45yoF with myasthenia gravis presents in respiratory distress. She requires urgent intubation. Which paralytic will you use?
Myasthenia gravis is an autoimmune neuromuscular disorder in which antibodies target nicotinic acetylcholine receptors at the neuromuscular endplate, preventing excitation/depolarization and subsequent muscle contraction.
Respiratory compromise or failure may occur due to weakening of diaphragm/accessory muscles. In the ED this will be a clinical diagnosis, however on the INSERVICE you will identify spirometry, or more specifically, the negative inspiratory force, as the “next step” in management for pts with MG.
When intubating, we know one paralytic is supposedly contraindicated, but why? And is there data to support this contraindication?
Short answer: No.
Succinylcholine is a depolarizing neuromuscular blocker. It is structurally similar to ACh, and binds to nicotinic ACh receptors on the neuromuscular endplate. This causes systemic depolarization (causing transient hyperkalemia, fasciculation), and remains on the receptor causing sustained depolarization and prevention of further stimulation by Ach. This results in paralysis. Sux remains attached to the endplate for several minutes until it diffuses away. When the drug is first injected, ~90% of it is hydrolyzed by Butyrylcholinesterase, so the effective dose is approximately 10% of that administered. BCHE is a plasma cholinesterase, distinct from acetylcholinesterase. ACh lives in the post-synaptic membrane, and hydrolyzes ACh rapidly to disrupt continued transmission. ACh does not hydrolyze succinylcholine. If you have a deficiency in BCHE (pseudocholinersterase deficiency), and you get sux, 100% of it is active, and you’ll be paralyzed for hours and clinicians may mistake this for severe neurologic pathology, plus you’ll be stuck in a paralyzed nightmare.
Patients are often prescribed cholinesterase inhibitors to improve symptoms of myasthenia gravis, such as pyridostigmine. These drugs decrease hydrolyzation of ACh at the endplate, increasing stimulation and muscle function. Pyridostigmine may decrease circulating BCHE, which could result in prolonged paralysis if given sux.
½ the crux of the sux contraindication is that due to the antibody mediated decreased # of ACh receptors, sux simply doesn’t have enough targets to create adequate paralysis for intubation. Multiple studies have shown that the dose of succinylcholine required to produce neuromuscular blockade is approximately double in patients with symptomatic MG. This was first performed in intubated patients in the OR, with ulnar nerve/hypothenar muscle EMG results plotted against slowly uptitrating succinylcholine doses. These studies versus controls demonstrated approximately double the amount of Sux was needed in pts with MG for neuromuscular blockage (0.8mg/kg vs 0.3mg/kg).
There is, however, a case report in anesthesia where a patient could not obtain vocal cord relaxation (thus be intubated) with 450mg of succinylcholine. The anesthesia literature has not directly studied the doses required to produce ideal intubating conditions in patients with MG, but multiple Anesthesiology review articles quote the EMG studies in the OR and conclude that sux should be safe in patients with MG, using standard ED RSI dose (1.5-2mg/kg), given that complete paralysis is documented at levels of 0.8mg/kg in studies.
A further and disputed claim is that there is risk for a worse hyperkalemic response. Some neuromuscular disease, such as muscular dystrophy or denervating disease such as ALS, MS, >72 hour spinal cord injury, etc, result in upregulation in the number of ACh receptors, which can cause an exaggerated hyperkalemic response when sux is given. However the converse is true in MG, where there is destruction of ACh receptors. Of yet, there is not data (I’ve found) to demonstrate a pathologic increase in plasma potassium with sux use in MG.
To summarize, though not directly studied, the anesthesiology literature subjectively supports the use of succinylcholine as needed for intubation in patients with myasthenia gravis, perhaps with slight increase in RSI dose (2.0mg/kg). There is not theoretical risk or report of hyperkalemic response.
Of note, the dose of roc is suggested to be decreased by half, to 0.6mg/kg in pt’s with MG.
Eisenkraft JB, Book WJ, Mann SM, Papatestas AE, Hubbard M. Resistance to succinylcholine in myasthenia gravis: a dose-response study. Anesthesiology. 1988 Nov;69(5):760-3
M. Abel, J.B. Eisenkraft Anesthetic implications of myasthenia gravis Mt Sinai J Med, 69 (2002), pp. 31–37
Dillon FX. Anesthesia issues in the perioperative management of myasthenia gravis. Semin Neurol. 2004 Mar;24(1):83-94. Review.
Levitan R. Safety of succinylcholine in myasthenia gravis. Ann Emerg Med. 2005 Feb;45(2):225-6.
Baraka A. Suxamethonium block in the myasthenic patient. Correlation with plasma cholinesterase. Anaesthesia. 1992 Mar;47(3):217-9