While being treated for the acute respiratory distress syndrome, a 27-year-old woman developed profound hyperkalemia and cardiac arrest following the administration of succinylcholine chloride (SCh). She had none of the risk factors previously described for development of severe hyperkalemia following SCh administrations; however, she had been intermittently treated with nondepolarizing neuromuscular blocking drugs throughout the course of her illness. We suggest that immobilization of critically ill patients with pharmacologic neuromuscular blockade may predispose them to severe hyperkalemia and cardiac arrest following administration of SCh. SCh should be used with great caution in such patients. (CHEST 1997; 111:248-50)
Key words: cardiac arrest; hyperkalemia; immobilization; neuromuscular blockade
Abbreviations: AChR = acetylcholine receptor; IV= intravenously; SCh=succinylcholine chloride
Neuromuscular blocking agents are life-saving drugs in emergencies and have a limited, but important, role in facilitating mechanical ventilation in selected patients.[1,2] Unfortunately, prolonged muscle weakness and other important adverse effects have been described with these agents.[1,2] Succinylcholine chloride (SCh) has been reported to cause severe hyperkalemia in patients with burns, trauma, severe infection, or a variety of neurologic conditions.[1,3] The patient presented herein had hyperkalemia and a cardiac arrest within minutes following the administration of SCh. She did not have any of the risk factors for this response that have previously been reported. We propose that the prolonged use of nondepolarizing neuromuscular blocking agents along with immobility and disuse atrophy predisposed her to this adverse drug reaction.
CASE REPORT
A 27-year-old woman was admitted to another hospital with chickenpox and respiratory failure requiring mechanical ventilation On hospital day 6, she developed a leak in the endotracheal tube cuff and was reintubated after receiving midazolam (5 ma, IV), vecuronium bromide (0.5 ma, IV), and SCh (110 ma, IV). Tracheostomy was performed on hospital day 10. Two days later, she was transferred to the University of Utah Medical Center Medical ICU for management of severe acute respiratory distress syndrome. She was paralyzed with vecuronium bromide during transport. The patient was treated with acyclovir, sedation, mechanical ventilator, and parenteral nutrition. Initial ventilator management required the use of 100% inspired oxygen and high positive end-expiratory pressure. A standard tracheostomy tube was replaced with an endotracheal tube through the tracheostomy because tracheal injury and dilation, in combination with high airway pressures, resulted in a large air leak around the tracheostomy tube balloon. Between hospital days 14 and 25, she was heavily sedated and paralyzed with intermittent boluses of pancuronium bromide or vecuronium bromide to facilitate mechanical ventilation.
On day 31, the chronic air leak around her endotracheal tube cuff worsened and caused agitation, respiratory distress, hypercarbia, and respiratory acidosis. An attempt to blindly advance the endotracheal tube, which was 2 cm proximal to the desired position, was unsuccessful. The patient was sedated with 2 doses of midazolam (4 ma, IV), was paralyzed with SCh (100 ma, IV), and the tube was advanced over a fiberoptic bronchoscope without difficulty. While the bronchoscope was skill in the endotracheal tube, the patient developed a wide-complex tachycardia followed by ventricular fibrallation and asystole. Advanced cardiac life support was immediately started, samples for arterial blood gases and serum electrolytes were sent to the laboratory, and treatment for presumed hyperkalemia (IV administered calcium gluconate, insulin, and glucose) was instituted. Arterial blood gas determination at that time revealed pH, 7.35; PaC[O.sub.2], 67 mm Hg; and Pa[O.sub.2], 72 mm Hg; serum electrolyte values showed K+ to be 13.1 mEq/L. There was no evidence for hemolysis of the specimen; 20 min after cardiac arrest, her rhythm returned to sinus tachycardia in response to treatment for hyperkalemia and advanced cardiac life support. Another sample for serum electrolytes drawn during the cardiac arrest revealed [K.sup.+] to be 10 mEq/L, and those drawn 5 min after the return to sinus tachycardia showed [K.sup.+] as 5.0 mEq/L. The patient was alert and oriented and without neurologic deficit within 2 h of the arrest. Muscle tone was normal, and serial enzyme analysis did not suggest significant muscle injury. Serial ECGs and cardiac enzymes showed no evidence of a myocardial infarction.
Two days following the cardiac arrest, electromyography was performed. There was abundant spontaneous muscle activity with fibrillation at all sites tested, positive sharp waves, and no evidence of polyneuritis. These findings were considered typical of denervation. The patient's lung function and muscle strength continued to improve, and she was liberated from the ventilator on hospital day 58. Three days later, she was transferred back to the referring hospital where she made steady progress and was discharged home in good condition 2 weeks later.
