We are happy to see that our editorial1prompts discussion, even though the points raised by Larach et al. result mainly from the removal of the designated statement of the global context of the editorial. Three points of criticism were made: (1) the interpretation of the in vitro contracture test result of the boy (Groom et al. 2), (2) possible indicators for individuals at risk for nonanesthetic malignant hyperthermia (MH), and (3) the alleged blaming of the parents.
Regarding item 1: As Larach et al. correctly noted, the American and European protocols have been compared and found to be mostly concordant. However, Islander and Twetman differentiate between inclusion and exclusion of the MH equivocal results.3Simply put, 9 of 74 MH-susceptible results according to the North American protocol using 3% halothane were MH equivocal according to the European protocol using 2% halothane as trigger; that is 12%. Therefore, the in vitro contracture test of the boy could very well be considered MH equivocal by European standards. But more importantly, the message of the editorial was that the in vitro contracture test may not reliably identify persons at risk. This message becomes clear in the editorial by the statement: “In addition positive In Vitro Contracture Test results were found in only 24% of 45 individuals with exertional heat stroke,4and in 83% of 12 patients with exercise-induced rhabdomyolysis.5Therefore more appropriate test protocols in vitro (heat, oxidative stress, and nitrogen species as triggers) or in vivo (using 31P MRI)6need to be developed.”
Regarding item 2: Again, the statement about possible indicators for individuals at risk for nonanesthetic MH was taken from the original context. It is very clear from the whole paragraph and the statements made immediately preceding the statement in question that we are stating our opinion—in accordance with the purpose of an editorial—and drawing our own conclusions from the cases reported by Groom et al. 2“Alternatively only one RyR1 mutation (i.e. , in only 16% of the tetrameric RyR1 complexes, all four RyR1 subunits are impaired) might be sufficient if combined with a second mutation that is associated with a congenital myopathy. Therefore MH susceptible individuals presenting with ophthalmoplegia and muscle hypotonia, hypertrophy, or spasms will be at risk for nonanesthetic MH.” Therefore, it is evident that we are not citing a large-scale human study but rather identifying ophthalmoplegia, muscle hypotonia, hypertrophy, and spasms as possible indicators of an undetected, underlying myopathy.
Regarding item 3: Nowhere in the text do we assign any blame to the parents. We state, “As children have less developed compensation mechanisms for increased body heat and a higher incidence of MH events than adults (1:15,000 vs. 1:100,000),7their parents should be particularly careful.” Obviously, the parents must be more careful with any temperature elevation in children at risk than are parents of unaffected children. A personal or family history of heat intolerance should cause avoidance of hot environments, exhausting physical exertion, high fever, and all drugs that increase heat production and reduce heat dissipation. During an episode, cooling should be started immediately until dantrolene can be infused, as in a typical MH crisis. In the meantime, the recommendations given in our editorial have been supported by authorities in the field.8,9To avoid secondary organ damage, treatment in an intensive care unit is mandatory. The protection offered by various drugs against oxidative muscle damage should be tested as second-line therapy in MH animals, such as the naturally occurring MH-susceptible swine and transgenic mouse. The induction of MH by heat and the protection of MH by hypothermia have been described for these animals.10,11
