(275752203) Resuscitation Fluids

The New England Journal of Medicine
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T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e
re/iew article
Critical Care Medicine
Simon R. *infer& M.D.& and Jean0oui+ Vincent& M.D.& !h.D.& Editors
Re+u+citation *luid+
John A. M,1urgh& M.2.& 2.-h.& !h.D.& and Michael 3. M,then& M.D.& M.2.& 2.S.
luid re+u+citation with colloid and cr,+talloid +olution+ i+
a u1i4uitou+ inter/ention in acute medicine. The +election and u+e of
re+u+cita0 tion f luid+ i+ 1a+ed on #h,+iological #rinci#le+& 1ut clinical #ractice
i+ deter0
*
mined largel, 1, clinician #reference& with mar5ed regional /ariation. No ideal
re+u+citation f luid e6i+t+. There i+ emerging e/idence that the t,#e and do+e of
re+u+citation f luid ma, affect #atient0centered outcome+.
De+#ite what ma, 1e inferred from #h,+iological #rinci#le+& colloid +olution+ do
not offer +u1+tanti/e ad/antage+ o/er cr,+talloid +olution+ with re+#ect to hemod,0
namic effect+. Al1umin i+ regarded a+ the reference colloid +olution& 1ut it+ co+t i+ a
limitation to it+ u+e. Although al1umin ha+ 1een determined to 1e +afe for u+e a+ a
re+u+citation f luid in mo+t criticall, ill #atient+ and ma, ha/e a role in earl, +e#+i+&
it+ u+e i+ a++ociated with increa+ed mortalit, among #atient+ with traumatic 1rain
injur,. The u+e of h,dro6,eth,l +tarch 78ES9 +olution+ i+ a++oci0 ated with
increa+ed rate+ of renal0re#lacement thera#, and ad/er+e e/ent+ among #atient+ in
the inten+i/e care unit 7I-U9. There i+ no e/idence to recommend the u+e of other
+emi+,nthetic colloid +olution+.
2alanced +alt +olution+ are #ragmatic initial re+u+citation f luid+& although there
i+ little direct e/idence regarding their com#arati/e +afet, and eff icac,. The u+e of
normal +aline ha+ 1een a++ociated with the de/elo#ment of meta1olic acido+i+ and
acute 5idne, injur,. The +afet, of h,#ertonic +olution+ ha+ not 1een e+ta1li+hed.
All re+u+citation f luid+ can contri1ute to the formation of inter+titial edema&
#articularl, under inf lammator, condition+ in which re+u+citation f luid+ are u+ed
e6ce++i/el,. -ritical care #h,+ician+ +hould con+ider the u+e of re+u+citation f luid+
a+ the, would the u+e of an, other intra/enou+ drug. The +election of the +#ecif ic f
luid +hould 1e 1a+ed on indication+& contraindication+& and #otential to6ic effect+ in
order to ma6imi:e eff icac, and minimi:e to6icit,.
8 i + t o r , o f * l u i d R e + u + c i t a
t i o n
In $;%'& Ro1ert ewin+ de+cri1ed the effect+ of the intra/enou+ admini+tration of
an al5alini:ed +alt +olution in treating #atient+ during the cholera #andemic. 8e
o1+er/ed that <the 4uantit, nece++ar, to 1e injected will #ro1a1l, 1e found to de0
#end u#on on the 4uantit, of +erum lo+t= the o1ject 1eing to #lace the #atient in
nearl, hi+ ordinar, +tate a+ to the 4uantit, of 1lood circulating in the /e++el+.>
$
The
o1+er/ation+ of ewin+ are a+ rele/ant toda, a+ the, were nearl, '((
,ear+ ago.
A+anguinou+ f luid
re+u+citation in the
modern era wa+
ad/anced 1, Ale6i+
8artmann& who modif
ied a #h,+iologic +alt
+olution de/elo#ed in
$;;? 1, Sidne, Ringer
for reh,dration of
children with
ga+troenteriti+.
'
@ith
the de/elo#ment of
1lood fractionation in
$A)$& human al1umin
wa+ u+ed for the f ir+t
time in large 4uantitie+
for re+u+citation of
#atient+ who were
1urned during the attac5
on !earl 8ar1or in the
+ame ,ear.
Toda,& a+anguinou+ f
luid+ are u+ed in
almo+t all #atient+
undergoing general
*rom the Uni/er+it, of New South @ale+& the Di/i+ion of -ritical -are
and Trauma& 3eorge In+titute for 3lo1al 8ealth& and the De#artment
of Inten+i/e -are Medi0 cine& St. 3eorge 8o+#ital B all in S,dne, 7
J.A.M.9= and the National In+titute for 8ealth Re+earch& Uni/er+it,
-ollege on0 don 8o+#ital+ 2iomedical Re+earch -en0 tre& ondon
7M.3.M.9. Addre++ re#rint re4ue+t+ to Dr. M,1urgh at the De#art0
ment of Inten+i/e -are Medicine& St. 3eorge 8o+#ital& 3ra, St.&
Cogarah ''$D& S,dne,& NS@& Au+tralia& or at jm,1urghE
georgein+titute.org.au.
N Engl J Med
2013;369:1243-51.
DOI:
10.1056NEJMra1
20!62"
Copyright 2013
Massachusetts Medical
Society.
n engl j med %FA=$% nejm.org +e#tem1er 'F& '($%
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#
-a#illar,
E$%ili&ri%'
umen
(ealt)
*
gl*c+c
al*,
-
.ea/*
Da'a
ged
gl*c+c
al*,
Re
d
cel
l+
Endothel
ial cel
!la+
ma
#rot
ein+
Endothel
ial cel
!la+
ma
#rot
ein+
Endothel
ial cel
/olume. Since /enou+ return i+ in
e4uili1rium with cardiac out#ut&
+,m#atheticall, mediated re+#on+e+
regulate 1oth efferent ca#acitance
7/enou+9 and afferent conductance
7arterial9 cir0 culation+ in addition to
m,ocardial contractilit,.
%
Adjuncti/e thera#ie+ to f luid
re+u+citation& +uch a+ the u+e of
catecholamine+ to augment cardiac
contraction and /enou+ return& need to
1e con0 +idered earl, to +u##ort the
failing circulation.
)
In addition& change+ to the
microcirculation in /ital organ+ /ar,
widel, o/er time and under dif0 ferent
#athologic +tate+& and the effect+ of f luid
admini+tration on end0organ function
+hould 1e con+idered along with effect+
on intra/a+cular /olume.
