Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia developed in a 4-year-old Thoroughbred horse following 3 hours and 15 minutes of halothane anesthesia, with supplementary succinylcholine. Clinical signs included fever, sweating, hyperventilation, tachycardia, and decreased blood pressure followed by a rapid increase in blood pressure. Biochemical aberrations included hypocalcemia, hyperkalemia, hyperphosphatemia, myoglobinuria, and high creatine phosphokinase and ornithine carbamyl transferase activities. Treatment consisted initially of surface cooling with cold water, alcohol and ice, IV administration of cooled balanced electrolyte solutions and sodium bicarbonate, and removal from the anesthetic and rebreathing circuit. Oxygen was given by endotracheal insufflation. The rectum was then packed with ice, the horse was moved to a recovery raft and pool, and his body was packed in ice. Xylazine and dantrolene were given during recovery from anesthesia. Following recovery, treatment consisted of administration of balanced electrolyte solutions, calcium borogluconate, potassium penicillin, meperidine, and additional dantrolene. Muscle biopsy demonstrated exaggerated contracture responses to halothane and caffeine, confirming a diagnosis of malignant hyperthermia. The horse was returned to training following a routine postsurgical convalescent period.
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PMID:Malignant hyperthermia in a halothane-anesthetized horse. 734 3

A 17-year-old male received general anesthesia for repair of a torn right knee anterior cruciate ligament. The medical history revealed manic-depressive psychosis, treated with lithium carbonate and sertraline hydrochloride, and asthma for which the patient occasionally used an albuterol inhaler. Induction with propofol, isoflurane, nitrous oxide, and oxygen was uneventful. Anesthesia was maintained by isoflurane, nitrous oxide, and oxygen. During the first 90 minutes after induction, a persistent mild elevation in end-tidal carbon dioxide was noted, and several possible causes for this elevation were subsequently ruled out. A diagnosis of malignant hyperthermia was made when the patient exhibited tachycardia and a temperature increase, although some discussion remained regarding the possibility of neuroleptic malignant syndrome. The patient was treated successfully using a malignant hyperthermia protocol. Malignant hyperthermia may prove fatal if effective treatment is delayed. Favorable outcome and patient prognosis rely on astute vigilance, accurate diagnosis, and swift, appropriate treatment.
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PMID:Differential diagnosis of malignant hyperthermia: a case report. 892 98

This study examines the chronologic relationship of the biochemical and clinical development of malignant hyperthermia (MH) in susceptible swine. Four pigs previously established by challenge to be susceptible to MH were studied. Monitors included end-tidal CO2 (ETCO2), transcutaneous oxygen saturation (Spo2), intraarterial blood pressure, rectal temperature, electrocardiogram (ECG), and train-of-four twitch measurements. Calcium-selective microelectrodes were used to monitor changes in the concentration of free myoplasmic calcium ([Ca2+]i). The animals were studied in the resting state, during the development of the syndrome, and after treatment with dantrolene sodium. The increase in [Ca2+]i preceded the increase in ETCO2 that preceded a decrease in Spo2 that preceded the classic first sign, tachycardia, and all preceded the increase in rectal temperature. Dantrolene reversed all of these physiologic changes in the same order of precedence as the increase.
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PMID:Myoplasmic calcium changes precede metabolic and clinical signs of porcine malignant hyperthermia. 797 79

We describe a case of generalized muscle rigidity in a 2-year-old patient with Freeman-Sheldon syndrome undergoing surgery for eventration of the diaphragm after anesthetic induction with halothane and succinylcholine. Anesthetic induction was by mask with oxygen, nitrous oxide and halothane, with succinylcholine as a muscle relaxant. Approximately 10 minutes after start of induction, muscular rigidity appeared and developed rapidly, becoming severe and compromising ventilation. Tracheal intubation was attempted without success, owing to stiffness of the masseter muscles. Sodium dantrolene 2.5 mg/kg was administered and relaxation was achieved immediately for both masseter and peripheral muscles, such that the patient recovered spontaneous breathing. We conclude that there is risk of association between Freeman-Sheldon syndrome and malignant hyperthermia.
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PMID:[Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction]. 805 48

Muscle tissue is unique in its requirement and ability to undertake very rapid and co-ordinated changes in energy supply and oxygen flux during contraction. Several studies have suggested that this renders the tissue particularly prone to oxygen radical-mediated damage. Free radicals have been postulated to play a role in muscle damage induced by different forms of exercise and in various pathological disorders, such as the muscular dystrophies, malignant hyperthermia and alcoholic myopathy. However, conclusive evidence for a fundamental role for free radicals and protective effect of antioxidants remains elusive in all these situations and much further work on the relevant pathogenetic mechanisms is still required.
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PMID:Free radicals and muscle damage. 822 Oct 28

