New Perspectives on Neuromuscular Blockade and Reversal--A Relaxed Update

Presented by Sarah E. Giron, PhD, CRNAUniversity of Southern CaliforniaClinical Assistant Professor of AnesthesiologyEmail: sarah.giron@med.usc.edu

¤W

hile this p

rese

ntatio

n wa

s de

velo

pe

d ind

ep

end

ently o

f influe

nce

s or fina

ncia

l ince

ntives fro

m M

erc

k, I do

d

isclo

se tha

t I have

co

nsulted

for M

erc

k Sharp

& D

ohm

e

Co

rpo

ratio

n in the p

ast a

nd c

ontinue

to p

rovid

e

ed

uca

tiona

l lec

tures fo

r them

. I do

not o

wn sto

ck, no

r ha

ve I re

ce

ived

any m

onie

s or b

ene

fits to p

rese

nt this info

rma

tion to

you to

da

y. If you ha

ve a

ny que

stions

ab

out m

y involve

me

nt with M

erc

k ple

ase

do

not he

sitate

to

co

ntac

t me

at sa

rah.g

iron@

me

d.usc

.ed

u.

My D

isclo

sure To

You:

Prese

ntatio

n Ob

jec

tives

¤Re

view

and

disc

uss the p

hysiolo

gic

and

p

harm

ac

olo

gic

al ro

les o

f neuro

musc

ular

blo

cka

de

in the c

are

of the

surgic

al

pa

tient.

¤Esta

blish the

imp

lica

tions o

f neuro

musc

ular

blo

cka

de

in curre

nt CRN

A p

rac

tice

.

¤C

om

pa

re a

lterna

tive, ne

w ne

urom

uscula

r b

loc

kad

e m

od

alitie

s.

¤Re

view

curre

nt neuro

musc

ular

blo

cking

ag

ents a

nd c

urrent re

versa

l o

ptio

ns for surg

ica

l pa

tients.

¤Pre

sent ne

urom

uscula

r blo

cka

de

m

onito

ring style

s and

co

mp

are

their

use in c

urrent C

RNA

pra

ctic

e.

http://w

ww

.ca

rtoo

nstoc

k.co

m/d

irec

tory/r/re

me

dia

l.asp

Prese

ntatio

n Ove

rview

¤N

euro

musc

ular Blo

cka

de

(NM

B)¤

Physiolo

gy a

nd Pha

rma

co

log

y of N

MB

¤D

ep

ola

rizing vs. N

on-D

ep

ola

rizing A

ge

nts

¤M

onito

ring o

f NM

B

¤Re

versa

l of N

MB

¤A

nticho

lineste

rase

s¤

Antic

holine

rgic

s¤

Suga

mm

ad

ex

(Bridio

n®)

¤O

ther A

ge

nts Being

De

velo

pe

d

Ne

urom

uscula

r Bloc

kad

e

¤A

Quic

k Ana

tom

ic a

nd

Physiolo

gic

Revie

w

¤The

Ne

urom

uscula

r Junc

tion (N

MJ)

¤M

oto

r Ne

rve Te

rmina

l (p

resyna

ptic

).

¤M

oto

r End Pla

te o

f M

uscle

Fibe

rs (p

ostsyna

ptic

).

¤A

s a m

oto

r nerve

p

ote

ntial re

ac

hes the

te

rmina

l, Ca

2+

cha

nnels o

pe

n and

c

ause

Ac

h filled

ve

sicle

s to fo

rm a

nd

op

en into

the syna

ptic

c

left.

http://mynotes4usm

le.tumblr.com

/post/34773331063/houseofmind-the-neurom

uscular-junction-nmj-is

Physiolo

gy o

f NM

B

¤O

nce

Ac

h co

mb

ines w

ith bo

tha

lpha

sub

units of the

nico

tinic re

ce

pto

r on

the p

ostsyna

ptic

me

mb

rane

, the

cha

nnel is o

pe

ned

ca

using K

+to

d

iffuse o

ut and

Na

+a

nd C

a2+

to

diffuse

in. This diffusio

n initiate

s a

de

po

lariza

tion w

hich (if it re

ac

hes the

thre

shold

po

tentia

l) initiate

s an a

ctio

n p

ote

ntial a

nd c

ause

s a m

uscle

c

ontra

ctio

n.

http://www.blobs.org/science/article.php?article=39

Ac

tion Po

tentia

l co

nt.

It All Sta

rted

with C

urare

http://he

rbo

laria

.wikia

.co

m/w

iki/Cura

rehttp

://ethno

bo

tany09.p

rovid

enc

e.w

ikispa

ce

s.net/C

urare

http://lisa

swrito

pia

.co

m/flying

-de

ath/

A Re

laxing

Histo

ry…

We

lliver. (2012). A

AN

A J, S11-17.

1884 First p

ublishe

d

study o

n C

urare

1941 C

urare

first used

in surg

ica

l pa

tients

1949 G

alla

mine

&

Me

toc

urine

de

velo

pe

d

1951 Suc

cinylc

holine

d

eve

lop

ed

1958 First ne

rve

stimula

tor

introd

uce

d

1964-68 The

first stero

ida

l N

MBA

s introd

uce

d:

Alc

uronium

and

Pa

ncuro

nium 1981

Ve

curo

nium

& A

trac

urium

introd

uce

d

1994 Ro

curo

nium &

C

isatra

curium

d

eve

lop

ed

1991 M

ivac

urium

introd

uce

d 2000

Rap

ac

uronium

intro

duc

ed

De

po

larizing

vs. No

n-De

po

larizing

M

uscle

Rela

xants

¤D

ep

ola

rizing M

uscle

Rela

xants: Suc

cinylc

holine

¤Sux is the

only d

ep

ola

rizing m

uscle

rela

xantin c

linica

l use. It

has a

rap

id o

nset (30-60se

c) a

nd sho

rtd

uratio

n(3-5min).

