Family History Of Malignant Hyperthermia Research Articles

A Single-Center Retrospective Review of Patients with Suspected Malignant Hyperthermia Susceptibility.

Purpose The diagnosis of malignant hyperthermia susceptibility (MHS) has significant implications for the perioperative period that may persist for generations. Anesthetic medication options are reduced, anesthetic workstations require preparation to reduce exposure to inhaled volatile anesthetics, and patients may be excluded from surgery at ambulatory centers. In this study, we sought to better characterize the etiology of MHS diagnoses in our health system and the downstream effects of this diagnosis on anesthetic care. Methods We retrospectively reviewed the electronic medical records of 55 patients with a documented concern for MHS who received care at University of Florida (UF) Health between 2014 and 2020. We characterized the etiology of the patient's MHS diagnosis, whether this diagnosis was supported by formal genetic or muscle contracture testing, and the details of the recorded anesthetics that were delivered to these patients. Results The 55 patients with suspected MHS were evenly split between those with a family history of malignant hyperthermia (MH) (28/55) and those with a concern for MHS in their personal medical history (27/55). Of the 28 patients with a family history of MH, 16 reported that the affected family member was a first-degree relative, and two of these 16 reported that the affected family member had undergone confirmatory muscle contracture testing. Of the 27 patients with a personal history suspicious for MHS, two had undergone confirmatory genetic testing, and two patients had anesthetic records available for review where intraoperative MH was suspected and treated with dantrolene. An additional four patients were told of a concern about MHS due to another underlying diagnosis. No patients with a personal history suspicious of MHS had undergone confirmatory muscle contracture testing. These 55 patients underwent 87 anesthetics, and exclusively non-triggering anesthetic techniques were utilized in nearly all cases. In pediatric patients, some perioperative challenges were identified, related to the avoidance of mask inhalational induction. Only six of these 87 anesthetics occurred at our ambulatory surgery centers, a proportion (6.9%) lower than that of the general surgical population at UF Health (20.0%). Conclusions Among patients suspected to be MH susceptible in our health system over a six-year period, a minority (8/55) were supported by clear records of a prior MH event, confirmatory genetic or muscle contracture testing, or an underlying diagnosis closely linked to MH. The vast majority had limited documentation supporting their MH risk but continued to be treated with non-triggering anesthetics and were less likely to have surgery at an ambulatory surgery center than our overall surgical population. Among pediatric patients, some anesthetic challenges related to delivering non-triggering anesthetics were identified. Improving the documentation of index cases of MH and increasing referrals to clinical geneticists and genetic testing may be a viable route to decreasing the proportion of suspected MHS patients with a poorly characterized risk profile.

Risk-Stratifying Patients at an Increased Risk of Malignant Hyperthermia: Improving Safety by Expanding Beyond Classic Tenets

Malignant hyperthermia (MH) is classically described as an autosomal dominant myopathy involving type 1 ryanodine receptor (RYR1), which predisposes affected individuals to potentially life-threatening sequela when exposed to volatile anesthetics or depolarizing skeletal muscle relaxants, such as succinylcholine. In cases where malignant hyperthermia or anesthetic induced rhabdomyolysis (AIR) is triggered, significant morbidity and often mortality can result. In an ambulatory anesthetic setting, family history of malignant hyperthermia and history of anesthetic-related events is typically utilized to screen out susceptible individuals. Furthermore, in cases where suspicion of increased risk for MH susceptibility is present, volatile agents and depolarizing muscle relaxants are avoided, per recommendations of Malignant Hyperthermia Association of US. However, MH phenotype has been found to be inherited with incomplete penetrance and variable expression. Investigations into the molecular genetics of MH have revealed over 400 different variants in the RYR1 gene, with fewer than 40 variants that have been functionally characterized. Exome studies have suggested that the incidence of RYR1 variants in general population is as high as 1 in 2000-3000 persons. These data suggest that potential for triggering malignant hyperthermia is much greater than previously estimated, even if a fulminant reaction is not encountered. Estimates based on genomic analysis call for increased index of suspicion in patient selection for ambulatory anesthesia, compelling for improved risk stratification, as well as improved level of preparedness to treat malignant hyperthermia. This is especially pertinent for providers that administer anesthesia to pediatric populations, as pediatric patients have been documented to exhibit MH/AIR response in the absence of volatile anesthetic exposure.

Perioperative management in a malignant hyperthermia susceptible patient

Malignant hyperthermia (MH) is a rare genetic disorder. Susceptible one could suffer fatal condition if the patient is exposed to triggers. MH can be seen in many general anesthesia procedures using volatile anesthetics. In susceptible patients who will be undergoing surgery, the most important is to prevent intraoperative MH despite overcoming the crisis. This case will discuss an elective spine surgery performed in a patient with a family history of MH.

