Depolarizing Neuromuscular Blocking Drugs (D-NMBDs)

Depolarizing neuromuscular blocking agents (of which succinylcholine is the sole agent currently available for clinical use) act as ACh receptor agonists. The initial effect of D-NMBD binding is depolarization followed by muscle contraction. The blockade that follows contraction is caused by the relatively slow hydrolysis of the drug relative to that of ACh. Persistence of the D-NMBD at the receptor site renders adjacent sodium channels inactive. Repolarization is therefore delayed, and successive nerve impulses find the muscle refractory to depolarization.

Succinylcholine is used to achieve rapid (<60 seconds) paralysis and is frequently used for patients who are at risk for regurgitation of gastric contents during emergent intubation. Recovery from the paralytic effects of succinylcholine is also rapid because of rapid degradation of the drug by butyrylcholinesterase. This “rapid on, rapid off” effect is particularly beneficial for spontaneously breathing patients in whom positive pressure ventilation might be detrimental or in cases where securing the airway via endotracheal intubation may be difficult and rapid resumption of spontaneous ventilation is desired. Succinylcholine in rare instances can be delivered by a continuous infusion but is usually not used for prolonged paralysis in critically ill patients.

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.