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Malignant Hyperthermia
Hyperpyrexia Malignant
Malignant hyperthermia is a rare genetic condition occuring during general anesthesia characterized by severe hyperthermia, acidosis, rigid muscles and rhabdomyolysis.

Images

WIKIDATA, Public Domain
WIKIDATA, Public Domain
WIKIDATA, CC BY-SA 4.0

Presentation

We also discuss the reasons for the shift in typical clinical presentation. [ncbi.nlm.nih.gov]

Entire Body System

  • Fever

    In both cases, the discontinuation of rocuronium therapy was followed by the rapid diminution of fever over 12-36 hours. [ncbi.nlm.nih.gov]

    J Pediatr Orthop 1994; 14:799–801Angel, JD Blasier, RD Allison, R Lenhardt R, Negishi C, Sessler DI: Perioperative fever. [doi.org]

    After 4 h of operation, the child went through convulsions, high fever and succumbed within a few hours. High fever was not detected in a timely manner, which is one of the main symptoms of MH. [spandidos-publications.com]

  • High Fever

    After 4 h of operation, the child went through convulsions, high fever and succumbed within a few hours. High fever was not detected in a timely manner, which is one of the main symptoms of MH. [spandidos-publications.com]

    fever, which, if not immediately reversed, can lead to tissue damage or death. [science.sciencemag.org]

    Muscle rigidity, breakdown of muscle fibers ( rhabdomyolysis ), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate are some of the effects of this potentially life-threatening condition. [medicinenet.com]

    This exposure can lead to muscle rigidity, very high fever, failure of other organs (kidney, lung), abnormal blood clotting and other life-threatening complications. [wakehealth.edu]

  • Rigor

    We observed severe generalized rigors, hyperthermia, tachycardia, and a respiratory rate of 50 breaths per minute. [hindawi.com]

    Classic symptoms include hemodynamic instability, combined with acidosis, rigor, and hyperthermia. During cardiopulmonary bypass, these signs may be obscured, delaying correct diagnosis and lifesaving treatment. [circuit.perfusion.com]

    […] caffeine sensitivity of MHS muscle is mediated by an increase in the resting myoplasmic Ca 2+ concentration (Lopez et al., 2000 ), the effect of caffeine on the Ca 2+ and Mg 2+ affinities of the A- and I-sites of the MHS and normal RyR1 have not been rigorously [web.archive.org]

  • Chills

    Other measures to reduce core body temperature include administering chilled 0.9% sodium chloride solution I.V.; placing ice packs at his groin, axillae, and neck; and applying a temperature-regulating blanket. Monitor his core body temperature. [journals.lww.com]

    For example, active-liquid systems operate by chilling water and circulating it through a garment; the skin surface area is thereby cooled through conduction. [en.wikipedia.org]

Respiratoric

  • Tachypnea

    In response to the acidosis, patients breathing spontaneously develop tachypnea that only partially compensates. [msdmanuals.com]

    Many features of a typical malignant hyperthermia episode were present, including tachydysrhythmia, tachypnea, and fever in association with metabolic acidosis, hyperCKemia, myglobinemia, and rapid recovery without residual effects upon administration [ncbi.nlm.nih.gov]

Cardiovascular

  • Tachycardia

    Pathologic response in MH include increase in oxygen consumption, increase in endtidal CO2, tachycardia, hyperthermia, hyperkalemia and muscle rigidity. Immediate recognition and treatment are crucial to avoid lethal outcome. [ncbi.nlm.nih.gov]

    Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO 2. [msdmanuals.com]

    Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO2. [merckmanuals.com]

  • Hypertension

    He showed the earlier clinical signs, such as elevation of end-tidal $CO_2$, tachycardia, and hypertension. After prompt administration of dantrolene, operation was continued with profopol and midazolam. [chikd.org]

    After a preprocedural pain block for elective right shoulder arthroscopy, a 53-year-old hypertensive white man developed chest pain. In the operating room, he had increased blood pressure. [ncbi.nlm.nih.gov]

    Disease (1) increased ETCO2 (2) tachycardia (3) tachypnoea (4) masseter spasm (if develops this convert to a MH safe anaesthetic) (5) muscle rigidity (6) temp increase (late) – 1 C\15min intra-op & 4\24 post op tachyarrhythmia difficulty ventilation hypertension [lifeinthefastlane.com]

    Just click on your patient’s weight and you have many categories to choose from: Blades/Tubes/LMA/Gases All our Anesthesia Drugs Local Anesthetics Labor and Delivery (detailed) Antihypertensive Meds Beta Blockers Hypertensive Meds/Pressors Asthma (Mild [play.google.com]

  • Hypotension

    After 10 minutes of halothane anesthesia, the patient became tachycardic, hypotensive, hypoxemic, and hyperthermic, and the halothane was discontinued. He was packed in ice and subsequently recovered uneventfully. [newswise.com]

