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A novel ECL sensor for the detection of PMD based on the quenching effect of GDY on Ru(bpy) 3 2+ ECL and the competitive host–guest interaction between Q[8], PMD and Fc. Strong anodic Ru(bpy) 3 2+ ECL was obtained at a Q[8] modified electrode. Fc terminated DNA could be used to immobilize GDY onto the electrode through the host–guest interaction between Q[8] and Fc, leading to the decrease of anodic ECL. PMD could replace Fc from the cavity of Q[8] and release GDY from the electrode, leading to the recovery of ECL intensity. As a result, an "on–off-on" mode ECL sensor was designed. [Display omitted] • Graphdiyne exhibited apparent inhibiting effect on Ru(bpy) 3 2+ ECL. • The competitive interaction between Fc, PMD, and Q[8] could bring signal variation. • PMD could be sensitively detected based on inhibiting effect and host–guest interaction. Graphdiyne (GDY) is considered as another promising carbon material in biosensing field. However, the application of GDY in ECL sensing is in its infancy stage, and different roles of GDY are urgent to be discovered. In this work, strong anodic Ru(bpy) 3 2+ electrochemiluminescence (ECL) was obtained at a cucurbit[8]uril (Q[8]) modified electrode. Although GDY exhibited electrocatalytic effect on the oxidation of Ru(bpy) 3 2+, an apparent inhibiting effect of GDY on the ECL signal was observed due to the energy transfer. An "on-off-on" mode ECL sensor was fabricated to detect pancuronium (PMD) based on the competitive host–guest interaction between ferrocene (Fc), PMD and Q[8]. Fc modified single-stranded DNA was immobilized onto the surface of GDY, which could be attached onto the electrode through the interaction between Fc and Q[8]. The quenching effect of GDY could apparently decrease ECL signal. PMD exhibited stronger combining ability with Q[8] than Fc, and could replace Fc from the cavity of Q[8], leading to the recovery of ECL signal. The variation of ECL intensity changed linearly with the PMD concentration in the range of 10 nM to 50 μM with a detection limit of 5 nM (3σ). The proposed sensor has high sensitivity, outstanding specificity and accuracy, indicating that GDY has promising potential application in ECL sensing field based on its inhibiting effect. [ABSTRACT FROM AUTHOR]

ABSTRACT PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

Background and Aims: Local anaesthetics are drugs that are widely used in clinical practice. However, the effects of these drugs on the neuromuscular junction and their influence on the blockade produced by non-depolarising neuromuscular blocking drugs are still under investigation. The aim of this study was to evaluate, in vitro, the influence of a 50% enantiomeric excess bupivacaine mixture on neuromuscular transmission and neuromuscular block produced by pancuronium. Methods: Rats were distributed into three groups (n = 5) according to the drug studied namely, 50% enantiomeric excess bupivacaine mixture (5 μg/mL); pancuronium (2 μg/mL); 50% enantiomeric excess bupivacaine mixture + pancuronium. The following parameters were evaluated: (1) Effects of a 50% enantiomeric excess bupivacaine mixture on membrane potential (MP) and miniature endplate potentials (MEPPs); (2) amplitude of diaphragmatic response before and 60 min after the addition of a 50% enantiomeric excess bupivacaine mixture; the degree of neuromuscular block with pancuronium and pancuronium combined with a 50% enantiomeric excess bupivacaine mixture. Results: A 50% enantiomeric excess bupivacaine mixture did not alter the amplitude of muscle response (MP) but decreased the frequency and amplitude of MEPP. The block produced by pancuronium was potentiated by a 50% enantiomeric excess bupivacaine mixture. Conclusion: A 50% enantiomeric excess bupivacaine mixture used alone did not affect neuromuscular transmission, but potentiated the neuromuscular block produced by pancuronium. No action was shown on the muscle fibre, and alterations on MEPPs demonstrated a presynaptic action.

During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Analgesia is meant to reduce the pain produced by surgery. To fulfil this requirement various drugs such as alcohol, opium, hashish and balladona have been used in the past by the Egyptians and Chinese for the control of pain during surgery when the anesthesia was not known. Glucose is a carbohydrate required for energy. During the process of metabolism of glucose the source storage come into play. Nervous influence, enzymatic action and hormonal involvement also have a significant role. Aim: The aim of the study was the study of blood glucose level changes during general anesthesia in patients under surgery. Materials and methods: The present study was done in the department of Anesthesiology during the year 2015-2016, 60 patients with age group of 25-65 years along with different sex distribution. Results: Regarding the anaesthesia group, there were 15 patients in the age group of 25-35 years and 36-45 years each.14 patients were in age group 46-55 years, while 16 patients in the age group of 56-65 years. Out of 60 patients 33 patients (55%) were male patients while remaining 27 patients (45%) were female patients. Conclusion: Present study showed that there is very highly significant rise in blood glucose level during the ether anesthesia while in case of relaxants there is only significant rise in blood glucose level. [ABSTRACT FROM AUTHOR]

Byline: Garima. Choudhary, Rashmi. Syal, Rakesh. Kumar, Manoj. Kamal We report a case of an 8-year-old girl who presented with syncopal attacks and a history of viral illness a month [...]

