovigilance analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex. The results of the pharmacovigilance signal analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex.
PubMed: 31452867
DOI: 10.1177/2042098619869077 -
The Journal of Pediatric Pharmacology... 2022Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium...
Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium is one neuromuscular blocking agent used for this purpose; however, there are limited data regarding its use in pediatric patients with renal failure. Although predominantly considered to be metabolized by the liver, there are numerous adult cases and 1 pediatric case report that have described extended paralysis from vecuronium due to renal failure. The proposed mechanism is accumulation of renally cleared active metabolites. This case report describes an infant with vecuronium exposure during continuous renal replacement therapy who experienced prolonged neuromuscular blockade for several days after the agent was stopped. This highlights the importance of considering renal function when selecting neuromuscular blocking agent.
PubMed: 35558355
DOI: 10.5863/1551-6776-27.4.400 -
Se Pu = Chinese Journal of... Jul 2021Vecuronium, rocuronium, and pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when...
Vecuronium, rocuronium, and pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when using such muscle relaxants. Rapid determination of the concentration of these muscle relaxants in blood can provide valuable information for early clinical diagnosis. As quaternary ammonium compounds, these muscle relaxants are highly polar. Hence, they cannot be retained effectively on reversed-phase chromatographic columns with conventional mobile phases. These quaternary ammonium muscle relaxants are mainly separated by ion-pair chromatography. Using an ion-pairing reagent can help improve the retention capabilities of quaternary ammonium muscle relaxants. Nevertheless, the sensitivity of MS detection is significantly decreased because of ionic inhibition caused by the ion-pairing reagent in the mobile phase. Furthermore, ion-pairing reagents can pollute the MS system. A method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the simultaneous determination of the three quaternary ammonium muscle relaxants in blood. The blood samples were diluted and subjected to high-speed centrifugation. The supernatant was purified on a Bond Elut AL-N solid phase extraction column and then filtered through a 0.45 μm microporous membrane. The quaternary ammonium muscle relaxants were separated on a ZIC-cHILIC analytical column (50 mm×2.1 mm, 3.0 μm) with gradient elution. Acetonitrile and 0.1% formic acid aqueous solution were used as mobile phases. The separated compounds were analyzed by tandem MS with an electrospray ionization (ESI) source in positive and multiple reaction monitoring (MRM) modes. The matrix effects of vecuronium, rocuronium, and pancuronium in blood were 88.1% to 95.4%. The calibration curves for vecuronium, rocuronium, and pancuronium showed good linear relationships in each range, and all correlation coefficients () were > 0.996. The limits of detection of vecuronium, rocuronium, and pancuronium were 0.2-0.8 ng/mL, with the corresponding limits of quantification being 0.5-2.0 ng/mL. The recoveries of vecuronium, rocuronium, and pancuronium were 92.8% to 110.6%, with relative standard deviations (RSDs) of 3.2%-9.4%. This method is sensitive, accurate, and easy to operate, and it can be used to rapidly determine vecuronium, rocuronium, and pancuronium in blood.
Topics: Ammonium Compounds; Chromatography, High Pressure Liquid; Humans; Neuromuscular Agents; Pancuronium; Rocuronium; Solid Phase Extraction; Tandem Mass Spectrometry; Vecuronium Bromide
PubMed: 34227366
DOI: 10.3724/SP.J.1123.2020.09020 -
Antioxidants (Basel, Switzerland) Dec 2022Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends...
Therapeutic Administration of Oxcarbazepine Saves Cerebellar Purkinje Cells from Ischemia and Reperfusion Injury Induced by Cardiac Arrest through Attenuation of Oxidative Stress.
Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide/saline) or oxcarbazepine (200 mg/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates ≥ 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.
PubMed: 36552657
DOI: 10.3390/antiox11122450 -
Cells Jan 2023Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as...
Therapeutic Hypothermia after Cardiac Arrest Attenuates Hindlimb Paralysis and Damage of Spinal Motor Neurons and Astrocytes through Modulating Nrf2/HO-1 Signaling Pathway in Rats.
Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 ± 0.5 °C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA/ROSC. The rats of the CA/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA/ROSC and normothermia-treated groups. In the CA/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA/ROSC and hypothermia-treated group, interleukin-1β (IL-1β, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis).
Topics: Animals; Male; Rats; Astrocytes; Heart Arrest; Heme Oxygenase-1; Hindlimb; Hypothermia; Hypothermia, Induced; Motor Neurons; NF-E2-Related Factor 2; Paralysis; Rats, Sprague-Dawley; Signal Transduction
PubMed: 36766758
DOI: 10.3390/cells12030414 -
BMC Anesthesiology Oct 2021The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest.
METHODS
Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias.
RESULTS
Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study.
CONCLUSIONS
Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03346057 .
Topics: Aged; Bradycardia; Cholinergic Agents; Double-Blind Method; Female; Glycopyrrolate; Humans; Male; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Tachycardia; Vecuronium Bromide
PubMed: 34711192
DOI: 10.1186/s12871-021-01477-5 -
Biochemical Pharmacology Oct 2021Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate...
Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate acetylcholine binding and function. Using radioligand binding experiments we investigated their binding mode. We show that neuroactive steroids bind to two binding sites on muscarinic receptors. Their affinity for the high-affinity binding site is about 100 nM. Their affinity for the low-affinity binding site is about 10 µM. The high-affinity binding occurs at the same site as binding of steroid-based WIN-compounds that is different from the common allosteric binding site for alcuronium or gallamine that is located between the second and third extracellular loop of the receptor. This binding site is also different from the allosteric binding site for the structurally related aminosteroid-based myorelaxants pancuronium and rapacuronium. Membrane cholesterol competes with neurosteroids/neuroactive steroids binding to both high- and low-affinity binding site, indicating that both sites are oriented towards the cell membrane..
Topics: Allosteric Regulation; Androstanes; Androstenes; Animals; Benzimidazoles; Binding Sites; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Gallamine Triethiodide; Humans; Neuromuscular Nondepolarizing Agents; Neurosteroids; Receptors, Muscarinic; Vecuronium Bromide
PubMed: 34324870
DOI: 10.1016/j.bcp.2021.114699