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

The use of procainamide or procaine for treatment of malignant hyperthermia is commonly recommended. The skeletal muscle relaxant dantrolene has also been indicated for treatment of this complication during anesthesia. In the present study, effects of procainamide and dantrolene were compared in malignant hyperthemia-susceptible (MHS) pigs in vivo and on MHS muscle from human patients in vitro. The ED50 for dantrolene block of indirectly evoked twitch tension was 0.85 mg/kg in MHS pigs. A final cumulative dose of 2 mg/kg resulted in 68 per cent block of the twitch response. In contrast, procainamide at a final cumulative dose of 14 mg/kg had no effect on twitch response of the MHS pigs. Dantrolene, 3 micrometer, in vitro (approximately 0.8 mg/kg in vivo) was effective in preventing or reversing the abnormal halothane-induced contracture response of human MHS muscle strips. Procainamide, 0.11 mM, a dose approximating clinical levels (about 22 mg/kg), had no effect on basal twitch response or on the abnormal halothan-induced contracture of MHS human muscle. These results confirm the effectiveness of dantrolene and the lack of effectiveness of procainamide in the treatment of malignant hyperthemia.
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PMID:Rationale for dantrolene vs. procainamide for treatment of malignant hyperthermia. 43 84

Experiments are described which demonstrate that dantrolene sodium effectively terminates the syndrome of malignant hyperpyrexia induced in susceptible swine by exposure to halothane. Dantrolene is also shown to block initiation of the syndrome of malignant hyperpyrexia by halothane in MHS swine. Therapeutic use of this drug in patients with anaesthetic-induced malignant hyperpyrexia appears to be indicated.
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PMID:Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium. 114 76

An acute episode of a malignant hyperthermia-like syndrome is described which occurred after suxamethonium and isoflurane anaesthesia in a 41-year-old healthy male patient undergoing a minor elective hand operation. Dantrolene therapy rapidly reversed the life-threatening signs. Laboratory results appeared to confirm the suspicion of malignant hyperthermia. However, the in vitro contracture test, which was carried out according to the standards of the European Malignant Hyperthermia Group, was equivocal.
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PMID:A case of malignant hyperthermia? 161 11

The authors report on the course of a fulminant malignant hyperthermia (MH) associated with laminectomy in a 29-year-old man who had been healthy up to that time. Succinylcholine and isoflurane were considered to be the causative triggering agents. Progression could be prevented due to an early suspicion raised by end-expiratory CO2 measurement: treatment was instituted immediately (Dantrolene 2mg/kg body weight, oxygen hyperventilation, external cooling, etc.) Serum creatine kinase increased up to almost 50,000 U/l associated with massive myoglobinuria. Residue-free restitution was achieved within a few days. Decisive for an early detection of MH is the routine performance of end-expiratory CO2 measurement which is definitely superior to temperature control and significantly reduces the time that elapses before treatment is initiated.
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PMID:[The early diagnosis of malignant hyperthermia--the place of end-expiratory CO2 monitoring]. 178 8

Hyperthermia from septic shock may be indistinguishable from malignant hyperthermia. Dantrolene may be given in septicemia if the diagnosis is unclear. To determine if dantrolene is safe to use in sepsis, two studies were performed. In study 1, 18 anesthetized dogs in which profound septic shock was induced with 5 mg/kg of intravenous Escherichia coli endotoxin were randomized to receive (30 min later) intravenous injections of 10 mg/kg of dantrolene solution, the diluent of dantrolene, or maintenance intravenous fluids alone. The use of dantrolene solution and the diluent of dantrolene resulted in similar but transient statistically significant increases in the cardiac filling pressures and cardiac outputs and decreases in the vascular resistances compared with the control dogs. In a second study, 185 rats were randomized into five equal groups. Groups 1, 2, and 3 received 15 mg/kg of intraperitoneal Escherichia coli endotoxin followed 30 min later by 10 mg/kg of dantrolene solution, the diluent of dantrolene, or normal saline. Groups 4 and 5 received normal saline followed by dantrolene or normal saline. The survival of groups 1, 2, and 3 was less at 24 h (P less than 0.0001) than that of either control group, but was not significantly different from one another. The results suggest dantrolene can be administered safely under clinical conditions where the cause of hyperthermia and shock cannot clearly be ascribed to malignant hyperthermia or septicemia.
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PMID:Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats. 186 22

