Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
Jose
ph F
. Ans
win
e, M
DJo
seph
F. A
nsw
ine,
MD
Sta
ff A
nest
hesi
olog
ist
Pin
nacl
e H
ealth
Hos
pita
lsH
arris
burg
, PA
Clin
ical
Ass
ocia
te P
rofe
ssor
of
Ane
sthe
siol
ogy
Pen
nsyl
vani
a S
tate
Uni
vers
ity
Hos
pita
l
Rev
ersa
l of N
euro
mus
cula
r
Rev
ersa
l of N
euro
mus
cula
r
Blo
ckad
eB
lock
ade
Def
initi
ons
Def
initi
ons
ED95
-dos
e re
quire
d to
pro
duce
95%
sup
pres
sion
of
the
first
twitc
h re
spon
se.
2xED
95–
the
ED95
mul
tiplie
d by
2 /
com
mon
ly u
sed
as th
e st
anda
rd in
tuba
ting
dose
for a
NM
BA
.T1
and
T4–
first
and
four
th tw
itch
heig
hts
(usu
ally
gi
ven
as a
% o
f the
orig
inal
twitc
h he
ight
).
Ons
et T
ime
–en
d of
inje
ctio
n of
the
NM
BA
to 9
5%
T1 s
uppr
essi
on.
Rec
over
y Ti
me
–tim
e fro
m in
duct
ion
to 2
5%
reco
very
of T
1 (N
MB
As
are
read
ily re
vers
ed w
ith
acet
ylch
olin
este
rase
inhi
bito
rs a
t thi
s po
int).
Rec
over
y In
dex
–tim
e fro
m 2
5% to
75%
T1.
Phar
mac
okin
etic
s an
d Ph
arm
acok
inet
ics
and
Phar
mac
odyn
amic
sPh
arm
acod
ynam
ics
Wha
t is
Phar
mac
okin
etic
s?Th
e pr
oces
s by
whi
ch a
dru
g is
abs
orbe
d, d
istri
bute
d,
met
abol
ized
and
elim
inat
ed b
y th
e bo
dy.
Wha
t is
Phar
mac
odyn
amic
s?Th
e st
udy
of th
e ac
tion
or e
ffect
s of
a d
rug
on li
ving
or
gani
sms.
Or,
it is
the
stud
y of
the
bioc
hem
ical
and
ph
ysio
logi
cal e
ffect
s of
dru
gs.
For e
xam
ple;
rocu
roni
um re
vers
ibly
bin
ds to
the
post
syn
aptic
en
dpla
te, t
here
by, i
nhib
iting
the
bind
ing
of
acet
ylch
olin
e.
Stru
ctur
al C
lass
es o
f St
ruct
ural
Cla
sses
of
Non
depo
lariz
ing
Rel
axan
tsN
onde
pola
rizin
g R
elax
ants
Ster
oids
: roc
uron
ium
bro
mid
e, v
ecur
oniu
m b
rom
ide,
pa
ncur
oniu
m b
rom
ide,
pip
ecur
oniu
m b
rom
ide.
Ben
zylis
oqui
nolin
ium
s: a
tracu
rium
bes
ylat
e,
miv
acur
ium
chl
orid
e, d
oxac
uriu
m c
hlor
ide,
ci
satra
curiu
m b
esyl
ate
Isoq
uino
lone
s: c
urar
e, m
etoc
urin
e
Ons
et o
f par
alys
is is
affe
cted
by:
Ons
et o
f par
alys
is is
affe
cted
by:
Dos
e(r
elat
ive
to E
D95
)Po
tenc
y(n
umbe
r of m
olec
ules
)K
EO(p
lasm
a eq
uilib
rium
con
stan
t -ch
emis
try/b
lood
flow
) —
dete
rmin
ed b
y fa
ctor
s th
at m
odify
acc
ess
to th
e ne
urom
uscu
lar j
unct
ion
such
as
card
iac
outp
ut, d
ista
nce
of th
e m
uscl
e fro
m th
e he
art,
and
mus
cle
bloo
d flo
w
(pha
rmac
okin
etic
var
iabl
es).
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
90.0
100.
0
060
120
180
240
300
360
420
480
Tim
e (s
ec)
% of Peak Effect
Roc
uron
ium
Vecu
roni
um
Cis
atra
curiu
mAt
racu
rium
Ons
et T
ime
of N
onde
pola
rizin
g N
MB
As
Ons
et T
ime
of N
onde
pola
rizin
g N
MB
As
Kop
man
et a
l. A
nest
h A
nalg
199
9;89
:104
6-9
Ons
et* a
nd re
cove
ry fr
om b
lock
Ons
et* a
nd re
cove
ry fr
om b
lock
Effe
cts
of a
nest
hetic
s on
clin
ical
dur
atio
n Ef
fect
s of
ane
sthe
tics
on c
linic
al d
urat
ion
of ro
curo
nium
bro
mid
e 0.
3 m
g/kg
of ro
curo
nium
bro
mid
e 0.
3 m
g/kg
Ago
ston
S. E
ur J
Ana
esth
esio
l S
uppl
. 199
4;9:
107-
11
Neu
rom
uscu
lar B
lock
ing
Age
nts:
N
euro
mus
cula
r Blo
ckin
g A
gent
s:
Dru
g In
tera
ctio
ns (a
nest
hetic
s)D
rug
Inte
ract
ions
(ane
sthe
tics)
Req
uire
men
ts fo
r NM
BA
s w
ill b
e re
duce
d by
10
% to
25%
whe
n us
ing
pote
nt in
hala
tiona
l ag
ents
suc
h as
isof
lura
ne.
Ther
e ap
pear
s to
be
no c
hang
e in
re
quire
men
ts fo
r NM
BA
s w
hen
usin
g pr
opof
ol
or o
ther
IV a
nest
hetic
s.
