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review article
critical care medicine
Simon R. Finfer, M.D., and Jean-Louis Vincent, M.D., P .D., Editors

!irculator" S oc#
Jean-Louis Vincent, M.D., P .D., and Daniel De $ac#er, M.D., P .D.

From t e De%artment of &ntensive !are, 'rasme (os%ital, )niversit* Li+re de $ru,elles, $russels. -ddress re%rint re.uests to Dr. Vincent at t e De%artment of &ntensive !are, 'rasme )niversit" (os%ital, Rte. de Lenni# /0/, $-1020 $russels, $elgium, or at jlvincen3ul+.ac.+e.
N Engl J Med 2013;369:172634. DOI: 10.10 6!NEJMra120"943
Copyright Society. 2013 Massachusetts Medical

oc# is t e clinical e,%ression of circulator" failure t at results in inade.uate cellular o,"gen utili4ation. S oc# is a common condi- tion in critical care, affecting a+out one t ird of %atients in t e intensive care unit 5&!)6.1 - diagnosis of s oc# is +ased on clinical,

emod"namic, and +io-

c emical signs, w ic can +roadl" +e summari4ed into t ree com%onents. First, s"stemic arterial "%otension is usuall" %resent, +ut t e magnitude of t e "%oten- sion ma" +e onl" moderate, es%eciall" in %atients wit c ronic "%ertension. 7"%i- call", in adults, t e s"stolic arterial %ressure is less t an 80 mm (g or t e mean arterial %ressure is less t an 20 mm (g, wit associated tac "cardia. Second, t ere are clinical signs of tissue "%o%erfusion, w ic are a%%arent t roug t e t ree 9windows: of t e +od";< cutaneous 5s#in t at is

cold and clamm", wit vasocon- striction and c"anosis, f indings t at are most evident in low-f low states6, renal 5urine out%ut of =0.> ml %er #ilogram of +od" weig t %er our6, and neurologic 5altered mental state, w ic t"%icall" includes o+tundation, disorientation, and confusion6. 7 ird, "%erlactatemia is t"%icall" %resent, indicating a+normal cellular o,"gen meta+olism. 7 e normal +lood lactate level is a%%ro,imatel" 1 mmol %er liter, +ut t e level is increased 5?1.> mmol %er liter6 in acute circulator" failure.
Pa t o% " s iol o g ic a l M e c isms
not

an
necessaril" e,clusive,

S oc# results from four %otential, and %at o% "siological mec anisms@< "%ovolemia

5from internal or e,ternal f luid loss6, cardiogenic fac- tors 5e.g., acute m"ocardial infarction, end-stage cardiom"o%at ", advanced valvular eart disease, m"ocarditis, or cardiac arr "t mias6, o+struction 5e.g., %ulmonar"
em+olism, cardiac tam%onade, or tension %neumot ora,6, or distri+utive factors 5e.g., severe se%sis or ana% "la,is from t e release of inf lammator" mediators6 5Fig. 1- and t e interactive gra% ic, availa+le at A'JM.org6. 7 e f irst t ree mec - anisms are c aracteri4ed +" low cardiac out%ut and, ence, inade.uate o,"gen trans- %ort. &n distri+utive s oc#, t e main def icit lies in t e %eri% er", wit decreased s"stemic vascular resistance and altered o,"gen e,traction. 7"%icall", in suc cases cardiac out%ut is ig , alt oug it ma" +e low as a result of associated m"ocardial de%ression. Patients wit acute circulator" failure often

An interactive graphic showing initial assessment of shock is available at NEJM.org

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ave a com+ination of t ese mec anisms. For e,am%le, a %atient wit distri+utive s oc# from severe %ancreatitis, ana% "la,is, or se%sis ma" also ave "%ovolemia and cardiogenic s oc# from m"ocardial de%ression.

