Hipertermia maligna / Malignant hyperthermia

Resumen: La hipertermia maligna es un raro desorden farmacogenético potencialmente mortal, que se presenta como una respuesta hipermetabólica a los anestésicos volátiles y relajantes musculares despolarizantes en individuos susceptibles. Esta susceptibilidad se asocia a mutaciones en tres genes: RYR1, CACNA1S y STAC3. Puede manifestarse con síntomas leves o como una crisis fulminante, con rabdomiólisis severa, fibrilación ventricular e insuficiencia renal y circulatoria aguda, por lo tanto, el pronóstico depende de qué tan pronto se sospeche del diagnóstico y qué tan rápido se inicie el tratamiento. El diagnóstico definitivo se basa en una prueba de sensibilidad en biopsia muscular fresca y en pruebas genéticas. La mejor manera de prevenir un evento es la detección precoz de los pacientes susceptibles así como contar con el equipo para responder ante una crisis en cada centro donde se administren anestésicos volátiles y la capacitación del personal. Esta revisión sintetiza los conceptos actuales clínicos y biomédicos para detección, prevención, diagnóstico y manejo de la hipertermia maligna.

Abstract: Malignant hyperthermia is a rare, life-threatening pharmacogenetic disorder which presents as a hypermetabolic response to volatile anesthetics and depolarizing muscle relaxants in susceptible individuals. This susceptibility is associated with mutations in three genes: RYR1, CACNA1S and STAC3. Can manifest with mild symptoms or as a fulminant crisis, with severe rhabdomyolysis, ventricular fibrillation and acute renal and circulatory failure, therefore the prognosis depends on how soon the diagnosis is suspected and how fast treatment is started. The definitive diagnosis is based on a fresh muscle biopsy sensitivity test and genetic testing. The best way to prevent an event is the early detection of susceptible, as well as have equipment to respond to a crisis in each center where volatile anesthetics are administered and the training of staff. This review synthesizes current clinical and biomedical concepts for detection, prevention, diagnosis and management of malignant hyperthermia.

Effect of sevoflurane on the inflammatory response during cardiopulmonary bypass in cardiac surgery: the study protocol for a randomized controlled trial.

BACKGROUND: Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial. METHODS: We plan to include one hundred patients undergoing elective coronary artery bypass graft with cardiopulmonary bypass who will be randomized to receive either volatile anesthetics during cardiopulmonary bypass or total intravenous anesthesia. The primary endpoint of the study is to assess the inflammatory response during cardiopulmonary bypass by measuring PMN-elastase serum levels. Secondary endpoints include serum levels of other pro-inflammatory markers (IL-1ß, IL-6, IL-8, TNFα), anti-inflammatory cytokines (TGFß and IL-10), and microRNA expression in peripheral blood to achieve possible epigenetic mechanisms in this process. In addition clinical endpoints such as presence of major complications in the postoperative period and length of hospital and intensive care unit stay will be assessed. DISCUSSION: The trial may determine whether adding volatile anesthetic during cardiopulmonary bypass will attenuate the inflammatory response. TRIAL REGISTRATION: ClinicalTrials.gov NCT02672345 . Registered on February 2016 and updated on June 2020.

Oxidative stress, DNA damage, inflammation and gene expression in occupationally exposed university hospital anesthesia providers.

