Introduction 1
(MH) is a rare but life-threatening pharmacogenetic disorder triggered by certain anesthetic agents, leading to a hypermetabolic crisis in skeletal muscles. Without prompt treatment, MH can result in severe complications, including cardiac arrest, kidney failure, and death.
Dantrolene sodium (Dantrium) injection is the only specific antidote for malignant hyperthermia (MH) and has revolutionized its management since its introduction in 1979. Let’s simplify MH and understand its global and Indian prevalence.
Malignant Hyperthermia: 1
MH is an autosomal dominant disorder caused by mutations in the ryanodine receptor (RYR1) gene, which regulates calcium release in muscle cells.
In susceptible individuals, calcium is released uncontrollably when triggered- leading to muscle spasms and other issues that may be fatal. Triggers include volatile anesthetics (e.g., halothane, sevoflurane) or succinylcholine, and exposure to these leads to uncontrolled calcium release, which results in:
- Severe muscle rigidity, especially the facial masseter muscle spasming is one of the first signs of MH.
- Acidosis and hypercapnia (due to excessive CO₂ production)
- Hyperkalemia and arrhythmias (risk of cardiac arrest)
- Rhabdomyolysis, or the breakdown of muscles, causes the broken-down muscle substances to reach the kidneys, leading to kidney failure. This is why individuals with MH will have dark brown-colored urine.
- Hypermetabolism (skyrocketing body temperature, sometimes exceeding 42°C/107.6°F) usually one of the last few signs of MH.
Exercise-Induced Malignant Hyperthermia and Susceptibility Testing 1
While Malignant Hyperthermia (MH) is most commonly triggered by anesthetic agents, rare cases of exercise-induced MH (also called exertional rhabdomyolysis or heat stroke-like episodes) have been reported in genetically susceptible individuals. This occurs due to RYR1 mutations, which can cause abnormal calcium release in muscles during extreme physical exertion, leading to:
- Severe muscle breakdown (rhabdomyolysis)
- Dangerous hyperthermia (even in non-anesthetic settings)
- Risk of kidney failure and cardiac complications
How to Know If You Are Susceptible to MH? 2, 3
1.Family History of MH or Unexplained Anesthetic Deaths – If a relative had a severe reaction to anesthesia, genetic testing is recommended.
2.Previous Adverse Reaction to Anesthesia – Unexplained high fever, muscle rigidity, or cardiac instability during past surgery.
3.Exercise-Induced Episodes – Repeated episodes of severe muscle pain, dark urine (myoglobinuria), or heat stroke after intense exercise.
4.Genetic Testing – Confirms RYR1 or CACNA1S gene mutations (available in specialized labs like AIIMS, Delhi).
5.Caffeine-Halothane Contracture Test (CHCT) – The gold standard for diagnosis (performed on muscle biopsy in select centers).
Prevention and Living with MH-Susceptiblity: 1
- Stay hydrated and avoid extreme heat/exertion if prone to exercise-induced episodes.
- Carry a Medical Alert ID stating MH susceptibility OR consider wearing a medical alert bracelet. It may be beneficial in susceptible individuals for avoiding delays in diagnosis.
- If anybody in the family has had a MH episode, get tested and mention it before any surgical procedures involving general anesthesia.
- Avoiding all triggering anesthetics and ensuring MH-safe anesthesia protocols (using non-triggering agents like propofol). Making sure that the treating hospital has Dantrium available for use in-case of a MH episode.
Prevalence of Malignant Hyperthermia Worldwide vs. India 5, 6, 7
Global Prevalence :
- Estimated incidence: 1 in 5,000 to 1 in 100,000 anesthetic exposures.
- Higher prevalence in Caucasian populations due to genetic predisposition.
- Mortality rate without Dantrolene: 70-80%; with Dantrolene: <5%.
MH in India: An Underreported Crisis 5, 6, 7
- Lack of awareness among anesthesiologists in rural areas.
- No centralized MH registry, leading to underdiagnosis.
- Estimated MH deaths in India: 50-100 annually (likely to be much higher due to unreported cases).
- Global MH deaths have drastically reduced due to Dantrolene availability, but India still faces shortages, leading to preventable deaths.
Dantrium: The Game-Changer in MH Mortality 1, 4
Before Dantrolene, MH mortality was >80%. Today, with prompt Dantrolene administration:
- Mortality drops to <5% if treated early.
- Delayed treatment (>30 mins) increases death risk to 30%.
How Dantrolene Works 1, 10
- Mechanism: Inhibits calcium release from sarcoplasmic reticulum(a part of the cell), stopping muscle hypermetabolism.
Benefits of Dantrium Injection 10
1.Rapid Reversal of MH Crisis – Stops all the horrifying symptoms- muscle rigidity, hyperthermia, and acidosis.
2.Prevents Kidney Failure – By curbing rhabdomyolysis or muscle breakdown, Dantrium reduces the risk of kidney failure. 8
3.Prevents Organ damage: Protects the body from cardiac failure and brain injury which happen in untreated MH.9
4..Safe for All Ages – Effective in children and adults.
5. No Equivalent Alternative – No other drug can replace Dantrolene for MH.
6.Dantrium maybe indicated in hyperthermia induced by MDMA toxicity in some cases. 11
Dantrium in Indian Hospitals: A Critical Shortage 5, 6, 7
While developed nations stock Dantrolene in every operating theater, India faces challenges:
- Limited availability – Only tertiary care hospitals (AIIMS, PGIMER, Tata Memorial) keep stocks.
- Lack of training – Many anesthesiologists, especially, in rural areas have never used Dantrolene.
Efforts to improve access: 5
- MH emergency kits to be introduced in medical colleges.
- Awareness campaigns and training programs for anesthesiologists to ensure early diagnosis and immediate treatment of MH.
- Mandating Dantrium stocks in all hospitals utilizing general anesthesia.
In Conclusion: Dantrium Saves Lives 1, 4
Malignant Hyperthermia remains a deadly but treatable condition, and Dantrolene sodium injection is the only definitive cure. While global MH mortality has plummeted thanks to Dantrium, India still struggles with accessibility and awareness. Ensuring Dantrolene availability in every surgical center, along with anesthesiologist training, can prevent countless deaths. Dantrium is more than a wonder of modern science—it’s a lifeline for MH-susceptible individuals.
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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://www.ncbi.nlm.nih.gov/books/NBK430828/
2.https://www.bjanaesthesia.org/article/S0007-0912(17)31112-1/fulltext
3.https://pubmed.ncbi.nlm.nih.gov/9523799/
4.https://www.ijca.in/html-article/21388
6.Malignant Hyperthermia in India https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.2010.06532.x
7.https://www.e-jnic.org/m/journal/view.php?number=112
9.https://pubmed.ncbi.nlm.nih.gov/19460614/
10.https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/018264s042lbl.pdf
11.https://pubmed.ncbi.nlm.nih.gov/20925170/
