April 3, 1997

Subject:

• CARDIAC ARREST IN CHILDREN AND ADOLESCENT PATIENTS RECEIVING SUCCINYLCHOLINE

• SUCCINYLCHOLINE-INDUCED HYPERKALEMIA

Dear Anesthesia Practitioner:

Bristol-Myers Squibb Company wants to call your attention to two life-threatening events that may occur with the use of succinylcholine, and to alert you to important changes being made to the product label for SUCOSTRIN brand succinylcholine.

• Except when used for emergency tracheal intubation or in instances where immediate securing of the airway is necessary,

• Succinylcholine is contraindicated in patients after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury because succinylcholine administration to such individuals may result in severe hyperkalemia which may result in cardiac arrest. The risk of hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury. The risk is dependent on the extent and location of the injury. The precise time of onset and the duration of the risk period are not known.

CARDIAC ARREST IN CHILDREN AND ADOLESCENT PATIENTS RECEIVING SUCCINYLCHOLINE

There have been several reports of cardiac arrest following administration of succinylcholine to apparently healthy children and adolescent patients who were subsequently found to have undiagnosed myopathies. In most cases, patients experienced acute rhabdomyolysis with hyperkalemia and cardiac arrest. ^1-4

Because children and adolescent patients are more likely than adults to have such undiagnosed myopathies, a non-depolarizing neuromuscular blocking drug should be used for routine elective surgery in these patients. Succinylcholine remains the drug of choice when emergency intubation or immediate securing of the airway is indicated.

SUCCINYLCHOLINE-INDUCED HYPERKALEMIA

Clinical reports have demonstrated an association between hyperkalemia and the administration of succinylcholine to certain populations with catabolic states. First described in burn patients, the phenomenon is now recognized in patients with severe abdominal infections, tetanus, massive trauma and neuromuscular disease. Over a dozen case reports and letters have been published reporting hyperkalemia after administration of succinylcholine to patients with burns, massive trauma, stroke and spinal cord injury. ^5-15 A common denominator appears to be either massive tissue destruction or CNS injury with muscle wasting.

Attempts have been made to identify the period of risk. ^5,16,17 Skeletal muscle denervation hypersensitivity usually develops over several weeks but can occur as early as one to two days after injury. In an experimental canine model, hyperkalemia following succinylcholine administration developed seven days after denervation. ¹¹ In humans, the hyperkalemic response to succinylcholine can persist for over six months after neural injury. ^6,10 Insufficient data exist to define the period of risk for development of succinylcholine-induced hyperkalemia after major burns or neuromuscular injuries.

The enclosed package insert for SUCOSTRIN brand succinylcholine has been revised to incorporate these and a number of other important changes. Please carefully read the entire enclosed package insert. If you have questions about this matter, please contact our Drug Information Department (800-321-1335).

Sincerely,

Walter G. Jump, Pharm.D.
Senior Director
Medical & Regulatory Operations

1. Delphin E, et al. Use of succinylcholine during elective pediatric anesthesia should be re-evaluated. Anesth Analg. 1987; 66:1190-1192.

2. Gurgey A. Malignant hyperthermia is a patinet with sickle cell anemia. Turk J Pediatr 1989; 31:245-248.

3. Mehler H, et al. Cardiac arrest during induction of anesthesia with halothane and succinylcholine in an infant. Severe hyperkalemia and rhabdomyolysis due to a suspected myopathy and/or malignant hyperthermia. Anaesthetist. 1991; 40:497-501.

4. Rosenberg H, Gronert GA. Intractable cardiac arrest in children given succinylcholine. Anesthesiol. 1992; 77:1054 (letter).

5. Cooperman LH. Succinylcholine-induced hyperkalemia induced by succinylcholine. JAMA. 1970;213:1867-1871.

6. Gronert GA, Theye RA. Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology. 1975; 43:89-99.

7. John DA, et al. Onset of succinylcholine-induced hyperkalemia following denervation. Anesthesiology. 1976; 45:294-299.

8. Tobey RE. Paraplegia, succinylcholine and cardiac arrest. Anesthesiology. 1979;32:359-364.

9. Tobey RE, et al. The serum potassium response to muscle relaxants in neural injury. Anesthesiology. 1972; 37:332-337.

10. Tolmie JD, et al. Succinylcholine danger in the burned patient. Anesthesiology. 1967; 28:467-470.

11. Mazze RI, et al. Hyperkalemia and cardiovascular collapse following administration of succinylcholine in the traumatized patient. Anesthesiology. 1969; 31:540-547.

12. Nash CL, et al. Succinylcholine, paraplegia, and intraoperative cardiac arrest. A case report. J Bone Joint Surg. 1981;63A:1010-1012.

13. Walker DE, et al. Succinylcholine-induced ventricular fibrillation in the paralyzed urology patient. J Urol. 1975; 113:11-13.

14. Walters FJ, Nott MR. The hazards of anesthesia in the injured patient. Br J Anaesth. 1977;49:707-720.

15. Williams, CH, et al. Effect of intravenously administered succinylcholine on cardiac rate and rhythm and arterial blood pressure in anesthetized men. Anesthesiology. 1961; 22:947.
16. Carter JG, et al. Effect of spinal cord transection on neuromuscular function in the rat. Anesthesiology. 1981; 55:542-546.

17. Stone WA, et al. Succinylcholine-induced hyperkalemia in dogs with transected siatic nerves or spinal cords. Anesthesiology. 1970; 32:515-519.