Malignant hyperthermia in maxillofacial surgery: Literature review supported by case presentation.

OBJECTIVE: Malignant hyperthermia (MH) is characterized by a state of hypermetabolism after exposure to halogenated inhalational anesthetics or succinylcholine. The aims of this study were to carry out an updated review on the subject and report an illustrative case of MH in urgent maxillofacial surgery. MATERIAL AND METHODS: A search of the PubMed/MEDLINE database using the keyword "malignant hyperthermia" was performed including articles published over the last 11 years in English, Spanish or Portuguese. Exclusion criteria were similar presentations but not associated with MH and cases not related to the use of anesthetic drugs as a trigger of the condition. CASE REPORT: A 45-year-old man (75 kg, ASA status IE) with a negative family history for neuromuscular diseases, victim of a car accident with a facial fracture, underwent surgery under balanced general anesthesia and developed signs of MH 4 h after anesthesia induction. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed, subsequently, by muscle biopsy. RESULTS/DISCUSSION: Overall, 44 cases of MH were found. According to the recent literature, MH shows a male predilection (3:1) and the mean age of patients is 32.2 ± 22.2 years. The most frequently cited causative agents were sevoflurane (30.5%), isoflurane (22.2%), and sevoflurane + succinylcholine (13.8%). The most common clinical indicators included hypercarbia (88.8%), hyperthermia (86.1%), and tachycardia (63.8%). Dantrolene was administered in 24 cases. The outcome was favorable in 31 cases (86.1%). The in vitro muscle contracture test (IVCT) was performed in only 15 patients and all of them tested positive. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed by muscle biopsy. CONCLUSION: The mortality from MH is still high and an early clinical diagnosis and specific treatment with dantrolene are necessary for a favorable outcome. A complete understanding will allow better management of patients with MH. At present, the best management is to identify susceptible patients and to avoid triggering agents, combined with vigilant monitoring.

Impact of a digital manual for guidance on malignant hyperthermia: patient education.

BACKGROUND: Malignant hyperthermia (MH) is a rare, hereditary disease with a hypermetabolic response to volatile anesthetics/succinylcholine. Susceptible patients face difficulties due to a lack of knowledge about MH. As informational materials could increase knowledge and adherence to prevention/therapy, digital information about rare diseases validated for patients is needed. Our objective was to evaluate the following: (1) the impact of digital manuals on the knowledge/quality of life of MH patients and (2) access to MH services. MATERIALS AND METHODS: Fifty MH-susceptible patients filled out a virtual questionnaire twice (demographic/economic/clinical data, MH knowledge and impact on daily life, and SF-36 quality of life). Test groups 1 (n = 17) and 2 (n = 16) were evaluated 30 and 180 days after receiving a digital manual, and the control group (n = 17; without manual) was evaluated after 180 days. We collected the MH service data about the number of contacts. RESULTS: Twenty-four (48%) patients reported problems in personal/professional life, sports, clinical/surgical/dental treatments, and military service, in addition to concerns about emergency care and complaints of sequelae. The percentage of correct answers in the second MH knowledge questionnaire increased for test group 2 (62% vs. 74.1%; unpaired t test, p < 0.01), was significantly greater in test groups 1 (68.1%) and 2 (74.1%) than in the control group (56.5%; Kruskal-Wallis, p < 0.05), and correlated with more time studying the manual and reports of MH-related problems (multiple regression, p < 0.05). CONCLUSIONS: The digital manual improved patients' MH knowledge. Online contacts with the MH service increased, allowing greater information dissemination. As informational materials could increase knowledge/adherence to prevention/therapy, digital information about MH validated for patients should be implemented.

Malignant hyperthermia in Mazovia Province - are we adequately prepared?