Purpose: This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia. Methods: Male Sprague-Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle. Arousal responses to microinjection of nicotine into the lateral ventricle were assessed with or without pretreatment with intraventricular pancuronium. The intravenous 50 % effective dose (ED) and 95 % effective dose (ED) for neuromuscular blockade with pancuronium administered in a cumulative fashion at 1.1 % isoflurane were calculated. Results: Intraventricular pancuronium dose-dependently reduced the response to tail clamping, and the dose required to show immobilization of 50 % of rats (intraventricular ED) was 1.62 µg/kg. Pretreatment with pancuronium at 6 µg/kg significantly reduced the effect of awakening by nicotine under isoflurane anesthesia ( P = 0.044). The intravenous ED and ED for neuromuscular blockade were 63 µg/kg (90 % confidence interval [CI] 52-75 µg/kg) and 133 µg/kg (90 % CI 109-158 µg/kg), respectively. The ratio of intraventricular ED to intravenous ED was 0.026. Conclusion: Pancuronium microinjection into the lateral ventricle dose-dependently enhances the depth of isoflurane anesthesia, which might be caused by inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum. Intravenous injection of pancuronium at high doses might increase the cerebrospinal concentration to a level at which an effect can be observed. [ABSTRACT FROM AUTHOR]

Intravenous regional anesthesia requires a tiny practice to obtain good results and proves economical. We evaluated the efficacy of fentanyl (1 µg/kg) and pancuronium (0.5 mg) in lower doses with 0.25% lignocaine (1.5 mg/kg) for intravenous regional anesthesia for upper limb surgeries for a period not exceeding one hour, additionally we also compared the above study with standard Bier's block i.e. intravenous regional anaesthesia with 0.5% lidocaine (0.5 mg/kg body weight). This study was conducted in a medical college government general hospital, in Andhra Pradesh over the period of 3 years during 2001 to 2004. Fifty patients belonging to ASA grade I and grade II undergoing upper limb surgery were selected. Patients were included if they were undergoing upper limb surgeries for a period not exceeding one hour. These patients were assigned in a randomized, double fashion to two groups: Group A received 0.6 ml/kg of 0.5 % lidocaine (3 mg/kg) and Group B received 0.6 ml/kg of 0.25 % lidocaine (1.5 mg/kg) plus fentanyl (1 µgm/kg) and pancuronium (0.5 mg). The patients were observed for two hours after the release of the tourniquet for any complications like bradycardia, hypotension, and convulsions etc. The present was compared with standard Bier's block, i.e., 0.5% lidocaine (3 mg/kg body weight). Data was presented as Mean±SD, actual numbers and percentages and analyzed using SPSS version 16. In this study, 50 patients undergoing various upper limbs, surgeries were given intravenous regional anesthesia which included 38 males and 12 females. The postoperative analgesia was slightly greater in Group B compared to Group A. The onset of sensory and a motor blockade were earlier in Group A patients when compared to Group B patients. Short delay observed with this new method in the onset of sensory and motor blockade should be noted and the start of surgical procedures delayed until 15-20 minutes after tourniquet inflation. There was no difference in the quality of analgesia and muscle relaxation between two groups. The triple combination of lidocaine, fentanyl and pancuronium can be considered as is safe and effective since the dose of lignocaine can be reduced to a non-toxic level with the same quality of anesthesia. However, the limiting factor in this new technique is a short delay in the onset of sensory and motor blockade compared to standard Bier's block. [ABSTRACT FROM AUTHOR]

Background and Aims: Local anaesthetics are drugs that are widely used in clinical practice. However, the effects of these drugs on the neuromuscular junction and their influence on the blockade produced by non-depolarising neuromuscular blocking drugs are still under investigation. The aim of this study was to evaluate, in vitro, the influence of a 50% enantiomeric excess bupivacaine mixture on neuromuscular transmission and neuromuscular block produced by pancuronium. Methods: Rats were distributed into three groups (n = 5) according to the drug studied namely, 50% enantiomeric excess bupivacaine mixture (5 μg/mL); pancuronium (2 μg/mL); 50% enantiomeric excess bupivacaine mixture + pancuronium. The following parameters were evaluated: (1) Effects of a 50% enantiomeric excess bupivacaine mixture on membrane potential (MP) and miniature endplate potentials (MEPPs); (2) amplitude of diaphragmatic response before and 60 min after the addition of a 50% enantiomeric excess bupivacaine mixture; the degree of neuromuscular block with pancuronium and pancuronium combined with a 50% enantiomeric excess bupivacaine mixture. Results: A 50% enantiomeric excess bupivacaine mixture did not alter the amplitude of muscle response (MP) but decreased the frequency and amplitude of MEPP. The block produced by pancuronium was potentiated by a 50% enantiomeric excess bupivacaine mixture. Conclusion: A 50% enantiomeric excess bupivacaine mixture used alone did not affect neuromuscular transmission, but potentiated the neuromuscular block produced by pancuronium. No action was shown on the muscle fibre, and alterations on MEPPs demonstrated a presynaptic action. [ABSTRACT FROM AUTHOR]

