“No, succinylcholine should not be used routinely for elective pediatric surgery.”

No, succinylcholine should be used only when the clinician deems it necessary to have a relaxant with a rapid onset and short duration since the many side effects range from troublesome to life threatening.

The well-documented, undesirable side effects of succinylcholine include muscle pain, cardiovascular changes, arrhythmias and cardiac arrest, increases in intraocular and intragastric pressure, masseter spasm, myoglobinemia, myoglobinuria, association with malignant hyperthermia (MH), and hyperkalernia in susceptible patients. The risk of hyperkalemia has been highlighted recently with case reports of patients with unsuspected muscle disorders, primarily Duchenne’s muscular dystrophy. It is for this reason that the FDA Anesthetic and Life Support Drugs Advisory Committee and the Pilot Drug review team, along with the four manufacturers of succinylcholine, have recently stated that succinylcholine is contraindicated for routine use in children and adolescents except for emergency tracheal intubation or in instances where immediate securing of the airway is necessary.

Many Side Effects

In children, the incidence of relatively minor and easily treatable side effects, such as bradycardia, muscle pain, and increase in intraocular or intragastric pressure is high. We modify our practice habits because of the common occurrence of many of these side effects. For example, we routinely administer atropine when we use succinylcholine. Also, patients may be pretreated with a non-depolarizing neuromuscular blocking drug in the hope of preventing muscle fasciculations and muscle pain. The increase in intraocular pressure may be attenuated with intravenous or inhalational anesthetic agents prior to administration of succinylcholine. If we are concerned about the increase in intragastric pressure and the risk of regurgitation and aspiration, then we apply cricoid pressure until the trachea is intubated. We adapt our method of anesthesia practice to avoid the side effects of the drugs we choose to administer.

Another group of side effects of succinylcholine has a lower incidence, may be dose-related, and is of debatable importance. Masseter spasm on induction of anesthesia may be a normal response to succinylcholine, (1) or the first indication of MH. Some advocate canceling the procedure, while others recommend continuing the procedure with halothane. (2) Is the child with masseter spasm more likely to have myoglobinuria postoperatively, and should we look for myoglobinuria in all children who receive succinylcholine? Myoglobinuria may also be a normal reaction to succinylcholine. (3-5) Patients with masseter spasm or myoglobinuria are difficult to counsel postoperatively because our information is incomplete. An example from our institution is a child who experienced myoglobinuria in the recovery room after receiving succinylcholine during a tonsillectomy, and then returned for treatment of a bleeding tonsil within six hours of his first operation. Is succinylcholine the drug of choice for this emergency procedure, with the possible increased risk of triggering MH? This child returned for two direct laryngostomies to evaluate hoarseness and eventually underwent removal of a laryngeal granuloma. Is halothane still the drug of choice for these short ENT procedures? The family required extensive counseling regarding the safety of anesthetic agents in their child, and not all the answers were clear. If succinylcholine was not used routinely, perhaps many such problems would be avoided.

Serious Complications

The most dramatic complications of succinylcholine are hyperkalemic cardiac arrest and MH. These complications, although admittedly rare, are potentially line-threatening. Hyperkalemic cardiac arrest is most likely to occur in patients with certain disease states: neurological disease (paraplegia or stroke), massive trauma, muscular dystrophies, myotonia, burns, or MH. Twenty cases of hyperkalemic arrest, 11 of which were fatal, were reported from 1990 through 1993.1 Family history and creatine kinase levels identify only some patients with muscular dystrophy or other occult myopathies before elective surgery. In addition, patients susceptible to MH cannot be determined by the history and laboratory examinations preoperatively. These patients are at risk for life-threatening consequences when succinylcholine is chosen instead of a non-depolarizing drug.

