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Succinylcholine-induced cardiac dysrhythmias are many and varied. The drug stimulates all cholinergic autonomic receptors: nicotinic receptors on both sympathetic and parasympathetic ganglia[93] and muscarinic receptors in the sinus node of the heart. In low doses, both negative inotropic and chronotropic responses may occur. These responses can be attenuated by previous administration of atropine. With large doses of succinylcholine, these effects may become positive[94] and tachycardia ensues. A prominent clinical manifestation of generalized autonomic stimulation is the development of cardiac dysrhythmias, principally sinus bradycardia, junctional rhythms, and ventricular dysrhythmias. Clinical studies have described these dysrhythmias under various conditions in the presence of the intense autonomic stimulus of tracheal intubation. It is not entirely clear whether the cardiac irregularities are due to the action of succinylcholine alone or due to the added presence of extraneous autonomic stimulation.
The autonomic mechanism involved in sinus bradycardia is stimulation of cardiac muscarinic receptors in the sinus node, which is particularly problematic in individuals with predominantly vagal tone, such as children who have not received atropine.[95] [96] Sinus bradycardia has also been noted in adults and appears more commonly when a second dose of the drug is given approximately 5 minutes after the first.[97] The bradycardia may be prevented by thiopental,[98] [99] atropine,[98] ganglion-blocking drugs, and nondepolarizing neuromuscular blockers.[98] [100] The implication from this information is that direct myocardial effects, increased muscarinic stimulation, and ganglionic stimulation may all be involved in the bradycardiac response. The higher incidence of bradycardia after a second dose of succinylcholine[100] suggests that the hydrolysis products of succinylcholine (succinylmonocholine and choline) may sensitize the heart to a subsequent dose.
Nodal rhythms commonly occur after the administration of succinylcholine. The mechanism probably involves relatively greater stimulation of muscarinic receptors in the sinus node and, as a result, suppression of the sinus mechanism and emergence of the atrioventricular node as the pacemaker. The incidence of junctional rhythm is greater after a second dose of succinylcholine but is prevented by previous administration of dTc.[98] [100]
Under stable anesthetic conditions, succinylcholine lowers the threshold of the ventricle to catecholamine-induced dysrhythmias in the monkey and dog. Circulating catecholamine concentrations increase fourfold and potassium concentrations increase by a third after succinylcholine administration in dogs.[101] Similar increases in catecholamine levels are also observed after the administration of succinylcholine to humans.[102] [103] Other autonomic stimuli, such as endotracheal intubation,[104] hypoxia, hypercapnia, and surgery, may be additive to the effect of succinylcholine. The possible influence of drugs such as digitalis, tricyclic antidepressants, monoamine oxidase inhibitors, exogenous catecholamines, and halothane, all of which may lower the ventricular threshold for ectopic activity or increase the arrhythmogenic effect of catecholamines, must be considered as well. Ventricular escape beats may also occur as a result of severe sinus and atrioventricular nodal slowing secondary to succinylcholine administration. The development of ventricular dysrhythmias is further encouraged by the release of potassium from skeletal muscle as a consequence of the depolarizing action of the drug.
The administration of succinylcholine to an otherwise well individual for an elective surgical procedure increases plasma potassium levels by approximately 0.5 mEq/L. This increase in potassium is due to the depolarizing action of the relaxant. With activation of the acetylcholine channels, movement of sodium into the cells is accompanied by movement of potassium out of the cells. This slight increase in plasma potassium levels is well tolerated by individuals and generally does not cause dysrhythmias.
Several early reports suggested that patients in renal failure may be susceptible to a hyperkalemic response to succinylcholine.[105] [106] [107] Nevertheless, more controlled studies have shown that renal failure patients are no more susceptible to an exaggerated response to succinylcholine than are those with normal renal function. [108] [109] [110] [111] [112] One might postulate that patients who have uremic neuropathy may be susceptible to succinylcholine-induced hyperkalemia, although evidence supporting this view is scarce.[107] [112]
Severe hyperkalemia may follow the administration of succinylcholine to patients with severe metabolic acidosis and hypovolemia.[113] In rabbits, the combination of metabolic acidosis and hypovolemia results in a high resting potassium level and an exaggerated hyperkalemic response to succinylcholine. [114] In this situation, the potassium originates from the gastrointestinal tract and not from muscle, as in the classic hyperkalemic response.[115] In patients with metabolic acidosis and hypovolemia, correction of the acidosis by hyperventilation and sodium bicarbonate administration should be attempted before administration of succinylcholine. Should severe hyperkalemia occur, it can be treated with immediate hyperventilation, 1.0 to 2.0 mg calcium chloride intravenously, 1 mEq/kg sodium bicarbonate, and 10 U regular insulin in 50 mL 50% glucose for adults or, for children, 0.15 U/kg regular insulin in 1.0 mL/kg 50% glucose.