Pharmacogenetics of cytochromes P-450. Cytochromes P-450 are a large family of enzymes found in all living species whose function is the activation of molecular oxygen which, in turn, will oxidize an organic substrate. They are divided in two groups: one including the constitutive enzymes that intervene in vital processes such as cholesterol synthesis, cholesterol transfer into steroid and sex hormones, prostaglandin synthesis, etc.; the other group including the inducible enzymes, responsible of the metabolism of exogenous substances. Their concentration increases in the presence of specific substrates, like herbicides, cigarette smoke, hydrocarbons, insecticides, etc.. Of the latter group, the genetic polymorphism of two families is described. Family I is involved in the metabolism of polycyclic aromatic hydrocarbons: an allele codifying for a low activity cytoplasmic receptor (autosomic recessive inheritance) and a high affinity one (recessive inheritance) are present. The transformations carried out by the cytochromes P-450 give origin to intermediate reactive products, epoxides, that bonding to nucleoproteins or nucleic acids, can have either toxic or carcinogenic action. Therefore, the subjects with high affinity genes have an increased risk of cancer. This phenomenon, relating to pulmonary cancer, has been demonstrated in cigarette smokers. Family II is the group of greatest pharmacogenetic and clinical interest, since it is responsible of the polymorphism of the response to different drugs, such as halothane, (malignant hyperthermia), ethanol (alcohol intolerance), nitrosamine, (cancer), debrisoquine (hypotension), spartein (excessive uterine contractions). An increased or reduced ability to metabolize specific substances is the consequence: the pharmacological effects can therefore vary very much in the two classes of carriers of different alleles. Possible future applications of these polymorphisms in clinical practice are discussed.
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PMID:[Pharmacokinetics of cytochrome P-450]. 823 56

At present the in vitro caffeine-halothane contracture test is the only test to predict susceptibility to malignant hyperthermia (MH) with acceptable sensitivity and specificity. Anaesthesia is necessary for the excision of muscle bundles from the vastus lateralis muscle. MATERIAL AND METHODS. Between 1983 and 1991, muscle biopsies were taken from 350 patients, 233 children and 117 adults. In 197 cases, trigger-free general anaesthetics were supplemented by ventilation, via mask in 124 cases and via tracheal intubation in 73 cases. One hundred and fifty-three muscle biopsies were performed under regional or local anaesthesia with or without sedation. Fourteen of the patients with regional anaesthesia needed an additional general anaesthetic to tolerate the operation. For premedication midazolam was administered orally. The general anaesthetics consisted of etomidate or propofol with fentanyl or alfentanil, always with nitrous oxide and oxygen. For local anaesthesia we used procaine or prilocaine. During the first 3 years local infiltration of the thigh was used, but subsequently direct nerve blockade of the femoral nerve and the lateral cutaneous femoral nerve was preferred. RESULTS. In all cases of general anaesthesia and in 91.6% of cases of regional anaesthesia operating conditions were very good. Fourteen (8.4%) of the patients with regional anaesthesia needed an additional general anaesthetic. There were no severe complications noticed. Moderate complications were found in 29 of the 194 paediatric general anaesthesias (15%) and in 5 of the 117 regional anaesthesias in adults (4%); all were easy to treat. The 50 paediatric regional anaesthesias and the three general anaesthesias in adults were without complications. DISCUSSION. For muscle biopsies, trigger-free general anaesthesia can be recommended as well as peripheral nerve blockades. Complete monitoring is necessary, even for this minor procedure: ECG, blood pressure, pulse oximetry, capnometry, measurement of body temperature and blood gas status. Differential diagnosis in negative test results. In patients who suffer an anaesthetic incident, the following disease must be considered: myopathies (especially the congenital myopathies and muscular dystrophies), respiratory problems due to pulmonary infection and obstruction, metabolic disorders of various origins, and the problem of masseter spasm.
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PMID:[Diagnosis of malignant hyperthermia susceptibility. 2. Anesthesia for muscle biopsy. Differential diagnosis in negative test results]. 825 Feb 2