Pot
entia
tion
of N
on D
epol
ariz
ing
Age
nts
Pot
entia
tion
of N
on D
epol
ariz
ing
Age
nts
Aci
d-ba
se a
nd e
lect
roly
te d
istu
rban
ces
a. re
spira
tory
aci
dosi
s,b.
mag
nesi
um,
c. c
alci
um,
d. K
+D
rugs
:a.
Ane
sthe
tic in
hala
tion
agen
ts
b. A
ntib
iotic
s H
ypot
herm
iaA
ll th
e ab
ove
are
com
mon
ly p
rese
nt a
t the
end
of a
n an
esth
etic
and
in th
e re
cove
ry ro
om.
Key
Poi
nts:
Eld
erly
and
K
ey P
oint
s: E
lder
ly a
nd
Neu
rom
uscu
lar B
lock
ers
Neu
rom
uscu
lar B
lock
ers
Ther
e is
a s
light
ly s
low
er o
nset
of n
euro
mus
cula
r bl
ocka
de (l
ikel
y se
cond
ary
to s
low
er d
eliv
ery
of
rocu
roni
um to
the
neur
omus
cula
r end
plat
e (K
eo))
.Th
ere
is a
slo
wer
offs
et s
econ
dary
to a
dec
reas
ed
met
abol
ism
of r
ocur
oniu
m (d
ecre
ased
org
an m
ass
and
over
all f
unct
ion
with
nor
mal
agi
ng).
Var
iabi
lity
is m
ore
likel
y as
we
get o
lder
bec
ause
di
seas
e pr
oces
ses
affe
ctin
g th
e ph
arm
acok
inet
ics
and
phar
mac
odyn
amic
s of
NM
BA
s ar
e lik
ely
to b
e pr
esen
t.
Key
Poi
nts:
Chi
ldre
n an
d K
ey P
oint
s: C
hild
ren
and
Neu
rom
uscu
lar B
lock
ers
Neu
rom
uscu
lar B
lock
ers
Ther
e is
a fa
ster
ons
et in
neo
nate
s bu
t a d
elay
ed
offs
et.
This
is li
kely
sec
onda
ry to
an
imm
atur
e ne
urom
uscu
lar e
ndpl
ate
lead
ing
to a
qui
cker
ons
et,
and
an im
mat
ure
liver
and
kid
neys
lead
ing
to s
low
er
met
abol
ism
and
a d
elay
ed o
ffset
. In
chi
ldre
n (1
to 5
yea
rs),
the
onse
t tim
e an
d th
e du
ratio
n ap
proa
ch y
oung
adu
lts a
s or
gan
syst
ems
com
plet
e th
eir d
evel
opm
ent.
Som
e Ph
ysio
logy
(of
Som
e Ph
ysio
logy
(of
the
Neu
rom
uscu
lar
the
Neu
rom
uscu
lar
junc
tion)
junc
tion)
Wha
t are
we
talk
ing
abou
t?W
hat a
re w
e ta
lkin
g ab
out?
The
Neu
rom
uscu
lar J
unct
ion
(NM
J)Th
e N
euro
mus
cula
r Jun
ctio
n (N
MJ)
The
NM
J is
a c
hem
ical
syn
apse
with
a n
euro
nal p
re-s
ynap
tic
term
inal
whe
re A
ch is
rele
ased
, and
a p
ost-s
ynap
tic
mem
bran
ew
here
the
chol
iner
gic
rece
ptor
s re
side
.A
ch is
syn
thes
ized
in th
e pr
e-sy
napt
ic te
rmin
al b
y ch
olin
e-O
-ac
etyl
tran
sfer
ase
from
cho
line
and
acet
ate.
Ach
is s
tore
d in
the
cyto
plas
m o
f the
pre
-syn
aptic
term
inal
and
tra
nspo
rted
into
ves
icle
s w
hich
are
mov
ed in
to p
ositi
on fo
r re
leas
e. E
ach
vesi
cle
cont
ains
app
roxi
mat
ely
5 x
10 to
the
3rd
mol
ecul
es o
f Ach
.Th
e ve
sicl
es a
re a
ligne
d ex
actly
opp
osite
the
conv
olut
ions
(w
here
nic
otin
ic re
cept
ors
are
conc
entra
ted
on th
e po
st-
junc
tiona
l mus
cle
mem
bran
e).
A
cety
lcho
lines
tera
se (A
chE
) is
pres
ent i
n th
e ar
ea o
f the
ch
olin
ergi
c re
cept
or to
dea
ctiv
ate
the
Ach
.
The
Neu
rom
uscu
lar J
unct
ion
The
Neu
rom
uscu
lar J
unct
ion
Stru
ctur
e of
the
Ace
tylc
holin
e St
ruct
ure
of th
e A
cety
lcho
line
Rec
epto
rR
ecep
tor
It is
a p
enta
mer
ic s
ite.
The
five
subu
nits
are
arr
ange
d in
a ro
sette
aro
und
a N
a-K
ioni
c ch
anne
l.E
ach
rece
ptor
has
two
Ach
rece
ptiv
e si
tes.
Two
Ach
mol
ecul
es m
ust b
ind
to th
e re
cept
or to
ope
n th
e ch
anne
l.Th
e po
tenc
y of
a N
MB
A d
epen
ds o
n ho
w w
ell t
he
agen
t fits
into
the
rece
ptor
(e. g
. cis
-atra
curiu
m [0
.1-
0.2
mg/
kg] i
s m
ore
pote
nt th
an ro
curo
nium
[0.6
m
g/kg
], th
eref
ore,
it m
ust b
e a
bette
r “fit
” with
the
re
cept
or).
The
Ace
tylc
holin
e R
ecep
tor
The
Ace
tylc
holin
e R
ecep
tor
Phys
iolo
gy o
f the
Neu
rom
uscu
lar
Phys
iolo
gy o
f the
Neu
rom
uscu
lar
Junc
tion
Junc
tion
An
actio
n po
tent
ial r
esul
ts in
rele
ase
of A
ch a
t the
pre
-syn
aptic
te
rmin
al.