T h e !h , + i o l o g , o f * l
u i d
R e + u + c i t a t
i o n
*or decade+& clinician+ ha/e 1a+ed their
+election of re+u+citation f luid+ on the
cla++ic com#art0 ment model B +#ecif
icall,& the intracellular f luid
com#artment and the inter+titial and
intra/a+cular com#onent+ of the
e6tracellular f luid com#art0 ment and
the factor+ that dictate f luid di+tri1u0
tion acro++ the+e com#artment+. In $;AF&
Engli+h #h,+iologi+t Erne+t Starling
found that ca#illar0 ie+ and #o+tca#illar,
/enule+ acted a+ a +emi#er0 mea1le
mem1rane a1+or1ing f luid from the in0
ter+titial +#ace.
?
Thi+ #rinci#le wa+
ada#ted to identif, the h,dro+tatic and
oncotic #re++ure gra0 dient+ acro++ the
+emi#ermea1le mem1rane a+ the
#rinci#al determinant+ of tran+/a+cular
e6change.
F
Recent de+cri#tion+ ha/e 4ue+tioned
the+e cla++ic model+.
D
A we1 of
mem1rane01ound gl,0 co#rotein+ and
#roteogl,can+ on the luminal
0ig%re 1. 1+le +2 t)e End+t)elial 3l*c+cal*, .a*er in t)e 45e +2 1e5%5citati+n
0l%id5.
The +tructure and function of the endothelial
gl,cocal,6 la,er& a we1 of mem1rane01ound
gl,co#rotein+ and #roteogl,can+ on endothelial
cell+& are 5e, determinant+ of mem1rane
#ermea1ilit, in /ariou+ /a+cular organ +,+0 tem+.
!anel A +how+ a health, endothelial gl,cocal,6 la,er&
and !anel 2 +how+ a damaged endothelial
gl,cocal,6 la,er and re+ultant effect on #er0
mea1ilit,& including the de/elo#ment of inter+titial
edema in +ome #atient+& #articularl, tho+e with inf
lammator, condition+ 7e.g.& +e#+i+9.
ane+the+ia for major +urger,& in
#atient+ with +e/ere trauma and 1urn+&
and in #atient+ in the I-U. It i+ one of
the mo+t u1i4uitou+ inter/en0 tion+ in
acute medicine.
*luid thera#, i+ onl, one com#onent
of a com#le6 hemod,namic re+u+citation
+trateg,. It i+ targeted #rimaril, at
re+toring intra/a+cular
+ide of endothelial cell+ ha+ 1een identif
ied a+ the endothelial gl,cocal,6 la,er
;
7*ig. $9. The +u1gl,cocal,6 +#ace
#roduce+ a colloid oncotic #re++ure that
i+ an im#ortant determinant of
tran+ca#illar, f low. Nonfene+trated
ca#illarie+ throughout the inter+titial
+#ace ha/e 1een iden0 tif ied& indicating
that a1+or#tion of f luid doe+ not occur
through /enou+ ca#illarie+ 1ut that f
luid from the inter+titial +#ace& which
enter+ through a +mall num1er of large
#ore+& i+ re0 turned to the circulation
#rimaril, a+ l,m#h that i+ regulated
through +,m#atheticall, mediated
re+#on+e+.
A
The +tructure and function of the
endothelial gl,cocal,6 la,er are 5e,
determinant+ of mem0 1rane
#ermea1ilit, in /ariou+ /a+cular organ
+,+0
$')
)
-r itic a l - a r e
Medicine
tem+. The integrit,& or <lea5ine++&> of
thi+ la,er& and there1, the #otential for
the de/elo#ment of inter+titial edema&
/arie+ +u1+tantiall, among organ
+,+tem+& #articularl, under inf
lammator, condition+& +uch a+ +e#+i+&
$(
and after +urger, or trauma& when
re+u+citation f luid+ are common0 l,
u+ed.
T h e I d e a l R e + u + c i t a t i o
n * l u i d
The ideal re+u+citation f luid +hould 1e
one that #roduce+ a #redicta1le and
+u+tained increa+e in intra/a+cular
/olume& ha+ a chemical com#o+i0 tion a+
clo+e a+ #o++i1le to that of e6tracellular f
luid& i+ meta1oli:ed and com#letel,
e6creted without accumulation in
ti++ue+& doe+ not #ro0 duce ad/er+e
meta1olic or +,+temic effect+& and i+
co+t0effecti/e in term+ of im#ro/ing
#atient outcome+. -urrentl,& there i+ no
+uch f luid a/ail0 a1le for clinical u+e.
Re+u+citation f luid+ are 1roadl,
categori:ed into colloid and cr,+talloid
+olution+ 7Ta1le $9. -olloid +olution+
are +u+#en+ion+ of molecule+ within a
carrier +olution that are relati/el, inca0
#a1le of cro++ing the health,
+emi#ermea1le ca#illar, mem1rane
owing to the molecular weight of the
molecule+. -r,+talloid+ are +olution+ of
ion+ that are freel, #ermea1le 1ut contain
con0 centration+ of +odium and chloride
that deter0 mine the tonicit, of the f
luid.
!ro#onent+ of colloid +olution+ ha/e
argued that colloid+ are more effecti/e in
e6#anding intra/a+cular /olume 1ecau+e
the, are retained within the intra/a+cular
+#ace and maintain col0 loid oncotic
#re++ure. The /olume0+#aring effect of
colloid+& a+ com#ared with
cr,+talloid+& i+ con+idered to 1e an
ad/antage& which i+ con0 /entionall,
de+cri1ed in a $G% ratio of colloid+ to cr,+talloid+ to
maintain intra/a+cular /olume. Semi+,nthetic
colloid+ ha/e a +horter duration of effect than
human al1umin +olution+ 1ut are acti/el,
meta1oli:ed and e6creted.
!ro#onent+ of cr,+talloid +olution+ ha/e ar0 gued
that colloid+& in #articular human al1umin& are
e6#en+i/e and im#ractical to u+e a+ re+u+ci0 tation f
luid+& #articularl, under f ield0t,#e condi0 tion+.
-r,+talloid+ are ine6#en+i/e and widel, a/aila1le
and ha/e an e+ta1li+hed& although un0 #ro/en& role
a+ f ir+t0line re+u+citation f luid+. 8owe/er& the
u+e of cr,+talloid+ ha+ cla++icall, 1een a++ociated
with the de/elo#ment of clini0 call, +ignif icant
inter+titial edema.