Considering the importance and lack of data of toxicogenomic approaches on occupational exposure to anesthetics, we evaluated possible associations between waste anesthetic gases (WAGs) exposure and biological effects including oxidative stress, DNA damage, inflammation, and transcriptional modulation. The exposed group was constituted by anesthesia providers who were mainly exposed to the anesthetics sevoflurane and isoflurane (10 ppm) and to a lesser degree to nitrous oxide (150 ppm), and the control group was constituted by physicians who had no exposure to WAGs. The oxidative stress markers included oxidized DNA bases (comet assay), malondialdehyde (high-performance liquid chromatography [HPLC]), nitric oxide metabolites (ozone-chemiluminescence), and antioxidative markers, including individual antioxidants (HPLC) and antioxidant defense marker (ferric reducing antioxidant power by spectrophotometry). The inflammatory markers included high-sensitivity C-reactive protein (chemiluminescent immunoassay) and the proinflammatory interleukins IL-6, IL-8 and IL-17A (flow cytometry). Telomere length and gene expression related to DNA repair (hOGG1 and XRCC1), antioxidant defense (NRF2) and inflammation (IL6, IL8 and IL17A) were evaluated by real-time quantitative polymerase chain reaction. No significant differences (p > .0025) between the groups were observed for any parameter evaluated. Thus, under the conditions of the study, the findings suggest that occupational exposure to WAGs is not associated with oxidative stress or inflammation when evaluated in serum/plasma, with DNA damage evaluated in lymphocytes and leucocytes or with molecular modulation assessed in peripheral blood cells in university anesthesia providers. However, it is prudent to reduce WAGs exposure and to increase biomonitoring of all occupationally exposed professionals.

Development of a prototype anti-pollution filter for volatile anesthetics.

INTRODUCTION: The use of volatile agents during cardiopulmonary bypass allows a "single drug anesthesia" and is associated with reduced peak postoperative troponin levels. Connecting the exhaust systems to the oxygenator's gas outlet port is mandatory and allows to prevent operating room (but not atmospheric) pollution by volatile agents. The aim of this study was to create a prototype filter for volatile agents and to test its adsorption efficacy during an ex-vivo simulated conventional cardiopulmonary bypass test. METHODS: We carried out bench tests to conceive a prototype filter that could prevent room and environment pollution without damaging membrane oxygenators. We performed the tests at the Engineering Center for Circulatory Assistance Laboratory, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. Bench tests included simulation of integral adsorption tests, filter dimensions and design, flow versus pressure curve, sizing, and tightness. RESULTS: Calgon AT 410 was the best kind of activated charcoal granules for adsorption of sevoflurane, isoflurane, and desflurane. Filter dimension tests showed that a chamber of 30-cm width over 10-cm diameter filled with 200 g of the Calgon AT410 granules was the minimum required to fully adsorb sevoflurane for 90 min. Adsorption tests showed that the prototype filter fully adsorbed isoflurane in 100 ± 2.3 min, sevoflurane in 95 ± 3.4 min, and desflurane in 95 ± 4.3 min. CONCLUSION: The new version of our prototype filter adsorbed most of the volatile anesthetics agents during an ex-vivo simulated conventional cardiopulmonary bypass test.

Inhalational anesthesia maintenance with the Janus facial mask for transcatheter aortic-valve replacement: a case series / Manutenção da anestesia inalatória com a máscara facial Janus para substituição de válvula aórtica transcateter: uma série de casos

Abstract Background and objectives Aortic stenosis is the most common type of heart valve disease. Percutaneous aortic valve replacement has become the alternative for patients considered at high risk for surgery. Controlled mechanical ventilation with tracheal intubation has been the choice for this type of procedure, however the use of noninvasive ventilation in cardiac patients has shown to be beneficial. Janus is a novel full-face mask that allows application of noninvasive ventilation support during anesthesia. Our main objective was to evaluate the feasibility of transcatheter aortic valve replacement with prolonged transesophageal echocardiographic monitoring under deep inhalational sedation delivered through a new mask for noninvasive ventilation. Methods A case series observational study that included five patients with critical aortic stenosis that underwent inhalational anesthesia with sevoflurane for transcatheter aortic valve replacement in a hybrid room of a teaching hospital. Standard monitors and bispectral index were used, followed by inhalational induction and placement of the Janus mask. Anesthesia was maintained with sevoflurane. Patients were transferred to intensive care unit after the procedure. Complications related to the mask use, transesofageal echocardiography accessibility and respiratory implications to the patients were recorded. Results All procedures were uneventful and no major complications were observed intraoperatively. One patient presented CO2 retention (50 mmHg) and sevoflurane leak around the central opening of the mask, both without clinical significance. Conclusions The use of inhalational anesthesia with the facial mask Janus is a safe and efficient alternative to general anesthesia with tracheal intubation for transcatheter aortic valve replacement and can easily accommodate the use of transesophageal echocardiography intraoperatively.