¤U

nlike N

on-D

ep

ola

rizers, Sux’s a

ctio

n in musc

le re

laxa

tion

oc

curs b

ec

ause

it mim

ics the

ac

tion o

f Ac

h . Ne

urom

uscula

r b

loc

kad

e d

eve

lop

s be

ca

use the

de

po

larize

d m

em

bra

ne

ca

nnot re

spo

nd to

subse

que

nt rele

ase

s of A

ch (Pha

se I

blo

cka

de

).

¤A

single

larg

e d

ose

, rep

ea

ted

do

ses o

r a c

ontinuo

us infusion

lea

ds to

po

stjunctio

nal m

em

bra

nes tha

t do

not re

spo

nd to

A

ch no

rma

lly. This ca

n be

ca

used

by re

ce

pto

r d

ese

nsitizatio

n, ion c

hanne

l blo

cka

de

or e

ntranc

e o

f Sux into

the ske

leta

l musc

le c

ytop

lasm

(Phase

II blo

cka

de

).

Side

Effec

ts of Suc

cinylc

holine

Why W

e Like

It:

¤Sp

onta

neo

us ventila

tion b

y the p

atie

nt resum

es ra

ther

quic

kly.

Why W

e D

on’t:

¤C

ard

iac

Dysrhythm

ias

¤Bra

dyc

ard

ia, junc

tiona

l rhythms a

nd sinus a

rrest.

¤H

ype

rkale

mia

¤Susta

ined

op

ening

of p

ostjunc

tiona

lrec

ep

tors a

re

asso

cia

ted

with le

aka

ge

of K+ o

n ave

rag

e 0.5

mEq

/liter. H

ype

rkale

mia

ma

y oc

cur in p

atie

nts with

musc

ular d

ystrop

hy, burns, a

nytime

there

’s skele

tal

musc

le a

trop

hy (96 hrsto

6 mo

nths afte

r injury), se

vere

traum

a a

nd up

pe

r mo

tor ne

uron le

sions.

¤M

yalg

ia¤

Fasic

ulatio

ns(o

uch!)

Side

Effec

ts of Suc

cinylc

holine

¤M

yog

lob

inuria¤

From

skele

tal m

uscle

da

ma

ge

.

¤Inc

rea

sed

Intrag

astric

Pressure

¤Se

co

nda

ry to inte

nsity of m

uscle

fasic

ulatio

ns.

¤Inc

rea

sed

Intrao

cula

r Pressure

¤M

axim

um inc

rea

ses se

en 2-4 m

in afte

r ad

ministra

tion a

nd c

an

last 5-10m

in.

¤Inc

rea

sed

ICP

¤Susta

ined

Skele

tal M

uscle

Co

ntrac

tion

¤Inc

om

ple

te ja

w re

laxa

tion a

nd m

asse

ter m

uscle

rigid

ity ca

n b

e se

en o

cc

asio

nally in c

hildre

n

¤M

alig

nant H

ype

rtherm

ia

No

n-De

po

larizing

Musc

le

Rela

xants

¤U

nlike Sux, N

on-D

ep

ola

rizing M

uscle

Rela

xants (N

DM

Rs) ac

t thro

ugh c

om

pe

titive a

ntag

onism

at the

NM

J. Only o

ne

alp

ha sub

unit on the

nico

tinic re

ce

pto

r nee

ds to

be

b

loc

ked

to p

reve

nt ac

tion p

ote

ntial p

rop

ag

atio

n.

http://www.sagentpharm

a.com/rocuroni

um-brom

ide-injection.html

http://www.bedfordlabs.com

/our_products/online_catalog/products/vecuronium

.html

http://hospira.com/products_an

d_services/drugs/PANCURONI

UM_BROMIDE

http://whataf

y.com/atracu

rium-

besylate-injection.html

https://www.anesthesio

logyhub.com/mivacron.

html

https://www.anesthesiologyh

ub.com/nim

bex.html

A Sum

ma

ry

Gustafson & Brow

n US Pharm

.2017;42(1):HS16-H

S20.

Spo

ntane

ous Re

versa

l of

ND

MRs

¤Sp

onta

neo

us reve

rsal is slo

w a

nd unp

red

icta

ble

.

¤Re

sidua

l blo

ck is a

ssoc

iate

d w

ith rare

but p

ote

ntially

serio

us risks: asp

iratio

n, imp

aire

d hyp

oxic

ventila

tory

resp

onse

, pulm

ona

ry co

mp

lica

tions (yuc

k!)Ca

rroll e

t al. (1998). A

naes, 53, 1169–1173.

Let’s Ta

lk Ab

out H

ow

We

Mo

nitor

Para

lysis

http://salestores.com/sunm

ed81053601.html

http://neuromuscular-m

onitoring.anesthesia-research.com/

http://en.wikipedia.org/w

iki/Neurom

uscular_monitoring

¤“W

hen ne

urom

uscula

r blo

cking

ag

ents a

re

ad

ministe

red

, mo

nitor ne

urom

uscula

r resp

onse

to

asse

ss de

pth o

f blo

cka

de

and

de

gre

e o

f re

co

very.”