Safe Drugs Available

Because of the significant side effects associated with succinylcholine administration, anesthesiologists have been searching for a non-depolarizing muscle relaxant with rapid, reliable onset of complete, neuromuscular blockades, short duration of action, and minimal cardiovascular side effects. Today, we have many such drugs to produce rapid relaxation. They include mivacurium, rocuronium, and perhaps atracurium and vecuronium as well. Priming techniques or administration of more than 3 to 4 times the intubation dose of relaxant will also produce rapid onset paralysis. In addition, in recent years there there has been more discussion of monitoring techniques available to judge the depth of neuromuscular blockade in pediatric patients, as well as the appropriate time to administer reversal agents. Therefore, the hesitancy to use non-depolarizing drugs in pediatric patients because of fear of persistent paralysis should be less prevalent.

In summary, the elective use of succinylcholine in pediatric anesthesia should be abandoned. The unwanted side effects of succinylcholine are well known. More important, viable alternatives to succinylcholine now exist for intermediate or long surgical procedures. With short-acting non-depolarizing relaxants available, succinylcholine is obsolete for routine anesthesia care.

Dr. Woelfel is Associate Professor of Anesthesiology, University of Pittsburgh School of Medicine, and staff anesthesiologist at Children’s Hospital of Pittsburgh, Pittsburgh, PA.

References

1. Van Der Spek AFL, Fang WB, Ashton-Miller JA, et al: Increased masticatory muscle stiffness during limb muscle flaccidity associated with succinylcholine administration. Anesthesiology 69:11,1988.

2. Littleford JA, Patel LR, Bose D, et al: Masseter muscle spasm in children: Implications of continuing the triggering anesthetic. Anesth Analg 72:151-160,1991.

3. Ryan JF, Kagen LJ, Hyman Al: Myoglobinemia after a single dose of succinylcholine. N Engl J Med 285:824825,1971.

4. Harrington JF, Ford DJ, Striker TW: Myoglobinemia and myoglobinuria after succinylcholine in children. (Abstract) Anesthesiology 59,A439,1983.

5. Plotz J: Succinylcholine in children (Letters to the Editor). Anesth Analg 67:798-W2,1988.

6. Kent RS: Revised label regarding use of succinylcholine in children and adolescents: I (Correspondence). Anesthesiology 80:244-245, 1994.

“Yes, succinylcholine can be used routinely with safety in children.”

by Robert C. Morell, M.D., and Jeffrey M. Berman, M.D.

Succinylcholine has been used in pediatric anesthesia for more than 40 years. Currently, no other neuromuscular blocking agent has the same pharmacokinetic profile relative to speed of onset and duration of action. Furthermore, there is no substitute for succinylcholine when intramuscular administration is required. Controversy regarding the ‘routine’ use of succinylcholine in children was recently fueled by a labeling change initiated by one manufacturer of the drug and the FDA. As of November 1993, succinylcholine became contraindicated in children and adolescent patients “except when used for emergency tracheal intubation or in instances where immediate securing of the airway is necessary.” (1) The rationale for this labeling change was based on a total of 36 cases of unexpected cardiac arrest which were reported to occur after the administration of succinylcholine to .apparently’ healthy children and adolescents who were subsequently found to have myopathies. (2)

Decree Unacceptable

This contraindication by decree is unacceptable to many anesthesiologists, including recognized experts in pediatric anesthesia. Recent published letters by Badgwell et al (3) Lennan et al (4) and Morell et al. (5) voice strong opposition to the label change and advocate the continued use of succinylcholine in pediatric patients. These cardiac arrests, while temporally associated with the administration of succinylcholine, may have multiple etiologies. Although many of the reports document hyperkalemia, several cases report either normokalemia or fail to report serum potassium. Bradycardia during halothane induction is not uncommon in children. Due to their high vagal tone, hypoxia or stimulation of certain reflexes may also result in asystole.

The FDA’s decision to issue a contraindication rather than a warning was based on the inability to predict which patients may be at risk for sudden cardiac arrest following the administration of succinylcholine, and the lack of effective management should that event occur. (2,6) Although predictability of adverse drug reactions is desirable, we must always be ready for the unexpected. Prompt and proper treatment is paramount. In many of the cited cases of hyperkalemic cardiac arrest, including one fatality, calcium was not administered despite measured serum potassium levels in excess of 10 mEq/L. (7-9) In hyperkalemia, the resting membrane potential moves closer to the threshold for depolarization. Calcium is crucial in treating hyperkalemia because calcium raises this threshold, directly antagonizing the electrophysiologic effect of potassium. The appropriate administration of glucose and insulin or sodium bicarbonate, which moves potassium intracellularly, is not as effective nor as rapid.