INTRODUCTION: Malignant hyperthermia (MH) is a life-threatening syndrome caused by sudden skeletal muscle hypermetabolism in response to inhalation anaesthetics and depolarising relaxants. The estimated incidence of MH is between 1 : 10,000 and 1 : 250,000 anaesthetic procedures. In Poland the incidence of MH is unknown. Dantrolene is imported as a life-saving drug and temporally authorised for sale. The aim of the study is to assess the incidence of MH and access to dantrolene in the Mazovia Province. METHODS: Anonymous questionnaires were sent to anaesthesia departments in the Mazovia Province after prior contact by phone and e-mail. The survey was approved by the local ethical review board. RESULTS: Completed surveys were received from 60 respondents which represents 72% of anaesthesiology departments in Mazovia. In the last 5 years there have been 4 episodes of MH in the Mazovia Province. Three patients survived the MH crisis. In a centre that did not have access to dantrolene, the patient died. Dantrolene is found only in 11 (18.3%) anaesthesiology departments in Mazovia. Only 6 (10%) hospitals are able to administer dantrolene within 5 minutes of suspecting MH crisis, while 5 centres may receive it after a few days. Only 38% of units have an algorithm for dealing with MH crisis in the operating theatres. CONCLUSIONS: MH is rare, but if untreated, it can be fatal. Therefore prompt diagnosis and treatment are crucial to avoid fatal outcome. Every centre using inhalational anaesthetics and/or succinylcholine should have dantrolene. To ensure the safety of our patients, we must be better prepared.

Lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 / List of essential drugs for the management of patients admitted to intensive care units with suspected or confirmed diagnosis of COVID-19

En el transcurso de la pandemia de COVID-19, numerosos países, de ingresos bajos, medianos y alto, han visto agotadas sus reservas de medicamentos esenciales necesarios para el manejo de los pacientes con COVID-19 en las unidades de cuidados intensivos (UCI). El plan de preparación para emergencias sanitarias de los países requiere incluir una lista de medicamentos esenciales y otros dispositivos médicos necesarios en las UCI para afrontar emergencias sanitarias. La lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 es un documento de orientación fundamental que ayuda a los sistemas de salud de los países a priorizar los medicamentos esenciales que deben estar ampliamente disponibles y ser asequibles para manejar los pacientes en las UCI durante las situaciones de emergencia sanitaria, en este caso con sospecha o diagnóstico confirmado de COVID-19. Está dirigida a las autoridades sanitaras y a los encargados del manejo del sistema de salud de los países. Esta lista incluye fundamentalmente los medicamentos considerados esenciales para el manejo de los cuadros clínicos que con se observan con mayor frecuencia en pacientes hospitalizados en UCI a causa de una infección por SARS-CoV-2. No se incluyen la mayoría de los medicamentos que comúnmente se encuentran en las UCI para el manejo de otras patologías, comorbilidades o la estabilización del paciente (p. ej., insulina o antihipertensivos), salvo aquellos que pueden requerirse para el tratamiento o apoyo (p. ej., bloqueantes neuromusculares o anestésicos) de las dolencias generadas por la infección. Tampoco se incluyen medicamentos específicos para el tratamiento de la infección por SARS-CoV-2, puesto que no existe, por el momento, evidencia científica de alta calidad que avale su uso, salvo en el contexto de ensayos clínicos controlados. Un equipo de expertos en el tema realizó una búsqueda de información sobre la atención de pacientes en UCI durante la pandemia de COVID-19, en Medline (a través de PubMed), Cochrane, Tripdatabase, Epistemonikos y en buscadores generales de internet (Google). Se identificaron también revisiones o guías generadas por ministerios de Salud de varios países de la Región de las Américas, la Organización Mundial de la Salud (OMS), la Organización Panamericana de la Salud (OPS), el Instituto Nacional de Salud y Excelencia Clínica (NICE) de Reino Unido, los Centros para el Control y la Prevención de Enfermedades (CDC) de Estados Unidos y los Institutos Nacionales de Salud (NIH) de Estados Unidos.

Personalized pediatric anesthesia and pain management: problem-based review.

Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging 'personalized medicine.' Although oncology spearheaded the clinical implementation of personalized medicine, other specialties are rapidly catching up. In anesthesia, classical examples of genetically mediated idiosyncratic reactions have been long known (e.g., malignant hyperthermia and prolonged apnea after succinylcholine). The last two decades have witnessed an expanding body of pharmacogenetic evidence in anesthesia. This review highlights some of the prominent pharmacogenetic associations studied in anesthesia and pain management, with special focus on pediatric anesthesia.

Comparing the insertion and ventilation of laryngeal mask airway according to the patient's head position and muscle relaxation use. A prospective clinical trial.