¤A

AN

A Sta

nda

rds o

f Nurse

Ane

sthesia

Prac

tice

p.2

https://w

ww

.aa

na.c

om

/do

cs/d

efa

ult-sourc

e/p

rac

tice

-aa

na-c

om

-we

b-

do

cum

ents-(a

ll)/stand

ard

s-for-nurse

-ane

sthesia

-pra

ctic

e.p

df?sfvrsn=e

00049b1_2

Mo

nitoring

http://intra

op

era

tivene

urom

onito

ring.c

om

/train-o

f-four/

¤C

entra

l musc

les re

co

ver e

arlie

r than p

erip

hera

l musc

les (i.e

. your

dia

phra

gm

rec

ove

rs faste

r than yo

u ad

duc

tor p

ollic

is).¤

Ho

we

ver yo

ur co

rruga

tor sup

erc

iliirec

ove

rs faste

r than the

upp

er

airw

ay a

nd a

dd

ucto

r po

llicis

(i.e. o

vere

stima

tes the

de

gre

e o

f re

co

very).

¤A

TOF ra

tio ≥ 0.9 a

t the a

dd

ucto

r po

llicis

is co

nside

red

ad

eq

uate

re

co

very.

Subje

ctive

vs. Ob

jec

tive M

onito

ring

¤Sub

jec

tive M

onito

ring¤

Also

know

n as Q

ualita

tive

mo

nitoring

.¤

Usua

lly pe

rform

ed

with a

p

erip

hera

l nerve

stim

ulato

r and

visual o

r ta

ctile

asse

ssme

nt of

twitc

hes a

nd fa

de

.¤

Perfo

rme

d in le

ss than

40% o

f pa

tients. 1

¤O

nce

the TO

F ratio

e

xce

ed

s 0.40, mo

st c

linicia

ns ca

nnot d

ete

ct

eithe

r tac

tile o

r visual

fad

e. 2

1.Tho

mse

n et a

l. (2015). Br J Ana

esth, 115, i89-94.2.

Vib

y-Mo

ge

nsen

et a

l. (1985). Anesthesiol, 63, 440-443.

3.Phillip

s et a

l. (2013). Ana

esthIntensive C

are, 41, 374-379.

¤O

bje

ctive

Mo

nitoring

¤A

lso kno

wn a

s Q

uantita

tive m

onito

ring.

¤U

sually p

erfo

rme

d w

ith a

nerve

stimula

tor tha

t ca

n c

alc

ulate

TOF ra

tio.

¤Pe

rform

ed

in less tha

n 17%

of p

atie

nts. 3

http://fro

mne

wto

icu.c

om

/blo

g/2016/3/1

1/train-o

f-four

Ho

w d

o W

e M

ea

sure Re

versa

l in N

DM

Rs?

% o

f Rec

ep

tors

Bloc

ked

Twitc

hes

on TO

F

Clinic

al Re

spo

nse

99-1000 Tw

itche

s Fla

cc

id p

atie

nt

95D

iap

hrag

m M

ove

s

901 Tw

itch

Ab

do

mina

l rela

xatio

n

ad

eq

uate

for m

ost

ab

do

mina

l pro

ce

dure

s

754 Tw

itche

s Tid

al V

olum

e a

nd V

ital

Ca

pa

city N

orm

al

50Pa

ss inspira

tory p

ressure

test

30H

ea

d lift a

nd ha

nd-g

rip

sustaine

d

¤The

5-sec

hea

d lift

wa

s unab

le to

id

entify TO

F ratio

s a

s low

as 0.5 in

mo

re tha

n 70% o

f p

atie

nts. 1-2

¤5-se

c te

tanic

fad

e

ca

n only b

e

relia

bly d

ete

cte

d

whe

n the TO

F ratio

is ≤ 0.3. 3

1.Eike

rma

nne

t al. (2003). A

nesthesiol, 98, 1333-1337.

2.Pe

de

rsen e

t al.(1990). A

nesthesiol, 73, 835-839.3.

Ca

pro

n et a

l. (2006). Anesth

Analg, 102, 1578-

84.

Why Re

verse

Ne

urom

uscula

r Blo

cka

de

?¤

To fa

cilita

te sp

onta

neo

us resp

iratio

n and

ve

ntilatio

n.

¤Sho

rten tim

e in o

pe

rating

roo

m.

¤A

void

resid

ual b

loc

k and

its asso

cia

ted

risks.

¤Re

versa

l of N

DM

Rs is asso

cia

ted

with

de

cre

ase

d risk o

f po

stop

era

tive

mo

rtality a

nd c

om

a. 1

¤D

ec

rea

se the

risk of p

atie

nts e

xpe

rienc

ing the

very

unple

asa

nt effe

cts

of re

sidua

l blo

ck.

¤20-40%

of p

atie

nts exp

erie

nce

re

sidua

l NM

B in the PA

CU

2-3

1.A

rbo

usM

H e

t al. (2005). A

nesthesiol,102, 257–268.2.

He

iere

t al. (2012). Br J A

naesth, 108, 444-451.3.

Fortie

r et a

l. (2015). Anesth

Analg, 121, 366-372.

Disa

dva

ntag

es o

f Antic

holine

stera

ses

¤The

se a

ge

nts ca

nnot re

verse

pro

found

blo

cka

de

.

