Transcript xenon, suggamadex,Recent advances

Recent advances – 1 – MGMC
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab. DCA,
Dip. Software statistics,
PhD(physiology)
Xenon
• Xenon derives its name from the Greek for
`stranger' because of its rarity, representing
0.0875 ppm.
• It is odorless, nonpungent, nontoxic,
nonexplosive, environmentally friendly
A bit history
• Discovered in 1898, it is manufactured by fractional
distillation of air and is used commercially for lasers,
high intensity lamps, ash bulbs, jet propellant in the
aerospace industry, X-ray tubes, and in medicine.
• Anesthetic practice for fifty years …
• Xenon potently inhibits N-methyl-D-aspartate
(NMDA) receptors non-competitively,
• with little effect on GABA A receptors or nonNMDA glutamatergic receptors
• Xenon has been reported to competitively
inhibit 5HT3 A receptor
• MAC value of 63 % -- 71 %
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Blood gas partition coefficient of 0.15 %
Fast in and out
Better than nitrous and desflurane
Ideal in opd procedures
CVS
• Hemodynamic stable
• No change in HR –
• -decreased cortisol and catecholamines
• Less need for fentanyl
• Normal LV function assessed by TEE
CNS
xenon increases CBF;
despite changes in CBF, reactivity to carbon dioxide is
maintained , changes in blood flow can be reversed
with hyperventilation
• CMRO2 may not change
• Analgesic
• in contrast to other anaesthetics that require
anaesthetic or supra‐anaesthetic doses to act as a
neuroprotectant, xenon may be effective at more
clinically acceptable concentrations
Greatness
• xenon has no mutagenic or carcinogenic
properties.
• No embryotoxic or teratogenic changes were
found in pregnant women
• No malignant hyperthermia
• No damage to liver and kidney profiles
• No damage to coagulation and platelet
profiles
Then what's the problem
• The cost will work out 350 US $ for a case
• Recycling may decrease
• xenon appears to be environmentally safe.
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Summary
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Stranger
B/G 0.15
MAC - 71%
Fastest recovery
Cardiostable
Neuroprotective
Analgesia
Cost
Recycling
Sugammadex
Sugammadex
• Anton Bom working for a cyclodextrin to
solubilize rocuronium
• Found it engulfing
• Possibly tested in vivo
• Reversal agent for future ??
• Su – sugar ----- gammadex – gamma
cyclodextrin
Cyclodextrin molecule with water solubility and lipid engulfment
• Sugammadex exerts its action by forming very tight
complexes in 1:1 ratio with steroidal neuromuscular
blocking drugs (rocuronium > vecuronium >>
pancuronium) and functions as an irreversible
chelating agent.
• Bound suggamadex eliminated via the kidney
Aminosteroid only
• Sugammadex has no effect on acetylcholinesterase.
• This eliminates the need for anticholinergic drugs, thus
avoiding their undesirable side effects.
• It
is
ineffective
against
succinylcholine
and
benzylisoquinolinium neuromuscular blockers, such as
mivacurium, atracurium and cisatracurium
• Sugammadex at doses of 2.0- 4.0 mg /kg has
been shown to safely reverse moderate NMB
induced by rocuronium in a dose dependent
manner in surgical patient
• 0.5 Vs 7.5 minutes
• Even after rocuronium infusions
• 16 mg /kg – CICV situations with rocuronium
Formulation
• The drug is available in IV formulation only;
vials of 200 mg (2 ml) or 500 mg (5 ml) and is
for non-refrigerated storage
• Old age pediatrics – ok
• But less than 2 years – ??
Side effects
• hypotension, coughing, movement, vomiting, dry
mouth,
parosmia,
a
sensation
of
changed
temperature
• Paresthesia
of
the
arm
of
intravenous
administration
• Endogenous steroidal hormones and steroidal drugs
lack the quaternary nitrogen which rocuronium and
vecuronium possess- no clinical impact
• should be avoided in pregnant and lactating
patients till studies are conducted and its
safety is proven.
• Kidney failure – go for cis atracurium rather
than sugammadex
• Around 4000 rupees
After reversal, surgeon tells , I have
forgotten to keep drainage tube
Yes we can give back rocuronium
But better use nonsteroidal drugs
Tips
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Relaxant use during skin closure – ok
CICV – best
No recurarization, but --Knowledge of TOF count and dosage
adjustment of sugammadex needed
• Rocuronium-sugammadex complex can be
displaced by fusidic acid or high doses of
flucloxacillin
Summary
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Gamma cyclo dextrin
Water and fat soluble
Encapsulation of amino steroids –
but endo steroids
Rapid reversal without anticholinesterase side
effects , CICV !!
• 2 – 16 mg / kg --Recurarization ?? side effects ?
• Re injection ? Kidney failure , pregnancy ,
• less than 2 years ?