JUSTIFICATIVA E OBJETIVOS: Bupivacaina e o farmaco de escolha para anestesia regional por causa da eficacia, longa duracao e do bloqueio motor menos intenso. Bupivacaina (S75-R25) e uma mistura de isomeros opticos que contem 75% de levobupivacaina (S-) e 25% de dextrobupivacaina (R+) e foi criada por uma companhia farmaceutica brasileira. Este estudo comparou a eficacia e seguranca de bupivacaina S75-R25 com vasoconstritor e ropivacaina para o sistema cardiovascular em bloqueio do plexo braquial. METODOS: Pacientes foram randomizados para receber bloqueio do plexo braquial com bupivacaina S75-R25 (Grupo B) com epinefrina 1:200.000 ou ropivacaina (Grupo R), ambos os farmacos a 0,50%, em 30 mL ECG continuo (Holter) foi registrado durante todo o procedimento, bem como a escala de forca de Lovett, alem de monitoramento (frequencia cardiaca, oximetria de pulso e pressao arterial nao invasiva). A incidencia de eventos adversos foi comparada com os testes do qui-quadrado ou exato de Fisher. RESULTADOS: Quarenta e quatro pacientes foram estudados. Nao houve diferenca significativa em relacao a idade, peso, altura, genero e tempo cirurgico. Nao houve diferenca entre arritmias supraventriculares antes ou depois do bloqueio do plexo braquial, independentemente do anestesico local escolhido. A perda de sensibilidade foi mais rapida no Grupo B (23,1 ± 11,7 min) em comparacao com o Grupo R (26,8 ± 11,5 min), embora nao significativa (p = 0,205, teste t de Student). Houve uma reducao da frequencia cardiaca, observada durante a monitoracao continua de 24 horas (Holter). CONCLUSAO: Este estudo demonstrou eficacia semelhante entre bupivacaina S75-R25 e ropivacaina para bloqueio do plexo braquial, com incidencias semelhantes de arritmias supraventriculares.

/pdf/estudo-comparativo-entre-bupivacaina-s75-r25-e-ropivacaina-2ullx9tggw.pdf

Estudo comparativo entre bupivacaína (S75-R25) e ropivacaína para avaliar a segurança cardiovascular em bloqueio do plexo braquial

Pharmacotherapy is a key component of anesthesiology and intensive care medicine. The individual genetic profile influences not only the effect of pharmaceuticals but can also completely alter the mode of action. New technologies for genetic screening (e.g. next generation sequencing) and increasing knowledge of molecular pathways foster the disclosure of pharmacogenetic syndromes, which are classified as rare diseases. Taking into account the high genetic variability in humans and over 8000 known rare diseases, up to 20 % of the population may be affected. In summary, rare diseases are not rare. Most pharmacogenetic syndromes lead to a weakening or loss of pharmacological action. In contrast, malignant hyperthermia (MH), which is the most relevant pharmacogenetic syndrome for anesthesia, is characterized by a pharmacologically induced overactivation of calcium metabolism in skeletal muscle. Volatile anesthetic agents and succinylcholine trigger life-threatening hypermetabolic crises. Emergency treatment is based on inhibition of the calcium release channel of the sarcoplasmic reticulum by dantrolene. After an adverse pharmacological event patients must be informed and a clarification consultation must be carried out during which the hereditory character of MH is explained. The patient should be referred to a specialist MH center where a predisposition can be diagnosed by the functional in vitro contracture test from a muscle biopsy. Additional molecular genetic investigations can yield mutations in the genes for calcium-regulating proteins in skeletal muscle, e.g. ryanodine receptor 1 (RyR1) and calcium voltage-gated channel subunit alpha 1S (CACNA1S). Currently, an association to MH has only been shown for 35 mutations out of more than 400 known and probably hundreds of unknown genetic variations. Furthermore, MH predisposition is not excluded by negative mutation screening. For anesthesiological patient safety it is crucial to identify individuals at risk and warn genetic relatives; however, the legal requirements of the Patients Rights Act and the Human Genetic Examination Act must be strictly adhered to. Specific features of insurance and employment law must be respected under consideration of the Human Genetic Examination Act.

[Pharmacogenetics in anesthesia and intensive care medicine : Clinical and legal challenges exemplified by malignant hyperthermia].

Background and objectives Bupivacaine is a first choice for regional anesthesia considering its effectiveness, long duration and less motor blockade Bupivacaine (S75-R25) is a mixture of optical isomers containing 75% levobupivacaine (S-) and 25% dextrobupivacaine (R+) created by a Brazilian pharmaceutical company This investigation compared cardiac safety and efficacy of bupivacaine S75-R25 with vasoconstrictor and ropivacaine for brachial plexus blockade Methods Patients were randomized to receive brachial plexus anesthesia with either bupivacaine S75-R25 with epinephrine 1:200,000 (bupi) or ropivacaine (ropi), both at 050%, in 30 mL solution We registered a continuous Holter ECG throughout the procedure, as well as the Lovett scale of force in addition to monitoring (heart rate, pulse oximetry and non-invasive blood pressure) The incidence of adverse events was compared with the chi-square or Fisher test Results We allocated forty-four patients into two groups They did not show any difference related to age, weight or height, gender, as well as for surgical duration Supraventricular arrhythmias were not different before or after the plexus blockade, independent of the local anesthetic chosen Loss of sensitivity was faster for the bupivacaine group (231 ± 117 min) compared to the ropivacaine one (268 ± 115 min), though not significant (p = 0205, Student t) There was a reduction in the cardiac rate, observed during the twenty-four-hour Holter monitoring Conclusions This study showed similar efficacy between bupivacaine S75-R25 for brachial plexus blockade and ropivacaine, with similar incidences of supraventricular arrhythmias

