Recurrent malignant hyperthermia after scoliosis correction surgery

Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).

Treatment of malignant glioma using hyperthermia

Thirty pathologically diagnosed patients with grade Ⅲ-Ⅳ primary or recurrent malignant glioma （tumor diameter 3-7 cm） were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com- bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. Dudng 3 months a^er hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper- thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80% of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra- dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.

The current status of malignant hyperthermia

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 CACNA1 S 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.

Post-Operative Malignant Hyperthermia Complicated by Rhabdomyolysis: Case Report

Malignant hyperthermia (MH) is a rare but fatal complication that develops under general anesthesia. Particularly, reports of postoperative MH are rare. This report describes the very rare case of a 29-year-old woman with neurological impairment complicated by rhabdomyolysis due to postoperative MH with an onset 30 hours after laparoscopic Nissen fundoplication and open gastrostomy, and the successful medical treatment of MH. We review the literature on this type of relationship between postoperative MH and neurological impairment, and discuss the clinical features of this complication. Furthermore, the usefulness of magnetic resonance imaging for the diagnosis of rhabdmyolysis caused by postoperative MH was explored.

A Case of Atypical Postoperative Malignant Hyperthermia after the Eighth General Anesthesia in a Child with Cheilognathopalatoschisis

Background and Objectives: Postoperative malignant hyperthermia (MH) occurs after discontinuation of volatile anesthetics or in the early postoperative period after general anesthesia. We experienced a case of atypical postoperative MH identified by dark reddish-brown urine produced 40 min after the end of eighth general anesthesia in an 11-year-old male with cheilognathopalatoschisis. Case Report: Anesthesia was induced using thiamylal, fentanyl citrate, remifentanil, rocuronium, and maintained with sevoflurane, fentanyl citrate, remifentanil. The patient was observed clenching his teeth, tachycardia, profuse perspiration, shivering-like motion, and hyperpnoea from the end of the operation to return to the HCU ward, whereas the maximum of axillary temperature was 37.9°C. Although these abnormal symptoms and vital signs were disappeared, abnormally high level of CK, AST, ALT, LDH, ALP, and myoglobinuria were recognized. We decided to not administer dantrolene hydrate because his vital signs and daily activity were restored to those observed preoperatively. However, the patient was continued infusion therapy for 9 days after the operation until the blood and urine test values returned to the preoperative ones. Conclusions: We experienced atypical postoperative MH identified by dark reddish-brown urine 40 min after the end of eighth general anesthesia. We decided not to administer dantrolene hydrate because his vital signs and daily activity were restored to those observed preoperatively when we recognized abnormally high level of CK, AST, ALT, LDH, ALP, and myoglobinuria. Consequently, rhabdomyolysis continued and in 9 days, the abnormally high values of CK, AST, ALT, LDH, and ALP recovered to the reference value.

Malignant Hyperthermia: Evaluation of “<i>Organon</i>” 9426 in Malignant Hyperthermia Susceptible Pigs

Control pigs required 109.9 ug/kg/min and MHS pigs required 72.4 ug/kg/min infusion of Organon 9426 to maintain a 90% block. It appears that Organon 9426 is only one-third to one-half as potent as Vecuronium in pigs. The fact that MHS pigs only require 66% of the infusion dose to maintain a 90% block suggests that there is difference in the neuromuscular effect of Organon 9426 in MHS vs. control pigs. A linear regression analysis of the dose response data to Organon 9426 in MHS pigs indicated that 427.033 ug/kg would be required to produce a 100% neuromuscular blockade vs. 586.31 ug/kg in control pigs. Nine of the ten MHS pigs did not develop MH or show any signs of impending MH during the halothane and succinylcholine challenge at the end of the infusion period. Organon 9426 is the first muscle relaxant to offer significant protective action at a clinical dose. This suggests that there is an allosteric site on the sodium channel (acetylcholine receptor) which regulates the flow of sodium ions through the sodium channel. Organon 9426 may be therapeutically effective in an active MH case [1].

