Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study

Abstract Introduction Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. Objective To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. Methods We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). Results Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). Conclusions Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Fatigue, depression, and physical activity in patients with malignant hyperthermia: a cross-sectional observational study

Abstract Background Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. Objective The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. Methods A cross-sectional observational study was carried out with three groups - 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). Results There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9 ± 1.9 vs. 3.9 ± 2, t-test unpaired, p< 0.05). Conclusion We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.

Anesthesia for muscle biopsy to test susceptibility to malignant hyperthermia / Anestesia durante biópsia muscular para teste de suscetibilidade à hipertermia maligna

Abstract Introduction Malignant hyperthermia is an autosomal dominant pharmacogenetic disorder, characterized by hypermetabolic crisis triggered by halogenated anesthetics and/or succinylcholine. The standard method for diagnosing malignant hyperthermia susceptibility is the in vitro muscle contracture test in response to halothane-caffeine, which requires muscle biopsy under anesthesia. We describe a series of anesthetic procedures without triggering agents in malignant hyperthermia, comparing peripheral nerve block and subarachnoid anesthesia. Method We assessed the anesthetic record charts of 69 patients suspected of malignant hyperthermia susceptibility who underwent muscle biopsy for in vitro muscle contracture in the period of 7 years. Demographic data, indication for malignant hyperthermia investigation, in vitro muscle contracture test results, and surgery/anesthesia/recovery data were analyzed. Results Sample with 34 ± 13.7 years, 60.9% women, 65.2% of in vitro muscle contracture test positive. Techniques used: peripheral nerve blocks — lateral femoral and femoral cutaneous, latency 65 ± 41 min — (47.8%); subarachnoid anesthesia (49.3%), and total venous anesthesia (1.4%). There was 39.4% failure of peripheral nerve block and 11.8% of subarachnoid anesthesia. Adverse events (8.7%) occurred only with subarachnoid blockade (bradycardia, nausea, and transient neurological syndrome). All patients remained in the post-anesthesia care unit until discharge. Age and weight were significantly higher in patients with blockade failure (ROC cut-off point of 23.5 years and 59.5 kg) and blockade failure was more frequent in the presence of increased idiopathic creatine kinase. Conclusion Anesthesia with non-triggering agents has been shown to be safe in patients with malignant hyperthermia susceptibility. Variables such as age, weight, and history of increased idiopathic creatine kinase may be useful in selecting the anesthetic technique for this group of patients.

Resumo Introdução Hipertermia maligna é uma doença farmacogenética autossômica dominante, caracterizada por crise hipermetabólica desencadeada por anestésicos halogenados e/ou succinilcolina. O padrão para diagnóstico da suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano-cafeína, para o qual é necessária biopsia muscular sob anestesia. Descrevemos uma série de anestesias sem agentes desencadeantes na hipertermia maligna e comparamos bloqueios de nervo periférico e anestesias subaracnóideas. Método Foram analisados os prontuários/fichas anestésicas de 69 pacientes suspeitos de susceptibilidade à hipertermia maligna, submetidos à biópsia muscular para teste de contratura muscular in vitro durante sete anos. Analisamos dados demográficos, indicação para investigação de hipertermia maligna, resultado do teste de contratura muscular in vitro e dados da cirurgia/anestesia/recuperação. Resultados Amostra com 34 ± 13,7 anos, 60,9% mulheres, 65,2% de teste de contratura muscular in vitro positivos. Técnicas empregadas: 47,8% bloqueios de nervo periférico (femoral e cutâneo femoral lateral, latência 65 ± 41 minutos), 49,3% anestesias subaracnóideas e 1,4% anestesia venosa total. Falha em 39,4% dos bloqueios de nervo periférico e 11,8% das anestesias subaracnóideas. Eventos adversos (8,7%) como bradicardia, náuseas e síndrome neurológica transitória só ocorreram com bloqueio subaracnóideo. Todos os pacientes permaneceram na sala de recuperação pós-anestésica até liberação. Idade e peso foram significativamente maiores nos pacientes com falha no bloqueio (ponto de corte da curva ROC de 23,5 anos e 59,5 Kg) e esta foi mais frequente na presença de aumento idiopático de creatinoquinase. Conclusão Anestesia com agentes não desencadeantes mostrou-se segura em pacientes suscetíveis à hipertermia maligna. Variáveis como idade, peso e antecedente de aumento idiopático de creatinoquinase podem ser úteis para selecionar a técnica anestésica nesse grupo.

