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The Journal of International Medical... Jun 2020This study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate...
OBJECTIVE
This study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation.
METHODS
HUVECs were cultivated with 5% CO at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10, 10, and 10 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates.
RESULTS
The neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times.
CONCLUSIONS
The findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.
Topics: Androstanols; Atracurium; Human Umbilical Vein Endothelial Cells; Humans; Neuromuscular Blockade; Pharmaceutical Preparations; Vecuronium Bromide
PubMed: 32588688
DOI: 10.1177/0300060520910888 -
Pediatric Emergency Care Jun 2020Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the... (Review)
Review
Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the United States by the Food and Drug Administration for adult use. However, there are ongoing clinical trials investigating its use in the pediatric population. Before approval in adult use in the United States, several adverse effects were noted to occur in patients receiving sugammadex in clinical trials including prolonged QT interval, bradycardia, hypersensitivity reactions, and prolongation of coagulation parameters. Additional investigations further elucidated the risks of these adverse events. Sugammadex is approved for use in children older than 2 years in other countries in Europe and Asia. Investigations suggest that the efficacy, safety, and pharmacokinetic profile is similar in children when compared with adults. Published pediatric data favor the use of sugammadex in children older than 2 years, but there are some data in young children younger than 2 years. Case reports discuss the use of sugammadex in pediatric patients with neuromuscular diseases. Although sugammadex is typically used in the operating room for reversing neuromuscular blockade for surgical procedures, there is a small but important role for sugammadex use in the emergency department. In cases where rapid neurological examination is required after neuromuscular blockage with rocuronium or vecuronium, sugammadex can assist in facilitating a timely comprehensive neurological examination where pharmacologic or surgical management may depend on examination findings such as in the case of cerebral vascular accident, status epilepticus, or traumatic brain injury. Some clinicians have advocated for the use of sugammadex in the cannot intubate, cannot ventilate scenario. However, caution should be exercised in this situation as reversal of paralysis can take up to 22 minutes to occur.
Topics: Child; Diagnostic Techniques, Neurological; Emergency Medicine; Humans; Neuromuscular Blockade; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 32483081
DOI: 10.1097/PEC.0000000000002126 -
European Journal of Anaesthesiology Oct 2020Drug errors during neuraxial anaesthesia or analgesia are not well known. (Review)
Review
BACKGROUND
Drug errors during neuraxial anaesthesia or analgesia are not well known.
OBJECTIVES
To review the clinical consequences associated with incorrect administration of neuromuscular blocking drugs (NMBDs) during spinal or epidural anaesthesia, and to investigate human factors and strategies available to help prevent such errors.
DESIGN
A review of reports of neuraxial administration of NMBDs in humans.
DATA SOURCES
Published reports of errors involving NMBDs. We searched the period between 1965 and 2019.
ELIGIBILITY CRITERIA
Error reports in any language. Nonneuraxial drug errors were excluded.
RESULTS
We identified 20 reports involving seven different NMBDs inadvertently administered via the epidural or intrathecal routes. All patients developed systemic neuromuscular junction blockade. Fourteen errors occurred while patients were awake. The onset of action was delayed following epidural rocuronium and suxamethonium. The duration of action was prolonged following epidural administration of vecuronium, pancuronium, cisatracrium and suxamethonium. Five patients required emergency airway interventions. Intrethecal gallamine caused convulsions and muscle spasms migrating up the body. Syringe swap was the primary cause for the majority of errors and perceptual errors were the most common. Implementation of recommendations could have prevented the errors.
CONCLUSION
Following the epidural injection of NMBDs the effects are delayed and prolonged. There was no serious morbidity reported following neuraxial administration of the NMBDs used in current practice. Perceptual errors resulting in incorrect syringe choice were the commonest cause. Four measures can be introduced to reduce such errors.
