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Dra. Ana Julia Maycomea Sombra Hipertermia Maligna 1INTRODUCCIN Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc. La hipertermia maligna (HM) es un trastorno hereditario del msculo esqueltico. En la exposicin a agentes desencadenantes (por ejemplo, succinilcolina, agentes anestsicos halogenados voltiles), los individuos afectados desarrollan un sndrome hipermetablico caracteriza por rigidez muscular, hipercapnia, acidosis, arritmias y la hipertermia. MH fue descrita por primera vez en 1960 por Denborough y Lovell [1], pero puede haber sido responsable de algunas de las muertes anteriores atribuidas a anestesia con ter y cloroformo.2La incidencia clnica de HM en la poblacin depende de la susceptibilidad a la HM y el uso de anestsicosLa incidencia de episodios de HM en la poblacin general es de 1:100 000 anestesiasEs ms frecuente en (2:1) y < 19 aos (45-65%) INCIDENCIA Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate

INCIDENCEThe clinical incidence of malignant hyperthermia (MH) for a given population depends upon the prevalence of MH susceptibility and use of triggering anesthetics. (See"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Prevalence'.)The incidence of episodes of MH in the general population is estimated as 1:100,000 administered anesthetics [6]. This is probably an underestimate because unrecognized, mild, or atypical reactions occur due to variable penetrance of the inherited trait. Approximately half of patients who develop acute MH have one or two uneventful exposures to triggering agents [7,8].EpidemiologyMH occurs in all ethnic groups in all parts of the world. Reactions occur more frequently in males than females (2:1) [6,7,9]. Children under 19 years account for 45 to 52 percent of reported events [7,9].

Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate3Sndrome fulminante (rigidez muscular, acidosis, hipercalemia, arritmias, hipertermia, aumento CK, mioglobinuria): 1 /220 000 pacientes AGB 1/62 000 -Succinilcolina+ halogenado Pocos reportes en embarazadas y parturientas Anestesia regional Frecuencia baja INCIDENCIA Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

EPIDEMIOLOGY Ording[3] reviewed the incidence of MH in Denmark and noted that the incidence of the fulminant syndrome (e.g., muscle rigidity, acidosis, hyperkalemia, arrhythmias, hyperthermia, increased creatine kinase [CK] levels, myoglobinuria) was 1 in 220,000 patients who received general anesthesia, and 1 in 62,000 when succinylcholine was combined with a volatile halogenated agent. MH (either mild or fulminant) was suspected in 1 in 16,000 patients who received anesthesia of any type. The male to female ratio was 1.4:1.[3] There is some geographic variation in the incidence of MH.There are few reports of MH developing during pregnancy and parturition. [4] [5] [6] [7] [8] [9] [10] The infrequent occurrence during pregnancy probably reflects both the low frequency of this disorder in the general population and the widespread use of local and regional anesthetic techniques in obstetric patients.Email to Colleague Print Version

Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

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Los pacientes susceptibles tienen anormalidades genticas en los receptores de m. esqueltico, permitiendo una acumulacin excesiva de Ca++ en presencia de ciertos anestsicos. Durante un episodio de MH, las manifestaciones clnicas son debidas al hipermetabolismo celular: contraccin muscular, rabdomiolisis, metabolismo anaerbico, acidosis, etc.

alignant hyperthermia-susceptible (MHS) patients have genetic skeletal muscle receptor abnormalities, allowing excessive calcium accumulation in the presence of certain anesthetic triggering agents. Very little is known about the specific mechanisms by which anesthetics interact with these abnormal receptors to trigger an MH crisis [4,5,10]. During an episode of MH, the clinical manifestations are due to cellular hypermetabolism, leading to sustained muscular contraction and breakdown (rhabdomyolysis), anaerobic metabolism, acidosis, and their sequelae.5FISIOPATOLOGIA Trastorno en la regulacin del calcio en el m. esqueltico Receptor de RYR (canal calcio del RS)Onda de despolarizacin RYRLiberacin de Ca al citosolInteraccin de miosina y actina Contraccin Muscular Susceptible HM Umbral de activacin Agentes desencadenantes Liberacin Ca++ Contraccin Uso energa (ATP) , consumo O2, CO2 , lactato, calor Contractura irreversible CK, K+, mioglobina, H. sensible a lipasa, Ca+ intracelular PATHOPHYSIOLOGY MH is the result of a disorder in the regulation of calcium in skeletal muscle. In MH-susceptible pigs the ryanodine receptor is the calcium-release channel of the sarcoplasmic reticulum.[11] The ryanodine receptor is a protein that spans the gap between the terminal cisternae of the sarcoplasmic reticulum and the transverse tubule. [12] [13] When an electrical impulse sets off a wave of depolarization down the T tubule, it causes the ryanodine receptor to open up channels, allowing calcium to escape into the myoplasm.[14] This binds troponin, allowing actin and myosin filaments to interact, resulting in contraction.In the muscle of MH-susceptible patients, the activation threshold for the release of sarcoplasmic calcium is reduced. In the presence of volatile halogenated agents an increased release of calcium from the sarcoplasmic reticulum [15] [16] and activation of the actin-myosin contraction system occur, causing an augmentation of contraction. This process is accompanied by the use of energy (adenosine triphosphate [ATP]), increased oxygen consumption, and increased production of carbon dioxide, lactate, and heat. When the heat within the muscle cannot be dispersed, irreversible contracture results. Ultimately, breakdown of the muscle cell and the release of CK, potassium, and myoglobin occur. Increased hormone-sensitive lipase activity in the mitochondria may augment calcium release, leading to calcium-induced calcium release, which further increases contraction. [17] [18] Dantrolene inhibits excitation-contraction coupling, and succinylcholine, caffeine, and volatile halogenated agents increase it.Wappler et al.[19] recently suggested that the 5-hydroxytryptamine (5-HT) system might be involved in the development of MH. In vivo and in vitro experiments using 5-HT agonists and antagonists demonstrated that 5-HT agonists may initiate MH in MH-susceptible pigs and humans. The precise mechanism is unknown.[19]Email to Colleague Print Version