Profile of malignant hyperthermia susceptibility reports confirmed with muscular contracture test in Brazil / Perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular no Brasil

Abstract Background and objectives: Malignant hyperthermia is an autosomal dominant hypermetabolic pharmacogenetic syndrome, with a mortality rate of 10%-20%, which is triggered by the use of halogenated inhaled anesthetics or muscle relaxant succinylcholine. The gold standard for suspected susceptibility to malignant hyperthermia is the in vitro muscle contracture test in response to halothane and caffeine. The determination of susceptibility in suspected families allows the planning of safe anesthesia without triggering agents for patients with known susceptibility to malignant hyperthermia by positive in vitro muscle contracture test. Moreover, the patient whose suspicion of malignant hyperthermia was excluded by the in vitro negative muscle contracture test may undergo standard anesthesia. Susceptibility to malignant hyperthermia has a variable manifestation ranging from an asymptomatic subject presenting a crisis of malignant hyperthermia during anesthesia with triggering agents to a patient with atrophy and muscle weakness due to central core myopathy. The aim of this study is to analyze the profile of reports of susceptibility to malignant hyperthermia confirmed with in vitro muscle contracture test. Method: Analysis of the medical records of patients with personal/family suspicion of malignant hyperthermia investigated with in vitro muscle contracture test, after given written informed consent, between 1997 and 2010. Results: Of the 50 events that motivated the suspicion of malignant hyperthermia and family investigation (sample aged 27 ± 18 years, 52% men, 76% white), 64% were investigated for an anesthetic malignant hyperthermia crisis, with mortality rate of 25%. The most common signs of a malignant hyperthermia crisis were hyperthermia, tachycardia, and muscle stiffness. Susceptibility to malignant hyperthermia was confirmed in 79.4% of the 92 relatives investigated with the in vitro muscle contracture test. Conclusion: The crises of malignant hyperthermia resembled those described in other countries, but with frequency lower than that estimated in the country.

Resumo Justificativa e objetivo: Hipertermia maligna é uma síndrome farmacogenética hipermetabólica, autossômica dominante, com mortalidade entre 10%-20%, desencadeada por uso de anestésico inalatório halogenado ou relaxante muscular succinilcolina. O padrão-ouro para pesquisa de suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano e à cafeína. A determinação da suscetibilidade nas famílias suspeitas permite planejar anestesias seguras sem agentes desencadeantes para os pacientes confirmados como suscetíveis à hipertermia maligna pelo teste de contratura muscular in vitro positivo. Além disso, o paciente no qual a suspeita de hipertermia maligna foi excluída pelo teste de contratura muscular in vitro negativo pode ser anestesiado de forma convencional. Suscetibilidade à hipertermia maligna tem manifestação variável, desde indivíduo assintomático que apresenta crise de hipertermia maligna durante anestesia com agentes desencadeantes, até paciente com atrofia e fraqueza muscular por miopatia central core disease. O objetivo deste trabalho é analisar o perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular in vitro. Método: Análise das fichas de notificação dos pacientes com suspeita pessoal/familiar de hipertermia maligna investigados com teste de contratura muscular in vitro, após assinatura do termo de consentimento, entre 1997-2010. Resultados: Dos 50 eventos que motivaram a suspeita de hipertermia maligna e a investigação familiar (amostra com 27 ± 18 anos, 52% homens, 76% brancos), 64% foram investigados por crise de hipertermia maligna anestésica, com mortalidade de 25%. Sinais mais comuns da crise de hipertermia maligna foram hipertermia, taquicardia e rigidez muscular. Suscetibilidade à hipertermia maligna foi confirmada em 79,4% dos 92 parentes investigados com teste de contratura muscular in vitro. Conclusão: Crises de hipertermia maligna assemelharam-se às descritas em outros países, porém com frequência inferior à estimada no país.

Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy / Reação atípica à anestesia em distrofia muscular de Duchenne/Becker

Abstract Background and objectives Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Case report Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040 IU.L-1 (normal 174 IU.L-1). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. Conclusion On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia.

