Managing Malignant Hyperthermia: The Essential Role of Dantrium

What is Malignant hyperthermia?

Malignant Hyperthermia (MH) is a life-threatening condition triggered by certain anesthetic drugs which maybe administered during medical procedures. This severe reaction is caused by specific anesthetic gases, which are commonly used to numb the body and block pain, sometimes in combination with muscle relaxants that temporarily paralyze the muscles for the duration of the procedure.1

Impact of Malignant Hyperthermia on a person's life:

Individuals prone to malignant hyperthermia, when exposed to these drugs, have a severe reaction which may lead to a rapid increase in heart rate and body temperature, a condition known as hyperthermia. In addition to this, they may experience quick and shallow breathing, muscle rigidity and an increase in acid levels in the blood and tissues (acidosis).

It maybe fatal without an intervention.

Symptoms to look out for: 1, 2
1. Rapid & shallow breathing.

2. Elevated ETCO2(End-tidal Carbon Dioxide)

3. Muscle rigidity, especially of the Masseter (a facial muscle)

4. Abnormal and rapid heart rate.

5. Rhabdomyolosis: Extreme muscle weakness due to breaking down of damaged muscle tissues which causes release of muscular substances like myoglobin, creatine kinase, and electrolytes into the bloodstream, leading to multiple issues in the entire body. 3
6. Brown Coloured urine: The release of damaged muscle components causes some of them to get excreted in the urine giving it a brown, bloody appearance.

7. “Mottled” skin: A patchy appearance of the skin due to the muscle rigidity and breakdown.
8.  Hyperthermia: Abnormally high temperature, although the disease itself is called Malignant Hyperthermia, hyperthermia itself is usually a late sign, other symptoms like rapid breathing, muscle rigidity and irregular heart-rate tend to develop earlier. It is characterized by a rapid rise in core temperature (1-2°C every 5 minutes). Severe cases (above 44°C) can cause increased oxygen use, carbon dioxide production, organ dysfunction, and blood clotting issues. 2, 5

 

Who is affected?
Many people with this condition may not realize that they have it unless they experience a serious reaction to anesthesia during surgery or if they are tested for it (especially if a family member had a similar bad reaction). 2


Genetic predisposition: MH is classified as a pharmacogenetic skeletal muscle disorder, it affects individuals with certain gene mutations, these mutations can only be diagnosed via genetic testing as these individuals are not phenotypically different than the normal population, which means that their genetic mutation does not affect how they generally appear. 2

Individuals at risk have mutations in the RYR1, CACNA1S, or STAC3 genes. These mutations are responsible for predisposing an individual to an episode of MH when a person is exposed to certain anesthetics or other triggers. 2

 


Malignant hyperthermia doesn’t always happen every time anesthesia is used. In fact, many individuals who experience a severe reaction have been given the same drug before without any problems.

 

 

To be Noted: Genetic Malignant hyperthermia susceptibility is  inherited- caused by a dominant gene. Most people with MHS have a parent who also has it, although the parent may not have had an MH episode. It's unclear how often MHS is caused by a new genetic change. Each child of someone with MHS has a 50% chance of inheriting the condition. 2

Prenatal testing is available if a known MH-related gene change exists in the family.

 

Diagnosis: The diagnosis is confirmed through a muscle biopsy with a contracture test or by genetic testing to identify mutations in the RYR1 gene associated with MH.

The in vitro contracture test (IVCT) is the gold standard for diagnosis. 4

The IVCT is performed by taking a small sample of muscle tissue, typically from the thigh or calf & testing it for contractions upon exposure to MH triggers such as halothane, succinylcholine and caffeine.

 

Although malignant hyperthermia usually occurs in people without major health issues, it is linked to certain inherited muscle disorders, such as central core disease, multiminicore disease, and STAC3 disorder.1,2

 

Manifestation of MH:

The way Malignant Hyperthermia manifests can be pretty dramatic, and in susceptible individuals- strenuous exercise can also trigger it. 2

Immediate medical intervention is crucial to manage MH. Upon prompt  induction of Dantrium, the risk of mortality drops down to less than 5%.5

 

Consequences of MH:

MH left untreated is almost always fatal, with mortality as high as 70%. 5

·         Organs such as the heart and kidneys may begin to fail, which can lead to cardiac arrest and kidney failure.

