Anesthesia

John F. Kihlstrom
University of California,
Berkeley
Randall C. Cork
Louisiana State
University Medial
Center


Note: An edited version of this article appeared in: M. Velmans & S.
Schneider (Eds.), The Blackwell Companion to Consciousness (Oxford,
U..: !lac"#ell, $%%&).

'he p(rpose of )eneral anesthesia is to render s(r)ical patients
(nconscio(s, and th(s insensitive to pain and o*livio(s to events
occ(rrin) d(rin) the proced(re. +or this reason, anesthesia ,, li"e
sleep and coma often enters into philosophical and scientific
disc(ssions of conscio(sness. -o# do #e "no# that the patient is
(nconscio(s. Appearances to the contrar/ not#ithstandin), are there
reasons to thin" that anestheti0ed patients are act(all/ conscio(s after
all. Ass(min) that the/ are act(all/ (nconscio(s, is it possi*le for
them to ac1(ire and retain (nconscio(s memories of pain and s(r)ical
events. 2hat can the *iolo)ical mechanisms of )eneral anesthesia tell
(s a*o(t the ne(ral correlates of conscio(sness.

!he "volution of #eneral Anesthesia
Up (ntil the middle of the 34
th
cent(r/, anesthesia #as not a feat(re of
s(r)er/. 5nstead, patients #ere simpl/ re1(ired to #ithstand the pain
of the proced(re, perhaps #ith the aid of alcohol, opiates (s(ch as
la(dan(m), a *ite,*oard, and ph/sical restraints. -(mphre/ 6av/
(3&&7,37$4), the pioneerin) electrochemist, discovered the effects of
nitro(s oxide on headache and dental pain d(rin) his research on
respirator/ ph/siolo)/8 *(t his report #ent (nnoticed in the medical
comm(nit/ and the s(*stance #as 1(ic"l/ consi)ned to (se at
9la()hin) )as9 parties. 5n 37:;, -orace 2ells, an American dentist,
attempted to (se nitro(s oxide for anesthesia d(rin) a dental
extraction, *(t the demonstration failed. !(t on Octo*er 3<, 37:<,
2illiam Morton, another dentist, emplo/ed ether in the s(r)ical
removal of a t(mor #ith no si)ns or reports of pain in the patient. 'hat
event is no# cele*rated in hospitals and medical schools thro()ho(t
the #orld as 9Ether 6a/9 (+enster, $%%3). Morton died in 37<7, and his
tom*stone in =am*rid)es Mo(nt A(*(rn =emeter/ carries the
follo#in) epitaph, composed */ !i)elo#:
5nventor and >evealer of 5nhalation Anesthesia:
!efore 2hom, in All 'ime, S(r)er/ #as A)on/8
!/ 2hom, ?ain in S(r)er/ #as Averted and Ann(lled8
Since 2hom, Science has =ontrol of ?ain.
Soon thereafter, chloroform #as introd(ced as an alternative to ether,
#hich had an (npleasant odor and other side effects. Anesthesia #as
also extended from s(r)er/ to o*stetrics, altho()h some ph/sicians
had 1(alms a*o(t dan)ers to the neonate, @(een Victoria essentiall/
ended the de*ate #hen she received chloroform for the *irth of her
ei)hth child, ?rince Aeopold. Bevertheless, some professionals and
others contin(ed to de*ate a 9calc(l(s of s(fferin)9 */ #hich some
individ(als, and some conditions, #ere deemed more #orth/ of
anesthesia than others (?ernic", 347;).
6e*ates aside, pro)ress in anesthesia contin(ed. 5n 37<7, nitro(s
oxide, mixed #ith ox/)en to circ(mvent dr(),ind(ced asph/xia, #as
introd(ced to medicine after havin) served for half a cent(r/ as
entertainment at 9la()hin) )as9 parties. Also that /ear, follo#in) the
development of the h/podermic needle, morphine #as added to the
proced(re to red(ce the amo(nt of inhalant re1(ired to prod(ce
anesthesia, and to prevent shoc", na(sea, and other ne)ative
se1(elae. 5n 37&< the se1(ential (se of nitro(s oxide and ox/)en to
ind(ce anesthesia, and ether or chloroform to maintain it, #as
introd(ced. 5n the mid,377%s, cocaine and its derivatives, s(ch as
novocaine, Coined morphine as adC(ncts to anal)esic practice.
'hro()ho(t the $%
th
cent(r/, the techni1(es for deliverin) and
maintainin) anesthesia #ere improved (Stoeltin) & Miller, $%%%).
!e)innin) in the 34D%s, a s(ccession of dr()s #ere introd(ced for the
rapid ind(ction of anesthesia: *ar*it(rates s(ch as thiopental (sodi(m
pentothal), then *en0odia0epines s(ch as dia0epam and mida0olam
*e)an to s(*stit(te for *ar*it(rates8 and most recentl/ propofol, a
s/nthetic dr() #hich also permits rapid recover/ from anesthesia, #ith
fe#er lin)erin) aftereffects. Altho()h inhaled anesthetics s(ppress
vol(ntar/ responses to #hat are e(phemisticall/ called 9s(r)ical
stim(li9, c(rare #as introd(ced in the 34:%s to s(ppress invol(ntar/,
reflexive responses as #ell. 5t has since *een replaced */ dr()s s(ch
as de,t(*oc(rarine, vec(roni(m, and s(ccin/lcholine. A ne#
)eneration of inhalational a)ents incl(din) halothane, enfl(rane, and
isofl(rane, #hich #ere less volatile than ether and less toxic than
chloroform, came into (se after 2orld 2ar 55. More recentl/,
intraveno(s opioid anesthetics s(ch as fentan/l and s(fentan/l, as #ell
as ne# dr()s to ind(ce anesthesia, s(ch as propofol, have emer)ed as
alternatives to inhalational a)ents.
