Neuromuscular Blocking Agents

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Neuromuscular blocking agents (NMBAs) or muscle relaxants remain an integral component in the administration of anesthesia. Since the early 1900s, NMBAs have supported the evolution of surgical procedures and improved the safety and quality of emergency interventions. Significant advances continue to enhance the understanding of neuromuscular transmission physiology and the pharmacology of muscle relaxants. The use of NMBAs and their respective reversal agents have contributed significantly to clinical anesthesia as currently practiced. Interestingly, muscle relaxants have taken the same path as the inhalational anesthetic agents—rapid onset and a short duration of action. Muscle relaxants are not used exclusively in the field of anesthesia; in postanesthesia care units (PACUs), intensive care units, and emergency department settings, these drugs may be needed to enhance patient care. Muscle relaxants are used: (1) for the facilitation of endotracheal intubation; (2) for procedures that necessitate muscle relaxation such as intraperitoneal and thoracic surgery; (3) in ophthalmic surgery for relaxation of the extraocular muscles; (4) for termination of a laryngospasm and elimination of chest wall rigidity, which can occur after rapid intravenous injection of a potent opioid; and (5) for the facilitation of mechanical ventilation with the production of total paralysis of the respiratory muscles. As the health care industry prioritizes improved patient outcomes, the safe use and monitoring of NMBAs will continue to focus on anesthesia care and quality improvement. A thorough understanding of the significant components of NMBAs is essential for the PACU nurse.


Acceleromyography The measurement of force (mass × acceleration) produced when nerve stimulation is applied to a muscle.

Acceleromyography Device A monitor that displays the train-of-four ratio (TOFR) for quantitative analysis of neuromuscular blockade.

Action Potential The passage of an electric impulse at any point on the nerve fiber where the inside becomes positive and the outside becomes negative, referred to as action current.

Anticholinesterase A drug that inhibits or inactivates the action of acetylcholinesterase.

Antimuscarinic (Anticholinergic) A drug that blocks acetylcholine receptors’ effects and results in parasympathetic nerve impulses’ transmission inhibition.

Clinical Duration In reference to the use of NMBAs, the time from administering the drug to 25% recovery of the train-of-four twitch response.

Defasciculation A result of administering a subclinical dose of a nondepolarizing skeletal muscle relaxant to prevent the skeletal muscle twitches that occur after the depolarizing administration of skeletal muscle relaxant succinylcholine.

Depolarizing Skeletal Muscle Relaxant A skeletal muscle relaxant that, after administration, produces skeletal muscle twitches by stimulating the nicotinic receptors on the neuromuscular endplate, remaining on the end plate for 3 to 5 minutes, which leads to muscle paralysis. Skeletal muscle function returns as the pseudocholinesterase metabolizes the succinylcholine, which usually takes between 3 and 5 minutes.

End-Plate Potential (EPP) One action potential at the myoneural junction.

Excitation-Contraction (E-C) Coupling The entire process of muscle contraction, starting with the electric and then the chemical stimulus to the process of the release of calcium in the sarcoplasmic reticulum, which causes the muscle fibers (actin and myosin) to slide and thus contract.

Extraocular Muscles The six sets of muscles that control the movement of the eyeball.

Fasciculations Skeletal muscle twitches.

Muscarinic Subset receptors of the parasympathetic nervous system.

Myopathy An abnormal condition of skeletal muscle characterized by muscle weakness and wasting.

Neurotransmission Combined electric and chemical transmission of an impulse.

Nicotinic Subset of the parasympathetic nervous system.

Nondepolarizing Agents Drugs that cause paralysis of skeletal muscle by blocking neural muscular transmission at the myoneural junction.

Onset Time In reference to the use of NMBAs, the time from administering the drug to maximum effect.

Postoperative Pulmonary Complications Alterations in baseline pulmonary function due to induction of general anesthesia that persists in the postoperative period and may impact patient outcomes.

Pseudocholinesterase An enzyme that acts like cholinesterase and metabolizes acetylcholine.

Qualitative Monitoring Visual and tactile interpretation of force generated by a nerve stimulator on a muscle.