AC
h in
tera
cts
with
(neu
rom
uscu
lar)
NM
rece
ptor
s at
the
end-
plat
e.D
epol
ariz
atio
n of
the
end-
plat
e m
embr
ane
resu
lts.
Mus
cle
cont
ract
ion
is in
itiat
ed.
AC
h is
inac
tivat
ed b
y ac
etyl
chol
ines
tera
se (A
ChE
).M
echa
nism
s of
Neu
rom
uscu
lar B
lock
ade
Rec
epto
r blo
ckad
e (n
on-d
epol
ariz
ing
agen
ts)
Dep
olar
izat
ion
of th
e en
d-pl
ate
(dep
olar
izin
g ag
ents
)Th
e ef
fect
of n
euro
mus
cula
r blo
ckad
e is
ske
leta
l mus
cle
para
lysi
s.
The
post
The
post
-- syn
aptic
term
inal
: a
syna
ptic
term
inal
: a
redu
ndan
t sys
tem
redu
ndan
t sys
tem
So, h
ow d
o w
e re
vers
e So
, how
do
we
reve
rse
neur
omus
cula
r blo
ckad
e?ne
urom
uscu
lar b
lock
ade?
Roc
uron
ium
bro
mid
e 0.
6 m
g/kg
Roc
uron
ium
bro
mid
e 0.
6 m
g/kg
reve
rsal
of b
lock
reve
rsal
of b
lock
Ther
e ar
e tw
o co
mpo
nent
s Th
ere
are
two
com
pone
nts
invo
lved
with
the
reve
rsal
of
invo
lved
with
the
reve
rsal
of
neur
omus
cula
r blo
ckad
e; re
mov
al
neur
omus
cula
r blo
ckad
e; re
mov
al
of th
e N
MB
A fr
om th
e of
the
NM
BA
from
the
neur
omus
cula
r jun
ctio
n by
ne
urom
uscu
lar j
unct
ion
by
redi
strib
utio
n an
d m
etab
olis
m,
redi
strib
utio
n an
d m
etab
olis
m,
and
chem
ical
reve
rsal
with
Ach
E an
d ch
emic
al re
vers
al w
ith A
chE
inhi
bito
rs.
in
hibi
tors
.
Ace
tylc
holin
este
rase
(Ach
E) In
hibi
tors
A
cety
lcho
lines
tera
se (A
chE)
Inhi
bito
rs
Neo
stig
min
e (p
rost
igm
in),
edro
phon
ium
(ten
silo
n),
pyrid
ostig
min
e (m
estin
on) a
re m
ost c
omm
only
use
d as
reve
rsal
ag
ents
.Th
eir p
rimar
y m
ode
of a
ctio
n is
the
inhi
bitio
n of
Ach
E (th
eref
ore
allo
win
g th
e ne
urot
rans
mitt
er a
cety
lcho
line
to b
e pr
esen
t at t
hene
urom
uscu
lar j
unct
ion
long
er).
Ons
et o
f act
ion:
Edr
opho
nium
(1-2
min
), N
eost
igm
ine
(7-1
1 m
in),
pyrid
ostig
min
e (1
6 m
in)
The
reas
on fo
r the
rapi
d on
set o
f edr
opho
nium
as
com
pare
d to
th
e ot
her t
wo
is n
ot c
lear
. A
ll th
ree
inhi
bit A
chE
as
soon
as
they
bi
nd w
ith th
e en
zym
e.
Neo
stig
min
e an
d py
ridos
tigm
ine
are
hydr
olyz
ed b
y Ac
hE.
The
enzy
me
is c
arba
myl
ated
in th
e pr
oces
s re
duci
ng it
s ab
ility
to
hydr
olyz
e ac
etyl
chol
ine.
Edr
opho
nium
is n
ot b
roke
n do
wn
by A
chE.
The
inte
ract
ion
is
com
petit
ive
and
reve
rsib
le.
The
actu
al d
urat
ion
of a
ctio
n of
all
thre
e is
1-2
hou
rs.
We
neve
r se
e it
clin
ical
ly in
the
OR
bec
ause
the
neur
omus
cula
r blo
ckin
g ag
ents
are
usu
ally
met
abol
ized
fast
er.
Dos
ing
of A
chE
Inhi
bito
rsD
osin
g of
Ach
E In
hibi
tors
Edr
opho
nium
–0.
5 –
1.0
mg/
kg
(M
ax. e
ffect
1 m
inut
e)N
eost
igm
ine
-0.
03 –
0.06
mg/
kg
(Max
. effe
ct 7
min
utes
)P
yrid
ostig
min
e –
0.25
mg/
kg
(Max
. effe
ct 1
0-13
min
utes
)
The
dura
tion
of a
ctio
n fo
r all
thre
e ag
ents
is a
bout
1-2
ho
urs.
Ant
icho
liner
gic
Dru
gs (d
osin
g) w
ith 0
.5
Ant
icho
liner
gic
Dru
gs (d
osin
g) w
ith 0
.5
to 1
.0 m
g/kg
Edr
opho
nium
or 5
0 to
70
to 1
.0 m
g/kg
Edr
opho
nium
or 5
0 to
70
mic
rogr
am/k
g N
eost
igm
ine
mic
rogr
am/k
g N
eost
igm
ine
Atr
opin
e–
10 m
icro
gram
/kg
Gly
copy
rrol
ate
–5
to 1
0 m
icro
gram
/kg
(Usu
ally
giv
en o
ne m
inut
e be
fore
Ed
roph
oniu
m)
Ant
agon
ism
of r
ocur
oniu
m b
rom
ide
Ant
agon
ism
of r
ocur
oniu
m b
rom
ide
(0.6
mg/
kg)
(0.6
mg/
kg)
Ada
pted
from
: Nag
uib
et a
l Ane
sthe
siol
ogy
1993
;79:
739-
745
N =
neo
stig
min
e
E =
edro
phon
ium
chl
orid
e
Ant
agon
ism
of r
ocur
oniu
m b
rom
ide
Ant
agon
ism
of r
ocur
oniu
m b
rom
ide
(0.6
mg/
kg)
(0.6
mg/
kg)
Ada
pted
from
: Nag
uib
et a
l Ane
sthe
siol
ogy
1993
;79:
739-
745
Is th
ere
a di
ffere
nt m
echa
nism
of
Is th
ere
a di
ffere
nt m
echa
nism
of
actio
n be
twee
n A
chE
inhi
bito
rs?
