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)

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

A 31-year old male developed malignant hyperthermia (MH) during the initial minutes of Halothane induction. CPK rose to 6120 U/ml and decreased to normal levels as the patient became afebrile over a 10 day period of cooling measures and metabolic management. Muscle weakness, predominantly proximal and depressed deep tendon reflexes were found upon examination during convalescence. Muscle biopsy showed neurogenic changes characterized by fiber type grouping and targetoid fibers. CPK was elevated in one of the patient's children. This case supports the view of underlying hereditary neuromyopathy in MH.
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PMID:Neuromyopathy in malignant hyperthermia. 58 Feb 62

An eight-year-old male suffered from long-standing proximal muscle weakness, dramatically aggravated by febrile episodes. Neuromuscular work-up disclosed a myopathy with multiple central cores of non-familial nature. The presence of central cores in this patient as well as in the myopathy of malignant hyperpyrexia might suggest a pathophysiological basis common to both conditions.
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PMID:Myopathy with multiple central cores. A case with hypersensitivity to pyrexia. 58 99

We describe a development of a malignant hyperthermia (MH) syndrome, partially aborted by therapy, in a child with central core disease and congenital dislocating hips. Patients with central core disease appear to be more susceptible to MH; possibly those with elevated serum creatine phosphokinase levels, as in our patient, are especially susceptible. We review the clinical and pathologic aspects, possible pathogenesis, and treatment of the MH syndrome. An increased calcium level within the muscle fiber is suggested as the major cytodestructive factor, and that increase could be consequent to a plasmalemmal susceptibility to the provoking drugs hypothesized to be the basic defect in MH. Prevention of the full manifestations of MH is predicated on (1) a high index of suspicion in the search for history of anesthetic complications in the patient and his family, with or without evident neuromuscular disease, (2) recognition that there is a somewhat greater risk of MH developing in a patient who has certain "musculoskeletal" abnormalities or muscle weakness but that is not-except for central core disease-a classic clinicopathologically defined disease, (3) close monitoring of patients during anesthesia, and (4) if the syndrome develops, prompt therapeutic measures, including cessation of anesthesia.
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PMID:Malignant hyperthermia and central core disease in a child with congenital dislocating hips. 63 52

Malignant hyperthermia (MH) is a pharmacogenetic myopathy triggered by a variety of anaesthetic agents and muscle relaxants. In humans, susceptibility to MH is inherited as an autosomal dominant trait, and susceptible patients do not show a clinically relevant myopathy unless having suffered from a MH crisis. Homozygosity for the MHS trait is thought to be an uncommon finding, and so far only a few cases of patients suggested to be homozygous for MH on the basis of pedigree information were reported and described as having a more severe form of this condition resulting in clinical symptoms also in the absence of triggering agents. We report clinical findings in a patient with chronic myopathy beginning at the age of 2 yr and associated with a number of unique features, the most important being a family history of MHS present in both parents. She became symptomatic with marked muscular weakness and elevated serum CK levels. A muscle biopsy showed a distinct enlargement and increase of muscle mitochondria. In the in vitro contracture test the patient's muscle responded with unusually high contractures already at basal levels of triggering agents indicating a particularly severe MHS condition. DNA markers for the MHS1 locus, described previously on chromosome 19q12-13.2 in Irish and Canadian pedigrees, could not be used to confirm her homozygous state because our molecular genetic studies had previously excluded the MHS trait in this pedigree from this locus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic myopathy in a patient suspected of carrying two malignant hyperthermia susceptibility (MHS) mutations. 130 Jan 87

We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness.
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PMID:Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. 158 53

Toxic myopathies are an uncommon manifestation of chemotherapeutic agents. Most myopathies are characterized by a weakness affecting proximal limb-muscles more than distal ones. Steroids, chloroquine and ipecac syrup are the most common drugs inducing myopathies. Toxic myositis is rare and reported with D-penicillamine abuse. Myotoxicity of local agents injection such as anesthetics, steroids or antibiotics is also known. Congenital myopathies such as malignant hyperthermia, hypokalemic periodic paralysis or paroxysmal myoglobinuria may also be induced by drugs but are very rare.
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PMID:[Muscular diseases in relation to drug consumption]. 256 73

A 55-year-old, malignant hyperthermia-susceptible patient underwent myocardial revascularization without incident. Six hours postoperatively, he developed what was initially diagnosed as an MH crisis, for which he received intravenous dantrolene. The resultant muscle weakness prolonged the duration of postoperative mechanical ventilation and likely contributed to the development of a postoperative pneumonia. Plasma dantrolene levels were measured for the first 48 hours postoperatively and correlated with clinical findings. On reviewing the patient's perioperative course, it was felt that the hypermetabolic state was not due to MH. The patient's pattern of rewarming following hypothermic cardiopulmonary bypass was similar to non-MH-susceptible patients. Because of the difficulty in diagnosing a MH crisis after hypothermic bypass, it is recommended that patients receive prophylactic dantrolene preoperatively and after bypass. Nondepolarizing muscle relaxants should be given postoperatively to prevent shivering and respiratory acidosis while patients rewarm.
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PMID:Rewarming following hypothermic cardiopulmonary bypass in the malignant hyperthermia-susceptible patient: implications for diagnosis and perioperative management. 291 39

Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.
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PMID:Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients. 305 38

We studied the cases of fifteen patients who had central core disease, a non-progressive congenital myopathy that is usually inherited as an autosomal dominant trait. As infants, the patients had poor muscle tone and developmental delay, and as adolescents and adults, they had varying degrees of proximal muscle weakness and tended to use the Gower maneuver. The most common musculoskeletal problems were dislocation or subluxation of the hip, pes planus, and hypermobility of the joints. The most serious orthopaedic problems were in the hips: ten patients had a total of nine dislocations and six subluxations, nine being present at birth and six developing later. Only nine hips were stable after the initial treatment, and there was a propensity for hip-joint contractures. Scoliosis and patellar instability were also seen. Although patients who have central core disease have been reported to be at increased risk for malignant hyperthermia, this did not occur in our patients.
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PMID:Orthopaedic aspects of central core disease. 340 75


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