    Later signs include complex arrhythmias, cyanosis, hypoxia, hypotension, electrolyte abnormalities, rhabdomyolysis and severe hyperthermia. Hyperthermia is a late sign. Rhabdomyolysis is a sign of the severity of the condition. [patient.info]

    •Bradycardia •Bronchiolitis •Burns •Cardiac Arrest •Coma •Congenital Heart Disease •Croup •Diabetic Ketoacidosis •Fever •Head Injury •Hyperkalaemia •Hypertensive Crises •Hypoglycaemia •Hypokalaemia •Hypomagnesaemia •Hypophosphataemia •Hyponatraemia •Hypotension [play.google.com]

    Signs and Symptoms Approximate number of patients (when available) Abnormality of the coagulation cascade - Autosomal dominant inheritance - Elevated serum creatine phosphokinase - Fever - Hyperkalemia - Hyperphosphatemia - Hypotension - Malignant hyperthermia [web.archive.org]

    CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ] 0003236 Hypotension [rarediseases.info.nih.gov]

Skin

  • Sweating

    Clinical manifestations include: CO 2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending [ncbi.nlm.nih.gov]

    They can include: Severe muscle rigidity or spasms Rapid, shallow breathing and problems with low oxygen and high carbon dioxide Rapid heart rate Irregular heart rhythm Dangerously high body temperature Excessive sweating Patchy, irregular skin color [mayoclinic.org]

    […] signs Inappropriately elevated carbon dioxide production, which is manifested as raised end-tidal CO on capnography or as tachypnea if the patient is breathing spontaneously Increased oxygen consumption Mixed metabolic and respiratory acidosis Profuse sweating [revonto.com]

    The main risk factor for hyperthermia is the lack of ability to sweat. People that are dehydrated or who are older in age may not produce the sweat they need to regulate their body temperature[26]. [en.wikipedia.org]

    […] increased ETCO2 (2) tachycardia (3) tachypnoea (4) masseter spasm (if develops this convert to a MH safe anaesthetic) (5) muscle rigidity (6) temp increase (late) – 1 C\15min intra-op & 4\24 post op tachyarrhythmia difficulty ventilation hypertension sweating [lifeinthefastlane.com]

  • Erythema

    Less than twenty minutes after initiation of volatile anesthesia, profound skin erythema and hyperthermia were installed, with the body temperature reaching 41 Celsius degrees. [pubs.sciepub.com]

    […] reconstitution, dantrolene is stable at room temperature for 6 hours when protected from light. 18 Adverse effects associated with dantrolene include loss of grip strength, muscle weakness, drowsiness, dizziness, and injection site reactions, including pain, erythema [healio.com]

Musculoskeletal

  • Myalgia

    We present four recently referred cases to illustrate this point: one late-onset case, two patients with slowly progressive hypercapnia as the sole sign and a fourth patient with postoperative myalgias and elevated creatine kinase. [ncbi.nlm.nih.gov]

    Before an anaesthetic ask about unclear complications from previous anaesthesia, muscle disorders in the family, myalgia, muscle cramps and dark urine. If there is suspicion, check CK. If in doubt, use a trigger-free anaesthetic. [patient.info]

    Roberts, M, Vrancken, AF, van der Pol, WL, de Coo, RI, Manzur, AY, Yau, S, Abbs, S, King, A, Lammens, M, Hopkins, PM, Mohammed, S, Treves, S, Muntoni, F, Wraige, E, Davis, MR, van Engelen, B, Jungbluth, H Mutations in RYR1 are a common cause of exertional myalgia [anesthesiology.pubs.asahq.org]

  • Muscle Spasticity

    It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), and 2,4-dinitrophenol poisoning,[2][3] and the related compounds dinoseb and [en.wikipedia.org]

    [Spasticity 2006] Spasticity refers to the often painful involuntary tensing, stiffening or contracting of muscles. [medmk.com]

Neurologic

  • Confusion

    Signs of an MH reaction are non-specific and may be confused with the presentation of other problems such as sepsis and overheating of a patient. A high index of suspicion is needed to be aware of an early presentation of MH. [ncbi.nlm.nih.gov]

    Some degree of increased muscular tone is usually present, which may be confused with the lead-pipe rigidity seen with NMS. [calpoison.org]

    Flushed skin Sweating An abnormally rapid or irregular heartbeat Rapid breathing or uncomfortable breathing Brown or cola-colored urine Very low blood pressure (shock) Confusion Muscle weakness or swelling after the event Many people who carry a gene [drugs.com]

    Nevertheless, severe CNS impairment, such as confusion, delirium, coma or seizures, was required in all cases. [journals.plos.org]