Quantitative Monitoring Mechanical measurement of force generated by a nerve stimulator on a muscle to calculate the TOFR.

Recovery Index In reference to the use of NMBAs, the time from the train-of-four twitch index of 25% to 75% recovery of the twitch response.

Total Duration of Action In reference to the use of NMBAs, drug administration’s time to 90% recovery of the train-of-four twitch response.

Train-of-Four Ratio (TOFR) A term used in reference to NMBAs in which a comparison is made between the fourth twitch of the train-of-four and the first twitch; when the fourth twitch is 90% of the first twitch, recovery from the NMBA is indicated.

Physiology of neuromuscular transmission

Understanding the physiology of neuromuscular transmission is challenging but rewarding. Due to the frequent and routine intraoperative and postoperative use of drugs that alter neuromuscular function, a review of the neuromuscular system’s anatomy and physiology is essential, with an emphasis on the receptor sites’ chemical changes. Activation of skeletal muscle is both an electric and a biochemical event. The term conduction refers to the passage of an impulse along an axon to a muscle fiber. Transmission applies to the passage of a neurotransmitter substance across a synaptic cleft (neuromuscular junction). The combined electric and chemical event is called neurotransmission.1

As the fine terminal branch of a motor neuron approaches the muscle fiber, it loses its myelin sheath. It forms an expanded terminal that lies close to a specialized muscle membrane area called the end plate. Between the end of the muscle fiber and the end plate is the synaptic cleft or neuromuscular junction. This space between the nerve and muscle fibers is approximately 20 to 30 nm wide. Acetylcholine is the biochemical neurotransmitter involved in the initiation of muscle contraction. Acetylcholine or cholinergic receptors are classified as nicotinic and muscarinic, respectively. The acetylcholine receptors are stimulated by acetylcholine. Anticholinesterase drugs such as neostigmine (Prostigmin), edrophonium chloride (Tensilon, Enlon), and pyridostigmine (Regonol) produce an increase in acetylcholine at the acetylcholine receptor. Therefore, the pharmacologic effects of the anticholinesterase drugs are on both the nicotinic and muscarinic receptors.

The nicotinic receptors are further classified as either N1 or N2 receptors.1 The N1 receptors are located at the presynaptic cleft and influence the release of acetylcholine. The N2 receptors are situated on the postsynaptic cleft in the neuromuscular junction and, when occupied by acetylcholine, open their channels to allow the flow of ions down the cell membrane resulting in skeletal muscle contraction (Fig. 23.1). The nondepolarizing NMBAs such as pancuronium (Pavulon) produce a block of the N2 receptor and thus cause an inability of the channel to conduct ions, which results in skeletal muscle paralysis. Extrajunctional nicotinic receptors are located throughout the skeletal muscles. Their activity is typically suppressed by regular neural activity. However, when a patient has prolonged sepsis, inactivity, denervation, or burn trauma in the skeletal muscles, there is a proliferation of these extrajunctional nicotinic receptors. As a result, these patients usually have an exaggerated hyperkalemic response when succinylcholine is administered.1

Presynaptic cell shows A c C O A converted to C o A. Choline in the presence of C A T converts to A C h, which releases outside the cell. The membrane has presynaptic N 1 receptor on the membrane. Arrows from A C h point toward muscarinic receptor, nicotinic type 2 receptor, acetylcholinesterase (A C h E), choline plus acetate, and presynaptic N 1 receptor through positive charge. A chart below summarizes the details for receptors as follows: • Muscarinic receptor: Agonists: Glaucoma; Antagonists: Dilate pupil, dilate airway, stabilize bladder, reduce gut motility, prevent bradycardia, antiemetic, and antiparkinsonian. • Nicotinic type 2 receptor: Agonists: Depolarizing muscle relaxant, Antagonists: Competitive muscle relaxant. • Acetylcholinesterase: Inhibitors: Glaucoma, dementias.