6Hipertermia malignaAnestesicos (halotano), cafena, neurolpticos (fluofenacina), ejerciciocalorhipermetabolismoFalla renalArritmia cardiacaAumento de calcio intracelularFalla de mecanismos reguladores de liberacin de calcioContractura Desacople de fosforilacin oxidativarabdiomilisisCO2O2H+TaquicardiaDao cerebralEn personas predispuestas geneticamente expuestas a: mioglobinaK+efectoresAnestsicos voltiles HalotanoIsofluranoSevofloranoDesfluranoEnflurano

Relajantes musculares Succinilcolina

AGENTES DESECADENANTES Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

TRIGGERING AGENTSThe vast majority of cases of malignant hyperthermia (MH) have occurred while the patient was receiving a volatile anesthetic agent (eg, halothane,isoflurane,sevoflurane,desflurane) with or without administration ofsuccinylcholine[7].MH has been reported following administration ofsuccinylcholinein the absence of an inhalational agent (eg, to facilitate endotracheal intubation). The majority of such cases come from a series of 129 patients who were biopsy-proven MH-susceptible (MHS); 20 of whom manifested their signs of MH with succinylcholine alone (without coadministration of a volatile agent) [30].Acute MH has also been reported in MHS patients exposed to heat stress or vigorous exercise. (See"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Exertional rhabdomyolysis'.) In addition, there are several reports of children that developed spontaneous fatal MH under normal living conditions. Postmortem, these children demonstrated abnormal ryanodine receptor mutations that likely conferred MHS [31,32].MHS patients may not consistently develop the acute syndrome with every anesthetic exposure. While an acute MH crisis may develop at first exposure to a triggering agent, the average patient has had previous exposures prior to having a documented reaction [9].

halothane, enflurane, isoflurane, desflurane, sevoflurane9EMBARAZO E HIPERTERMIA MALIGNA: FISIOLOGIA MATERNA EMBARAZO NORMAL Metabolismo basal, consumo O2, vent/min, HCO3, buffer base(mantener pH normal), Alcalosis respiratoria compensada (* HM )PARTO Metabolismo basal, consumo O2,, vent/min Piruvato y lactato (metabolismo anaerobio y aerobio) +Hiperventilacin durante contraccin Hipoventilacin entre contracciones PaO2Analgesia Obsttrica Compresin Aorto-Cava GC, TA, perfusin utero-plancentaAcelera la acidosis durante una crisis de HM Maternal Physiology Basal metabolic rate, oxygen consumption, and minute ventilation increase during pregnancy.[90] Serum bicarbonate, buffer base, and base excess decrease to maintain normal pH. Thus the pregnant patient typically has a compensated respiratory alkalosis. The decreased buffering capacity could adversely affect the pregnant woman during an episode of MH.Oxygen consumption and minute ventilation increase further during labor.[91] Maternal lactate and pyruvate concentrations increase steadily during labor, indicating an increase in both aerobic and anaerobic metabolism.[92] Hyperventilation during contractions may result in periods of hypoventilation between contractions, which may adversely affect the Pao2 of both the mother and fetus. These metabolic and physiologic responses to pain are similar to those that occur during MH. Effective epidural analgesia decreases oxygen consumption and minute ventilation.[91] If tachycardia and hyperventilation occur despite effective analgesia, they are more likely to signal an episode of MH.

Aortocaval compression from the pregnant uterus results in decreased cardiac output, hypotension, and decreased uteroplacental perfusion. Thus aortocaval compression may accelerate the occurrence of acidosis during an episode of MH. Aortocaval compression hinders resuscitative efforts during cardiac arrest, [93] [94] and evacuation of the uterus (i.e., delivery of the fetus) facilitates maternal resuscitation. The same may be true during an episode of MH. The obstetrician may need to deliver the fetus to facilitate maternal resuscitation during a fulminant case of MH.