Wha
t ac
tion
betw
een
Ach
E in
hibi
tors
? W
hat
do w
e kn
ow?
do w
e kn
ow?
Edr
opho
nium
and
neo
stig
min
e ar
e no
t equ
ally
ef
fect
ive
espe
cial
ly w
ith m
ore
inte
nse
leve
ls o
f bl
ocka
de.
The
onse
t of e
drop
honi
um is
fast
er th
an th
e ot
hers
ev
en th
ough
the
inhi
bitio
n of
Ach
E is
felt
to o
ccur
im
med
iate
ly u
pon
its b
indi
ng w
ith a
ll of
the
agen
ts.
Edr
opho
nium
ass
iste
d an
tago
nism
of A
chE
is k
now
n to
hav
e a
“flat
ter”
dose
-resp
onse
cur
ve th
an th
at o
f ne
ostig
min
e.
Dos
e / R
espo
nse
Cur
ves
(Ach
E D
ose
/ Res
pons
e C
urve
s (A
chE
Inhi
bito
rs)
Inhi
bito
rs)
Ace
tylc
holin
este
rase
Inhi
bito
rs:
Ace
tylc
holin
este
rase
Inhi
bito
rs:
Poss
ible
Alte
rnat
ive
Mec
hani
sms
of
Poss
ible
Alte
rnat
ive
Mec
hani
sms
of
Act
ion
Act
ion
Pre
syna
ptic
effe
cts
(eith
er b
y di
rect
ly
bind
ing
to, o
r by
havi
ng a
n in
crea
sed
amou
nt o
f Ach
pre
sent
at t
he
pres
ynap
tic re
cept
or)
Dire
ct a
ctio
n (b
indi
ng) a
t the
po
stsy
napt
ic a
cety
lcho
line
rece
ptor
Cei
ling
Effe
ct o
f Ace
tylc
holin
este
rase
C
eilin
g Ef
fect
of A
cety
lcho
lines
tera
se
Inhi
bito
rsIn
hibi
tors
Side
Effe
cts
of A
chE
Inhi
bito
rsSi
de E
ffect
s of
Ach
E In
hibi
tors
card
iac
arrh
ythm
ias
(esp
ecia
lly
brad
ycar
dia)
bron
choc
onst
rictio
nin
crea
sed
saliv
atio
n?
incr
ease
d in
cide
nce
of n
ause
a an
d vo
miti
ng (m
any
stud
ies
disa
gree
with
th
is h
ypot
hesi
s)w
eakn
ess
in c
erta
in p
atie
nt p
opul
atio
ns
Dra
wba
cks
to A
cety
lcho
lines
tera
se
Dra
wba
cks
to A
cety
lcho
lines
tera
se
Inhi
bito
rs
Inhi
bito
rs
They
are
“ind
irect
” act
ing
agon
ists
for A
ch.
You
can
not e
ffect
ivel
y re
vers
e pr
ofou
nd (T
1 <
10%
ba
selin
e) b
lock
ade
of th
e ne
urom
uscu
lar j
unct
ion
(the
time
to a
chie
ving
ext
ubat
ion
crite
ria w
ith o
r with
out
reve
rsal
usi
ng a
n A
chE
inhi
bito
r fro
m a
pro
foun
d bl
ock
is th
e sa
me)
. M
ultip
le o
r exc
essi
ve d
oses
of
Ach
E in
hibi
tors
may
incr
ease
the
degr
ee o
f res
idua
l bl
ocka
de.
The
effe
ct is
not
sel
ectiv
e, th
eref
ore,
ther
e ar
e a
few
si
de e
ffect
s w
ith th
eir u
se s
uch
as; i
ncre
ased
sa
livat
ion,
bra
dyca
rdia
, tea
ring,
mio
sis
and
bron
choc
onst
rictio
n.
They
mus
t be
give
n w
ith o
ther
dru
gs s
uch
as a
tropi
ne
and
glyc
opyr
rola
te to
ant
agon
ize
the
mus
carin
ic
effe
cts
of A
ch.
Ach
E in
hibi
tors
are
not
true
“res
cue”
reve
rsal
age
nts
for t
he “c
anno
t ven
tilat
e / c
anno
t int
ubat
e” p
atie
nt.
The
Tim
e to
Ade
quat
e R
ever
sal w
ith
The
Tim
e to
Ade
quat
e R
ever
sal w
ith
Ach
E In
hibi
tors
Dep
ends
on
the
Ach
E In
hibi
tors
Dep
ends
on
the
Spec
ific
NM
BA
.Sp
ecifi
c N
MB
A.
Inte
rmed
iate
Act
ing
Age
nts
(e. g
. roc
uron
ium
, ve
curo
nium
) -7
–12
min
utes
Long
Act
ing
Age
nts
(e. g
. pan
curo
nium
, cur
are)
–20
–40
min
utes
How
do
we
asse
ss a
dequ
acy
of
How
do
we
asse
ss a
dequ
acy
of
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
Twitc
h M
onito
rTw
itch
Mon
itor
Trai
n O
f Fou
r (co
mpa
re th
e 4t
htw
itch
to th
e 1s
ttw
itch)
You
wan
t the
ratio
of t
he fo
urth
/firs
t tw
itch
to b
e >
0.7
(act
ually
cur
rent
thou
ght i
s th
at a
ratio
of >
0.9
is
need
ed).