¤A

de

qua

te re

versa

l is not a

lwa

ys po

ssible

and

there

is alw

ays

a risk o

f resid

ual b

loc

kad

e (N

atio

nal A

vera

ge

s site 16-42%

ha

ve re

sidua

l blo

cka

de

in the PA

CU

). 1

¤M

urphy e

t al. sho

we

d 88%

of p

atie

nts have

resid

ual b

loc

kad

e

at e

xtuba

tion. 1

¤Ko

pm

an

et a

l. show

ed

that 50%

of p

atie

nts have

resid

ual

blo

cka

de

in PAC

U. 2

¤PA

CU

nurses re

po

rt that re

sidua

l NM

B is one

of the

three

mo

st c

ritica

l eve

nts that the

y fac

e tha

t req

uires e

me

rge

ncy

interve

ntion. 3

¤O

nset tim

es o

f antic

holine

stera

ses a

re d

iffere

nt:¤

Endro

pho

nium1-2 m

in¤

Ne

ostig

mine

7-11 min

1.A

nesAna

lg2005; 100:1840-1845.

2.A

nesAna

lg2004; 98: 102-106.

3.Stra

uss & Le

wis (2015). O

R Nurse, 9, 24-30.

Antic

holine

stera

ses c

ont.

Side

Effec

ts:

¤D

ec

rea

ses in b

loo

d p

ressure

se

co

nda

ry to d

ec

rea

ses in SV

R

¤Bra

dyc

ard

ia

¤Po

orly m

eta

bo

lized

by re

nal

failure

pa

tients (50%

of

Ne

ostig

mine

and

75% o

f End

rop

honium

and

Pyrid

ostig

mine

are

rena

llym

eta

bo

lized

)

¤Enha

nce

s ga

stric se

cre

tions

¤Inc

rea

ses m

otility o

f GI tra

ct

¤Inc

rea

sed

incid

enc

e o

f PON

V

¤Inc

rea

se p

rod

uctio

n of se

cre

tions

¤Bro

ncho

co

nstrictio

na

nd

incre

ase

d a

irwa

y resista

nce

¤M

iosis

¤D

ec

rea

sed

IOP

¤The

refo

re, the

se a

ge

nts should

be

a

dm

inistere

d w

ith an

Antic

holine

rgic

!!

Antic

holine

rgic

s

¤U

sed

for the

ir sed

ative

and

antisio

log

og

ue p

rop

ertie

s

¤Tre

atm

ent fo

r bra

dyc

ard

ia (A

trop

ine m

ore

so tha

n Glyc

op

yrola

te

or Sc

op

ola

mine

)

¤G

iven c

onc

om

itantly w

ith an a

nticho

lineste

rase

for re

versa

l of

musc

le b

loc

kad

e

¤Re

laxe

s bilia

ry and

urethra

l smo

oth m

uscle

¤Bro

ncho

dila

tion

¤Pre

ventio

n of m

otio

n sickne

ss

¤Sid

e Effe

cts:

¤C

entra

l Antic

holine

rgic

Syndro

me

: CN

S ma

nifesta

tions suc

h re

stlessne

ss, som

nole

nce

, halluc

inatio

ns and

unco

nscio

usness c

an

result.

Antic

holine

rgic

s co

nt.

Atro

pine

Sco

po

lam

ineG

lyco

pyrro

late

Sed

atio

n+

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y1 2018, V

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19. d

oi:10.1097/A

LN.0000000000002028 Info

gra

phic

c

rea

ted

by Jo

natha

n P. Wa

nde

rer &

Jam

es P.

Rathm

ell.

INFOGRAPHICS IN ANESTHESIOLOGY

411Innate

Imm

uneD

ysfunctionin

Trauma

Patients:From

Pathophysiology

toTreatm

ent(C

linicalConcepts

andC

omm

entary)R

ecentinsightsintoposttraum

aticim

mune

dysfunctionhave

definednew

targetsfor

imm

unointerventionthat

holdprom

iseforimproving

outcomesin

suchcriticallyill

patients.

271H

ighIntraoperative

InspiredO

xygenD

oesN

otIncrease

Postoperative

Supplem

entalO

xygenR

equirements

High

inspiredoxygen

may

bereasonable

inlow

errisk

surgeryto

improve

wound

oxygenation.

347A

ccuracyofU

ltrasound-guidedN

erveB

locksofthe

Cervical

ZygapophysialJointsU

ltrasoundim

agingw

asanaccurate

techniqueforcervi-

calzygapophysialjointnerveblocksinvolunteers.Seethe

accompanyingEditorialV

iewon

page236.

353E

stimation

oftheC

ontributionofN

orketamine

toK

etamine-

inducedA

cuteP

ainR

eliefandN

eurocognitiveIm

pairment

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ealthyVolunteers

Norketam

inehasan

effectoppositeto

thatofketamine

onpain

relief.

399S

evereE

mergence

Agitation

afterM

yringotomy

ina

3-yr-oldC

hild(C

aseS

cenario)Em

ergenceagitation,the

associatedrisk

factors,andits

preventionand

treatmentare

discussed.

243Factors

Affecting

Adm

issionto

Anesthesiology

Residency

inthe

United

States:C

hoosingthe

Futureof

Our

Specialty

The

proportionofanesthesiology

residentsfromU

.S.medicalschoolshasm

orethan

dou-bled

since1995.T

hisretrospective

cohortstudy

evaluatedthe

2010and

2011residency

applicantsto

determine

thefactorsassociated

with

asuc-cessful

admission

toresi-

dencytraining

programs.