Muscular body build and male sex are independently associated with malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is a disorder of the regulation of calcium in skeletal muscle. Muscular individuals have been shown to have a 13.6-fold increased risk of death during malignant hyperthermia (MH) episodes and are more likely to experience a recurrence after initial treatment. Twenty-five percent of severe MH episodes have occurred in elite athletes. This study investigated the association between MHS and muscular body build. Data were obtained from existing reports in the North American Malignant Hyperthermia Registry, including the Report of Muscle Biopsy and Contracture Testing (caffeine-halothane contracture test [CHCT]) as well as Adverse Metabolic or Muscular Reaction to Anesthesia (AMRA) reports. Malignant hyperthermia susceptible individuals were compared with MH negative individuals with regard to body build and reason for testing. Males were also compared with females. Both the CHCT and the AMRA forms were reviewed for comments. Of the 1,292 individuals diagnosedwith MHS by CHCT, males were more likely to be diagnosed with the disorder than females (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.99 to 2.7; P < 0.001). Muscular individuals were more likely to be diagnosed with MHS than non-muscular individuals (OR, 1.94; 95% CI, 1.51 to 2.49; P < 0.001). Males were more likely to be tested after having a possible MH episode (OR, 2.33; 95% CI, 1.45 to 2.1; P < 0.001). Logistic regression showed that male sex (OR, 2.28; 95% CI, 1.93 to 2.7; P < 0.001) and muscular body build (OR, 2.17; 95% CI, 1.21 to 3.9; P = 0.01) were independently predictive of MHS. The interaction between muscular body build and male sex was not significant (P = 0.13). Indications for testing, MH episode vs family history of MH, did not differ between muscular and non-muscular individuals (P = 0.44). Eight of 839 AMRAs and two reports of CHCT had comments describing athletic abilities. Ryanodine receptor type 1 (RYR1) gene mutations were found in five of these athletes. Muscular body build and male sex are strongly associated with MHS.

Is It Exertional Heatstroke or Something More? A Case Report

BackgroundHeat stroke, heat-related illness, and malignant hyperthermia all present with hyperthermia. The former two are common presentations in the emergency department (ED). On the other hand, malignant hyperthermia (MH) is an uncommon but equally dangerous condition that requires prompt recognition and specific treatment with dantrolene sodium and avoidance of certain medications to reduce morbidity and mortality. Recent research focusing on nonanesthetic or exercise-induced MH has demonstrated a relationship between certain gene mutations and malignant hyperthermia susceptibility. Case ReportWe report the case of a 19 year-old man with a family history of MH who was treated for exertional heat stroke, but despite cooling and adequate fluid resuscitation, demonstrated worsening rhabdomyolysis that subsequently responded to the administration of dantrolene sodium. Why Should An Emergency Physician Be Aware of This?This case illustrates the importance of recognizing the potential relationship between exertional heat stroke and malignant hyperthermia. The overlap between heat stroke and malignant hyperthermia susceptibility has important implications in the treatment and evaluation of patients presenting with signs and symptoms of heat stroke or heat-related illness in the ED.

Targeted exon capture and NGS to investigate an undefined myopathy reveal RYR1 variants

Background The family under investigation consists of parents and two daughters, one being the proband. The mother and the proband have elongated facial features. The father and second daughter appear normal. The older daughter presented for elective tonsillectomy aged 8 years. She had severe masseter spasm after suxamethonium. The rest of the procedure was carried out under total intravenous anaesthesia. No blood gas analysis could be done, but a creatine kinase next day was significantly elevated (2934). This led to study of both parents. There was no family history of malignant hyperthermia but an undefined myopathy was suspected in mother and daughter. Both mother and father were diagnosed malignant hyperthermia (MH) susceptible by in vitro contracture test (IVCT). This prompted a DNA analysis for variants associated with MH.

An ex utero intrapartum treatment procedure in a patient with a family history of malignant hyperthermia

In the EXIT (ex utero intrapartum treatment) procedure, after uterine incision, uterine relaxation is maintained to prevent placental separation and the fetus is supported via the placenta until the airway is successfully established. The traditional method to maintain uterine relaxation is with the use of high-dose potent inhaled anesthetics during general anesthesia. A patient with a family history of malignant hyperthermia required an EXIT procedure. The history of malignant hyperthermia precluded the use of potent inhaled anesthetics and an alternate plan using propofol and remifentanil infusions for anesthesia and nitroglycerin 16μg/kg/min for uterine relaxation allowed for good surgical conditions. The presence of malignant hyperthermia required an alternate plan and close collaboration in order to ensure good patient outcome.

In-vitro contracture testing for susceptibility to malignant hyperthermia: can halothane be replaced?