Presynaptic cell shows A c C O A converted to C o A. Choline in the presence of C A T converts to A C h, which releases outside the cell. The membrane has presynaptic N 1 receptor on the membrane. Arrows from A C h point toward muscarinic receptor, nicotinic type 2 receptor, acetylcholinesterase (A C h E), choline plus acetate, and presynaptic N 1 receptor through positive charge. A chart below summarizes the details for receptors as follows: • Muscarinic receptor: Agonists: Glaucoma; Antagonists: Dilate pupil, dilate airway, stabilize bladder, reduce gut motility, prevent bradycardia, antiemetic, and antiparkinsonian. • Nicotinic type 2 receptor: Agonists: Depolarizing muscle relaxant, Antagonists: Competitive muscle relaxant. • Acetylcholinesterase: Inhibitors: Glaucoma, dementias.

Fig. 23.1 Presynaptic and postsynaptic nicotinic (N1 and N2) receptors. (From Waller D, Sampson AP. Medical Pharmacology & Therapeutics. 5th ed. Elsevier; 2018. pp. 73–90.)

The muscarinic receptors are also subdivided into five subtypes (M1-M5) receptors. M1 receptors are located in the autonomic ganglia and the central nervous system, and M2 receptors are located in the heart and salivary glands. Atropine and glycopyrrolate (Robinul) block both the M1 and the M2 receptors.2

Acetylcholine is formed in the nerve cell’s body and cytoplasm of the nerve terminal and is stored in the small membrane-enclosed vesicles for subsequent release. A quantum is the amount of acetylcholine stored in each vesicle and represents approximately 10,000 molecules of acetylcholine. The presynaptic membrane contains discrete areas of specialization thought to be transmitter release sites. These presynaptic active zones lie directly opposite the N2 cholinergic receptors located on the postsynaptic membrane. This alignment ensures that the acetylcholine quickly diffuses directly to the N2 receptors on the postsynaptic membrane and in a high concentration. The N2 receptor, which responds to the neurotransmitter acetylcholine, is a glycoprotein that is an integral part of the neuromuscular junction’s postsynaptic membrane (see Fig 23.2). A positive feedback mechanism also exists at the neuromuscular junction. Acetylcholine has a presynaptic action; therefore, acetylcholine receptors are located on the presynaptic membrane. This positive feedback mechanism enhances the mobilization and release of acetylcholine. Finally, the enzyme that hydrolyzes acetylcholine is acetylcholinesterase attached to connective tissue within the neuromuscular junction.3

Myoneural junction at resting state shows associated labels (clockwise) as follows: Axon, myelin sheath, microtubules, mitochondria, vesicles containing acetylcholine, acetylcholine receptor, conducting cleft (junctional fold), motor end plate area, acetylcholinesterase, N 2 cholinergic receptors, synaptic cleft, and synaptic knob (nerve terminal).

Myoneural junction at resting state shows associated labels (clockwise) as follows: Axon, myelin sheath, microtubules, mitochondria, vesicles containing acetylcholine, acetylcholine receptor, conducting cleft (junctional fold), motor end plate area, acetylcholinesterase, N 2 cholinergic receptors, synaptic cleft, and synaptic knob (nerve terminal).

Fig. 23.2 Myoneural junction at resting state.

The initiation of skeletal muscle contraction occurs as a result of applying a threshold stimulus. An action potential travels down the axon, causing depolarization of the presynaptic membrane. As a result of this depolarization, the membrane permeability for calcium ions increases, and the calcium enters or influxes into the presynaptic membrane. Calcium acts to unite the vesicle to the presynaptic membrane and causes the rupture of that coalesced membrane, thus releasing acetylcholine into the fluid of the synaptic cleft (Fig. 23.3).

Action potential is applied along axon. Synaptic knob has acetylcholine receptor and release sites on the outer membrane. Acetylcholine is released in the gap. Calcium ions move toward synaptic knob. Post-synaptic cell has N 2 cholinergic receptors and acetylcholinesterase on the membrane.

Action potential is applied along axon. Synaptic knob has acetylcholine receptor and release sites on the outer membrane. Acetylcholine is released in the gap. Calcium ions move toward synaptic knob. Post-synaptic cell has N 2 cholinergic receptors and acetylcholinesterase on the membrane.

Fig. 23.3 Myoneural junction when threshold stimulus is applied.