A Review of the Factors Affecting the Incidence of Malignant Hyperthermia in the Greater Kansas City Area

Malignant Hyperthermia (MH) is a rare genetic disease. However, it is devastating when it occurs in a patient. MH is usually triggered by inhalational anesthetics and/or depolarizing muscle relaxants. Public awareness of MH has increased with the presentation of an episode on the television program, “House”, and the availability of web-based information. For over 20 years, the MH susceptible pig has been used in experiments by our group as an animal model for MH in humans. The incidence of Malignant Hyperthermia in the Greater Kansas City Area has declined dramatically since the introduction of Sevoflurane in 1992 as the anesthetic of choice (over 60% usage rate) in most surgical procedures. Historically, Malignant Hyperthermia was reported to occur at a rate of 1:50,000 during surgical procedures [1]. In the Greater Kansas City Area, Malignant Hyperthermia (MH) occurred at a rate of 1:53,636 during the 1965-1985 time period, as there were 38 MH cases in 35 patients [2]. During the past ten years (1996-2006), there were only 2 cases of MH, representing an incidence rate of 1:597,240. That decrease is an 11.13 fold (or 89%) decrease which is very significant. Despite the reduced incidence of Malignant Hyperthermia, two recent cases of MH that result in deaths in Wisconsin and Florida make it imperative that MH is recognized early and appropriate treatment initiated without delay. We have expanded our analysis of the futile cycle mechanism that underlies the MH syndrome. MH is equivalent to the rapid discharge of a battery by a short circuit.

Malignant hyperthermia: A runaway thermogenic futile cycle at the sodium channel level

Malignant Hyperthermia (“MH”)—the rapid onset of extremely high fever with muscle rigidity—is caused by a runaway heat production futile cycle mediated via the sodium channels at the myoneural receptor sites. MH is not triggered by non-depolarizing muscle relaxants;however, depolarizing muscle relaxants may trigger it [1]. Here we present a de novo hypothesis of how MH is triggered and develops. We believe that the acetylcholine receptor/sodium channels in the muscles of MH susceptible pigs initiate MH by allowing an increased flux of sodium ions when it is depolarized by acetylcholine or other depolarizing agents, such as succinylcholine and Halothane. Our theory is consistent with our observations of the effects of general anesthetics over twenty years. Succinylcholine is a depolarizing agent that is a potent MH trigger. Acetylcholine, the natural depolarizing muscle activator, may trigger MH if the susceptible patient or animal is exposed to sufficient stress, i.e., during strenuous activity, such as transport, fighting, breeding, etc. Halothane apparently destabilizes the myoneural sodium channels, which rapidly induces MH. The increased sodium channel activity releases heat with cascades that further releases of heat which results in the rapid onset of MH. MH susceptible pigs have increased action potential amplitudes at their myoneural junctions that are abnormally long in duration. This increased activity is thought to induce hypertrophy of muscle mass, increase metabolic rate, and cause other physical manifestations. When slaughtered, this increased metabolic activity causes the rapid post mortem release of heat in the muscles of MH susceptible pigs and, at the same time, the accumulation of low acidity, all of which denatures the muscle proteins to result in a pale, soft, exudative, pork meat considered to be of lesser quality for human consumption. The potency of inhalation anesthetics as a MH triggers varies widely. The inhalation anesthetic Halothane is a strong trigger of MH, causing MH within minutes of exposure. In contrast, the anesthetic Sevoflurane is a very weak trigger of MH, requiring several hours of inhalation exposure to trigger MH. Because of this, changing from Halothane to Sevoflurane as the general anesthetic of choice for surgeries in hospitals in the Greater Kansas City area during 1994 to 2006 led to an 11-fold decrease in the incidence of MH, from 1:50,000 to 1:550,000 [11]. One non-depolarizing muscle relaxant, Organon 9426 (“Rocuronium”) temporarily prevents MH in MH susceptible pigs when they are given sufficient dosages of it before being challenged with either Halothane or succinylcholine. Binding Rocuronium to the myoneural receptor sites apparently stabilizes them, thereby preventing increased sodium channel activity, and resulting MH. However, other non-depolarizing muscle relaxants do not have this protective effect— for examples Vecuronium, Arduan, and Organon 9616 do not. Uncoupling of mitochondria is not the source of accelerated heat production in MH susceptible pigs, as heart, liver, and skeletal muscle mitochondria isolated from MH susceptible pigs are all competent.

