Neuromuscular blocking agents: Uses, common brands, and safety info

Although a startling concept, the neuromuscular blocking agent (NMBA) drug class is used to induce complete muscle paralysis within seconds to minutes. The purpose of these drugs in operating rooms, intensive care units (ICU), and emergency rooms is to facilitate the placement of a breathing tube, the use of a ventilator, or surgery. They must be given concurrently with anesthetic drugs that impair consciousness to prevent awareness of paralysis. NMBAs serve an important role during the most critical times of medical treatment, but they entail significant risks. Understanding the different types of these agents, as well as their mechanism of action, adverse effects, and costs, will be the goal of this review.

Other neuromuscular blocking agents

• Vecuronium

• Pancuronium

• Nimbex (cisatracurium)

• Mivacurium

• Atracurium

What are neuromuscular blocking agents?

Neuromuscular blocking drugs are medications that induce paralysis. Complete muscle relaxation permits easier tracheal intubation, which is insertion of a breathing tube into the trachea. Intubation is done prior to initiating mechanical ventilation (breathing machine use) in someone having surgery or critically ill patients. The lack of muscle resistance during paralysis can also be helpful throughout the duration of certain surgical procedures, such as laparoscopic and robotic surgeries. Therefore, the use of NMBAs can be seen with both the induction or start of anesthesia and the maintenance of anesthesia.

These agents are all administered through an intravenous (IV) line most commonly. Anesthesiologists, healthcare providers who specialize in anesthesia and analgesia, are most adept with the use of NMBAs and anesthetic drugs, as well as analgesics (pain medicines). Critical care and emergency medicine providers may also use these drug classes when necessary.

How do neuromuscular blocking agents work?

Muscles contract after being told to do so by nerves. The meeting of a nerve cell and muscle cell’s endplate is termed the neuromuscular junction (NMJ). At the NMJ, the end of an activated nerve cell releases acetylcholine (ACh), a signaling chemical that is also found in the central nervous system (CNS) and peripheral nervous system. ACh within the NMJ binds to nicotinic receptors of a skeletal muscle cell or muscarinic receptors of a smooth muscle cell, ultimately inducing contraction. Skeletal muscles attach to bones and produce voluntary motion when they contract, while involuntary smooth muscles are found in internal organs such as bronchial tubes, the bladder, and the gastrointestinal tract.

When neuromuscular blockers bind to the nicotinic receptor, they prevent acetylcholine from accessing the receptor. By doing so, they interrupt neuromuscular transmission and avert skeletal muscle contraction. Unfortunately, NMBAs do exert a neuromuscular block via muscarinic receptors as well, which explains some of their adverse effects.

The one depolarizing NMBA succinylcholine binds to and stimulates the nicotinic receptor, briefly causing muscle activity called fasciculations or twitching before blocking acetylcholine access to the receptor. Paralysis occurs after the fasciculations have resolved. 

Succinylcholine’s agonist followed by blocking action at the nicotinic receptor contrasts with the multiple different nondepolarizing NMBA medications. Nondepolarizing agents are antagonists of the receptor. They attach to the receptor and produce no stimulation of the muscle and prevent ACh access to the receptor.

Monitoring the depth of paralysis is an important part of using both depolarizing and nondepolarizing neuromuscular blocking agents. Electrical stimulators are often placed on the skin of the face or arm, and ideally, a device is also used to gauge the muscle’s response. The nerve stimulation is given in sets of four impulses, each set known as a train-of-four. 

When time alone is judged as insufficient to reverse the effects of NMBAs, the healthcare provider can use a reversal agent. Neostigmine is a cholinesterase inhibitor drug. It curbs the action of acetylcholinesterase, the enzyme that breaks down ACh. Via this mechanism, neostigmine administration leads to more ACh at the NMJ, which overcomes the NMBA’s effect. Its use is usually coupled with atropine or glycopyrrolate to counteract neostigmine’s untoward muscarinic receptor effects like bradycardia and abdominal cramps.

What are neuromuscular blocking agents used for?

• Neuromuscular blockade induction

• Neuromuscular blockade maintenance

• Rapid sequence intubation

Types of neuromuscular blocking agents

Depolarizing NMBAs

Succinylcholine is the only depolarizing agent used in clinical practice. Brand names include Quelicin and Anectine. It has several advantages and disadvantages compared to nondepolarizing options. Rapid onset of action within a minute and an ultra-short duration of action make it ideal for some circumstances. 

Rapid sequence intubation is a procedure used to quickly insert a breathing tube in an individual who is acutely ill or requiring emergency surgery. At the start of the procedure, prior to tube insertion, an anesthetic drug is given for sedation along with a NMBA. The goal is get the tube inserted in a minimum amount of time to prevent aspiration or the breathing in of body fluids. Succinylcholine serves the needs of rapid sequence intubation well with its quick onset and offset of action. To avoid this NMBA’s potential for causing bradycardia (slow heart rate), a dose of atropine is sometimes given in advance.

The pharmacokinetics of succinylcholine is different from most neuromuscular blocking drugs. It is broken down by butyrylcholinesterase, also known as pseudocholinesterase. The duration of action can be unexpectedly prolonged if one has a deficiency of butyrylcholinesterase.

Another unexpected and more dangerous complication of succinylcholine is malignant hyperthermia. This condition is a metabolic crisis triggered by inhaled anesthetics and rarely succinylcholine, which results in muscle rigidity and elevated heart rate, breathing rate, and temperature. Fortunately, it can be treated and reversed once recognized, and any personal or family history of malignant hyperthermia leads to avoidance of further succinylcholine use.