S
usta
ined
Tet
anus
D
oubl
e B
urst
Stim
ulat
ion
TOF
is u
sual
ly a
sses
sed
by v
isua
l ins
pect
ion
and
not
usin
g qu
antit
ativ
e m
easu
res
(acc
eler
omyo
grap
hy
and
mec
hano
myo
grap
hy).
Sus
tain
ed T
etan
us a
nd D
oubl
e B
urst
Stim
ulat
ion
are
also
ver
y di
fficu
lt to
qua
ntify
.
How
do
we
asse
ss a
dequ
acy
of
How
do
we
asse
ss a
dequ
acy
of
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
Oth
er C
linic
al In
dica
tors
Oth
er C
linic
al In
dica
tors
Hea
d Li
ft (5
or 1
0 se
cond
s)Le
g Li
ft (in
chi
ldre
n)H
and
Gra
spN
egat
ive
Insp
irato
ry F
orce
(NIF
)H
ead
Lift
> 10
sec
onds
is b
est,
but s
omet
imes
it is
har
d to
get
th
e pa
tient
to fo
llow
the
com
man
d to
lift
his/
her h
ead.
Kop
man
et.
al. (
1997
) –th
e to
ngue
dep
ress
or te
st –
If a
patie
nt
can
gras
p a
tong
ue d
epre
ssor
bet
wee
n hi
s/he
r tee
th a
nd it
ca
nnot
be
pulle
d ou
t, th
e TO
F is
like
ly >
0.8
5 an
d up
per a
irway
m
uscu
lar f
unct
ion
is li
kely
inta
ct.
Som
e H
isto
rySo
me
His
tory
Ali
et. a
l. (1
970
and
1971
) –W
hen
4 st
imul
i wer
e de
liver
ed a
t 0.
5-s
inte
rval
s, th
ere
was
a p
rogr
essi
ve fa
de o
f suc
cess
ive
resp
onse
s de
pend
ing
on th
e ex
tent
of c
urar
izat
ion.
TO
F w
as
defin
ed.
At v
alue
s of
> 0
.7, n
o ev
iden
ce o
f par
alys
is w
as n
oted
.E
ngba
ek e
t. al
. (19
89) –
This
stu
dy d
escr
ibed
the
tech
niqu
e of
“d
oubl
e bu
rst s
timul
atio
n” in
resp
onse
to c
ompl
aint
s of
di
fficu
lties
in th
e cl
inic
al a
sses
smen
t of T
OF
fade
.B
rull
et. a
l. (1
990)
–Th
ey n
oted
a c
lose
line
ar re
latio
nshi
p be
twee
n TO
F an
d do
uble
bur
st s
timul
atio
n.
How
do
we
asse
ss T
OF
fade
?H
ow d
o w
e as
sess
TO
F fa
de?
Mec
hano
myo
gram
(MM
G),
EM
G a
nd a
ccel
ogra
phy
can
be
used
, how
ever
the
equi
pmen
t can
be
expe
nsiv
e an
d di
fficu
lt to
us
e.M
ost o
f us
rely
on
the
subj
ectiv
e as
sess
men
t of t
he T
OF.
Vib
y-M
ogen
sen
et. A
l. (1
985)
–TO
F fa
de w
ent f
requ
ently
un
dete
cted
(eve
n va
lues
as
low
as
abou
t 0.4
).D
upui
s et
. al.
(199
0) –
Sust
aine
d te
tanu
s w
as n
oted
at T
OF
ratio
s of
< 0
.5.
Dre
nck
et. a
l. (1
989)
–Th
e ab
ility
to id
entif
y fa
de in
crea
sed
to a
le
vel o
f 0.6
with
dou
ble
burs
t stim
ulat
ion
(stil
l not
> 0
.7).
Rem
embe
r tha
t man
y be
lieve
that
a T
OF
ratio
> 7
0% is
stil
l in
adeq
uate
(> 9
0% is
nee
ded)
.
Cla
ssic
Tea
chin
g St
ates
that
a
Cla
ssic
Tea
chin
g St
ates
that
a
TOF
ratio
of 0
.7 (A
li et
. al.
1981
) TO
F ra
tio o
f 0.7
(Ali
et. a
l. 19
81)
is a
n A
ppro
pria
te L
evel
of
is a
n A
ppro
pria
te L
evel
of
Rev
ersa
l for
Ext
ubat
ion.
Rev
ersa
l for
Ext
ubat
ion.
Wha
t is
an a
ppro
pria
te T
OF
ratio
for
Wha
t is
an a
ppro
pria
te T
OF
ratio
for
adeq
uate
reve
rsal
(wha
t som
e st
udie
s ad
equa
te re
vers
al (w
hat s
ome
stud
ies
have
not
ed)?
have
not
ed)?
TOF
ratio
of 0
.63
–Yo
u m
ay s
ee p
atie
nts
com
plai
n of
diff
icul
ty
brea
thin
g an
d sw
allo
win
g as
wel
l as
a de
crea
sed
insp
irato
ry
forc
e an
d pe
ak fl
ow ra
te.
TOF
ratio
of 0
.7 to
0.7
5 –
You
may
see
dip
lopi
a, d
ecre
ased
grip
st
reng
th, i
nabi
lity
to s
it up
with
out a
ssis
tanc
e, fa
cial
wea
knes
s an
d di
fficu
lty s
wal
low
ing
and
spea
king
. A
lso,
stu
dies
hav
e sh
own
decr
ease
d co
ordi
natio
n of
eso
phag
eal m
uscu
latu
re a
nd
phar
ynge
al d
ysfu
nctio
n le
adin
g to
a 4
to 5
fold
incr
ease
in th
e ris
k of
asp
iratio
n (E
rikss
on e
t. al
. 199
7).