The

sample

represented58%

ofthetotalnationalapplicantpool;66%

ofthe

applicantssuccessfully

matched

toanes-

thesiology.Theoddsforasuc-

cessfulmatch

were

higherforapplicantsfrom

U.S.m

edicalschools,

thosew

ithU

nitedStates

Medical

LicensingExam

inationscoresgreater

than210,

youngerappli-

cants,and

females.

Priorgraduate

educationor

peer-review

edpublicationsdid

notofferanyadvantage.T

hisstudysuggeststhe

potentialforageand

genderbiasinthe

selectionprocess.Seetheaccom

panyingEditorialView

onpage

230.

302W

hatFactors

Affect

IntrapartumM

aternalTemperature?

AP

rospectiveC

ohortS

tudy:MaternalIntrapartum

Temperature

The

causeofrises

inintrapartum

maternaltem

peratureis

notknown.In

thisprospective

studyof81

wom

enscheduled

forlaborinduction,hourlyoraltem

peratureswere

recordedand

analyzedbased

onrace,

bodym

assindex,

durationof

labor,and

time

toepidural.

Overall,tem

peratureroseina

significantlineartrendovertim

e.Positivetemperaturetrends

wereassociated

with

significantlylongertimefrom

mem

branerupturetodeliveryand

higherbody

mass

index.Tem

peratureslopes

didnot

differbefore

compared

with

afterepidural

analgesia.Thisstudy

suggeststhatepiduralanalgesiaalonedoesnotincreasetherisk

ofhightem

peraturesinintrapartum

wom

en.

321P

ostoperativeQ

TIntervalP

rolongationin

Patients

Undergoing

Noncardiac

Surgery

underG

eneralA

nesthesia

Electrocardiograms(EC

G)can

identifyabnorm

alcardiacrepolarization

byobservation

ofaprolonged

QT

interval.QT

intervalprolongationisoften

causedby

drugsandcan

resultinsudden

cardiacdeath.In

thisancillarystudy

tothe

Vitam

insinN

itrousOxide

trial,serialpostoperative

12-leadEC

Gw

ereobtained

from469

patientsundergoingm

ajornoncardiacsurgery

undergeneralanesthesia.Eighty

percentofpatientsexperienced

asignificantQ

Tintervalprolongation,and

approximatelyhalfhad

increasesgreaterthan440

msattheend

ofsurgery.O

nepatient

developedtorsade

depointes.D

rugsassociated

with

prolongedQ

Tintervalincluded

isoflurane,methadone,ketorolac,cefoxitin,zosyn,unasyn,epinephrine,

ephedrine,andcalcium

.Although

theexactcauseoftheassociationbetw

eenperioperatively

administered

drugsandQ

Tintervalprolongation

isnotknown,furtherstudyisw

arrantedto

determine

theclinicalrelevance.

THISM

ONTHIN

balt6/z7i-anesth/z7i-anesth/z7i00812/thismonth

panickesS!

2456/29/12

22:41Art:

Input-ebh

PACU

= postanesthesia care unit; TOF = train-of-four.

Infographic created by Jonathan P. Wanderer, Vanderbilt U

niversity Medical C

enter, and James P. Rathm

ell, Brigham and W

omen’s H

ealth Care/H

arvard Medical

School. Illustration by Annemarie Johnson, Vivo Visuals. Address correspondence to D

r. Wanderer: jonathan.p.w

anderer@vanderbilt.edu.

1. Murphy G

S, Szokol JW, A

vram M

J, Greenberg SB

, Shear TD, D

eshur MA

, Benson J, N

ewm

ark RL, M

aher CE: N

eostigmine adm

inistration after spontaneous recovery to a train-of-four ratio of 0.9 to 1.0: A

randomized controlled trial of the effect on neurom

uscular and clinical recovery. AN

ESTHESIO

LOG

Y 2018; 128:27–37

2. Brull SJ, N

aguib M: H

ow to catch unicorns (and other fairytales). A

NESTH

ESIOLO

GY 2018; 128:1–3

3. Viby-Mogensen J, Jensen N

H, Engbaek J, O

rding H, Skovgaard LT, C

hraemm

er-Jørgensen B: Tactile and visual evaluation of the response to train-of-four nerve stim

ulation. A

NESTH

ESIOLO

GY 1985; 63:440–3

Anesth

esiology, V 128 •

No 1

January 2018

Com

plex Information for A

nesthesiologists Presented Q

uickly and Clearly

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nloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/journals/jasa/936634/ on 04/02/2018

Suga

mm

ad

ex

Bom

A e

t al. (2002). A

ngewC

hemIntEd

Engl,41, 266–270.

Wha

t is Suga

mm

ad

ex?

¤A

cyc

lod

extrin

¤C

yclic

olig

osa

cc

harid

e c

arb

ohyd

rate

s that a

re

ca

pa

ble

of e

nca

psula

ting ”g

uest” m

ole

cule

s.¤

Cyc

lod

extrin

pre

pa

ratio

ns are

curre

ntly used

in a

numb

er o

f ora

l me

dic

atio

ns from

Ibup

rofe

n to

Me

top

rolo

l to O

me

pra

zole

to e

nhanc

e so

lubility

and

stab

ility, incre

ase

bio

ava

ilab

ility and

d

ec

rea

se g

astric

ulce

ratio

n. 1

¤U

sually re

nally

exc

rete

d.

¤Su

refe

rs to the

suga

r co

mp

one

nt and

ga

mm

ad

ex

refe

rs to the

structura

l co

mp

one

nt γ-cyc

lod

extrin.

