Dissertations / Theses on the topic 'Succinylcholine'

Refrigerated Stability of Diluted Succinylcholine, Pancuronium, and Atracurium. T. Archibald1, S. Brown1, A. Gonzalez-Estrada2 1College of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN2Quillen College of Medicine, Allergy and Clinical Immunology, East Tennessee State University, Johnson City, TN The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely succinylcholine, pancuronium, and atracurium, for skin prick/intradermal testing. Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Each drug was prepared with an n = 5 for each dilution, using a different newly opened product for each series. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days (day 0, 1, 2, 4, 7, and 14), one milliliter aliquots of each dilution were removed, filtered, and analyzed against freshly prepared set of reference dilutions. The results are expressed as beyond use date (BUD), defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for succinylcholine diluted by 10x and 100x is 48 and 24 hours, respectively. The1000x dilution is also stable for 24 hours.Higher dilutions of succinylcholine (10,000x to100,000x) should be used immediately following preparation (within less than 24 hours), as the potency of these dilutions had decreased below 90% at the 24 hr sampling. .Pancuronium diluted by 10x and 100x, had a BUD of 48 hours, and the1,000x dilution was stable for 24 hours.As with the succinylcholine, the 10,000x and 100,000x dilutions expressed potency of <90% at 24 hours. .Atracurium diluted to 10x had a BUD of 96 hours, the100x dilution is stable for 24 hours yet higher dilutions (1,000x to 10,000x) do not persist beyond 24 hours. . The 100,000x dilution of atracurium was unknown, given than the signal intensity was too weak to monitor by our LC-MS/MS method. With increasing dilution factors, the stability of these drugs in saline decreases, associated with an increasing deviation between samples and freshly prepared references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.

A simple, precise "reaction rate" assay for plasma cholinesterase based on a succiny1choline substrate has been developed. It's ability to define individuals at risk of succiny1choline sensitivity and identify those who had experienced apnoea was superior to the previously best available assay. However it was not able to identify abnormal forms of cholinesterase which could hydrolyze conventional assay substrates but not succinylcholine. It was-concluded that if these forms exist their numbers are small. The failure to identify such cholinesterase types may have been because'the substrate concentration chosen for the assay was higher than that found"pharnacologically. However investigation of the kinetics of the succiny1choline-cholinesterase interaction showed that this was not the case. The assay was applied to the assessment of liver dysfunction and compared to three established methods was superior. All assays identified patients with severe liver disease but the succinylcholine-based one identified more patients with moderate/mild disease. The assay was also used to investigate the clinical observation that children require a higher dose of succiny1choline for muscle relaxation than adults. Infants were found to have higher succiny1choline activities than adults which is compatible with their relative resistance to the drug. Finally cholinesterase measurements were made, using a range of substrates including succinylcholine, in a variety of animal species. Results show that only when succiny1choline is used as the substrate for'the assay of cholinesterase does enzyme activity correlate with tolerance to it's muscle relaxant properties. The choice of procedure for the analysis of any biochemical variable depends on a number of criteria including ease of assay, precision, accuracy and cost; however the primary consideration should be the ability of the method to provide clinically useful information. Based on all these criteria, in particular the latter, succiny1choline must be considered as the substrate of choice.

