Malignant hyperthermia when dantrolene is not readily available.

BACKGROUND: Malignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in susceptible individuals by volatile anesthetics or succinylcholine, or both. Unfortunately, the specific medicine dantrolene is not readily available in many countries including China. The aim of this study was to find the characteristics of malignant hyperthermia under the situation that dantrolene is not readily available. METHODS: The cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. The inclusion criteria were the MH episodes only related to anesthesia. The exclusion criteria were dubious MH episodes only caused by Ketamine administration or MH episodes irrelevant to anesthesia. Independent samples t-test and Pearson's chi-squared test were applied to assess the difference between the survived and death cases. RESULTS: Ninety-two cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. Median (IQR [range]) age was 18.5 (11.8-37.0 [0-70.0]) years. Compared with the survived cases, the death cases had higher maximum end-tidal partial pressure of CO2 (P = 0.033), the maximum arterial partial pressure of CO2 (P = 0.006), temperature first measured when the patient was first discovered abnormal (P = 0.012), and maximum temperature (P < 0.001). Besides, the death cases had less minimum pH (P < 0.001) and higher potassium (P < 0.001) and were more likely to have coagulation disorders (p = 0.018). Concerning treatment, cases used furosemide (P = 0.024), mannitol (P = 0.029), blood purification treatment (P = 0.017) had the advantage on the outcome. Creatine phosphokinase, myoglobin, and MB isoenzyme of creatine phosphokinase differed greatly among cases during the first week. 43 (46.7%) cases had congenital diseases. 12 (13.0%) cases were reported with abnormal laboratory test results or abnormal signs that are possibly relevant before anesthesia. CONCLUSIONS: In countries that dantrolene is not readily available, early warning, diagnosis, and prompt effective therapies are crucial for MH patients to survive.

Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines.

Faced with a malignant hyperthermia crisis, the immediate access to sufficient dantrolene is essential to achieve the best possible outcome for the patient. However, malignant hyperthermia crises are rare, and there may be administrative pressures to limit the amount of dantrolene stocked or, in some countries, not to stock dantrolene at all. There are no published guidelines to support anaesthetic departments in their effort to ensure availability of sufficient dantrolene for the management of malignant hyperthermia crises. After a literature review that confirmed a lack of clinical trials to inform this guideline, we undertook a formal consensus development process, in which 25 members of the European Malignant Hyperthermia Group participated. The consensus process used a modified web-based Delphi exercise, in which participants rated the appropriateness of statements that covered the dosing regimen for dantrolene in a malignant hyperthermia crisis, the types of facility that should stock dantrolene, and the amount of dantrolene that should be stocked. The resulting guidelines are based on available evidence and the opinions of international malignant hyperthermia experts representing a large group of malignant hyperthermia laboratories from around the world. Key recommendations include: the dosing regimen of dantrolene should be based on actual body weight, dantrolene should be available wherever volatile anaesthetics or succinylcholine are used, and 36 vials of dantrolene should be immediately available with a further 24 vials available within 1 h.

Consensus Statement of the Malignant Hyperthermia Association of the United States on Unresolved Clinical Questions Concerning the Management of Patients With Malignant Hyperthermia.

At a recent consensus conference, the Malignant Hyperthermia Association of the United States addressed 6 important and unresolved clinical questions concerning the optimal management of patients with malignant hyperthermia (MH) susceptibility or acute MH. They include: (1) How much dantrolene should be available in facilities where volatile agents are not available or administered, and succinylcholine is only stocked on site for emergency purposes? (2) What defines masseter muscle rigidity? What is its relationship to MH, and how should it be managed when it occurs? (3) What is the relationship between MH susceptibility and heat- or exercise-related rhabdomyolysis? (4) What evidence-based interventions should be recommended to alleviate hyperthermia associated with MH? (5) After treatment of acute MH, how much dantrolene should be administered and for how long? What criteria should be used to determine stopping treatment with dantrolene? (6) Can patients with a suspected personal or family history of MH be safely anesthetized before diagnostic testing? This report describes the consensus process and the outcomes for each of the foregoing unanswered clinical questions.

[Stocks of dantrolene in anesthesia and intensive care units in Germany : Nationwide online survey with 1673 participants]. / Dantrolenbevorratung in Anästhesie und Intensivmedizin in Deutschland : Bundesweite Onlineumfrage mit 1673 Teilnehmern.

BACKGROUND: A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0-2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness. OBJECTIVE: The goal of this study was an analysis of the stocking situation of dantrolene in Germany. A national survey was conducted amongst members of the German Society of Anaesthesia and Intensive Care (DGAI). MATERIAL AND METHODS: A questionnaire consisting of 19 items was posted online to all DGAI members from 2 September to 30 September 2015. The questionnaire dealt with characterization of the participants, the administration of triggering substances in the operating room and in the ICU of the respective hospitals. The main part covered the amount of stocked dantrolene, the place of storage and emergency availability of stocked dantrolene from elsewhere. RESULTS: The questionnaire was posted online to 12,415 DGAI members with a response rate of 13.5% (n = 1673). The highest response rate was from 259 directors and heads of anesthesiology units representing 28.3%. In total 93,7% of participants use volatile anesthetics and 82,3% use succinylcholine. In the event of an MH-crisis 40.4% of participants have 36 or more vials of dantrolene available within 5 min, 27.4% have only 24 vials and 18.7% only have 12 vials. Of the anesthesiologists in outpatient surgery 70.6% have a dantrolene stock of less than 36 vials. In those cases with insufficient dantrolene stock, 35.5% of hospitals have no agreement with neighboring hospitals. In the ICU setting, 51.8% of responding participants indicated the use of volatile anesthetics, but only 25.7% stock dantrolene in the ICU. For succinylcholine, 77.3% stated using the drug in the ICU, and 26.0% have a dantrolene stock in the ICU. CONCLUSION: Almost all anesthesiologists participating in the online survey use volatile anesthethics and/or succinylcholine. Whereas almost all participants have access to dantrolene, more than half of the units have a stock of dantolene, which is less than that recommended by the DGAI. In the case of low dantrolene stock, only 61% of anesthesia departments have access to additional dantrolene within a time frame of 15min . The results of this online survey demonstrate that the stock of dantrolene may be insufficient in some German hospitals and anesthesiology practices.