5n c(rrent practice, )eneral anesthesia *e)ins #ith a pre,operative
visit */ the anesthetist. 5mmediatel/ *efore the operation, the patient
t/picall/ receives a *en0odia0epine sedative, follo#ed */ an inf(sion of
ox/)en to displace nitro)en in the l(n)s. 5n rapid sequence induction,
a short,actin) dr() s(ch as thiopental or propofol is emplo/ed to
ind(ce initial (nconscio(sness *efore administerin) ne(rom(sc(lar
*loc"ade to prod(ce m(scle relaxation (the anesthetic e(phemism for
total paral/sis of the s"eletal m(sc(lat(re). 5n an alternative
proced(re, called inhalation or mask induction, the patient ma/ receive
nitro(s oxide and ox/)en pl(s a volatile anesthetic8 in this case,
ho#ever, anesthesia develops more slo#l/. S(*se1(entl/, inhalants
s(ch as isofl(rane, desfl(rane, or sevofl(rane) ma/ *e (sed to
maintain anesthesia ind(ced */ other dr()s. 5n intravenous
anesthesia, the inhalants are replaced */ dr()s s(ch as s(fentan/l and
propofol. 5n an/ event, *eca(se of the (se of m(scle relaxants, the
patient m(st *e respirated thro()h int(*ation of the trachea. At the
end of the operation, the patient ma/ receive a dr() s(ch as
neost/)mine to reverse the ne(rom(sc(lar *loc"ade and permit the
res(mption of normal *reathin), as #ell as morphine to help alleviate
postoperative pain. An/ resid(al inhaled anesthetic is removed */ the
patients normal respiration.
'he techni1(e C(st descri*ed, "no#n as balanced anesthesia, achieves
the tripartite )oals of )eneral anesthesia: sedation, loss of
conscio(sness (sometimes referred to as 9narcosis9 or 9h/pnosis9),
and m(scle relaxation. !/ contrast, vario(s forms of local or regional
anesthesia can *e achieved */ inCection of local anesthetics s(ch as
lidocaine into the s(*arachnoid (spinal anesthesia) or epid(ral
(epidural anesthesia) spaces of the spinal cord, or the peripheral
nerves s(ppl/in) some *od/ part (nerve block). 5n s(ch proced(res,
ade1(ate anesthesia is defined more narro#l/ as a loss of tactile
sensation, and there is no loss of conscio(sness. 5n conscious
sedation, local or re)ional anesthetics are com*ined #ith
*en0odia0epine sedatives: a)ain, there is no )eneral loss of
conscio(sness, tho()h the (se of *en0odia0epines #ill li"el/ render the
patient amnesic for the proced(re. 5n hypesthesia, s(*clinical doses of
)eneral anesthetics are administered to nonpatient vol(nteers for
st(dies of learnin) and memor/ (Andrade, 344<).

Mehanisms of Anesthesia
Altho()h modern scientific medicine )enerall/ disdains 9empirical9
treatments that are "no#n to *e efficacio(s, even tho()h their
scientific *ases are not "no#n, the mechanisms (nderl/in) )eneral
anesthesia remain a matter of considera*le m/ster/. As a first pass, it
seems pla(si*le that )eneral anesthetics reversi*l/ disr(pt ne(ral
activit/ */ inhi*itin) either ne(ral excita*ilit/ or s/naptic activit/.
!e/ond that, thin)s )et m(r"/.
'o complicate thin)s f(rther, the vario(s classes of anesthetic a)ents
appear to have some#hat different mechanisms of action (Stoeltin) &
Miller, $%%%). +or example, man/ intraveno(s 9h/pnotic9 dr()s ,,
incl(din) propofol, *ar*it(rates s(ch as thiopental, and
*en0odia0epines s(ch as dia0epam ,, appear to interact #ith )amma,
amino*(t/ric acid (EA!A), an inhi*itor/ ne(rotransmitter, to increase
the time that chloride ion channels are open, res(ltin) in a
h/perpolari0ation of cell mem*ranes. -o#ever, "etamine, another
intraveno(s anesthetic, interacts #ith excitator/ N,meth/l,6,aspartate
(BM6A) receptors instead. Bat(ral and s/nthetic opioid anesthetics
s(ch as fentan/l, of co(rse, act on opioid receptors, inhi*itin)
pres/naptic release of ne(rotransmitters s(ch as acet/lcholine and
s(*stance ?. -o#ever, even in hi)h doses these dr()s do not, */
themselves, ind(ce loss of conscio(sness. +or this p(rpose, the/ are
often com*ined #ith nitro(s oxide and ox/)en. Bitro(s oxide, for its
part, has effects on BM6A receptors similar to those of "etamine.
=(rrent evidence is *roadl/ consistent #ith anesthetic action on *oth
s/naptic excitation and inhi*ition, #ith the contri*(tion of each process
var/in) from a)ent to a)ent.
'he molec(lar and cell(lar mechanisms */ #hich inhaled anesthetics
s(ch as isofl(rane achieve their effects have *een s(*Cect of intense
investi)ation and de*ate (+ran"s & Aie*, 344:). Accordin) to the M/er,
Overton r(le "no#n since the late 34
th
cent(r/, there is a stron)
correlation *et#een the potenc/ of an anesthetic )as and its sol(*ilit/
in lipids, s())estin) that the expansion of nerve cell mem*ranes
effectivel/ mi)ht close the ion channels */ #hich sodi(m enters the
cell to ind(ce an action potential. 5t is no# *elieved that the inhalants
*ind directl/ to specific poc"ets of relevant proteins rather than
alterin) the lipid *ila/er itself. 5n this #a/, the/ create a d/namic *loc"
of channels involved in s/naptic excitation8 some anesthetics also
intensif/ s/naptic inhi*ition. Altho()h the )eneral vie# is that
anesthetics act on the posts/naptic side, there are some indications
that the/ inhi*it pres/naptic ne(rotransmitter release as #ell.
