1. Recovery from NMBA : problems and solutions
Wirat Wasinwong
Anesthesia department
Faculty of Medicine
Prince of Songkla University

2. Muscle relaxant 1912 : curare 1970s : pancuronium
1980s : vecuronium, cisatracurium, mivacurium, rocuronium
rapacuronium

3. Ideal muscle relaxant Onset Duration Metabolite/accumulation Safety
Reversibility
Cost

4. Rocuronium Dose 0.6-0.9 mg/kg Onset 60-90 sec. Duration 20-40 min.
Minimal cardiovascular effect
Hepatorenal excretion

5. Dam and Goldman
“ Today, the most common cause of postoperative respiratory inadequacy is the use and misuse of muscle relaxant drugs”
Anesthesiology 1961; 22:

6. Postoperative residual curarization (PORC)
1979
Residual postoperative weakness
Incomplete recovery
Ventilatory complications

7. Kopman, Yee and Neuman
“ normal vital muscle function, including normal pharyngeal function, requires the TOF ratio at the adductor pollicis to recover to > 0.9 ”
Anesthesiology 1997; 86:765-71

8. relationship between receptor occupancy and neuromuscular monitoring

9. no neuromuscular block
A.H. Bom , Dept. Pharmacology, Organon Newhouse, Scotland, UK

10. Minimal residual paralysis
Impair pharyngeal muscle function
Reduce lower esophageal sphincter tone
Increase risk
Aspiration
Upper airway obstruction
Impair hypoxic ventilatory response
Eriksson LI, et al. Anesthesiology 1997;87:
Eikerman M, et al. Anesthesiology 2003; 98:
Eriksson LI, et al. Anesthesiology 1993;78:

11. Incidence of residual block
Study year n TOF NDMR PORC reverse
Cammu G <O cisatracurium % Y
rocuronium
Gatke MR < roc with TOF
without TOF
Hayes AH < vecuronium
atracurium
rocuronium
Baillaed C <O vecuronium N
Berg H < pancuronium
atr, vec
Shorten GD panc with TOF
wthout TOF

12. Debeane B,et al. Anesthesiology,2003;98(5):1042-8

13. Naguib M, et al. Br J Anaesth 2007;98(3):302-16.

14. Murphy GS,et al. Anesth Analg 2004,98:193-200

15. Berg H,et al. Acta Anaesthesiol Scand 1997;41:1095

16. Pancuronium in cardiac surgery
Increase duration of weaning and tracheal extubation
Significant muscle weakness after tracheal extubation
Murphy GS, et al. Anesth Analg 2002;95: Murphy GS, et al. Anesth Analg 2003;96:1301-7
Thomas R, et al. Anaesthsia 2003;58:265-70

17. How to avoid PORC Avoid long acting NMBA Avoid unnecessary deep block
Antagonize block at the end
Do not initiate reversal before
Spontaneous muscle activity presents
3 or 4 response of TOF
Use reliable clinical evaluation
Objective neuromuscular monitoring

18. Objective neuromuscular monitoring is evidence based practice
Ericksson LI. Anesthesiology 2003;98:

19. Claudius C, et al. Anesthesiology 2008;8(6):1117-40

20. Claudius C, et al. Anesthesiology 2008;8(6):1117-40

21. Neuromuscular blockade reversal

22. Disadvantages of anticholinesterases
Inability to antagonize profound block
Relatively slow onset of action to peak1
neostigmine (7–11 min)
pyridostigmine (15–20 min)
Muscarinic effects
bradycardia and hypotension
bronchoconstriction and excessive secretions
nausea and vomiting
1. Bevan DR et al. Anesthesiology. 1992; 77:785–805

23. Sugammadex

24. top / bottom view
side view
a-cyclodextrin
6 glucose units
b-cyclodextrin
7 glucose units
g-cyclodextrin
8 glucose units