    Hyperthermia from neurological disease may include little or no sweating, lack of heart rate change, and confusion or delirium. Other signs and symptoms vary. [en.wikipedia.org]

  • Altered Mental Status

    Serotonin toxicity is characterized by a triad of altered mental status, autonomic effects, and neuromuscular excitation. [calpoison.org]

    Neuroleptic malignant syndrome is characterized by muscle rigidity, hyperthermia, hyperkalemia, acidosis, autonomic instability, and altered mental status most often occurring after the use of neuroleptic agents such as haloperidol, but it has also been [healio.com]

  • Agitated Delirium

    Cocaine-associated agitated delirium and the neuroleptic malignant syndrome. Am J Emerg 1996;14:425-428 51.-TSAI G. et al: Neuroleptic Malignant Syndrome Associated with clozapine treatment. [uninet.edu]

Workup

Neurology workup revealed the presence of a known causative ryanodine receptor (RYR1) mutation for MH, c.7522C>T; p.R2508C. Furthermore, the neurology workup diagnosed the child with King-Denborough syndrome (KDS). [ncbi.nlm.nih.gov]

She was administered 2 liters of normal saline and a workup for possible infection ensued. Her sister later arrived and stated that her paroxetine dose was doubled from 20 to 40 mg last week and that she may have taken a few extra pills. [calpoison.org]

Serum

  • Hypercapnia

    The following tachycardia, hypercapnia and hyperthermia led to the diagnosis of malignant hyperthermia. Symptoms were relieved dramatically after the discontinuation of sevoflurane. [ncbi.nlm.nih.gov]

  • Creatine Phosphokinase Increased

    […] kinase Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine [rarediseases.info.nih.gov]

Treatment

If these complications occur even with initial treatment with dantrolene, our experiences may be useful adjunctive treatments to consider. [ncbi.nlm.nih.gov]

Management and Treatment How is malignant hyperthermia treated? The main treatment for malignant hyperthermia is a drug called dantrolene (Dantrium®). Anesthesiologists administer this drug immediately if they suspect malignant hyperthermia. [my.clevelandclinic.org]

Quarterly drills on reconstitution of dantrolene and treatment of malignant hyperthermia were also deemed to be necessary. [doi.org]

FDA-Approved Treatments The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. [web.archive.org]

Prognosis

Prognosis The syndrome is likely to be fatal if untreated but thanks to the dramatic progress in understanding the clinical manifestations and pathophysiology of the syndrome, the mortality from MH has dropped from over 80%, thirty years ago, to less [orpha.net]

[…] inotropes as needed HCO3 2-4mEq/kg Dantrolene 2.5mg/kg every 5min (total dose 10mg/kg/day – continuous infusion or treat recurrence (25%)) cardiac arrhythmias -> beta blockers & lignocaine. high K+ -> glucose-insulin & frusemide watch for DICCK Q6hrly PROGNOSIS [lifeinthefastlane.com]

[…] surgery, tell your surgeon, primary care doctor and anesthesiologist if you: Have a family history of malignant hyperthermia Have had one or more episodes of heat stroke or exercise-induced hyperthermia Have muscle symptoms or a known muscle disease Prognosis [drugs.com]

Etiology

DNA samples were collected from 885 patients in 4 groups: severe statin myopathy (n=197), mild statin myopathy (n=163), statin-tolerant controls (n=133), and non-drug-induced myopathies of unknown etiology characterized by exercise-induced muscle pain [ncbi.nlm.nih.gov]

References:[1][2][4] Malignant hyperthermia Summary Epidemiology Etiology Pathophysiology Clinical features Diagnostics Differential diagnoses Treatment [amboss.com]

Epidemiology

Epidemiology References:[1][2] Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

Epidemiologic data on the geographic variation in MH prevalence is scant. The objective of this study is to examine the prevalence of recorded MH diagnosis in patients discharged from hospitals in four states in the United States. [ncbi.nlm.nih.gov]

Our aim was to present the most recent data concerning epidemiology, genetics, pathophysiology, clinical course, treatment, and diagnosis of MH. [termedia.pl]

Pathophysiology

Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006. [ncbi.nlm.nih.gov]

The pathophysiologic changes of MH are due to an uncontrolled rise in myoplasmic calcium, which activates biochemical processes related to muscle activation. [orpha.net]

References:[1][2][4] Malignant hyperthermia Summary Epidemiology Etiology Pathophysiology Clinical features Diagnostics Differential diagnoses Treatment [amboss.com]

Prevention

Prevention Can malignant hyperthermia be prevented? Malignant hyperthermia is difficult to prevent unless you know you have the genetic mutation that causes it or you have a family history of the condition and have told your anesthesiologist. [my.clevelandclinic.org]

This prevented us from making a definitive diagnosis in our patient. [ncbi.nlm.nih.gov]

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