Di f f e r e n t i a l Di a g n o s i s
Se%tic s oc#, a form of distri+utive s oc#, is t e most common form of s oc# among %atients in t e &!), followed +" cardiogenic and "%ovolemic s oc#C o+structive s oc# is relativel" rare 5Fig. 1$ and 1!6. &n a trial involving more t an

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1B00 %atients wit s oc# w o were randoml" as- signed to receive eit er do%amine or nore%ine% - rine, se%tic s oc# occurred in B;D of t e %atients, cardiogenic s oc# in 1BD, "%ovolemic s oc# in 1BD, ot er t"%es of distri+utive s oc# in ED, and o+structive s oc# in ;D.E 7 e t"%e and cause of s oc# ma" +e o+vious from t e medical istor", % "sical e,amination, or clinical investigations. For e,am%le, s oc# after traumatic injur" is li#el" to +e "%ovolemic 5due to +lood loss6, +ut cardiogenic s oc# or distri+utive s oc# ma" also occur, alone or in com+ination, caused +" suc conditions as cardiac tam%onade or s%inal cord injur". - full clini- cal e,amination s ould include assessment of s#in color and tem%erature, jugular venous dis- tention, and %eri% eral edema. 7 e diagnosis can +e ref ined wit %oint-of-care ec ocardio- gra% ic evaluation, w ic includes assessment for %ericardial effusion, measurement of left and rig t ventricular si4e and function, assessment for res%irator" variations in vena cava dimensions, and calculation of t e aortic velocit"Ftime inte- gral, a measure of stro#e volume. G enever %os- si+le, focused ec ocardiogra% " s ould +e %er- formed as soon as %ossi+le in an" %atient %resenting wit s oc# 5Fig. 1-6.>,B

alt oug t e e,act treatments t at are used to reac t ose goals ma" differ. - useful mnemonic to descri+e t e im%ortant com%onents of resuscitation is t e V&P rule2< ventilate

5o,"gen administration6, in-

& n i t i a l - %%ro a c t o t e Pa t i e n t i n S c#

'arl", ade.uate emod"namic su%%ort of %atients in s oc# is crucial to %revent worsening organ d"sfunction and failure. Resuscitation s ould +e started even w ile investigation of t e cause is ongoing. Hnce identified, t e cause must +e cor- rected ra%idl" 5e.g., control of +leeding, %ercuta- neous coronar" intervention for coronar" s"n- dromes, t rom+ol"sis or em+olectom" for massive %ulmonar" em+olism, and administration of anti- +iotics and source control for se%tic s oc#6. )nless t e condition is ra%idl" reversed, an arterial cat eter s ould +e inserted for monitoring of arterial +lood %ressure and +lood sam%ling, %lus a central venous cat eter for t e infu- sion of f luids and vasoactive agents and to guide f luid t era%". 7 e initial management of s oc# is %ro+lem-oriented, and t e goals are t erefore t e same, regardless of t e cause,
7 e Aew 'ngland Journal of Medicine

fuse 5f luid resuscitation6, and %um% 5administra- tion of vasoactive agents6.

#ent ilat $r% &'(( $rt

7 e administration of o,"gen s ould +e started im- mediatel" to increase o,"gen deliver" and %revent %ulmonar" "%ertension. Pulse o,imetr" is often unrelia+le as a result of %eri% eral vasoconstric- tion, and %recise determination of o,"gen re.uire- ments will often re.uire +lood gas monitoring. Mec anical ventilation +" means of a mas# rat er t an endotrac eal intu+ation as a lim- ited %lace in t e treatment of s oc# +ecause tec nical failure can ra%idl" result in res%irator" and cardiac arrest. (ence, endotrac eal intu+ation s ould +e %erformed to %rovide invasive mec anical ventilation in nearl" all %atients wit severe d"s%nea, "%o,emia, or %ersistent or wors- ening acidemia 5%(, =2.@06. &nvasive mec anical ventilation as t e additional +enef its of reduc- ing t e

o,"gen demand of res%irator" muscles and decreasing left ventricular afterload +" increasing intrat oracic %ressure. -n a+ru%t decrease in arterial %ressure after t e initiation of invasive mec anical ventilation strongl" suggests "%ovolemia and a decrease in venous return. 7 e use of sedative agents s ould +e #e%t to a minimum to avoid furt er decreases in arterial %ressure and cardiac out%ut.
)l'id *e+'+citati$n