OBJECTIVES: To assess the insertion and ventilation of the laryngeal mask airway (LMA) classic while using different head positions with or without muscle relaxant. METHODS: This is a double-blind randomized clinical trial. Patients scheduled for ureteral calculus surgery at Shanghai General Hospital, Shanghai, China were recruited between November 2017 and November 2018. A total of 132 adults were consecutively selected. Patients were randomly divided into 4 groups according to head positioning and muscle relaxant use. An 8-cm-high pillow was used to achieve the sniffing position. The insertion time, initial peak pressure (Ppeak), mean pressure (Pmean) of the airway during intermittent positive pressure ventilation (primary endpoint) and fiberoptic score of the LMA position (secondary endpoint) were evaluated via electronic bronchoscopy through the mask bar. All adverse events were recorded. Results: Data were analyzed by ANOVA, 2-way ANOVA, Chi-squared, Cochran-Mantel-Haenszel, and Kruskal-Wallis tests. The insertion time required for the first attempt, fiberoptic score, Ppeak and Pmean did not differ among the groups. However, the incidence of adverse events in groups not using muscle relaxant was higher than in those using muscle relaxant. Conclusion: Use of a sniffing position and muscle relaxant slightly eased the insertion of the LMA but did not affect the fiberoptic score or ventilation parameters. Using a muscle relaxant, but not the sniffing position, reduced the incidence of adverse effects.

Eficacia de tres dosis de succinilcolina en la inducción de secuencia rápida / Effectiveness of three doses of succinylcholine in rapid sequence induction

Introducción: La intubación de secuencia de rápida es un procedimiento que minimiza el tiempo necesario para asegurar la vía respiratoria en pacientes con alto riesgo de broncoaspiración. Objetivo: Comparar la eficacia de tres dosis de succinilcolina en la inducción de secuencia rápida en pacientes con estómago y la calidad de la intubación, así como los efectos secundarios de dichos fármacos. Métodos: Se realizó un estudio observacional, de corte transversal para evaluar la calidad de la intubación con inducción de secuencia rápida en pacientes de urgencia, con estómago lleno. Se administraron 0,4 mg/kg de succinilcolina al grupo I, 0,6 mg/kg al grupo II y 1 mg/kg al grupo III. En todos los pacientes se evaluó la vía respiratoria. El estudio se realizó en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras" entre agosto de 2013 y 2016. Resultados: El tiempo de visualización de las cuerdas vocales fue rápido en los tres grupos. Los mejores resultados se obtuvieron en el grupo III, seguido del grupo II. Las condiciones de intubación fueron excelentes en el grupo III (90 %), buenas en grupo II (80 %) y regulares en el grupo I (70 %). Las variables hemodinámicas mostraron diferencias significativas entre grupos (p=0,008). Conclusiones: Se determinó la eficacia del empleo de tres dosis de succinilcolina en la inducción de secuencia rápida, con intubación óptima y segura cuando se empleó la succinilcolina a dosis de 1 mg/kg; pero con mayor porcentaje de alteraciones hemodinámicas como efectos adversos(AU)

Introduction: Rapid sequence intubation is a procedure that minimizes the time required to guarantee the respiratory airway in patients with high risk of bronchoaspiration. Objectives: To compare the quality of intubation with three doses of succinylcholine in rapid sequence induction in patients with full stomach, as well as the side effects of such drugs. Methods: An observational, cross-sectional study was carried out to assess the quality of intubation with rapid sequence intubation in emergency patients and with full stomach. The group I was administered 0.4 mg/kg of succinylcholine; the group II, 0.6 mg/kg; and the group III 1 mg/kg. The respiratory airway was assessed in all patients. The study was carried out in Hermanos Ameijeiras Clinical Surgical Hospital, between August 2013 and 2016. Results: The time of visualization of the vocal folds was fast in the three groups. The best results were obtained in the group III, followed by the group II. The intubation conditions were excellent in the group III (90%), good in the group II (80%), and fair in the group I (70%). The hemodynamic variables showed significant differences among the three groups (p=0.008). Conclusions: The effectiveness was determined of using three doses of succinylcholine in rapid sequence intubation, with optimal and safe intubation when succinylcholine was used at doses of 1 mg/kg, but it had a higher percentage of hemodynamic alterations as adverse effects(AU)

Consensus Statement of the Malignant Hyperthermia Association of the United States on Unresolved Clinical Questions Concerning the Management of Patients With Malignant Hyperthermia.

