Chapter 6
Use of Neuromuscular Blocking Agents
Physiology of Neuromuscular Excitation
Acetylcholine (ACh) is the primary chemical messenger responsible for mediating neuromuscular transmission. ACh serves as the messenger not only for neural communication at the neuromuscular junction but also for many central nervous system pathways, autonomic ganglia, and postganglionic parasympathetic nerve endings. When a nerve impulse arrives at the nerve terminal of the neuromuscular junction, intracytoplasmic vesicles containing ACh fuse with the nerve cell membrane, and the contents are released into the synapse. The ACh binds to the nicotinic ACh receptor (AChR) on the muscle cell, causing a conformational change and increasing the cellular permeability to sodium. When a sufficient number of sodium channels open, the transmembrane potential exceeds −50 mV and, as a result, the membrane depolarizes, creating an action potential that propagates to the entire motor unit and results in muscular contraction. The process of contraction requires calcium and is inhibited by magnesium.
Mechanism of Neuromuscular Blocking Drugs
Depolarizing Neuromuscular Blocking Drugs (D-NMBDs)
Of note, succinylcholine has potentially dangerous cardiac side effects that may preclude its use in some critically ill patients. Arrhythmias caused by autonomic stimulation (via nicotinic receptors on both sympathetic and parasympathetic ganglia) include sinus tachycardia, sinus bradycardia, junctional rhythms, and sinus arrest. Marked hyperkalemia following succinylcholine administration can lead to ventricular fibrillation or asystole. In most individuals, an increase in serum potassium level of 0.5 mEq/L is expected. This rise in serum potassium results from the depolarization of ACh receptors (primarily extrajunctional) and subsequent potassium release from muscle cells. Patients who have sustained denervation injuries or disorders (e.g., spinal cord transection, amyotrophic lateral sclerosis [ALS]) may have a much larger increase in serum potassium concentration, to the point of hyperkalemic cardiac arrest, if given succinylcholine. Patients with recent burns and muscular dystrophies are also at risk of life-threatening hyperkalemia after succinylcholine. Although renal failure per se is not a contraindication to succinylcholine use, its use is contraindicated in patients with hyperkalemia resulting from renal failure or other etiologies (e.g., digoxin toxicity [see Chapters 39 and 81]). Labeling by the Food and Drug Administration (FDA) also indicates cautious use in patients with renal failure because of prolongation of the blockade.