'he concept of *alanced anesthesia implies that there are li"el/ to *e a
n(m*er of separate mechanisms #or"in) to)ether to prod(ce
anal)esia (lac" of pain), a sleepli"e loss of conscio(sness (sometimes
referred to as 9h/pnosis9), immo*ilit/ (vol(ntar/ responses to s(r)ical
stim(li, as opposed to the spinal reflexes s(ppressed */ m(scle
relaxants s(ch as vec(roni(m), and amnesia (lac" of memor/ for
s(r)ical events). Accordin) to one proposal, inhalants s(ch as
isofl(rane, #hich ind(ce *oth immo*ilit/ and amnesia, achieve these
effects */ different ro(tes: immo*ilit/ */ actin) on EA!A receptors in
the spinal cord, and amnesia */ s(ppressin) activit/ in the
hippocamp(s.
As it happens, the specific proteins affected */ inhaled anesthetics are
receptors for EA!A, amon) other ne(rotransmitters. 'h(s, the inhaled
anesthetics ma/ share a mechanism #ith the intraveno(s anesthetics
after all. Alon) the same lines, the inhaled anesthetics share some
pharmacolo)ical properties, s(ch as tolerance, #ithdra#al, and cross,
tolerance, #ith alcohol and sedative h/pnotics s(ch as *ar*it(rates. On
the other hand, there are no# a n(m*er of anesthetic a)ents that
violate the Me/er,Overton r(le, and it is "no#n some )ases can *ind
to the proteins implicated in anesthesia /et not ca(se anesthesia.
Altho()h m(ch attention has foc(sed on EA!A, -ans +lohr has
implicated BM6A instead (+lohr, $%%%). !oth nitro(s oxide and
"etamine act as anta)onists on BM6A receptors, *loc"in) )l(tamate,
an excitator/ ne(rotransmitter as does xenon, a ne#l/ developed
anesthetic. Even if the intraveno(s anesthetics share a final common
path#a/ #ith some inhaled anesthetics, other inhalants ma/ achieve
the same effects */ rather different means.
Some theorists have so()ht to solve the m/ster/ of anesthesia */
invo"in) another m/ster/, namel/ 1(ant(m theor/. >o)er ?enrose, a
!ritish mathematical ph/sicist, and St(art -ameroff, an American
anesthesiolo)ist, have famo(sl/ spec(lated that conscio(sness is a
prod(ct of certain processes descri*ed */ 1(ant(m theor/ (-ameroff,
34478 ?enrose, 344:). !riefl/, 1(ant(m coherence (*/ #hich individ(al
particles are (nified into a #ave f(nction) prod(ces a (nified conscio(s
self8 non,local entan)lement (#hich connects separate particles) is
responsi*le for associative memor/8 1(ant(m s(perposition (*/ #hich
particles sim(ltaneo(sl/ exist in t#o or more states) prod(ces
alternative (nconscio(s mental representations8 and the collapse of
the #ave f(nction (*/ #hich particles attain a definite state) *rin)s
one of these alternative mental states into conscio(s a#areness.
2ithin the context of this theor/, -ameroff has f(rther proposed that
these processes ta"e place in microt(*(les ,, proteins fo(nd in the
#alls of ne(rons that are shaped li"e hollo# t(*es.
Altho()h the conventional vie# is that microt(*(les serve a str(ct(ral
f(nction, s(pportin) the str(ct(re of the cell, it is also tr(e that the/
are *(ilt o(t of proteins and certain proteins are "no#n to *e the
site of anesthetic activit/. ?enrose and -ameroff contend that
conscio(sness is act(all/ a prod(ct of processes occ(rrin) in this
microt(*(lar c/tos"eleton, #hich are in t(rn ma)nified */ the ne(ron
itself. 5n this vie#, anesthetics exert their effects on the specific
proteins that ma"e (p these microt(*(les, disr(ptin) the 91(ant(m
coherence9 and th(s the conscio(s a#areness that it )enerates. As
opposed to conventional theories of anesthesia, #hich foc(s on
processes operatin) at the s/napse, the -ameroff,?enrose theor/
shifts attention to processes operatin) inside the ne(ral cell itself. 'he
?enrose,-ameroff theor/ of *oth conscio(sness and anesthesia has
attracted a )reat deal of interest, *(t at this sta)e it remains hi)hl/
spec(lative, and has *een critici0ed on *oth lo)ical and empirical
)ro(nds (Er(sh & =h(rchland, 344;).

Anesthesia and A$areness
=linicall/, the s(ccess of )eneral anesthesia is mar"ed */ three
criteria:
the patients lac" of response to intraoperative stim(lation d(rin) the
s(r)ical proced(re itself8
(pon a#a"enin), the patient reports no a#areness of pain d(rin) the
proced(re8
nor does the patient report an/ memories of other s(r)ical events.
5nformation relevant to these iss(es is t/picall/ )leaned from a *rief
post,operative intervie# in #hich the patient is as"ed s(ch 1(estions
as 92hat #as the last thin) /o( remem*er *efore /o( #ent to sleep.