¤FD

A a

pp

rove

d fo

r use in U

S in De

ce

mb

er 2015.

¤First c

om

me

rcia

lly ava

ilab

le 2008

¤Kno

wn a

s Bridio

n® w

orld

wid

e.

1. Tiwa

ri, Tiwa

ri, & Ra

i (2010). J Pharm

acy a

nd Bioa

lliedSciences, 2, 72–79.

https://www.merckconnect.com

/bridion/dosing.htm

l?hcpUser=yes

Wha

t is Suga

mm

ad

ex c

ont.

¤V

ery w

ate

r solub

le (hyd

rop

hilic o

utside

, hyd

rop

hob

ic insid

e)

¤Fo

rms a

1:1 co

mp

lex w

ith Roc

or

Ve

c--Lo

w d

issoc

iatio

n rate

.

¤W

orks o

n Am

inoste

roid

alN

DM

Rs (Ro

c>V

ec

). 1

¤Is no

w re

ferre

d to

as a

Sele

ctive

Re

laxa

nt Binding

Ag

ent (SRBA

).

¤It is no

t a re

ce

pto

r drug

, it is a c

onta

iner

drug

.

¤C

ontra

indic

ate

d in se

vere

rena

l im

pa

irme

nt pa

tients.

1. SuyK e

t al. (2007). A

nesthesiol,106, 283-288.

Ad

ministra

tion

¤Sug

am

ma

de

xis a

NM

B reve

rsal a

ge

nt. ¤

For use

in ad

ult surgic

al p

atie

nts only.

¤Fo

r reve

rsal o

f only Ro

curo

nium a

nd V

ec

uronium

.

¤Is a

vaila

ble

as 100 m

g/c

c p

rep

ara

tion in 2 c

c a

nd 5 c

c via

ls.

¤Sug

am

ma

de

xis a

dm

inistere

d IV

.¤

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mp

atib

le w

ith vera

pa

mil, o

nda

nsetro

n and

ranitid

ine.

¤The

me

cha

nism o

f ac

tion invo

lves e

nca

psula

ting, b

inding

and

ina

ctiva

ting Ro

c o

r Ve

c.

¤Thro

ugh ina

ctiva

tion, a

co

nce

ntratio

n gra

die

nt oc

curs shifting

the

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ay fro

m the

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J, reve

rsing p

ara

lysis.

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spe

ed

in whic

h the re

versa

l take

s pla

ce

is de

pe

nde

nt on the

le

vel o

f rela

xatio

n and

do

se o

f Suga

mm

ad

ex. It is d

ose

d

ep

end

ent.

Ad

ministra

tion

¤H

orm

ona

l co

ntrac

ep

tives c

an b

ec

om

e le

ss effe

ctive

se

co

nda

ry to a

low

ering

of the

free

pla

sma

c

onc

entra

tions.

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ounse

l your fe

ma

les p

atie

nts of c

hild b

ea

ring a

ge

to use

b

ac

k up c

ontra

ce

ptio

n 7 da

ys afte

r surge

ry.

Do

sing

¤N

o d

ose

ad

justme

nts nee

d to

be

ma

de

in ge

riatric

, ca

rdia

c o

r p

ulmo

nary p

atie

nts with no

rma

l rena

l functio

n.

¤N

o d

osa

ge

ad

justme

nt nec

essa

ry for m

ild to

mo

de

rate

rena

l im

pa

irme

nt.

¤H

ow

eve

r, it is co

ntraind

ica

ted

in seve

re re

nal im

pa

irme

nt p

atie

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sing

¤D

osing

is ba

sed

on a

ctua

l bo

dy

we

ight , no

t ide

al b

od

y we

ight.

¤D

osing

is ba

sed

on the

de

gre

e o

f m

uscle

rela

xatio

n.

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r 2/4 TOF tw

itche

s, the d

ose

is 2 m

g/kg

¤Fo

r 1-2 PTC tw

itche

s, the d

ose

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g/kg

¤To

reve

rse RSI d

ose

of Ro

c, 16

mg

/kg sho

uld b

e a

dm

inistere

d 3

min a

fter the

RSI do

se.

¤Be

sure to

give

the re

co

mm

end

ed

d

ose

or yo

u ma

y run into

rec

urrenc

e o

f NM

B/rec

urariza

tion.

https://w

ww

.shuttersto

ck.c

om

/sea

rch/fa

t+thin

Do

sing c

ont.

¤If ne

urom

uscula

r blo

cka

de

wo

uld ne

ed

to b

e re

-e

stab

lished

afte

r a re

versa

l with Sug

am

ma

de

x, Sux, M

ivac

urium, C

isatra

curium

or A

trac

uriumc

ould

be

c

onsid

ere

d.

¤If a

n am

inoste

roid

alN

MB is use

d, fo

llow

the ta

ble

be

low

:

Minim

um W

aiting

Time

NM

BA &

Do

se to

be

A

dm

inistere

d

5 minute

s1.2 m

g/kg

Roc

uronium

4 hours

0.6 mg

/kg Ro

curo

nium0.1 m

g/kg

Ve

curo

nium

Re-A

dm

inistratio

n of Ro

c o

r Ve

cA

fter Re

versa

l with Sug

am

ma

de

x(up

to 4 m

g/kg

)

Pharm

ac

okine

tics

Bom

A e

t al (2003). A

nesthesiol, 99, A1158.

Gijse

nbe

rgh

et a

l. (2005). Anesthesiol,103, 695–703.