Pha
ryng
eal f
unct
ion
retu
rns
to n
orm
al w
ith a
TO
F ra
tio o
f 0.9
.TO
F of
0.8
5 –
You
may
see
gen
eral
dis
com
fort,
mal
aise
, pto
sis,
an
d bl
urre
d vi
sion
.TO
F of
0.9
–Yo
u m
ay s
ee s
igni
fican
t vis
ual d
istu
rban
ces
such
as
dip
lopi
a an
d di
fficu
lty tr
acki
ng o
bjec
ts.
Rec
ent s
tudi
es in
Hum
ans
Indi
cate
R
ecen
t stu
dies
in H
uman
s In
dica
te
that
the
“Bar
” fo
r an
Acc
epta
ble
that
the
“Bar
” fo
r an
Acc
epta
ble
Leve
l of R
ecov
ery
of
Leve
l of R
ecov
ery
of
Neu
rom
uscu
lar F
unct
ion
shou
ld
Neu
rom
uscu
lar F
unct
ion
shou
ld
be R
aise
d to
a T
OF
Rat
io o
f
be R
aise
d to
a T
OF
Rat
io o
f
> 0.
90.
> 0.
90.
Clin
ical
Eva
luat
ion
Clin
ical
Eva
luat
ion
Dam
and
Gul
dman
n (1
961)
–de
scrib
ed th
e “h
ead
lift”
as a
re
liabl
e si
gn o
f mus
cle
pow
er [d
idn’
t spe
cify
the
dura
tion]
Man
y ha
ve d
emon
stra
ted
that
a h
ead
lift f
or >
5 s
econ
ds is
a
relia
ble
indi
cato
r of a
dequ
ate
reve
rsal
of n
euro
mus
cula
r bl
ocka
deA
li et
. al.
(197
1) –
no p
atie
nt w
ith a
TO
F ra
tio <
0.4
cou
ld li
ft hi
s/he
r hea
d of
f of t
he b
ed
Hut
ton
et. a
l. (1
976)
–5
seco
nd h
ead
lift h
owev
er d
oes
not
guar
ante
e th
at v
olun
tary
func
tion
has
retu
rned
to n
orm
al o
r tha
tth
ey a
re c
omfo
rtabl
e.M
any
patie
nts
will
not
follo
w th
e co
mm
and
to li
ft th
eir h
ead,
or
they
will
not d
o it
seco
ndar
y to
pai
n fro
m th
e su
rgic
al s
ite.
Usi
ng “h
and
grip
” is
muc
h le
ss re
liabl
e.In
infa
nts,
a le
g lif
t cor
rela
ted
with
a “N
IF” (
nega
tive
insp
irato
ry
forc
e) o
f -58
cm
H2O
to -7
1 cm
H2O
ther
efor
e it
is a
reas
onab
le
indi
cato
r of r
etur
n of
neu
rom
uscu
lar f
unct
ion
in th
is p
opul
atio
n.
Neg
ativ
e In
spira
tory
For
ce (N
IF)
Neg
ativ
e In
spira
tory
For
ce (N
IF)
Ben
dixe
n et
. al.
–Th
ey s
ugge
sted
that
the
max
imum
neg
ativ
e pr
essu
re (n
egat
ive
insp
irato
ry fo
rce
gene
rate
d ag
ains
t a c
lose
d ai
rway
) cou
ld b
e a
mea
sure
men
t of v
entil
ator
y re
serv
e.W
esco
tt et
. al.
(196
2) –
sugg
este
d th
at a
s lit
tle a
s -2
0 cm
H2O
in
dica
ted
suffi
cien
t ven
tilat
ory
rese
rve.
-25
cm H
2O to
-30
cm H
2O b
ecam
e an
acc
epta
ble
goal
for
dete
rmin
ing
reco
very
of n
euro
mus
cula
r fun
ctio
n.H
owev
er, i
t has
bee
n sh
own
that
a h
ead
lift o
f 5 s
econ
ds
corr
elat
ed w
ith a
NIF
of -
50 c
m H
2O.
Pav
lin e
t. al
. -At
-25
cm H
2O o
r les
s N
IF, n
o pa
tient
cou
ld
swal
low
or m
aint
ain
an a
irway
.
How
do
we
asse
ss a
dequ
acy
of
How
do
we
asse
ss a
dequ
acy
of
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
reve
rsal
of n
euro
mus
cula
r blo
ckad
e?
(Joe
’s R
ules
)(J
oe’s
Rul
es)
(1) T
witc
h M
onito
r –(2
) Clin
ical
Indi
cato
rs –
(3) O
ur
unde
rsta
ndin
g of
the
usua
l dur
atio
n of
act
ion
of a
pa
rticu
lar N
MB
AR
ule
1 -I
f any
one
of t
he th
ree
indi
cato
rs is
not
ad
equa
te, r
ever
sal i
s in
dica
ted.
Rul
e 2
–If
ther
e ar
e m
ore
than
one
ane
sthe
sia
prov
ider
invo
lved
in th
e ca
se, e
very
one
mus
t agr
ee
on th
e ad
equa
cy o
f rev
ersa
l of n
euro
mus
cula
r bl
ocka
de.
If no
t, re
vers
al is
indi
cate
d.R
ule
3 –
The
side
effe
cts
of re
vers
al a
gent
s ar
e an
noyi
ng, t
he c
ompl
icat
ions
of p
rem
atur
e ex
tuba
tion
coul
d be
dea
dly.
Shou
ld y
ou re
vers
e or
not
?Sh
ould
you
reve
rse
or n
ot?
Rec
over
y is
qui
cker
and
mor
e re
liabl
e w
ith in
term
edia
te a
ctin
g ag
ents
.Lu
nn e
t. A
l. –
11of
32
deat
hs d
ue to
ane
sthe
sia
wer
e se
cond
ary
to
post
-ope
rativ
e re
spira
tory
failu
re.