Introduction Many agents, including muscle relaxants, influence neuromuscular function. Although in vitro and in situ measurement systems of skeletal muscular contractility have been developed and in use for years, no convenient device and parameter are available to examine the time course of the acute effects of such agents on neuromuscular function in conscious mice. Methods We created a two-compartment device consisting of a transparent, wide, acrylic chamber with a foot shock grid, and an attached, opaque narrow tunnel to measure neuromuscular performance. A mouse placed into the wide chamber, quickly enters the narrow tunnel. We attached a string to the tail of the mouse to measure the developed tugging force when the mouse entered the narrow tunnel. Results After administering the muscle relaxants suxamethonium, vecuronium, and pancuronium, the peak tugging force decreased maximally at 3 or 5 min after administration, and recovered within 20 min. These responses to the muscle relaxants were dose-dependent. Discussion Tugging force is an objective and reproducible parameter for examining the time course of an acute change in neuromuscular function. [ABSTRACT FROM AUTHOR]

Objective To compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker. Study design Retrospective, non-randomized comparison. Animals Norwegian Land Race pigs ( Sus scrofa domesticus) weighing mean 42 ± SD 3 kg. Methods One hundred and sixteen animals from four different research protocols premedicated with identical doses of ketamine, diazepam, atropine and isoflurane, and anaesthetised with pentobarbital, fentanyl, midazolam and N2O were arranged into three uniform groups with respect to neuromuscular blocking agent: pancuronium bolus of 0.063 mg kg−1 followed by 0.14 mg kg−1 hour−1 ( n = 54), low-dose vecuronium 0.4 mg kg−1/0.2 mg kg−1 hour−1 ( n = 29) and high-dose vecuronium 0.6 mg kg−1/0.3 mg kg−1 hour−1 ( n = 33). Results The majority of cardiovascular parameters demonstrated no significant differences between groups. For heart rate, there was an overall group difference, p = 0.036. Dromotropy was low in the pancuronium group, with an increased normalised PR-interval compared to the high-dose vecuronium group, median 0.200 interquartile range (0.190, 0.215) versus 0.182 (0.166, 0.199), p < 0.05. Left ventricular compliance was increased in pancuronium-treated animals, demonstrated as a reduction in the nonlinear end-diastolic pressure volume relationship β compared to both vecuronium groups, 0.021 (0.016, 0.025) versus 0.031 (0.025, 0.046) and 0.031 (0.022, 0.048), p < 0.05. The linear end-diastolic pressure volume relationship EDPVRlin was reduced as well in the pancuronium group, compared to the low-dose vecuronium group, 0.131 (0.116, 0.169) versus 0.181 (0.148, 0.247), p < 0.05. Conclusions There are only minor haemodynamic differences when using pancuronium compared to vecuronium in the fentanyl-pentobarbital-midazolam-N2O anesthetised domestic pigs. Furthermore, increasing doses of vecuronium have minimal haemodynamic effects. Clinical relevance Experimental studies in pigs using either pancuronium or vecuronium as a neuromuscular blocking agent are comparable with regard to cardiac and haemodynamic performance. [ABSTRACT FROM AUTHOR]