·          Furthermore, a dangerous blood clotting disorder known as disseminated intravascular coagulation may develop, which can disrupt normal clotting and lead to excessive bleeding or clotting problems throughout the body

 

Without fast and appropriate medical intervention, these complications can be fatal. Malignant hyperthermia is a medical emergency, and understanding the risks and symptoms is crucial to preventing and managing this potentially deadly reaction. 5

 

What is done to manage MH:

1.      Immediate discontinuation of the triggering agents.

2.      Administration of DANTRIUM (Dantrolene Sodium)

3.      Supportive measures to curb hyperthermia, electrolyte imbalances & acidosis.

 

The Life-saving role of Dantrium: 7

Dantrium Intravenous (dantrolene sodium) is a skeletal muscle relaxant mainly used in the emergency treatment for malignant hyperthermia.

How it works:


Normally, calcium is released to help muscles contract. In MH, however, abnormally high amount of calcium is released from the skeletal muscle cells, causing muscles to contract too much and raise body’s temperature.


Dantrolene works by stopping the excessive release of calcium in muscles during malignant hyperthermia (MH). It inhibits the Ryanodine receptor that controls calcium release, which reduces muscle contraction and lowers body temperature, curbing the crisis.

 

Precautions with DANTRIUM usage:

When using Dantrium (dantrolene) IV, there are several important precautions to keep in mind: 6, 7

  1. Monitoring vital signs: During a medical procedure involving use of known triggers, it's important to monitor vital signs not only for an early MH diagnosis, but also during and after Dantrium administration.
  2. Liver function: Hepatotoxicity (toxicity of the liver) is rare with Dantrium IV as it is short-term but liver damage and failure has been reported- damage is linked to the duration and dosage of dantrium. 7
  3. Drug interactions: Dantrolene may interact with other medications, including other muscle relaxants, anaesthetics, and certain drugs used for treating heart conditions. It is crucial to inform your healthcare provider about any medications you're taking.
  4. Injection site reactions: IV dantrolene may cause pain, irritation, or inflammation at the injection site. Your doctor must ensure no extravasation or leaking of dantrium takes place as its pH can cause tissue necrosis.
  5. Pregnancy and breastfeeding: Dantrolene should only be used during pregnancy if absolutely necessary, as it can cross the placenta. Very less data is available on quantity of dantrolene that passes into breast milk, so it should be used with caution in breastfeeding women.


Events such as: aplastic anemia, leukopenia, lymphocytic lymphoma, and heart failure have been reported in patients receiving oral Dantrolene capsules, DANTRIUM IV has no such incidents reported that may be directly linked to its administration in MH treatment.

Although there are no absolute contraindications for short-term life-saving usage of DANTRIUM IV in treating MH, it is essential to always follow the prescribed guidelines and give a thorough medical history to the doctor for individual concerns before administering Dantrium. 6

Side effects:

1.      Loss of grip strength and muscle fatigue: Driving and operating machinery must be avoided for a while upon receiving DANTRIUM therapy, it has been reported that post-dantrium therapy one can experience loss of grip strength as well as loss of strength in muscles, particularly leg muscles. 7

2.      Lightheadedness and nausea: Both have been reported along with drowsiness for upto 48 hours post-administration. 7

 

 

Conclusion:

Dantrium IV is a well-studied drug that has played the most crucial role in drastically bringing down the mortality rate of MH in the past few decades, its benefits do seem to outweigh the side-effects, it is an absolute boon to individuals who are at risk for MH, any medical facility using known MH triggers should ideally keep DANTRIUM at hand. Rx4u allows procurement of  this medicine , making it accessible to patient in dire need in India.

For individuals battling rare conditions like Malignant Hyperthermia, obtaining the right treatment can feel overwhelming. Rx4u serves as a bridge, turning hope into reality by streamlining the process and making critical medications more accessible when they are needed the most.

Note:

The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.

 

References:

1: https://medlineplus.gov/genetics/condition/malignant-hyperthermia/

2. https://pmc.ncbi.nlm.nih.gov/articles/PMC1867813/

3. https://pmc.ncbi.nlm.nih.gov/articles/PMC4365849/#:~:text=INTRODUCTION-,Rhabdomyolysis%20is%20a%20complex%20medical%20condition%20involving%20the%20rapid%20dissolution,3

4. https://pubmed.ncbi.nlm.nih.gov/26188342/  

5. https://my.clevelandclinic.org/health/diseases/17945-malignant-hyperthermia

6.https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018264s025lbl.pdf

7. https://www.medsafe.govt.nz/profs/datasheet/d/dantriumivinj.pdf

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