At a recent consensus conference, the Malignant Hyperthermia Association of the United States addressed 6 important and unresolved clinical questions concerning the optimal management of patients with malignant hyperthermia (MH) susceptibility or acute MH. They include: (1) How much dantrolene should be available in facilities where volatile agents are not available or administered, and succinylcholine is only stocked on site for emergency purposes? (2) What defines masseter muscle rigidity? What is its relationship to MH, and how should it be managed when it occurs? (3) What is the relationship between MH susceptibility and heat- or exercise-related rhabdomyolysis? (4) What evidence-based interventions should be recommended to alleviate hyperthermia associated with MH? (5) After treatment of acute MH, how much dantrolene should be administered and for how long? What criteria should be used to determine stopping treatment with dantrolene? (6) Can patients with a suspected personal or family history of MH be safely anesthetized before diagnostic testing? This report describes the consensus process and the outcomes for each of the foregoing unanswered clinical questions.

[Certain and controversial components of "rapid sequence induction"]. / Sichere und kontroverse Komponenten der "rapid sequence induction".

Rapid sequence induction (RSI) is a specific technique for anesthesia induction, which is performed in patients with an increased risk for pulmonary aspiration (e.g. intestinal obstruction, severe injuries and cesarean section). The incidence of acute respiratory distress syndrome (ARDS) is very low but 10-30% of anesthesia-related deaths are caused by the consequences of ARDS. The classical RSI with its main components (i.e. head-up position, avoidance of positive pressure ventilation and administration of succinylcholine) was published nearly 50 years ago and has remained almost unchanged. The modified RSI consists of mask ventilation before endotracheal intubation is performed or the use of non-depolarizing muscle relaxants. Succinylcholine 1.0 mg/kg or rocuronium 1.0-1.2 mg/kg should be administered to achieve excellent intubation conditions. The use of cricoid pressure was a cornerstone of RSI after its introduction in 1961; however, after controversial discussions in recent years, cricoid pressure has lost its importance. Before surgery gastric emptying with a nasogastric tube is mandatory in patients with ileus and passage or defecation disorders.

Perioperative Gabapentin Improves Patient-Centered Outcomes After Inguinal Hernia Repair.

INTRODUCTION: Over 5,300 inguinal hernia repairs (IHR) were performed in the Military Health System in 2015. Chronic pain can be a debilitating complication, occurring in up to 34% of patients after IHR and impacts mission readiness. Gabapentin has been shown to be effective for postoperative analgesia in a variety of operations. We evaluated the effect of a short course of perioperative gabapentin on chronic pain after IHR. METHODS: This was a double-blinded, randomized study involving male patients ≥18 years old with an initial inguinal hernia and no history of chronic pain or psychiatric disorder. Patients chose laparoscopic or open surgery and were then randomized to receive gabapentin 300 mg before surgery, then three times daily for 6 doses or placebo. There were 50 patients randomized to both the gabapentin and placebo groups for a total of 100 patients. Main outcomes were pain and health status, assessed with a visual analogue scale (VAS) and the Short Form-12v2 (SF-12v2). Assessments were performed preoperatively and 1, 6, 12, and 24 months postoperatively. Analysis of variance was used to compare groups. RESULTS: From the initial 100 patients, 19 withdrew or were excluded. Thus, 81 patients remained, 40 receiving gabapentin and 41 placebo. Throughout the 24-month follow-up, there was no difference in VAS pain scores between the gabapentin and placebo groups (p = 0.867). Beyond 1 month of follow-up, SF-12v2 physical component score (PCS) scores were improved in the gabapentin group (p = 0.039). When comparing open to laparoscopic groups, SF-12v2 PCS scores were improved in the laparoscopic group (p = 0.046) and SF-12v2 mental component summary scores were improved in the open group (p = 0.041). CONCLUSIONS: Perioperative gabapentin was not effective in decreasing chronic pain after IHR; however, patient perception of physical health, as measured by SF-12v2, did improve.

The Effect of Remifentanil on Succinylcholine Induced Changes in Serum Potassium and Creatine Kinase: A Prospective Randomized Double blind Study.