Data Support Sux

In short, we believe that the arguments attempting to justify the contraindication of succinylcholine in children and adolescents are flawed and not supported by the available data. In response, we put forth the following arguments:

1. Succinylcholine following halothane does not carry the same risk as succinylcholine following thiopental. Out of 23 reported cases of sudden cardiac arrest after succinylcholine, 20 documented the administration of halothane prior to the administration of succinylcholine. There were 2 cases in which isoflurane and I case in which cyclopropane were administered prior to succinylcholine. None of these cases involved an intravenous induction with sodium pentothal.”‘ It has been demonstrated by several investigators that the choice of induction agent can significantly affect serum potassium levels after succinylcholine, and that benzodiazepines and sodium pentothal may attenuate the usual rise in potassium.’ The clinical experience of Lerman and others supports these observations.’

2. Adolescents are not the same patients as infants and young children. Although it may be difficult to make the diagnosis of Duchenne muscular dystrophy in an infant or young child, most anesthesiologists would have little trouble recognizing this myopathy in a 14 or 15-year-old. It is interesting to note that among Dr. Schulte-Sasse’s nine reported cases of sudden cardiac arrest in apparently ‘healthy’ children, two carried a preoperative diagnosis of a myopathy, yet succinylcholine was still administered. The ability to predict patients at risk was not an issue in at least these two cases.

3. Succinylcholine is useful and unique in many situations where emergent or immediate securing of the airway is not mandatory. The scenario of the suspected difficult intubation may arise in which, despite the adequacy of mask ventilation after induction, the anesthesiologist does not wish to ‘burn any bridges’ by using a non-depolarizing muscle relaxant with a slower onset and longer duration. The utility of succinylcholine administered as an infusion for suspension microlaryngoscopy is without equal, particularly when the surgery requires that the vocal cords be absolutely immobile for indeterminate periods of time.

In summary we believe that succinylcholine is as safe and efficacious today as it was last year and the year before. Halothane is a potent trigger for malignant hyperthermia. However, we have yet to contraindicate halothane in the pediatric population because we have recognized the adverse reactions and have developed effective means of treating a potentially lethal complication. Hyperkalemia after succinylcholine is no different. It is no different than anaphylaxis after prolamine or low molecular weight dextran or penicillin. Anaphylaxis, in fact, accounts for more than 500 deaths in the United States annually, with an incidence which may be as high as I in every 3,000 inpatients.’ We must always expect the unexpected and treat each of our patients accordingly, with our best training, experience and judgment. The choice of muscle relaxant in a pediatric patient should be weighed against the risks and benefits in the individual case. Succinylcholine should not be chosen at random, nor should any drug. Until a muscle relaxant with as favorable a pharmacokinetic and pharmacodynamics profile is developed and released, the use of succinylcholine should be directed by the anesthesiologist, not by corporate or governmental officials. The unique properties of succinylcholine expand its utility far beyond the emergent scenario.

Dr. Morell is Assistant Professor W Dr. Berman is an Instructor, Department of Anesthesia, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.

References

1. Package Insert: Anectine (Succinylcholine Chloride) Injection, USP. Burroughs Wellcome Company, June 1993.

2. Kent RS: Revised label regarding use of succinylcholine in children and adolescents: I and 11 [Reply]. Anesthesiology 1994;80:244-245.

3. Badgwell JM, Hall SC, Lockhart C: Revised label regarding use of succinylcholine in children and adolescents: 11 [Letter]. Anesthesiology 1994;80:243.