Resumo Justificativa e objetivos A estenose aórtica é o tipo mais comum de doença valvular cardíaca. A substituição percutânea de válvula aórtica tornou-se a alternativa para pacientes cirúrgicos considerados de alto risco. A ventilação mecânica controlada com intubação traqueal tem sido a escolha para esse tipo de procedimento; porém, o uso de ventilação não invasiva em pacientes cardíacos mostrou ser benéfico. Janus é uma nova máscara facial que permite a aplicação de suporte à VNI durante a anestesia. Nosso objetivo primário foi avaliar a viabilidade da substituição transcateter de valva aórtica com monitoração ecocardiográfica transesofágica prolongada sob sedação inalatória profunda através de uma nova máscara para ventilação não invasiva. Métodos Estudo observacional de série de casos que incluiu cinco pacientes com estenose aórtica em fase crítica, submetidos à anestesia inalatória com sevoflurano para substituição transcateter de valva aórtica em uma sala híbrida de um hospital universitário. Monitores padrão e índice bispectral foram usados, seguidos de indução inalatória e colocação da máscara Janus. A anestesia foi mantida com sevoflurano. Os pacientes foram transferidos para a unidade de terapia intensiva após o procedimento. As complicações relacionadas ao uso da máscara, a acessibilidade da ecocardiografia transesofágica e as implicações respiratórias para os pacientes foram registradas. Resultados Todos os procedimentos transcorreram sem incidentes e não foram observadas complicações maiores no intraoperatório. Um paciente apresentou retenção de CO2 (50 mmHg) e vazamento de sevoflurano em torno da abertura central da máscara, ambos sem significância clínica. Conclusões O uso de anestesia inalatória com a máscara facial Janus é uma opção segura e eficiente à anestesia geral com intubação traqueal para substituição transcateter de valva aórtica e pode facilmente acomodar o uso de ecocardiografia transesofágica no intraoperatório.

[Inhalational anesthesia maintenance with the Janus facial mask for transcatheter aortic-valve replacement: a case series]. / Manutenção da anestesia inalatória com a máscara facial Janus para substituição de válvula aórtica transcateter: uma série de casos.

BACKGROUND AND OBJECTIVES: Aortic stenosis is the most common type of heart valve disease. Percutaneous aortic valve replacement has become the alternative for patients considered at high risk for surgery. Controlled mechanical ventilation with tracheal intubation has been the choice for this type of procedure, however the use of noninvasive ventilation in cardiac patients has shown to be beneficial. Janus is a novel full-face mask that allows application of noninvasive ventilation support during anesthesia. Our main objective was to evaluate the feasibility of transcatheter aortic valve replacement with prolonged transesophageal echocardiographic monitoring under deep inhalational sedation delivered through a new mask for noninvasive ventilation. METHODS: A case series observational study that included five patients with critical aortic stenosis that underwent inhalational anesthesia with sevoflurane for transcatheter aortic valve replacement in a hybrid room of a teaching hospital. Standard monitors and bispectral index were used, followed by inhalational induction and placement of the Janus mask. Anesthesia was maintained with sevoflurane. Patients were transferred to intensive care unit after the procedure. Complications related to the mask use, transesofageal echocardiography accessibility and respiratory implications to the patients were recorded. RESULTS: All procedures were uneventful and no major complications were observed intraoperatively. One patient presented CO2 retention (50mmHg) and sevoflurane leak around the central opening of the mask, both without clinical significance. CONCLUSIONS: The use of inhalational anesthesia with the facial mask Janus is a safe and efficient alternative to general anesthesia with tracheal intubation for transcatheter aortic valve replacement and can easily accommodate the use of transesophageal echocardiography intraoperatively.

A Novel Anti-Pollution Filter for Volatile Agents During Cardiopulmonary Bypass: Preliminary Tests.