BACKGROUND AND AIM OF THE WORK: Succinylcholine is still included as drugs favored by anesthetists because of its rapid onset and short duration of action. However, it can bring about complications such as hyperkalemia and increased serum creatine phosphokinase (CPK). This study aims at evaluating the effects of remifentanil on succinylcholine-induced postoperative changes in serum potassium and CPK. METHODS: In this study, 59 patients with short term lower abdominal surgery were randomly divided into two groups. In the first group (control group), 2 ml normal saline was used before injecting anesthetic drugs while in the second group (study group), 1 mcg/kg of remifentanil was injected. The patients were anesthetized with a combination of fentanyl (1 mg/kg) and propofol (2 mg/kg). Besides, succinylcholine (1.5 mg/kg) was used for muscle relaxation and tracheal intubation. Serum potassium (before and  5 min after tracheal intubation), CPK (before anesthetic injection and  24 h after surgery) and hemodynamic parameters (including systolic, diastolic and mean arterial blood pressure and heart rate) were recorded. RESULTS: Serum levels of potassium and CPK before and after induction of anesthesia showed no significant difference in both groups. Systolic, diastolic, and mean arterial blood pressure and heart rate in both groups after induction significantly changed. Compared to saline, remifentanil significantly stabilized hemodynamic changes after intubation. CONCLUSIONS: The results suggest that remifentanil has no prophylactic effect on succinylcholine-induced CPK and potassium levels. However, it improves stability of hemodynamic variables.

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

Desarrollo tecnológico de succinilcolina infantil 100 mg, inyectable en solución / Technological development of 100 mg infant succinylcoline, injectable in a solution

Objetivo: desarrollar una nueva formulación inyectable en solución acuosa de succinilcolina, para uso pediátrico. Métodos: se utiliza la materia prima cloruro de succinilcolina con demostrada calidad para el diseño de la formulación. Fueron ensayadas tres variantes de formulación, durante seis meses, a una temperatura de 25±2 oC y una humedad relativa de 60±5 por ciento, se analiza la influencia de los componentes y el envase sobre el contenido del fármaco. Resultados: la formulación envasada en bulbos 6R, sin agentes preservantes, se selecciona como la mejor variante. Los tres lotes a escala de laboratorio cumplieron con los parámetros de calidad establecidos y se realizó el escalado piloto. Conclusiones: se comprobó la factibilidad del desarrollo del inyectable en solución de succinilcolina infantil 100mg(AU)

Objective: to develop a new injectable formulation in aqueos solution of succinylcoline for pediatric uses. Methods: the raw material for the formulation was succinylcoline chloride with proven quality for this design. Three variants of formulation were tested for six months at a temperature of 25±2 oC and relative humidity of 60±5 percent. The influence of the components and of the packing on the contents of the drug was analyzed. Results: the formulation packed in flasks 6R with no preserving agent was chosen as the best. Three batches at lab scale met the set quality parameters and also a pilot scale-up was performed. Conclusions: the feasibility of the development of an injectable product in 100mg infant succinylcoline solution(AU)

Enfoque basado en riesgo desde la etapa de desarrollo del producto succinilcolina infantil 100 mg / Risk-based approach from the development phase of 100mg infant succinylcoline product

Introducción: en la actualidad las guías emitidas por la Agencia de Medicamentos y Alimentos, de los EU considera que los procesos fallan porque las fuentes no son debidamente identificadas, eliminadas o controladas y plantean un nuevo enfoque de Buenas Prácticas de Producción basado en riesgos. Objetivo: aplicar un enfoque basado en riesgos en el aseguramiento de la calidad desde la etapa de desarrollo del producto succinilcolina 100 mg. Métodos: se realizó una breve descripción del proceso mediante un diagrama de bloque, se empleó el Árbol de Fallas como herramienta para identificar las posibles fuentes de falla; la valoración de riesgos partiendo de la identificación de las posibles fuentes de fallos se ejecutó a través de un método matricial. Se identificó un orden de prioridad en la toma de acciones correctivas para eliminar o mitigar el riesgo de ocurrencia. Resultados: el diagrama de bloque permitió tener un conocimiento sobre el proceso, lo que contribuyó de forma decisiva a un mejor ejercicio de la gestión de riesgos. El Árbol de Fallas resultó útil al revelar de forma gráfica las diferentes combinaciones de fallos e interrelaciones entre causa y efecto que pudieran dar lugar al evento tope indeseado. El método empleado para la valoración de riesgos permitió determinar las prioridades, siendo el tiempo extensivo de llenado (fuera de 2-8 °C) el componente crítico a considerar con especial atención; si se tiene en cuenta que la estabilidad de este producto se puede afectar a temperaturas superiores a estas, por lo que disponer de un plan de acciones correctivas acorde a los riesgos identificados permitirá la eliminación o mitigación de las mismas. Conclusiones: la herramienta de gestión de riesgos permitió identificar desde la etapa de desarrollo del producto succinilcolina 100 mg, las principales fuentes de fallas relacionadas con este proceso(AU)