T , #e + o f R e + u + c i t a t i o n * l
u i d
3lo1all,& there i+ wide
/ariation in clinical #rac0
tice with re+#ect to the
+election of re+u+citation f
luid. The choice i+
determined largel, 1,
regional and clinician
#reference+ that are 1a+ed on
in+ti0 tutional #rotocol+&
a/aila1ilit,& co+t& and com0
mercial mar5eting.
$$
-on+en+u+ document+ a1out
the u+e of re+u+citation f
luid+ ha/e 1een de/el0 o#ed
and directed #rimaril, at
+#ecif ic #atient
#o#ulation+&
$'0$)
1ut +uch
recommendation+ ha/e 1een
1a+ed largel, on e6#ert
o#inion or low0 4ualit,
clinical e/idence. S,+tematic
re/iew+ of randomi:ed&
controlled trial+ ha/e
con+i+tentl, +hown that there
i+ little e/idence that
re+u+cita0 tion with one t,#e
of f luid a+ com#ared with
an0 other reduce+ the ri+5 of
death
$?
or that an, +olu0 tion
i+ more effecti/e or +afer
than an, other.
$F
#
l
&
%
'
i
n
8uman al1umin 7) to ?H9 in
+aline i+ con+idered to 1e the reference
colloidal +olution. It i+ #ro0 duced 1, the
fractionation of 1lood and i+ heat0
treated to #re/ent tran+mi++ion of
#athogenic /iru+e+. It i+ an e6#en+i/e
+olution to #roduce and di+tri1ute& and
it+ a/aila1ilit, i+ limited in low0 and
middle0income countrie+.
In $AA;& the -ochrane Injurie+ 3rou#
Al1u0 min Re/iewer+ #u1li+hed a meta0
anal,+i+ com0 #aring the effect+ of
al1umin with tho+e of a range of
cr,+talloid +olution+ in #atient+ with
h,#o/olemia& 1urn+& or
h,#oal1uminemia and concluded that
the admini+tration of al1umin wa+
a++ociated with a +ignif icant increa+e in
the rate of death 7relati/e ri+5& $.F;= A?H
conf idence inter/al I-IJ& $.'F to '.'%=
!K(.($9.
$D
De+#ite it+ limitation+&
including the +mall +i:e of the in0 cluded
+tudie+& thi+ meta0anal,+i+ cau+ed +u10
+tantial alarm& #articularl, in countrie+
that u+ed large amount+ of al1umin for
re+u+citation.
A+ a re+ult& in/e+tigator+ in Au+tralia
and New Lealand conducted the Saline
/er+u+ Al1umin *luid E/aluation
7SA*E9 +tud,& a 1linded& ran0 domi:ed&
controlled trial& to e6amine the +afet, of
al1umin in FAAD adult+ in the I-U.
$;
The +tud, a++e++ed the effect of
re+u+citation with
)H al1umin& a+ com#ared with +aline&
on the rate of death at '; da,+. The
+tud, +howed no +ignif icant difference
1etween al1umin and +a0 line with
re+#ect to the rate of death 7relati/e
ri+5& (.AA= A?H -I& (.A$ to $.(A= ! M
(.;D9 or the de/elo#ment of new organ
failure.
$')?
6a&le 1. 6*7e5 and C+'7+5iti+n5 +2 1e5%5citati+n 0l%id5.8
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+tarch +tarch +tarch +tarch +tarch gelatin gelatin
"+molarit, 'A$ '?( %
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Q To con/ert the /alue+ for #ota++ium to milligram+ #er deciliter& di/ide 1, (.'??;. To con/ert the /alue+ for calcium to milligram+ #er deciliter& di/ide 1, (.'?(. To con/ert the /alue+ for
magne+ium to milligram+ #er deciliter& di/ide 1, (.)$$).
-r itic a l - a r e Medicine
Additional anal,+e+ from the SA*E +tud, #ro0 /ided new
in+ight+ into f luid re+u+citation among #atient+ in the I-U.
Re+u+citation with al1umin wa+ a++ociated with a +ignif icant
increa+e in the rate of death at ' ,ear+ among #atient+ with
traumatic 1rain injur, 7relati/e ri+5& $.F%= A?H -I& $.$D to '.'F=
! M (.((%9.
$A
Thi+ outcome ha+ 1een attri1uted to
increa+ed intracranial #re+0 +ure& #articularl, during
the f ir+t wee5 after in0 jur,.
'(
Re+u+citation with
al1umin wa+ a++ociated with a decrea+e in the
adju+ted ri+5 of death at
'; da,+ in #atient+ with +e/ere +e#+i+ 7odd+ ra0 tio&
(.D$= A?H -I& (.?' to (.AD= ! M (.(%9& +ugge+t0 ing a
#otential& 1ut un+u1+tantiated& 1enef it in #atient+
with +e/ere +e#+i+.
'$
No +ignif icant 1e0 tween0grou#
difference in the rate of death at
'; da,+ wa+ o1+er/ed among #atient+ with h,#o0
al1uminemia 7al1umin le/el& R'? g #er liter9 7odd+
ratio& (.;D= A?H -I& (.D% to $.(?9.
''
In the SA*E +tud,& no +ignif icant difference in
hemod,namic re+u+citation end #oint+& +uch a+ mean
arterial #re++ure or heart rate& wa+ o1+er/ed 1etween
the al1umin and +aline grou#+& although the u+e of
al1umin wa+ a++ociated with a +ignifi0 cant 1ut
clinicall, +mall increa+e in central /enou+ #re++ure.
The ratio of the /olume+ of al1umin to the /olume+
of +aline admini+tered to achie/e the+e end #oint+
wa+ o1+er/ed to 1e $G$.).
In '($$& in/e+tigator+ in +u10Saharan Africa
re#orted the re+ult+ of a randomi:ed& controlled trial
B the *luid E6#an+ion a+ Su##orti/e Ther0 a#,
7*EAST9 +tud,
'%
B com#aring the u+e of 1olu+e+ of
al1umin or +aline with no 1olu+e+ of re+u+citation f
luid in %$)$ fe1rile children with im#aired #erfu+ion. In thi+ +tud,&
1olu+ re+u+ci0 tation with al1umin or +aline re+ulted in +imilar rate+ of
death at ); hour+& 1ut there wa+ a +ig0 nif icant increa+e in the rate of
death at ); hour+ a++ociated with 1oth thera#ie+& a+ com#ared
with no 1olu+ thera#, 7relati/e ri+5& $.)?= A?H -I&
$.$% to $.;F= ! M (.((%9. The #rinci#al cau+e of death in the+e #atient+
wa+ cardio/a+cular col0 la#+e rather than f luid o/erload or
neurologic cau+e+& +ugge+ting a #otentiall, ad/er+e interac0 tion
1etween 1olu+ f luid re+u+citation and com0 #en+ator, neurohormonal
re+#on+e+.
')
Although thi+ trial wa+ conducted in a +#ecif ic #ediatric
#o#ulation in an en/ironment in which critical care facilitie+ were
limited or a1+ent& the re+ult+ call into 4ue+tion the role of 1olu+ f luid
re+u+ci0 tation with either al1umin or +aline in other #o#ulation+ of
criticall, ill #atient+.