Neste estudo foram comparados os efeitos do pancurônio e do vecurônio em cães submetidos a facectomia extracapsular. Foram utilizados 24 cães hígidos, de diferentes sexos e raças, com idade média de 6,8 ± 2,0 anos e peso médio de 10,0 ± 6,4 quilos. Os animais receberan como medicação pré-anestésica acepromazina. A anestesia foi induzida através do uso de midazolam e tiopental, sendo a manutenção da anestesia realizada com halotano em oxigênio a 100% com auxílio de aprelho com sistema circular. Posteriormente a este protocolo, os animais foram distribuídos em dois grupos: grupo I onde imediatamente antes do início da cirurgia, receberam pancurônio e o grupo II onde no mesmo momento receberam vecurônio, sendo observados os períodos de latência através da paralisação respiratória e o hábil através da recuperação da respiração espontânea, assim como o período de centralização do globo ocular. Previamente a administração do bloqueador neuromuscular e aos 1, 5, 10, 15 e 20 minutos da sua aplicação foram avaliadas a freqüência e ritmo cardíaco, a pressão arterial sistólica, média e diastólica e a saturação periférica da hemoglobina, sendo os valores obtidos submetidos a análise estatística, não tendo sido observadas diferenças estatisticamente signifcativas entre os valores obtidos. Os valores médios e desvios-padrões dos períodos de latência do pancurônio e do vecurônio foram respectivamente 93,5 ± 38,9 e 80,8 ± 25,5 segundos, considerados adequados, uma vez que possibilitam a rápida instituição da ventilação controlada sem que ocorresse hipoxemia. A centralização do globo ocular foi obtida em 31,4 ± 18,2 segundos com pancurônio e 39,8 ± 19,7 segundos com vecurônio, apresentando estes resultados difirença estatisticamente significativa. O período hábil do pancurônio foi significativamente maior que o do vecurônio (respectivamente 33,6 ± 7.1 e 23,9 ± 6,3 minutos), porém os dois agentes possuem duração suficiente para a realização do procedimento cirúrgico em questão.In this study the effects of pancuronium and vecuronium were compared in dogs submitted to lens extraction. Twenty four healthy male and female dogs, of different breeds, with 6.8 ± 2.0 years and mean weight of 10.0 ± 6.4 kilograms were used. All animals received acepromazine as the pre-anesthetic medication. Anesthesia was induced with midazolam and thiopentone and halothane was used as the maintenance agent in 100% oxygen with a circular system. After this animals were randomized in two groups: animals of group I received pancuronium and those from group II received vecuronium. Onset time evaluated by means of respiratory arrest as well as duration of action were verified by the moment spontaneous respiration reassumed and time to eye centralisation. Heart rate and rhythm, systolic, meand and diastolic blood pressure as well as hemoglobin saturation were measured before neuromuscular block administration and 1, 5, 10, 15 and 20 minutes after its administration. Data were submitted to statistical analyzes that consisted of analyzes of variance (ANOVA) for repeated measures fallowed by Tukey post test for the evaluation of the different moments in the same group and Student T test for the differences between the groups. The statistical analyses did not show any difference between treatments or between different moments in the group. Mean values and standard deviation of onset time for pancuronium and vecuroniun were 93.5 ± 38.9 and 80.8 ± 25.5 seconds respectively, that were considered adequate once hypoxemia did not occurr when controlled ventilation were instituted. Eye centralization occurred 31.4 ± 18.2 seconds after pancuronium and 39.8 ± 19.7 seconds after vecuronium and these values were statistically different. Duration of action of pancuratium was significantly longer than that werified for vecuroniun and this values were 33.6 ± 7.1 and 23.9 ± 6.3 minutes. Nevertheless both agents showed a reasonable duration of action and the surgical procedure could be performed unevetfully.

Novel and rapid capillary electrophoresis-coupled tandem mass spectrometry (CE-MS/MS) and capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) methods have been developed for the separation and determination of three neuromuscular blocking agents: pancuronium, vecuronium, and rocuronium. In both cases, the separation was conducted in background electrolytes based on acidic acetate-ammonium buffers to avoid possible decomposition of the analytes that are known to be unstable in alkaline media. Baseline resolution of the analytes was achieved in the presence of modified γ-cyclodextrin by CE with C4D detection. The two detection techniques were compared with regard to analytical figures of merit including linear dynamic range, limit of detection, limit of quantification, precision, and accuracy. The calibration curves showed good linearity for both detection methods examined (characterized by r2 ≥ 0.9908). The LODs of the CE-MS/MS and the CE-C4D methods differed at least by two orders of magnitude considering all analytes. The differences in precision and accuracy of these methods were evaluated and discussed. The assays of pancuronium, vecuronium, and rocuronium in commercial injection solutions by CE-MS/MS and CE-C4D were performed and the results compared. [ABSTRACT FROM AUTHOR]

The 2 Hz train-of-four ratio ( TOFratio) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. Uncertainty about the usefulness of the TOFratio to control safe recovery from curarization prompted us to investigate the muscarinic and adenosine neuromodulation of tetanic (50 Hz) fade induced by antinicotinic agents at concentrations that cause a 25% reduction in the TOFratio ( TOFfade)., Tetanic fade caused by d-tubocurarine (1.1 μmol/L), pancuronium (3 μmol/L) and hexamethonium (5.47 mmol/L) was attenuated by blocking presynaptic inhibitory muscarinic M2 and adenosine A1 receptors with methoctramine (1 μmol/L) and 1,3-dipropyl-8-cyclopentylxanthine (2.5 nmol/L), respectively. These compounds enhanced rather than decreased tetanic fade induced by cisatracurium (2.2 μmol/L), but they consistently attenuated cisatracurium-induced TOFfade. The effect of the M1 receptor antagonist pirenzepine (10 nmol/ L) on fade produced by antinicotinic agents at 50 Hz was opposite to that observed with TOF stimulation. Blockade of adenosine A2A receptors with ZM 241385 (10 nmol/L) attenuated TOFfade caused by all antinicotinic drugs tested, with the exception of the 'pure' presynaptic nicotinic antagonist hexamethonium. ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium., The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A2A receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade. [ABSTRACT FROM AUTHOR]