Topics: Humans; Neuromuscular Blockade; Pharmaceutical Preparations; Rocuronium; Succinylcholine; Vecuronium Bromide
PubMed: 32371827
DOI: 10.1097/EJA.0000000000001232 -
JNMA; Journal of the Nepal Medical... 2019Bronchospasm represents the clinical manifestation of bronchial muscles contraction resulting in reduced alveolar air flow. Non-allergic mechanisms or anaphylaxis...
Bronchospasm represents the clinical manifestation of bronchial muscles contraction resulting in reduced alveolar air flow. Non-allergic mechanisms or anaphylaxis underlie the genesis of perioperative bronchospasm, a potential anaesthetic disaster. Early recognition and treatment are crucial. We report a rare incident of anaphylactic bronchospasm without hypotension during general anaesthesia. Urticaria appeared in chest and abdomen suggesting anaphylaxis. After the event resolved with bronchodilators, surgery continued uneventfully. Vecuronium was the most probable culprit but confirmation was not possible as the patient was lost to follow up. Rarely, perioperative anaphylaxis presents only with bronchospasm that requires prompt attention to avoid adverse outcome. Keywords: allergy; anaphylaxis; bronchial spasm; general anesthesia.
Topics: Adult; Anaphylaxis; Anesthesia, General; Bronchial Spasm; Bronchodilator Agents; Humans; Male; Vecuronium Bromide
PubMed: 32323660
DOI: No ID Found -
Heliyon Mar 2020Neuromuscular blocker agent namely; Vecuronium bromide (VEC) was quantified through developing a simple reversed phase liquid chromatographic (RP-LC) method, in drug...
Neuromuscular blocker agent namely; Vecuronium bromide (VEC) was quantified through developing a simple reversed phase liquid chromatographic (RP-LC) method, in drug substance and in drug product. The proposed method could quantify VEC in the presence of its degradation products produced from exposing VEC to different stress conditions as recommended by the International Conference on harmonization (ICH) guidelines. Acidic (2M HCl), basic (2MNaOH) hydrolysis, oxidation (3% HO), photolysis (UV light at 254nm), and thermal (135 °C) degradation were estimated by exposing the drug substances to different stress conditions. The separation of the drug from its degradation products was successfully conducted on Tracer Extrasil CN (150 × 4.6mm; 5μm) column using O-phosphoric acid (pH6; 0.05M)-acetonitrile (50:50v/v) as mobile phase. The detection and quantification was done with UV detection at210nm.The validation data were found to be acceptable over a concentration range10-120 μg/ml. The limit of quantification (LOQ) and detection (LOD) were 8.10 and 2.67 μg/ml, respectively. The proposed method met all criteria for validation in accordance with the International Conference on harmonization (ICH) guidelines. The presented work monitored the degradation profile for VEC under various stress conditions and provided a simple LC method for its routine analysis. The structures of the forced degradation products had been described in details using the MS data and the possible degradation pathways were outlined. Besides, the results obtained from the developed method compared statistically with that of the official method indicting high accuracy and precision.
PubMed: 32195388
DOI: 10.1016/j.heliyon.2020.e03530 -
Critical Care Explorations Jan 2020We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry...
OBJECTIVES
We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.
DESIGN
We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children's Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.
SETTING
PICU of a quaternary, free-standing children's hospital.
PATIENTS
Children admitted to the hospital who received vecuronium and/or esmolol infusion.
MEASUREMENTS AND MAIN RESULTS
Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel-blood gas) sodium within 12 hours of the vecuronium administration ( < 0.0018). Esmolol showed a similar trend ( = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.
CONCLUSIONS
Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.
PubMed: 32166293
DOI: 10.1097/CCE.0000000000000073 -
Antioxidants (Basel, Switzerland) Jan 2020Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we...
Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague-Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA.
PubMed: 31906329
DOI: 10.3390/antiox9010038 -
Journal of Cerebral Blood Flow and... Dec 2020We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical...
