Can Succinylcholine Be Abandoned ?

1. Can Succinylcholine Be Abandoned ? Presented by R2 康庭瑞

2. History • The introduction of succinylcholine into clinical practice in 1951 was a seminal development in the history of anesthesia • Succinylcholine, despite its many side effects, has been used for more than 50 yr as the standard neuromuscular blocking drug (NMBD) to facilitate tracheal intubation

3. Features of succinylcholin • A rapid onset of action (30~60 seconds), short-duration (typically less than 10 minutes) depolarizing NMBD • Rapidly produces a more profound effect at the vocal cords than at the adductor pollicis muscle • Can be used in relatively small doses to treat intractable laryngospasm and is effective in infants and small children when given IM

4. Side effects • Cardiovascular • Hyperkalemia and myoglobinemia • Increase intragastric, intraocular, intracranial pressure • Malignant hyperthermia • Pulmonary edema and hemorrhage • Occult myopathies • Prolong paralysis • Generalized contractions / Masseter spasm

5. Profound cardiovascular effects • Resembling to Ach, they affect cholinergic receptors in addition to NMJ entire para-sympathetic nervous system and parts of the sympathetic nervous system • Variable and paradoxical effects on the cardiovascular system • Nicotinic receptors in parasym. And sym. ganglia and muscarinic receptors in SA node increase or decreased BP and HR • The metabolite, succinylmonocholin, excites SA node and results in breadycardia Anesthesiology 1957; 58:519–23

6. Profound cardiovascular effects • In the infant and small child, profound sustained sinus bradycardia (50–60 bpm) is often observed; rarely asystole occurs • Nodal rhythm and ventricular ectopic beats are seen in approximately 80% of children given a single IV injection of S.C.C • In adults and in children, the incidence of bradycardias and other dysrhythmias are more frequent after a second dose of succinylcholine without atropine protection • The use of S.C.C in children should be reserved for emergency intubation or immediate securing of the airway is necessary, e.g., laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible

7. Hyperkalemia • In normal adults, S.C.C increases plasma potassium concentration by 0.3–0.5 mmol/L • Not reliably prevented by pretreatment with nondepolarizer • Conditions causing susceptibility to S.C.C induced hyperkalemia： Anaesthesia 1982; 37:802–5

8. Intragastric pressure • Directly related to the intensity of muscle fasciculations • Pressures as high as 40 cm H2O, cardioesophageal sphincter mechanism may become incompetent and regurgitation and aspiration may occur

9. Intraocular pressure • The major increase in IOP is caused by contraction of extraocular muscles, dilation of choroidal vessels is a contributory factor • IOP begins to increase within 60 s, peaks at 2~3 min, then decreases to control in 5~7 min after succinylcholine administration • Increased IOP can result in extrusion of vitreous and possible loss of vision in a penetrating wound of the eye Can Anaesth Soc J 1986; 33: 195–208 Anesthesiology 2003; 99: 220-3

10. intracranial pressure • Caused an increase in afferent muscle spindle activity as well as an increase in cerebral blood flow • Increased central venous and intracerebral venous pressure • More dramatic in the face of diminished autoregulation associated with acute brain injury Anesth Analg. 1983; 62:1006-9 Br JAnaesth. 1996; 77: 607-11

11. Malignant hyperthermia • The incidence of MH in patients anesthetized with volatile anesthetics and given succinylcholine has been estimated at 1:4,000 to 1:40,000 • Trismus or masseter spasm accompanied by rigidity of the entire body may be associated with a high incidence of MH • Profound rigidity or violent fasciculation, increase in heart rate, a rapid increase in temperature, and in increase in etCO2 • History and family history of MH Anesth Analg 2000; 90: S24-8

12. Pulmonary edema and hemorrhage • Several young children who developed fulminant pulmonary edema within minutes after IM succinylcholine • Responded to continuous positive pressure ventilation • Acute elevation of systemic vascular resistance and an acute decrease in pulmonary vascular resistance Anesth Analg 1981; 60:220–3.

13. Alternatives to succinylcholine

14. Rocuronium • A nondepolarizing, steroidal NMBD similar to vecuronium but with one-eighth to one-tenth the potency. The reduced potency produces a more rapid onset of paralysis Anesthesiology 1989; 70:915–20 • Bolus administration of 0.6 mg/kg (2 × ED95) produces complete neuromuscular blockade of the adductor pollicis in infants and children in 1.1 and 1.3 min • The onset time to maximal block was shorter with succinylcholine but intubating conditions were comparable Pediatr Anaesth 1994; 4:173–7 • Larger doses of rocuronium (0.9–1.2 mg/kg) have been suggested as part of a rapid sequence induction technique Br J Anaesth 1996; 77:335–8

15. Rocuronium versus succinylcholine for rapid sequence induction intubation (Cochrane Review) Cochrane Database of Systematic Reviews. (1):CD002788, 2004

16. Objectives: To determine if rocuronium creates comparable intubating conditions to succinylcholine during RSI intubation • Search strategy: MEDLINE (1966-March 2000), EMBASE (1988-March 2000) and the Cochrane Central Register of Controlled Trials (March 2000) for randomized controlled trials (RCT) or controlled clinical trials (CCT) relating to the use of rocuronium and succinylcholine