Regional hyperthermia combined with intrapleural chemotherapy in patients with malignant pleural effusion

Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P < 0.01), 86.7% vs 56.3% (P > 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.

Survey of Long-Term Sequelae in Survivors of a Malignant Hyperthermia Reaction

BACKGROUND: Malignant Hyperthermia (MH) is a potentially fatal, autosomal dominant disorder associated with administration of volatile anesthetics and/or the depolarizing paralytic succinylcholine. Symptoms include muscle rigidity, tachycardia, elevated body temperature, and metabolic acidosis, which are secondary to accelerated skeletal muscle metabolism. MH susceptibility can be a chronic condition, and some MH susceptible patients may develop symptoms subsequent to anesthetic exposure. OBJECTIVE: This is the first study examining the sequelae of an MH event after hospital discharge. METHODS: A survey was sent to patients who voluntarily registered with the North American Malignant Hyperthermia Registry, which included questions on severity of symptoms predominating prior to the MH event, one month after the MH event, and presently on a scale of 1 - 10 with a free text option to expound further. Participants were also asked about their opinions on causality between MH and these symptoms. RESULTS: Twenty-three responses were analyzed (34.8% response rate). Participants were categorized by their age at the time of the MH event and years since the event. Most (83%) stayed in the ICU between 1 - 4 days, and 39% experienced the event over 25 years ago. While 43% did not attribute any long-term symptoms to their MH event, all others believed that certain symptoms were linked, including muscle pain (90%), muscle cramps (75%), muscle weakness (100%), back/joint pain (36%) and depression/anxiety (42%). CONCLUSIONS: Our study concluded that long-lasting morbidities may be attributed to an MH event. Chronic musculoskeletal symptoms are experienced by the majority of patients who experience acute MH.

Influence of intraperitoneal perfusion chemotherapy combined with deep hyperthermia on the malignant molecule expression in ascites of patients with ovarian cancer complicated by ascites

Objective: To explore the influence of intraperitoneal perfusion chemotherapy combined with deep hyperthermia on the malignant molecule expression in ascites of patients with ovarian cancer complicated by ascites. Methods: A total of 80 patients with ovarian cancer complicated by ascites who were treated in this hospital between March 2015 and January 2017 were retrospectively analyzed and divided into the control group (n=43) and the study group (n=37). Control group received intraperitoneal perfusion chemotherapy and study group underwent intraperitoneal perfusion chemotherapy combined with deep hyperthermia. The differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were compared between the two groups before and after treatment. Results: Before treatment, the differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were not statistically significant between the two groups. After treatment, proliferation gene TCEAL7 mRNA expression in ascites of study group was higher than that of control group whereas Clusterin, HOTAIR, ROCK and TNFAIP8 mRNA expression were lower than those of control group;invasion gene DUSP10 mRNA expression in ascites was higher than that of control group whereas MTA1, Nek2, Stathmin and IFITM1 mRNA expression were lower than those of control group;autophagy genes LC3-Ⅱ, Beclin1 and PTEN mRNA expression in ascites were higher than those of control group. Conclusion:Intraperitoneal perfusion chemotherapy combined with deep hyperthermia can effectively balance the expression of proliferation, invasion and autophagy genes in ascites, and ultimately reduce the malignancy of the tumor in patients with ovarian cancer complicated by ascites.