4. Lerman J, Berdock SE, Bissonnette B, et al: Succinylcholine warning. Can j Anaesth 1994;41:165.

5. Morell RC, Berman JM, Royster RL, Petrozza PH, Kelly JS, Colonna DM: Revised label regarding use of succinylcholine in children and adolescents: I [Letter]. Anesthesiology 1994;80:242.

6. Katz L, Wright C, Harter J, Zung M, Scally D, Spyker D: Revised label regarding use of succinylcholine in children and adolescents: I and 11 [Reply]. Anesthesiology 1994;80:243-244.

7. Stelzner J, Kretz FJ, Rieger A, Reinhart K: Anesthefikainduzieiter herzsillstand. Anaesthesist 1993;42:4446.

8. Schulte-Sasse VU, Eberlein HJ, Schmucker 1, Underwood D, Wolbert R: sollte die verwendung von succinylcholin in der kinderanasthesie neu uberdacht werden? Anaesthesiol Reanimat 1993;18:13-19.

9. Mehler J, Bachour H, Simons F, Wolpers K: Herzstillstand wahrend der narkoseeinleitung mit hatothan und suceinylcholin bei einem saugling. Anaesthesist 1991;40:497-501.

10. Seay AR, Ziter FA, Thompson JA: Cardiac arrest induction of anesthesia in Duchenne muscular dystrophy. J Pediatr 1978,93:88-90.

11. Genever EE: Suxamethonium-induced cardiac arrest in unsuspected pseudohypertrophic muscular dystrophy. Br J Anaesth 1971;43:984-986.

12. Solares G, Herranz JL, Sanz MD: Suxamethonium induced cardiac arrest as an initial manifestation of Duchenne muscular dystrophy. Br J Anaesth 19860:576.

13. Delphin E, Jackson D, Rothstein P: Use of succinylcholine during elective pediatric anesthesia should be reevaluated. Anesth Analg 1987;66:1190-1192.

14. Linter SPK, Thomas PR, Withington PS, Hall MG: Suxamethonium associated hypertonicity and cardiac arrest in unsuspected pseudohypertrophic muscular dystrophy. Br J Anaesth 1982;54:1331-1332.

15. Wilhoit RD, Brown RE Jr, Bauman LA: Possible malignant hyperthermia in a 7-week-old infant. Anesth Analg 1989;68:68M91.

16. Wang JM, Stanley TH: Duchenne muscular dystrophy and malignant hyperthermia two case reports. Can Anaesth Soc j 1986;33:492-497.

17. Arnould JF, Bigot A, Steenbeke L, David A, Mussini JM: Arret circulatoire lors d’une anesthesie generale chez un enfant porteur d’une myopathie de Duchenne meconnue. Ann Fr Anesth Reanim 1986;5:612614.

18. Oudesluys-Murphy AM, van Berkel M, van den Brand HM: Unexplained sudden death under general anaesthesia. Lancet 1985;1:696-697.

19. Hendemn WAV: Succinylcholine-induced cardiac west in unsuspected Duchenne muscular dystrophy. Can Anaesth Soc j 1984;31:444 44 .

20. Vatashsky E, Aronson HB: Intravenous flunitrazepam in the prevention of the side effects of succinylcholine. Isr j Med Sci 1982;18:587-589.

21. Roelofse JA, Hartshorne JE: Serum potassium after enflurane-succinylcholine induction of anesthesia in children receiving rectal midazolam

as premedication. Anesth Prog 1992;39:69-72.

22. Keneally JP, Bush GH: Changes in serum potassium after suxamethonium in children. Anaesth Intens Care 1974,2:147-150.

23. Magbagbeola JAO, Adadevoh BY, Durowoju JEO: Influence of ether anaesthesia on suxamethonium-induced hyperkalaemia. Anaesthesia 1974;29:429-434.

24. Konchigeri HN, Tay C-H: Influence of pancuronium on potassium efflux produced by succinylcholine. Anesth Analg 1976;55:474-477.

25. Bochner BS, Lightenstein LM: Anaphylaxis [Review]. N Engl j Med 1991;324:17&5-1790. February 16, 1994