2hat #as the first thin) /o( remem*er #hen /o( #o"e (p. =an /o(
remem*er an/thin) in *et#een these t#o periods. 6id /o( dream
d(rin) /o(r operation.9. Eval(ated in these terms, anesthesia is
almost al#a/s s(ccessf(l. Bevertheless, the (se of m(scle relaxants in
*alanced anesthesia ma"es it possi*le to perform s(r)er/ (nder li)hter
doses of anesthetic a)ents increasin) the ris" of intraoperative
a#areness and postoperative recall at the same time as the/ decrease
the ris" of anesthetic mor*idit/. 5t #as also reco)ni0ed earl/ on that
the (se of m(scle relaxants increased the ris"s f(rther, */ preventin)
inade1(atel/ anestheti0ed patients from comm(nicatin) their
intraoperative a#areness to the s(r)ical team a sit(ation
reminiscent of -arlan Ellisons science,fiction classic, I Have No
Mouth and I Must cream (34<&).
Bevertheless, the incidence of anesthetic a#areness is extremel/ lo#,
#ith recent estimates of s(r)ical a#areness hoverin) aro(nd %.$F of
)eneral s(r)ical cases (Gones & A))ar#al, $%%3). A 9closed case9
anal/sis of ;,:7% malpractice claims a)ainst anesthesiolo)ists from
34&% to 3444 fo(nd onl/ $$ cases of alle)ed intraoperative a#areness
and another &7 cases of postoperative recall. Occasionall/, the incident
is so serio(s as to res(lt in post,tra(matic stress disorder8 *(t more
commonl/, the patient is left #ith onl/ va)(e and nondistressin) ,,
memories of intraoperative events. 5n )eneral s(r)er/, intraoperative
a#areness and postoperative recall are (s(all/ attri*(ta*le to li)ht
anesthesia, machine malf(nction, errors of anesthetic techni1(e, and
increased anesthetic re1(irements for example, on the part of
patients #ho are o*ese or a*(se alcohol or dr()s. 'he incidence of
s(r)ical recall arises in special circ(mstances, s(ch as tra(ma, cardiac,
or o*stetrical s(r)er/, #here cardiovasc(lar circ(mstances dictate
li)hter planes of anesthesia. Even then, the incidence of s(r)ical recall
is remar"a*l/ lo# in part *eca(se even in the a*sence of
anesthesia, the *en0odia0epines often (sed for sedation are
themselves amnestic a)ents (?olster, 344D). 5n fact, modern
anesthetic practice ma/ (nderestimate the incidence of intraoperative
awareness */ interferin) #ith postoperative memory. 'hat is to sa/,
an inade1(atel/ anestheti0ed patient ma/ *e a#are of s(r)ical events
at the time the/ occ(r, *(t *e (na*le to remem*er them later *eca(se
of sedative,ind(ced antero)rade amnesia.
-o#ever lo#, the possi*ilit/ of s(r)ical a#areness means that, in
addition to monitorin) vario(s aspects of vital f(nction d(rin) the
operation, the anesthetist m(st also monitor the patients state of
conscio(sness, or anesthetic depth (Ehoneim, $%%3a). 'his tas" #o(ld
*e made easier if ps/cholo)/ and co)nitive science co(ld reach
consens(s on the ne(ral or *ehavioral correlates of conscio(sness. 5n
the a*sence of s(ch criteria, anesthesiolo)ists have often *een forced
to improvise. One set of standards simpl/ relies on meas(res of
anesthetic potenc/. >esearch has determined the minimum alveolar
concentration (MA=) of inhalant #hich prevents movement in response
to s(r)ical stim(lation in ;%F of patients8 M!C"aware is the
concentration re1(ired to eliminate a#areness of the stim(lation. As a
r(le, MA=,a#a"e is ro()hl/ half of MA=, s())estin) that some of the
movement in response to s(r)ical stim(lation is mediated */
s(*cortical str(ct(res, and does not necessaril/ reflect conscio(s
a#areness. Similar standards for ade1(ate anesthesia, *ased on *lood
plasma levels, have *een #or"ed o(t for intraveno(s dr()s s(ch as
propofol.
5t sho(ld *e noted that the operational definition of MA=,A#are means
that ;%F of patients #ill *e a#are of s(r)ical events despite the
presence of anesthetic ,, altho()h a dose amo(ntin) to a*o(t 3.D MA=
does seem to do the tric". Bevertheless, it is important to s(pplement
"no#led)e of dose,response levels #ith more direct eval(ations of the
patients conscio(s a#areness. Unfort(natel/, man/ o*vio(s clinical
si)ns of conscio(sness s(ch as tal"in) or m(scle movement in
response to s(r)ical stim(lation are o*viated */ the (se of m(scle
relaxants. Accordin)l/, some anesthesiolo)ists rel/ on pres(med
a(tonomic si)ns of conscio(sness, s(ch as the #$T score *ased on
the patients *lood press(re, heart rate, s#eatin), and secretion of
tears.