Malignant hyperthermia as a rare complication of local lidocaine injection:A case report

BACKGROUND Malignant hyperthermia(MH)is a hypermetabolic disorder of skeletal muscles triggered by exposure to volatile anesthetics and depolarizing muscular relaxants.It manifests with clinical presentations such as tachycardia,muscle rigidity,hyperpyrexia,and rhabdomyolysis in genetically predisposed individuals with ryanodine receptor or calcium voltage-gated channel subunit alpha1 S mutations.Local anesthetics,such as lidocaine,are generally considered safe;however,complications can arise,albeit rarely.Lidocaine administration has been reported to induce hypermetabolic reactions resembling MH in susceptible individuals.The exact mechanism by which lidocaine might trigger MH is not fully understood.Although some mechanisms are postulated,further research is needed for a better understanding of this.CASE SUMMARY We present the case of MH in a 43-year-old male patient with an unknown genetic predisposition following a lidocaine injection during a dental procedure.This case serves as a reminder that while the occurrence of lidocaine-induced MH is rare,lidocaine can still trigger this life-threatening condition.Therefore,caution should be exercised when administering lidocaine to individuals who may be susceptible to MH.It is important to note that prompt intervention played a crucial role in managing the patient’s symptoms.Upon recognizing the early signs of MH,aggressive measures were initiated,including vigorous intravenous normal saline administration and lorazepam.Due to the effectiveness of these interventions,the administration of dantrolene sodium,a specific antidote for MH,was deferred.CONCLUSION This case highlighted the significance of vigilant monitoring and swift action in mitigating the detrimental effects of lidocaine-induced MH.Caution should be exercised when administering lidocaine to individuals who may be predisposed to MH.It is very important to be aware and vigilant of the signs and symptoms of MH as early recognition and treatment intervention are important to prevent serious complications to decrease mortality.

猪恶性高温综合征（MHS）基因群体检测及部分片段DNA序列研究

本研究主要包括：（１）建立了猪ＭＨＳ基因检测的ＰＣＲ－ＲＦＬＰ方法。该方法具有准确、快速和无侵害的特点；（２）利用猪ＭＨＳ基因的ＰＣＲ－ＲＦＬＰ方法对中国现有猪种２０个群体的ＭＨＳ基因座位的基因和基因型频率进行了检测。结果表明，属于中国的本地品种五指山猪、香猪，引进品种约克夏猪，均不含有ＭＨＳ基因；在中国本地品种二花脸猪和民猪中，发现存在ＭＨＳ基因，且民猪的频率较高（０．１５６２）；培育品种北京花猪，引进品种丹系长白猪和杜洛克猪，均有ＭＨＳ基因；引进品种皮特兰猪、比系长白猪，ＭＨＳ基因频率最高，分别为０．９５２０和０．９４３２；（３）猪ＲＹＲ１／ＣＲＣ基因部分ＤＮＡ序列品种间比较，ＭＨＳＮＮ香猪和二花脸猪的１８４３位为“Ｃ”，而ＭＨＳｎｎ为“Ｔ”；

丹系长白猪恶性高温综合症(p MHS)基因的检测分析

采集 91头丹系长白种猪耳组织样品 ,用高盐法提取DNA ,特异性扩增包含C184 3在内的CRC/RYR1660bp片段 ,用HhaⅠ进行直接酶切 ,根据电泳图谱确定MHS基因座位上的基因型。结果表明 :91头丹系长白猪中 ,杂合猪 (MHSN/MHSn)为 10头 ,占 10 98% ,纯合阴性猪 81头占89 0 2 % ,没有发现纯合阳性猪。MHSN 和MHSn 的基因频率分别为 0 94 51和 0 0 549。结合国内已有的测定结果 ,认为目前我国丹系长白猪群中MHSN 及MHSn 的基因频率分别为 0 90 86和0 0 914。

天津白猪MHS基因群体遗传结构分析

采集46头天津白种猪耳组织样，用高盐法提取DNA，特异性扩增包含C1843在内的CRC／RYR1660hp片段，用HhaI进行直接酶切，根据电泳图谱确定MHS基因座位上的基因型。结果表明：46头天津白猪中，杂合猪（MHSN／MHSn）为5头，占10．87％，纯合阴性猪41头占89．13％，没有发现纯合阳性猪。MSNN和MSNn的基因频率分别为0．9456和0．0544。

Controlled Local Hyperthermia and Magnetic Hyperthermia of Surface (Skin) Cancer Diseases

