Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Malignant hyperthermia is a potentially fatal condition inducible by volatile anaesthetics and/or suxamethonium in genetically susceptible individuals. A disturbed calcium homeostasis in skeletal muscle (possibly in the ryanodin receptor) results in elevated myoplasmatic calcium. The latter causes muscle contraction and a hypermetabolic state, clinically observed as rigidity, fever, hypercarbia, metabolic acidosis and hyperkalemia. Arythmia ensues. Dantrolene inhibits the release of calcium and can halt the process if the diagnosis is made early. A fatal incident of probable malignant hyperthermia in a 13 year old boy is described and evaluated according to a multifactorial clinical grading scale. The value of the in vitro contracture test to diagnose malignant hyperthermia is discussed. Suggestions concerning the treatment of masseterspasm rigidity, an acute episode of malignant hyperthermia, and safe anaesthesia for susceptible patients are presented.
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PMID:[Malignant hyperthermia--still a current and dangerous problem]. 777 Aug 53

Malignant hyperthermia (MH) is a rare condition consisting of increased temperature and rigidity with mild to fulminant manifestation during anesthesia. Sevoflurane was thought to be a less potent triggering agent of MH; however, in literature review, the onset of MH after exposure to sevoflurane may be associated with calcium release from the sarcoplasmic reticulum. We present here a case of rarely-seen delayed MH induced by an inhalation agent of low-inducing probability, sevoflurane, after the second exposure to which within a short period of time. The patient was a five years old boy who received sevoflurane anesthesia for repeat orthopedic surgery within two days. Gradual elevation in heart rate, abrupt hypercarbia and hyperthermia were observed 90 min after induction. Dantrolene was administrated immediately with effective therapeutic response. Eventually, the patient recovered without any complication as an aftermath. Gradually elevated heart rate during the second exposure to sevoflurane was the atypical sign in the episode of MH in this case. One plausible explanation for the development of delayed onset of MH is the latent effect of the volatile anesthetic on the skeletal muscles. Therefore, it is worth noting for the anesthesiologists to recognize the possibility of an atypical MH and be alert for the possible occurrence of MH during routine anesthetic practice.
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PMID:Delayed onset of sevoflurane-induced juvenile malignant hyperthermia after second exposure. 1797 24

Dantrolene is the drug of choice in treatment of malignant hyperthermia. However, dantrolene is hepatotoxic; thus prolonged use is not recommended in patients with active hepatic disease such as acute hepatitis or active cirrhosis because it may result in fatal hepatic failure. Use of dantrolene in a patient with end-stage liver disease undergoing liver transplantation (LTx) in whom suspected malignant hyperthermia developed has been reported rarely. Its effect on the liver allograft, which has sustained cold, warm, and reperfusion injuries, is currently unknown. We report a case in which low-dose dantrolene administered intravenously during LTx was effective in treating hyperthermia, hypercapnia, and hyperkalemia. Furthermore, its reported hepatotoxic effect seemed to not affect recovery of the allograft after LTx.
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PMID:Low-dose dantrolene is effective in treating hyperthermia and hypercapnia, and seems not to affect recovery of the allograft after liver transplantation: case report. 2043 Jan 90

Malignant hyperthermia (MH) is a rare and life-threatening pharmacogenetic disorder triggered by volatile anesthetics, the depolarizing muscle relaxant succinylcholine, and rarely by strenuous exercise or environmental heat. The exact prevalence of MH is unknown, and it varies from 1:16 000 in Denmark to 1:100 000 in New York State. The underlying mechanism of MH is excessive calcium release from the sarcoplasmic reticulum (SR), leading to uncontrolled skeletal muscle hyper-metabolism. Genetic mutations in ryanodine receptor type 1 ( RYR1) and CACNA1S have been identified in approximately 50% to 86% and 1% of MH-susceptible (MHS) individuals, respectively. Classic clinical symptoms of MH include hypercarbia, sinus tachycardia, masseter spasm, hyperthermia, acidosis, muscle rigidity, hyperkalemia, myoglobinuria, and etc. There are two types of testing for MH: a genetic test and a contracture test. Contracture testing is still being considered as the gold standard for MH diagnosis. Dantrolene is the only available drug approved for the treatment of MH through suppressing the calcium release from SR. Since clinical symptoms of MH are highly variable, it can be difficult to establish a diagnosis of MH. Nevertheless, prompt diagnosis and treatments are crucial to avoid a fatal outcome. Therefore, it is very important for anesthesiologists to raise awareness and understand the characteristics of MH. This review summarizes epidemiology, clinical symptoms, diagnosis and treatments of MH and any new developments.
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PMID:The current status of malignant hyperthermia. 3230 61