The acetylcholine molecules released from the nerve terminal into the synaptic cleft are subject to two main processes: (1) attachment to N2 cholinergic receptors located on the postsynaptic membrane, which leads to an opening of calcium channels resulting in the movement of sodium into the region and generating an end-plate potential (EPP), and (2) attachment of the acetylcholine to the presynaptic nicotinic receptor, which enhances the release of more acetylcholine. When enough EPPs are generated, an action potential is propagated and spread throughout the muscle, causing a change in the muscle sarcolemma’s ionic permeability. This process results in the release of calcium from the sarcoplasmic reticulum with a resultant increase in free calcium concentration in the muscle fiber. The flow of calcium results from conformation changes at voltage-sensing dihydropyridine (DHP) receptors that open the ryanodine (RyR) calcium release channels within the sarcoplasmic reticulum. Genetic mutations within the DHP and RyR receptors are thought to contribute to malignant hyperthermia after anesthesia exposure3 (see Chapter 53). The process of excitation-contraction (E-C) coupling then takes place within that skeletal muscle cell. The physiologic outcome of E-C coupling is the contraction of the skeletal muscle. The increased concentration of calcium in the muscle fiber leads to an interaction between troponin-tropomyosin and actin. This interaction causes the active sites on actin to be exposed, interacting with myosin and sliding together, thus resulting in muscle contraction. This sliding of actin and myosin is sometimes called the sliding filament mechanism.3 The muscle fibers’ contraction is terminated when calcium is pumped back into the muscle fibers’ sarcoplasmic reticulum. The calcium is stored in the sarcoplasmic reticulum for use when another action potential is generated.

Regulation and control of skeletal muscle contraction are also based on the enzymatic breakdown of acetylcholine. As previously discussed, the stimulus must be strong enough to release enough acetylcholine to bind to the postsynaptic N2 cholinergic receptor. This competition process between the postsynaptic N2 receptor and acetylcholinesterase allows for some degree of regulation of the excitation process and the recovery of the muscle cell membrane. The molecules of acetylcholine either diffuse randomly to the N2 receptor or are destroyed by acetylcholinesterase located in the presynaptic and postsynaptic membranes. As the concentration gradient begins to decrease because of the destruction of acetylcholine by acetylcholinesterase, the N2 receptor gives up its acetylcholine, which is then destroyed, and the skeletal muscle relaxes. A small portion of the acetylcholine can escape the acetylcholinesterase in the synaptic cleft and migrate into the extracellular fluid and, from there, into the plasma. Acetylcholine within the plasma is then destroyed by butyrylcholinesterase (also called plasma cholinesterase or pseudocholinesterase), produced in the liver.1

Pharmacologic overview of commonly used muscle relaxants

With the anatomy and physiology of neuromuscular transmission as background, the nondepolarizing and depolarizing skeletal muscle relaxants’ principal pharmacologic actions are discussed. Table 23.1 presents a pharmacologic overview of the commonly used skeletal muscle relaxants.

Table 23.1

Pharmacologic Overview of Commonly Used Neuromuscular Blocking Drugs

Pancuronium (Pavulon) Vecuronium Bromide (Norcuron) Atracurium Besylate (Tracrium) Cisatracurium Besylate (Nimbex) Rocuronium Bromide (Zemuron)
Nondepolarizing Yes Yes Yes Yes Yes
Depolarizing No No No No No
Intubation dose (IV mg/kg) 0.06–0.1 0.08–0.1 0.4–0.5 0.1–0.2 0.1
Intubation time (injection to relaxation; min) 4 2.5–3 2–2.5 2.8–3.4 1–2
Muscle relaxation dose (IV mg/kg) 0.04–0.08 0.05–0.06 0.2–0.5 2.5 0.6–1.0
Recovery time (min) 84–114 30–60 30–45 55–75 30–90
Reversible Yes Yes Yes Yes Yes
Time to reversal (after initial dose; min) 40–60 25–30 (for 0.1 mg/kg), 40–80 (for 0.2 mg/kg) 20–35 10–15 5–10
Cumulative effects Yes Slight No No No
Fasciculations and muscle soreness No No No No No
Risk of histamine release Slight to none No Minimal No No
Cardiovascular effects Slight increase in pulse and increase in BP None Few None None

BP, Blood pressure; IV, intravenous.

