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Background: Diabetic neuropathic pain is a known complication of diabetes mellitus (DM) and results from the complex interaction of various factors affecting the nervous system. Yokuansan (YKS) is a versatile traditional Japanese herbal medicine with a wide range of applications, especially in pain management and neurological manifestations. YKS has analgesic properties for nerve damage and is a potential treatment for DM-induced neuropathic pain, especially in patients with diabetic neuropathy. Thus, we examined the anti-allodynic effect of YKS on DM-induced neuropathic pain. Methods: All experiments were performed on 6-week-old male Sprague-Dawley rats. DM and diabetic neuropathy were induced in rats with streptozotocin. Mechanical allodynia was assessed using dynamic plantar esthesiometry. Additionally, we conducted an immunological assessment of microglia cell changes in the spinal cord and an experiment to clarify the involvement of serotonin. Results: Diabetes significantly reduced withdrawal thresholds in rats during the initial two weeks of the experiment, which stabilized thereafter. However, this effect was not investigated in the control group. We assessed, using the dynamic plantar test, the anti-allodynic effects of orally administered YKS (1 g/kg). Daily YKS administration significantly increased the withdrawal threshold in DM animals. Additionally, oral YKS reduced the expression of Ibal-1-positive microglia. To elucidate the mechanism of action of YKS, we explored the involvement of serotonin (5-hydroxytryptamine [5-HT]) receptors in mediating its effects. Intrathecal administration of 5-HT receptor antagonists (WAY-100635, ketanserin, and ondansetron) inhibited the protective effects of YKS. Conclusions: YKS exhibited an anti-allodynic effect, suggesting that YKS may activate 5-HT receptors in the spinal cord, thereby alleviating diabetic neuropathic pain.
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Transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported to have better efficacy during anesthesia induction compared to conventional mask ventilation, including improved oxygenation and prolonged safe apnea time. This study reports on the effectiveness of the THRIVE system during modified electroconvulsive therapy (mECT) for a patient experiencing severe hypoxia. A 78-year-old female patient with bipolar disorder received maintenance mECT every four weeks. She previously experienced a significant hypoxic event, with oxygen saturation (SpO2) dropping to 50% following electrical stimulation. In response, we employed the THRIVE system, designed to deliver high-flow, 100% oxygen, thereby extending apnea tolerance. The implementation of THRIVE ensured a stable oxygen supply, maintaining oxygen saturation levels above 95% throughout the mECT procedure. THRIVE is useful for treating hypoxia that occurs due to the unavoidable lack of ventilation during mECT.
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BACKGROUND: We used transcatheter aortic valve implantation (TAVI) procedure time to investigate the association between surgical team maturity and outcome. METHODS: Among patients who underwent TAVI between October 2015 and November 2019, those who had Sapien™ implanted with the transfemoral artery approach were included in the analysis. We used TAVI procedure time and surgery number to draw a learning curve. Then, we divided the patients into two groups before and after the number of cases where the sigmoid curve reaches a plateau. We compared the two groups regarding the surveyed factors and investigated the correlation between the TAVI procedure time and survey factors. RESULTS: Ninety-nine of 149 patients were analysed. The sigmoid curve had an inflection point in 23.2 cases and reached a plateau in 43.0 cases. Patients in the Late group had a shorter operating time, less contrast media, less radiation exposure, and less myocardial escape enzymes than the Early group. Surgical procedure time showed the strongest correlation with the surgical case number. CONCLUSION: The number of cases required for surgeon proficiency for isolated Sapien™ valve implantation was 43. This number may serve as a guideline for switching the anesthesia management of TAVI from general to local anesthesia.
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Curva de Aprendizaje , Tempo Operativo , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estudios Retrospectivos , Masculino , Femenino , Anciano de 80 o más Años , Anciano , Competencia Clínica , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/cirugíaRESUMEN
BACKGROUND: Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. CASE PRESENTATION: We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. CONCLUSIONS: Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.