Comparative study related to cardiovascular safety between bupivacaine (S75-R25) and ropivacaine in brachial plexus block.

Purpose: This study aimed to examine the effect of postoperative addition of a local anesthetic agent to irrigation fluid on the alleviation or prevention of pain after transurethral resection of the prostate (TURP). Patients and Methods: This prospective, double blind, placebo-controlled study included 50 patients aged 50 to 87 years. The patients were randomized into two groups. As each patient began to experience postoperative pain after spinal anesthesia wore off, 30 mL of 2% prilocaine was injected into the irrigation solution bags, and the bladder was irrigated (prilocaine group). The irrigation solution used in the control group was prilocaine-free. Visual analog scale (VAS) scoring was used to assess the severity of pain. Bladder irrigation in all patients was discontinued 1 day postsurgery. Results: There was not a statistical difference in surgical parameters between the two groups. All patients in the prilocaine group were satisfied with the analgesic efficacy of prilocaine, except for...

Prilocaine irrigation for pain relief after transurethral resection of the prostate.

Der Einsatz von Pharmaka ist ein wesentlicher Bestandteil der arztlichen Tatigkeit in Anasthesie und Intensivmedizin. Das individuelle genetische Profil beeinflusst nicht nur die Wirkung von Pharmaka, sondern kann diese komplett verandern. Neue genetische Verfahren („next generation sequencing“) und zunehmendes Wissen uber molekulare Stoffwechselwege decken pharmakogenetische Syndrome auf, die den seltenen Erkrankungen zugeordnet werden. Im Hinblick auf die hohe genetische Variabiltat beim Menschen und bei uber 8000 bekannten seltenen Erkrankungen, kann man davon ausgehen, dass bis 20 % der Bevolkerung betroffen sind. In der Summe sind seltene Erkrankungen nicht selten. Die meisten pharmakogenetischen Syndrome resultieren in einer Abschwachung oder einem Verlust der pharmakologischen Wirkung. Im Gegensatz dazu zeichnet sich die maligne Hyperthermie (MH) – als wichtigstes pharmakogenetisches Syndrom der Anasthesie – durch eine pharmakologisch induzierte Uberaktivierung des skelettmuskularen Kalziumstoffwechsels aus. Volatile Anasthetika und Succinylcholin triggern lebensbedrohliche hypermetabole Krisen. Die Notfalltherapie basiert auf der Inhibition des Kalziumfreisetzungskanals des sarkoplasmatischen Retikulums durch Dantrolen. Im Anschluss muss eine Sicherungsaufklarung durchgefuhrt werden, in welcher auch auf den erblichen Charakter der MH eingegangen wird. Der Patient sollte an ein spezielles MH-Zentrum verwiesen werden. Hier kann die MH-Pradisposition mit dem funktionellen In-vitro-Kontrakturtest an einer Muskelbiopsie diagnostiziert werden. In einer zusatzlichen molekulargenetischen Untersuchung kann sich eine Mutation in den Genen von skelettmuskularen kalziumregulierenden Proteinen (RyR1, CACNA1S) ergeben. Aktuell konnte ein Zusammenhang zur MH allerdings nur fur 35 Mutationen von uber 400 bekannten und vermutlich noch hunderten unbekannten genetischen Veranderungen nachgewiesen werden. Auserdem schliest ein fehlender Mutationsnachweis die Anlage zur MH nicht aus. Fur die anasthesiologische Patientensicherheit ist es unabdingbar, Risikopersonen zu identifizieren und die genetisch Verwandten zu warnen. Hierbei sind die gesetzlichen Vorgaben des Patientenrechtegesetzes sowie des Gendiagnostikgesetzes strikt einzuhalten. Unter Beachtung des Gentechnikgesetztes ergeben sich Besonderheiten bei versicherungs- und arbeitsrechtlichen Fragestellungen.