Introduction: the guidelines presently issued by the Food and Drug Agency of the United States considers that processes fail because the sources are not duly identified, eliminated or controlled and submit a new approach of Good Manufacture Practice based on risks. Objective: to apply a risk-based approach to the quality assurance from the development phase of the 100 mg succinylcoline product. Methods: the process was briefly described through a block diagram with Failure Tree as a tool for identification of possible sources of failures; the risk assessment based on the detection of the possible sources of failures was made with the matrix method. An order of priority was given in the implementation of corrective actions to eliminate or mitigate the risk of occurrence. Results: the block diagram allowed knowing the process, which contributed in a decisive way to a better application of risk management. The Failure Tree proved to be useful when showing in a graphical way the different failure combinations and interrelations between cause and effect that might give rise to the unwanted top event. The method for the risk assessment made it possible to determine priorities, being the long time of filling (not within 2 to 8oC) the critical component to be specially considered if one takes into account that stability of the product may be affected by higher temperatures, therefore, a plan of corrective actions according to the identified risks will allow their elimination or mitigation. Conclusions: the risk management tool allowed identifying the main process-related sources of failures from the very development phase of the 100 mg succinylcoline product.

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

BACKGROUND: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers. METHODS: In a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro. RESULTS: A total of 200 patients met the inclusion criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by volatile anesthetics and 81% by a combination of both. Patients were 70% male and 50% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles. CONCLUSIONS: An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.

[Analysis of difficult intubation factors in bariatric surgery. Influence of the choice of neuromuscular blocker on the availability of sugammadex]. / Análisis de los factores de intubación difícil en cirugía bariátrica. Influencia en la elección del bloqueante neuromuscular de la disponibilidad de sugammadex.

OBJECTIVE: To determine the incidence of difficult tracheal intubation (DTI), as well as predictive factors for DTI and what influences the choice of the neuromuscular blocking agent (succinylcholine or rocuronium). METHODS: This is an observational, prospective study on consecutive bariatric surgery patients. Tracheal intubation was performed by direct laryngoscopy with a preformed tracheal tube. DTI was considered when there was a Cormack-Lehane classification of iii-iv or when it was necessary to apply the DTI algorithm, which consisted in the use of Frova guide, and Airtraq video-laryngoscope as second choice, and finally awaking the patient and sugammadex reversal if rocuronium was the selected neuromuscular blocking agent. Thereafter, tracheal intubation was performed using an awake fibroscopic technique RESULTS: One hundred and sixty six patients were included. In one case, conscious fiberscope tracheal intubation was performed. Succinylcholine was selected for 14 patients, and rocuronium for 151 patients. Fifteen patients had a DTI (9%): in 4 Airtraq was deemed necessary. One patient received sugammadex to reverse neuromuscular blockade. Conscious tracheal intubation represented 1.2% (95% CI; 0.3-4%). DTI was associated with Mallampati score of 3-4 (odds ratio, 3 [95% CI; 1.37-6.8], sensitivity of 33%, specificity of 91%) and with thyromental distance<6cm (odds ratio, 4.8 [95% CI; 1.45-16]; sensitivity of 53%; specificity of 79%). CONCLUSION: Rescue airway protocol with Frova and Airtraq avoided the use of sugammadex, except in one patient.

The effect of preoperative consumption of potatoes on succinylcholine-induced block and recovery from anesthesia.