Compresin aorto-cava obstaculiza los esfuerzos de resucitacin durante el paro cardiaco , [ 93 ] [ 94 ] y la evacuacin del tero (es decir , la salida del feto ) facilita la reanimacin materna . El mismo puede ser cierto durante un episodio de HM. El obstetra puede tener que entregar el feto para facilitar la reanimacin materna durante un caso fulminante de HM.10

CK concentrations are not diagnostic of MH. During pregnancy, there is a slight decrease in CK levels during the first trimester. CK levels remain stable until term, when they increase by approximately 50%. At delivery, there is an abrupt increase in the CK concentration, followed by a return to normal by 6 weeks postpartum ( Figure 46-1 and Table 46-2 ).[95] The increased CK concentration results from increases in both the CK-M fraction (skeletal muscle) and the CK-B fractions (myometrium, placenta, and fetal blood). Postpartum CK levels are higher in nulliparous patients, regardless of differences in length of labor.[96] Mean plasma CK activity is approximately 50% higher in African-Am

Las concentraciones de CK no son diagnsticos de MH . Durante el embarazo, hay una ligera disminucin en los niveles de CK durante el primer trimestre . Niveles de CK se mantienen estables hasta el trmino , cuando aumentan en aproximadamente un 50 % . En el parto , se produce un aumento brusco en la concentracin de CK , seguido de un retorno a la normalidad a las 6 semanas despus del parto (Figura 46-1 y la Tabla 46-2 ) . [ 95 ] El aumento de concentracin de CK resultados de aumentos tanto en la CK fraccin M ( msculo esqueltico ) y las fracciones CK- B ( miometrio , placenta, y la sangre fetal) . Niveles de CK posparto son ms altos en pacientes nulparas , independientemente de las diferencias en la duracin del parto . [ 96 ] La media de actividad de CK en plasma es de aproximadamente 50 % mayor en los afroamericanos que en los caucsicos o asiticosericans than in Caucasians or Asians11HM es una enfermedad autosmica dominante = 50% si el padre es susceptible EFECTOS EN EL FETO Y EL RECIEN NACIDO

Evitar los agentes desencadenantes Effects on the Fetus and Newborn MH often is inherited as an autosomal dominant gene. In these cases, there is a 50% chance that the infant of an MH-susceptible parent also will be MH susceptible. All anesthetic agents cross the placenta. Small quantities of succinylcholine also cross the placenta. This knowledge should prompt the anesthesiologist to question the choice of anesthetic agents for an MH-negative mother whose fetus has an MH-susceptible father. In this situation, the anesthesiologist should avoid the use of triggering agents until after delivery.There is only one published report of suspected MH in a newborn.[100] The condition is rare in infancy, and some reports of infant MH may represent an undiagnosed myopathy. [62] [101] [102]Email to Colleague Print Version

12ANALGESIA Canalizar Monitorizar temperatura, FC, TA, ECG Evitar compresin aorto-cavaManejo de la paciente susceptible de hmMANAGEMENT OF THE MH-SUSCEPTIBLE PARTURIENT Ideally, an anesthesiologist evaluates every MH-susceptible patient before hospitalization for labor and delivery. Clearly, the obstetrician should consult an anesthesiologist immediately after the admission of each MH-susceptible patient. All hospitals and birthing facilities should be prepared to provide care for MH-susceptible patients. Adequate supplies of dantrolene (at least 36 vials), sterile water, and sodium bicarbonate should be immediately available.Analgesia for Labor Soon after admission, a large-gauge intravenous catheter should be placed in each MH-susceptible patient. Maternal temperature, heart rate, and blood pressure should be monitored throughout labor. During early labor, it may be acceptable to monitor temperature and heart rate intermittently to facilitate maternal ambulation, if desired. Once active labor is established, frequent monitoring of the maternal heart rate and temperature should be initiated. Continuous ECG and axillary temperature monitoring are ideal once the parturient is confined to bed. (Measurement of axillary temperature allows placement of a temperature probe in close proximity to large muscle groups.) Of course, aortocaval compression should be avoided throughout labor and delivery.Most agents that are used to provide intrapartum analgesia are considered safe for the MH-susceptible parturient ( Table 46-3 ). Both the obstetrician and anesthesiologist should encourage the early administration of epidural analgesia. Relief of pain causes decreased maternal stress (as reflected by decreased catecholamine,[103] cortisol,[104] and adrenocorticotrophic hormone [ACTH] concentrations) and decreased maternal metabolism and oxygen consumption.[105] Although experts continue to debate the role of stress in human MH,[17] it is best to decrease stress when possible. Further, the anesthesiologist may extend epidural anesthesia for vaginal delivery or cesarean section if necessary. Extension of epidural anesthesia allows the anesthesiologist to avoid administration of general anesthesia.

