not permitted.

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MINERVA ANESTESIOL 2002;68:248-51

How useful is the bispectral index

in the management of ICU patients?
J. BALL

I f you want to objective ly quantify the level of
sedation the intuitive solution must be to monitor
the brain dire c t ly. H oweve r, due to the complexity
of this organ, and our limited understanding of
consciousness, this remains a daunting challenge.
For many ye a rs, re s e a rchers have inve s t i gated the
electrical activity of the brain and its re l ationship
with conscious leve l . O ver the last few ye a rs, a
d e r ived va r i able from the EEG, the Bispectra l
Index (BIS), has been developed, which appears to
correlate quite well with the level of pharmacologi-
cal sedation.
Key w or ds: I n t e ns ive care units - Bispectra l
index - Critical care - Electroencephalography.
From basic EEG to BIS 1, 2
The el ectri cal acti vi ty of the br ai n can
be measur ed by pl acin g el ectr odes on the
scal p. However the tr ansduced si gnal
al so contains the electri cal activi ty of
the scal p muscl es, the hear t and even
el ectr i cal devi ces ar ound the pati ent and
EEG monitor . Despi te thi s, the brain ’s
electrical activi ty can be identi fied by
i ts char acter i sti c ampl i tude and fr e-
quency patter n s. Th ese h av e been
grouped i nto four bands: beta ( 14-30
Hz, ver y l ow ampli tude) associ ated wi th
mental activity and the earl y stages of
or other proprietary information of the Publisher.
F rom the Lecturer in Intensive Care
Medicine
St George’s Hospital Medical School,
ampli tude) pr edomi nant i n r el axed con-
sci ous subj ects; theta ( 4-7 Hz, l ow-
medi um ampl itude) and delta ( 0.5- 3.5
H z, hi gh ampl i tude) both of whi ch
become i ncr easi ngl y pr omi nent wi th
decr easin g consci ous l evel . For neur odi -
agnostic pur poses up to 19 channels ( -
scal p el ectr odes) are r ecor ded sim ul ta-
neously . I nterp r etati on of the ra w data i s
a hi ghl y compl ex task, whi ch i s i mpos-
si bl e i n r eal ti me wi thout the ai d of
compl ex computer pr ocessi ng. B y
employin g such analy sis, the prop or-
tion, power and coherence of the el ectr i -
cal activ ity wit hi n each fr equency band
can be measur ed, and thi s br oadly cor -
re l ates wi th the l evel of consci ousness.
B I S was devel oped by per for mi ng
detailed analysis on the EEGs of 1,5 00
patients undergoing general anaesthe-
sia, induced and maintained by a varie -
ty of hypnotics and analgesics. By sta-
ti sti cal l y anal ysi ng the str ength of
cor r el ati on between a number of the
descr i pti ve par ameter s gener ated by

anaesthesi a; al ph a ( 8 - 1 3 Hz, l ow
Address reprint requests to: J Ball - St. George’s
Hospital Medical School - Cranner Terrace, london,
UK.
the EEG analys is, and the detail ed cl ini-
cal assessment of the depth of sedation,
r esear cher s i denti fi ed 3 par ameter s,
whic h, in weighted combina tion, mir-

