Malignant hyperthermia
<p>Abstract</p> <p>Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-04-01
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| Series: | Orphanet Journal of Rare Diseases |
| Online Access: | http://www.OJRD.com/content/2/1/21 |
| _version_ | 1819039593419243520 |
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| author | Pollock Neil James Danielle Davis Mark Rosenberg Henry Stowell Kathryn |
| author_facet | Pollock Neil James Danielle Davis Mark Rosenberg Henry Stowell Kathryn |
| author_sort | Pollock Neil |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the <it>RYR-1 </it>gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the <it>in vitro </it>contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%.</p> |
| first_indexed | 2024-12-21T08:55:40Z |
| format | Article |
| id | doaj.art-77670c053afb473690fd8b25e7d7b0a1 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T08:55:40Z |
| publishDate | 2007-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-77670c053afb473690fd8b25e7d7b0a12022-12-21T19:09:35ZengBMCOrphanet Journal of Rare Diseases1750-11722007-04-01212110.1186/1750-1172-2-21Malignant hyperthermiaPollock NeilJames DanielleDavis MarkRosenberg HenryStowell Kathryn<p>Abstract</p> <p>Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the <it>RYR-1 </it>gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the <it>in vitro </it>contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%.</p>http://www.OJRD.com/content/2/1/21 |
| spellingShingle | Pollock Neil James Danielle Davis Mark Rosenberg Henry Stowell Kathryn Malignant hyperthermia Orphanet Journal of Rare Diseases |
| title | Malignant hyperthermia |
| title_full | Malignant hyperthermia |
| title_fullStr | Malignant hyperthermia |
| title_full_unstemmed | Malignant hyperthermia |
| title_short | Malignant hyperthermia |
| title_sort | malignant hyperthermia |
| url | http://www.OJRD.com/content/2/1/21 |
| work_keys_str_mv | AT pollockneil malignanthyperthermia AT jamesdanielle malignanthyperthermia AT davismark malignanthyperthermia AT rosenberghenry malignanthyperthermia AT stowellkathryn malignanthyperthermia |