The o1+er/ation+ in the+e 5e, +tudie+ chal0
lenge #h,+iologicall, 1a+ed conce#t+
a1out the efficac, of al1umin and it+ role
a+ a re+u+citation +olution. In acute
illne++& it a##ear+ that the hemo0 d,namic
effect+ and effect+ on #atient0centered
outcome+ of al1umin are largel,
e4ui/alent to tho+e of +aline. @hether
+#ecif ic #o#ulation+ of #atient+&
#articularl, tho+e with +e/ere +e#+i+& ma,
1enef it from al1umin re+u+citation
remain+ to 1e determined.
;e'i5*nt)etic
C+ll+id5
The limited a/aila1ilit, and relati/e
e6#en+e of human al1umin ha/e #rom#ted
the de/elo#ment and increa+ing u+e of
+emi+,nthetic colloid +olu0 tion+ during
the #a+t )( ,ear+. 3lo1all,& 8ES +olu0
tion+ are the mo+t commonl, u+ed
+emi+,nthetic colloid+& #articularl, in
Euro#e.
$$
"ther +emi+,n0 thetic colloid+
include +uccin,lated gelatin& urea0 lin5ed
gelatinP#ol,geline #re#aration+& and de60
tran +olution+. The u+e of de6tran
+olution+ ha+ largel, 1een +u#er+eded 1,
the u+e of other +emi0 +,nthetic +olution+.
8ES +olution+ are #roduced 1,
h,dro6,eth,l +u1+titution of am,lo#ectin o1tained from
+or0 ghum& mai:e& or #otatoe+. A high degree of +u10
+titution on gluco+e molecule+ #rotect+ again+t
h,drol,+i+ 1, non+#ecif ic am,la+e+ in the 1lood& there1,
#rolonging intra/a+cular e6#an+ion& 1ut thi+ action
increa+e+ the #otential for 8ES to accumulate in
reticuloendothelial ti++ue+& +uch a+ +5in 7re+ulting in
#ruritu+9& li/er& and 5idne,.
The u+e of 8ES& #articularl, high0molecular0 weight
#re#aration+& i+ a++ociated with alteration+ in coagulation
B +#ecif icall,& change+ in /i+co0 ela+tic mea+urement+
and f i1rinol,+i+ B al0 though the clinical con+e4uence+
of the+e effect+ in +#ecif ic #atient #o#ulation+& +uch a+
tho+e undergoing +urger, or #atient+ with trauma& are
undetermined.
'?
Stud, re#ort+ ha/e 4ue+tioned the +afet,
of concentrated 7$(H9 8ES +olution+ with a molecular
weight of more than '(( 5D and a molar +u1+titution
ratio of more than (.? in #atient+ with +e/ere +e#+i+& citing
increa+ed rate+ of death& acute 5idne, injur,& and u+e of
renal0 re#lacement thera#,.
'F&'D
-urrentl, u+ed 8ES +olution+ ha/e reduced
concentration+ 7FH9 with a molecular weight of
$%( 5D and molar +u1+titution ratio+ of (.%; to
(.)?. The, are a/aila1le in /ariou+ t,#e+ of cr,+0 talloid
carrier +olution+. 8ES +olution+ are wide0 l, u+ed in
#atient+ undergoing ane+the+ia for major +urger,&
#articularl, a+ a com#onent of goal0directed
#erio#erati/e f luid +trategie+&
';
a+
$')D
a f ir+t0line re+u+citation f luid in militar, the0 ater+&
'A
and
in #atient+ in the I-U.
$$
2ecau+e of the #otential that +uch
+olution+ ma, accumu0 late in ti++ue+& the recommended
ma6imal dail, do+e of 8ES i+ %% to ?( ml #er 5ilogram of 1od,
weight #er da,.
In a 1linded& randomi:ed& controlled trial in/ol/ing ;((
#atient+ with +e/ere +e#+i+ in the I-U&
%(
Scandina/ian
in/e+tigator+ re#orted that the u+e of FH 8ES 7$%(N(.)'9& a+
com#ared with RingerO+ acetate& wa+ a++ociated with a +ignif i0
cant increa+e in the rate of death at A( da,+ 7relati/e ri+5&
$.$D= A?H -I& $.($ to $.%(= ! M (.(%9 and a +ignificant %?H
relati/e increa+e in the rate of renal0re#lacement thera#,.
The+e re+ult+ are con+i+tent with #re/iou+ trial+ of $(H 8ES
7'((N(.?9 in +imilar #atient #o#ulation+.
'D
In a 1linded& randomi:ed& controlled +tud,& called the
-r,+talloid /er+u+ 8,dro6,eth,l Starch Trial 7-8EST9&
in/ol/ing D((( adult+ in the I-U& the u+e of FH 8ES 7$%(N(.)9&
a+ com#ared with +aline& wa+ not a++ociated with a +ignif icant
dif0 ference in the rate of death at A( da,+ 7relati/e ri+5& $.(F=
A?H -I& (.AF to $.$;= ! M (.'F9. 8ow0 e/er& the u+e of 8ES
wa+ a++ociated with a +ig0 nificant '$H relati/e increa+e in the
rate of renal0 re#lacement thera#,.
%$
2oth the Scandina/ian trial and -8EST +howed no +ignif
icant difference in +hort0term hemod,namic re+u+citation end
#oint+& a#art from tran+ient increa+e+ in central /enou+ #re+0
+ure and lower /a+o#re++or re4uirement+ with 8ES in
-8EST. The o1+er/ed ratio of 8ES to cr,+talloid in the+e
trial+ wa+ a##ro6imatel,
$G$.%& which i+ con+i+tent with the ratio of al1u0 min to +aline
re#orted in the SA*E +tud,
$;
and in other recent 1linded&
randomi:ed& controlled trial+ of 8ES.
%'&%%
In -8EST& 8ES wa+ a++ociated with increa+e+ in urine
out#ut in #atient+ at low ri+5 for acute 5idne, injur, 1ut with
#arallel increa+e+ in +e0 rum creatinine le/el+ in #atient+ at
increa+ed ri+5 for acute 5idne, injur,. In
addition& the u+e of 8ES wa+ a++ociated with
an increa+ed u+e of 1lood #roduct+ and an
increa+ed rate of ad/er+e e/ent+& #articularl,
#ruritu+.
%$
@hether the+e re+ult+ are generali:a1le to
the u+e of other +emi+,nthetic colloid
+olution+& +uch a+ gelatin or #ol,geline
#re#aration+& i+ un0 5nown. A recent
o1+er/ational +tud, ha+ rai+ed concern a1out
the ri+5 of acute 5idne, injur, a++ociated with
the u+e of gelatin +olution+.