Nondepolarizing NMBAs

The second category of NMBAs includes both aminosteroid and benzylisoquinolinium versions. Understanding the distinct pharmacology of these compounds can help to understand how specific ones are chosen by healthcare professionals. The steroidal, nondepolarizing NMBAs are a diverse offering. Rocuronium acts within one to two minutes and has only an intermediate duration of action, a profile that makes it an alternative to succinylcholine for rapid sequence intubation. Vecuronium has a shorter duration of action than rocuronium, but a longer delay in achieving effectiveness negates its use when time is of the essence. Conversely, pancuronium has such a long duration of action that it is rarely used, due to fear of residual degrees of paralysis. The aminosteroids have an additional reversal option, sugammadex, that other NMBAs do not.

Cisatracurium is produced under the brand name Nimbex. It takes effect in about five minutes and has an intermediate duration of action. Cisatracurium does so without inducing problematic histamine release like its chemically similar compound, atracurium. Mivacurium, a short-acting NMBA, is also hampered by histamine release, which can result in skin flushing, tachycardia (fast heart rate), and hypotension (low blood pressure).

Who can take neuromuscular blocking agents?

Can men and women take neuromuscular blocking agents?

Men and women can both take NMBAs as long as there are no contraindications to using them.

Can you take neuromuscular blocking agents while pregnant or breastfeeding?

Barring contraindications, NMBAs can be used during pregnancy, although safety data is not abundant. Caution is advised with use while breastfeeding based on limited safety data.

Can children take neuromuscular blocking agents?

Succinylcholine, rocuronium, and pancuronium have Food and Drug Administration (FDA) indications for use in children. The indications are more limited for other NMBAs, down to only 7 weeks of age and older for vecuronium, 1 month and older for cisatracurium and atracurium, and 2 years and older for mivacurium. 

Succinylcholine use in children is limited by specific concerns. Succinylcholine’s penchant for causing bradycardia is more common in children and may be prevented with pretreatment with atropine or glycopyrrolate. The chance of undiagnosed muscular dystrophy in children is another concern related to succinylcholine. The drug can induce a life-threatening development of hyperkalemia (high blood levels of potassium) in these children.

Can seniors take neuromuscular blocking agents?

Seniors can take NMBAs, but healthcare professionals may choose different specific agents based on patient factors. For example, steroid NMBAs are typically more long acting in seniors, so they may be avoided. If renal (kidney) impairment is present, benzylisoquinoline NMBAs may be preferable. 

Are neuromuscular blocking agents safe?

Black box warnings

The FDA has required its highest level of warning for succinylcholine. The warning relates to rare incidences in which rhabdomyolysis (muscle breakdown) and resultant hyperkalemia has developed after succinylcholine dosing in children with previously undiagnosed muscular dystrophy. Hyperkalemia can cause ventricular dysrhythmia (abnormal heart rhythm), cardiac arrest (cessation of heart activity), and death. The advisory states that treatment for hyperkalemia should be administered if cardiac arrest develops after succinylcholine dosing. Furthermore, the FDA advises that use of the drug in children be limited to emergency intubation or situations where immediate securing of the airway is necessary.

Vecuronium and pancuronium both have a black box warning from the FDA regarding who should administer the drugs. The FDA specifies that only individuals who have been adequately trained with the drug’s actions, characteristics, and hazards should administer it.

Recalls

• Succinylcholine [11/12/2021]

• Cisatracurium [1/27/2021]

• Succinylcholine [9/12/2019]

• Succinylcholine [6/18/2019]

Restrictions

As previously mentioned, succinylcholine has some unique restrictions:

• It should be avoided by anyone with a history of hypersensitivity allergic reactions to it or its class.

• Succinylcholine should not be used by anyone with acute major trauma or burn, acute extensive muscular denervation, acute upper motor neuron injury, or elevated intraocular (eye) pressures. 

• Personal or family history of malignant hyperthermia or myopathy (muscle disorder) also precludes succinylcholine use. 

There are a number of other conditions which could increase the risk of succinylcholine and may require adjustment, monitoring, or avoidance of the drug.

The list of contraindications is substantially shorter for nondepolarizing NMBAs. They should not be used by anyone with a history of hypersensitivity allergic reactions to the individual drug or other members of the drug class. Otherwise, there are conditions that require caution with use of certain nondepolarizing NMBAs and possibly dosing adjustments or avoidance. 

Are neuromuscular blocking agents controlled substances?

NMBAs are not listed as controlled substances by the Drug Enforcement Administration (DEA).

Common neuromuscular blocking agents side effects

Succinylcholine can commonly cause muscle fasciculations (twitching), myalgias (muscle pain), elevated intraocular pressure, and jaw rigidity. Across the NMBA drug class, the following are common potential adverse effects.

• Hypertension or hypotension (high or low blood pressure)

• Tachycardia or bradycardia (high or low heart rate)

• Sialorrhea (excessive salivation)

• Skin rash or flushing

• Muscle weakness

• Bronchospasm (tightening of the bronchial tubes)

How much do neuromuscular blocking agents cost?

While generic rocuronium may only cost $11 per vial, a brand-name NMBA can be substantially more. The choice of NMBA is generally made by the hospital-based specialist who is administering it. In other circumstances, putting forth the effort to review different options within a drug class and debate between brand and generic versions is often worth the time investment. If time permits, such as prior to undergoing scheduled surgery rather than emergency uses of NMBAs, ask your provider about using a SingleCare discount card to reduce your drug costs.