17. 40 studies were identified; 26 were combined for analysis • Overall, rocuronium was inferior to succinylcholine, with a RR=0.87 (95%CI = 0.81 to 0.94) (N=1606) • In the group that used propofol for induction of anesthesia, the intubation conditions were similar, with a RR=0.96 (95%CI = 0.87 to 1.06) (N=640) • Conclusion: Succinylcholine created superior intubation conditions to rocuronium when comparing excellent intubation conditions • Intubation conditions were not statistically different between succinylcholine and rocuronium when propofol was used

18. Rapacuronium • The first nondepolarizing relaxant to have both rapid onset and a short duration of neuromuscular blockade • In a large multicenter study, rapacuroniurn 1.5 mg/kg was compared with S.C.C 1.0 mg/kg. When laryngoscopy was started at 50 s, good-to-excellent intubating conditions were seen in 89.4% and 97.4% of cases, respectively Br J Anaesth 1999; 82:537–41 • Cardiovascular side effects and histamine release tend to be more common with low potency drugs, which also have faster onsets. Rapacuroniurn produces mild dose-related tachycardia and hypotension, but these changes are short-lived, and do not seem to be histamine-related Anesth Analg 2000; 90: S2-6

19. Rapacuronium • Bronchospasm or increased airway pressures after tracheal intubation have been reported by several investigators. The incidence of such events was 10.7% after rapacuronium compared with 4.1% after succinylcholine Br J Anaesth 1999; 82:537–41 • Conclusion: The onset time approaches that of succinylcholine, but duration is still slightly longer. Cardiovascular side effects are larger than those of most drugs introduced recently into clinical practice. Respiratory effects still require investigation Anesth Analg 2000; 90: S2-6

20. GW280430A • Asymmetric mixed-tetrahydroisoquinolinium chlorofumarate • Of the drugs in clinical practice, the closest structural resemblance is mivacurium J Med Chem 2003; 46:2502–15 • The onset, almost as rapid as succinylcholine, may be sufficient to facilitate RSI in most clinical situations Anesth Analg 2001; 93:954–9 • Clinically significant histamine release occurred in one of four subjects Anesthesiology 2004; 100:768–73 • May never be released into clinical practice, but it is quite conceivable that a drug closely related to it will be. Anesthesiology 2004; 100:763–4

21. Priming techniques • Small subparalyzing dose, “priming dose,” of a nondepolarizing NMBD several minutes before the “intubating dose” • Large enough to cause approximately 75% occupancy of end-plate receptors but small enough not to cause unpleasant symptoms • Depends on the choice of the relaxant, the size of the priming dose (approximately 15%–20% of the ED95), the intubating dose (multiple of the ED95), and the interval between the two doses • Atracurium, vecuronium, pipecuronium, pancuronium, and rocuronium Anesthesiology 1985; 62:392–5 Anesth Analg 1997; 85:663–6

22. Timing techniques • Administration of a single bolus of nondepolarizing NMBD before the IV induction drug • Ptosis with diplopia or a reduction in hand grip are the usual clinical end points of weakness • The onset of neuromuscular blockade seems faster with timing techniques (60 s) than priming techniques (90 s) and with larger doses of NMBDs • Atracurium, vecuronium, and rocuronium Anesth Analg 1993; 76:998–1003

23. Synergistic mixtures • Combinations of nondepolarizing relaxants, accelerated onset and delayed recovery • Pancuronium with mivacurium • Vecuronium with mivacurium • Rocuronium with mivacurium • Atracurium with mivacurium • Atracurium with vecuronium • The clinical use of these observations is unclear Anesth Analg 1993; 76:998–1003 Anesthesiology 1994; 81:388–95

24. Pre-preparation of succinylcholine: significant waste for questionable benefit Anaesthesia 2004; 59:211

25. Past— “This is a powerful reason to always have succinylcholine drawn up before any anaesthetic” when considering the treatment of laryngospasm Lee's Synopsis of Anaesthesia, 12th edn., 1999: 266 • Now— More “airway-friendly” drugs (e.g. propofol and sevoflurane), advances in fibreoptic intubating techniques and improved monitoring

26. Laryngospasm—perioperative • Remove the stimulus including stopping the surgery if appropriate • CPAP with 100% O2 with or without positive pressure ventilation • Jaw thrust with pressure in the “laryngospasm notch” • Deepen anesthesia with propofol or sevoflurane • Using a short-acting potent intravenous opioid (e.g. alfentanil) if a painful stimulus is the cause • Consider succinylcholine in a dose as low as 0.1 mg/kg

27. Laryngospasm—postoperative • Propofol used at a dose of 0.8 mg.kg 1 has been shown to relieve laryngeal spasm successfully in most children following the removal of a LMA • In the adult population the equivalent dose of propofol is approximately one quarter of the standard induction dose • Deepening of anesthesia can also be achieved with inhalational agents • Intravenous succinylcholine is the relaxant of choice for most clinicians; the dose used varies considerably, from a standard dose of 1.0 mg/kg to as little as 0.1 mg/kg

28. Summary • S.C.C is still the standard NMBD for rapid sequence intubation until a non-depolarizing muscle relaxant with rapid onset, short duration of action and minimal side-effect profile becomes available • Its routine pre-preparation prior to every anesthetic is no longer necessary

29. Have a nice day !!