5n modern practice, most methods for monitorin) the depth of
anesthesia involve the central nervo(s s/stem. Anal/ses of the EEE
po#er spectr(m (derived */ a fast +o(rier transform of the ra# EEE
si)nal) sho# that anestheti0ed patients t/picall/ have a median EEE
fre1(enc/ of $,D -0 or less, #ith 9spectral ed)e fre1(encies9, at the
ver/ hi)h end of the distri*(tion, #ithin or *elo# the ran)e of alpha
activit/ (7,3$ -0). Another derivative of the ra# EEE is provided */
*ispectral anal/sis, #hich emplo/s a complicated set of
transformations to /ield a bispectral inde% (!5S) that ran)es from close
to 3%% in s(*Cects #ho are normall/ a#a"e, to val(es #ell (nder <% in
patients #ho are ade1(atel/ anestheti0ed. Another common
monitorin) techni1(e emplo/s event,related potentials (E>?s, also
"no#n as evo"ed potentials, or E?s) elicited in the EEE */ #ea"
somatosensor/, a(ditor/, or even vis(al stim(lation. Ade1(ate
anesthesia red(ces the amplit(de of the vario(s pea"s and tro()hs in
the E>?, as #ell as the latenc/ of vario(s components representin)
*rainstem response and earl/ and late cortical responses. Of co(rse,
the late 9co)nitive9 components of the E>? #o(ld *e expected to
disappear entirel/ d(rin) ade1(ate anesthesia. An !&# inde% of
conscio(sness reflects the de)ree to #hich three 9midlatenc/9
components of the a(ditor/ E>? are dela/ed #ith respect to their
normal occ(rrence *et#een $% and :; milliseconds after the stim(l(s.
Altho()h most ph/siolo)ical indices of anesthetic depth have *een
validated a)ainst s(ch criteria as movement in response to painf(l
s(r)ical stim(lation, the/ have also *een compared to vario(s aspects
of memor/ performance (erssens & Se*el, $%%3). 5n one st(d/, a
%.$F end,tidal concentration (a meas(re related to MA=) of isofl(rane
prod(ced a s(*stantial impairment of performance on a contin(o(s
reco)nition test even over retention intervals as short as 7 seconds,
#hile a %.:F end,tidal concentration red(ced reco)nition after D$
seconds to 0ero. Another st(d/ sho#ed similar effects for lo# and hi)h
doses of propofol. 5n a st(d/ comparin) mida0olam, isofl(rane,
alfentan/l, and propofol, a ;%F red(ction in recall #as associated #ith
an avera)e !5S score of 7<, #hile an avera)e !5S of <: /ielded
red(ctions of 4;F.
Of co(rse, the simple fact that anesthesia impairs recall does not mean
that anestheti0ed patients lac" on,line a#areness of #hat is )oin) on
aro(nd them. 5n principle, at least, the/ co(ld experience an
antero)rade amnesia for s(r)ical events similar to that #hich occ(rs in
conscio(s sedation. 5n the a*sence of a relia*le and valid ph/siolo)ical
index of conscio(s a#areness somethin) that is not li"el/ to *e
availa*le an/ time soon #hat is needed is some "ind of direct
*ehavioral meas(re of a#areness, s(ch as the patients self,report.
5n *alanced anesthesia, of co(rse, s(ch reports are precl(ded */ the
(se of m(scle relaxants. !(t a variant on *alanced anesthesia "no#n
as the isolated 'orearm technique (5+') act(all/ permits s(r)ical
patients to directl/ report their level of a#areness in response to
commands and 1(eries (>(ssell, 3474). !eca(se m(scle relaxants
tend to *ind relativel/ 1(ic"l/ to receptors in the s"eletal m(sc(lat(re,
if the flo# of *lood is temporaril/ restricted to one forearm */ means
of a to(rni1(et, the m(scles in that part of the *od/ #ill not *e
paral/0ed. And therefore, the patient can respond to the anesthetists
instr(ction to s1(ee0e his or her hand, or raise their fin)ers that is,
if the/ are a#are of the command in the first place.
5nterestin)l/, response to the 5+' is not hi)hl/ correlated #ith
ostensi*le clinical si)ns of conscio(sness. Bor does it predict
postoperative recollection of intraoperative events. 5n one st(d/, more
than :%F of patients receivin) )eneral anesthesia for caesarian
section responded positivel/ to commands8 /et onl/ a*o(t $F had
even fra)mentar/ recollections of the proced(re. On the ass(mption
that a patient #ho responds discriminativel/ to ver*al commands is
clearl/ conscio(s to some extent, the 5+' indicates that intraoperative
a#areness is some#hat )reater than has previo(sl/ *een *elieved. On
the other hand, discriminative *ehavior also occ(rs in the a*sence of
percept(al a#areness, as in cases of 9s(*liminal9 perception, mas"ed
primin), and *lindsi)ht Hsee Meri"le, =hapter I8 2eis"rant0, =hapter
I8 6river, =hapter IJ. Estimates of intraoperative a#areness ma/
indeed *e s(ppressed */ an antero)rade amnesia, #hich effectivel/
prevents patients from remem*erin), and th(s reportin), an/
a#areness that the/ experienced d(rin) s(r)er/.

Unonsious %roessin& 'urin&
Anesthesia
2hile ade1(ate )eneral anesthesia a*olishes conscio(s recollection of
s(r)ical events */ definition, it is possi*le that (nconscio(s (or, for
that matter, conscio(s) intraoperative perception ma/ lead to
(nconscio(s postoperative memor/ that infl(ences the patients
s(*se1(ent experience, tho()ht, and action o(tside of phenomenal
a#areness. Altho()h clinical lore #ithin anesthesiolo)/ incl(des the
9fat lad/ s/ndrome9, in #hich an over#ei)ht patients postoperative
disli"e of her s(r)eon is traced to (n"ind remar"s he made a*o(t her
*od/ #hile she #as anestheti0ed, doc(mented cases are hard to find.
5n the late 34;%s and earl/ 34<%s 6avid =hee", a Aos An)eles
ph/sician and h/pnotherapist, descri*ed a n(m*er of patients #ho,
#hen h/pnoti0ed, remem*ered meanin)f(l so(nds that occ(rred in the
operatin) room partic(larl/ ne)ative remar"s. =hee" claimed to
have corro*orated these reports, and attri*(ted (nexpectedl/ poor
postoperative o(tcomes to (nconscio(s memories of (nto#ard s(r)ical
events. Unfort(natel/, the intervie# method he emplo/ed, h/pnotic
9ideomotor si)nalin)9, is hi)hl/ s(scepti*le to experimenter *ias, and
information that #o(ld corro*orate s(ch memories is not al#a/s
availa*le. Accordin)l/, the possi*ilit/ cannot *e excl(ded that
patients postoperative 9memories9, recovered thro()h this
techni1(e, are confa*(lations.
