Neuromuscular blockade is frequently used in anesthesia to facilitate endotracheal intubation, optimize surgical conditions, and assist with mechanical ventilation in patients who have reduced lung compliance. Neuromuscular blocking agents (NMBAs) come in two forms: depolarizing neuromuscular blocking agents (e.g., succinylcholine) and nondepolarizing neuromuscular blocking agents (e.g., rocuronium, vecuronium, atracurium, cisatracurium, mivacurium). The class of NMBAs used for achieving neuromuscular blockade must be selected carefully based on patient factors, the type of procedure being performed, and clinical indication.

Depolarizing neuromuscular blockers: Succinylcholine is the depolarizing neuromuscular blocker of choice. It is widely used due to its rapid onset and short duration of action, making it ideal for rapid sequence inductions. Its mechanism of action involves binding to post-synaptic cholinergic receptors on the motor endplate, which causes rapid depolarization, fasciculation, and flaccid paralysis. [1] Usually paralysis takes place approximately 1 minute after administration and lasts approximately 7-12 minutes. [2] Succinylcholine is metabolized by plasma pseudocholinesterase. If the patient has pseudocholinesterase deficiency, this can lead to prolonged neuromuscular blockade that may require postoperative mechanical ventilation. [3]

Nondepolarizing neuromuscular blockers: Nondepolarizing neuromuscular blockers can be divided into two classes based on their chemical structure: steroidal (e.g., rocuronium, vecuronium, pancuronium) or benzylisoquinolinium (e.g., mivacurium, atracurium, cisatracurium). Nondepolarizing neuromuscular blockers are competitive acetylcholine (ACh) antagonists that bind directly to nicotinic receptors on the postsynaptic membrane, thus blocking the binding of ACh so the motor endplate cannot depolarize. [4] This leads to muscle paralysis.

Monitoring neuromuscular blockade: Train-of-four (TOF) stimulation is the most common method utilized to monitor the extent of neuromuscular blockade. It consists of four consecutive 2 Hz stimuli to a chosen muscle group, and the respective number of twitches evoked, also known as train-of-four count (TOFC), provides information on the patient’s recovery from neuromuscular blockade.

• TOFC of 1 = >95% of receptors blocked
• TOFC of 2 = 85-90% of receptors blocked
• TOFC of 3 = 80-85% of receptors blocked
• TOFC of 4 = 70-75% of receptors blocked [5]

The train-of-four ratio (TOFR) is determined by dividing the amplitude of the fourth twitch to the amplitude of the first twitch. If the TOFR is <0.9, this indicates residual neuromuscular blockade and necessitates the use of a reversal agent. Reversal of neuromuscular blockade is commonly achieved with neostigmine, an anticholinesterase, and glycopyrrolate. However, sugammadex can also be used as a reversal agent if a steroidal NMBA was used.

Adverse Effects: Succinylcholine use should be avoided in patients with severe hyperkalemia, significant burns, denervating disease, and a history of malignant hyperthermia. [6] Nondepolarizing neuromuscular blockers may cause histamine release associated with hemodynamic instability. Slowing the infusion rate or pre-treating with antihistamines can reduce the incidence. [7]

Drug Interactions: 

• Antimicrobials - Aminoglycosides, tetracyclines, polymyxins, and clindamycin can potentiate neuromuscular blockade. [8]
• Inhaled anesthetics can potentiate neuromuscular blockade when used with nondepolarizing NMBAs. [9]
• Anti-seizure drugs - Chronic treatment with anti-seizure medications can make a patient resistant to nondepolarizing NMBAs. [7]
• Lithium can potentiate neuromuscular blockade in both depolarizing and nondepolarizing NMBAs. [10]
• Local anesthetics can potentiate neuromuscular blockade in both depolarizing and nondepolarizing NMBAs. [7]

Neuromuscular blockers are commonly administered during anesthesia to assist with endotracheal intubation and improve surgical conditions. It is important to understand when each class of NMBAs should be used and when they should be avoided. The depth of paralysis should be closely monitored via TOF for the duration of the procedure, and the physician should always be aware of potential medications, physiologic derangements, or genetic disorders that could lead to potentiation of neuromuscular blockade, leading to postoperative complications.

The healthcare team, i.e., clinicians, nurses, and pharmacists, must work together to make sure that patients undergoing neuromuscular blockade are carefully monitored for adverse events. A complete medication list for the patient is necessary before administering a NMBA to prevent clinically significant drug interactions, and a pharmacist can perform medication reconciliation to answer any questions or address concerns other healthcare team members may have. [Level V]