Dantrolene is the only known specific treatment of malignant hyperthermia (MH). Following official approval an intravenous formulation of dantrolene became clinically available for emergency treatment of MH. At that time it had been anticipated, that with dantrolene therapy combined with constant vigilance each case of MH could be treated successfully and the mortality rate should be close to zero. Surprisingly enough, reports of death due to MH continue to be published up to the present. Analysis of case reports revealed the following reasons for the discrepancy between the expectations and the clinical reality: 1. Delay in early diagnosis due to preoccupation with the name-giving symptom hyperthermia: lack of MH-sensitive monitoring (i.e. capnometry, pulse oximetry, blood gas analysis). 2. Preoccupation with non specific facets of therapy: measures such as cooling, change of the anaesthesia machine, transfer of the patient to the intensive care unit or the administration of drugs which have been shown to be ineffective in treating MH may not only be a waste of time, but fully disregard the prime factor in therapy--intravenous administration of dantrolene. 3. Administration of an insufficient amount of dantrolene and delayed start of specific therapy due to failure to have immediate access to intravenous dantrolene. 4. Failure to increase minute ventilation immediately after making the diagnosis to meet elevated metabolic demands. A recommendation is presented how to diagnose, to treat and prevent MH, considering present day diagnostic and therapeutic measures in the presence of the presumptive diagnosis of MH.
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PMID:[Reasons for the persistent lethality of malignant hyperthermia and recommendations for its reduction]. 188 26

In malignant hyperthermia, dantrolene, a drug assumed to possess calcium channel blocking properties, effectively suppresses supraventricular and ventricular arrhythmias. To investigate antiarrhythmic properties of dantrolene, six patients (three women and three men, age 42 +/- 18 yr) with symptomatic atrioventricular (AV)-nodal reentry tachycardia were studied. Electrocardiographic measurements included sinus cycle length, PQ-interval, width of the QRS-complex, and QT- and rate-corrected QT-interval. During the electrophysiologic study, effective refractory periods of the right atrium, AV node, right ventricle, and AV-nodal conduction intervals were determined, and AV-nodal reentry tachycardia was induced in all patients. Dantrolene was administered intravenously over a period of 15 min at doses of 1.0, 1.5, or 3.0 mg/kg in two patients each. The dosage was not further increased because of side effects at the dose of 3.0 mg/kg. After the infusion of dantrolene, the electrocardiographic measurements and electrophysiologic study were repeated. The plasma concentrations of dantrolene ranged from 1.69 to 6.61 micrograms/ml at the time of the electrophysiologic study. After dantrolene administration, the sinus cycle length shortened from 686 +/- 80 to 622 +/- 55 ms (P less than 0.05). No significant changes of any other parameter could be demonstrated after intravenous dantrolene. AV-nodal reentry tachycardia remained inducible in all patients without change of the tachycardia cycle length and without change in coupling intervals of tachycardia-inducing extrastimuli. Antiarrhythmic properties of dantrolene could not be demonstrated in patients with AV-nodal reentry tachycardia at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous dantrolene does not exhibit calcium channel blocking effects on the cardiac conduction system in humans. 192 68

A 5-year-old girl susceptible to malignant hyperthermia underwent total repair of tetralogy of Fallot. The initial operation was canceled because of abrupt hyperthermia and metabolic acidosis of unknown cause. Dantrolene was given orally as preoperative treatment and administered intermittently during surgery. Postoperative hyperthermic crisis was successfully treated with intravenous dantrolene combined with surface cooling, gastric tube irrigation with cold saline, and alcohol vaporization.
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PMID:Correction of tetralogy of Fallot accompanied by malignant hyperthermia. Case report. 193 19

So far there is no causal treatment for Duchenne muscular dystrophy up to now, it has been proven, however, that its course can be considerably improved by an early contracture-prophylactic operation of both lower limbs--mostly between age 4 and 6 years--as well as by a surgical stabilization of the spine before any progressive scoliosis appears, that is at the very beginning of the wheel-chair stage: Walking and standing ability can be prolonged for several years and a significant scoliosis can be avoided. A decisive prolongation of life can be achieved by treating the fatal respiratory insufficiency with timely started mechanical ventilation. Our first experiences have shown, that there is no proven justification for a reserved attitude against early lower limb surgery in view of modern anaesthesia. Malignant hyperthermia-reaction and hyperkalaemia are the known anaesthetic rise factors of operations in Duchenne muscular dystrophy. However, we could exclude virtually these rises by choosing the right anaesthesia and by a comprehensive monitoring routine. If need be, malignant hyperthermia can be treated effectively by using the obligatory antidote (Dantrolene). In view of an expected causal treatment in future, early detection of Duchenne muscular dystrophy by newborn screening ("CK-Test") as well as a comprehensive stage-depending treatment programme (early surgery/mechanical ventilation) are nowadays of outstanding importance.
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PMID:[Duchenne muscular dystrophy--contracture preventive operations of the lower extremities with special reference to anesthesiologic aspects]. 202 63


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