Ima

ge

from

http

s://en.w

ikipe

dia

.org

/wiki/Sug

am

ma

de

x#/m

ed

ia/File

:Sug

am

ma

de

x_sod

ium_3D

_front_vie

w.p

ng

¤Sug

am

ma

de

xis re

nally e

xcre

ted

.¤

The Et1/2

is 2 hours in a

n ad

ult with

norm

al re

nal func

tion.

¤>90%

is exc

rete

d in the

urine o

ver 24

hours.

¤V

Dis 11-14 lite

rs in ad

ults with no

rma

l re

nal func

tion.

¤Pla

sma

cle

ara

nce

is 88 cc

/min.

¤N

o m

eta

bo

lites.

¤N

o d

iffere

nce

in pha

rma

co

kinetic

s w

ith resp

ec

t to g

end

er o

r rac

e.

Ad

verse

Effec

ts

¤H

ype

rsensitivity re

ac

tions, inc

luding

a

nap

hylaxis, ha

ve b

ee

n rep

orte

d.

¤The

incid

enc

e c

ited

is 0.3% o

r 1/299 sub

jec

ts.

¤H

ype

rsensitivity o

cc

urred

with the

16 m

g/kg

do

se.

¤Bra

dyc

ard

ia ha

s be

en re

po

rted

.

¤W

hile no

antic

holine

rgic

nee

ds to

be

a

dm

inistere

d w

ith Suga

mm

ad

ex,

trea

t ap

pro

pria

tely.

¤Risk o

f pro

long

ed

NM

B.

¤Sug

am

ma

de

xm

ight no

t wo

rk on

ce

rtain p

atie

nts--Mo

nitor a

lwa

ys!http://forum

s-archive.secondlife.com/327/03/244341/1.htm

l

Tole

rab

ility

¤Risk o

f ble

ed

ing:

¤D

ose

s up to

16 mg

/kg ha

ve b

ee

n re

po

rted

to inc

rea

se c

oa

gva

lues b

y 25%

for 1 ho

ur.

¤H

ow

eve

r the c

linica

l trial d

id no

t show

a

n incre

ase

in blo

od

loss o

r ane

mia

.

¤Be

aw

are

, esp

ec

ially if yo

ur pa

tient

has a

know

n co

ag

ulop

athy, if the

y a

re re

ce

iving the

rap

eutic

a

ntico

ag

ulatio

n/throm

bo

pro

phyla

xis.

Gijse

nbe

rgh

et a

l. (2005). Anesthesiol,103, 695–703.

https://w

ww

.npg

.org

.uk/co

llec

tions/se

arc

h/po

rtrait/m

w62694

/Brea

thing-a

-vein

Just Ho

w Fa

st Is It?

NM

B Ag

ent

Suga

mm

ad

ex

(2 mg

/kg)

Ne

ostig

mine

/G

lyco

pyrro

late

(50 mc

g/kg

+ 10 mc

g/kg

)

Roc

uronium

1.4 minute

s21.5 m

inutes

Ve

curo

nium2.1 m

inutes

29 minute

s

Me

dia

n Time

to Full Re

versa

l (TOF ra

tio to

0.9) from

Mo

de

rate

Blo

cka

de

(T2 )

NM

B Ag

ent

Suga

mm

ad

ex

(4 mg

/kg)

Ne

ostig

mine

/G

lyco

pyrro

late

Roc

uronium

2.7 minute

sN

A

Ve

curo

nium2.1 m

inutes

NA

Me

dia

n Time

to Full Re

versa

l (TOF ra

tio to

0.9) from

De

ep

Blo

cka

de

(PTC 1-2)

Loo

king to

the Future

https://w

ww

.inde

pe

nde

nt.co

.uk/arts-e

nterta

inme

nt/tv/fea

tures/b

ac

k-to-the

-future-w

hy-the

-jetso

ns-is-the-m

ost-influe

ntial-tv-sho

w-o

f-the-20th-c

entury-8225272.htm

l

If I have

see

n further tha

n o

thers, it is b

y stand

ing up

on

the sho

ulde

rs of g

iants.

-Isaa

c N

ew

ton

Ga

ntac

urium¤

A ne

w c

lass o

f isoq

uinoline

NM

B know

n as

chlo

rofum

ara

tes.

¤D

eve

lop

ed

as a

n ultra

short a

cting

, rap

id o

nset

NM

B.

¤M

eta

bo

lized

by c

ysteine

a

dd

uctio

n and

pH

-se

nsitive hyd

rolysis.

¤M

eta

bo

lites ha

ve no

ne

urom

uscula

r pro

pe

rties.

¤N

o re

nal a

nd he

pa

tic

involve

me

nt in elim

inatio

n.

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ac

od

ynam

ics/Pha

rma

co

kinetic

s

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an tria

ls, the ED

95o

f Ga

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uriumw

as fo

und to

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0.19 m

g/kg

¤O

nset tim

e is le

ss than 3 m

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r at 4 X ED

95d

ose

, onse

t tim

e c

an b

e sho

rtene

d to

1.5 min

¤D

uratio

n of a

ctio

n is ~10-15 min (sp

onta

neo

us reve

rsal to

TOF

≥ 0.9)

¤C

an b

e re

verse

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ith an a

nticho

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rase

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fera

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dro

pho

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ith it’s pe

ak e

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to TO

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¤C

an b

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verse

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ith L-cyste

ine¤

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ine is a

n am

ino a

cid

¤U

sed

in pa

renta

l nutrition

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bo

lus do

se o

f 10-50 mg

/kg fo

r reve

rsal, no

toxic

ity¤

De

pe

nding

on w

hen it is a

dm

inistere

d fo

r reve

rsal, c

an

shorte

n the d

uratio

n of a

ctio

n by 2-6 m

in

Side

Effec

ts

¤D

ose

de

pe

nde

nt transie

nt c

ard

iova

scula

r side

effe

cts

have

be

en o

bse

rved

in hum

ans.