Objective To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMBmod: train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research. Study design Prospective cross-sectional study. Animals Five pigs (median body weight: 60 (range 60-63) kg). Methods Anaesthesia was induced with xylazine, ketamine, atropine and midazolam and maintained with isoflurane in O2:air and fentanyl. Pigs received 0.1 mg kg−1 pancuronium initial bolus to reach NMBmod followed by 0.1 mg kg−1 hour−1 constant rate infusion (CRI). During anaesthesia a twitch count of 3 or measureable T4/T1 ratio indicated unsatisfactory NMB. In this case additional 0.4 mg boluses of pancuronium were administered IV to effect in addition to the CRI. Descriptive statistical analysis was performed to express the median and range of the bolus and CRI dose of pancuronium in pigs. Cardiovascular parameters were analyzed at selected time points with Friedman Repeated Measures Analysis on Ranks. Spearman Rank test was used to evaluate correlation between parameters. Results Acceleromyographic monitoring of NMB is feasible in anaesthetized pigs. The median initial dose and rate of pancuronium required to achieve NMBmod were 0.10 (range 0.10-0.13) mg kg−1 and 0.11 (range 0.10-0.21) mg kg−1 hour−1, respectively. The administration rate showed considerable individual variation. Conclusions and clinical relevance These pancuronium doses can be used as a guideline to achieve NMBmod in pigs as part of a balanced anaesthetic protocol. Instrumental NMB monitoring is essential because of individual kinetic variations and compliance to monitoring guidelines. [ABSTRACT FROM AUTHOR]

Abstract: Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chromosomal changes have not been observed in vivo, this is most likely due to DNA repair mechanisms, apoptosis, or cellular senescence. Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies. In this study, the P388 murine B cells were cultured in vitro, and spectral karyotyping (SKY) was utilized to uncover genomewide changes. Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability. These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents. Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results. [Copyright &y& Elsevier]

Abstract: Background: Pancuronium, vecuronium, rocuronium, and mivacurium are nondepolarizing neuromuscular blocking agents that affect the cardiovascular system with different potencies. Their cardiovascular effects are clinically significant in the anesthetic management of patients, particularly those undergoing cardiac surgery. Objective: We aimed to compare the cardiac effects of these compounds, such as heart rate and developed force, in one species under identical experimental conditions in isolated rat atria. Methods: The left or right atria of rats were removed and suspended in organ baths. Pancuronium, vecuronium, rocuronium, or mivacurium were added cumulatively (10–9–10–5 M) in the presence and absence of the nonselective β-blocker propranolol (10–8 M) and the noradrenaline reuptake inhibitor desipramine (10–7 M), and heart rate changes were recorded in spontaneously beating right atria. Left atrial preparations were stimulated by electrical field stimulation using a bipolar platinum electrode, and the effects of cumulative concentrations of these nondepolarizing neuromuscular blocking agents on the developed force in the presence and absence of propranolol (10–8 M) and desipramine (10–7 M) were recorded. Results: Pancuronium increased heart rate in a dose-dependent manner compared with the control group (P < 0.027). Vecuronium, rocuronium, and mivacurium also increased heart rate in a dose-dependent manner, but the changes were not statistically significant. Although propranolol decreased the pancuronium heart rate effect (P < 0.05), it did not change the heart rate effects with vecuronium, rocuronium, or mivacurium. Desipramine did not change the heart rate effects of vecuronium, rocuronium, mivacurium, or pancuronium. All 4 drugs increased developed force in a dose-dependent manner; the increases were significant at 10–5 M concentration for pancuronium and at 10–6 and 10–5 M concentrations for vecuronium, rocuronium, and mivacurium (P < 0.038). These increases in developed force were abolished with the addition of propranolol. Desipramine did not change the developed force effects of any of the 4 drugs. Conclusions: The heart rate effect of pancuronium and developed force effects of pancuronium, vecuronium, rocuronium, and mivacurium may occur via direct stimulation of β receptors. Although our investigation was an in vitro study, the effects found may be important especially under pathologic conditions, such as hypertension, in which patients usually use β-blocking agents, which cause β receptor upregulation. [Copyright &y& Elsevier]