Malignant hyperthermia is a potentially lethal inherited hypermetabolic syndrome that develops in susceptible individuals following administration of depolarising neuromuscular relaxants or volatile anaesthetics. Genetic analysis can only confirm a diagnosis of malignant hyperthermia in about 70%, and in the remainder an in-vitro contracture test, with halothane and caffeine, on muscle obtained from open muscle biopsy is required to establish the diagnosis. As the licence for clinical use of halothane expired in 2005, its continuing availability is in doubt. More modern volatile anaesthetics such as enflurane, isoflurane, desflurane and sevoflurane are less potent triggers of malignant hyperthermia in humans and pigs. The aim of this study was to investigate whether these agents can be considered possible substitutes for halothane in a modified in-vitro contracture test. With institutional review board approval and prior written consent, muscle bundles of 30 patients with a personal or family history of malignant hyperthermia were investigated. Of these, 13 were diagnosed malignant hyperthermia susceptible and 17 nonsusceptible. Surplus muscle was tested with increasing concentrations of enflurane, isoflurane, desflurane and sevoflurane. There were no differences in weight, length or predrug tension of the muscle bundles. At increasing concentration, all volatile anaesthetics except sevoflurane induced significantly greater contractures in malignant hyperthermia susceptible compared to malignant hyperthermia nonsusceptible muscle. In malignant hyperthermia susceptible muscle bundles, halothane led to significantly higher contractures compared to the other investigated substances. Halothane was the strongest discriminator for malignant hyperthermia in the in-vitro contracture tests. It remains the ideal substance for diagnostic testing and cannot simply be replaced by other agents in this test.

Dexmedetomidine as the primary anesthetic agent during cardiac surgery in an infant with a family history of malignant hyperthermia

Malignant hyperthermia (MH) is an acute hypermetabolic crisis triggered in susceptible patients by the administration of succinylcholine or a volatile anesthetic agent. When providing anesthetic care for MH-susceptible agents, a total intravenous anesthetic (TIVA) technique is frequently chosen. When choosing the components for TIVA, several options exist including the combination of propofol or dexmedetomidine with an opioid. We present our experience with the use of dexmedetomidine as a key component of the anesthetic regimen in a 5-month-old infant with a family history of MH. Previous reports of the use of dexmedetomidine in MH-susceptible patients are reviewed and its benefits in such patients discussed.

Operating Room Desensitization as a Novel Treatment for Post–Traumatic Stress Disorder after Intraoperative Awareness

Operating Room Desensitization as a Novel Treatment for Post–Traumatic Stress Disorder after Intraoperative Awareness

Le blues du méthylène : prévenir les réactions indésirables aux médicaments non anesthésiques

NE of the main focuses in the training of anesthesiologists is the art of applied clinical pharmacology. The many and diverse drugs that we use daily have near instantaneous actions, satisfying the need for “immediate gratification” that attracted many of us to this field. We are also well trained in anticipating and treating the unintended effects of our pharmacologic armamentarium. These range from common side effects such as hypotension or hypoventilation, to sporadic reactions such as anaphylaxis. To complicate matters, the incidence of adverse drug reactions is influenced by factors such as age, ethnicity, pre-existing medical conditions and concurrent drug therapy. For example, we can predict that elderly, diabetic or hypertensive patients may have an exaggerated blood pressure response to induction agents, or that angiotensin converting enzyme inhibitor and beta adrenergic blocking drugs may alter the hemodynamic response to anesthetics. In this way, we constantly anticipate reactions and tailor our anesthetic techniques to account for these factors. Similarly, many patients present with a history of allergic reactions to medications; these drugs can easily be avoided. We can also predict a higher incidence of such reactions in patients with other known sensitivities, such as the increased incidence of reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in patients with allergy to aspirin, 1 or an alteration in response to meperidine in patients receiving monoamine oxidase inhibitors. 2 A family history of malignant hyperthermia or cholinesterase deficiency prompts special precautions due to the known genetic transmission of these traits. Frequently, it is not the drug compound that is responsible for reactions, but rather preservatives in the preparations, such as local anesthetics with the preservatives methylparaben in patients with a history of sunscreen allergy, and sodium metabisulfite in patients with sulfite allergy. 3 There is, however, an increasing demand on the anesthesiologist to administer (and thereby assume responsibility for) a variety of non-anesthetic drugs. In addition, drugs, or other potential allergens such as disinfectant preparations, are frequently administered by surgeons and nurses, with the expectation that the “resuscitation expert” at the head of the table will deal with any potential reactions. A list of commonly used agents that fall into this category is provided in the Table; this list is not comprehensive, and there are new drugs with potential reactions being added almost daily.

Central core disease with family history of malignant hyperthermia: report of one case.