248 MINERVA ANESTESIOLOGICA Aprile 2002

not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, MINERVA MEDICA COPYRIGHT®
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
HOW USEFUL IS THE BISPECTRAL INDEX IN THE MANAGEMENT OF ICU PATIENTS?
BIS 100 Awake
Response to normal voice
80
Response to loud commands
or mild-moderate physical
stimulus
60
Low probability of explicit recall
Unresposive to verbal stimuli
40
20
Burst suppression
0 Flat line EEG
Fig. 1.—BIS range guidelines.
ror ed the depth of sedation. They went
on to develop a complex algorithm util-
isi ng these three parameters to derive
a sin gle measure of the depth of seda-
tion, whic h they terme d the Bis pectral
Index; a non- line ar scale from 0-1 00
(Fig . 1). They then prospectively vali-
dated the algorithm on a furthe r group
of p ati ents u n der goi n g gen er al
anaesthesia.
BIS, EMG and SR
The onl y commer ci al l y avai l able stand
alone BIS monit or is the A- 2000 pr o-
duced by Aspect Medi cal Systems (N ew-
ton, M A, U SA; h ttp:/ / w w w .-
aspectms.com) , al though a number of
I CU moni tor s now have B I S modul es
avai labl e. All employ a bi frontal sensor
or other proprietary information of the Publisher.
that connects to an anal ogue to digi tal
si gnal conver ter ( DSC) . I n addition to
the BIS , the moni tor s di splay three oth-
er par ameter s ( si gnal qual i ty i ndex,
Vol. 68, N. 4
BALL
EMG and suppre ssi on ra tio) and a ra w,
single channel, continuous, EEG wave-
form , al l of which provi de useful in for -
mation. The commonest art efact affect-
i ng the BI S is EM G fr om the fr ontal i s
muscl e. Unfor tunatel y, EM G si gnal fr e-
quencies ( 30- 300 Hz) over l ap with the
top end of the EEG fr equenci es. These
signals therefore cannot be completely
separa ted and hence if a patient gener-
ates an EMG si gnal i n the 30- 50 Hz band
this wi ll i ncrease the BIS . I n order to
aler t the cl in i cian to thi s possibil it y,
the str ength of any si gnal in the 70- 110
Hz fr equency band i s i ndi cated by an EM G
bar on the monitor. The complex r ela-
tionshi p between EEG and EMG si gnal s i s
such that typicall y, as a patient’s depth
of sedati on i ncr eases, thei r EMG activi ty
fal ls .3 However , as sedati ve drugs pr e-
domi nantly affect the hi gher br ai n cen-
tr es and movement ( EM G activi ty) i s to
a si gni fi cant extent contr ol l ed by the
spin al cor d, ci r cumstances can ar ise ,
especi al l y i n r esponse to a nox i ous
stimul us, wher eby pr ofoundl y sedated
pati ents ex hi bi t hi gh EM G acti vi ty
re sulti ng fr om spi nal re flexes. Thus an
esti mate of the str ength of EMG activi ty
is vital in the i nterpr etation of the BIS
i n non-paralysed patients.4 Last year ,
the BIS hardware and software under-
went a maj or upgr ade ter med BI S XP
( ex panded per for mance) . Thi s has
i mpr oved the detection and filtering of
EMG and other ar tefacts, though by no
means removed them enti r el y.
The suppr ession ra tio ( SR) quanti fi es
the perc entage of the last 60 seconds in
whi ch the EEG was is oel ectr i c. The SR i s
most useful in monit oring neurological
pati ents, i n whom one of the goal s of
sedati on i s barb i tur ate coma. I t can al so
pr ovi de val uabl e i nfor mati on i n l ess
heavi l y sedated pati ents. The SR tends to
be zer o until the BI S fall s i nto the 20s.
The SR then in cr eases r apidly as the BIS
fal l s fur ther . Devi ati ons fr om thi s
expected patter n, such as a pati ent wi th
an SR of 35% and a BI S of 55, can alert
the cl i nician to the possi bi l i ty of a fals e-
MINERVA ANESTESIOLOGICA 249
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, MINERVA MEDICA COPYRIGHT®
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
BALL HOW USEFUL IS THE BISPECTRAL INDEX IN THE MANAGEMENT OF ICU PATIENTS?
l y el evated BI S or the pre sence of or gan-
i c br ai n pathol ogy.
Validation
Si nce i ts development, BIS has been
r epeatedl y v al i dated as a depth of
anaesthesia monitori ng tool . Unsur pri s-
i ngl y, B I S l evel al so cor r el ates wel l
with the phases of nor mal sl eep 5 and i n
addi ti on, cor r el ates wel l wi th gl obal
brain metabolic activity. 6 BIS has also
been vali dated agai nst a number of seda-
tion scor in g systems in a di ver se r ange
of ICU patients.7-9 Its val idity i s l ar gel y
unaffected by the extr emes of age, at
l east i n anaesthesi a.10-12 BI S has been
successfull y empl oyed in moni tor i ng the
depth of sedation with a wi de varie ty of
agents, although appears to be unreli-
abl e when uti l i sed wi th ketami ne 13, 14 or
xenon.15 There i s also a complex rela-
ti onshi p between BI S and opi ates.16, 17 I t
appear s that l oss of consci ou sn ess
i nduced by pr opofol , benzodi azepi nes
and vol ati le agents occur s at l ower doses
and at hi gh BI S l evel s when pati ents are
pr e tr eated with opiates, thus i mpl yi ng