%)
8owe/er& the+e +olution+ ha/e not 1een
+tudied
in high04ualit, randomi:ed& controlled trial+ to date. In light of current
e/idence of the lac5 of clinical 1enef it& #otential ne#hroto6icit,& and
increa+ed co+t& the u+e of +emi+,nthetic colloid+ for f luid re+u+citation in
criticall, ill #atient+ i+ diff icult to ju+tif,.
Cr*5tall+id5
Sodium chloride 7+aline9 i+ the mo+t commonl, u+ed cr,+talloid +olution on
a glo1al 1a+i+& #ar0 ticularl, in the United State+. Normal 7(.AH9 +a0 line
contain+ +odium and chloride in e4ual con0 centration+& which ma5e+ it
i+otonic a+ com#ared with e6tracellular f luid. The term <normal +aline>
come+ from the +tudie+ of red0cell l,+i+ 1, Dutch #h,+iologi+t 8artog
8am1urger in $;;' and
$;;%& which +ugge+ted that (.AH wa+ the concen0 tration of +alt in human
1lood& rather than the actual concentration of (.FH.
%?
The +trong ion difference of (.AH +aline i+ :ero& with the re+ult that the
admini+tration of large /olume+ of +aline re+ult+ in a h,#erchlore0 mic
meta1olic acido+i+.
%F
Ad/er+e effect+ +uch a+ immune
%D
and renal
%;
d,+function ha/e 1een attri1uted to thi+ #henomenon& although the clinical
con+e4uence+ of the+e effect+ i+ unclear.
%A
-oncern a1out +odium and water o/erload a++ociated with +aline
re+u+citation ha+ re+ulted in the conce#t of <+mall /olume> cr,+talloid
re+u+citation with the u+e of h,#ertonic +aline 7%H& ?H&
and D.?H9 +olution+. 8owe/er& the earl, u+e of
h,#ertonic +aline for re+u+citation& #articularl, in #atient+
with traumatic 1rain in0 jur,& ha+ not im#ro/ed either
+hort0term or long0 term outcome+.
)(
-r,+talloid+ with a chemical com#o+ition that
a##ro6imate+ e6tracellular f luid ha/e 1een termed
<1alanced> or <#h,+iologic> +olution+ and are de0 ri/ati/e+
of the original 8artmannO+ and RingerO+ +olution+.
8owe/er& none of the #ro#rietar, +o0 lution+ are either
trul, 1alanced or #h,+iologic
)$
7Ta1le $9.
2alanced +alt +olution+ are relati/el, h,#o0 tonic
1ecau+e the, ha/e a lower +odium concen0 tration than
e6tracellular f luid. 2ecau+e of the in+ta1ilit, of
1icar1onate0containing +olution+ in #la+tic container+&
alternati/e anion+& +uch a+ lactate& acetate& gluconate& and
malate& ha/e 1een u+ed. E6ce++i/e admini+tration of
1alanced +alt +olution+ ma, re+ult in h,#erlactatemia&
meta0 1olic al5alo+i+& and h,#otonicit, 7with com0
#ounded +odium lactate9 and cardioto6icit, 7with acetate9.
The addition of calcium in +ome +olu0
$');
tion+ ma, generate microthrom1i with citrate0
containing red0cell tran+fu+ion+.
3i/en the concern regarding an e6ce++ of +odium
and chloride a++ociated with normal +aline& 1alanced +alt
+olution+ are increa+ingl, recommended a+ f ir+t0line
re+u+citation f luid+ in #atient+ undergoing +urger,&
$%
#atient+ with trauma&
$)
and #atient+ with dia1etic
5etoacido0 +i+.
)'
Re+u+citation with 1alanced +alt
+olution+ i+ a 5e, element in the initial treatment of #a0
tient+ with 1urn+& although there i+ increa+ing concern
a1out the ad/er+e effect+ of f luid o/er0 load& and a
+trateg, of <#ermi++i/e h,#o/olemia> in +uch #atient+ ha+
1een ad/ocated.
)%
A matched0cohort o1+er/ational +tud, com0 #ared the
rate of major com#lication+ in '$% #a0 tient+ who recei/ed
onl, (.AH +aline and D$) #a0 tient+ who recei/ed onl, a
calcium0free 1alanced +alt +olution 7!la+ma,te9 for
re#lacement of f luid lo++e+ on the da, of +urger,.
))
The
u+e of 1al0 anced +alt +olution wa+ a++ociated with a
+ignifi0 cant decrea+e in the rate of major com#lication+
7odd+ ratio& (.DA= A?H -I& (.FF to (.AD= !K(.(?9& including
a lower incidence of #o+to#erati/e in0
fection& renal0re#lacement thera#,& 1lood tran+0 fu+ion& and
acido+i+0a++ociated in/e+tigation+.
In a +ingle0center& +e4uential& o1+er/ational I-U +tud,&
)?
the
u+e of a chloride0re+tricti/e f luid +trateg, 7u+ing lactated and
calcium0free 1alanced +olution+9 to re#lace chloride0rich
intra/enou+ f luid+ 7(.AH +aline& +uccin,lated gelatin& or )H
al1umin9 wa+ a++ociated with a +ignif icant de0 crea+e in the
incidence of acute 5idne, injur, and the rate of renal0
re#lacement thera#,. 3i/en the wide+#read u+e of +aline 7S'((
million liter+ #er ,ear in the United State+ alone9& the+e data
+ugge+t that a randomi:ed& controlled trial e60 amining the
+afet, and eff icac, of +aline& a+ com#ared with a 1alanced
+alt +olution& i+ war0 ranted.
D o + e a n d V o l u m e +
The re4uirement+ for and re+#on+e to f luid re0 +u+citation
/ar, greatl, during the cour+e of an, critical illne++. No +ingle
#h,+iological or 1io0 chemical mea+urement ade4uatel, ref
lect+ the com#le6it, of f luid de#letion or the re+#on+e to
6a&le 2. 1ec+''endati+n5 2+r 0l%id 1e5%5citati+n in #c%tel* Ill :atient5.
0l%id5 5)+%ld &e ad'ini5tered <it) t)e 5a'e ca%ti+n t)at i5 %5ed <it) an* intra=en+%5 dr%g.
-on+ider the t,#e& do+e& indication+& contraindication+& #otential for to6icit,& and co+t.
0l%id re5%5citati+n i5 a c+'7+nent +2 a c+'7le, 7)*5i+l+gical 7r+ce55.
Identif, the fluid that i+ mo+t li5el, to 1e lo+t and re#lace the fluid lo+t in e4ui/alent /olume+.
