Mohammed Nabaz Fadhil
Fifth stage – group/A
Pharmacy department
Pseudocholinesterase (PCE) is an enzyme found in the plasma that the liver produces. It plays a key role in breaking down common anesthetics like succinylcholine and mivacurium, as well as local anesthetics such as cocaine. People with a normal version of this enzyme can quickly break down succinylcholine and mivacurium, usually in under 10 minutes for succinylcholine. However, those with a genetic deficiency have a faulty enzyme that doesn’t metabolize these drugs effectively, resulting in longer-lasting muscle paralysis. This deficiency can be inherited in different ways, either homozygous or heterozygous, or it can be acquired. Pseudocholinesterase deficiency, also known as butyrylcholinesterase deficiency, is a rare condition where the body struggles to break down neuromuscular blocking agents like succinylcholine and mivacurium in the bloodstream [1].
History and Physical
Pseudocholinesterase deficiency is usually identified only after a patient has a long-lasting neuromuscular blockade from regular doses of succinylcholine or mivacurium. When taking a medical history, it’s crucial to ask about any past experiences with anesthesia that required extended mechanical ventilation due to neuromuscular issues. Additionally, it’s important to check if there’s a family history of pseudocholinesterase deficiency.
Patients who have certain health conditions, such as cancer, severe burns, heart attacks, congestive heart failure, pregnancy, liver problems, hemodialysis, or chronic infections, might develop the acquired type of pseudocholinesterase deficiency. These conditions can lead to a significant drop in the levels of the pseudocholinesterase enzyme, making the patient more susceptible to prolonged neuromuscular blockade after standard doses of succinylcholine or mivacurium. Some medications such as organophosphate insecticides, MAO inhibitors, and anticholinesterase drugs can also lower the activity of pseudocholinesterase. This reduction can compound other existing enzyme deficiencies, whether inherited or acquired.
There aren’t any specific physical exam signs linked to pseudocholinesterase deficiency. Patients may either show normal physical exam results (inherited type) or exhibit findings related to their specific health conditions (acquired type) [2].
Succinylcholine-Related Apnea
Even though it has some negative side effects, like high potassium levels and irregular heartbeats, succinylcholine is still a widely used neuromuscular blocker because it works quickly and doesn’t last long. It’s often used to help relax the muscles for procedures like endotracheal intubation.
Normally, succinylcholine is broken down quickly into inactive substances called succinylmonocholine and choline by an enzyme known as PCE. When PCE levels are normal, the muscle paralysis caused by succinylcholine lasts about 10 to 12 minutes, which is the time it takes for muscle function to return after a dose of 1 mg/kg. This enzyme is so efficient that only about 5% of the drug actually makes it to the neuromuscular junction. The half-life for eliminating succinylcholine is estimated to be between 2 to 4 minutes.
However, people who have low levels of PCE or a different version of this enzyme might find that their recovery from muscle paralysis after receiving succinylcholine or mivacurium is slower. Mivacurium is a newer, short-acting muscle relaxant that also relies on PCE for breakdown. In individuals with very low PCE activity, the paralysis can last anywhere from a few minutes to as long as 8 hours [3].
Case
A 38-year-old woman came in for a hysteroscopy and myomectomy. Her medical history included exercise-induced asthma, fibroids, and headaches. There were no significant issues in her family history. She was a social drinker and had previously smoked. The physical examination showed no abnormalities, and her ASA classification was 2.
Before the procedure, she received 2 mg of Midazolam and was pre-oxygenated. General anesthesia was started with 100 mg of lidocaine and 200 mg of Propofol. An attempt to place a laryngeal mask airway (LMA) was unsuccessful, so she was given 100 mg of IV Succinylcholine for a smooth endotracheal intubation. Anesthesia was maintained with 70% oxygen and desflurane. Her initial vital signs were normal, and the surgery took about 30 minutes. During the procedure, she also received 4 mg of Dexamethasone, 4 mg of Ondansetron, 50 mg of Ketamine, and 30 mg of Ketorolac. After the surgery, the patient felt very weak, with a Medical Research Council (MRC) score of 0 and no visible muscle contractions. The neuromuscular train-of-four ratio showed 0 out of 4 twitches. She was re-sedated with Propofol and then moved to the post-anesthesia care unit (PACU), where mechanical ventilation continued. Neuromuscular monitoring was ongoing. After 360 minutes, she was successfully extubated when the train-of-four ratio showed 4 out of 4 twitches and an MRC muscle score of 5.
A dibucaine number test confirmed the diagnosis, showing a dibucaine number of 44, indicating she had heterozygosity for pseudocholinesterase deficiency [4].
Treatment / Management
People with pseudocholinesterase deficiency usually find out they have it after they experience long-lasting muscle paralysis from normal doses of succinylcholine and mivacurium. The main way to treat this condition is by providing respiratory support through mechanical ventilation until the muscle paralysis goes away on its own. Doctors can check if motor function is returning by using nerve stimulation. During this time, patients should stay sedated to prevent them from being aware of their surroundings while they wait for their muscle function to come back. It’s generally considered safer to use supportive treatment with sedation and mechanical ventilation until recovery, which typically takes just a few hours, rather than trying to reverse the paralysis with plasma transfusions or other medications that haven’t been very effective in the past.
For those who have already been diagnosed with pseudocholinesterase deficiency, it’s important to avoid using the depolarizing muscle relaxant succinylcholine and the non-depolarizing muscle relaxant mivacurium. Instead, other non-depolarizing muscle relaxants like atracurium, rocuronium, and vecuronium can be safely used in future anesthesia procedures [2].
Reference
- Choksi D, Marfatia GN, Mehta P. CASE REPORT OF PSEUDOCHOLINESTERASE ENZYME DEFICIENCY. INDIAN JOURNAL OF APPLIED RESEARCH [Internet]. 2024 Jun 1;29–30. Available from: https://doi.org/10.36106/ijar/7903975
- Trujillo R, West WP. Pseudocholinesterase deficiency [Internet]. StatPearls – NCBI Bookshelf. 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541032/
- Dell DD, Kehoe C. Plasma cholinesterase deficiency. Journal of PeriAnesthesia Nursing [Internet]. 1996 Oct 1;11(5):304–8. Available from: https://doi.org/10.1016/s1089-9472(96)90086-6
- Jevaughn D, Anita V, Geetha S. Pseudocholinesterase deficiency and patient perspectives. International Journal of Anesthetics and Anesthesiology [Internet]. 2021 Dec 31;8(2). Available from: https://doi.org/10.23937/2377-4630/1410124