that BI S mer el y r eflects the concentr a-
ti on of hypnoti c dr ug. However , for a
given dose of a hypnotic dr ug, the BI S
level re sponse to a noxious stim ulu s is
damped by opi ate admi ni str ati on.18 A
si mi l ar set of phenomena may ex i st
durin g co-adm i nistration of hypnotics
and neuromuscular bl ocker s, 19 al though
thi s i s compli cated by the in abil i ty to
di ffer enti ate between hi gh fr equency
EEG and l ow fr equency EM G. Thi s i s
compl i cated fur ther , i n cr i ti cal l y i l l
patie nts, as they tend to have l ow EEG
power that r enders the BIS algori thm
more susceptibl e to EMG ar tefact.20 In
essence, the effect on BI S of r educi ng
affer ent cort i cal i nput remai ns uncl ear .
or other proprietary information of the Publisher.
How can you use the BIS
in clinical practice?
250 MINERVA ANESTESIOLOGICA
Monitorin g a patient’s BI S in the I CU
per mi ts a conti nuous and obj ecti ve
assessment of their level of sedation. It
is ar guabl y, r elativel y easy to detect i f a
patient i s under sedated, as one or more
of the i denti fie d goal s of sedation wi l l
have fai l ed, the obvi ous ex cepti on to
thi s bei ng a pati ent who’ s r ecei vi ng
neuromuscl ular blockade. Under these
ci r cumstances, concer n for the pos-
si bi li ty of patient awar eness commonly
r esul ts i n del i ber ate over sedati on.
However , by uti l is i ng a BI S moni tor ,
sedation can be titr ated to achieve a tar-
get BIS of <60, ensur ing that the pos-
si bi l i ty of awar eness i s effecti vel y
re moved (p robabi lit y of re cal l <5% 21,
22 but al l owi ng the mi ni mal dose of
sedation to be admini stered to achie ve
thi s. Over sedati on i n non- par al ysed
pati ents can si mi l ar l y be r educed by
targetin g specifi c ra nges of BI S values.
However, the int erpre tation of the BIS
scal e shown i n Figure 1, shoul d be con-
si dere d a gui del i ne and not defin i ti ve.
Any B I S val ue must be i nter pr eted
al ongside both the tr aditi onal assess-
ment tool s ( pati ent behavi our and
physiologic al para meters ) and the SQI,
EM G and SR. BI S offers useful additional
i nform ation and should not be consid-
er ed a stand alone r eplacement. For a ny
i ndi vi dual pati ent, the maxi mum BI S
l evel that corr elates wit h the sedation
goals for that patient need to be deter-
mi ned. Star tin g targets can be taken as a
“ r esti ng” B I S of 4 0 - 6 0 and a “ -
r esponse to noxi ous sti mul us” BI S of
60-8 0. Usi ng these tar gets, together
wi th the tr adi ti onal goal s descr i bed
above allo ws contin uous monit ori ng and
hence aggressi ve tit rat ion of hypnotic
and anal gesi c dr ugs. I n addi ti on, the
obser ved patter n of BIS and haemody-
namic par ameter s (Ī other s) can, for
exampl e, i ndi cate that an i ncr ease i n
an al gesi c r ather th an h y p noti c i s
re qui re d to achi eve the sedation goals .
Aprile 2002
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, MINERVA MEDICA COPYRIGHT®
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
HOW USEFUL IS THE BISPECTRAL INDEX IN THE MANAGEMENT OF ICU PATIENTS?
Potential other uses for BIS monitoring
Though cur r en tl y th e su bj ect of
r esearch i nter est only , BI S monit or -
i ng may pr ove to be a useful tool for
br ai n moni tor i ng i n pati ents wi th a
wi de var i ety of cer ebr al i nsul ts. BI S
appears to demonstrate limited neuro-
di agnosti c abi l i ti es i n di seases as
diver se as dementia, 11 epi lep sy 23 and
head injury .24, 25
Conclusions
BI S offers in terp r etable conti nuous
E E G mon i tor i n g to cr i ti cal l y i l l
patients. It has the potential to facili -
tate accur ate and aggr essi ve sedati ve
ti tr ati on and per haps have a r ol e i n
neur odi agnosi s. However , i t r emai ns
to be demonstr ated i n cl i ni cal tr i al s
th at m on i tor i n g B I S i n cr i ti cal l y
pati ents re sul ts i n i mpr oved car e, i n
parti cular , a reduction in the negativ e
effects of excessive sedation.
Riassunto
Come e perché quantificare il l i vello di seda -
zione
Se si vuole quantificar e oggettivame nte il
l i v el l o di sedazi one, l a sol uzi one i ntui ti v a
deve essere il monitora ggio cerebrale diret-
to. Comunque, data la compless itą di questo
or gano, e l a nostr a l i mi tata compr ensi one
della coscie nza, questa ri mane una spave n-
tosa sfid a. P er mo lti a nni, i rice rca tori h an-
no investigato l’attivi tą elettrica del cer vel-
lo e la sua relaz ione con il liv ello d i cosc ien-
za. Negli ultimi anni) Ź stata svilu ppata una
var iabile derivata dall’E EG, l’In dice Bisp et-
tra le (BIS ), che appare correla re abbastanza
bene con il liv ello dell a sedazione farmac olo-
or other proprietary information of the Publisher.
Vol. 68, N. 4 MINERVA ANESTESIOLOGICA
BALL
gia.
Par ole chiave: Sedazione - Terap ia intensiva
- Bispe ctral index.
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251