The prototypical nondepolarizing skeletal muscle relaxants are pancuronium and vecuronium (Norcuron). Pancuronium is an inhibitor of acetylcholine, is chemically viewed as two acetylcholine-like fragments, and has a bulky inflexible nucleus. This drug attaches to the N2 cholinergic receptors on the postsynaptic membrane and prevents depolarization. The skeletal muscle relaxant vecuronium has a chemical structure similar to a monoquaternary compound. This drug’s principal pharmacologic action blocks the postsynaptic N2 cholinergic receptor; thus, it stops acetylcholine from binding to the receptor, which results in a competitive neuromuscular blockade. The nondepolarizing skeletal muscle relaxants block the presynaptic cholinergic receptor, resulting in the acetylcholine binding, preventing activation of the positive feedback mechanism.4

The pharmacologic actions of the nondepolarizing skeletal muscle relaxants can be reversed with anticholinesterase drugs such as neostigmine. In effect, these drugs increase acetylcholine quantum at the postsynaptic membrane by preventing the destruction of acetylcholine by acetylcholinesterase. This process promotes a more effective competition by releasing acetylcholine with the nondepolarizing skeletal muscle relaxant occupying the N2 receptor. Because of the increased availability and mobilization of the acetylcholine, the concentration gradients favor acetylcholine and remove the nondepolarizing agents from the N2 receptor with the resultant return to normal contraction of the skeletal muscle.

The principal depolarizing skeletal muscle relaxant is succinylcholine (Anectine, Sucostrin). The molecular structure of this drug resembles two back-to-back acetylcholine molecules. Because of this structure, succinylcholine has the same effects as acetylcholine. Like acetylcholine, the succinylcholine molecule has a positively charged quaternary ammonium portion. This positively charged molecule is attracted by electrostatic action to the negatively charged N2 receptor. When the succinylcholine attaches to the receptor, a brief depolarization period occurs, manifested by transient muscular fasciculations. Succinylcholine also attaches to and activates the presynaptic acetylcholine receptor. This activation has an immediate effect of increased mobilization of acetylcholine in the motor nerve terminals, explaining why fasciculations are commonly observed after administering an intravenous bolus of succinylcholine. After the depolarization of the N2 receptor takes place, succinylcholine promotes and maintains the receptor in a depolarized state and prevents repolarization. Succinylcholine has a brief duration of action because of its rapid hydrolysis of the succinylcholine by the enzyme pseudocholinesterase, which is contained in the liver and plasma. The succinylcholine actions cannot be pharmacologically reversed and depend on diffusion away from the neuromuscular junction and metabolism by plasma cholinesterase.5

Nondepolarizing neuromuscular blocking agents

Long-Acting Nondepolarizing Skeletal Muscle Relaxants

Pancuronium Bromide

Pancuronium bromide (Pavulon) was introduced into clinical anesthesia in 1972. This drug has shown value (particularly in terms of its safety, cardiovascular stability, and skeletal muscle relaxant properties) and has been traditionally used in cardiac anesthesia. Because of a significant risk of postoperative complications from neuromuscular weakness, pancuronium is less common in current practice but beneficial to review.6

Chemically, pancuronium bromide is a biquaternary aminosteroid related to the androgens; however, it has no hormonal activities. Pancuronium is reversible with an anticholinesterase agent, such as neostigmine, administered in combination with an anticholinergic such as glycopyrrolate or atropine. This particular skeletal muscle relaxant has been clinically difficult to reverse pharmacologically within the first 20 to 30 minutes after injection. In the PACU, if a skeletal muscle relaxant is needed for a short duration, another reversible skeletal muscle relaxant, such as rocuronium, vecuronium, or cisatracurium, should be chosen. Approximately 30 to 40 minutes after injection, pancuronium can usually be reversed with the combination of an anticholinesterase and anticholinergic drug preparation. Pancuronium historically was used for surgical procedures that lasted more than 1 hour, as it is well suited for patients who need complete muscle relaxation with continuous mechanical ventilation. The dose for adults is approximately 0.08 to 0.1 mg/kg body weight. Relaxation lasts 60 to 85 minutes. If relaxation is necessary past this initial period, subsequent doses should be decreased to 0.02 to 0.04 mg/kg body weight.