The first 2000 incidents reported to the Australian Incident Monitoring Study were analysed with respect to the role of the pulse oximeter. Of these 184 (9%) were first detected by a pulse oximeter and there were a further 177 (9%) in which desaturation was recorded. Of the 1256 incidents which occurred in association with general anaesthesia 48% were "human detected" and 52% "monitor detected". The pulse oximeter was ranked first and detected 27% of these monitor detected incidents; this figure would have been over 40% if an oximeter had always been used and its more informative modulated pulse tone relied upon instead of that of the "bleep" of the ECG. The pulse oximeter is the "front-line" monitor for endobronchial intubation, the fourth most common incident in association with general anaesthesia (it detected 87% of the 76 cases in which it was in use). It also played an invaluable role as a "back-up" monitor in 40 life-threatening situations in which "front-line" monitors (e.g. oxygen analyser, low pressure alarm, capnograph) were either not in use, were being used incorrectly or failed. Other situations detected, in order of frequency of detection, were: circuit disconnection, circuit leak, desaturation (severe shunt), oesophageal intubation, aspiration and/or regurgitation, pulmonary oedema, endotracheal tube obstruction, severe hypotension, failure of oxygen delivery, hypoxic gas mixture, hypoventilation, anaphylaxis, air embolism, bronchospasm, malignant hyperthermia, and tension pneumothorax.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Australian Incident Monitoring Study. The pulse oximeter: applications and limitations--an analysis of 2000 incident reports. 827 73

Three months before this study, susceptibility for malignant hyperthermia (MH) had been tested in 15 pigs. In all pigs, MH was triggered by administration of 1% halothane. Brain electrical activity was examined during therapy of MH with and without administration of dantrolene. From the EEG, power densities in selected frequencies and the median frequency of the power spectrum were calculated. Therapy was started when severe respiratory changes were observed (PaCO2 > 10 kPa, mixed venous oxygen tension (PvO2) < 4 kPa). At this time, heart rate exceeded 150 beat min-1, mean arterial pressure (MAP) was less than 60 mm Hg and median frequency was less than 2 Hz. EEG was isoelectric (n = 6) or showed slow polymorphic delta-activity. For therapy, administration of all anaesthetics was terminated, 100% oxygen was delivered and ventilation was increased four-fold. Acidosis was treated by administration of sodium bicarbonate 2-4 mmol litre-1 kg-1. Animals were allocated randomly to one of two groups: group I (control, n = 7) received no dantrolene; group II (n = 8) received dantrolene 2.5 mg kg-1 i.v. All variables were measured over a period of 60 min after therapy: EEG, HR and MAP were recorded continuously and blood-gas tensions, arterial potassium and glucose concentrations and pH were measured every 150 s. In group I (no dantrolene) minor, transient improvements in EEG activity were noted, but all animals died within 15-25 min after the start of therapy. In dantrolene-treated animals, EEG total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement of brain electrical activity during treatment of porcine malignant hyperthermia with dantrolene. 828 May 59

A 53-year-old woman was scheduled for elective surgery of a L4-L5 lumbar disc prolapse. Preoperatively, she reported of a hereditary muscle disease in her family which could be identified as familial hyperkalaemic periodic paralysis. In patients with familial periodic paralysis, only limited information is available in the current anaesthesiological literature. This is especially true of the hyperkalaemic form which was separated from the hypokalaemic form in 1957. Most patients suffering from periodic paralysis will develop myotonic symptoms in time, but evidence is lacking that the incidence of malignant hyperthermia (MH) is higher than in normals. However, abnormalities of the electrocardiogram (ECG) due to changes in the potassium serum levels are not unusual, and the anaesthesiologist must be aware of cardiac arrhythmias. In the present case, the patient was anaesthetized using fentanyl, midazolam, and vecuronium, and ventilated with 66% nitrous oxide in oxygen. Radial artery blood pressure, end-tidal CO2, and nasopharyngeal temperature were monitored continuously. Surgery was completed after 2 hours with no abnormalities in the intraoperative course. Recovery from anaesthesia was uneventful. During the postoperative follow-up for 1 week, further attacks of paralysis, intermittent sodium-potassium imbalance of the muscle cell membrane appears to be the primary pathogenetic factor. In this special disease, prevention of carbohydrate depletion and the avoidance of muscle relaxants are recommended in the anaesthesiological literature. However, a specified regimen of general anaesthesia has not yet been outlined. In our special case, the use of anaesthetics deemed to be safe in MH susceptible patients produced an uneventful perioperative course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anesthesia in familial hyperkalemic periodic paralysis]. 832 4


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