25. Hydrophilic exterior : polar hydroxyl group
Hydrophobic cavity

26. Carboxyethyl group
Quaternary nitrogen

27. Sugammadex Water-soluble complex formation
1:1 ratio with steroidal muscle relaxants
rocuronium > vecuronium >> pancuronium

28. Sugammadex
No effects on acetylcholinesterase or any other receptors (nicotinic, muscarinic)
Acid-base change: no effects on sugammadex efficacy

29. Pharmacokinetics Elimination half-life ≈100 min Clearance 120 mL/min
similar to normal glomerular filtration rate
Volume of distribution 18 L
> blood volume, but substantially < the volume of the extracellular space
59–80% of administered dose excreted in the urine over 24 h
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703

30. Sugammadex increases renal excretion of rocuronium
14% of an administered rocuronium dose is excreted in the urine within 0–24 h
With concomitant administration of sugammadex (8.0 mg/kg at 3 min) renal excretion of rocuronium within 0–24 h increased to 39–68%
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703

31. Sugammadex
Drugs that potentiate effects of neuromuscular blocking agents (Mg2+, aminoglycosides) may need higher sugammadex dose
Other steroids
Cortisone, atropine, verapamil
time < rocuronium
Clinical insignificant

32. Clinical studies

33. Randomized, placebo-controlled, assessor-blinded trial
Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex : A Dose-finding and Safety Study Sorgenfrei IF. Anesthesiology 2006; 104:667–74
Randomized, placebo-controlled, assessor-blinded trial
27 male patients.
0.6 mg/kg rocuronium
Sugammadex 0.5, 1, 2, 3 ,4 mg/kg at T2 of TOF

35. 5-min reversal after rocuronium
Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex A Multicenter, Dose-finding and Safety Study de Boer, HD, et al. Anesthesiology 2007; 107:239–44
phase II, multicenter,assessor-blinded, placebo-controlled, parallel study.
43 patients
5-min reversal after rocuronium
Adverse effects : diarrhea, light anesthesia

37. After rocuronium 0.6 mg/kg.
Early Reversal of Profound Rocuronium-induced Neuromuscular Blockade by Sugammadex in a Randomized Multicenter Study Efficacy, Safety, and Pharmacokinetics Sparr HJ, et al. Anesthesiology 2007; 106:935–43
98 male adult patients
Reversal at 3,5 and 15 min
After rocuronium 0.6 mg/kg.
Adverse effect: sucking, moving, glimace, cough

40. Anesth Analg 2007;104(3):569-74

41. Sugammadex 3 times more rapid than edrophonium
10 times more rapid than neostigmine

42. Side effects Hypotension Cough Vomitting Dry mouth Abnormal smell
Sensation of a changed temperature
Abnormal level of N-acetyl glucosaminidase in urine

43. Safety Biologically inactive Not bind to plasma proteins
Sugammadex well tolerated in studies to date
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703

44. Limitation succinylcholine, benzylisoquinolinium Ineffective
After reversing with sugammadex
: difficult ,unpredictable dose of rocuronium, vecuronium to re-establish block
: more intense block benzylisoquinolinium
: decrease dose

45. Limitation
Cost
Sugammadex-rocuronium complex in renal disease : unclear
Reverse profound block with inadequate dose : incomplete recovery

46. Approval of Sugammadex   11-Mar-08 07:05 pm 
Schering-Plough announces the FDA Advisory Committee unanimously recommends U.S. approval of sugammadex, the first and only selective relaxant binding agent ( ) -Update- Co announced that the U.S. Food and Drug Administration (FDA) Advisory Committee on Anesthetics and Life Support has recommended sugammadex for approval. After reviewing data on the safety

47. Gantacurium Lack of accumulation Dose 2.5-3 x ED95
Maximum block onset within 90 sec.
25-75% recovery index = 3 min.
7 min. for mivacurium
9 min. for rapacuronium
14 min. for cisatracurium
Clinical duration < 10 min.
Complete recovery to TOF>0.9 within 15 min.

48. Thank you