Neuromuscular Blockade

The goal of neuromuscular blockade in RSI is to obtain the optimal conditions for laryngoscopy as quickly as possible. The neuromuscular-blocking drug (NMB) is thus injected immediately after the injection of the induction agent. Complete neuromuscular blockade enables maximal laryngoscopic displacement of the tongue and mandible to optimize the view of the glottic aperture. In most children without anatomic deformities, glottic visualization is relatively simple once neuromuscular blockade is accomplished. Neuromuscular blockade also ensures that the vocal cords will be open, facilitating atraumatic passage of the endotracheal tube. There are many NMBs available, but only those with the most rapid times of onset can be recommended for RSI. These include the depolarizing NMB succinylcholine and two nondepolarizing NMBs, vecuronium and rocuronium.

While many practitioners may be more familiar with pancuronium which is inexpensive and has a long history of use in the emergency department, its long time of onset and very long duration of action make it a suboptimal choice for RSI.

SUCCINYLCHOLINE Succinylcholine, the only depolarizing NMB available in the United States, remains the drug of choice for RSI. While the US Food and Drug Administration has issued an advisory against its elective use in children, it continues to be approved for emergency airway management. The reason for the limitation of its use is that it has been associated with hyperkalemic arrest in children subsequently found to have underlying but undiagnosed myopathies (see below).

The advantages of succinylcholine include its extremely reliable and rapid time to onset of action; intubating conditions are obtained generally within 45 s. As noted, children become hypoxemic with apnea more rapidly than do adults, and even a 15-s advantage can be meaningful. Unlike nondepolarizing NMBs, duration of action is short. Spontaneous ventilation usually returns within 3 to 5 min. This is particularly important when ongoing neurologic assessment is desired, or when a difficult airway is anticipated or encountered, as options are preserved in the case of a failed intubation.

Unfortunately, the disadvantages of the drug are relatively numerous:

1. Hyperkalemia, with resultant cardiac arrest, is the most severe disadvantage. All patients experience a small rise, on the order of 0.5 meq/L, in their serum potassium following administration of succinylcholine. However, in certain subsets of patients, this rise is greatly exaggerated. Most of these are not likely to be a factor in an emergency department setting given the short time proximity of the injury or illness event to the need for intervention. In addition to myopathies, as mentioned above, other conditions that predispose to this occurrence include chronic immobilization, denervation lesions, spinal cord injuries, burns, crush injuries, and extensive necrotic soft tissue infections. The exaggerated response is due to unregulated proliferation of acetylcholine receptors on the muscle membrane. This response takes 2 to 3 days to occur after burns and neurologic injuries; thus, succinylcholine is safe to use in the immediate postinjury period in such patients.

2. Malignant hyperthermia can be triggered by succinylcholine in susceptible individuals. Since the lesion causing this disease is hereditary, patients known to have a history or a family history of malignant hyperthermia should not receive this agent.

3. Fasciculations precede the onset of neuromuscular blockade as the depolarization of the muscle membranes occurs. These uncontrolled muscle contractions are not inherently dangerous as long as the patient is protected from involuntary physical injury. Thought to increase the occurrence of myalgias, they can be prevented by preadministration of a small "defasciculating" dose (10 percent of an intubating dose) of a nondepolarizing NMB 2 min before succinylcholine is given.

4. Elevations in intracranial, intraocular, and intragastric pressures have been documented. Such rises are not reliably prevented by defasciculating premedication. However, they are transient, and their clinical importance is largely theoretical. In a patient in whom elevated intracranial pressure is a concern, securing the airway and providing ventilation (and thus controlling P co2) are of primary importance.

5. Bradycardia occurs unpredictably in some patients receiving succinylcholine and is more common after a second dose. When it does occur, hypoxia, rather than drug effect, should be the first consideration. This is of particular concern in small children and neonates, whose cardiac output is directly dependent on heart rate. Premedication with atropine 0.15 to 0.20 mg/kg is advisable in children under five years old or in any child with a heart rate less than 120 bpm.

6. Prolonged blockade, lasting hours instead of minutes, occurs in a small subset of patients who have decreased activity of plasma cholinesterase, the enzyme responsible for the inactivation of succinylcholine. This may be due either to a defective enzyme or to diminished levels of normal enzyme. The frequency of clinically significant prolongation in the population is roughly 1:3000. This condition is not inherently dangerous in and of itself. The implication is that occasionally a patient has a prolonged apparent absence of neurologic function that could be mistaken for central nervous system injury. Train-of-four monitoring, the elicitation of muscular response following a standardized series of four electrical pulses stimulating a particular nerve, is used primarily in the operating room and intensive care unit settings. Absence of any twitch response to train-of-four muscular stimulation 10 min after a dose of succinylcholine reflects prolonged neuromuscular blockade.

7. A small subset of patients develop masseter spasm on receiving succinylcholine, making intubation more difficult. These patients are at increased risk of developing myoglobinuria and have a higher propensity for developing malignant hyperthermia. Fewer than 1 percent of patients manifest this complication.

In the event that succinylcholine is contraindicated, a fast-acting nondepolarizing NMB may be chosen with the knowledge that the onset will be slightly slower and the duration of action substantially longer.

VECURONIUM Vecuronium was the first nondepolarizing NMB to be recommended for use in RSI. In order to obtain intubating conditions in 60 to 90 s, a dose of 0.3 to 0.4 mg/kg is given. This results in a duration of action of 90 to 150 min. Alternatively, if time permits, a "priming" dose of 0.01 mg/kg should be given 2 to 3 min before an intubating dose of 0.15 to 0.2 mg/kg. The priming technique entails no clinically significant issues, but it speeds the onset of intubating conditions after the intubating dose and shortens the duration of action to 60 to 75 min. Vecuronium is essentially devoid of hemodynamic effects and does not cause histamine release. It is stored as a powder that is easily diluted for use.

ROCURONIUM Rocuronium is similar to vecuronium in its lack of hemodynamic effects. It is somewhat less potent, giving it a more rapid time to onset of intubating conditions, sufficiently so that priming is not considered necessary. Doses of 0.9 and 1.2 mg/kg have been shown in adults to result in times to intubating conditions of 75 and 55 s, respectively, approaching the 45 s typical of succinylcholine.12 The duration of action is comparable to that of vecuronium 0.1 mg/kg at the 0.9 mg/kg dose and somewhat longer at the 1.2 mg/kg dose. Rocuronium is supplied as a solution that requires refrigeration, making it slightly less convenient to stock and store than vecuronium.

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