-on+ider +erum +odium& o+molarit,& and acidP1a+e +tatu+ when +electing a re+u+citation fluid.
-on+ider cumulati/e fluid 1alance and actual 1od, weight when +electing the do+e of re+u+citation fluid.
-on+ider the earl, u+e of catecholamine+ a+ concomitant treatment of +hoc5.
0l%id re$%ire'ent5 c)ange +=er ti'e in criticall* ill 7atient5.
The cumulati/e do+e of re+u+citation and maintenance fluid+ i+ a++ociated with inter+titial edema.
!athological edema i+ a++ociated with an ad/er+e outcome.
"liguria i+ a normal re+#on+e to h,#o/olemia and +hould not 1e u+ed +olel, a+ a trigger or end #oint for fluid re+u+cita0
tion& #articularl, in the #o+t0re+u+citation #eriod.
The u+e of a fluid challenge in the #o+t0re+u+citation #eriod 7T') hour+9 i+ 4ue+tiona1le.
The u+e of h,#otonic maintenance fluid+ i+ 4ue+tiona1le once deh,dration ha+ 1een corrected.
;7eci2ic c+n5iderati+n5 a77l* t+ di22erent categ+rie5 +2 7atient5.
2leeding #atient+ re4uire control of hemorrhage and tran+fu+ion with red cell+ and 1lood com#onent+ a+ indicated.
I+otonic& 1alanced +alt +olution+ are a #ragmatic initial re+u+citation fluid for the majorit, of acutel, ill #atient+.
-on+ider +aline in #atient+ with h,#o/olemia and al5alo+i+.
-on+ider al1umin during the earl, re+u+citation of #atient+ with +e/ere +e#+i+. Saline
or i+otonic cr,+talloid+ are indicated in #atient+ with traumatic 1rain injur,. Al1umin
i+ not indicated in #atient+ with traumatic 1rain injur,.
8,dro6,eth,l +tarch i+ not indicated in #atient+ with +e#+i+ or tho+e at ri+5 for acute 5idne, injur,.
The +afet, of other +emi+,nthetic colloid+ ha+ not 1een e+ta1li+hed& +o the u+e of the+e +olution+ i+ not recommended.
The +afet, of h,#ertonic +aline ha+ not 1een e+ta1li+hed.
The a##ro#riate t,#e and do+e of re+u+citation fluid in #atient+ with 1urn+ ha+ not 1een determined.
$')A
f luid re+u+citation in acute illne++. 8owe/er& +,+0 tolic
h,#oten+ion and #articularl, oliguria are widel, u+ed a+
trigger+ to admini+ter a <f luid challenge&> ranging from '((
to $((( ml of cr,+0 talloid or colloid for an adult #atient.
The u+e of cr,+talloid and colloid re+u+cita0 tion f luid+&
often #re+cri1ed 1, the mo+t junior mem1er+ of the clinical
team& in addition to h,#otonic <maintenance> f luid+& re+ult+
in in0 crea+ed cumulati/e do+e+ of +odium and water o/er
time.
)F
The+e increa+e+ are a++ociated with the de/elo#ment of
inter+titial edema with re+ul0 tant organ d,+function.
)D
A++ociation+ 1etween increa+ed cumulati/e #o+iti/e f luid
1alance and long0term ad/er+e outcome+ ha/e 1een
re#orted in #atient+ with +e#+i+.
);
In trial+ of li1eral /er+u+
goal0directed or re+tricti/e f luid +trategie+ in #atient+ with the
acute re+#irator, di+tre++ +,ndrome 7#articularl, in
#erio#erati/e #atient+9&
)A&?(
re+tricti/e f luid +trategie+ were
a++ociated with reduced mor1id0 it,. 8owe/er& +ince there i+ no
con+en+u+ on the def inition of the+e +trategie+& high04ualit,
trial+ in +#ecif ic #atient #o#ulation+ are re4uired.
)F
Although the u+e of re+u+citation f luid+ i+ one of the
mo+t common inter/ention+ in medicine& no currentl,
a/aila1le re+u+citation f luid can 1e con+idered to 1e ideal.
In light of recent high0 4ualit, e/idence& a rea##rai+al of
how re+u+cita0 tion f luid+ are u+ed in acutel, ill #atient+ i+
now re4uired 7Ta1le '9. The +election& timing& and
do+e+ of intra/enou+ f luid+ +hould 1e e/aluated a+
carefull, a+ the, are in the ca+e of an, other intra/enou+
drug& with the aim of ma6imi:ing eff icac, and
minimi:ing iatrogenic to6icit,.
Dr. M,1urgh re#ort+ recei/ing tra/el +u##ort and lecture
fee+& a+ well a+ grant +u##ort to hi+ in+titution& from
*re+eniu+ Ca1i= and Dr. M,then& recei/ing con+ulting fee+
#aid to him+elf and hi+ in+titution 1, A4i6& grant +u##ort
to hi+ in+titution from *re+eniu+ Ca1i& lecture fee+ and
tra/el +u##ort from 2a6ter& 2. 2raun& and *re+eniu+ Ca1i&
and fee+ for the de/elo#ment and #re+entation of
educational material+ from 2. 2raun. Dr. M,then al+o
re#ort+ organi:ing non#rof it educational conference+ for
the E/idence02a+ed !erio#erati/e Medicine 7E2!"M9
#roject& which ha+ recei/ed f inancial +u##ort from
2a6ter& 2. 2raun& 2eacon !harmaceutical+& -o+med&
-ranlea& Delte6& Edward+& *re+eniu+ Ca1i& Imacor&
iD-"& Ma+imo& Medgra#hic+& "rion !harma& !ul+ion&
and Vitalogra#h. No other #otential conf lict of intere+t
rele/ant to thi+ article wa+ re#orted.
Di+clo+ure form+ #ro/ided 1, the author+ are a/aila1le
with the full te6t of thi+ article at NEJM.org.
1e2erence 5
1. ewin+ R. Saline injection+ into the
/ein+. ondon Medical 3a:ette. A#ril D&
$;%'G'?D0F;.
2. ee JA. S,dne,
Ringer 7$;%)0$A$(9
and Ale6i+ 8artmann
7$;A;0$AF)9.
Anae+the0 +ia
$A;$=%FG$$$?0'$.
3. *un5 DJ& Jaco1+ohn E&
Cumar A. The role of
/enou+ return in critical illne++ and +hoc5.
I. !h,+iolog,. -rit -are Med
'($%=)$G'??0F'.
4. !er+ichini R& Sil/a S& Te1oul J& et al.