¤U

sually re

po

rted

at d

ose

s o

f 3 X ED95

¤Evid

enc

ed

by hyp

ote

nsion

and

refle

x tac

hyca

rdia

¤H

uma

ns show

signific

ant

do

se d

ep

end

ent

histam

ine re

lea

se:

¤Pre

sent in d

ose

s of 4 X ED

95

¤A

t low

er d

ose

s (2.5 X ED95 )

no hista

mine

rele

ase

¤

Evide

nce

d b

y flushing

http://www.cfhi-fcass.ca/SearchR

esultsNews/2010/10/01/f1ca3fcf-f9aa-

4dcb-a64c-a95f2bbadd8d.aspx

Sunag

a &

Lien. (2013). C

urrAnesthesiolRep, 3, 105-113.

de

Boe

r & C

arlo

s. (2018). CurrA

nesthesiolRep Piublishe

dO

nline d

oi:10.1007/s40140-018-0262-9.

Othe

r Ne

w H

orizo

ns…

¤O

ther iso

quino

linefum

ara

te a

ge

nts¤

CW

002¤

CW

011

¤Re

verse

d b

y a

dm

inistratio

n of the

a

mino

ac

id c

ysteine

.

¤C

W002 a

nd C

W011

have

slow

er re

versa

l tim

e a

nd lo

nge

r d

uratio

n of a

ctio

n tha

n Ga

ntac

urium.

https://w

ww

.red

bub

ble

.co

m/p

eo

ple

/co

mp

ound

che

m/w

orks/1380542

8-20-am

ino-a

cid

s?p=p

oste

r

Othe

r Ne

w H

orizo

ns…

¤Tro

pinylD

ieste

r De

rivative

s

¤The

se a

re a

lkalo

ids sim

ilar in struc

ture

to a

trop

ine a

nd sc

op

ola

mine

.

¤G

-1-64¤

Rap

id o

nset (~1 m

in)¤

Short D

uratio

n (5-11min)

¤Re

verse

d w

ith an a

nticho

lineste

rase

¤So

me

ca

rdia

c sid

e e

ffec

ts¤

No

cum

ulative

effe

cts w

ith infusion

or re

pe

ate

d d

ose

s

¤TA

AC

3¤

Rap

id O

nset (45-60

sec

)¤

Short D

uratio

n (~half

to ¾

dura

tion o

f Ro

curo

nium)

¤So

me

ca

rdia

c e

ffec

ts¤

In anim

al stud

ies, d

ose

d

ep

end

ent

hypo

tensio

n

We

lliver(2012). A

AN

A J, S11-17.

Ca

lab

ad

ions

¤C

ala

ba

dio

n1 a

nd 2 a

re

pa

rt of the

mo

lec

ular

co

ntaine

r fam

ily C

ucurb

it[n]urils.

¤First re

versa

l ag

ents to

re

verse

bo

tha

mino

stero

ida

nd

be

nzylisoq

uinolinium

NM

Bs.

¤W

orks b

y flexing

its g

lyco

lurilba

ckb

one

to

ac

co

mm

od

ate

bo

th roc

a

nd c

is.

¤Be

nzylisoq

uinoline

sm

ake

up

1/3 of the

ma

rket

volum

e o

f NM

Bs.

¤N

o sig

ns of re

cura

rizatio

n.

¤In p

rec

linica

l trials, 90-150

mg

/kg o

f Ca

lab

ad

ion

1 w

as a

ble

to re

verse

ro

curo

niuma

nd

cisa

trac

uriumto

a TO

F ≥ 0.9 w

ithin 1-2 min (84 vs.

87 sec

).

¤N

o e

ffec

ts on he

art ra

te,

blo

od

pre

ssure o

r ABG

p

ara

me

ters.

¤Fa

st rena

l elim

inatio

n:¤

90-100% w

ithin 1 hour

¤Inte

resting

ly ma

y also

be

re

versa

l for lo

ca

l a

nesthe

tic to

xicity.

Ho

ffma

n et a

l., (2013). Anesthesiol, 119

(2), 317-325.

In Co

nclusio

n¤

Our c

urrent p

rac

tice

in NM

B is im

pro

ving, b

ut it is still far fro

m

pe

rfec

t.¤

Patie

nt safe

ty is of the

utmo

st p

riority.

¤W

e c

urrently a

dm

inister m

uscle

re

laxa

tion a

nd re

verse

it in a

very c

om

ple

x ma

nner.

¤O

bje

ctive

or q

uantita

tive

mo

nitoring

of N

MB ne

ed

s to b

e

utilized

.

¤M

any a

ge

nts, ma

ny side

e

ffec

ts.

¤Sug

am

ma

de

xo

ffers a

n new

w

ay to

reve

rse Ro

c a

nd V

ec

.

¤Pro

mising

new

drug

s for N

MB

and

reve

rsal a

re c

om

ing, a

re

we

rea

dy?

https://w

ww

.kee

pc

alm

-o-m

atic

.co

.uk/p/ke

ep

-c

alm

-its-the-c

onc

lusion/