Malignant hypothermia is a serious medical condition in which the body responds negatively to a general anesthetic that uses volatile anesthetic substances or succinylcholine, a muscle relaxant commonly used during surgery. When malignant hypothermia occurs, it can induce severe muscle contractions and an extremely swift rise in body temperature that can be life threatening for the patient.
A new treatment for malignant hypothermia, however, is providing medical practitioners with a fast acting, reliable, safe, and effective method for reversing the signs of this concerning condition.
Ryanodex, which consists of an injectable dantrolene sodium solution, is the latest method of treatment for malignant hypothermia. In this article, we’ll take a look at the Ryanodex solution and find out how it works.
What is Malignant Hypothermia?
The root cause of malignant hypothermia is complex. Technically classified as a disease, the disorder is caused by the metabolism in the skeletal muscle rapidly speeding up.
There are a number of warning signs that can be used to identify malignant hypothermia when it occurs- symptoms such as hypercarbia, rigid muscle tissue, an extremely fast rise in body temperature, myolysis, tachycardia, acidosis and hyperkalemia are all key signs that a patient may be developing malignant hypothermia.
While dangerous, malignant hypothermia, or MH is relatively uncommon- only about one in every hundred thousand surgeries in adults cause HM. The phenomenon is more prevalent in children, occurring in one in every thirty thousands pediatric surgeries. Individuals with a specific genetic mutation are more likely to be susceptible to MH, with roughly one in every 2,000 patients possessing the relevant genetic code.
When malignant hypothermia occurs, it’s essential to act quickly and take action to prevent it immediately. Hypercarbia, or abnormally elevated carbon dioxide levels in the blood, is the most commonly reported clinical symptom that allows medical practitioners to identify the onset of malignant hypothermia. While the specific conditions of MH may vary from case to case, hypercarbia, tachycardia, and muscle rigidity are the most frequently reported clinical symptoms.
Treating malignant hypothermia is complex. The root cause of the disorder is an abnormally large calcium levels in skeletal muscle tissue. The high amount of fluid necessary to treat the disorder in the midst of a crisis situation, combined with time delays, make the treatment of MH problematic.
Stopping the administration of the agents that have triggered the MH response is the most important element of treating malignant hypothermia, which can delay the administration of a solution like Ryanodex and increase the likelihood of complications.
TIme is a pivotal aspect in treating MH. Every single delay that occurs in the treatment of malignant hypothermia increases the risk of dangerous further complications, with every 20 minute delay from the first sign of MH increasing the likelihood of complications occurring.
The high fluid volume complications that occur as a result of delayed MH treatment include conditions such as pulmonary edema, cellulitis, phlebitis, hyponatremia, and acute respiratory distress syndrome.
What is Ryanodex?
Ryanodex is an injectable solution that is able to keep patients cool in the midst of a malignant hyperthermia crisis in less than one minute. The solution consists of a unique, reformulated dantrolene sodium solution that leverages innovative nanotechnology that incorporates nanosuspension techniques to deliver fast acting results in treating MH.
The loading dose of 2.5mg/kg of dantrolene sodium can be rapidly reconstituted and subsequently administered in an incredibly short amount of time- less than one minute- which significantly lowers the risk of complications occurring.
Ryanodex holds a unique advantage over other approved dantrolene sodium formulations in that it possesses a higher concentration and purity level- one vial of Ryanodex contains 12.5 times more dantrolene than other solutions.
The ease of which Ryanodex can be administered makes it possible for a single anesthesia provider to perform the administration, allowing the patient care team to remain calm and focused during a crisis. Each 250 mg vial of Ryanodex can be reconstituted with just 5 ml of sterile water, and is ready for injection in just ten seconds.
The fast administration method and low fluid volume of the solution makes it ideal for treating MH, offering the advantage of lowering the risk of high fluid volume complications occurring. The Ryanodex solution can typically be used at a rate of one vial per individuals with a body weight up to 100kg, with a maximum cumulative dose of 10 mg/kg.
The Clinical Pharmacology of Ryanodex
Ryanodex contains dantrolene sodium, which is classified as a ryanodine receptor 1 antagonist. The pharmacology behind the mechanism of action of Ryanodex is complex, but is believed to function by inhibiting the release of calcium from the sarcoplasmic reticulum in skeletal muscle tissue, which leads to muscle relaxation.
A conclusive clinical trial that assessed the effects of dantrolene sodium in healthy volunteers has demonstrated the effectiveness of the Ryanodex solution. In the phase one trial, participants were dosed with an injectible suspension of dantrolene sodium through a continuous intravenous push via a forearm catheter. Patients were supplied with a 2.5mg/kg dose.
The trial resulted in a dose-proportionate increase in plasma exposure of dantrolene, with whole blood dantrolene remaining at a steady state for three hours after prophylactic intravenous dantrolene infusion was administered. The advantages of Ryanodex become apparent when it’s compared to other malignant hyperthermia treatment methods.
Ryanodex required only one to three vials for MH treatment, compared to the 12.5 to 36 vials necessary for treatment by other protocols. The Ryanodex protocol also uses 99% less sterile water, requiring just 5 ml to 15 ml of sterile water vs the 750 ml to 2160 ml sterile water required by other treatment protocols.
Able to be reconstituted and administered in less than one minute compared to the greater than 15 minute administration time of other protocols, Ryanodex is the best treatment method for MH available.
Ryanodex is supplied as single use vials containing 250 mg of dantrolene sodium as a lyophilized powder. The Ryanodex website provides the capacity to petition for formulary status or speak with a rep.