Fluid t era%" to im%rove microvascular +lood f low and increase cardiac out%ut is an essential %art of t e treatment of an" form of s oc#. 'ven %atients wit cardiogenic s oc# ma" +enef it from f luids, since acute edema can result in a decrease in t e effective intravascular volume. (owever, f luid administration s ould +e closel" monitored, since too muc f luid carries t e ris# of edema wit its unwanted conse.uences. Pragmatic end %oints for f luid resuscitation are difficult to define. &n general, t e o+jective is for cardiac out%ut to +ecome %reload-inde%en- dent 5i.e., on t e %lateau %ortion of t e Fran#F Starling curve6, +ut t is is diff icult to assess clinicall". &n %atients receiving mec anical ventila- tion, signs of f luid res%onsiveness ma" +e identi- fied eit er directl" from +eat-+"-+eat stro#e-volume measurements wit t e use of cardiac-out%ut monitors or indirectl" from o+served variations in %ulse %ressure on t e arterial%ressure tracing during t e ventilator c"cle. (owever, suc +edside inferences ave some limitations/ I nota+l",
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,rterial -%($ten+i$n

. /%(e+ $0 +-$c1
B;D Distri+utive 5se%tic6

-+sent

&ign+ $0 ti++'e -%($(er0'+i$n

.rain

Present

! ronic "%otensionJ S"nco%e 5if transient6

-ltered mental state

2irc'lat$r% +-$c1
7ac "cardia

ED Distri+utive 5nonse%tic6

;D H+structive 1BD

&1in
Mottled, clamm"

'levated +lood lactate

'stimate cardiac out%ut or SvH; Aormal or ig Low

1BD !ardiogenic ("%ovolemic

3idne%
Hliguria

!VP

Low

(ig

Aormal cardiac c am+ers and 5usuall"6 %reserved contractilit"

Small cardiac

Ec-$cardi$gra(-%
Large ventricles and %oor contractilit"

&n tam%onade< %ericardial effusion, small rig t and left ventricles, dilated inferior vena cavaC in %ulmonar" em+olism or %neumot ora,< dilated rig t ventricle, small left ventricle

c am+ers and normal or ig contractilit"

Di+tri4'ti5e +-$c1

6%($5$lemic +-$c1

2ardi$genic +-$c1

O4+tr'cti5e +-$c1

2
Di+tri4'ti5e +-$c1 6%($5$lemic +-$c1 2ardi$genic +-$c1

O4+tr'cti5e
H+struction

+-$c1
Vasodilatation Loss of %lasma or +lood volume

Ventricular failure

Pericardial tam%onade

)ig're 1. Initial ,++e++ment $0 &-$c1 &tate+. S own is an algorit m for t e initial assessment of a %atient in s oc# 5Panel -6, relative fre.uencies of t e main t"%es of s oc# 5Panel $6, and sc ematic re%resentations of t e four main t"%es of s oc# 5Panel !6. 7 e algorit m starts wit t e most common %resentation 5i.e., arterial "%otension6, +ut "%otension is sometimes minimal or a+sent. !VP denotes central venous %ressure, and SvH; mi,ed venous o,"gen saturation.

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t at t e %atient must receive ventilation wit relativel" large tidal volumes, ave no s%ontaneous +reat ing effort 5w ic usuall" re.uires t e administration of sedatives or even muscle rela,- ants6, and +e free of major arr "t mia and rig t ventricular d"sfunction. - %assive legraising test is an alternative met od8 +ut

Stimulation of t e %atient and an" ot er c ange in t era%" s ould +e avoided during t e test. Fluid c allenges can +e re%eated as re.uired +ut must +e sto%%ed ra%idl" in case of non- res%onse in order to avoid f luid overload.
#a+$acti5e ,gent+

Vasopressors

re.uires a ra%id- res%onse device, since t e effect is transient. Regardless of t e test used, t ere remains a gra" 4one in w ic it is diff icult to %redict a %atientKs res%onse to intravenous f luids.
- f luid-c allenge tec ni.ue s ould +e used to determine a %atientKs actual res%onse to f luids, w ile limiting t e ris#s of adverse effects. - f luid c allenge incor%orates four elements t at s ould +e def ined in advance.10 First,

