Clinical Pharmacology

SCh is comprised of two molecules of ACH linked by an ester bridge and, as such, is chemically similar to ACH. It stimulates all nicotinic and muscarinic cholinergic receptors of the sympathetic and parasympathetic nervous system to varying degrees, not just those at the neuromuscular junction. For example, stimulation of cardiac muscarinic receptors can cause bradycardia, especially when repeated doses are given to small children. Although SCh can be a negative inotrope, this effect is so minimal as to have no clinical relevance. SCh causes the release of trace amounts of histamine, but this effect is also not clinically significant. Initially, SCh depolarization manifests as fasciculations, but this is followed rapidly by complete motor paralysis. The onset, activity, and duration of action of SCh are independent of the activity of ACHE and instead depend on rapid hydrolysis by pseudocholinesterase (PCHE), an enzyme of the liver and plasma that is not present at the neuromuscular junction. Therefore, diffusion away from the neuromuscular junction motor endplate and back into the vascular compartment is ultimately responsible for SCh metabolism. This extremely important pharmacologic concept explains why only a fraction of the initial intravenous (IV) dose of SCh ever reaches the motor endplate to promote paralysis. As a result, larger, rather than smaller, doses of SCh are used for emergency RSI. Incomplete paralysis may jeopardize the patient by compromising respiration while failing to provide adequate relaxation to facilitate tracheal intubation.

Succinylmonocholine, the initial metabolite of SCh, sensitizes the cardiac muscarinic receptors in the sinus node to repeat does of SCh, which may cause bradycardia that is responsive to atropine. At room temperature, SCh retains 90% of its activity for up to 3 months. Refrigeration mitigates this degradation. Therefore, if SCh is stored at room temperature, it should be dated and stock should be rotated regularly.

Indications and Contraindications

SCh is dosed on a total body weight basis. In the emergency department, it may be impossible to know the exact weight of a patient, and weight estimates, especially of supine patients, have been shown to be notoriously inaccurate. In those uncertain circumstances, it is better to err on the side of a higher dose of SCh to ensure adequate patient paralysis. The serum half-life of SCh is less than 1 minute, so doubling the dose increases the duration of block by only 60 seconds. SCh is safe up to a cumulative dose of 6 mg per kg. At doses >6 mg per kg, the typical phase 1 depolarization block of SCh becomes a phase 2 block, which changes the pharmacokinetic displacement of SCh from the motor endplate. Although the electrophysiologic features of a phase 2 block resemble that of a nondepolarizing or competitive block (train-of-four fade and post-tetanic potentiation), the block remains nonreversible. This prolongs the duration of paralysis but is otherwise clinically irrelevant. The risk of an inadequately paralyzed patient who is difficult to intubate because of an inadequate dose of SCh greatly outweighs the minimal potential for adverse effects from excessive dosing.

In children younger than 10 years, length-based dosing is recommended, but if weight is used as the determinant, the recommended dose of SCh for emergency RSI is 2 mg per kg IV, and in the newborn (younger than 12 months), the appropriate dose is 3 mg per kg IV. Some practitioners routinely administer atropine to children younger than 12 months who are receiving SCh, but there is no high-quality evidence to support this practice. There is similarly no evidence that it is harmful. When adults or children of any age receive a second dose of SCh, bradycardia may occur, and atropine should be readily available.

Adverse Effects

The recognized side effects of SCh include fasciculations, hyperkalemia, bradycardia, prolonged neuromuscular blockade, MH, and trismus/masseter muscle spasm. Each is discussed separately.

Fasciculations

Fasciculations are believed to be produced by stimulation of the nicotinic ACH receptors. Fasciculations occur simultaneously with increases in intracranial pressure (ICP), intraocular pressure, and intragastric pressure, but these are not the result of concerted muscle activity. Of these, only the increase in ICP is potentially clinically important.

The exact mechanisms by which these effects occur are not well elucidated. In the past, it was recommended that nondepolarizing agents be given in advance of SCh to mitigate ICP elevation, but there is insufficient evidence to support this practice.

The relationship between muscle fasciculation and subsequent postoperative muscle pain is controversial. Studies have been variable with respect to prevention of fasciculations and subsequent muscle pain. Although there exists a theoretical concern regarding the extrusion of vitreous in patients with open globe injuries who are given SCh, there are no published reports of this potential complication. Anesthesiologists continue to use SCh as a muscle relaxant in cases of open globe injury, with or without an accompanying defasciculating agent. Similarly, the increase in intragastric pressure that has been measured has never been shown to be of any clinical significance, perhaps because it is offset by a corresponding increase in the lower esophageal sphincter pressure.

Hyperkalemia

Under normal circumstances, serum potassium increases minimally (0 to 0.5 mEq per L) when SCh is administered. In certain pathologic conditions, however, a rapid and dramatic increase in serum potassium can occur in response to SCh. These pathologic hyperkalemic responses occur by two distinct mechanisms: receptor upregulation and rhabdomyolysis. In either situation, potassium increase may approach 5 to 10 mEq per L within a few minutes and result in hyperkalemic dysrhythmias or cardiac arrest.

Hyperkalemia may also occur with rhabdomyolysis, most often that associated with myopathies, especially inherited forms of muscular dystrophy. When severe hyperkalemia occurs related to rhabdomyolysis, the mortality approaches 30%, almost three times higher than that in cases of receptor upregulation. This mortality increase may be related to coexisting cardiomyopathy. SCh is a toxin to unstable membranes in any patient with a myopathy and should be avoided.

Patients with the following conditions are at risk of SCh-induced hyperkalemia:

A. Receptor Upregulation

a. Burns—In burn victims, the extrajunctional receptor sensitization becomes clinically significant 3 to 5 days postburn. It lasts an indefinite period of time, at least until there is complete healing of the burned area. If the burn becomes infected or healing is delayed, the patient remains at risk for hyperkalemia. It is prudent to avoid SCh in burned patients beyond this window if any question exists regarding the status of their burn. The percent of body surface area burned does not correlate well with the magnitude of hyperkalemia. Significant hyperkalemia has been reported in patients with as little as 8% total body surface area burn (less than the surface of one arm), but this is rare. The majority of emergent intubations for burn patients are performed well within the safe 3- to 5-day window period. Should a later intubation become necessary, however, rocuronium or vecuronium provides excellent alternatives.

b. Denervation—