The drug succinylcholine (SCh) is known to produce contracture in two of the three classes of intrafusal muscle fibre whilst paralysing the third. Since the effects on afferent stretch sensitivity of contraction in each class of intrafusal muscle fibre are known, SCh can be used to assess the pattern of intrafusal termination of afferents studied electrophysiologically. This approach has previously been used to differentiate primary afferents from secondaries when alternative means were not applicable, but the aim of the present experiments has been to extend this work to allow the differentiation of primary afferents from classical spindle encapsulations (which have the full complement of intrafusal muscle fibres) and those from tandem encapsulations which lack a bag₁ fibre which would otherwise be activated by SCh. Three sets of experiments were performed. In the first, afferents from the cat neck extensor muscle biventer cervicis were studied, since this muscle is known to be particularly rich in tandem spindles. Four types of afferent response to intraarterial infusion of SCh were identified, three corresponding to the behaviour previously reported for hindlimb muscle spindle afferents. The fourth had not previously been seen, and showed features which indicated that the afferents activated by SCh in this way were probably the b₂c primary afferents arising in tandem muscle spindles. Other evidence in the form of the passive properties of these afferents was adduced to support this diagnosis. In the second series of experiments using the medial gastrocnemius muscle of the hindlimb, four patterns of SCh activation were again seen for muscle spindle afferents; these were all very similar to the patterns seen for biventer afferents, including that presumed to belong to b₂c primary afferents from tandem spindles. Additional evidence that b₂c primary afferents from tandem muscle spindles had been correctly identifed came from the measurement of their conduction velocities, which indicated that the majority of presumed b₂c primary afferents from tandem muscle spindles had conduction velocities which overlapped with those of slower b₁b₂c primary afferents from classical encapsulations, as was expected on histological grounds. In the final series of experiments, the spindles of origin of afferents from the tenuissimus muscle which had been studied electrophysiologically were located in the muscle, excised and studied histologically in serial transverse sections. Seven afferents were diagnosed by SCh as primaries arising in classical muscle spindles, and the histological reconstruction indicated that their parent spindles indeed contained all three intrafusal muscle fibre types. In contrast, the single afferent diagnosed by SCh and a b₂c primary arising in a tandem muscle spindle was subsequently found to innervate an encapsulation of a tandem spindle containing only two types of intrafusal muscle fibre. The histological evidence thus supports the SCh-based classification of primary afferents, and in particular indicates that b₂c primary afferents from tandem muscle spindles can be readily identified during electrophysiological experiments.

This study was conducted to determine if Mivacurium (Miv) was as effective as Vecuronium (Vec) in attenuating Succinylcholine (Sch)-induced fasciculations with muscle relaxant doses based upon ideal body weight (IBW). A quasi experimental design was used to study 60 patients who were randomly assigned to one of three groups. The two study groups were compared to a control group and each other with regards to the incidence and intensity of fasciculations. Either Vec (0.01 mg/kg (IBW)), Miv (0.02 mg/kg (IBW)), or saline (control) was administered in a double-blinded manner 3 minutes prior an intubating dose of Sch (IBW). Both pretreatment modalities resulted in a significant (p < .05) decrease in the incidence (Vec 40%, Miv 60%) and intensity of fasciculations when compared to saline (90%). No significant differences (p > .05) were found between the two pretreatment groups with regards to the incidence and intensity of fasciculations. It was concluded that Miv 0.02 mg/kg (IBW) attenuated Sch-induced fasciculations with the same efficacy as Vec 0.01 mg/kg (IBW).

Thesis (M.S.) -- Central Connecticut State University, 2008.
Thesis advisor: Ruth Rollin. "... in partial fulfillment of the requirements for the degree of Master of Science in Biological Sciences: Anesthesia." Includes bibliographical references (leaves 73-86). Also available via the World Wide Web.

Succinylcolin är ett icke-depolariserande muskelrelaxantia som används inom anestesisjukvård. En vanlig biverkning är postoperativ myalgi. Varför smärtan uppstår är inte helt klarlagd. Under många år har forskare runt om i världen försökt komma till rätta med problemet utan att helt lyckas.Olika läkemedel och strategier har prövats. En av de viktigaste uppgifter en sjuksköterska har är att förebygga och lindra lidande. Som anestesisjuksköterska finns det möjlighet att påverka den vård som ordineras. Syftet med studien var att undersöka vilka metoder som kan förebygga postoperativ myalgi orsakad av succinylcolin. En litteraturstudie baserad på tio vetenskapliga artiklar genomfördes. Resultatet visade att parecoxib preoperativt samt premedicinering med diklofenakplåster gav det bästa resultatet när det gäller reducerande av myalgi. Med hjälp av dessa så vanliga läkemedel kan onödigt lidande förebyggas och samhällsekonomiska resurser sparas.