Pharmakogenetik in Anästhesie und Intensivmedizin

Objective Local anesthetics (LA) are often administered in combination for regional anesthesia in order to obtain the specific advantages (onset and duration of effect) of each drug However, few data on the safety of such combinations are available and consequently plasma concentrations possibly associated with toxicity and interactions between the specific anesthetics are not sufficiently established We measured pharmacokinetics and toxicity parameters of prilocaine and ropivacaine after combined use as single doses in brachial plexus blockade Methods In an open clinical study using a combined dose regime (300 mg prilocaine followed immediately by 75 mg ropivacaine) total plasma concentrations of prilocaine and ropivacaine were measured serially in 60 patients using a gas-chromatographic method The data were analyzed regarding a relationship with central nervous and cardiovascular toxicity Results Following the administration in combination prilocaine and ropivacaine were rapidly absorbed Mean prilocaine peak plasma concentrations (mean Cmax = 151 microg/ml) were measured between 15 and 30 min after injection Highest ropivacaine plasma concentrations (mean Cmax = 112 microg/ml) were seen between 30 min and 1 hour after injection (calculated mean tmax = 44 min) One of 59 patients showed signs of myoclonus which were suspected of being due to intravascular injection There was no relevant cardiovascular toxicity observed in terms of changes in the QRS complex, PQ interval prolongation, AV dissociation, occurrence of extrasystoles or sinus arrest The pharmacokinetics of combined administration did not differ from those of prilocaine and ropivacaine given alone Conclusion The use of a combined prilocaine/ ropivacaine (300 mg/75 mg) dose regimen in patients given single dose for brachial plexus blockade can generally be regarded as safe with regard to peak plasma concentrations and cardiovascular toxicity and this holds true for patients with a higher perioperative risk profile (ASA III grading, American Society of Anesthesiologists) The considerable inter-individual variation in LA peak plasma concentrations observed in our patients and the one case of suspected accidental intravascular injection, highlight the necessity of adequate monitoring of the patients undergoing LA injections

Pharmacokinetics and clinical toxicity of prilocaine and ropivacaine following combined drug administration in brachial plexus anesthesia.

Background Malignant hyperthermia (MH) is an autosomal dominant metabolic myopathy. The in vitro contracture test (IVCT) is still considered to be the gold standard for diagnosing a disposition for MH. However, advances in genetic testing for MH disposition have supplemented or even replaced the invasive procedure of the IVCT. Information about MH can be obtained by either contacting the hotline for MH as a nationwide 24 h/7 days a week service or one of the regional MH centers. Methods The protocols of telephone conversations concerning MH at the MH Center University Leipzig were retrospectively analyzed. Data were collected from January 2011 to March 2015. Additionally, the results of the IVCT and genetic testing evolving from the counseling interviews were examined. Results A total of 205 telephone calls were documented during the period in question and an IVCT was performed as a consequence of 112 of the telephone calls. The IVCT resulted in 27 individuals being identified as MH susceptible which was subsequently diagnosed in 15 individuals with known familial MH disposition and 12 individuals were identified as new index patients. In 24 individuals a total of 13 different mutations were detected and of these 4 mutations were causative concerning MH. Of the 205 telephone calls 131 were private and 74 of medical professional origin. Among the private enquiries MH disposition within the family was a frequent reason for contacting the MH Center (61.8%). Conversations relating to MH-like symptoms during general anesthesia were carried out with 35.1% of medical doctors and with 22.9% of private callers. Advice about neuromuscular symptoms of unknown genesis was given to 15.3% of private individuals and to 24.3% of medical doctors. Overall MH topics were discussed with 23% (N = 17) of the medical profession and approximately half of these were anesthesiologists (N = 8). Not a single call was documented for the treatment of a suspected MH crisis. Conclusion Private individuals and families affected by a MH disposition often showed good compliance with respect to counseling and diagnostics for MH and contacted the MH center more often than medical doctors. A more comprehensive cooperation with the medical profession is preferable and necessary to obtain a systematic and broad synopsis of characteristic and uncharacteristic signs and symptoms of MH. The telephone conversations analyzed as well as the diagnostic results (IVCT and genetic testing) underline that MH disposition is still a current and relevant topic.

[Telephone enquiries on the topic of malignant hyperthermia: Evaluation of the content and subsequent diagnostic results at the MH Center Leipzig].

Hintergrund
Maligne Hyperthermie (MH) ist eine autosomal-dominant vererbbare Myopathie. Standardverfahren zur Diagnosestellung ist der In-vitro-Kontraktur-Test (IVKT), der zunehmend durch genetische Verfahren erganzt oder ersetzt wird. Als Anlaufstellen fur Fragen zur MH, einschlieslich einer nachfolgenden Diagnostik, dienen deutschlandweit die MH-Hotline und die regionalen MH-Zentren.

Telefonische Anfragen zum Thema maligne Hyperthermie

Telefonische Anfragen zum Thema maligne Hyperthermie: Auswertung der Inhalte und der resultierenden Diagnostikergebnisse am MH-Zentrum Leipzig

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Pharmacokinetics and clinical toxicity of prilocaine and ropivacaine following combined drug administration in brachial plexus anesthesia.

[Telephone enquiries on the topic of malignant hyperthermia: Evaluation of the content and subsequent diagnostic results at the MH Center Leipzig].

Telefonische Anfragen zum Thema maligne Hyperthermie

Telefonische Anfragen zum Thema maligne Hyperthermie: Auswertung der Inhalte und der resultierenden Diagnostikergebnisse am MH-Zentrum Leipzig