Kohlschütter and colleagues[116] found that four of nine patients with severe abdominal infections had an increase in serum potassium concentrations of as much as 3.1 mEq/L above baseline values after succinylcholine administration. These investigators found that in the case of intra-abdominal infections that persist for longer than 1 week, the possibility of a hyperkalemic response to succinylcholine should be considered.
Stevenson and Birch[117] described a single, well-documented case of a marked hyperkalemic response to succinylcholine in a patient with a closed head injury without peripheral paralysis.
In studying soldiers who had undergone trauma during the Vietnam War, Birch and associates[118] found that a significant increase in serum potassium did not occur in 59 patients until about 1 week after the injury, at which time a progressive increase in serum potassium occurred after the infusion of succinylcholine. Three weeks after injury, three of these patients with especially severe injuries showed marked hyperkalemia with an increase in serum potassium of greater than 3.6 mEq/L, sufficient to cause cardiac arrest. Birch and coworkers[118] found that prior administration of 6 mg dTc prevented the hyperkalemic response to succinylcholine. In the absence of infection or persistent degeneration of tissue, a patient is susceptible to the hyperkalemic response probably for at least 60 days after massive trauma or until adequate healing of damaged muscle has occurred.
In addition, patients with any number of conditions that have resulted in the proliferation of extrajunctional acetylcholine receptors, such as those with neuromuscular disease, are likely to have an exaggerated hyperkalemic response after the administration of succinylcholine. The response of these patients to neuromuscular blocking agents is reviewed in detail later in this chapter. Some of these disease states include cerebrovascular accident with resultant hemiplegia or paraplegia, muscular dystrophies, and Guillain-Barré syndrome. The hyperkalemia after administration of succinylcholine may be to such an extent that cardiac arrest ensues. For an in-depth discussion of the clinical and pathophysiologic aspects of succinylcholine-induced hyperkalemia, the reader is referred to a review by Gronert and Theye.[119]
Succinylcholine usually causes an increase in intraocular pressure (IOP). The increased IOP is manifested within 1 minute after injection, peaks at 2 to 4 minutes, and subsides by 6 minutes.[120] The mechanism by which succinylcholine increases IOP has not been clearly defined, but it is known to involve contraction of tonic myofibrils or transient dilatation of choroidal blood vessels, or both. Sublingual administration of nifedipine has been reported to attenuate the increase in IOP from succinylcholine, thus suggesting a circulatory mechanism.[121] Despite this increase in IOP, the use of succinylcholine for ophthalmic procedures is not contraindicated unless the anterior chamber is open. Although Meyers and coworkers[122] were unable to confirm the efficacy of precurarization in attenuating increases in IOP after succinylcholine, numerous other investigators have found that previous administration of a small dose of nondepolarizing neuromuscular blocker (such as 3 mg dTc or 1 mg pancuronium) will prevent a succinylcholine-induced increase in IOP.[123] Furthermore, Libonati and coauthors[124] described the anesthetic management of 73 patients with penetrating eye injuries who received succinylcholine with no loss of global contents. Thus, despite the potential concerns of Meyers and coworkers,[122] Libonati and colleagues[124] found that the use of succinylcholine, after pretreatment with a nondepolarizing neuromuscular blocker, in patients with penetrating eye injuries with a carefully controlled rapidsequence induction of anesthesia is an acceptable technique. Succinylcholine is only one of many factors, such as endotracheal intubation and "bucking" on the endotracheal tube, that may increase IOP.[122] Of prime importance is ensuring that the patient is well anesthetized and is not straining or coughing. Because nondepolarizing neuromuscular blockers with shorter times to onset of effect are now available, providing an anesthetic that allows for the trachea to be intubated rapidly without administering succinylcholine is now an option. Finally, should a patient's anesthesia become too light over the course of intraocular surgery, succinylcholine should not be given to immobilize the patient. Rather, the surgeon should be asked to pause while anesthesia is deepened. If necessary, the depth of neuromuscular blockade can also be increased with nondepolarizing relaxants.[125] In fact, coughing or "bucking" during a vitrectomy may cause serious postoperative eye damage with marked damage to vision.[126] Adequate anesthesia, with or without paralysis, is essential during eye surgery (also see Chapter 65 and Chapter 82 ).