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We thank the authors for their insightful and thoughtful commentary on our recent publication [...].
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Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca2+-induced Ca2+ release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC50 of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC50 (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC50 for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. RYR1 gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.
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Hipertermia Maligna , Canal Liberador de Calcio Receptor de Rianodina , Humanos , Canal Liberador de Calcio Receptor de Rianodina/genética , Hipertermia Maligna/tratamiento farmacológico , Hipertermia Maligna/genética , Calcio/metabolismo , Cafeína/farmacología , Fibras Musculares Esqueléticas/metabolismoRESUMEN
Ropivacaine is an amide local anesthetic with rare reports of anaphylaxis. To our knowledge, this is the first report of delayed nonimmune anaphylaxis induced by ropivacaine. A 70-year-old man underwent general anesthesia with a nerve block for a total knee arthroplasty. The patient developed symptoms of anaphylaxis 3.5 hours after receiving ropivacaine for femoral and tibial nerve blocks. A basophil activation test (BAT) revealed ropivacaine as the causative agent. Notably, anaphylaxis can be caused by medications even hours after their administration, and all administered drugs should be suspected of potentially causing anaphylaxis.
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Anafilaxia , Bloqueo Nervioso , Masculino , Humanos , Anciano , Ropivacaína/efectos adversos , Anestésicos Locales/efectos adversos , Anafilaxia/inducido químicamente , Amidas/efectos adversos , Bloqueo Nervioso/efectos adversosRESUMEN
Malignant hyperthermia is a pharmacogenetic disorder triggered by halogenated anesthetic agents in genetically predisposed individuals. Approximately 70 % of these individuals carry mutations in RYR1, the gene encoding the ryanodine receptor calcium channel of skeletal muscle. In this study, we performed functional analysis of 5 RYR1 variants identified in members from 8 families who had been diagnosed by the IVCT. Of the 68 individuals enrolled in the study, 43 were diagnosed as MHS, 23 as MHN, and 2 individuals were not tested. Here we demonstrate that the 5 RyR1 variants cause hypersensitivity to RyR1 agonist-mediated calcium release. According to the EMHG scoring matrix these five genetic variants can be classified as follows: c.8638G>A (p.E2880K) and c.11314C>T (p.R3772W) likely pathogenic, c.11416G>A (p.G3806R), c.14627A>G (p.K4876R) and c.14813T>C (p.I4938T), pathogenic (RefSeq NM_000540.3). We propose that the newly functionally characterized RYR1 variants, be included in the panel of variants to be used for the molecular diagnosis of MHS.
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Hipertermia Maligna , Humanos , Calcio/metabolismo , Predisposición Genética a la Enfermedad/genética , Hipertermia Maligna/genética , Músculo Esquelético , Mutación , Canal Liberador de Calcio Receptor de Rianodina/genéticaRESUMEN
(1) Background: Remimazolam is a novel benzodiazepine that prevents postoperative nausea and vomiting (PONV), is more effective than volatile anesthetics, and was recently approved for use in Japan. (2) Methods: This prospective, double-blind, randomized controlled trial study aimed to compare the efficacy of remimazolam and propofol as general anesthetics in terms of the incidence of PONV after laparoscopic gynecological surgery (UMIN000046237). High-risk female patients who underwent general anesthesia with either remimazolam or propofol for the maintenance of anesthesia were enrolled. The primary outcome was the incidence of PONV in the two groups (i.e., REM versus PROP) 2 h and 24 h after surgery. The incidence of vomiting without nausea, rescue antiemetic use, and the severity of nausea were also evaluated. (3) Results: No significant differences in PONV were identified between the REM and PROP groups at 2 h or 24 h. Furthermore, no differences were observed in any of the measured parameters, and no adverse events were reported. (4) Conclusions: The results of the present study suggest that remimazolam may be as effective as propofol in preventing PONV; however, further investigation is necessary to identify possible differences between these two agents.