Average size of hematite and magnetite micro and nanopowders and polydispersity index, zeta potential and distribution of particles were studied. Analysis showed that average size of the obtained particles for magnetite is 740.9 nm, for hematite particles 30 - 35 nm. Alternate current feed source was created for hyperthermia. Proceeding from the requirements of the objectives, the U type MnZn material magneto conductors were selected, in which 10.0 and 8.0 mm width gaps were cut and glass test tubes with magnetite or hematite suspensions were placed in them. Series of experiments at various field intensity and frequencies showed that for efficient magnetic hyperthermia therapy more powerful device was needed with frequency of up to 10 Mega Hertz to achieve the temperature 43°C - 45°C necessary for full activation of Neel and Brown mechanisms in particles. At the next stage, on the basis of experimental material the anticancer mono-therapeutic effect of hyperthermia and its adjuvant action in poly chemotherapeutic treatment was presented by the use of a device created by us “Lezi”. As a result of the experiment it was shown that in all animals (outbred albino mice, 3 months old) inhibition of cancer growth was fixed and intratumoral necrosis was developed, while after 7 and 10 sessions tumors were ulcerated, which refers to positive effect of the experiment (Conclusion of Pathologicanatomical Laboratory “PATGEO”, Tbilisi, Georgia ).

正颌术中恶性高热1例

恶性高热是全身麻醉过程中发生的一种罕见的危及生命的高热反应,危害严重且术前诊断困难。在大多数病例报告中,恶性高热最终通过高热发生后进行的基因检测得以确诊。目前,丹曲林是治疗恶性高热唯一的特效药,可以改善病例的预后。本文报道了1例发生于正颌术中的恶性高热,因发现及时且早期应用丹曲林,最终得以治疗成功,术后生化检查也仅出现肌红蛋白和肌酸激酶的轻微升高。

围手术期恶性高热护理培训方案的制订与应用

目的探讨构建的围手术期恶性高热护理培训方案在麻醉科护士培训中的应用效果。方法2023年10—11月对河南省郑州大学第一附属医院的72名麻醉科护士分为两组开展培训。试验组(36名)采用构建的围手术期恶性高热护理培训方案进行培训,培训大纲围绕七大模块展开;对照组(36名)采用常规的多媒体理论授课和视频演示的方法进行培训。比较两组学员的围手术期恶性高热护理能力评分、理论考核成绩,以及对培训效果的评价情况。结果试验组的围手术期恶性高热护理能力评分、理论考核成绩、培训和满意度效果评价均高于对照组,差异有统计学意义(P<0.05)。结论本研究所构建的围手术期恶性高热护理培训方案有助于提高麻醉科护士恶性高热护理能力,改善培训效果和培训质量。

特发性脊柱侧弯矫治术后并发恶性高热患者的护理

总结1例特发性脊柱侧弯患者术后并发恶性高热的护理体会。针对早期如何识别及处理恶性高热、如何管理体温及呼气末二氧化碳分压、如何正确使用丹曲林钠以及避免横纹肌溶解进展等问题。采取及早控制体温,持续监测核心体温及呼气末二氧化碳分压,合理使用丹曲林钠、监测肌酸激酶、碱化尿液等措施。经过11 d的治疗与护理,成功撤离呼吸机,转回病房治疗,并在术后第20天出院,出院随访3个月,患者状况良好。

深部高频热疗对放射性肺炎预防作用的临床研究

目的探讨深部高频热疗预防肺恶性肿瘤患者放射性肺炎发生的作用。方法非随机选取2020年1月—2022年11月在贵阳市第一人民医院血液肿瘤科进行放射治疗的84例肺恶性肿瘤患者,按不同的治疗方法分为对照组和热疗组,每组42例。对照组患者单独采用放化疗,热疗组患者在放化疗的同时采用深部高频热疗。比较两组放射性肺炎发生率、肺功能、炎性因子水平。结果热疗组患者放射性肺炎发生率为9.52%(4/42),低于对照组的38.10%(16/42),差异有统计学意义(χ^(2)=10.730,P<0.05)。治疗后,热疗组肺功能和炎性因子水平均优于对照组,差异有统计学意义(P均<0.05)。结论深部高频热疗预防放射性肺炎的效果确切。