 

Sugammadex, a gamma cyclodextrin discovered in 2007, provides a safe and effective alternative to drugs currently used in surgery by anesthesiologists. A problem in the current practice of anesthesia is the use of Succinylcholine, a neuromuscular blocking agent used for the cessation of the patient's skeletal muscle movement. Succinylcholine is used due to its unique fast onset and short duration, ideal for short procedures, difficult intubation scenarios, and rapid sequence intubation. However, it is used cautiously due to several risks such as causing myalgia, hyperkalemia, fasciculations, and increasing intracranial, intragastric, and intraocular pressure. Sugammadex provides a safer alternative to Succinylcholine because it allows immediate reversal of a neuromuscular blockade through a different mechanism, which does not lead to harmful adverse effects. Sugammadex works by encapsulating its target muscle relaxant, Rocuronium. Rocuronium is a relatively safer drug than Succinylcholine with a similar time of onset, but a very long duration of action. Since Sugammadex is able to immediately reverse the effects of Rocuronium, this combination of Rocuronium and Sugammadex provides the same desired effect as Succinylcholine but without the harmful side effects. The current most widely used reversal agent for muscle relaxation is Neostigmine. The problems with Neostigmine are that it can lead to residual paralysis and recurarisation if under dosed. It also produces unwanted cholinergic side effects that lead to cardiovascular instability. Due to this, the medical community is in need for a better reversal agent that can both quickly and completely reverse muscle paralysis without the need to manage unwanted side effects. Sugammadex is able to address both the problems of Succinylcholine and Neostigmine. Studies have shown Sugammadex to provide a faster, safer, and more predictable reversal of Rocuronium - induced neuromuscular blockade than Neostigmine. Sugammadex has shown to also achieve faster recovery from Rocuronium - induced muscle paralysis than the fast spontaneous recovery of Succinylcholine. With no serious adverse effects observed in these studies, the data supports the use of Sugammadex and its potential to replace the current standards of practice with Succinylcholine and Neostigmine. Furthermore, high dosage of Sugammadex has shown to be capable of immediately reversing profound neuromuscular blockades, an ability that no reversal drug currently in the market possesses. This enables the anesthesiologist to provide optimal muscle relaxation for the surgeon throughout the operation without the concern of being unable to reverse the patient in a timely manner. Studies on multiple patient population groups do not show any serious adverse effects are linked to using Sugammadex. There have been incidences of drug induced QTc prolongation in cardiac patients, but its cause was not determined to be related solely with Sugammadex. Sugammadex has shown to be the safer reversal agent compared to Neostigmine in cardiac, pulmonary, and renal patients. One problem that prevents the routine use of Sugammadex is its cost. The cost is significantly higher than Neostigmine. This cost is justified, however, due to staff costs saved from a faster patient recovery and shorter stay in the hospital. Therefore, while Sugammadex is definitely warranted over Succinylcholine due to its safety profile, its use over Neostigmine is dependent on each healthcare facility. While Sugammadex is currently under review by the Food and Drug Administration, it will evolve the practice of anesthesia if allowed into the United States market.