6espite these methodolo)ical pro*lems, =hee"s s())estion #as
s(*se1(entl/ s(pported */ !ernard Aevinson, #ho as an experiment
sta)ed a *o)(s crisis d(rin) s(r)er/. After the anesthesia had *een
esta*lished (#ith ether), the anesthesiolo)ist, follo#in) a script, as"ed
the s(r)eon to stop *eca(se the patients lips #ere t(rnin) *l(e.
After anno(ncin) that he #as )oin) to )ive ox/)en, and ma"in)
appropriate so(nds aro(nd the respirator, he informed the s(r)eon
that he co(ld carr/ on as *efore. One month later, Aevinson h/pnoti0ed
each of the patients all of #hom had *een selected for hi)h
h/pnoti0a*ilit/ and a*ilit/ to experience h/pnotic a)e re)ression and
too" them *ac" to the time of their operation. Aevinson reported that
fo(r of the ten patients had ver*atim memor/ for the incident, #hile
another fo(r *ecame a)itated and anxio(s8 the remainin) t#o patients
seemed rel(ctant to relive the experience. Aevinsons provocative
experiment s())ested that s(r)ical events co(ld *e perceived */ at
least some anestheti0ed patients, and preserved in memor/ even if
the memories #ere ordinaril/ (nconscio(s, and accessi*le onl/ (nder
h/pnosis.
6espite Aevinsons report, (nconscio(s perception d(rin) )eneral
anesthesia remained lar)el/ (nexplored territor/ (ntil the matter #as
revived */ -enr/ !ennett. 5nspired */ the apparent s(ccess of
=hee"s 9ideomotor si)nalin)9 techni1(e for revealin) (nconscio(s
memories, !ennett )ave anestheti0ed s(r)ical patients a tape,
recorded s())estion that, #hen intervie#ed postoperativel/, the/
#o(ld perform a specific *ehavioral response, s(ch as liftin) their
index fin)er or p(llin) on their ears. Altho()h no patient reported an/
conscio(s recollection of the s())estion, approximatel/ 7%F of the
patients responded appropriatel/ to the experimenters c(e. !ennett,
follo#in) =hee", s())ested that (nconscio(s memories #ere more
li"el/ to *e revealed #ith nonver*al than #ith ver*al responses.
At a*o(t the same time, Evans and >ichardson reported that
intraoperative s())estions, delivered d(rin) )eneral anesthesia, led to
improved patient o(tcome on a n(m*er of varia*les, incl(din) a
si)nificantl/ shorter postoperative hospital sta/. A)ain, the patients
had no conscio(s recollection of receivin) these s())estions. Altho()h
this st(d/ #as not concerned #ith memor/ per se, the apparent
effects of s())estions on post,s(r)ical recover/ certainl/ implied that
the s())estions themselves had *een processed, if (nconscio(sl/, at
the time the/ occ(rred.
As it happens, s(*se1(ent st(dies have failed to confirm the findin)s
of either !ennett et al. or Evans and >ichardson. And more recentl/, a
do(*le,*lind st(d/ inspired */ Aevinsons report, in #hich nonpatient
vol(nteers received s(*anesthetic concentrations of either desfl(rane
or propofol, failed to o*tain an/ evidence of memor/ for a sta)ed
crisis. Bevertheless, these pioneerin) st(dies, com*ined #ith an
increasin) interest in conscio(sness and (nconscio(s processin) #ithin
the #ider field of ps/cholo)/ and co)nitive science stim(lated a revival
of interest in 1(estions of a#areness, perception, and memor/ d(rin)
and after s(r)ical anesthesia, #hich have *een carried o(t #ith
pro)ressivel/ improved paradi)ms.
Of partic(lar importance to this revival #as the artic(lation, in the
347%s, of the distinction *et#een t#o different expressions of episodic
memor/ ,, explicit and implicit (Schacter, 347&). Explicit memor/ is
conscio(s recollection, as exemplified */ the individ(als a*ilit/ to
recall or reco)ni0e some past event. 5mplicit memor/, */ contrast,
refers to an/ chan)e in experience, tho()ht, or action that is
attri*(ta*le to a past event for example, savin)s in relearnin) or
primin) effects. +rom the 34<%s thro()h the 347%s, a )ro#in) *od/ of
evidence indicated that explicit and implicit memor/ #ere dissocia*le.
+or example, amnesic patients sho# primin) effects even tho()h the/
cannot remem*er the primin) events themselves8 and the/ can learn
ne# co)nitive and motor s"ills, even tho()h the/ do not remem*er the
learnin) experience. Similarl/, normal s(*Cects sho# savin)s in
relearnin) material that the/ can neither recall nor reco)ni0e as havin)
*een learned *efore. And, a)ain in normals, primin) is relativel/
(naffected */ man/ experimental manip(lations that have profo(nd
effects on recall and reco)nition. 5n a ver/ real sense, then, implicit
memor/ is (nconscio(s memor/, occ(rrin) in the a*sence of, or at
least independent of, the individ(als conscio(s recollection of the
past Hsee also ihlstrom, 6orfman, & ?ar", =hapter IJ. Accordin)l/,
the experimental paradi)ms developed for st(d/in) implicit memor/ in
amnesic patients and normal s(*Cects #ere soon adapted to the
1(estion of (nconscio(s processin) of intraoperative events in
anesthesia (ihlstrom, 344D8 ihlstrom & Schacter, 344%).