Unlike the rather consistent increase in IOP, the increase in intragastric pressure (IGP) caused by succinylcholine is quite variable. The increase in IGP from succinylcholine is presumed to be due to fasciculations of abdominal skeletal muscle, which is not surprising because more coordinated abdominal skeletal muscle activity (e.g., straight leg raising) may increase IGP to values as high as 120 cm H2 O. In addition to skeletal muscle fasciculations, the acetylcholine-like effect of succinylcholine may be partly responsible for the observed increases in IGP. Greenan[127] noted consistent increases in IGP of 4 to 7 cm H2 O with direct vagal stimulation.
Miller and Way[128] found that 11 of 30 patients essentially had no increase in IGP after succinylcholine. Nonetheless, 5 of 30 patients had an increase in IGP greater than 30 cm H2 O. The increase in IGP from succinylcholine appeared to be related to the intensity of fasciculations of the abdominal skeletal muscles. Accordingly, when fasciculations were prevented by previous administration of a nondepolarizing neuromuscular blocker, no increase in IGP was observed.
Are the increases in IGP after succinylcholine administration enough to cause incompetence of the gastroesophageal junction? Generally, IGP greater than 28 cm H2 O is required to overcome the competence of the gastroesophageal junction. However, when the normal oblique angle of entry of the esophagus into the stomach is altered, as may occur with pregnancy, an abdomen distended by ascites, bowel obstruction, or a hiatal hernia, the IGP required to cause incompetence of the gastroesophageal
Apparently, succinylcholine does not increase IGP appreciably in infants and children, possibly because of the minimal or absent fasciculations after administration of succinylcholine in these age groups.[129]
Succinylcholine has the potential to increase intracranial pressure. [130] The mechanisms and clinical significance of this transient increase are unknown, but the rise in intracranial pressure does not occur after pretreatment with nondepolarizing neuromuscular blockers.[131]
The incidence of muscle pain after administration of succinylcholine varies from 0.2% to 89%.[132] It occurs more frequently after minor surgery, especially in women and ambulatory rather than bedridden patients. [133] Waters and Mapleson[133] postulated that the pain is secondary to damage produced in muscle by the unsynchronized contractions of adjacent muscle fibers just before the onset of paralysis. That damage to muscle may occur has been substantiated by finding myoglobinemia and increases in serum creatine kinase after succinylcholine administration.[134] [135] [136] Previous administration of a small dose of a nondepolarizing neuromuscular blocker clearly prevents fasciculations from succinylcholine.[134] However, the efficacy of this approach in preventing muscle pain is questionable. Although some investigators claim that pretreatment with a defasciculating dose of a nondepolarizing neuromuscular blocker has no effect,[132] many believe that the pain from succinylcholine is at least attenuated.[135] [136] [137] Pretreatment with a prostaglandin inhibitor (lysine acetylsalicylate) has been shown to be effective in decreasing the incidence of muscle pain after succinylcholine.[138] This finding suggests a possible role for prostaglandins and cyclooxygenases in succinylcholine-induced myalgias. Other investigators have found that myalgias after outpatient surgery occur even in the absence of succinylcholine.[139] [140]
An increase in tone of the masseter muscle is a frequent response to succinylcholine in adults,[141] as well as children. [142] [143] [144] Meakin and associates[142] suggested that the frequent occurrence of spasm in children may be due to an inadequate dose of succinylcholine. In all likelihood, this increase in tone is an exaggerated contractile response at the neuromuscular junction and cannot be used to establish a diagnosis of malignant hyperthermia. Although an increase in tone of the masseter muscle may be an early indicator of malignant hyperthermia,[145] it is not consistently associated with malignant hyperthermia.[146] Currently, there is no indication to change to a "nontriggering" anesthetic in instances of isolated masseter spasm.[143]
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