A 10-month-old boy presented with gross motor delay and muscle weakness, especially in both lower limbs. At age 5, he developed lordosis, talipes, and planovalgus. His grandmother died of malignant hyperthermia during surgery. On neurological examination, he had mild proximal muscle weakness and atrophy, decreased deep tendon reflexes and Gowers' sign, but his intelligence was normal. The electromyogram showed myopathic pattern. Muscle biopsy revealed type 1 fiber atrophy and central core abnormalities. We report this case of central core disease with a family history of malignant hyperthermia during surgery.

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome

Testing for malignant hyperthermia.

Testing for malignant hyperthermia.

Sudden unexplained death in a patient with a family history of malignant hyperthermia

A 23-year-old healthy white male in excellent physical condition developed cardiac arrest and rigidity during moderate exercise. He had a strong family history of malignant hyperthermia (MH). Two hours postmortem, his temperature was noted to be markedly elevated [41 degrees C (106 degrees F)]. A review of the possible differential diagnoses point to MH as a reasonable etiology.

Malignant Hyperthermia During Sevoflurane Administration

Malignant Hyperthermia During Sevoflurane Administration

Greater than normal variability of Ca-induced Ca release in muscle fibers of a patient with a positive family history of malignant hyperthermia.

Greater than normal variability of Ca-induced Ca release in muscle fibers of a patient with a positive family history of malignant hyperthermia.

Prevention and Management in a Patient with Family History of Malignant Hyperthermia

Prevention and Management in a Patient with Family History of Malignant Hyperthermia

In Vitro Contracture Tests for Susceptibility to Malignant Hyperthermia

In an attempt to compare the results of physiologic contracture tests for malignant hyperthermia (MH) susceptibility between laboratories, a testing protocol was agreed upon by several investigators. This protocol was followed in order to determine which of several procedures is best able to identify MH susceptibility. Muscle biopsies were obtained from 12 normal control patients, 6 survivors of an MH episode, 24 patients who experienced succinylcholine-induced masseter muscle rigidity, 15 patients with a family history of MH, and 12 patients who had adverse reactions to anesthesia (not clearly MH). In all cases muscle strips were stimulated electrically and the contracture responses of different strips to halothane alone, caffeine alone, and caffeine in the presence of 1 % halothane were evaluated. In addition to the contracture response the caffeine-specific concentration was calculated (concentration of caffeine needed to produce a 1-g contracture). The procedures best able to discriminate MH positives from controls employed halothane alone or caffeine alone. Muscle contracture of 0.772 ± 0.585 g (mean ± SEM) was observed in biopsies from known MH susceptibles in response to 2 mM caffeine; the response of control muscle was significantly different (0.17 ± 0.209 g). Halothane contractures of 1.425 ± 1.098 g were recorded from muscle from known MH patients while contractures of 0.023 ± 0.169 g were found in control patients (significantly different). Using a caffeine-specific concentration of 2.2 mM, 10 of 15 normal people were misclassified as MH positive: using a halothane-caffeine-specific concentration of 0.7 mM, 4 of 15 normal people were misclassified as MH positive. Twelve of 21 patients presenting with succinylcholine-induced masseter muscle rigidity were MH positive, 50% of these had a family history of MH that was positive, and 1 of 12 with an “adverse” reaction to anesthesia was MH positive. The present results confirm the clinical utility of in vitro muscle testing in the diagnosis of MH and suggest other areas of usefulness including evaluation of the clinical significance of isolated adverse reactions to anesthesia and counseling of families having members known to be MH susceptible.

Malignant hyperthermia: current perspectives

The incidence, etiology, clinical manifestations, and management of malignant hyperthermia (MH) are reviewed. The syndrome of MH is recognized as one of the causes of anesthesia-related deaths. It is considered pharmacogenetic because both an abnormal gene and precipitating environmental factors are necessary to produce an acute reaction. Metabolic defects, involving a derangement of calcium dynamics, appear to be the common characteristic of susceptible individuals. Calcium release and uptake from the sarcoplasmic reticulum is altered when an individual with MH is exposed to certain anesthetic agents or triggering physical and emotional stresses. Muscle rigidity, tachycardia, tachypnea, and high fever can lead to other complications and death. Management of an acute reaction of MH includes cooling methods to lower body temperature, hyperventilation, sodium bicarbonate control of acidosis, maintenance of fluid and electrolyte balance, and the administration of dantrolene sodium. A thorough family history, baseline CPKs, caffeine-halothane contracture tests, and ultramicroscopic examination of muscle biopsy specimens are recommended as screening techniques. The early administration of dantrolene sodium in acute reaction of MH has been shown to rapidly alleviate the symptoms and ensuing severe complications. Individuals with a strong family history of MH or previous episodes may be treated with oral dantrolene sodium before surgery to effectively prevent a crisis, and after surgery to prevent recurrence.