HOT
TOPIC
Suggamadex
Final
clinical trials are currently underway in the United States and
Europe testing sugammadex, a member of a new class of reversal drugs,
which may dramatically alter the practice of anesthesiology. Su
refers to sugar and gammadex refers to the structural molecule,
a modified cyclodextrin.
Mechanism
of Action
The
three-dimensional structure of sugammadex resembles a doughnut with
a hydrophobic cavity and a hydrophilic exterior. Hydrophobic interactions
trap the drug into the cyclodextrin cavity (the doughnut hole) forming
a very tight complex at a 1:1 ratio with steroidal neuromuscular
blocking drugs (rocuronium > vecuronium >> pancuronium)
causing a rapid and long-acting reversal of neuromuscular blockade.
Side
Effects
Sugammadex
is biologically inactive, does not bind to plasma proteins, and
appears to be safe and well tolerated..
Effects
on Other Drugs
Steroids
Sugammadex
does form complexes with naturally occurring steroidal molecules
but at a much lower affinity.
Neuromuscular
Blocking Agents
This
drug cannot be used to reverse neuromuscular blockade induced by
succinylcholine and benzylisoquinolinium neuromuscular blockers.
Speed
of Recovery
Reversal
of neuromuscular blockade is exceedingly rapid. Sugammadex
(8 mg/kg IV) administered 3 minutes after rocuronium (0.6 mg/kg)
returned the TOF ration to 0.9 within 2 minutes. The speed
of recovery from neuromuscular blockade induced by rocuronium (1.2
mg/kg IV) followed by 3 min later by sugammadex (16 mg/kg IV) is
shorter than the spontaneous recovery of neuromuscular function
than from succinylcholine.
Impact
on the Practice of Anesthesiology
- Would
the use of sugammadex prevent anesthesiologists from encountering
a patient whose neuromuscular blockade is hard to reverse at the
end of surgery?
-
Would anesthesiologists still need to use neuromuscular function
monitoring with sugammadex?
-
If the rocuronium induction followed by sugammadex reversal achieves
or exceeds the reliability of succinylcholine, will this mark
the end of years of effort searching for the Holy Grail of Neuromuscular
Blocking Agents?
-
Will succinylcholine and the benzylisoquinolinium drugs (cis-atracurium
and atracurium) remain on the hospital formulary ?
Economic
Considerations
If
sugammadex is to replace neostigmine as an antagonist for rocuronium-induced
neuromuscular blockade, then this clinical decision will depend
in part on the cost of the drug and the improvement in patient outcomes
that occurs with its use.
Release
Date:
In
August 2008 Schering-Plough announced that the FDA issued a "not-approvable"
letter for sugammadex for the reversal of rocuronium- or vecuronium.
The company will work with the agency to address the issues noted
in the letter.
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