Pancuronium bromide does not produce ganglionic blockade, but it does block the M2 cholinergic receptors in the heart. Consequently, when pancuronium bromide is administered, a slight 10% to 15% increase in heart rate is observed.7 Pancuronium activates the sympathetic nervous system by promoting norepinephrine release and blocking its uptake at the adrenergic nerve endings. After administration of this drug, a modest increase in mean arterial pressure and cardiac output is produced. Although isolated histamine release cases have been reported, pancuronium can probably be used in patients with a marginal allergy history. Pancuronium bromide is compatible with anesthetic agents used clinically and is safe for most patients when a nondepolarizing skeletal muscle relaxant is indicated. However, pancuronium bromide is not indicated when a nondepolarizing muscle relaxant is to be used with caution. Also, pancuronium should not be used in patients undergoing chronic digitalis therapy because cardiac dysrhythmias have been reported. Finally, myocardial ischemia has been reported in patients with coronary artery disease when pancuronium is used. This ischemia is probably associated with the cardiac acceleration properties of the drug.

Pancuronium bromide should be avoided in patients with a history of myasthenia gravis. It is contraindicated in patients with renal disease because a significant portion of the drug is excreted unchanged in the urine. This agent is contraindicated in patients known to be hypersensitive to it or the bromide ion.

Intermediate-Acting Nondepolarizing Skeletal Muscle Relaxants

Vecuronium Bromide

Vecuronium (Norcuron) is a nondepolarizing skeletal muscle relaxant with a more rapid onset of action and a shorter duration of action than pancuronium. Vecuronium is pancuronium without the quaternary methyl group in the steroid nucleus. Because of this structural difference, vecuronium does not affect heart rate, arterial pressure, autonomic ganglia, or the alpha and beta adrenal receptors. The potency of vecuronium is equal to or slightly greater than that of pancuronium. Vecuronium has little or no cumulative effect. Although a portion of vecuronium is metabolized, most of the drug is excreted unchanged in the urine and bile. However, the neuromuscular blockade produced by vecuronium is not prolonged by renal failure. The duration of neuromuscular blockade produced by vecuronium is increased in patients with impaired hepatic function. Of clinical interest is that vecuronium, like atracurium, is less influenced by general inhalation anesthetics than is pancuronium.6 The pharmacologic action of vecuronium is easily reversed with the combination of an anticholinesterase and an anticholinergic drug.

The onset of action of vecuronium is between 2.5 and 3 minutes, with the standard dose of 0.08 mg/kg intravenously. Because of the rapid onset of action, vecuronium can be used in certain circumstances for rapid sequence intubation (RSI). In this instance, a doubling of the vecuronium dose to 0.2 mg/kg can be used to achieve intubation conditions within 45 seconds to 2 minutes. Vecuronium is primarily used for intraoperative skeletal muscle relaxation to improve surgical exposure and facilitate mechanical ventilation in the critical care setting. Long-term infusions of this drug in the critical care setting can result in prolonged recovery and an inability to pharmacologically reverse vecuronium because the metabolites are still in active form. If corticosteroid therapy is being used for patients with multiorgan failure, this prolonged effect can be exacerbated.

The dose is 0.05 to 0.2 mg/kg for skeletal muscle paralysis, and the onset is 1 to 3 minutes with a duration between 30 and 90 minutes. Prolonged skeletal muscle-relaxing effects can be prolonged with patients with hepatic disease. No significant cardiac effects for this drug have been reported.

Atracurium Besylate

Atracurium (Tracrium) is a nondepolarizing skeletal muscle relaxant that offers an advantage over other skeletal muscle relaxants. It does not depend on renal or hepatic mechanisms for its elimination. This quaternary ammonium compound breaks down in the absence of plasma enzymes through Hofmann elimination and, to a lesser extent, through ester hydrolysis. Hofmann elimination is a nonbiologic method of degradation that occurs at a physiologic temperature and pH.