Resumo Justificativa/objetivos Distrofia muscular de Duchenne/Becker afeta a musculatura esquelética e leva a fraqueza muscular progressiva e risco de reações atípicas anestésicas após exposição à succinilcolina ou halogenados. O objetivo do presente relato é descrever investigação e diagnóstico de paciente com distrofia muscular de Becker e revisar os cuidados necessários na anestesia. Relato de caso Paciente masculino, 14 anos, encaminhado por hiperCKemia (aumento crônico dos níveis séricos de creatinoquinase - CK), com valores de CK de 7.779-29.040 UI.L-1 (normal 174 UI.L-1). Apresentou discreto atraso da aquisição de marcos motores (sentou aos nove meses, andou aos 18). Antecedente de transplante hepático. No exame neurológico apresentava dificuldade para andar nos calcanhares, levantar miopático (apoiava mãos nas coxas para ficar de pé), palato arqueado alto, hipertrofia de panturrilhas, escápulas aladas, hipotonia muscular global e arreflexia. Havia insuficiência respiratória restritiva leve na espirometria (capacidade vital forçada: 77% do previsto). O teste de contratura muscular in vitro em resposta ao halotano e à cafeína foi normal. Estudo da distrofina muscular por técnica de Western blot mostrou redução da distrofina (20% do normal) para ambos os anticorpos (C e N-terminal), e permitiu o diagnóstico de distrofia muscular de Becker. Conclusão Na avaliação pré-anestésica, história de atraso do desenvolvimento motor, bem como sinais clínicos e/ou laboratoriais de miopatia, deve motivar avaliação neurológica, com o objetivo de diagnosticar miopatias subclínicas e planejar cuidados necessários para prevenir complicações anestésicas. Distrofia muscular de Duchenne/Becker, apesar de não conferir suscetibilidade aumentada à HM, pode levar a reações atípicas fatais na anestesia.

The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia

Ampicillin, a beta-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G signifi cantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

Tiopental altera a resposta nociceptiva de ratos jovens em longo prazo / Thiopental alters long term nociceptive response of young rats

The objective of this study was to evaluate the long term nociceptive response determined by use of two general anesthetics, one intravenous and the other inhalatory, in young animals. In the first experiment, the animals of 21 days of age were divided into control (saline) and thiopental (35 mg/kg, i.p.) groups. In the second experiment, rats of the same age were divided in two groups ­ halothane (2%) and control. In experiment 1, there was difference between groups ­ reduction of tail-flick latency in the group thiopental (P< 0.05). In experiment 2, there were no differences between groups or interaction between time versus group (F(1,19)=0.11 for groups, P>0.05; F(1,19)=0.032 for the interaction, P>0.05). The results obtained in this study showed that halothane did not alter the nociceptive response in young animals. However, the thiopental induced hyperalgesic response in rats. (AU)

O objetivo desse estudo foi avaliar a resposta nociceptiva a longo prazo relacionada ao uso de dois anestésicos gerais ­ um intravenoso e outro inalatório, em animais jovens. No primeiro experimento, os animais de 21 dias de idade foram divididos nos grupos controle (solução salina) e tiopental sódico (35 mg/kg, i.p.). No segundo experimento, animais de mesma idade foram divididos em dois grupos ­ halotano (2%) e controle. No Experimento 1, houve redução da latência de retirada da cauda no grupo tiopental (P<0,05). No Experimento 2, não houve diferença entre os grupos ou interação entre grupo x tempo (F(1,19)=0,11 para grupos, P>0,05; F(1,19)=0,032 para a interação, P>0,05). Os resultados obtidos nesse estudo demonstraram que o halotano não altera a resposta nociceptiva em animais jovens. Entretanto, o tiopental induziu resposta hiperalgésica nestes ratos.(AU)

Juan César García: social medicine as project and endeavor / Juan César García: a medicina social como projeto e realização

This paper analyses some aspects of the trajectory of the Argentinian physician and sociologist Juan César García (1932-1984) in the field of Latin American Social Medicine. Three dimensions constituting his basic orientations are highlighted: the elaboration of systematic and reflective social thought; a critical attitude in questioning teaching and professional practices; a commitment to the institutionalization and dissemination of health knowledge.

O artigo analisa aspectos da trajetória de Juan César García (1932-1984), médico e sociólogo argentino, no campo da medicina social latino-americana. Destaca três dimensões que constituem as suas orientações básicas no campo da saúde: a elaboração de um pensamento sobre o social, sistemático e reflexivo; uma atitude crítica na problematização do ensino e das práticas profissionais; um compromisso com a institucionalização e divulgação do saber sanitário.