Effect+ of nore#ine#hrine on mean +,+0
temic #re++ure and /enou+ return in hu0
man +e#tic +hoc5. -rit -are Med '($'=)(G
%$)F0?%.
5. Starling E8. "n the a1+or#tion of f lu0
id+ from connecti/e ti++ue +#ace+. J !h,+i0
ol $;AF=$AG%$'0'F.
6. Crogh A& andi+ EM& Turner A8. The
mo/ement of f luid through the human
ca#illar, wall in relation to /enou+ #re+0
+ure and to the colloid o+motic #re++ure of
the 1lood. J -lin In/e+t $A%'=$$GF%0A?.
". e/ic5 JR& Michel --. Micro/a+cular f
luid e6change and the re/i+ed Starling
#rinci#le. -ardio/a+c Re+ '($(=;DG$A;0
'$(.
!. @ein1aum S& Tar1ell JM& Damiano
ER. The +tructure and function of the
endothelial gl,cocal,6 la,er. Annu Re/
2iomed Eng '((D=AG$'$0FD.
9. @oodcoc5 TE& @oodcoc5 TM. Re/i+ed
Starling e4uation and the gl,cocal,6
model of tran+/a+cular f luid e6changeG an
im#ro/ed #aradigm for #re+cri1ing
intra0 /enou+ f luid thera#,. 2r J
Anae+th '($'=
$(;G%;)0A).
10. ee @& Slut+5, AS. Se#+i+ and
endo0 thelial #ermea1ilit,. N Engl J
Med '($(=
%F%GF;A0A$.
11. *infer S& iu 2& Ta,lor -& et al.
Re+u+0 citation f luid u+e in criticall,
ill adult+G an international cro++0
+ectional +tud, in
%A$ inten+i/e care unit+. -rit -are
'($(=$)G R$;?.
12. Dellinger R!& e/ , MM& -arlet
JM& et al. Sur/i/ing Se#+i+ -am#aignG
interna0 tional guideline+ for
management of +e0 /ere +e#+i+ and
+e#tic +hoc5G '((;. -rit -are Med
'((;=%FG'AF0%'D. IErratum& -rit -are
Med '((;=%FG$%A)0F.J
13. !owell0Tuc5 J& 3o+ling !& o1o
DN& et al. 2riti+h -on+en+u+
3uideline+ on In0 tra/enou+ *luid
Thera#, for Adult Surgi0 cal
!atient+ 73I*TASU!9. March '($$
7htt#GNNw w
w .1 a # e n .o r g .u 5 N# d f+ N1 a # e n U
#u1+Ngifta+u#.#df 9.
14. Ad/anced Trauma ife Su##ort
7ATS9 for doctor+. -hicagoG
American -ollege of Surgeon+
-ommittee on Trauma& '($' 7htt#GNNw
w w .f a c + .o r g Ntr a u m a Na tl+ Nin d e 6
.html9.
15. !erel !& Ro1ert+ I. -olloid+
/er+u+ cr,+talloid+ for f luid
re+u+citation in criti0 call, ill #atient+.
-ochrane Data1a+e S,+t Re/
'($'=FG-D(((?FD.
16. 2unn *& Tri/edi D. -olloid +olution+
for f luid re+u+citation. -ochrane Data1a+e
S,+t Re/ '($'=DG-D(($%$A.
1". -ochrane Injurie+ 3rou# Al1umin Re/iewer+.
8uman al1umin admini+tra0 tion in criticall, ill
#atient+G +,+tematic re/iew of randomi+ed controlled
trial+. 2MJ $AA;=%$DG'%?0)(.
1!. The SA*E Stud, In/e+tigator+. A com0 #ari+on of
al1umin and +aline for f luid re+u+citation in the
inten+i/e care unit. N Engl J Med '(()=%?(G'')D0?F.
19. Idem. Saline or al1umin for f luid re+u+0 citation in
#atient+ with traumatic 1rain injur,. N Engl J Med
'((D=%?DG;D)0;).
20. -oo#er DJ& M,1urgh J& *infer
S& et al. Al1umin re+u+citation for
traumatic 1rain injur,G i+
intracranial h,#erten+ion the
cau+e of increa+ed mortalit,V J
Neurotrau0 ma '($% March '$
7E#u1 ahead of #rint9.
21. *infer S& McE/o, S& 2ellomo
R& McAr0 thur -& M,1urgh J&
Norton R. Im#act of al1umin
com#ared to +aline on organ
function and mortalit, of #atient+
with +e/ere +e#+i+. Inten+i/e -are
Med '($$=
%DG;F0AF.
22. *infer S& 2ellomo R& McE/o, S& et
al. Effect of 1a+eline +erum al1umin
concen0 tration on outcome of
re+u+citation with al1umin or +aline in
#atient+ in inten+i/e care unit+G
anal,+i+ of data from the Sa0 line
/er+u+ Al1umin *luid E/aluation
7SA*E9 +tud,. 2MJ '((F=%%%G$()).
23. Maitland C& Ciguli S& "#o5a R& et
al.
$'?(
Mortalit, after f luid 1olu+ in African
chil0 dren with +hoc5. N Engl J Med
'($$=%F)G
');%0A?.
24. Maitland C& 3eorge E& E/an+ J& et
al. E6#loring mechani+m+ of e6ce++
mortal0 it, with earl, f luid
re+u+citationG in+ight+ from the *EAST
trial. 2M- Med '($%=$$G
F;.
25. 8artog -S& Reuter D& oe+che @&
8of0 mann M& Reinhart C. Inf luence
of h,0 dro6,eth,l +tarch 78ES9
$%(N(.) on hemo0 +ta+i+ a+ mea+ured
1, /i+coela+tic de/ice anal,+i+G a
+,+tematic re/iew. Inten+i/e -are Med
'($$=%DG$D'?0%D.
26. Schortgen *& acherade J-&
2runeel *& et al. Effect+ of
h,dro6,eth,l+tarch and gelatin on
renal function in +e/ere +e#+i+G a
multicentre randomi+ed +tud,.
ancet
'(($=%?DGA$$0F.
2". 2run5hor+t *M& Engel -& 2loo+ *&
et al. Inten+i/e in+ulin thera#, and
#enta+tarch re+u+citation in +e/ere
+e#+i+. N Engl J Med '((;=%?;G$'?0
%A.
2!. 2rand+tru# 2& S/end+en !E&
Ra+mu+0 +en M& et al. @hich goal for
f luid thera#, during colorectal
+urger, i+ followed 1, the 1e+t
outcomeG near0ma6imal +tro5e /olume
or :ero f luid 1alanceV 2r J
Anae+th
'($'=$(AG$A$0A.