Neuromuscular blocking agents (NMBAs) are often administered as a prolonged (> 24 hrs) continuous infusion in infants and children in the intensive care unit for a variety of reasons including facilitation of oxygenation and ventilation. No guidelines on the use of NMBAs in pediatric patients are available yet in the United States; however, pediatric guidelines are available in the United Kingdom. Based on a 2007 U.S. survey, the most commonly used nondepolarizing NMBAs for sustained neuromuscular blockade in critically ill children are pancuronium and vecuronium. Recent national drug shortages involving NMBAs have been reported for atracurium, cisatracurium, pancuronium, rocuronium, and vecuronium. Therefore, to explore alternative options for neuromuscular blockade, we conducted a literature search to identify articles evaluating prolonged use (> 24 hrs) of NMBAs administered by continuous infusion. The search was limited to English-language articles in the MEDLINE (1950-August 2010), EMBASE (1988-August 2010), International Pharmaceutical Abstracts (1970-August 2010), and Cochrane Library (1996-August 2010) databases. Relevant abstracts, reference citations, and manufacturers' product information were also reviewed. A total of 13 reports representing 208 children were included in the analysis. Many of the reports described wide interpatient variability in dosing for the specific NMBAs evaluated. Selection of the most appropriate NMBA should be based on the patient's clinical status, potential adverse effects, and pharmacoeconomics. All patients receiving sustained neuromuscular blockade should be monitored routinely to ensure that dosing is appropriate in order to obtain the desired level of blockade. The goal is to use the lowest dose possible in an effort to limit adverse effects or prolonged blockade. [ABSTRACT FROM AUTHOR]

A novel, sensitive and simple liquid chromatography method with charged aerosol detection (LC-CAD) for the simultaneous assay determination of pancuronium and its impurities (dacuronium and vecuronium) has been developed. The limit of quantitation for vecuronium and dacuronium was 1.64 and 3.42 μg mL−1, respectively. The elaborated method was validated for linearity, precision and accuracy. This LC-CAD method is expected to have potential application in routine analysis of pancuronium in substance and in pharmaceutical preparations. All impurities were confirmed using time-of-flight mass spectrometry with electrospray ionization. [ABSTRACT FROM AUTHOR]

We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 ± 3.3 Hz; mean ± SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. The concentrations required for approximately 25% fade were 413 µM for hexamethonium (26.8 ± 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 ± 2.55% fade), 0.32 µM for pancuronium (25.4 ± 2.2% fade), and 0.32 µM for cisatracurium (24.7 ± 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 µM, attenuated the fade induced by hexamethonium (to 16.0 ± 2.5% fade), d-tubocurarine (to 6.0 ± 1.6 fade), pancuronium (to 8.0 ± 4.0% fade), and cisatracurium (to 11.0 ± 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 ± 0.11% fade) and cisatracurium (to 13.3 ± 5.3% fade). Cisatracurium (0.32 µM) showed antiacetylcholinesterase activity (in plasma, 14.2 ± 1.6%; 6%; in erythrocyt 17.2 ± 2.66%) similar to that of pancuronium (0.32 µM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine. [ABSTRACT FROM AUTHOR]

Objectives: We studied in vivo growth of Escherichia coli in atracurium, rocuronium, mivacurium, cisatracurium, pancuronium, and vecuronium. Patients and Methods: The pathogen was exposed to atracurium, rocuronium, mivacurium, cisatracurium, pancuronium and vecuronium for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 h at room temperature, respectively. Results: The mean colony counts of Escherichia coli after exposure to rocuronium was significantly lower than the counts after exposure to atracurium, mivacurium, cisatracurium, pancuronium and vecuronium (p=0.002, 0.000, 0.000, 0.001, and 0.002, respectively). No significant difference was found with respect to the mean colony counts with atracurium, mivacurium, cisatracurium, pancuronium and vecuronium (p<0.05). Conclusion: Rocuronium had more powerful antimicrobial effects than the other neuromuscular agents. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the in vivo relation between muscle hardness during an electrically induced contracting state and neuromuscular functions (M-wave and developed tension). Sixteen Sprague-Dawley rats were deeply anesthetized with urethane. Muscle hardness was measured quantitatively at the mid-portion of the gastrocnemius (GS) muscle during tetanic contractions induced by electrical stimulation (50 Hz, 100 micros duration) of the sciatic nerve or of the muscle directly. The M-wave was recorded with a pair of wire electrodes inserted into the muscle, and the developed tension was monitored with a push-pull gauge. Muscle hardness, M-wave amplitude and developed tension increased rapidly with the onset of nerve stimulation. Similar but intensity-dependent increases in muscle hardness and tension were observed following direct tetanic stimulation of the muscle. The hardness measured during nerve stimulation was correlated with the amplitude of the M-wave (r = 0.62, P < 0.0001) and the developed tension (r = 0.85, P < 0.0001). These phenomena were suppressed by pancuronium treatment (2 mg/ml, i.v.). These results suggest that muscle tension might be the most important factor for transcutaneously measured muscle hardness induced by tetanic muscle contraction. [ABSTRACT FROM AUTHOR]