We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical vasodilative system derived from the nucleus basalis of Meynert (NBM). In pentobarbital-anesthetized rats, parietal cortical rCBF was recorded simultaneously with electromyogram (EMG) of jaw muscles, local field potentials of frontal cortex, multi-unit activity of NBM neurons, and systemic mean arterial pressure (MAP). When spontaneous rhythmic EMG activity was observed with cortical desynchronization, an increase in NBM activity and a marked rCBF increase independent of MAP changes were observed. A similar rCBF increase was elicited by repetitive electrical stimulation of unilateral cortical masticatory areas. The magnitude of rCBF increase was partially attenuated by administration of the GABAergic agonist muscimol into the NBM. The rCBF increase persisted after immobilization with systemic muscle relaxant (vecuronium). rCBF did not change when jaw muscle activity was induced by electrical stimulation of the pyramidal tract. The results suggest that activation of NBM vasodilator neurons contributes at least in part to the rCBF increase associated with masticatory muscle activity, and that the NBM activation is induced by central commands from the motor cortex, independently of feedback from brainstem central pattern generator or contracting muscles.
Topics: Animals; Arterial Pressure; Basal Nucleus of Meynert; Cerebral Cortex; Cerebrovascular Circulation; Electric Stimulation; Electromyography; Frontal Lobe; GABA-A Receptor Agonists; Male; Masticatory Muscles; Muscimol; Neuromuscular Nondepolarizing Agents; Neurons; Rats; Rats, Wistar; Vasodilation; Vecuronium Bromide
PubMed: 31847668
DOI: 10.1177/0271678X19895244 -
European Journal of Pharmaceutical... Jan 2020Neuromuscular blockers (NMBs) selectively block neuromuscular transmission at the N2-nicotinic receptor on motor neurons to paralyze skeletal muscles, and are mainly... (Randomized Controlled Trial)
Randomized Controlled Trial
Neuromuscular blockers (NMBs) selectively block neuromuscular transmission at the N2-nicotinic receptor on motor neurons to paralyze skeletal muscles, and are mainly used to facilitate tracheal intubation and surgical procedures. Rapid reversal is necessary in clinical practice to avoid profound block and reduce recovery time. Adamgammadex sodium is a modified γ-cyclodextrin derivative consisting of a lipophilic core and a hydrophilic outer end that forms an inactive tight inclusion complex with free molecules of rocuronium and vecuronium. In preclinical study, adamgammadex produced a concentration-dependent reversion effect of neuromuscular blockade induced by rocuronium in beagle dogs. Furthermore, adamgammadex had a less potential side effects than sugammadex and other clinical used neuromuscular block antagonists. In this study, the objective was to assess the safety, tolerability, and pharmacokinetics of single intravenous injection of adamgammadex in healthy volunteers. Approved by the China Food and Drug Administration, 52 healthy volunteers (half male and half female) were enrolled in this single-center, randomized, double-blind placebo-controlled study. No serious adverse effects were happened in this study. The overall frequency of adverse effects in adamgammadex was similar for that in placebo, and there was no specific adverse effect in adamgammadex. All of the volunteers bearing the adverse effects were recovered to normal without any treatment or intervention. In pharmacokinetic study, the value of half-time, T, and clearance were not changed significantly, and the C and AUC increased with a similar ratio of the escalating doses. For dose proportionality analysis of adamgammadex, the estimate of slope was close to 1, and it was not significantly different from 1 after doses (AUC, 0.9965 [90%CI, 0.9468, 1.046]; C, 0.9462 [90%CI, 0.8800, 1.012]). Therefore, adamgammadex exposure in plasma increased in a dose- proportional manner. The urinary route is a significant excretory pathway for adamgammadex, and it is mostly completed at 8 h. All the results in this study showed that adamgammadex may be a novel safe neuromuscular blockade reversal agent .
Topics: Adult; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Neuromuscular Blockade; Rocuronium; Vecuronium Bromide; Young Adult; gamma-Cyclodextrins
PubMed: 31678425
DOI: 10.1016/j.ejps.2019.105134