Atracurium is less potent than pancuronium and has a rapid onset of 1 to 3 minutes and a duration of action of 30 to 45 minutes. For endotracheal intubation in the PACU setting, 0.3 to 0.5 mg/kg of atracurium should provide adequate skeletal muscle relaxation for intubation in about 2.5 minutes.8 For maintenance of mechanical ventilation in the PACU setting, an infusion rate of 10 mcg/kg/min of atracurium may be used.9 When the infusion has been discontinued, spontaneous ventilation by the patient occurs in approximately 30 minutes. The effects can be reversed with a combination of anticholinesterase and antimuscarinic in 20 to 25 minutes after discontinuing the atracurium infusion.8

Atracurium has many distinct advantages, such as its neuromuscular blockade not being prolonged by renal failure or impaired hepatic function; it has little or no cumulative effect and is not influenced significantly by the specific general inhalation anesthetic dose or concentration. Finally, this drug has little or no cardiovascular effect and is easily antagonized with the combination of an anticholinesterase and an anticholinergic.

Cisatracurium Besylate

Cisatracurium (Nimbex) is a stereoisomer of atracurium that is approximately threefold more potent than atracurium but with fewer side effects; it is degraded by the same metabolic pathway as atracurium (i.e., the Hofmann elimination mechanism).

The average adult intubation dose of cisatracurium is 0.2 mg/kg and has an onset of approximately 90 seconds, a peak in 3 to 5 minutes, and a duration of action of 40 to 50 minutes. A supplemental dose of 0.03 mg/kg provides an additional 20 minutes of skeletal muscle relaxation. Cisatracurium can be administered in PACU to maintain a stable state of skeletal muscle relaxation via infusion at a rate of 1 to 2 mcg/kg/min.9

This drug has all the atracurium assets plus a significant advantage over atracurium of minor histamine release. It does not have any particular effect on the cardiovascular system. Because it undergoes an organ-independent clearance, it can be used in patients with hepatic or renal failure without a noticeable change in the duration of action. It is well suited for many patients who undergo intermediate to long surgical procedures.

Short-Acting Nondepolarizing Skeletal Muscle Relaxants

Rocuronium Bromide

Rocuronium (Zemuron) is a nondepolarizing skeletal muscle relaxant with a chemical structure related to vecuronium. It has a rapid onset (1 to 1.5 minutes) and a short duration of action of 30 to 120 minutes, depending on the total dose of the drug. The onset and duration of action are not altered in obese patients when the dose is based on the actual body weight. In patients older than 65 years, the duration of action is slightly prolonged. In pediatrics, the onset and duration are slightly faster.

Because rocuronium has such rapid effects and a short duration of action, spontaneous recovery from neuromuscular blockade is possible. However, suppose a patient arrives in the PACU with spontaneous ventilation after rocuronium administration during surgery that was not reversed with anticholinesterase and an anticholinergic. In that case, the patient still should be monitored in the PACU for neuromuscular function using a peripheral nerve stimulator (PNS). In addition to using the PNS, the patient should be evaluated for adequate clinical evidence of an adequate return of neuromuscular function, evaluating the 5-second head lift, sustained handgrip, an effective cough, and ventilation with a vital capacity of at least 15 mL/kg.5

Rocuronium can be used in patients with renal failure and has a low potential for histamine release. Although rare, its actions are prolonged in patients with cirrhosis of the liver. The muscle relaxant actions of rocuronium are potentiated by the inhalation anesthetics, predicting a total recovery from the neuromuscular blockade variable. Because rocuronium produces minimal cardiovascular effects, it does not have significant histamine-releasing effects.