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Purpose: Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. Methods: Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. Results: 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene (P = 0.047). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature (P < 0.001). The multivariable analysis also showed that the patient's temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. Conclusions: Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.
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Dantroleno , Hipertermia Maligna , Humanos , Estudios Retrospectivos , Temperatura Corporal , Pueblos del Este de Asia , Enfermedades RarasRESUMEN
BACKGROUND Hemophagocytic syndrome (HPS) is a rare syndrome characterized by abnormal activation of histiocytes and hemophagocytosis. We report the clinical management of recurrent HPS following 2 cesarean sections in the same patient. CASE REPORT A 33-year-old primiparous mother presented during her second trimester of pregnancy, and HPS was diagnosed based on pancytopenia, hyperferritinemia (13 170 ng/ml), and hemophagocytosis in bone marrow examination. Despite steroid therapy, her HPS did not improve. Following the delivery of a healthy premature infant, there was no improvement in HPS, and immunochemotherapy was started 4 days postoperatively. Thrombocytopenia and hyperferritinemia persisted but normalized over the next 2 months, and immunochemotherapy was discontinued after 6 months. About 1 year after chemotherapy, the patient became pregnant with her second child. At 35 weeks of gestation, recurrence of HPS was suspected, and a C-section was performed at 36 weeks of gestation. The surgery was complicated by placenta previa, and general anesthesia was initiated after successful delivery of the infant. Epidural anesthesia was not performed due to concerns for postoperative thrombocytopenia. CONCLUSIONS Interestingly, HPS was likely triggered twice by pregnancy in this patient. Although reports of HPS during pregnancy are rare, there have been reports of rapid deterioration and death. Early diagnosis and therapeutic intervention are essential.
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Hiperferritinemia , Linfohistiocitosis Hemofagocítica , Pancitopenia , Trombocitopenia , Femenino , Lactante , Niño , Embarazo , Humanos , Adulto , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/complicaciones , Mujeres Embarazadas , Hiperferritinemia/complicaciones , Pancitopenia/etiología , Trombocitopenia/complicacionesRESUMEN
Introduction: We compared the hemodynamics during general anesthesia with remimazolam and conventional anesthetics in patients with severe aortic stenosis (AS). Methods: This was a retrospective single-center analysis. We reviewed the records of 42 patients who underwent transcatheter aortic valve implantation with a transfemoral artery approach under general anesthesia from January to December 2020. Patients were divided into three groups based on the general anesthetic used for (induction/maintenance) remimazolam/remimazolam (Group R/R), propofol/sevoflurane (Group P/S), and midazolam/propofol (Group M/P). Vasopressor use (ephedrine, phenylephrine, and noradrenaline) was compared among the groups. Results: The number of patients in each group was 15 (Group R/R), 13 (Group P/S), and 14 (Group M/P), with no significant difference in background characteristics and intraoperative vital signs. For anesthesia induction, doses of ephedrine and phenylephrine used were significantly lower in Group R/R (ephedrine [mg]: Group R/R 2 [0-4] vs. Group P/S 8 [8-12], P < 0.001, Group R/R vs. Group M/P 5 [0-15], P = 0.39; phenylephrine (mg): Group R/R 0 [0-0.08] vs. Group P/S 0.15 [0.10-0.20], P = 0.03, Group M/P 0.21 [0.04-0.40], P = 0.08). For anesthesia maintenance, the noradrenaline dose used was low in the Group R/R (noradrenaline [µg/kg/min]: Group R/R 0.019 [0.015-0.039], Group P/S 0.042 [0.035-0.045], P = 0.02, Group M/P 0.048 [0.040-0.059], P < 0.01). Conclusion: In patients with severe AS, induction and maintenance of anesthesia with remimazolam resulted in less overall vasopressor use than conventional general anesthetics.