Neu
rom
uscu
lar b
lock
ade
was
a
defin
ite c
ontri
buto
r in
six
of th
e ca
ses.
Tire
t et.
Al.
–50
% o
f 65
deat
hs d
ue to
ane
sthe
sia
wer
e re
late
d to
pos
t-op
erat
ive
resp
irato
ry fa
ilure
.C
oope
r et.
Al.
–24
of 5
3 ad
mis
sion
s to
the
ICU
sec
onda
ry to
an
esth
esia
rela
ted
prob
lem
s w
ere
seco
ndar
y to
pos
t-ope
rativ
e re
spira
tory
failu
re a
nd re
sidu
al n
euro
mus
cula
r blo
ckad
e.B
ailla
rd e
t. A
l. –
With
an
incr
ease
d us
e of
qua
ntita
tive
mea
sure
men
ts o
f ne
urom
uscu
lar b
lock
ade
(TO
F) a
nd th
e us
e of
reve
rsal
age
nts,
resi
dual
bl
ocka
de (T
OF
< 90
%) d
ecre
ased
from
62%
to 3
% [b
etw
een
1995
and
20
04].
Deb
aene
et.
al. –
In p
atie
nts
not r
ecei
ving
reve
rsal
age
nts,
a T
OF
ratio
of
< 0
.7 o
ccur
red
37%
of t
he ti
me
two
hour
s af
ter a
sin
gle
dose
of
NM
BA
. C
aldw
ell e
t. al
. –Th
ey fo
und
a TO
F <
0.7
up to
4 h
ours
afte
r a s
ingl
e
intu
batin
g do
se o
f vec
uron
ium
.M
any
toda
y us
e a
TOF
> 90
% (i
nste
ad o
f > 7
0%) a
s an
indi
cato
r of
appr
opria
tere
turn
ofne
urom
uscu
larf
unct
ion.
Shou
ld y
ou re
vers
e or
not
? Sh
ould
you
reve
rse
or n
ot?
(con
tinue
d)
(con
tinue
d)
The
surg
ical
pat
ient
pop
ulat
ion
is b
ecom
ing
olde
r and
will
like
ly
have
the
pres
ence
of c
onco
mita
nt d
isea
se b
oth
lead
ing
to a
de
crea
sed
clea
ranc
e of
the
NM
BA
s.Fu
rther
mor
e, th
e po
pula
tion
is b
ecom
ing
incr
easi
ngly
mor
e de
bilit
ated
whe
n co
mpa
red
to a
few
yea
rs a
go.
Ane
sthe
tics
are
beco
min
g sh
orte
r act
ing
(e. g
. rem
ifent
anil,
de
sflu
rane
, sev
oflu
rane
and
pro
pofo
l), th
eref
ore,
pat
ient
s ar
e fu
lly a
wak
e m
ore
quic
kly.
Sur
gerie
s ar
e be
ing
done
on
an a
mbu
lato
ry b
asis
at i
ncre
asin
g ra
tes,
ther
efor
e, p
atie
nts
are
expe
cted
to b
e aw
ake,
wal
k ou
t of
the
cent
er a
nd b
e fu
nctio
nal a
t hom
e ea
rlier
.
Shou
ld y
ou re
vers
e or
not
?Sh
ould
you
reve
rse
or n
ot?
The
bene
fits
outw
eigh
the
risks
of g
ivin
g re
vers
al a
gent
s in
mos
t situ
atio
ns.
Wha
t do
I fre
quen
tly te
ll m
y te
enag
ers?
Wha
t do
I fre
quen
tly te
ll m
y te
enag
ers?
“You
can
mes
s up
any
thin
g if
you
try
hard
eno
ugh!
!!”
Org
259
69 (S
ugam
mad
ex)
Org
259
69 (S
ugam
mad
ex)
The
1stse
lect
ive
rela
xant
bin
ding
age
nt (S
RB
A)
It is
a s
ynth
etic
cyc
lode
xtrin
esp
ecia
lly d
esig
ned
to
bind
the
ster
oida
l NM
BA
rocu
roni
umO
rg 2
5969
cau
ses
a do
se d
epen
dant
fast
reco
very
of
neur
omus
cula
r blo
ckad
e of
rocu
roni
umIt
is ra
pidl
y ex
cret
ed b
y th
e ki
dney
sTh
e re
vers
al o
f the
neu
rom
uscu
lar b
lock
ade
is
depe
nden
t on
the
bind
ing
of th
e N
MB
A n
ot th
e ex
cret
ion
of th
e dr
ug b
y th
e ki
dney
s
Ther
e do
es n
ot a
ppea
r to
be s
igni
fican
t sid
e ef
fect
s w
ith th
is d
rug.
Org
259
69O
rg 2
5969
Org
259
69 (g
reen
) and
Org
259
69 (g
reen
) and
Roc
uron
ium
(blu
e)R
ocur
oniu
m (b
lue)
Org
259
69 a
dmin
iste
red
5 m
inut
es
Org
259
69 a
dmin
iste
red
5 m
inut
es
afte
r 1.2
mg/
kg o
f Roc
uron
ium
unt
il af
ter 1
.2 m
g/kg
of R
ocur
oniu
m u
ntil
TOF
> 90
%
TOF
> 90
%
plac
ebo
(n=4
)122
:05
2.0
mg.
kg-1
(n=
5)56
:30
min
utes
4.0
mg.
kg-1
(n=
5)15
:47
min
utes
8.0
mg.
kg-1
(n=
12)2
:45
min
utes
12.0
mg.
kg-1
(n=7
)1:2
3 m
inut
es16
.0 m
g.kg
-1 (n
=7)1
:55
min
utes
Sid
e E
ffect
s: T
hree
pat
ient
s ha
d Q
T pr
olon
gatio
n, b
ut n
one
wer
efe
lt to
be
seco
ndar
y to
OR
G 2
5969
. Tw
o re
actio
ns m
ay h
ave
been
sec
onda
ry to
OR
G
2596
9; d
iarr
hea
and
mov
emen
t und
er li
ght a
nest
hesi
a.