Potatoes contain solanaceous glycoalkaloids (SGAs), which inhibit both butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The present study investigated the effect of preoperative consumption of potatoes on succinylcholine-induced block and recovery from anesthesia. ASA I-II, adult patients, scheduled for elective surgery, were included in a randomized, blind and controlled study. Patients were randomly divided into two groups. Patients in Group P (n = 21) ate a standard portion of potatoes in their last meal prior to pre-operative fasting, while patients in Group C (n = 23) ate food not containing SGAs. Patients were premedicated with midazolam. Anesthesia was induced with thiopental and fentanyl, and maintained with sevoflurane in 50 % O2/air and fentanyl, as needed. Succinylcholine 1 mg kg(-1) was administered to facilitate endotracheal intubation. Duration of succinylcholine blockade, awakening and recovery times from anesthesia were measured. Serum BuChE levels were also measured at baseline and 4 time-points within 24 h post-consumption. Duration of succinylcholine-induced neuromuscular block, awakening and recovery time from anesthesia was significantly longer in Group P than in Group C (p < 0.05). Serum BuChE levels decreased at 6 h after consumption start in Group P. In addition, in both groups, BuChE levels markedly decreased after succinylcholine blockade, increased thereafter, but did not return to baseline within 24 h of consumption start. None of these differences observed in BuChE levels was statistically significant. This study suggests that potatoes eaten before anesthesia can prolong the duration of succinylcholine-induced neuromuscular block and delay recovery from anesthesia.

Pseudocolinesterasas plasmáticas: a propósito de un caso / Plasmatic pseudocholinesterase: a case report

ntroducción: La presencia de colinesterasa plasmática inhibida, disminuida o genéticamente atípica, produce bloqueo neuromuscular prolongado con el uso de succinilcolina. Objetivos: Presentar la evolución clínica de una paciente portadora de colinesterasa plasmática, con recuperación tardía por uso de succinilcolina. Presentación del caso: Se presenta evolución clínica de paciente femenina de 24 años de edad, con antecedentes de anomalía del raquis en estudio suspendido por gestación con alteraciones sensitivas en mitosis I (MI), internada en Hospital General Provincial Docente de Morón. Por embarazo a término y desproporción céfalo pélvica para operación cesárea. Examen físico y complementarios habituales negativos. En el quirófano se le realizó inducción con kethamina: 125 mg IV; atropina 0,5 mg IV y succinilcolina: 100 mg IV. Laringoscopia gentil, intubación fácil con tubo 7. Se acopló al ventilador SERVO 900D, con fracción inspirada de oxígeno (FiO2) de 0.5. Frecuencia respiratoria (FR) 12 x min y volumen corriente (VT) de 450 ml. El mantenimiento anestésico se realizó con oxígeno, aire comprimido, midazolam 5 mg IV y fentanyl: 150 µg IV, sin necesidad de repetir dosis de relajante muscular. Transcurrida 1 hora se valoró posibilidad de estar en presencia de colinesterasa atípica. Se administró una bolsa de plasma, sin obtener respuesta. Continuó intubada y acoplada al ventilador durante 6 horas a partir de la cual se recuperó y se extubó sin dificultad. Conclusiones: Ante la administración de succinilcolina nunca se debe olvidar la posibilidad de bloqueo neuromuscular prolongado por presencia de pseudocolinesterasa, pues es una complicación a tener en consideración.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: is rocuronium as effective as succinylcholine at facilitating laryngoscopy during rapid sequence intubation?

A short-cut review was carried out to establish whether rocuronium is as effective as succinylcholine at facilitating laryngoscopy during rapid sequence intubation (RSI). A total of 94 papers was found using the reported search, of which seven represented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is that rocuronium is as effective as succinylcholine at facilitating laryngoscopy during RSI.

Rapid sequence induction with rocuronium - a challenge to the gold standard.

Succinylcholine has been indicted on account of the diverse risks associated with its administration, which include hyperkalemia, vagal arrest, and malignant hyperthermia. However, it provides excellent intubating conditions reliably and quickly, characteristics that sustain its appeal for use in the intensive care unit, where airway management is challenging. There is an increasing body of evidence, outlined here, that rocuronium is an acceptable alternative to succinylcholine.