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      Isoflurane Induced Malignant Hyperthermia in a Patient with Glucose 6-Phosphate Dehydrogenase Deficiency and Growth Hormone Abuse

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          Abstract

          Malignant hyperthermia is a pharmacogenetic disorder in the regulation of calcium in skeletal muscles which is related to an uninhibited muscle hypermetabolic reaction to potent inhalation agents, the depolarizing muscle relaxant succinylcholine, and to stressors such as vigorous exercise and heat. MH is diagnosed by the clinical presentation of the disease and laboratory testing. There are a few previous studies working on if there is an association between the occurrence of malignant hyperthermia and the existence of glucose 6-phosphate dehydrogenase (G6PD) deficiency, and there was no report on growth hormone doping in the literature. So, our main goal was to show this rare case of malignant hyperthermia seen in a G6PD patient with growth hormone abuse who underwent surgery and to find if there is an association between G6PD deficiency, growth hormone abuse, and malignant hyperthermia. Our patient was a 17-year-old boy with right lower quadrant abdominal pain and tenderness who underwent appendectomy. At the end of the operation, the patient developed with an increased heart rate (sinus tachycardia), increased body temperature and end-tidal carbon dioxide (ETCO2) level, masseter muscle rigidity, and then, generalized body rigidity, so the malignant hyperthermia susceptibility was considered. The patient was managed by cooling down the patient and the administration of dantrolene. We could hypothesize that malignant hyperthermia might be associated with G6PD deficiency as a triggering factor, but has no association with recombinant human growth hormone (rhGH) abuse. Another main lesson which this study tells us is to make a careful and proper history taking before going on an operation for preoperative evaluation and identification of patients with any form of suspicious drug abuse in order not to receive volatile inhalational agents and, also, performing some preventive measures including avoidance of heat extremes and restricting athletic activity in a patient with a history of malignant hyperthermia, and if the malignant hyperthermia susceptibility is suspected, urgent management should be carried out. As the association between G6PD deficiency, human growth hormone abuse, and malignant hyperthermia has remained unclear up-to-date, further potent studies are seriously needed in the future.

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          Most cited references18

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          A clinical grading scale to predict malignant hyperthermia susceptibility.

          The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.
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            Postoperative malignant hyperthermia: an analysis of cases from the North American Malignant Hyperthermia Registry.

            The initial presentation of malignant hyperthermia (MH) may begin in the postoperative period. However, the maximal latency period between the end of anesthesia care and the onset of postoperative MH is unknown. The authors hypothesized that this latency period is short and is not manifested by hyperthermia as the initial presenting sign. The authors sought to test this hypothesis and to describe the clinical characteristics of postoperative MH by analysis of suspected cases in the North American Malignant Hyperthermia Registry. Of 528 possible or suspected cases of MH in the North American Malignant Hyperthermia Registry, the authors identified 64 possible reports of postoperative MH. The records were reviewed in detail by the authors, each of whom assigned a qualitative score of "likely," "not likely," "not enough information available," or "not applicable" (where MH was not the final definitive diagnosis). Postoperative MH was confirmed after a consensus meeting of the three senior authors who reviewed in detail all possible "likely" cases. The authors identified postoperative MH in 10 subjects. All received volatile agents and 5 also received succinylcholine. All demonstrated signs characteristic of acute MH, including generalized rigidity, hypercapnia and/or tachypnea, tachycardia, and hyperthermia. No subject demonstrated hyperthermia as the presenting sign. The latency period between the anesthesia finish time and the onset of a sign indicative of acute MH ranged from 0 to 40 min. Postoperative MH is uncommon, occurring in 10 of 528 suspected MH cases (1.9%) reported to the North American Malignant Hyperthermia Registry. Postoperative MH began shortly after completion of the anesthetic care. Hyperthermia was not a presenting sign of MH.
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              Perioperative management of the glucose-6-phosphate dehydrogenase deficient patient: a review of literature.

              Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in humans. It is estimated that about 400 million people are affected by this deficiency. The G6PD enzyme catalyzes the first step in the pentose phosphate pathway, leading to antioxidants that protect cells against oxidative damage. A G6PD-deficient patient, therefore, lacks the ability to protect red blood cells against oxidative stresses from certain drugs, metabolic conditions, infections, and ingestion of fava beans. The following is a literature review, including disease background, pathophysiology, and clinical implications, to help guide the clinician in management of the G6PD-deficient patient. A literature search was conducted in the following databases: PubMed, The Cochrane Library, Web of Science, OMIM, and Google; this was supplemented by a search for selected authors. Keywords used were glucose-6-phosphate dehydrogenase (G6PD) deficiency, anesthesia, analgesia, anxiolysis, management, favism, hemolytic anemia, benzodiazepines, codeine, codeine derivatives, ketamine, barbiturates, propofol, opioids, fentanyl, and inhalation anesthetics. Based on titles and abstracts, 23 papers and 1 website were identified. The highest prevalence of G6PD is reported in Africa, southern Europe, the Middle East, Southeast Asia, and the central and southern Pacific islands; however, G6PD deficiency has now migrated to become a worldwide disease. Numerous drugs, infections, and metabolic conditions have been shown to cause acute hemolysis of red blood cells in the G6PD-deficient patient, with the rare need for blood transfusion. Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine were not found to cause hemolytic crises in the G6PD-deficient patient. The most effective management strategy is to prevent hemolysis by avoiding oxidative stressors. Thus, management for pain and anxiety should include medications that are safe and have not been shown to cause hemolytic crises, such as benzodiazepines, codeine/codeine derviatives, propofol, fentanyl, and ketamine. The authors of this article make 5 particular recommendations: (1) Anyone suspected of G6PD deficiency should be screened; (2) exposure to oxidative stressors in these individuals should be avoided; (3) these patients should be informed of risks along with signs and symptoms of an acute hemolytic crisis; (4) the clinician should be able to identify both laboratory and clinical signs of hemolysis; and finally, (5) if an acute hemolytic crisis is identified, the patient should be admitted for close observation and care.
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                Author and article information

                Contributors
                Journal
                Case Rep Anesthesiol
                Case Rep Anesthesiol
                CRIA
                Case Reports in Anesthesiology
                Hindawi
                2090-6382
                2090-6390
                2020
                6 August 2020
                : 2020
                : 8888368
                Affiliations
                1General Surgery Department, Shahid Beheshti Hospital, Yasuj University of Medical Sciences, Yasuj, Iran
                2Anesthesiology Department, Shahid Beheshti Hospital, Yasuj University of Medical Sciences, Yasuj, Iran
                Author notes

                Academic Editor: Ilok Lee

                Author information
                https://orcid.org/0000-0002-2859-044X
                https://orcid.org/0000-0001-7797-4127
                Article
                10.1155/2020/8888368
                7429016
                16b5ff3e-3042-4357-9f48-9ae1c8437b80
                Copyright © 2020 Hojatolah Ravaei et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 April 2020
                : 28 June 2020
                : 2 July 2020
                Categories
                Case Report

                Anesthesiology & Pain management
                Anesthesiology & Pain management

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