Rocuronium can be used as an agent of choice for nondepolarizing RSI in the PACU when appropriate intubation doses are used because it has such a fast onset, and short duration of action is helpful in intraoperative and postoperative periods. At a dose of 0.6 to 1.0 mg/kg, rocuronium provides excellent intubating conditions in 60 to 90 seconds for both children and adults. Therefore, before the intubation is attempted, the patient should undergo ventilation with 100% oxygen until appropriate paralysis of the skeletal muscle occurs to facilitate the intubation. The maintenance dose for rocuronium for adults is between 0.1 and 0.2 mg/kg, and for children, it is 0.08 to 0.12 mg/kg intravenously. If rocuronium is to be used for continuous infusion, the initial rate is 0.01 to 0.012 mg/kg/min; at the desired level of neuromuscular blockade, this drug’s infusion can be individualized according to the patient’s twitch response as monitored with the use of the PNS. The research indicates that infusion rates can range from 0.004 to 0.016 mg/kg/min. An assessment of the maintenance dosing of rocuronium should be administered at 25% of control T1, three twitches of the train-of-four. The infusion solutions for rocuronium can be prepared using 5% glucose and water or lactated Ringer’s solution. When the infusion is completed, the unused portions of the infusion solutions should be discarded.4

Reversal of Nondepolarizing Neuromuscular Blocking Agents

For the restoration of neuromuscular transmission, the antagonist must displace the competitive NMBA from the nicotinic receptor sites and open the way for depolarization of the postjunctional membrane. The antagonist is an antiacetylcholinesterase that blocks the enzymatic action of acetylcholinesterase located in the postsynaptic clefts so that acetylcholine is not hydrolyzed. The result is a buildup of acetylcholine at the end plate at the N2 cholinergic receptor. The accumulated acetylcholine displaces the competitive NMBA, diffuses back into the plasma, and thus reestablishes neuromuscular transmission.

Neostigmine and pyridostigmine are usually the anticholinesterase drugs of choice because of their long duration of action and reliability compared with edrophonium chloride. However, research has shown that edrophonium chloride is an effective reversal agent of neuromuscular blockades produced by vecuronium and atracurium. Atropine or glycopyrrolate, both antimuscarinic (anticholinergic) drugs, can be administered immediately before or in conjunction with the anticholinesterase to minimize the muscarinic effects of the anticholinesterase drug. The muscarinic effects include bradycardia, salivation, miosis, and hyperperistalsis. These effects are produced at lower anticholinesterase-type drug concentrations when administered (acetylcholine nicotinic effects are at the autonomic ganglia and the neuromuscular junction).

Consequently, when an anticholinesterase drug is administered for reversal of the nondepolarizing NMBA at the N2 receptor, an antimuscarinic drug is also given to prevent the adverse muscarinic cholinergic effects associated with the high dose of anticholinesterase. Generally, 2.5 mg of neostigmine is the maximum dose necessary for reversal; however, the suggested limit is 5 mg. The method involves administration of 0.4 mg atropine or 0.2 mg glycopyrrolate intravenously over 1 minute, observation for an increase in the pulse rate, and then administration of 0.5 mg neostigmine intravenously and monitoring for the reversal. This procedure can be repeated until reversal has been achieved or until the limit of neostigmine that can be given is reached. If edrophonium chloride is indicated for reversal, the dose is 0.5 mg/kg with 0.007 mg/kg of atropine.

Neostigmine should be administered cautiously. Cardiac monitoring is essential, especially in elderly or debilitated patients and in patients with cardiac disease. Atrioventricular dissociation and other dysrhythmias, including torsade de pointes, can be initiated by the anticholinesterases.6

Pyridostigmine is an analog of neostigmine. It facilitates the transmission of impulses across the myoneural junction by inhibiting the destruction of acetylcholine by acetylcholinesterase. Clinical data indicate a lower incidence rate of muscarinic side effects with this drug than with neostigmine. Like neostigmine, pyridostigmine should be administered with caution in patients with bronchial asthma or cardiac problems. Signs of overdose are related to muscarinic and nicotinic receptor stimulation (Box 23.1). The muscarinic side effects are blocked with atropine or glycopyrrolate. Nicotinic responses can be blocked with drugs such as ganglionic or NMBAs. The recommended dose for reversal is 0.15 mg/kg of intravenous pyridostigmine combined with 0.007 mg/kg of intravenous atropine. Complete recovery occurs within 15 minutes in most patients; in other patients, 30 minutes or more may be necessary.

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May 20, 2023 | Posted by in NURSING | Comments Off on Neuromuscular Blocking Agents

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