Do Not Reverse Neuromuscular Blockade Unless the Patient is Warm
James F. Weller MD
Neuromuscular blocking agents (Table 123.1) are used routinely during general anesthesia to facilitate endotracheal intubation and to provide optimal surgical conditions. These drugs block transmission at the neuromuscular junction through their effects on the postsynaptic acetylcholine receptor. Since these drugs block transmission of impulses from the nerve to the muscle, they cannot prevent muscle contraction in response to direct application of electrical stimulation (e.g., from electrocautery).
The agents used to provide muscle relaxation fall into two classes: depolarizing and nondepolarizing. The only depolarizing agent used clinically in the United States is succinylcholine. Binding of succinylcholine to the postsynaptic acetylcholine receptor causes the channel to open, leading to an initial wave of depolarization that causes the muscle to fasciculate. However, unlike acetylcholine, succinylcholine remains bound to the receptor, leading to a period of flaccid paralysis lasting several minutes. It is degraded by plasma pseudocholinesterase and cannot be reversed.
The nondepolarizing neuromuscular relaxants work by competitive inhibition of acetylcholine at the same receptor site. The choice of nondepolarizer is generally made on the basis of time of onset, duration of action, and side-effect profile. Elimination generally involves renal and/or hepatic metabolism, which may also impact drug choice in some patients. Exceptions include mivacurium, which like succinylcholine is degraded by plasma pseudocholinesterase, and atracurium and cisatracurium, which are eliminated by Hoffman degradation (a nonenzymatic phenomenon that results in breakdown of these drugs at physiologic temperature and pH).
Because their physiologic effect depends upon competitive inhibition, the nondepolarizing agents can be “reversed” by administration of acetylcholinesterase inhibitors (e.g., neostigmine, edrophonium), which lead to accumulation of acetylcholine at the neuromuscular junction and elsewhere in the body. In order to prevent undesirable cholinergic side effects outside the neuromuscular junction (e.g., bradycardia, salivation, lacrimation), an antimuscarinic agent (e.g., glycopyrrolate, atropine) is generally administered concomitantly with the cholinesterase inhibitor.