Why are muscle relaxants used?
Facilitation of tracheal intubation
Rapid sequence induction
Paralysis important for certain types of surgery
Prevents patient movement during delicate surgery
E.g. Neuro or ocular
Allows patient’s ventilation to be controlled
Rapid onset and offset
Not pharmacologically reversible
Numerous s/e and c/i
Compete with ACh for binding at the α subunit of the
Blockade can be reversed with anticholinesterase
Drug Onset (s) Offset (min)
Suxamethonium 60 10
Atracurium 110 43
Mivacurium 170 16
Rocuronium 75 33
Vecuronium 180 33
Modified from Aitkenhead et al.
Allows indirect determination of neuromuscular
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
NDMB causes fade in the amplitude of the twitches
twitch affected first then 3nd
Ratio of amplitude of 4th
twitch = TOF ratio
TOF ratio for safe
extubation is 0.9 (Viby-
twitch must be visible
reversal to be effective
(van Miert et al. 1997) Atracurium
Sux. has rapid onset and offset but many s/e and often
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.
The answer – sugammadex?
A γ cyclodextrin molecule composed of 8 glucose mols
forming a ring
Designed to encapsulate aminosteroid NDMBs, especially
Sugammadex binds rocuronium v tightly and irreversibly
in a 1:1 ratio forming an H2O soluble complex
(Hunter et al. 2006)
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
Better than anticholinesterase?
Flockton et al. 2008
Compared time to recovery of TOF 0.9
followed by sugammadex 2mgkg-1
followed by neostigmine 50μgkg-1
Reversal given at appearance of T2
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)
Reversal of profound block
Standard anticholinesterases only effective after
appearance of T2
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
sugammadex given 3mins after rocuronium
Better than suxamethonium?
Naguib et al. 2007
Compare speed of recovery from 1.2mgkg-1
followed 3 mins later by 16mgkg-1
spontaneous recovery from 1mgkg-1
Total onset-offest time is faster for
rocuronium/sugammadex (4min 47) than suxamethonium
Suxamethonium produces superior intubating conditions
compared to rocuronium (Karcioglu et al. 2006)
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)
More rapid reversal than anticholinesterases with fewer
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
Rocuronium and sugammadex manufactured by Organon
Temptation to rely on rocuronium
Consider the patient
Advancement for advancement’s sake or real benefits?
Potential to use larger doses of rocuronium
Price of sugammadex??
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
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