Malignant hyperthermia (MH) is a critical event in anesthesiology. It is an autosomal dominant pharmaco-genetic syndrome of incomplete penetrance and variable aggressiveness, triggered by the exposure to depolarizing neuromuscular blockers and volatile anesthetics. It may have a fulminant onset and rapid course, with mortality rates close to 65% if a specific treatment is not administered.¹ The prevalence of the MH episodes ranges from 1:10,000 up to 1:220,000 cases per anesthesia administered.² In a study conducted in Bogotá, the estimated incidence was 1:65,000,³ while in Spain, the Carlos III Health Institute estimates and incidence of 1/14,000 cases in pediatric anesthesia and of 1/40,000 in adults.⁴ Notwithstanding its low incidence, the lethality of the condition makes it mandatory to develop competencies for managing the crisis, as timely identification and proper management reduce mortality to less than 10%.¹ However, due its low frequency, the clinic dose not provide the proper setting for training, as there are not enough cases for a traditional training. Furthermore, such mortality rates represent a very narrow margin of error and the consequences are unacceptable. Hence, developing simulation scenarios is an attractive option to develop the necessary skills when facing a potential crisis of MH. The anesthesiologist could respond efficiently to a potential real-life event, if adequately trained in a controlled and safe environment.

These simulation scenarios allow for making mistakes and understanding the consequences, with the possibility of repeating the procedure based on the feedback received. The use of simulators is in fact an accepted methodology, and its use is encouraged in medicine.⁵ Although the studies that have evaluated the benefits of simulation to develop competencies are not yet rigorous enough, the current evidence shows the importance and the potential benefits of simulation scenarios as part of medical training.^6,7

Chopra et al⁸ showed that anesthetists trained under a simulation model for MH respond faster, adhere more closely to the management guidelines, and their performance is better as compared against anesthesiologists who did not receive the training.

The availability of systems to simulate cases of MH is particularly interesting to develop skills in the management of a critical event during which the anesthetist is mostly liable for making the diagnosis and administering initial treatment.

Dantrolene is the only available agent in the clinic for the specific treatment of MH; its administration is essential in managing a crisis, and the reconstitution and preparation of the agent is a high-priority procedure when facing a crisis. Ideally, both the anesthesiologists and the nursing staff should have the knowledge to handle the medication.

A close relationship has been established between the time elapsed from the first sign of the crisis and the administration of dantrolene, with higher probability of complications from MH as time passes; proper monitoring, with emphasis in capnography and temperature, together with the prompt administration of dantrolene, prevents complications, and lowers mortality.^9,10 It has been shown that the risk of cardiac arrest is directly related to time, from the contact with the trigger and the start of therapy⁴; therefore, the dexterity and readiness to react in front of a crisis is a determining factor in a patient's survival.

The most widely commercialized presentation of dantrolene are the 20 mg vials of lyophilized dantrolene, with 3 g of mannitol and sodium hydroxide, to ensure a pH of 9.5. This preparation must be reconstituted in 60 ml of distilled water. This is a highly lipophilic drug, with low solubility in water,¹⁰ which makes the reconstitution difficult. The simulation scenarios have already identified the difficulty to dissolve the drug in distilled water as a critical point; the process may take up to 4 minutes per vial.¹¹ Keeping in mind the initial dose of 2.5 mg/kg, a 70-kg patient will need 9 vials just for the initial dose, requiring the effort of 3 of 4 full-time people. The lack of clarity about the process delays the start of therapy with a negative impact on the patient's outcome in the short and medium term.^4,12

Therefore, the recommendation is to be knowledgeable and have experience in doing the reconstitution to reduce the preparation time and promptly administer the medication. The solution must be vigorously stirred until it becomes clear, with no visible particles before adminis-tration.¹⁰ The agility to reconstitute is essential. The initial dantrolene dose of 2.5 mg/kg must be repeated every 15 minutes until the symptoms improve, with a maximum accumulated dose of 10 mg/kg.^1,13 So, in a worst case scenario, an average 70-kg patient would need 36 vials administered over the first hour of the crisis.

In addition, Dantrium (Intravenous, PAR pharmaceutical, Parkdale Road, MI, USA), the brand sold in Colombia and Spain, is distributed in 12 vial kits at a cost of $5,400,000 Colombian pesos (COP), which means a unit cost per vial of $450,000 COP. In Spain, the cost of treatment is 3000€.⁴ Therefore, wasting a vial due to wrongful reconstitution (eg, using dextrose or saline solution), in addition to causing delays in managing the crisis, represents an important economic loss during patient care, and using the actual drug for training purposes could imply wasting a very costly drug that occasionally has limited availability.

The relevance of the reconstitution process is reflected in the guidelines of our society. The checklists for malignant hypertension crisis management developed by the Colombian Society of Anesthesiology and Resuscitation (S.C.A.R.E.) since 2013 (available at: www.hiperter miamaligna.co) suggest appointing 1 single individual to dilute dantrolene (any staff member present during the response to the crisis). A similar recommendation is given by Kollmann-Camaiora et al⁴ in their clinical care protocol for managing MH. This proves the priority nature of this task, which is extremely relevant and complex so as to appoint 1 person (or even several) responsible for the its implementation.

So, we believe that dantrolene reconstitution is a relevant tool to develop competencies for managing a crisis of MH. Following is a description of the development of a simulation model for dantrolene reconstitution, using simple, low cost, and widely available materials. This model may be used as part of high-fidelity models in MH for training purposes when dealing with one of the critical points in crisis management.

In order to prepare a simulation vial for reconstitution using distilled water, we shall use a glass container that can be capped with a rubber plug as the ones used in operating room most vials (pharmacy-type glass bottle). One hundred milliliters medication bottles may be recycled (eg, Paracetamol). The vial content will be a mix of gelatin, which is difficult to dilute in room temperature water, simulating in this manner the difficulty faced when reconstituting the actual medication, so it is necessary to vigorously shake the vial in order to achieve the reconstitution. In order to make it look exactly like the commercial presentation, a label with the insert used in the dandrolene vials shall be used. The rubber plug must firmly cap the bottle to prevent any leaks during the simulation. The rest of the utensils normally used during the drug reconstitution will be used.

Materials to prepare a dantrolene reconstitution simulation kit (Fig. 1):

Figure 1 Source: Authors.

(1) Dantrolene vial for simulation:

Glass container (pharmacy-type bottle) of 60 or 100 ml: these containers are sold in perfume suppliers, the chemical industry, or manufacturers of glass products. These are low cost and easily available. The drug presentation is in 70 ml vials; however, 100 ml glass bottles are more easily available.

Figure 2 Source: Authors.

Supplemental material for the simulation:

(1)

60-ml syringe

MH is a critical event in anesthesia, which although rare, is potentially lethal. Using a simulation tool is extremely valuable developing the skills to confront a crisis. Dantrolene reconstitution plays a key role, as the administration of this drug in the shortest possible time is a priority. For this reason, exclusively dedicated staff is assigned to perform this task during the management of the crisis. We submit a simulation model that can be prepared with easily available materials in order to practice the skills for reconstitution of the drug.

Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data. The authors declare that they have followed the protocols of their work center on the publication of patient data.

Right to privacy and informed consent. The authors declare that no patient data appear in this article.