[200
5] [A
1117
] Rev
ersa
l of R
ocur
oniu
m-In
duce
d (1
.2 m
g.kg
-1) N
euro
mus
cula
r B
lock
by
Org
259
69: A
Mul
ti C
ente
r Dos
e Fi
ndin
g an
d Sa
fety
Stu
dy
“Firs
t Hum
an E
xpos
ure
of O
rg 2
5969
, a
“Firs
t Hum
an E
xpos
ure
of O
rg 2
5969
, a
Nov
el A
gent
to R
ever
se th
e A
ctio
n of
N
ovel
Age
nt to
Rev
erse
the
Act
ion
of
Roc
uron
ium
Bro
mid
e”.
Gijs
enbe
rgh
et. a
l.
Roc
uron
ium
Bro
mid
e”.
Gijs
enbe
rgh
et. a
l.
Ane
sthe
siol
ogy
2005
; 103
: 695
Ane
sthe
siol
ogy
2005
; 103
: 695
-- 703703
29 h
ealth
y m
ales
, Org
259
69 v
s. p
lace
bo, g
iven
3
min
utes
afte
r Roc
uron
ium
Bro
mid
e (0
.6 m
g/kg
)S
ix d
iffer
ent d
oses
of O
rg 2
5969
wer
e us
ed (0
.1
mg/
kg to
0.8
mg/
kg).
Sid
e ef
fect
s in
clud
ed; d
ry m
outh
, fas
cicu
latio
ns a
nd
pare
sthe
sias
. N
one
requ
ired
treat
men
t.W
ithin
2 m
inut
es, t
he p
atie
nts
rece
ivin
g 8
mg/
kg o
f O
rg 2
5969
reac
hed
a TO
F ra
tio o
f > 0
.9 w
ithin
two
min
utes
.C
oncl
usio
ns:
Org
259
69 w
as w
ell t
oler
ated
and
ve
ry e
ffect
ive
in re
vers
ing
Roc
uron
ium
Bro
mid
e in
29
hum
an v
olun
teer
s.
[Abs
trac
t A11
19] A
noth
er s
tudy
[A
bstr
act A
1119
] Ano
ther
stu
dy
look
ing
at R
ocur
oniu
m (0
.6 m
g/kg
) and
lo
okin
g at
Roc
uron
ium
(0.6
mg/
kg) a
nd
Vecu
roni
um (0
.1 m
g/kg
)Ve
curo
nium
(0.1
mg/
kg)
Roc
uron
ium
Vec
uron
ium
Pla
cebo
3
1:48
+/-2
1:00
(min
:sec
) 48
:45+
/-27:
530.
5 m
g/kg
3:
40+/
-1:0
2
7:43
+/-2
:34
1.0
mg/
kg
2:19
+/-0
:35
2:
30+/
-0:4
92.
0 m
g/kg
1:
43+/
-0:3
6
2:15
+/-0
:48
3.0
mg/
kg
1:53
+/-1
:10
1:
31+/
-0:3
24.
0 m
g/kg
1:
07+/
-0:1
8
1:24
+/-0
:28
Sid
e E
ffect
s: (r
ocur
oniu
m) t
achy
card
ia (v
ecur
oniu
m) a
bdom
inal
pai
n,
mild
ery
them
a, a
nd d
elay
ed re
cove
ry fr
om a
nest
hesi
a
Wha
t if y
ou h
ave
to re
intu
bate
(re
Wha
t if y
ou h
ave
to re
intu
bate
(re --
para
lyze
) afte
r the
use
of O
rg 2
5969
? pa
raly
ze) a
fter t
he u
se o
f Org
259
69?
Ant
on e
t. al
. (A
SA
abs
tract
s / A
-114
4 / 2
004)
“Afte
r ind
uctio
n of
neu
rom
uscu
lar b
lock
ade
with
rocu
roni
um a
nd ra
pid
reve
rsal
with
Org
25
969,
the
non-
ster
oida
l NM
BA
s (a
tracu
rium
, cis
-atra
curiu
m, m
ivac
uriu
m a
nd
succ
inyl
chol
ine)
wer
e st
ill p
oten
t and
ef
ficac
ious
.”“…
show
ing
that
Org
259
69 h
as a
ver
y lo
w
affin
ity fo
r non
-ste
roid
al N
MB
As.
”
(Sug
amm
adex
) Que
stio
ns y
et to
be
(Sug
amm
adex
) Que
stio
ns y
et to
be
answ
ered
:an
swer
ed:
Wou
ld S
ugam
mad
exbe
equ
ally
as
effe
ctiv
e af
ter a
pr
olon
ged
infu
sion
of v
ecur
oniu
m o
r roc
uron
ium
in
the
ICU
, or e
ven
repe
ated
dos
es in
the
OR
?
Wha
t dos
e of
Sug
amm
adex
is re
quire
d in
an
elde
rly
seve
rely
ill p
atie
nt, a
pat
ient
with
ele
ctro
lyte
ab
norm
aliti
es, o
r a p
atie
nt o
n m
ultip
le m
edic
atio
ns
know
n to
pot
entia
te N
MB
As?
“Rev
ersa
l of N
euro
mus
cula
r “R
ever
sal o
f Neu
rom
uscu
lar
Blo
ckad
e”; A
nest
hesi
olog
y, 7
7: 7
85B
lock
ade”
; Ane
sthe
siol
ogy,
77:
785
--80
5, 1
992
(Bev
an e
t. al
.)
805,
199
2 (B
evan
et.
al.)
Q
uest
ions
any
one?
??
??
?
?
?
??
?