13DrugRouteUseSafe MHLocal Anesthetic AgentsBupivacaineRegionalAnalgesia/anesthesiaYesLidocaineRegionalAnalgesia/anesthesiaYesIntravenousIntubation/arrhythmiaYes[*]RopivacaineRegionalAnalgesia/anesthesiaYes2-ChloroprocaineRegionalAnalgesia/anesthesiaYesOpioidsFentanylRegional, intravenousAnalgesiaYesMeperidineRegional, intravenousAnalgesiaYesMorphineRegional, intravenousAnalgesiaYesCOMMON ANESTHETIC DRUGS AND THEIR SAFETY IN MH-SUSCEPTIBLE WOMENDrugRouteUseSafe MHInduction AgentsSodium thiopentalIntravenousInductionYesPropofolIntravenousInductionYesEtomidateIntravenousInductionYesKetamineIntravenousAnalgesia/inductionYesBenzodiazepinesIntravenousAmnesia/anxiolysisYesNeuromuscular Blocking AgentsSuccinylcholineIntravenousMuscle relaxationNoRocuroniumIntravenousMuscle relaxationYesAtracuriumIntravenousMuscle relaxationYesDrugRouteUseSafe MHGeneral Anesthetic AgentsHalothane, enflurane, isoflurane, sevoflurane, desfluraneInhalationAnesthesia, uterine relaxationNoNitrous oxideInhalationAnalgesia/anesthesiaYes

Tachycardia Tachypnea Masseter spasm Generalized rigidity Elevated end-tidal concentration Cyanosis PRESENTACIN CLNICA Arrhythmia Acidosis Hyperkalemia Hyperpyrexia Myoglobinuria Increased CK levelMalignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDateTachycardia Tachypnea Masseter spasm Generalized rigidity Elevated end-tidal CO2 concentration Cyanosis Arrhythmia Acidosis Hyperkalemia Hyperpyrexia Myoglobinuria Increased CK level15Caractersticas clnicas Signos tempranos Rigidez del M. Masetero Incapacidad para abrir la boca de un paciente despus de la administracin de un agente desencadenanteHipercapnia Signo ms temprano Hipercapnia resistente al aumento de ventilacin minutoAGB + Ventilacin espontnea= etCO2 >60 mmHg y PaCO2 >65 mmHgRigidez Muscular Generalizada En presencia de bloqueo neuromuscular se considera patognomnico de MHMalignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDateCaractersticas clnicas Signos Tardios Cambios EKG relacionados a K+Ventricularectopy/ bigeminyTaquicardia/ Fibrilacin ventricular Generalmente es un signo tardoUsualmente ausente en el dx inicial Hipertermia Mioglobinuria Sangrado Excesivo Coluria (coca cola) Inicia a las 14 hrs despues del inicio de la crisis Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDateLater signsLater signs of MH are (table 2):Electrocardiogram changes related to hyperkalemia (see"Clinical manifestations of hyperkalemia in adults", section on 'Cardiac manifestations')Ventricularectopy/bigeminyVentriculartachycardia/fibrillationHyperthermiaMyoglobinuria (see"Clinical manifestations and diagnosis of rhabdomyolysis", section on 'Urine findings and myoglobinuria')Excessive bleedingHyperthermiaHyperthermia is generally a later sign of MH and is typically absent when the diagnosis is initially suspected. It is the first, or an early, sign in only a small proportion of cases [7]. The concept that acute MH generally begins in the postoperative period with isolated hyperthermia is a widespread misconception.MyoglobinuriaBrownish-, cola-, or tea-colored urine indicates the presence of myoglobinuria, which peaks about 14 hours after an acute MH episode.A number of reports have described seemingly normal patients with postoperative rhabdomyolysis and myoglobinuria without any of the other classic signs of MH. MH contracture testing in these patients may be positive; however, it is unclear whether this is due to true MH susceptibility or to a subclinical muscle disease resulting in false-positive test results [39-42]. (See"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'MH susceptibility testing'and"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Muscle disorders with rhabdomyolysis'.)

17Clinical signPercentage with signHypercarbia92.2Sinus tachycardia72.9Rapidly increasing temperature64.7Elevated temperature52.2Generalized muscular rigidity40.8Tachypnea27.1Masseter spasm26.7Sweating17.6Cola-colored urine13.7Cyanosis9.4Ventricular tachycardia3.5Excessive bleeding2.7Ventricular fibrillation2.4Prevalence of clinical signs during MH episodeData from: Larach MG, Gronert GA, Allen GC, et al. Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. Anesth Analg 2010; 110:498.Laboratorio Mixed metabolic and respiratory acidosis Hiperkalemia Creatine Kinase and Myoglubinuria Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc. Laboratory findingsTypical laboratory findings during acute MH are found in the table (table 3).Mixed metabolic and respiratory acidosisIn a series of 196 cases of MH crisis with arterial blood gas (ABG) measurements available, 99 percent of patients developed respiratory acidosis and 26 percent of these MH cases developed a metabolic acidosis (all but one also had respiratory acidosis) [7].HyperkalemiaElevated potassium levels from muscle breakdown can occur rapidly, especially in muscular patients.Elevated creatine kinase and myoglobinuriaPlasma creatine kinase (CK) and urine myoglobin levels peak approximately 14 hours after an acute MH episode. Peak CK levels depend upon the muscle mass of the patient and severity of muscle breakdown; in muscular patients, levels may exceed 100,000units/L.