Sevoflurane Output in the Isoflurane/Halothane Diamedica Draw-over Vaporiser

<p><b>INTRODUCTION</b>Draw-over anaesthesia remains an attractive option for conduct of anaesthesia in austere conditions. The Diamedica Draw-over Vaporiser (DDV) is a modern draw-over vaporiser and has separate models for isoflurane/halothane and sevoflurane.</p><p><b>MATERIALS AND METHODS</b>A laboratory study was done to measure sevoflurane output in an isoflurane/ halothane DDV. We did 3 series of experiments with the isoflurane/halothane DDV. We measured anaesthetic agent output in both push-over and draw-over setups, and at minute ventilation of 6 L/min and 3 L/min. Series 1 experiment was done with isoflurane in the DDV at ambient temperature of 20°C. Series 2 experiment was done with sevoflurane in the DDV at ambient temperature of 20°C. Series 3 experiment was done with sevoflurane in the DDV and with the DDV placed in a water bath of 40°C.</p><p><b>RESULTS</b>The sevoflurane output was found to be two-thirds of the isoflurane/ halothane DDV dial setting at ambient temperature of 20°C. With the DDV in a 40°C water bath, the sevoflurane output was found to be about the isoflurane/ halothane DDV dial settings.</p><p><b>CONCLUSION</b>In our experiment, we show that it is possible to use sevoflurane in an isoflurane/halothane DDV.</p>

Hemodynamic and antiarrhythmic effects of lidocaine or amiodarone in dogs anesthetized with halothane / Efeitos hemodinâmicos e antiarrítmicos da lidocaína ou amiodarona em cães anestesiados com halotano

The effects of continuous rate infusion of lidocaine or amiodarone on hemodynamic and arrhythmias induced by epinephrine in dogs anesthetized with halothane were evaluated. Thirty dogs were distributed into three groups: amiodarone group (AG), lidocaine group (LG), or control group (CG). Anesthesia was induced with etomidate and maintained with halothane. Thirty minutes later a bolus and continuous rate infusion (CRI) of amiodarone in AG, lidocaine in LG and NaCl at 0.9% in CG was administered. After 10 minutes, arrhythmias were induced by epinephrine CRI at 0.0001mg/kg/minute, which was increased in 0.0001mg/kg/minute every ten minutes, until 0.0003mg/kg/minute. The measurements were performed 30 minutes after the induction of anesthesia (T0), 10 minutes after beginning the drug CRIs (T1), 10 minutes after beginning epinephrine administration (T2) and 10 minutes after increasing epinephrine CRI (T3 and T4). In CG, at T3 heart rate (HR) was greater than in LG, while at T4, HR in GC was higher than in LG and AG. In LG and CG, from T2, central venous pressure (CVP), cardiac index (CI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), mean pulmonary arterial pressure (mPAP) increased. In AG, SAP, DAP and MAP it decreased from T1 to T3. The ventricular ectopic beats (VEB) were lower in AG. Amiodarone has better antiarrhythmogenic effects, although it was also associated with hypotension.

Avaliaram-se os efeitos da infusão contínua de lidocaína ou amiodarona sobre a hemodinâmica e as arritmias induzidas pela epinefrina em cães anestesiados com halotano. Trinta animais foram distribuídos em três grupos: grupo amiodarona (GA), grupo lidocaína (GL) ou grupo-controle (GC). A anestesia foi induzida com etomidato e mantida com halotano. Trinta minutos após, foram administrados bolus e infusão contínua (CRI) de amiodarona no GA, de lidocaína no GL e de NaCl a 0,9% no GC. Após 10 minutos, iniciou-se a CRI de epinefrina (0,0001mg/kg/minuto), aumentando-se 0,0001mg/kg/minuto a cada 10 minutos até 0,0003mg/kg/minuto. As mensurações foram realizadas 30 minutos após a indução anestésica (T0), 10 minutos após a CRI dos fármacos (T1), 10 minutos após a administração de epinefrina (T2) e a cada 10 minutos após o incremento na CRI de epinefrina (T3 e T4). A frequência cardíaca (FC) foi maior no GC que no GL em T3 e maior em GC que nos demais grupos em T4. A partir de T2, houve aumento na pressão venosa central (PVC), no índice cardíaco (IC), nas pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e na pressão média da artéria pulmonar (PAPm) no GL e no GC. No GA, PAS, PAD e PAM diminuíram de T1 a T3. Os batimentos ventriculares ectópicos (BVE) foram menores no GA. Amiodarona possui melhores efeitos antiarrítmicos, apesar de também estar associada com hipotensão.