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Anestésicos Generales , Estenosis de la Válvula Aórtica , Propofol , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Propofol/uso terapéutico , Estudios Retrospectivos , Efedrina , Anestesia General/métodos , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/cirugía , Fenilefrina/uso terapéutico , Norepinefrina/uso terapéutico , Válvula Aórtica/cirugíaRESUMEN
Background: Pain is a common symptom among cancer patients and directly affects their prognosis. As the leading drug for pain management, opioids are widely prescribed. So it is necessary to get people a correct understanding and application of opioids. In order to examine whether the use of high-dose opioids might affect survival and quality of life, this retrospective cohort study was performed to explore the outcomes of patients receiving high-dose opioids for pain management in a first-class tertiary hospital in China. Methods: We retrospectively searched medical records of inpatients and outpatients with pain who were treated with opioids in The First Affiliated Hospital, Zhejiang University School of Medicine from July to December 2021. Forty-three cases who were treated with high-dose opioids meeting inclusion criteria. Among these patients, 37 had cancer pain and 6 had neuropathic pain. All patients had regular follow-up when readmission until to April 7, 2022. Medical records of patients on high-dose opioids (equivalent to morphine ≥300 mg/d) was collected, including numerical rating scale (NRS), Karnofsky performance score (KPS), survival and adverse drug reactions (ADRs). Pain relief, quality of life, survival, and ADRs of patients after pain treatment were analyzed and evaluated. Results: The NRS score was significantly reduced and pain was relieved after high-dose opioid treatment. The before and after average NRS score of cancer pain was 5.2±1.6 vs. 2.2±1.1 points (P<0.001), neuropathic pain was 5.0±2.2 vs. 1.3±1.2 points (P<0.05), respectively. Although there is no statistical difference, quality of life showed a trend of improvement compared with before treatment. The before and after average KPS scores of cancer pain patients was 55.7±17.3 vs. 62.4±20.0, and neuropathic pain patients was 71.7±9.0 vs. 83.3±4.7. There were no intolerable ADRs. The median survival time was 238 days and 83 days in patients with cancer pain who received high-dose opioids and ultra-high dose opioids (equivalent to morphine ≥600 mg/d). Conclusions: Multimodal high-dose opioid pain treatments are important approaches to effectively relieve moderate to severe pain and improve the quality of life of patients. This study provides a clinical basis for future pain treatment with high-dose opioids.
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BACKGROUND: We measured catecholamine levels during periodic blood pressure fluctuations in patients with pheochromocytoma. CASE PRESENTATION: A 43-year-old man presented with periodic blood pressure fluctuations during surgery for a renal pelvic tumor. His blood levels of catecholamines (ng/mL) changed dramatically over a short time during blood pressure fluctuations: adrenaline 0.36 to 3.22, noradrenaline 0.47 to 1.98, and dopamine 0.02. After the diagnosis of pheochromocytoma, oral treatment with doxazosin 2 mg/day was administered, and left adrenalectomy was performed 4 months after the initial surgery. Periodic circulation fluctuations occurred after tracheal intubation at the time of anesthesia induction, but the degree of fluctuation was smaller than that of the first surgery. CONCLUSIONS: The data suggest that the periodic blood pressure fluctuations in pheochromocytoma patients are caused by changes in blood catecholamine levels. Our data suggests that alpha blockers may also be effective against the cyclic fluctuations that occur in patients with pheochromocytoma.
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BACKGROUND: Intraoperative superior vena cava (SVC) clamping causes hypotension and cerebral congestion. There is no established method for monitoring brain function during cerebral congestion. We encountered a case of cerebral congestion caused by unexpected SVC clamping. CASE PRESENTATION: A 64-year-old man underwent SVC clamping during lung tumor resection. The entropy and electroencephalogram monitoring values decreased with SVC clamping and increased in response to the release of congestion by phlebotomy and SVC declamping. CONCLUSIONS: Because entropy sharply reflects brain viability during cerebral congestion, it was considered helpful in evaluation of the monitoring of cerebral congestion.