19Laboratory studyTypical value in MHPatient conditionsCreatine kinase>20,000 international unitsWith succinylcholine>10,000 international unitsWithout succinylcholineUrine myoglobin>60 mcg/LSerum myoglobin>170 mcg/LSerum K>6 mEq/LWithout renal failurePaCO2>60 mmHgDuring controlled ventilation>65 mmHgDuring spontaneous ventilationArterial pH55 mmHg), which does not normalize with increasing ventilationGeneralized muscle rigidity, especially in the presence of neuromuscular blockadeHyperkalemia-related arrhythmias and electrocardiographic changesTachycardia (not explained by clinical scenario)Tachypnea (not explained by clinical scenario)MyoglobinuriaHyperthermiaLINICAL DIAGNOSISDuring an acute event, diagnosis of malignant hyperthermia (MH) is presumptive, based upon a presence of one or more of the typical clinical manifestations associated with MH (table 5). The diagnosis must be considered in all patients receiving triggering agents, as over 90 percent of patients developing acute MH episodes have negative family histories for MH, and over half have had uneventful general anesthetics in the past [7].Treatment must be initiated emergently, as soon as the diagnosis of MH is considered reasonable; this is often before other diagnoses in the differential can be definitively ruled out.Early clinical features reflect increased metabolic demand; the most important of these is the presence of a mixed metabolic and respiratory acidosis, presenting as an increased end-tidal carbon dioxide (ETCO2) level which does not normalize with increasing ventilation.MH should be suspected when one or more of the clinical features arise without another persuasive clinical explanation; more features increase the strength of the presumptive diagnosis:

21RigidityGeneralized muscular rigidity (sustained contracture) during anesthesia with triggering agentsSevere masseter muscle spasm shortly following succinylcholine administrationRhabdomyolysisCK >20,000 international units after anesthesia with succinylcholineCK >10,000 international units after anesthesia without succinylcholineCola-colored urine in perioperative periodUrine myoglobin >60 mcg/LSerum myoglobin >170 mcg/LSerum K >6 meq/L (without renal failure)Clinical indicators of acute malignant hyperthermiaAcidosisControlled ventilation:PETCO2>55PaCO2>60Spontaneous ventilation:PETCO2>60PaCO2>65Inappropriate hypercarbia (judgement)Inappropriate tachypnea (judgement)FeverInappropriate rapid increase in temperature (judgement)Inappropriate perioperative temperature >38.8C (judgement)TachycardiaInappropriate sinus tachycardiaVentricular tachycardia or ventricular fibrillationOtherBase excess below 8 mEq/LArterial pH 38.5 C)ArrhythmiasHyperkalemiaMyoglobinuriaIncreased CK levelDIAGNSTICO TypeSymptoms/signsRiskModerateInconclusive signs of MH involving metabolic and muscle abnormalities, with MH the probable diagnosis0.88MildSigns of metabolic derangement (pH > 7.3, body core temperature 38.5 C)0.14Masseter spasm with rhabdomyolysisCK level > 1500, myoglobinuria0.76Masseter spasm with signs of metabolic disturbanceArrhythmias, rising core temperature0.57Masseter spasm only0.28Unexplained perioperative death or cardiac arrest0.66OtherPostoperative pyrexia or rhabdomyolysis0.07LABORATORIO No se requiere para el diagnstico presuntivo Arterial blood gas with pH 6mEq/LCreatine kinase (CK) >10,000 international units (withoutsuccinylcholine)>20,000 international units (withsuccinylcholine)Serum myoglobin >170mcg/LUrine myoglobin >60mcg/LLaboratory studies are not required for presumptive diagnosis; findings which support the diagnosis include:

24Es el estndar de oro para el diagnstico de Hipertermia Maligna Durante la prueba, se expone el tejido fresco a halotano y cafena y se mide el grado de contraccin. Sensibilidad de 97% y especificidad 78% LABORATORIO Prueba de contractura Cafena/Halotano positivo.Espectroscopia de RMN como prueba de cribado no invasivo para MH.TESTING Susceptibility to MH is determined by a positive caffeine-halothane contracture test. During this test, fresh muscle is exposed to halothane and caffeine, and the degree of contraction is measured. The caffeine-halothane contracture test has been standardized in MH units throughout North America (the North American protocol)[71] and Europe (the European protocol).[72] This test is the gold standard for the diagnosis of MH. The sensitivity and specificity of the North American protocol are 97% and 78%, respectively.[73] Some false-positive results may occur.[74] Patients with a negative caffeine-halothane contracture test subsequently have received anesthesia with triggering agents without incident. [75] [76] [77] Some centers now add ryanodine or 4-chloro-m-cresol to the test to increase its accuracy.[78]Other centers are investigating the use of nuclear magnetic resonance spectroscopy as a noninvasive screening test for MH. Early acidosis and decreased phosphocreatine content occur during graded exercise in MH-susceptible patients.[79] Some of these changes occur with myopathies other than MH, and the investigators have emphasized that further studies are needed to determine whether this technology is suitable for screening for MH susceptibility.In the absence of muscle biopsy results, a parturient with a positive family history should be treated as if she were MH susceptible.Email to Colleague Print Version

