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.

In the normal-size adult patient, the recommended dose of SCh for emergency RSI is 1.5 mg per kg IV. In a rare, life-threatening circumstance when SCh must be given intramuscularly (IM) because of inability to secure venous access, a dose of 4 mg per kg IM may be used. Absorption and delivery of drug will be dependent on the patient’s circulatory status. IM administration may result in a prolonged period of vulnerability for the patient, during which respirations will be compromised, but relaxation is not sufficient to permit intubation. Active bag-mask ventilation will usually be required before laryngoscopy in this circumstance.

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 <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 posttetanic 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, so it is considered. When adults or children of any age receive a second dose of SCh, bradycardia may occur, and atropine should be readily available.

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

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 non-depolarizing 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.

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.

Two forms of postjunctional receptors exist: mature (junctional) and immature (extrajunctional). Each receptor is composed of five proteins arranged in a circular fashion around a common channel. Both types of receptors contain two α-subunits. ACH must attach to both α-subunits to open the channel and effect depolarization and muscle contraction. When receptor upregulation occurs, the mature receptors at and around the motor endplate are gradually converted over a 4- to 5-day period to immature receptors that propagate throughout the entire muscle membrane. Immature receptors are characterized by low conductance and prolonged channel opening times (four times longer than mature receptors), resulting in increasing release of potassium. Most of the entities associated with hyperkalemia during emergency use of SCh are the result of receptor upregulation. Interestingly, these same extrajunctional nicotinic receptors are relatively refractory to nondepolarizing agents, so larger doses of vecuronium, pancuronium, or rocuronium may be required to produce paralysis. This is not an issue in emergency RSI, where full intubating doses several times greater than the ED₉₅ for paralysis are used.

Hyperkalemia also may 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:

In both adults and children, repeated doses of SCh may produce bradycardia, and administration of atropine may become necessary.

Prolonged neuromuscular blockade may result from an acquired PCHE deficiency, a congenital absence of PCHE, or the presence of an atypical form of PCHE, any of the three of which will delay the degradation of SCh and prolong paralysis. Acquired PCHE deficiency may be a result of liver disease, chronic cocaine abuse, pregnancy, burns, oral contraceptives, metoclopramide, bambuterol, or esmolol. A 20% reduction in normal levels will increase apnea time about 3 to 9 minutes. The most severe variant (0.04% of population) will result in prolonged paralysis for 4 to 8 hours.

A personal or family history of MH is an absolute contraindication to the use of SCh. MH is a myopathy characterized by a genetic skeletal muscle membrane abnormality of the Ry¹ ryanodine receptor. It can be triggered by halogenated anesthetics, SCh, vigorous exercise, and even emotional stress. Following the initiating event, its onset can be acute and progressive, or delayed for hours. Generalized awareness of MH, earlier diagnosis, and the availability of dantrolene (Dantrium) have decreased the mortality from as high as 70% to <5%. Acute loss of intracellular calcium control results in a cascade of rapidly progressive events manifested primarily by increased metabolism, muscular rigidity, autonomic instability, hypoxia, hypotension, severe lactic acidosis, hyperkalemia, myoglobinemia, and disseminated intravascular coagulation. Temperature elevation is a late manifestation. The presence of more than one of these clinical signs is suggestive of MH.

Masseter spasm, once claimed to be the hallmark of MH, is not pathognomonic. SCh can promote isolated masseter spasm as an exaggerated response at the neuromuscular junction, especially in children.

The treatment for MH consists of discontinuing the known or suspected precipitant and the immediate administration of dantrolene sodium (Dantrium). Dantrolene is essential to successful resuscitation and must be given as soon as the diagnosis is seriously entertained. Dantrolene is a hydantoin derivative that acts directly on skeletal muscle to prevent calcium release from the sarcoplasmic reticulum without affecting calcium reuptake. The initial dose is 2.5 mg per kg IV, repeated every 5 minutes until muscle relaxation occurs or the maximum dose of 10 mg per kg is administered. Dantrolene is free of any serious side effects. In addition, measures to control body temperature, acid-base balance, and renal function must be used. All cases of MH require constant monitoring of pH, arterial blood gases, and serum potassium. Immediate and aggressive management of hyperkalemia with the administration of calcium gluconate, glucose, insulin, and sodium bicarbonate may be necessary. Interestingly, full paralysis with nondepolarizing NMBAs will prevent SCh-triggered MH. MH has never been reported related to the use of SCh in the emergency department. The MH emergency hotline number is 1-800-MH-HYPER 1-800-644-9737 (United States and Canada) 24 hours a day, 7 days a week. Ask for “index zero.” The e-mail address for the Malignant Hyperthermia Association of the United States (MHAUS) is mhaus@norwich.net, and the Web site is www.mhaus.org.