Endotracheal intubation in children undergoing cleft lip surgery. A comparative study between propofol and halothane

Endotracheal intubation is one of important step during the administration of general anesthesia. It is more so in pediatric patients with associated deformities like cleft lip and palate. Propofol, with its profound depressant effect on the airway reflexes, has a quick and smoother induction. Similarly, halothane is least expensive volatile anesthetic, sweaty to inhale and because of its safety profile. The intubating conditions with the use of intravenous propofol is superior to inhalational halothane with oxygen for tracheal intubation without muscle relaxants in children who undergo cleft lip surgery. In this prospective randomized study, 50 ASA I patients who where aged three to nine months, who were scheduled for cleft lips surgeries were included. Both group received halothane 3% by face mask with monitors attached [pulse oximeter, ECG, NIBP]. I.V line inserted, first group[propofol group] once patients become sleepy and respiration became regular and stop movement they received 2mg/kg propofol and E.T.T attempt within 0ne min.2nd group inhalational[halothane Group] until pupil been central and constricted and E.T.T attempted within 5 min. The intubation conditions were assessed by using Steyn's modification of the Helbo - Hansen intubating conditions score. The intubating conditions were better in group A than in group B. The group A patients [88%] significantly had more clinically acceptable intubating conditions than in group B[52%], [p=0.0015]. The intubating conditions with the use of intravenous propofol 2mg/kg is superior to inhalational 3% halothane with oxygen for tracheal intubation without muscle relaxants in children who undergo cleft lip surgery

[Comparison of hepatic enzymes level between operating room's staff and other wards' personnel]

Long exposure to inhalant anesthetic gases especially halothane, among the known hepatotoxic agents, is a serious health risk for the staff of operating room. Current study was performed to compare the level of hepatic enzymes between Operating's room staff and other therapeutic wards' personnel out of the operating room. A total of 100 personnel from educational hospitals were included and their demographic and occupational information were recorded. Hepatic function tests and bilirubin were analyzed. In cases with values more than normal, in order to rule out hepatitis B and C, Hbs-Ag, Hbs-Ab and HCV-Ab were tested. Demographic information and employment span were comparable in two groups. The average of ALT, AST were significantly higher among operating room's staff in comparison with the other group [P<0.05] and there was no significant difference between the average of GGT and ALP between two groups [P>0.05]. ALT, AST and GGT indicated significantly increase with the age of personnel [more than 40 years] and increase in employment period [more than 15 years]. The operating room's staff in educational hospitals of Ardabil may be exposed to hepatotoxic agents that caused significant rise in hepatic enzymes

O efeito dos anestésicos inalatórios halotano e sevoflurano em um modelo experimental de lesão hepática / Effects of the inhalational anesthetics halothane and sevoflurane on an experimental model of hepatic injury

JUSTIFICATIVA E OBJETIVOS: A lesão hepática pós-anestesia inalatória ainda é controversa. Estudos sugerem que agentes inalatórios geram uma resposta imune que pode provocar lesões hepáticas. O objetivo deste estudo é analisar o efeito dos anestésicos inalatórios halotano e sevoflurano no fígado de ratos submetidos à hipóxia e à reperfusão. MÉTODO: Foram utilizados 30 ratos Wistar pré-tratados com fenobarbital 0,1 por cento por cinco dias, com suspensão da medicação 24 horas antes do experimento, a fim de provocar a lesão hepática. Os animais foram distribuídos em cinco grupos com seis ratos cada. O Grupo C foi o de controle, sem qualquer tipo de tratamento; o Grupo F foi aquele no qual se induziu lesão hepática com fenobarbital; o Grupo Hipóxia foi exposto a 14 por cento de oxigênio (O2); o Grupo H recebeu halotano 1 por cento e 14 por cento de O2; e o Grupo S recebeu sevoflurano 2 por cento e 14 por cento de O2. Contadas 24 horas após a exposição dos gases, realizaram-se coletas de sangue para avaliação de transaminases (AST e ALT) e de amostras de fígado para avaliação histológica. Foram usados os testes de Análise de Variância não paramétrica de Kruskal-Wallis e, para comparação de médias, os testes de Newman-Keuls. RESULTADOS: A atividade enzimática revelou que os valores de média amostral de AST (280,33 para halotano, 181 para sevoflurano) e ALT (235 para halotano e 48,33 para sevoflurano) não indicaram diferença estatística significativa; os grupos testados apresentaram valores elevados. O sevoflurano, quando comparado com o halotano à microscopia óptica, apresentou índices menores de alteração morfológica, com p = 0,045 para esteatose, p = 0,0075 para infiltrado inflamatório e p = 0,0074 para necrose. CONCLUSÕES: O Grupo sevoflurano, quando comparado ao Grupo halotano, não apresentou lesão no parênquima hepático quando avaliado por microscopia óptica.