25Anestesia/ciruga Insuficiente anestesia/anestesia Insuficiente ventilacin/flujo de gas fresco Mal funcionamiento maquina Sobrecalentamiento Absorcin incrementa de CO2 durante laparoscopia

DIAGNSTICO DIFERENCIAL Enfermedades concomitantes Infeccin/septicemia Feocromocitoma Tormenta tiroidea Patologia cerebral Enfermedad neuromuscular Rabdomiolisis Presentes Signos musculares Hipercapnia Taquicardia Hipertensin Taquipnea CO2

Ausentes Presentes Hipercapnia Ac. Respiratoria Taquicardia Hipertensin

Ausentes Acidosis metablica Signos musculares Presentes Insuficiencia ventilatoria Hipercapnia

Ausentes Hipertermia Differential diagnosisA number of conditions may present perioperatively with clinical manifestations (eg, hypercapnia, tachycardia, muscle rigidity, rhabdomyolysis, hyperthermia, and arrhythmia) that are similar to those of acute MH. Although treatment for MH may have been initiated, it is imperative to continue to consider other causes so as not to miss an alternative diagnosis. (See'Clinical presentation'above.)Anesthesia/surgery-related issuesInsufficientanesthesia/analgesia Patients with insufficientanesthesia/analgesiacan have tachycardia, hypertension, and tachypnea (in a spontaneously-breathing patient), causing hypocarbia; muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) and hypercarbia would not be present.Insufficientventilation/freshgas flow Patients with insufficientventilation/freshgas flow commonly have hypercarbia, respiratory acidosis, and, possibly, tachycardia and hypertension; metabolic acidosis and muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present.Anesthesia machine malfunction A malfunctioning expiratory valve on the anesthesia machine will lead to rebreathing of exhaled CO2, with similar findings as for insufficient ventilation. A malfunctioning temperature probe may indicate hyperthermia that is not present.Overheating Fever alone, no matter how high, is not a useful indicator of acute MH. This may occur as a result of an infectious process or iatrogenic warming; the clinical situation should be taken into account. Postoperative fever is relatively common; in the absence of other signs and symptoms of MH, alternate diagnoses should be sought.Increased CO2absorption during laparoscopy Hypercarbia resistant to increases in minute ventilation may be due to continuous CO2absorption during laparoscopy. The presence of subcutaneous emphysema, or known insufflation of CO2into tissues, makes this a likely explanation. Tachycardia and hypertension are often noted during laparoscopy; muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) and metabolic acidosis would not be present.26Relacionados a Frmacos Anafilaxia Reaccin a transfusin Abuso de drogasAbstinencia a alcohol Sx Neuroleptico maligno Sndrome Serotoninrgico Efectos extrapiramidales de farmacos antisicoticosContaminantes pirogenos

DIAGNSTICO DIFERENCIAL Enfermedades concomitantes Infeccin/septicemia Feocromocitoma Tormenta tiroidea Patologia cerebral Enfermedad neuromuscular Rabdomiolisis Presentes Broncoespasmo Sibilancias presin va area vent/min PaCO2S. y s. dermatolgicos

Ausentes Signos musculares Presentes Fiebre Orina obscura Hipotensin Hipercalemia