29. McSwain NE& -ham#ion 8R&
*a1ian T-& et al. State of the art
of f luid re+u+ci0 tation '($(G
#reho+#ital and immediate
tran+ition to the ho+#ital. J
Trauma '($$=
D(GSu##lGS'0S$(.
30. !erner A& 8aa+e N&
3uttorm+en A2& et al.
8,dro6,eth,l +tarch $%(N(.)'
/er+u+ RingerO+ acetate in +e/ere
+e#+i+. N Engl J Med
'($'=%FDG$')0%). IErratum& N
Engl J Med '($'=%FDG);$.J
31. M,1urgh JA& *infer S&
2ellomo R& et al. 8,dro6,eth,l
+tarch or +aline for f luid
re+u+citation in inten+i/e care. N
Engl J Med '($'=%FDG$A($0$$.
32. Jame+ M*& Michell @&
Jou1ert IA& Ni0 col AJ& Na/+aria
!8& 3ille+#ie RS. Re+u+ci0 tation
with h,dro6,eth,l +tarch
im#ro/e+ renal function and
lactate clearance in
#enetrating trauma in a randomi:ed con0 trolled +tud,G
the *IRST trial 7*luid+ in Re+u+citation of Se/ere
Trauma9. 2r J An0 ae+th '($$=$(DGFA%0D('.
33. 3uidet 2& Martinet "& 2oulain T& et al. A++e++ment of
hemod,namic eff icac, and +afet, of FH
h,dro6,eth,l+tarch $%(N(.) /+. (.AH Na-l f luid
re#lacement in #atient+ with +e/ere +e#+i+G the -RWSTMAS
+tud,. -rit -are '($'=$F7%9GRA).
34. 2a,er "& Reinhart C& Sa5r W& et al. Re0 nal effect+ of
+,nthetic colloid+ and cr,+0 talloid+ in #atient+ with
+e/ere +e#+i+G a #ro+#ecti/e +e4uential com#ari+on. -rit
-are Med '($$=%AG$%%?0)'.
35. Awad S& Alli+on S!& o1o DN. The hi+tor, of (.AH
+aline. -lin Nutr '((;='DG
$DA0;;.
36. Morgan TJ& Ven5ate+h 2& 8all J. -r,+0 talloid +trong
ion difference determine+ meta1olic acid01a+e change
during acute normo/olaemic haemodilution. Inten+i/e
-are Med '(()=%(G$)%'0D.
3". Cellum JA& Song M& i J. Science re0 /iewG
e6tracellular acido+i+ and the im0 mune re+#on+eG
clinical and #h,+iologic im#lication+. -rit -are
'(()=;G%%$0F.
3!. 8adimioglu N& Saadaw, I& Saglam T& Ertug L& Dinc5an
A. The effect of differ0 ent cr,+talloid +olution+ on acid0
1a+e 1al0 ance and earl, 5idne, function after 5id0 ne,
tran+#lantation. Ane+th Analg '((;=
$(DG'F)0A.
39. 8and, JM& Soni N. !h,+iological ef0 fect+ of
h,#erchloraemia and acido+i+. 2r J Anae+th '((;=$($G$)$0
?(.
40. -oo#er DJ& M,le+ !S& McDermott *T& et al.
!reho+#ital h,#ertonic +aline re0 +u+citation of #atient+
with h,#oten+ion and +e/ere traumatic 1rain injur,G a ran0
domi:ed controlled trial. JAMA '(()='A$G
$%?(0D.
41. 3uidet 2& Soni N& Della Rocca 3& et
al. A 1alanced /iew of 1alanced
+olution+. -rit -are '($(=$)G%'?.
42. -hua 8R& Ven5ate+h 2& Stachow+5i
E& et al. !la+ma0,te $); /+ (.AH +aline
for
f luid re+u+citation in
dia1etic 5etoacido0
+i+. J -rit -are
'($'='DG$%;0)?.
43. Arlati S& Storti E&
!radella V& 2ucci &
Vitolo A& !ulici M.
Decrea+ed f luid /ol0
ume to reduce organ
damageG a new
a##roach to 1urn
+hoc5 re+u+citationV
A #reliminar, +tud,.
Re+u+citation
'((D=D'G
%
D
$
0
;
.
44. Shaw AD&
2ag+haw SM&
3old+tein S& et al.
Major com#lication+&
mortalit,& and
re+ource utili:ation
after o#en a1dominal
+urger,G (.AH +aline
com#ared to !la+ma0
,te. Ann Surg
'($'='??G;'$0A.
45. Wuno+ NM&
2ellomo R& 8egart,
-& Stor, D& 8o &
2aile, M. A++ociation 1etween a chloride0
li1eral /+ chloride0 re+tricti/e intra/enou+ f
luid admini+tration +trateg, and 5idne,
injur, in criticall, ill adult+. JAMA
'($'=%(;G$?FF0D'.
46. -orcoran T& Rhode+ JE& -lar5e S&
M,le+ !S& 8o CM. !erio#erati/e f luid
manage0 ment +trategie+ in major +urger,G
a +trati0 f ied meta0anal,+i+. Ane+th
Analg '($'=
$$)GF)(0?$.
4". -ordeman+ -& De aet I& Van Regen0
mortel N& et al. *luid management in
criticall, ill #atient+G the role of e6tra/a+0
cular lung water& a1dominal h,#erten0
+ion& ca#illar, lea5& and f luid 1alance.
Ann Inten+i/e -are '($'='GSu##l $GS$.
4!. 2o,d J8& *or1e+ J& Na5ada TA& @alle,
CR& Ru++ell JA. *luid re+u+citation in +e#0
tic +hoc5G a #o+iti/e f luid 1alance and ele0
/ated central /enou+ #re++ure are a++oci0
ated with increa+ed mortalit,. -rit -are
Med '($$=%AG'?A0F?.
49. The National 8eart& ung& and 2lood
In+titute Acute Re+#irator, Di+tre++ S,n0
drome 7ARDS9 -linical Trial+ Networ5.
-om#ari+on of two f luid0management
+trategie+ in acute lung injur,. N Engl J
Med '((F=%?)G'?F)0D?.
50. Mur#h, -V& Schramm 3E& Dohert,
JA& et al. The im#ortance of f luid manage0
ment in acute lung injur, +econdar, to
+e#tic +hoc5. -he+t '((A=$%FG$('0A.
Copyright 2013 Massachusetts
Medical Society.
2013 ic'>e rec+''endati+n5
The International -ommittee of Medical Journal Editor+ 7I-MJE9 ha+ re/i+ed and
renamed it+ Uniform Re4uirement+. The new I-MJE Recommendation+ for the
-onduct& Re#orting& Editing and !u1lication of Scholarl, @or5
in Medical Journal+ are a/aila1le at www.icmje.org.
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