5n o(r first st(d/, patients receivin) isofl(rane anesthesia for elective
s(r)er/ #ere pla/ed, thro()h earphones, an a(ditor/ list of 3; paired
associates consistin) of a familiar #ord as the c(e and its closest
semantic associate as the tar)et e.), ocean"water (ihlstrom,
Schacter, =or", & -(rt, 344%). 'he stim(l(s tape #as presented
contin(o(sl/ from the first incision to the last stitch, for an avera)e of
<& repetitions over an avera)e of ;% min(tes. 5n the recover/ room,
the patients #ere read the c(e terms from the stim(l(s list, as #ell as
a closel/ matched set of c(es from a control list of paired associates,
and as"ed to recall the #ord #ith #hich each c(e had *een paired on
the list read d(rin) s(r)er/: this constit(ted the test of explicit
memor/. +or the test of implicit memor/, the/ #ere read the same
c(es a)ain, and as"ed simpl/ to respond #ith the first #ord that came
to mind. 'he s(*Cects recalled no more tar)et #ords from the
presented list than from a control list, th(s sho#in) that the/ had ver/
poor explicit memor/ for the experience. On the free,association test,
ho#ever, the/ #ere more li"el/ to prod(ce the tar)eted response from
the presented list, compared to control tar)ets, th(s displa/in) a
primin) effect. =ompared to explicit memor/, #hich #as )rossl/
impaired (as #o(ld *e expected #ith ade1(ate anesthesia), implicit
memor/ #as relativel/ spared.
6espite this earl/ s(ccess, s(*se1(ent st(dies emplo/in) similar
paradi)ms prod(ced a mix of positive and ne)ative res(lts. +or
example, #e precisel/ replicated the proced(re descri*ed a*ove #ith
another )ro(p of patients receivin) s(fentan/l, and fo(nd that explicit
and implicit memor/ #ere e1(all/ impaired (=or", ihlstrom, &
Schacter, 344$). Altho()h the t#o st(dies, ta"en to)ether, s())ested
the interestin) h/pothesis that different anesthetic a)ents mi)ht have
different effects on implicit memor/, a more parsimonio(s concl(sion
mi)ht have *een that the isofl(rane effects #ere sp(rio(s. 5n a de*ate
at the Second 5nternational S/mposi(m on Memor/ and A#areness in
Anesthesia, held in 344$, experimental ps/cholo)ists and
anesthesiolo)ists a)reed in de*ate that memor/ for events d(rin)
anesthesia had not /et *een convincin)l/ demonstrated. Over the next
fe# /ears, ho#ever, the literat(re *e)an to settle, so that a
comprehensive 1(antitative revie# of :: st(dies co(ld concl(de that
ade1(atel/ anestheti0ed patients can, indeed, sho# postoperative
memor/ for (nconscio(sl/ processed intraoperative events (see also
!one*a""er, Gelicic, ?asschier, & !on"e, 344<8 =or", =o(t(re, &
ihlstrom, 344&8 Meri"le & 6aneman, 344<).

!he Limits of (m)liit Memory in
Anesthesia
Altho()h the more recent literat(re contin(es to contain a mix of
positive and ne)ative res(lts, there are simpl/ too man/ positive
findin)s to *e i)nored (Ehoneim, $%%3*). At the same time, the
literat(re contains eno()h ne)ative st(dies, and other anomalo(s
res(lts, to #arrant f(rther investi)ation. +or example, Meri"le and
6aneman concl(ded that the evidence for (nconscio(s processin)
d(rin) )eneral anesthesia #as not limited to 9indirect9 meas(res of
implicit memor/, and extended to 9direct9 meas(res of explicit
memor/ as #ell (Meri"le & 6aneman, 344<). 'his is a s(rprisin)
statement, )iven that ade1(atel/ anestheti0ed patients lac" conscio(s
recollection */ definition. -o#ever, these a(thors incl(ded in their
s(rve/ onl/ the fe# tests of explicit memor/ that enco(ra)ed
)(essin), and excl(ded the man/ st(dies that disco(ra)ed )(essin).
2hile )(essin) /ields a more exha(stive meas(re of conscio(s
recollection, it is also tr(e that )(essin) can *e *iased, (nconscio(sl/,
*/ primin) itself. 'herefore, it is li"el/ that some of the 9explicit9
memor/ identified */ Meri"le and 6aneman is, in fact, contaminated
*/ implicit memor/. 5n s(pport of this idea, a st(d/ emplo/in) the
9process dissociation9 proced(re confirmed that postoperative memor/
#as confined to a(tomatic primin) effects, and did not involve
conscio(s recollection (A(*"e, erssens, ?haf, & Se*el, 3444).
A persistin) iss(e is #hether postoperative implicit memor/ mi)ht *e
an artifact of fl(ct(ations in anesthetic depth #hich occ(r nat(rall/
d(rin) s(r)er/. 5n the st(d/ C(st descri*ed, even implicit memor/
varied as a f(nction of the patients level of anesthesia. ?atients
sho#ed more primin) for #ords presented at !5S levels a*ove <%, and
no primin) for items presented at !5S levels *elo# :%. A s(*se1(ent
st(d/ from the same )ro(p, #hich confined stim(l(s presentation to
!5S levels ran)in) from :% to <%, /ielded no evidence of implicit
memor/ (erssens, O(chi, & Se*el, $%%;). Altho()h implicit memor/
ma/ *e spared at a depth of anesthesia s(fficient to a*olish explicit
memor/, implicit memor/ itself ma/ *e a*olished at deeper levels.