Die Maligne Hyperthermie (MH) ist eine autosomal dominant vererbte latente metabolische Myopathie, die durch Exposition mit volatilen Anästhetika oder depolarisierenden Muskelrelaxantien vom Succinylcholin-Typ in disponierten Individuen zu einem potentiell lebensbedrohlichen hypermetabolen Syndrom der Skelettmuskulatur führen kann. Der Pathomechanismus basiert auf einer unkontrollierten sarkoplasmatischen Kalziumfreisetzung über funktionell veränderte Ryanodin- (RYR1) oder Dihydropyridinrezeptoren (DHPR) und resultiert in einer stark erhöhten Stoffwechselreaktion der Zelle. Die klinische Symptomatik umfasst Anstieg des Kohlendioxidpartialdrucks und der Körperkerntemperatur, sowie Tachykardie, Laktatazidose und erhöhte Muskelrigidität. Der Goldstandard für die Diagnostik einer MH-Veranlagung ist der Koffein-Halothan-In-vitro-Kontrakturtest (IVCT). Volatile Anästhetika sind unbestritten in der Lage eine MH-Krise auszulösen, während die Rolle von Succinylcholin bis heute kontrovers diskutiert wird. In dieser Studie wurde der Einfluß von Succinylcholin in der Entstehung einer MH-Krise an MH-veranlagten (MHS) und MH-nichtveranlagten (MHN) Schweinen untersucht. Es wurden die hämodynamischen und metabolischen Veränderungen nach Gabe von Succinylcholin, Halothan oder beider Substanzen analysiert. Hierfür wurden nach Zustimmung der lokalen Ethikkommission 27 MHS und 30 MHN Tiere narkotisiert und beatmet. Nach Narkoseeinleitung wurden CO2- Messsonden in der V. femoralis und dem M. triceps brachii platziert. Die Tiere wurden in 3 Versuchsgruppen unterteilt: Gruppe A erhielt Succinylcholin intravenös in einer Dosierung von 4mg/kg, Gruppe B Halothan in steigender Konzentration (0,5, 1.0 Vol%) und Gruppe C Succinylcholin und Halothan in Kombination. Die Vitalwerte wurden kontinuierlich überwacht. Vor Zugabe der Triggersubstanzen waren die Vitalwerte zwischen den MHS und MHN Tieren vergleichbar. In der Gruppe der MHN Tiere zeigten sich keine relevanten Änderungen der hämodynamischen und metabolischen Parameter. Succinylcholin oder Halothan induzierten signifikante metabolische und hämodynamische Veränderungen in den MHS Schweinen. In der Gruppe der MHS Tiere, die beide Substanzen in Kombination erhielten wurden diese Effekte noch potenziert. In dieser Studie konnte nachgewiesen werden, dass Succinylcholin als alleiniger Trigger eine MH auslösen kann. Im zweiten Teil der vorliegenden Arbeit wurden die Daten von 1124 Patienten, die sich aufgrund eines MH-verdächtigen Narkosezwischenfalls an der MH-Ambulanz in Würzburg zwischen 1974 und 2012 vorstellten und mittels eines IVCT untersucht wurden retrospektiv untersucht. In die Studie wurden 198 Patienten eingeschlossen. Der intraoperative Verlauf wurde anhand von Narkoseprotokollen rekonstruiert. 60 Patienten wurden als MHS, 18 als MHSh (muskuläre Kontrakturentwicklung nur nach Halothan Exposition), 3 als MHSc (muskuläre Kontrakturentwicklung nur nach Koffein Exposition) und 117 als MHN klassifiziert. Succinylcholin wurden zur Narkoseführung in 90% aller MHS Patienten und 89% aller MHN Patienten verwendet. Succinylcholin wurde in 21% der MHS Patienten als einziger MH-Trigger eingesetzt. Ausschließlich volatile Anästhetika kamen in 10% der MHS Patienten zum Einsatz. In einem Großteil der MHS und MHN-Fälle fiel nach Gabe von Succinylcholin ein Masseterspasmus auf. Herzrhythmusstörungen und erhöhte CO2 Werte waren ebenfalls häufig zu beobachten. Dantrolen wurde nur in wenigen Fällen appliziert. Zusammenfassung: Succinylcholin konnte in unserer Studie eine MH als alleiniger Trigger auszulösen. Die Kombination von Halothan und Succinylcholin verstärkt die hämodynamischen und metabolischen Veränderungen im Verlauf einer MH deutlich. Neuere Inhalationsanästhetika sind zwar weniger potent als Halothan, können aber ebenfalls eine MH auslösen. Die MH ist somit auch heute noch eine ernst zu nehmende Komplikation in der Anästhesie, die zum Tode des Patienten führen kann. Jeder Anästhesist und Intensivmediziner muss in der Lage sein dieses Krankheitsbild zu erkennen und zu therapieren. Bei Anwendung von MH-Triggersubstanzen in der Narkoseführung muss Dantrolen als Mittel der Wahl für eine Therapie zur Verfügung stehen