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Dantrolene is currently the only drug known to specifically treat malignant hyperthermia (MH) crises. Although dantrolene attenuates Ca2+ disorders by acting mainly on the ryanodine receptor type 1 (RYR1), some patients who manifest MH without RYR1 variants have also been successfully treated with dantrolene. Thus, dantrolene appears to have an inhibitory effect on patients with and without RYR1 variants. This study aimed to investigate whether the effects of dantrolene differed depending on the presence or absence of RYR1 variants using muscle cells from MH-predisposed individuals. The study participants were individuals diagnosed with MH predisposition by the Ca2+-induced Ca2+ release rate test. They were genetically tested and divided into two groups: with and without RYR1 variants. We investigated whether these two groups showed differences in the changes in the half-maximal effective concentration (EC50) for caffeine and the resting intracellular Ca2+ concentration ([Ca2+]i) before and after dantrolene administration. Dantrolene administration significantly increased the EC50 (P < 0.0001) and decreased the resting [Ca2+]i (P < 0.0001). The inhibitory effects of dantrolene and the presence of RYR1 variants showed no statistically significant interactions related to the EC50 (P = 0.59) and resting [Ca2+]i (P = 0.21). In conclusion, the presence or absence of RYR1 variants does not appear to influence the effect of dantrolene.
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Hipertermia Maligna , Cafeína/farmacología , Calcio/metabolismo , Dantroleno/farmacología , Humanos , Hipertermia Maligna/tratamiento farmacológico , Hipertermia Maligna/genética , Mutación , Canal Liberador de Calcio Receptor de Rianodina/genéticaRESUMEN
We detected three chicken astrovirus strains in 4-day-old broiler chickens with high mortality and visceral gout and one strain from 150-day-old hens without clinical symptoms in Saga prefecture, Japan. Phylogenetic analysis based on ORF2 amino acid sequences revealed that the strains from the visceral gout cases belonged to subgroup Bi, and the strain from hens without clinical symptoms belonged to subgroup Aiii. Our study showed that CAstV had infiltrated into Saga prefecture, Japan. This is the first report of CAstV in Japan.
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Infecciones por Astroviridae , Avastrovirus , Gota , Enfermedades de las Aves de Corral , Animales , Infecciones por Astroviridae/epidemiología , Infecciones por Astroviridae/veterinaria , Avastrovirus/genética , Pollos , Femenino , Japón/epidemiología , Filogenia , Enfermedades de las Aves de Corral/epidemiologíaRESUMEN
BACKGROUND: Occlusion or malposition of the venous cannula during cardiopulmonary bypass (CPB) increases central venous pressure (CVP). When high CVP is measured, we need to determine if it is actually high or if it is measured due to catheter occlusion or technical problems with the measurement. CASE PRESENTATION: We experienced a case of excessively high CVP due to malposition of the venous cannula during CPB. A 78-year-old woman underwent an aortic arch replacement for acute aortic dissection. During CPB, CVP increased up to 78 mmHg, and the time above 50 mmHg was 48 min. In this case, ultrasonography of the internal jugular vein (IJV) was useful to confirm high CVP. CONCLUSIONS: Ultrasonography is now a familiar diagnostic tool and can be used at any time. We should consider ultrasonography as the first choice for diagnosing the cause of high CVP during CPB.