Ausentes Signos musculares Cocana: MDMA:Metanfetaminas Drug-related issuesAnaphylaxis Reduced blood pressure may be seen in both anaphylaxis and MH. Anaphylaxis leads to bronchospasm, wheezing, and increased airway pressures, causing lower minute ventilation and thus increased PaCO2; MH-related hypercarbia persists despite higher minute ventilation (from tachypnea or increasing ventilator settings). Ninety percent of anaphylactic episodes include skin symptoms and signs. Muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present with anaphylaxis. (See"Anaphylaxis: Rapid recognition and treatment", section on 'Definition and diagnosis'.)Transfusion reaction Signs common to both transfusion reaction and MH may include fever, brown urine, hypotension, and signs of hyperkalemia. Concomitant transfusion of blood products should raise this possibility. (See"Immunologic blood transfusion reactions".)Drugs of abuse A number of drugs of abuse may cause signs that overlap with MH:Cocaine may cause tachycardia, cardiac arrhythmias, hypertension, and rhabdomyolysis. (See"Cocaine: Acute intoxication".)MDMA (ecstasy) may cause tachycardia, cardiac arrhythmias, hypertension, hyperthermia, and rhabdomyolysis. It may also lead to serotonin syndrome. (See"MDMA (ecstasy) intoxication"and"Serotonin syndrome".)Methamphetamine may lead to tachycardia, hypertension, sudden cardiovascular collapse, and tachypnea. (See"Methamphetamine intoxication".)Alcohol withdrawal Delirium tremens generally begins 48 to 96 hours after the last drink, and may include tachycardia, hypertension, and fever. (See"Management of moderate and severe alcohol withdrawal syndromes".)Neuroleptic malignant syndrome The slow onset of neuroleptic malignant syndrome (NMS) (heralded by mental status changes evolving over one to three days) generally distinguishes it from MH. Both syndromes may include fever, rigidity, and autonomic instability, but NMS does not generally occur during administration of general anesthesia. (See"Neuroleptic malignant syndrome".)Serotonin syndrome This can result from excess ingestion or inadvertent interactions of the many drugs that increase serotonergic activity. It has many signs in common with MH (tachycardia, volatile blood pressure, hyperthermia, and muscle rigidity), as well as elevated CK and metabolic acidosis; but serotonin syndrome may also have signs not seen in MH (tremor, clonus, hyperreflexia, akathisia, and dilated pupils). (See"Serotonin syndrome".)Extrapyramidal side effects of antipsychotic medications These can include muscle spasms, but rapid onset and characteristic localization (usually neck, tongue, or jaw) distinguish them from MH. (See"Pharmacotherapy for schizophrenia: Side effect management", section on 'Extrapyramidal symptoms'.)Pyrogenic contaminants Pyrogenic contaminants to intravenous solutions can cause fever.Coexisting medical conditionsInfection/septicemia Sepsis may be accompanied by fever, metabolic acidosis, and elevations in CK; this makes it difficult to distinguish from MH. Generalized rigidity would not be seen in sepsis. Other perioperative causes of fever are much more common than acute MH. Patients undergoing surgery involving endothelial surfaces (gastrointestinal tract, urogenital tract, etc) are particularly prone to develop fever, which can be due to transient bacteremia or the effects of anestheticsand/orsurgery on the hypothalamic thermoregulatory system [49,50].Pheochromocytoma Undiagnosed pheochromocytoma may present during surgery with episodic severe hypertension and tachycardia. (See"Clinical presentation and diagnosis of pheochromocytoma".)Thyroid storm Thyroid storm may occur in patients with untreated hyperthyroidism, precipitated by surgery or trauma. Symptoms which overlap with MH include tachycardia, cardiac arrhythmia, and hyperthermia to 104 to 106F. Hypotension and cardiovascular collapse may develop. Muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present with thyroid storm. Mental status changes and gastrointestinal symptoms of thyroid storm are not apparent under general anesthesia. (See"Thyroid storm".)Cerebral pathology Fever may result from hypoxic encephalopathy, intracranial bleed, traumatic brain injury, or meningitis.Neuromuscular disorders Patients with various muscular disorders, including Duchenne and Becker muscular dystrophy, may develop rhabdomyolysis or hyperkalemia when exposed to volatile anesthetics orsuccinylcholine; this is not fulminant MH (although these drugs are contraindicated in patients with these conditions). Other disorders (myotonias, osteogenesis imperfecta) may have increased muscular symptomatology or fever during anesthesia without other signs of MH. (See"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Muscle diseases needing non-triggering anesthetics'.)Rhabdomyolysis Rhabdomyolysis may occur from other causes and must be distinguished from MH by the clinical situation. (See"Causes of rhabdomyolysis".)

27Relacionados a Frmacos Infeccin/Septicemia Feocromocitoma Tormenta tiroidea Patologa cerebral Desordenes neuromusculares Rabdomiolisis

DIAGNSTICO DIFERENCIAL Enfermedades concomitantes Infeccin/septicemia Feocromocitoma Tormenta tiroidea Patologia cerebral Enfermedad neuromuscular Rabdomiolisis Presentes Hipertensin severa Taquicardia

Presentes Fiebre Acidosis metbolica CK

Ausentes Rigidez generalizada Taquicardia, arritmia, hipertermiaHipotensin y colapso CV Ausentes Signos musculares Coexisting medical conditionsInfection/septicemia Sepsis may be accompanied by fever, metabolic acidosis, and elevations in CK; this makes it difficult to distinguish from MH. Generalized rigidity would not be seen in sepsis. Other perioperative causes of fever are much more common than acute MH. Patients undergoing surgery involving endothelial surfaces (gastrointestinal tract, urogenital tract, etc) are particularly prone to develop fever, which can be due to transient bacteremia or the effects of anestheticsand/orsurgery on the hypothalamic thermoregulatory system [49,50].Pheochromocytoma Undiagnosed pheochromocytoma may present during surgery with episodic severe hypertension and tachycardia. (See"Clinical presentation and diagnosis of pheochromocytoma".)Thyroid storm Thyroid storm may occur in patients with untreated hyperthyroidism, precipitated by surgery or trauma. Symptoms which overlap with MH include tachycardia, cardiac arrhythmia, and hyperthermia to 104 to 106F. Hypotension and cardiovascular collapse may develop. Muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present with thyroid storm. Mental status changes and gastrointestinal symptoms of thyroid storm are not apparent under general anesthesia. (See"Thyroid storm".)Cerebral pathology Fever may result from hypoxic encephalopathy, intracranial bleed, traumatic brain injury, or meningitis.Neuromuscular disorders Patients with various muscular disorders, including Duchenne and Becker muscular dystrophy, may develop rhabdomyolysis or hyperkalemia when exposed to volatile anesthetics orsuccinylcholine; this is not fulminant MH (although these drugs are contraindicated in patients with these conditions). Other disorders (myotonias, osteogenesis imperfecta) may have increased muscular symptomatology or fever during anesthesia without other signs of MH. (See"Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Muscle diseases needing non-triggering anesthetics'.)Rhabdomyolysis Rhabdomyolysis may occur from other causes and must be distinguished from MH by the clinical situation. (See"Causes of rhabdomyolysis".)