Malignant hyperthermia (MH) is an autosomal dominant potentially lethal metabolic myopathie, which develops in predisposed individuals after exposure to trigger substances: depolarizing neuromuscular blocking agents and volatile anesthetics. In skeletal muscles of MH susceptible (MHS) individuals, mutated ryanodine receptors (RYR1) or dihydropyridin receptors (DHPR) lead to a massive intracellular Ca2+-release with an enhanced mitochondrial energy consumption. Besides an overwhelming production of carbon dioxide, clinical signs of MH include heat production, tachykardia, lactat acidosis and an increase of muscle rigidity. The standard procedure for diagnosing MH-susceptibility is the halothane-caffeine-contracture test (IVCT), which requires an invasive muscle biopsy. The impact of volatile anaesthetics to induce MH is abundantly clear, while the role of succinylcholine still remains controversial. To evaluate the influence of succinylcholine on porcine MH events, the hemodynamic and metabolic responses in MH susceptible (MHS) and non-susceptible (MHN) swine following either succinylcholine or halothane application alone or a combination of both substances were analyzed. 27 MHS and 30 MHN pigs were anaesthetized and mechanically ventilated after the approval of the local animal care committee. Fiberoptic probes for continuous pCO2 -measurement were inserted into the femoral vein and the triceps muscle. Group A received succinylcholine 4 mg/kg, group B incremental doses of halothane (0.5, 1.0, 2.0 vol%) and group C succinylcholine and halothane simultaneously. Vital signs were recorded continuously. Prior to drug application measured values did not differ between MHS and MHN. Succinylcholine and halothane lead to significant hemodynamic and metabolic changes in MHS swine. The combination of both pharmacological agents potentiated the observed effects. Consequently succinylcholine acted as an independent and supportive factor during onset of an MH episode. In the second part of the study, patients data of a suspected MH episodes during general anesthesia were analyzed, referred to the Wuerzburg MH unit between 1974 and 2012. Only patients with a suspected MH episode during general anesthesia and patients who underwent an IVCT were included in the investigation. The incidents were evaluated retrospectively using anesthetic documentation and medical records. Between 1974 and 2012 a total of 198 patients were tested. 60 patients were diagnosed MH-susceptible, 18 MHSh (pathological muscle contracture only after halothane exposure), 3 MHSc (pathological muscle contracture only after coffein exposure) and 117 MH-non-susceptible by IVCT. 90% of the MHS patients and 89% of the MHN patients unterwent a general anaesthesia with the use of succinylcholin. 21% of the MHS patients received only succinylcholine and in 10% of the MHS patients only volatile anaesthetics were applied. In the majority of the cases masseter spasm after succinylcholine had been the primary symptom. Cardiac arrhythmias and hypercapnia frequently occurred in the early course of the events. Interestingly, dantrolene treatment was initiated in a few cases only. Conclusion: Succinylcholine was able to induce an MH crisis in our study as a sole trigger. The combination of succinylcholine and a volatile anaesthetic amplified the hemodynamic and metabolic changes. Modern inhalation anesthetics are less potent trigger substances, but were also able to induce a fulminant MH. MH is still an important anesthetic complication. Every anesthesist must be aware of this life-threatening syndrome at any time. Dantrolene must be readily available wherever MH triggering agents are used for anesthesia