Abstract: A simultaneous determination method of quaternary amino steroidal muscle relaxants, pancuronium (PAN), vecuronium (VEC), and 17-monodesacetyl pancuronium (17-OH-PAN), 3,17-bisdesacetyl pancuronium (3,17-OH-PAN), 3-monodesacetyl vecuronium (3-OH-VEC), 3,17-bisdesacetyl vecuronium (3,17-OH-VEC) in human serum was developed using liquid chromatography–electrospray ionization-mass spectrometry (LC–ESI-MS). The weak cation exchange cartridge was useful for the extraction of these compounds. Under optimized LC–ESI-MS conditions, these compounds were almost fully separated within 6.5min. Linear responses over the concentration range 0.25–50.0ng/mL were demonstrated for each compound. The developed method successfully detected VEC, 3-OH-VEC and 3,17-OH-VEC in serum intravenously administered with VEC. The level of 3-OH-VEC was higher than other compounds. This suggested that 3-OH-VEC was useful as a forensic probe in VEC administration. [Copyright &y& Elsevier]

Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built-in self-destruct mechanism that makes them especially useful in kidney or liver failure, and the vecuronium group, which are especially free from unwanted side effects. Of this latter group, the compound rocuronium is of especial interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors.British Journal of Pharmacology (2006) 147, S277–S286. doi:10.1038/sj.bjp.0706404 [ABSTRACT FROM AUTHOR]

Abstract: Despite the availability of modern neuromuscular blocking agents with short or intermediate duration of action, incidence of residual neuromuscular blockade remains very high. Evidences have been recently provided that residual curarization must be defined as a train-of-four ratio below 0.9 at the thumb adductor during the recovery period after anaesthesia. Residual curarization may be associated with serious adverse events related to respiratory depression, pharyngeal dysfunction, hypoxemia and prolongation of the length of stay in the recovery room. Appropriate choice of drugs, perioperative monitoring of neuromuscular function and large indications of pharmacological reversal may reduce the incidence of residual curarization and improve the patient''s safety in the postoperative setting. [Copyright &y& Elsevier]

Background: In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and sensitivity can be explained by the decreased acetylcholine receptor concentration that is caused by the disease. Methods: Functional acetylcholine receptors were reduced by administration of α-bungarotoxin or by injecting monoclonal antibodies against rat acetylcholine receptors (experimental autoimmune myasthenia gravis). After induction of anaesthesia, the model was set up and perfusion of the tibialis anterior muscle with blood was started. After stabilization of the twitch, rocuronium or pancuronium were infused until 90% block was obtained. Twitch data and infusion data were recorded and used to calculate the time course of effect and potency. Results: The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the a-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls. Conclusion: This study shows that the increased sensitivity to neuromuscular-blocking agents in myasthenia gravis can be accounted for by a decreased number of acetylcholine receptors. It also shows that the antegrade perfused rat peroneal nerve anterior tibialis muscle model is a suitable model to study the effects of myasthenia gravis on the time course of effect of neuromuscular blocking agents. [ABSTRACT FROM AUTHOR]

Abstract: The neuromuscular blocking agents in routine clinical use may be classed as depolarizing or nondepolarizing. Suxamethonium is the only example of the depolarizing group and is an agonist at the neuromuscular receptor. It has the most rapid onset and the shortest duration of action, though it has a number of important unwanted side-effects. Its duration is prolonged by deficiency or absence of plasma cholinesterase. The nondepolarizing group act by competitive antagonism of acetylcholine at the receptor sites. The long acting agents (e.g. pancuronium) are little used in modern anaesthesia. The intermediate acting agents (atracurium, cisatracurium, vecuronium, rocuronium) are currently the most popular. They are versatile and predictable in action and recovery. Mivacurium is the only short acting agent available and is broken down by plasma cholinesterase. A reversal agent is required to restore neuromuscular function by biasing the equilibrium within the neuromuscular junction back towards acetylcholine. Reversal agents function by inhibiting acetylcholinesterase in a reversible fashion. Edrophonium is the shortest acting and only suitable for reversing a light to moderate block. Neostigmine is the most reliable. It is necessary to give an antimuscarinic agent at the same time to counteract parasympathomimetic side-effects. New reversal agents that actively bind relaxant molecules are under development but it seems unlikely that any new neuromuscular blocking agents will appear in the near future. [Copyright &y& Elsevier]