BACKGROUND AND OBJECTIVES: Hepatic injury after inhalational anesthesia is controversial. Studies have suggested that inhalational agents generate an immune response that can provoke hepatic injury. The objective of this study was to analyze the effects of the inhalational agents halothane and sevoflurane on the liver of rats submitted to hypoxia and reperfusion. METHODS: Thirty Wistar rats, pretreated with 0.1 percent phenobarbital for 5 days, with discontinuation of the drug 24 hours before the experiment to cause hepatic injury, were used. Animals were distributed in five groups of six rats each. The control group (C) did not receive any treatment; in the F group, phenobarbital was used to induce hepatic injury; the Hypoxia group was submitted to 14 percent oxygen (O2); the H group received 1 percent halothane and 14 percent O2; and the S group received 2 percent sevoflurane and 14 percent O2. Twenty-four hours after exposure to the gases, blood samples were collected to evaluate transaminases (AST and ALT), and liver samples were collected for histological evaluation. Kruskal-Wallis Analysis of Variance and the Newman-Keuls test were used. RESULTS: Enzymatic activity mean values of AST (280.33, for halothane, 181, for sevoflurane) and ALT (235 for halothane, and 48.33, for sevoflurane) did not show significant differences, and all groups showed elevated values. Compared to halothane on optical microscopy, sevoflurane had lower indices of morphologic changes with p = 0.045, for steatosis, p = 0.0075, for inflammatory infiltrate, and p = 0.0074, for necrosis. CONCLUSIONS: Compared to the halothane group, sevoflurane did not show injuries of the liver parenchyma on optical microscopy.

JUSTIFICATIVA Y OBJETIVOS: La lesión hepática postanestesia inhalatoria todavía es algo controversial. Algunos estudios sugieren que los agentes inhalatorios generan una respuesta inmune que puede provocar lesiones hepáticas. El objetivo de este estudio fue analizar el efecto de los anestésicos inhalatorios halotano y sevoflurano en el hígado de ratones que fueron sometidos a la hipoxia y a la reperfusión. MÉTODO: Fueron utilizados 30 ratones Wistar tratados previamente con fenobarbital al 0,1 por ciento durante cinco días, con suspensión de la medicación 24 horas antes del experimento para provocar la lesión hepática. Los animales fueron distribuidos en cinco grupos con seis ratones cada uno. El grupo C fue el de control, sin ningún tipo de tratamiento; el grupo F fue aquel en el cual se indujo la lesión hepática con fenobarbital; el grupo Hipoxia se expuso a un 14 por ciento de oxígeno (O2); el grupo H recibió halotano al 1 por ciento y al 14 por ciento de O2; y el grupo S recibió sevoflurano al 2 por ciento y al 14 por ciento de O2. Contadas 24 horas después de la exposición de los gases, se realizó la recolección de sangre para la evaluación de las transaminasas (AST y ALT), y de las muestras de hígado para la evaluación histológica. Fueron usados los test de Análisis de Variancia no paramétrica de Kruskal-Wallis, y para la comparación de los promedios se usaron los test de Newman-Keuls. RESULTADOS: La actividad enzimática arrojó valores de promedio de muestra de AST (280,33 para halotano, 181 para sevoflurano y ALT 235 para halotano y 48,33 para sevoflurano), que no indicaron diferencia estadística significativa: los grupos testados presentaron valores elevados. El sevoflurano, cuando fue comparado con el halotano a la microscopía óptica, presentó índices menores de alteración morfológica, con p = 0,045 para esteatosis, p = 0,0075 para infiltrado inflamatorio y p = 0,0074 para necrosis. CONCLUSIONES: El grupo sevoflurano, cuando se comparó con el grupo h...

Recuperação anestésica e efeitos hemodinâmicos da infusão contínua de tiopental versus halotano na manutenção da anestesia em pacientes submetidos à cirurgia ocular / Anesthetic recovery and hemodynamic effects of continuous thiopental infusion versus halothane for maintenance anesthesia in patients undergoing ocular surgery