OBJECTIVE: Concerns regarding pollution of the operating room by volatile anesthetics and effects on atmospheric ozone depletion exist. Volatile agents commonly are used during cardiopulmonary bypass to provide anesthesia independent of any supposed myocardial protective effects. The authors' aim was to create and to assess the performance of a prototype filter for volatile agents to be connected to the cardiopulmonary bypass circuit to avoid the emission of volatile agents to the operating room, and also to the environment without causing damage to the membrane oxygenator. DESIGN: Observational trial. SETTING: University hospital. PARTICIPANTS: Prototype filter for volatile agents. INTERVENTIONS: The prototype filter was tested in a single ex vivo experiment. The main data measured during the test were pressure drop to detect interference with the performance of the oxygenator, back pressure to detect overpressure to the outlet gas jacket of the oxygenator, analysis of exhaled sevoflurane after the membrane oxygenator, and after the filter to detect any presence of sevoflurane. MEASUREMENTS AND MAIN RESULTS: The prototype filter adsorbed the sevoflurane eliminated through the outlet portion of the oxygenator. During the entire test, the back pressure remained constant (4 mmHg) and pressure drop varied from 243 mmHg to 247 mmHg. CONCLUSION: The prototype filter was considered suitable to absorb the sevoflurane, and it did not cause an overpressure to the membrane oxygenator during the test.

MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design

Objective: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless,small Randomized Controlled Trials have failed to demonstrate a survival advantage. Thus, whethervolatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable.Design: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio.Setting: Tertiary and University hospitals.

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics.

An intriguing question in 3D-QSAR lies on which conformation(s) to use when generating molecular descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice can cause misinterpretation of the QSAR model. The present computational work reports the conformational analysis of the volatile anesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane) in the gas phase and also in polar and nonpolar implicit and explicit solvents to show that stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors.

Inhalation induction with sevoflurane in adult cardiac surgery patients. A case series.

INTRODUCTION: Anesthesia induction through volatile agents is a well-established technique in several fields but not in adult patients undergoing cardiac surgery. Successful inhalation induction requires a poorly soluble, reasonably potent and minimally irritant agent, and the benefits associated to this technique include reduced incidence of hypothermia and hypotension and lower costs when compared to some intravenous anesthetics agents. METHODS: Fifty-six patients undergoing coronary artery bypass grafting were observed at the induction of general anesthesia with sevoflurane in oxygen by facial mask. All patients received 2% sevoflurane in 100% oxygen initially for 30 seconds. The inspired concentration of sevoflurane was increased to 7% until loss of consciousness and then reduced back to 2%. Next, intravenous 0.5 µg/kg sufentanil and 0.1 mg/kg pancuronium were administered. Volume-controlled ventilation was started before tracheal intubation. RESULTS: All 56 patients tolerated the inhalational induction. No patient presented signs of airway irritation. Hypotension occurred in 30 patients and was managed with low dose phenylephrine. CONCLUSIONS: This case series showed that inhalation induction is feasible and safe even in adult patients undergoing cardiac surgery.

Sevoflurane anesthesia deteriorates pulmonary surfactant promoting alveolar collapse in male Sprague-Dawley rats.

General anesthesia is frequently associated to transient hypoxemia and lung atelectasis. Although volatile anesthetics are safe and widely used, their potential role on anesthesia-induced pulmonary impairment has not been fully explored. In this study, we investigated the effect of volatile anesthetic sevoflurane on pulmonary surfactant composition and structure that could contribute to atelectasis. After 30 min of sevoflurane anesthesia, Sprague-Dawley rats showed increased levels of lyso-phosphatidylcholine and decreased levels of phosphatidylcholine associated with significant impairment in lung mechanics and alveolar collapse, but showed no deterioration of alveolar fluid reabsorption when compared to control group of rats anesthetized with pentobarbital. Exposure to sevoflurane altered the thermotropic profile of surfactant model membranes, as detected by fluorescence anisotropy. In this sense, sevoflurane-promoted fluidification of condensed phases could potentially impair the ability of surfactant films to sustain the lowest surface tensions. In conclusion, the observed changes in surfactant composition and viscosity properties suggest a direct effect of sevoflurane on surfactant function, a factor potentially involved in anesthetic-induced alterations in lung mechanics.