Still, it is not clear that the a*olition of implicit memor/ is a *enefit
#orth the ris"s of maintainin) ver/ deep levels of anesthesia
thro()ho(t s(r)er/.
Explicit and implicit memor/ are also dissociated in conscious sedation,
an anesthetic techni1(e that is increasin)l/ pop(lar in o(tpatient
s(r)er/. 5n conscio(s sedation, the patient receives medication for
anal)esia and sedation, and perhaps re)ional anesthesia, *(t remains
conscio(s thro()ho(t the proced(re. 5t is #ell "no#n that hi)h doses
of sedative dr()s have amnesic effects on their o#n, s(ch that
patients often have poor memor/ for events that occ(rred d(rin) the
proced(re. As it happens, sedative amnesia prod(ced */ dr()s s(ch as
dia0epam or propofol also dissociates explicit and implicit memor/
(=or", -eaton, & ihlstrom, 344<8 ?olster, 344D). As #ith )eneral
anesthesia, st(dies emplo/in) the process,dissociation proced(re
confirm that sedative amnesia impairs conscio(s recollection, *(t
spares a(tomatic primin) effects.
Most #or" on implicit memor/ emplo/s tests of repetition priming,
s(ch as stem, or fra)ment,completion, in #hich the tar)et item
recapit(lates, in #hole or in part, the prime itself for example, #hen
the #ord ashtray primes completion of the stem ash". >epetition
primin) can *e mediated */ a perception,*ased representation of the
prime, #hich holds information a*o(t the ph/sical properties of the
item, *(t not a*o(t its meanin). !(t there are other forms of primin),
s(ch as semantic primin), #here the relationship *et#een prime and
tar)et is *ased on 9deeper9 processin) of the prime for example,
#hen the prime cigarette primes completion of the stem ash" #ith
"tray as opposed to "can. Semantic primin) re1(ires more than
ph/sical similarit/ *et#een prime and tar)et, and m(st *e mediated
*/ a meanin),*ased representation of the prime. 'he distinction
*et#een repetition and semantic primin) is sometimes s(*tle. +or
example, in the isofl(rane st(d/ descri*ed earlier, the paired
associates presented as primes #ere lin"ed */ meanin), *(t *eca(se
*oth elements of the pair #ere presented at the time of st(d/, the
primin) effect o*served co(ld have *een mediated */ a perception,
*ased representation, rather than a meanin),*ased one. 'he point is
that implicit memor/ follo#in) s(r)ical anesthesia is fairl/ #ell
esta*lished #hen it comes to repetition primin), *(t concl(sions a*o(t
semantic primin) are m(ch less sec(re. +e#er st(dies have emplo/ed
semantic primin) paradi)ms, and relativel/ fe# of these st(dies have
/ielded (nam*i)(o(sl/ positive res(lts (Ehoneim, $%%3*). 5f semantic
primin) occ(rs at all follo#in) )eneral anesthesia, it is most li"el/ to
occ(r for items presented at relativel/ li)ht levels of anesthesia, as
indicated */ indices s(ch as !5S. At deeper planes of anesthesia,
implicit memor/ if it occ(rs at all is li"el/ to *e limited to
repetition primin).
'he distinction *et#een perception,*ased and meanin),*ased primin)
ma/ have implications for the (se of intraoperative s())estions to
improve post,s(r)ical o(tcome. 5f implicit memor/ follo#in)
anesthesia is limited to repetition primin), impl/in) that the
anestheti0ed patients state of conscio(sness does not permit
semantic anal/sis of the intraoperative messa)e, it is hard to see ho#
s(ch s())estions co(ld have an/ effects at all. 5n fact, a comparative
st(d/ fo(nd that intraoperative s())estions had no more effect on
postoperative pain than did pre,operative s())estions of the same sort
or, for that matter, the pre, and intraoperative readin) of short
stories. 5ntraoperative s())estions #ill do no harm, and patients ma/
derive some 9place*o9 *enefit from the simple "no#led)e that the/ are
receivin) them d(rin) s(r)er/. 'o the extent that intra,operative
s())estions do some )ood, the limitations on information processin)
d(rin) anesthesia ma/ mean that an/ positive effects are more li"el/
to *e mediated */ their prosod/, and other ph/sical feat(res, than */
their meanin): a soothin) voice ma/ *e more important that #hat the
voice sa/s. 5f anesthesiolo)ists #ant patients to respond to the specific
semantic content of therape(tic messa)es, s(ch messa)es are
pro*a*l/ *etter delivered #hile patients are a#a"e, d(rin) the pre,
operative visit that is alread/ esta*lished as the standard of care.

(m)liit Memory or (m)liit %ere)tion*
?rimin) effects are evidence of implicit memor/, *(t the/ can also
serve as evidence of implicit perception a term coined to refer to the
effect of an event on experience, tho()ht, and action, that is
attri*(ta*le to a stim(l(s event, in the a*sence of (or independent of)
conscio(s perception of that event (ihlstrom, !arnhardt, & 'atar/n,
344$). 5mplicit perception is exemplified */ 9s(*liminal9 perception of
de)raded stim(li, as #ell as ne(rolo)ical s/ndromes s(ch as
9*lindsi)ht9 and ne)lect Hsee Meri"le, =hapter I8 2eis"rant0, =hapter
I8 6river, =hapter IJ. 5n )eneral anesthesia, the patients are
pres(ma*l/ (na#are of the primin) events at the time the/ occ(rred.
+or that reason, evidence of implicit memor/ follo#in) )eneral
anesthesia is also evidence of implicit perception.

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