From the Guidelines
Genetic Abnormality Causing Resistance to Anesthesia and Intolerance to Pain Medication
It is crucial to consider RYR1 mutation, a genetic abnormality that affects the ryanodine receptor gene, as a primary cause of resistance to anesthesia and intolerance to pain medication, particularly in the context of malignant hyperthermia susceptibility 1.
Key Points
- Malignant Hyperthermia (MH): A rare but potentially fatal pharmacogenetic disease triggered by certain anesthetics, with a genetic basis linked to mutations in the RYR1 gene 1.
- RYR1 Mutation Screening: Genetic testing for RYR1 mutations can help identify individuals at increased risk of developing MH, guiding the choice of anesthetics and pain management strategies 1.
- Clinical Implications: Patients with RYR1 mutations may require alternative anesthetics and pain medications to avoid triggering MH or experiencing adverse reactions, highlighting the importance of genetic testing and personalized medicine in anesthesia and pain management 1.
Alternative Considerations
While other genetic conditions, such as pseudocholinesterase deficiency and porphyria, can also affect anesthetic and pain medication metabolism, the RYR1 mutation is specifically associated with malignant hyperthermia susceptibility and resistance to certain anesthetics 1.
Conclusion is not allowed as per the guidelines, so the response ends here.
From the FDA Drug Label
Plasma cholinesterase deficiency may also account for diminished tolerance to ester-type local anesthetics. The genetic abnormality that causes resistance to anesthesia and intolerance to pain medication (analgesics) is plasma cholinesterase deficiency 2 3.
- This deficiency can lead to diminished tolerance to ester-type local anesthetics.
- It is a key factor to consider when administering local anesthetics, as it can affect the patient's response to the medication.
From the Research
Genetic Abnormality Causing Resistance to Anesthesia
- Pseudocholinesterase deficiency is a rare genetic or acquired disorder that affects the body's ability to metabolize choline esters such as succinylcholine and mivacurium 4, 5, 6, 7.
- This deficiency can be inherited as an autosomal recessive trait, occurring in approximately 1 in 3,200 to 1 in 5,000 people 5.
- The genetic abnormality is caused by a mutation in the butyrylcholinesterase (BCHE) gene, which provides instructions for making the pseudocholinesterase enzyme 7.
Effects on Anesthesia and Pain Medication
- Pseudocholinesterase deficiency can lead to prolonged recovery from paralysis following general anesthesia in which succinylcholine or mivacurium are administered 4, 5, 6.
- Patients with this deficiency may experience increased sensitivity to anesthetic agents, such as succinylcholine and mivacurium 7.
- The deficiency can also result in prolonged duration of action of muscle relaxants that are hydrolyzed by pseudocholinesterase, such as mivacurium 8.
Diagnosis and Management
- A detailed history and family history of anesthesia complications can help identify patients at risk of pseudocholinesterase deficiency 5.
- In cases of unexpected prolonged muscle relaxation after mivacurium, pseudocholinesterase deficiency should be considered and its activity measured 8.
- Anesthesia providers must understand the pathophysiology of pseudocholinesterase deficiency and be prepared to safely and effectively manage patients who show signs and symptoms consistent with the disorder 6.