Discussion
SCh, a depolarizing neuromuscular blocking agent, causes a rise in serum [K.sup.+] of up to 1.0 mEq/L which peaks within 2 to 5 min and then quickly returns to baseline in normal individuals.[3-5] This is due to [K.sup.+] efflux from skeletal muscle at the neuromuscular junction. Patients with burns, trauma, infections, or neuromuscular disorders have a greater than normal [K.sup.+] efflux that may occasionally cause severe hyperkalemia.[6] It is proposed that these patients have developed extrajunctional acetylcholine receptors (AChRs) and, therefore, [K.sup.+] is released from the entire muscle instead of the neuromuscular junction alone.[6, 7] The extrajunctional AChRs are structurally different from those at the neuromuscular junction, more sensitive to SCh, and have ion channels that remain open longer after depolarization, possibly allowing more [K.sup.+] to exit.[7-9] Diminished [K.sup.+] uptake, a deficiency in acetylcholinesterase, and terminal nerve sprouting also may contribute to hyperkalemia.[10-12]
This patient's cardiac arrest was secondary to hyperkalemia, as evidenced by elevated serum [K.sup.+] and characteristic electrocardiographic changes. The close temporal association with administration of SCh implicates this drug. The patient did not have any of the disorders previously associated with an abnormal response to SCh.[1, 3] We did not see profound muscle rigidity or evidence of significant muscle injury in response to SCh in this patient. We propose that the chronic use of nondepolarizing neuromuscular blocking agents, with associated immobilization and disuse atrophy, predisposed this patient to severe hyperkalemia and cardiac arrest in response to SCh. Proliferation of AChRs, increased sensitivity to SCh, and heightened release of [K.sup.+] in response to SCh occur after 14 days of immobility in animals.[13] While this may not be problematic if it occurred in only a single muscle group, total body immobilization with disuse atrophy may lead to a sufficient release of [K.sup.+] to cause cardiac arrest. This patient's electromyogram displayed findings typical of denervation which likely resulted from the chronic use of nondepolarizing neuromuscular blocking agents. Denervation in other clinical situations has been associated with heightened [K.sup.+] release following SCh.[3] In animals, prolonged use of nondepolarizing muscle relaxants may lead to AChR upregulation that is independent of immobility,[14] which may explain the mechanism behind the altered response to SCh. It is interesting that this patient received SCh on hospital day 6 without adverse effect. At that time, she was premedicated with vecuronium bromide which may reduce the [K.sup.+] release associated with SCh.[4] A more likely explanation is that upregulation of AChR had not yet occurred in this patient.
In summary, we report a patient who developed hyperkalemia and cardiac arrest following administration of SCh. We suggest that the prolonged use of nondepolarizing muscle relaxants along with immobilization and disuse atrophy predisposed her to this adverse drug reaction. There are three previous case reports of an exaggerated release of [K.sup.+] following the administration of SCh in the absence of obvious risk factors;[15-17] however, prolonged use of neuromuscular blocking agents did not appear to be a factor in these cases. We suggest that SCh should be used with extreme caution in patients who have had chronic exposure to muscle relaxants in critical care settings. This may represent yet another complication of neuromuscular blockade in the ICU.
ACKNOWLEDGMENTS: We thank John R. Michael, MD, for his review of the manuscript and the nurses and medical residents in the Medical ICU at the University of Utah Medical Center, Salt Lake City, for excellent care of this patient.
References
[1] Hunter JM. New neuromuscular blocking drugs. N Engl J Med 1995; 332:1691-99
[2] Hansen-Flaschen J, Cowen J, Raps EC. Neuromuscular blockade in the intensive care unit: more than we bargained for. Am Rev Respir Dis 1993; 147:234-36
[3] Yentis SM. Suxamethonium and hyperkalaemia. Anaesth Intensive Care 1990; 18:92-101
[4] Weintraub HD, Heisterkamp DV, Cooperman LH. Changes in plasma potassium concentration after depolarizing blockers in anesthetized man. Br J Anaesth 1969; 41:1048-52
[5] Mazze RI, Escue HM, Houston JB. Hyperkalemia and cardiovascular collapse following administration of succinylcholine to the traumatized patient. Anesthesiology 1969; 31:540-47
[6] Gronert GA, Theye RA. Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology 1975; 43:89-99
[7] Martyn JAJ, White DA, Gronert GA, et al. Up-and-down regulation of skeletal muscle acetylcholine receptors. Anesthesiology 1992; 76:822-43
[8] Mishina M, Takai T, Imoto K, et al. Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 1986; 321:406-11
[9] Gu Y, Hall ZW. Immunological evidence for a change in subunits of the acetylcholine receptor in developing and denervated rat muscle. Neuron 1988; 1:117-25
[10] Harris EJ, Nicholls JG. The effect of denervation on the rate of entry of potassium into frog muscle. J Physiol 1956; 131:473-76
[11] Snider WD, Harris GL. A physiological correlate of disuse-induced sprouting at the neuromuscular junction. Nature 1979; 281:69-71
[12] Axelsson J, Thesleff S. A study of supersensitivity in denervated mammalian skeletal muscle. J Physiol 1959; 147:178-93
[13] Fung DL, White DA, Jones BR, et al. The onset of disuse-related potassium efflux to succinylcholine. Anesthesiology 1991; 75:650-53
[14] Hogue CW Jr, Ward JM, Itani MS, et al. Tolerance and upregulation of acetylcholine receptors follow chronic infusion of d-tubocurarine. J Appl Physiol 1992; 72:1326-31
[15] Laycock JRD, Loughman E. Suxamethonium-induced hyperkalaemia following cold injury. Anaesthesia 1986; 41: 739-41
[16] George AL Jr, Wood CA Jr. Succinylcholine-induced hyperkalemia complicating the neuroleptic malignant syndrome [letter] Ann Intern Med 1987; 106:172
[17] Hemming AK, Charlton S, Kelly P. Hyperkalaemia, cardiac arrest, suxamethonium and intensive care. Anaesthesia 1990; 45:990-91
(*) from the Section of Pulmonary and Critical Care Medicine, Department of Medicine Overton Brooks Veterans Affairs Medical Center and Louisiana State University School of Medicine, Shreveport, (Dr. Markewitz), and the Medicine Service, Veterans Affairs Medical Center and Department of Medicine (Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine), University of Utah School of Medicine, Salt Lake City (Dr. Elstad).
This work was supported by Department of Veterans Affairs Medical Research Funds. Manuscript received April 17, 1996; revision accepted August 2. Reprint requests: Dr. Elstad, CVRTI (Bldg. 500), University of Utah, Salt Lake City, UT 84112
COPYRIGHT 1997 American College of Chest Physicians
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