Changes in the parameters of acid-base status and blood gas analysis in 3 main methods of anaesthesia in dogs were investigated. The experiment was carried out in 22 male and female dogs, matched for breed, age and body weight and divided into 3 groups. Animals from the first group (n = 8) were subjected to standard inhalation anaesthesia using halothane. Those from the second group (n = 7) received balanced anaesthesia using pancuronium, and those from the third group (n = 7) received epidural lumbosacral anaesthesia using lidocaine. Arterialised capillary blood samples were obtained from all animals in the following periods: immediately before anaesthesia (0 min), during premedication (30 min), during deep anaesthesia (120 min), after recovery (about 140 min) and the next day (24 h). The acid-base and blood gas parameters (pH, PaCO2, PaO2, HCO3, TCO2, ABE, SBE, SBC, SAT, and O2CT) were determined. The results showed that during the deep stages of halothane and balanced anaesthesia primary noncompensated respiratory acidosis and overoxygenation developed. These changes were only eliminated during the recovery period. The epidural anaesthesia was not accompanied by any changes in blood gas and acid-base status. [ABSTRACT FROM AUTHOR]

The present study was designed to determine the stability of pancuronium in postmortem blood and liver during storage. Results were obtained using the method by Kerskes et al. [C.H.M. Kerskes, K.J. Lusthof, P.G.M. Zweipfenning, J.P. Franke, The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS, J. Anal. Toxicol. 26 (2002) 29-34.], modified and validated in our laboratory. Target analytes were isolated after enzymatic hydrolysis followed by solid phase extraction (BondElut C18 column). Internal standardisation was carried out using laudanosine and the target ions were monitored by LC-ESI-MS (monitoring ions m/z 358 for IS and 286 for pancuronium). Materials were taken from a 46-year-old woman, who had been found dead. A syringe (2 ml) and an empty ampoule of Pavulon (4 mg/2 mL) were found in her hand. The residual volume of fluid in the syringe was 0.7 ml. An autopsy was performed six days after death. It revealed a needle mark on the left thigh. Postmortem materials (muscle from the injection site, blood and liver) and the syringe with fluid were stored for four months in a freezer at -20 °C. The initial pancuronium concentrations were 81 ng/mL in blood and 532 ng/g in liver. The analyte was stable when stored at -20 °C in blood even up to seven months. In liver samples its concentrations were variable. Pancuronium in blood stored at 20 °C underwent degradation very rapidly. After three months of storage these blood samples had concentrations not greater about 10% of the initial value. The degradation patterns of pancuronium depended on temperature and the biological matrix. [Copyright &y& Elsevier]

Background: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function.Methods: Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug.Results: Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001).Conclusion: Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation. [ABSTRACT FROM AUTHOR]

A new high-performance liquid chromatography (HPLC) method was developed for the quality control of pancuronium bromide and its degradation products. The HPLC method used a 5-μm Supelcogel ODP-50 (150×4 cm) column with acetonitrile–CH3OH–water–F3CCOOH (20.5:74.9:0.1, v/v) as the mobile phase (pH value 2.0 adjusted with trifluoroacetic acid) at a flow-rate 0.8 ml/min and UV detection at 210 nm. The Beer’s law plots were found to be linear over the concentration range 0.4–1.2 mg/ml of pancuronium bromide and 0.04–0.08 mg/ml of desacetyl degradation products (R2=0.9995). The RSD of the peak areas was 1.09% and the recovery was 102.43%. The RSD value shows good precision, acceptable accuracy and reproducibility of the new method for the determination of pancuronium bromide in presence of its desacetyl degradation products. The method is rapid and sensitive enough to be used for Pavulon injection analysis. [Copyright &y& Elsevier]

A detailed anaesthetic technique for baboons ( Papio anubis) undergoing heterotopic abdominal cardiac xenotransplantation is described. Twenty-two baboons served as transplant recipients. Donors were either crossbred farm pigs ( Sus scrofa) ( n = 4) or transgenic pigs ( Sus scrofa) ( n = 18) expressing human complement regulatory proteins on the endothelium. Intra-operative management was complicated by the physiological consequences of infrarenal, abdominal aortic cross-clamping, in addition to the immunological sequelae related to cross-species transplantation. In choosing anaesthetics for this procedure, we considered the need for maximal cardiac stability throughout a long surgical procedure that required abdominal aortic cross-clamping to facilitate the implantation of an oversized porcine cardiac graft. Baboons received a balanced anaesthetic consisting of inhaled isoflurane in oxygen, intravenous fentanyl and intravenous pancuronium. The pharmacological techniques employed were found to be safe and reliable and were well tolerated by our recipients without any significant side-effects. [ABSTRACT FROM AUTHOR]

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