28Diagnstico diferencial DE HIPERTERMIA Y TAQUICARDIA en el embarazo Hipertermia Deshidratacin e infeccin (corioamnioitis, IVU)Respuestas normales:dolor, ansiedad y fiebre TaquicardiaDIFFERENTIAL DIAGNOSIS OF FEVER DURING PARTURITION Infection: chorioamnionitis, urinary tract infection, other infections (e.g., influenza, viral illness) Environmental temperature Epidural anesthesia Dehydration/labor MH Drug reactions: cocaine, atropine, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, neuroleptic malignant syndrome, prostaglandinsDIFFERENTIAL DIAGNOSIS OF TACHYCARDIA DURING PARTURITION Fever Anxiety Blood loss Hypotension Drug reactions: cocaine, atropine, beta-adrenergic tocolytic agents MHThe hallmark signs of MH may be present during normal labor (Boxes 46-4 and 46-5 [4] [5]). Other causes of fever and tachycardia in the MH-susceptible parturient should be excluded. Tachycardia and tachypnea are normal responses to pain, anxiety, and fever. Fever may be a sign of dehydration and infection. Pain and infection (e.g., chorioamnionitis, urinary tract infection) are much more common during parturition than MH. Normal parturients may have a gradual increase in temperature during epidural analgesia.[118] This may be accompanied by a corresponding increase in maternal and fetal heart rate. Box 46-4

DIFFERENTIAL DIAGNOSIS OF TACHYCARDIA DURING PARTURITION Pain Fever Anxiety Blood loss Hypotension Drug reactions: cocaine, atropine, beta-adrenergic tocolytic agents MH

29MANAGEMENT OF MH CRISIS 1. Discontinue all triggering agents. 2. Hyperventilate with 100% oxygen. Disconnect vaporizers if possible. Change carbon dioxide absorbent and tubing when possible. (The machine does not have to be changed immediately.) 3. Administer dantrolene 2.5 mg/kg intravenously (up to 10 mg/kg). 4. Continue dantrolene until temperature, heart rate, and end-tidal CO2 return to normal. 5. Perform serial blood gas measurements. Treat acidosis with sodium bicarbonate 1 to 2 mEq/kg. MANAGEMENT OF MH CRISIS 6. Treat hyperkalemia with glucose and insulin. 7. Treat arrhythmias with procainamide. (Arrhythmias may not develop if dantrolene is administered early.) 8. Cool the patient (e.g., cold intravenous solutions, cooling blanket, lavage of body cavities with cold solutions). 9. Maintain urine output with fluids, mannitol, and/or furosemide. 10. Postoperatively, counsel the patient and refer her for muscle biopsy.

1. Discontinue all triggering agents. 2. Hyperventilate with 100% oxygen. Disconnect vaporizers if possible. Change carbon dioxide absorbent and tubing when possible. (The machine does not have to be changed immediately.) 3. Administer dantrolene 2.5 mg/kg intravenously (up to 10 mg/kg). 4. Continue dantrolene until temperature, heart rate, and end-tidal CO2 return to normal. 5. Perform serial blood gas measurements. Treat acidosis with sodium bicarbonate 1 to 2 mEq/kg. 6. Treat hyperkalemia with glucose and insulin. 7. Treat arrhythmias with procainamide. (Arrhythmias may not develop if dantrolene is administered early.) 8. Cool the patient (e.g., cold intravenous solutions, cooling blanket, lavage of body cavities with cold solutions). 9. Maintain urine output with fluids, mannitol, and/or furosemide. 10. Postoperatively, counsel the patient and refer her for muscle biopsy.

30Call for help:Call for MH equipment and drug cart; notify the surgeon; complete surgical procedure as soon as feasible; callMH Hotline: 1-800-644-9737(US); outside US: 1-209-417-3722Initiate support:Discontinue inhalational agents and succinylcholine; hyperventilate with 100% oxygen; use non-triggering agents for the remainder of the procedure; intubate with endotracheal tubeGive dantrolene:Initial bolus dose 2.5 mg/kgIV rapid continuous push. Continue to administer dantrolene in 1 mg/kg increments until symptoms abate (ie, hypercarbia and/or rigidity resolve).Dantrium and Revonto vs RyanodexWatch for reversal of clinical signs (end tidal CO2should begin to normalize); repeat as needed. Cumulative total doses up to or exceeding 10 mg/kg may occasionally be requiredAcute treatmentGet blood gas/labs:Venous gas (femoral) may be better than arterial gas to follow hypermetabolismGive bicarbonate for acidosis:Sodium bicarbonate 1 to 2 mEq/kg IV push over 5 to 10 minutesCool the patient:Start when core temp >39C; stop when core temp