PURPOSE: To investigate anesthesia recovery and hemodynamic status in patients under thiopental infusion or halothane maintenance anesthesia undergoing ocular surgery. METHODS: Fifty-nine voluntary patients undergoing ocular surgery in Farabi hospital were allocated to one of two maintenance anesthesia groups: inhaled halothane, 0.8 to 1 per cent, (group I, n=37) and thiopental infusion, 10 to 12 mg/kg/hour, (group II, n=22). Hemodynamic parameters were recorded at the time of patient entrance to the operation room and at the 1, 2, 5, 10, 15, 20, 25, 30, 35, and 40 minutes following anesthesia. Anesthesia recovery variables were also compared between the two groups. RESULTS: In group I, arterial blood pressure at 10 to 40 min and heart rate at 1 and 25 min after the administration of anesthetics were significantly lower when compared with group II (W ²= 25.10, p= 0.005). Arterial oxygen saturation was similar in the two groups over the whole points of time. The time intervals between the end of surgery and beginning of the first body movements and respiratory efforts were significantly longer in group received halothane (p<0.001). CONCLUSION: Continuous infusion of thiopental can be applied effectively and safely for maintenance of anesthesia. In comparison with halothane, it is associated with lower changes of intraoperative hemodynamics and faster anesthesia recovery.

OBJETIVO: Investigar a recuperação anestésica e as condições hemodinâmicas em pacientes submetidos a infusão de tiopental ou hatotano na manutenção da anestesia na cirurgia ocular. MÉTODOS: Cinquenta e nove voluntários submetidos a cirurgia ocular no Hospital Farabi foram distribuídos em dois grupos de manutenção anestésica: Grupo I (n=37) inalação halotano, 0,8 a 1 por cento e Grupo II (n=22) infusão de tiopental, 10 a 12 mg/kg/hora. Foram registrados parâmetros hemodinâmicos da entrada dos pacientes na sala operatória até 1, 2, 5, 10, 15, 20, 25, 30, 35 e 40 minutos durante a anestesia. Variáveis de recuperação anestésica foram também comparados entre ambos os grupos. RESULTADOS: No Grupo I a pressão arterial nos 10 a 40 minutos e avaliação cardíaca em um e 25 minutos após a administração dos anestésicos foram significantes mais baixos comparados com o Grupo II (W²=25.10, p=0.005). A saturação de oxigênio foi similar nos dois grupos durante todos procedimentos. Os intervalos de tempo entre o final da cirurgia e início dos primeiros movimentos e a respiração foram significativamente mais prolongados no grupo que recebeu halotoano (p<0.001). CONCLUSÃO: A infusão continua de tiopental pode ser aplicado efetivamente e com segurança na manutenção da anestesia. Em comparação com halotano as mudanças hemodinâmicas foram menores e a recuperação anestésica mais rápida.

Comparison of induction and recovery characteristics of halothane and sevoflurane among infants

The aim of this study was to compare the induction and recovery characteristics associated with Halothane and Sevoflurane anesthesia in infants undergoing herniotomy. A total number of 100 infants who underwent herniotomy at King Hussein Medical Center between July 2008 and February 2009, under general anesthesia were allocated to receive either Sevoflurane [n=50] or Halothane [n=50] anesthesia. Induction times, recovery times and induction and recovery complications were recorded. The time of induction was shorter with Sevoflurane than with Halothane. The incidence of excitement was higher in Sevoflurane group than in Halothane group during both induction and recovery. Recovery time was significantly shorter with Sevoflurane group than halothane group. Sevoflurane, when used for infants, has the advantage of faster speed of induction and more rapid recovery than Halothane, which may make it suitable alternative to the later

Survey of malignant hyperthermia in Korea: Report for the necessity of establishing the center for caffeine and halothane contracture test in Korea: a questionnaire

BACKGROUND: Malignant hyperthermia (MH) has a high mortality rate and a family history. Then, caffeine and halothane contracture test (CHCT), generally used to detect MH susceptibility, is needed for early detection. The aim of this survey is to collect the opinion about establishment of the center for CHCT in Korea. METHODS: A people who were anesthesiologists working in the training hospital of Korea participated the survey between January and March 2011. Usual anesthetic drug during general anesthesia including volatile agents, opioids, muscle relaxants, incidence, diagnoses and treatments of MH, and opinion about establishment of the center for CHCT, were investigated. RESULTS: A total of 105 people who were anesthesiologists working in Korea were registered, they answered that 33 anesthesiologists (32%) met MH patient, and MH occurred once in a decade. If there is a diagnostic method such as CHCT in Korea, 89 anesthesiologists (89%) will recommend the test for the patients and their family. CONCLUSIONS: Many anesthesiologists want to recommend the CHCT for patients and their family. But, in Korea, it is impossible because there is no laboratory available for CHCT. Now, we considered carefully to establish the laboratory available for CHCT.

Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine. Deaths due to MH have been reported in Brazil. The first Malignant Hyperthermia Diagnostic and Research Center in Latin America was inaugurated in 1993 at the Federal University of Rio de Janeiro, Brazil. The center followed the diagnostic protocols of the North America MH Group, in which the contractures of biopsies from the vastus lateralis muscle are analyzed after exposure to caffeine and halothane (CHCT). CHCT was performed in individuals who survived, their relatives and those with signs/symptoms somewhat related to MH susceptibility (MHS). Here, we report data from 194 patients collected over 16 years. The Southeast (N = 110) and South (N = 71) represented the majority of patients. Median age was 25 (4-70) years, with similar numbers of males (104) and females (90). MHS was found in 90 patients and 104 patients were normal. Abnormal responses to both caffeine and halothane were observed in 59 patients and to caffeine or halothane in 20 and 11 patients, respectively. The contracture of biopsies from MHS exposed to caffeine and halothane was 1.027 ± 0.075 g (N = 285) and 4.021 ± 0.255 g (N = 226), respectively. MHS was found in patients with either low or high blood creatine kinase and also, with a low score on the clinical grading scale. Thus, these parameters cannot be used with certainty to predict MHS. We conclude that the CHCT protocol described by the North America MH Group contributed to identification of MHS in suspected individuals at an MH center in Brazil with 100 percent sensitivity and 65.7 percent specificity.

Clinical features and diagnosis for Chinese cases with malignant hyperthermia: a case cluster from 2005 to 2007 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Malignant hyperthermia (MH), manifesting as MH crisis during and/or after general anesthesia, is a potentially fatal disorder in response to volatile anesthetics and depolarizing muscle relaxants. Though typical features of MH episode can provide clues for clinical diagnosis, MH susceptibility is confirmed by in vitro caffeine-halothane contracture test (CHCT) in western countries. It is traditionally thought that MH has less incidence and fewer typical characteristics in Chinese population than their western counterparts because of the different genetic background. In this study, we investigated the clinical features of MH in Chinese cases and applied the clinical grading scale and CHCT for diagnosis of MH.</p><p><b>METHODS</b>A cluster of three patients with MH, from January 2005 to December 2007, were included in the study. Common clinical presentations and the results of some lab examinations were reported in detail. The method of the clinical grading scale of diagnosis of MH was applied to estimate the qualitative likelihood of MH and predict MH susceptibility. Muscle fibers of femoral quadriceps of the patients were collected and CHCT was performed to confirm the diagnosis of MH.</p><p><b>RESULTS</b>The clinical grading scales of diagnosis of the disease for these cases were all ranked grade D6, suggesting almost diagnosed ones. And the results of caffeine test were positive correspondingly, indicating that the patients should be diagnosed as MH susceptibility (MHS) according to diagnostic criteria of the North America MH group, which were already confirmed by clinical presentations and biochemical results.</p><p><b>CONCLUSIONS</b>These Chinese cases manifest as MH crisis. The clinical grading scale of diagnosis of MH may provide clues for clinical diagnosis. CHCT can also be used in confirming diagnosis of MH in Chinese cases though they have different genetic background from their western counterparts.</p>

Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.

Comparison of the effect of sevoflurane and halothane anesthesia on the fall in heart rate as a predictor of successful single shot caudal epidural in children

To investigate the effect of sevoflurane anesthesia on heart rate HR fall with the injection of the initial drug in caudal space to confirm the correct needle placement. After the ethical approval was obtained from the hospital-s ethics committee, a prospective, randomized, clinical study was designed in Yeditepe University Hospital, in 2007. Children aged 1-12 years, scheduled for infraumblical surgery under general anesthesia, and caudal block were included in the study. Anesthesia was induced, and maintained by sevoflurane in group S n = 85, and by halothane in group H n = 82. Baseline HR was recorded before the caudal block was performed. The HR changes during the initial dose, and total drug injection were recorded followed by 2 more HR recordings taken 5, and 10 minutes after caudal injection. The success of the block was recorded by a blind observer. There were 167 children included in the study. Caudal block success was 96.5% in group S, and 97.6% in group H. Basal HR was 110.9 +/- 10.9 in group S, and 105.9 +/- 10.1 in group H. Following the initial drug injection, mean HR was 109.8 +/- 10.9 in group S, and 102.9 +/- 9.9 in group H. It was significantly lower than the baseline in group H. The only significant decrease in the HR of the patients in group S was at the tenth minute following caudal injection. The decrease in HR with drug injection has no value to predict the success of caudal block under sevoflurane anesthesia