Definition/Introduction

Neuromuscular blockade is frequently used in anesthesia to facilitate endotracheal intubation, optimize surgical conditions, and assist with mechanical ventilation in patients with reduced lung compliance. Neuromuscular blocking agents (NMBAs) come in two forms: depolarizing neuromuscular blocking agents (eg, succinylcholine) and nondepolarizing neuromuscular blocking agents (eg, 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 induction. Its mechanism of action involves binding to postsynaptic cholinergic receptors on the motor endplate, which causes rapid depolarization, fasciculation, and flaccid paralysis. [1] Usually, paralysis takes approximately 1 minute after administration and lasts approximately 7 to 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 classified into two classes based on their chemical structure: steroidal (eg, rocuronium, vecuronium, pancuronium) or benzylisoquinoline (eg, 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 to 90% of receptors blocked
• TOFC of 3 = 80 to 85% of receptors blocked
• TOFC of 4 = 70 to 75% of receptors blocked[5]

The train-of-four ratio (TOFR) is determined by dividing the amplitude of the fourth twitch by 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 is used.[6]

Issues of Concern

 Depolarizing NMBAs (eg, succinylcholine)

• Neuromuscular Disorders: Succinylcholine causes transient hyperkalemia. In conditions associated with denervation and increased extrajunctional nicotinic acetylcholine receptors (nAChRs), like spinal cord injury and burn patients, administration may be life-threatening. Myasthenia gravis patients are resistant to succinylcholine.
• Obesity: The dose of succinylcholine in obese patients should be based on total body weight to achieve optimal intubating conditions.
• Kidney Diseases: Succinylcholine remains an option for patients with renal disease, provided their potassium levels are within the normal range.
• Malignant hyperthermia: Avoid succinylcholine in patients with diagnosed malignant hyperthermia or a family history of malignant hyperthermia.[7]

Nondepolarizing NMBAs

• Neuromuscular Disorders: Sensitivity to nondepolarizing NMBAs can vary or increase in individuals with neuromuscular disorders, necessitating careful monitoring. Patients with myasthenia gravis are notably sensitive to these agents.
• Burn Injuries: An increased presence of nAChRs due to burn injuries leads to resistance to nondepolarizing NMBAs, shortening their duration of action.
• Age-Related Considerations: In older adults, the effects of steroidal nondepolarizing NMBAs can be prolonged due to various physiological changes. 
• Obesity: Studies on the effects of obesity on nondepolarizing NMBAs have been inconclusive, but it's generally recommended to calculate doses based on ideal body weight plus an additional 10%.
• Liver and Kidney Diseases: Benzylisoquinolinium NMBAs are a good choice because their elimination isn't reliant on these organs.
• Physiological Factors: Hypothermia can prolong the effects of nondepolarizing NMBAs. Hypermagnesemia potentiates the effects of these drugs, while hypercalcemia can diminish their efficacy. Acidosis or alkalosis can lengthen or shorten the effects of nondepolarizing NMBAs, respectively.[8]

Drug interactions

• Antimicrobials like aminoglycosides, tetracyclines, polymyxins, and clindamycin can potentiate neuromuscular blockade.[9]
• Inhaled anesthetics can potentiate neuromuscular blockade when used with nondepolarizing NMBAs.[10]
• Anti-seizure medications can make patients resistant to nondepolarizing NMBAs.
• Lithium can potentiate neuromuscular blockade in both depolarizing and nondepolarizing NMBAs.[11]
• Local anesthetics can potentiate neuromuscular blockade in both depolarizing and nondepolarizing NMBAs.

Clinical Significance

Neuromuscular blockers are commonly administered during anesthesia to assist with endotracheal intubation and improve surgical conditions. It is essential 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.

Of particular interest to the anesthesia care team, pseudocholinesterase (butyrylcholinesterase) deficiency may prolong the neuromuscular blockade of succinylcholine or mivacurium. Pseudocholinesterase metabolizes these drugs in the plasma to inactive forms. Prolongation of neuromuscular blockade due to pseudocholinesterase deficiency is most pronounced in patients who are homozygous for a defective pseudocholinesterase enzyme. Other factors can affect the levels of pseudocholinesterase in the plasma, like pregnancy, advanced age, severe liver disease, burn injuries, and drug interactions.[3]

Nursing, Allied Health, and Interprofessional Team Interventions

The healthcare team, ie, physicians, certified registered nurse anesthetists (CRNA), and pharmacists, must work together to ensure that patients undergoing neuromuscular blockade are carefully monitored for adverse events. A complete medication list for the patient is necessary before administering an NMBA to prevent significant drug interactions, and a pharmacist should perform medication reconciliation to avoid drug interactions and medication errors and report to the anesthesiologist in case of discrepancy. An interprofessional team approach between pharmacists and the anesthesia care team improves the safety of perioperative care.[12]

Nursing, Allied Health, and Interprofessional Team Monitoring

The following are the recommendations from the 2023 American Society of Anesthesiologists (ASA) practice guidelines for neuromuscular blockade.[6] 

• Due to its low sensitivity, ASA recommends not relying solely on clinical assessment for neuromuscular blockade.
• Select quantitative monitoring over qualitative assessment to control residual neuromuscular blockade.
• Clinicians should confirm a TOF ratio ≥ 0.9 before extubation when utilizing quantitative monitoring.
• Utilize the adductor pollicis muscle for neuromuscular monitoring.
• Avoid using ocular muscles for neuromuscular monitoring.
• Clinicians can consider neostigmine as a suitable alternative to sugammadex at the minimal depth of neuromuscular blockade.
• Consider neostigmine antagonism at minimal neuromuscular blockade depth when using atracurium or cisatracurium to avoid residual blockade. ASA suggests that in the absence of quantitative monitoring, it is advisable to allow a minimum of 10 minutes to elapse after neostigmine-induced reversal to reasonably ensure adequate recovery of the block before proceeding with extubation.