Sugammadex - a revolution in anaesthesia?

1. James Harper

2. Why are muscle relaxants used?
Facilitation of tracheal intubation
Rapid sequence induction
Paralysis important for certain types of surgery
E.g. abdominal
Prevents patient movement during delicate surgery
E.g. Neuro or ocular
Allows patient’s ventilation to be controlled
ITU

3. Muscle Relaxants
Depolarising
Suxamethonium
Rapid onset and offset
Not pharmacologically reversible
Numerous s/e and c/i
Non-depolarising
Compete with ACh for binding at the α subunit of the
nAChR
Blockade can be reversed with anticholinesterase
Drug Onset (s)Offset (min)
Suxamethonium60 10
Atracurium 110 43
Mivacurium 170 16
Rocuronium 75 33
Vecuronium 180 33
Modified from Aitkenhead et al.

4. ACh e
ACh
NDMB
Neostig.

5. Neuromuscular monitoring
Allows indirect determination of neuromuscular
transmission
Should be performed whenever a NMB is used (Eriksson
et al. 2003)
Train-of-four (TOF) twitch response
Electric current applied in bursts of 4 to the ulnar nerve
Response in adductor policis measured
(acceleromyography)
NDMB causes fade in the amplitude of the twitches
4
th
twitch affected first then 3
nd
, 2
nd
and 1
st

Ratio of amplitude of 4
th
:1
st
twitch = TOF ratio

6. Train-of-four
TOF ratio for safe
extubation is 0.9 (Viby-
Mogensen 2000)
2
nd
twitch must be visible
for anticholinesterase
reversal to be effective
(van Miert et al. 1997)
Atracurium

7. Current problems
Sux. has rapid onset and offset but many s/e and often
c/i
What would the alternative be for R.S.I?
Rocuronium has rapid onset but in a ‘cannot intubate
cannot ventilate’ situation return to spontaneous breathing
is too slow
Reversal of profound ND blockade is not possible
PORC vs inadequate blockade
Lack NM monitoring despite recommendation →
unrecognised PORC (Grayling 2007, Eriksson 2003)
Reversal with neostigmine/edrophonium +
parasympatholytic cumbersome. CVS effects and PONV.

8. The answer – sugammadex?
A γ cyclodextrin molecule composed of 8 glucose mols
forming a ring
Designed to encapsulate aminosteroid NDMBs, especially
rocuronium (rocuronium>vecuronium>>pancuronium)
Sugammadex binds rocuronium v tightly and irreversibly
in a 1:1 ratio forming an H
2
O soluble complex
(Hunter et al. 2006)
(Naguib 2007)

9. Modifed from Naguib 2007

10. Sugammadex – mechanism of action
Sugammadex has its action in the plasma, not at the NMJ
Rocuronium is encapsulated in the plasma
Concentration gradient between free rocuronium in the
plasma and rocuronium at the NMJ
Rocuronium diffuses away from the NMJ into the plasma
where it is chelated by sugammadex
nAChRs become free at the NMJ allowing neuromuscular
transmission to resume
Gijsenbergh et al. 2005

11. Better than anticholinesterase?
Flockton et al. 2008
Compared time to recovery of TOF 0.9
Rocuronium 0.6mgkg
-1
followed by sugammadex 2mgkg
-1
Cisatracurium 0.15mgkg
-1
followed by neostigmine 50μgkg
-1
Reversal given at appearance of T
2
Mean time to recovery
Rocuronium/sugammadex 1.9 min
Cisatracurium/neostigmine 9.0 min (p<0.0001)
Greater change in HR in neostigmine group (glycopyrrolate)

12. Reversal of profound block
Standard anticholinesterases only effective after
appearance of T
2
Sparr et al. 2007
98 anaesthetised patients given rocuronium 0.6mgkg
-1
Randomised to varying doses of sugammadex or placebo 3,
5 or 15 mins after rocuronium
Recovery to 0.9 TOF reduced from 52.1 mins to 1.8 mins
when 8mgkg
-1
sugammadex given 3mins after rocuronium

13. Better than suxamethonium?
Naguib et al. 2007
Compare speed of recovery from 1.2mgkg
-1
rocuronium
followed 3 mins later by 16mgkg
-1
sugammadex with
spontaneous recovery from 1mgkg
-1
suxmaethonium
Total onset-offest time is faster for
rocuronium/sugammadex (4min 47) than suxamethonium
(9min 23)
Suxamethonium produces superior intubating conditions
compared to rocuronium (Karcioglu et al. 2006)

14. Is sugammadex safe?
No serious adverse effects have been reported to date
QT ↑ (Gijsenbergh et al.), transient BP↓ (de Boer et al.) and
↑ urinary N-acetyl glucosaminidase (Flockton et al.)
Rocuronium/sugammadex excreted mainly in the urine
(Gijsenbergh et al.) – renal failure?
No known effect on any receptor system, no need for
anti-muscarinic – cardiovascular stability
Equally effective under maintenance anaesthesia with
propofol as sevoflurane (unlike neostigmine) (Vanacker
et al. 2007)

15. Applications
More rapid reversal than anticholinesterases with fewer
s/e
More rapid turnaround of surgical patients
Ability to antagonise a profound block
Larger doses of rocuronium can be used with confidence
Less PORC in the absence of neuromuscular monitoring
Rapid onset-offset of rocuronium/sugammadex
Could replace suxamethonium for R.S.I

16. Considerations
Ethical
Rocuronium and sugammadex manufactured by Organon
Temptation to rely on rocuronium
Consider the patient
Advancement for advancement’s sake or real benefits?
Economic
Potential to use larger doses of rocuronium
Price of sugammadex??

17. Conclusions
Sugammadex is a more efficacious reversal agent of
rocuronium than anticholinesterases
Replacement of anticholinesterases → benefits for the
patient, anaesthetist and surgeon
Suxamethonium may be replaced for R.S.I
Fewer s/e and c/i with rocuronium/sugammadex
More rapid onset-offset profile?
Routine use of sugammadex will depend upon economic
considerations

19. References
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th
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20. References
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