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Many anesthetics, including Propofol, have been reported to induce elevation of intracellular calcium, and we were interested to investigate the possible contribution of calcium elevation to the mechanism of the newly approved remimazolam actions. Remimazolam is an intravenous anesthetic first approved in Japan in July 2020, and is thought to exert its anesthetic actions via γ-aminobutyric acid A (GABAA) receptors; however, the precise mechanisms of how remimazolam elevates intracellular calcium levels remains unclear. We examined the remimazolam-induced elevation of intracellular calcium using SHSY-5Y neuroblastoma cells, COS-7 cells, HEK293 cells, HeLa cells, and human umbilical vein endothelial cells (HUVECs) loaded with fluorescent dyes for live imaging. We confirmed that high concentrations of remimazolam (greater than 300 µM) elevated intracellular calcium in a dose-dependent manner in these cells tested. This phenomenon was not influenced by elimination of extracellular calcium. The calcium elevation was abolished when intracellular or intraendoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that calcium was mobilized from the ER. Inhibitors of G-protein coupled receptors (GPCRs)-mediated signals, including U-73122, a phospholipase C (PLC) inhibitor and xestospongin C, an inositol 1,4,5-triphosphate receptors (IP3R) antagonist, significantly suppressed remimazolam-induced calcium elevation, whereas dantrolene, a ryanodine receptor antagonist, did not influence remimazolam-induced calcium elevation. Meanwhile, live imaging of ER during remimazolam stimulation using ER-tracker showed no morphological changes. These results suggest that high doses of remimazolam increased intracellular calcium concentration in a dose-dependent manner in each cell tested, which was predicted to be caused by calcium mobilization from the ER. In addition, our studies using various inhibitors revealed that this calcium elevation might be mediated by the GPCRs-IP3 pathway. However, further studies are required to identify which type of GPCRs is involved.
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Benzodiazepinas/farmacología , Calcio/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Cafeína/farmacología , Línea Celular , Dantroleno/farmacología , Retículo Endoplásmico/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/química , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Transducción de Señal/efectos de los fármacos , Tapsigargina/farmacologíaRESUMEN
BACKGROUND: Malignant hyperthermia (MH) is an inherited muscle disorder induced by volatile anesthetics and depolarizing muscle relaxants. While the incidence of MH is high in young, there are few reports on the clinical features of pediatric MH. In this study, we selected pediatric cases from an MH database and analyzed the clinical findings by age group. We hypothesized that there would be age-related differences in the clinical characteristics. METHODS: A retrospective analysis of MH data collected in our database during 1960 to 2020 was performed to identify pediatric subjects (≤18 years) with a Clinical Grading Scale of ≥35, indicating "very likely" or "almost certain" MH. We compared clinical characteristics among the 0 to 24 month, 2 to 12 year, and 13 to 18 year (youngest, middle, and oldest, respectively) age groups. RESULTS: Data were available for 187 patients: 15 in the youngest age group, 123 in the middle-aged group, and 49 in the oldest age group. Of these, 55 patients (29.4%) had undergone muscle biopsy and muscle contracture test. The mortality rates during the study period were 13.3%, 13.8%, 20.4%, and 15.5% in the youngest, middle, and oldest cohorts and overall, respectively. In contrast, the overall mortality rate from 2000 to 2020 was 8.8%. The most frequent initial symptoms of MH were elevated temperature (46.7%) and generalized muscular rigidity (26.7%) in the youngest cohort, masseter spasm (35.0%) and generalized muscular rigidity (19.5%) in the middle cohort, and elevated end-tidal carbon dioxide (26.5%) and tachycardia (22.4%) in the oldest cohort. Physical examination revealed that elevated temperature, sinus tachycardia, and respiratory acidosis occurred frequently in all groups. The middle cohort had high frequencies of masseter spasm (58.4%; P = .02) and dark urine (75.5%; P = .01) compared to those in the oldest groups, and had a higher peak creatine kinase level compared to those in the 3 groups. Skeletal muscle symptoms tended to be more common in patients administered succinylcholine (generalized muscular rigidity, P = .053; masseter spasm, P < .0001; dark urine, P < .0001). In particular, masseter spasm and dark urine were more common in the middle cohort when succinylcholine was administered (masseter spasm: versus youngest cohort, P = .06, versus oldest cohort, P = .027; dark urine: versus youngest cohort, P = .0072, versus oldest cohort, P = .0015). CONCLUSIONS: The clinical characteristics of pediatric patients with MH vary according to age group. The difference in initial symptoms of MH depending on age group is noteworthy information for the early diagnosis of MH.