&f "%otension is severe or if it %ersists des%ite f luid administration, t e use of vaso%ressors is indicated. &t is acce%ta+le %ractice to administer

t e t"%e of f luid must +e selected. !r"stalloid solutions are t e f irst c oice, +ecause t e" are well tolerated and c ea%. 7 e use of al+umin to correct severe "- %oal+uminemia ma" +e reasona+le in some %a- tients.11 5detailed e,amination of t e c oice of resuscitation f luids was %rovided in a %revious article in t is series1; and t us is not included in t is review.6 Second, t e rate of f luid adminis- tration must +e def ined. Fluids s ould +e infused ra%idl" to induce a .uic# res%onse +ut not so fast t at an artificial stress res%onse develo%sC t"%icall", an infusion of @00 to >00 ml of f luid is administered during a %eriod of ;0 to @0 min- utes.1@ 7 ird, t e o+jective of t e f luid c allenge must +e def ined. &n s oc#, t e o+jective is usu- all" an increase in s"stemic arterial %ressure, alt oug it could also +e a decrease in eart rate or an increase in urine out%ut. Finall", t e safet" limits must +e def ined. Pulmonar" edema is t e most serious com%lication of f luid infusion. -l- t oug it is not a %erfect guideline, a limit in central venous %ressure of a few millimeters of mercur" a+ove t e +aseline value is usuall" set to %revent f luid overload.1@

a vaso%ressor tem%oraril" w ile f luid resuscita- tion is ongoing, wit t e aim of discontinuing it, if %ossi+le, after "%ovolemia as +een corrected. -drenergic agonists are t e f irst-line vaso- %ressors +ecause of t eir ra%id onset of action, ig %otenc", and s ort alf-life, w ic allows eas" dose adjustment. Stimulation of eac t"%e of adrenergic rece%tor as %otentiall" +enef icial and armful effects. For e,am%le, L-adrenergic stimulation can increase +lood f low +ut also in- creases t e ris# of m"ocardial isc emia as a result of increased eart rate and contractilit". (ence, t e use of iso%roterenol, a %ure Ladrenergic agent, is limited to t e treatment of %atients wit severe +rad"cardia. -t t e ot er e,treme, M-adrenergic stimulation will increase vascular tone and +lood %ressure +ut can also decrease cardiac out%ut and im%air tissue +lood f low, es%eciall" in t e e%atos%lanc nic region. For t is reason, % en"l- e% rine, an almost %ure M-adrenergic agent, is rarel" indicated.

Ge consider nore%ine% rine to +e t e vaso%ressor of f irst c oiceC it as %redominantl" M-adrenergic %ro%erties, +ut its modest L-adrener- gic effects el% to maintain cardiac out%ut. -dministration generall" results in a clinicall" signif icant increase in mean arterial %ressure, wit little c ange in eart rate or cardiac out%ut. 7 e usual dose is 0.1 to ;.0 Ng %er #ilogram of +od" weig t %er minute. Do%amine as %redominantl" L-adrenergic effects at lower doses and M-adrenergic effects at ig er doses, +ut its effects are relativel" wea#. Do%aminergic effects at ver" low doses 5=@ Ng %er #ilogram %er minute, given intravenousl"6 ma" selectivel" dilate t e e%atos%lanc nic and renal circulations, +ut controlled trials ave not s own a %rotective effect on renal function,1E and its routine

use for t is %ur%ose is no longer recommended. Do%aminergic stimulation ma" also ave undesired endocrine effects on t e "%o- t alamicF%ituitar" s"stem, resulting in immunosu%%ression, %rimaril" t roug a reduction in t e release of %rolactin.
&n a recent randomi4ed, controlled, dou+le+lind trial, do%amine ad no advantage over nor- e%ine% rine as t e first-line vaso%ressor agentC moreover, it induced more arr "t mias and was associated wit an increased ;/-da" rate of deat among %atients wit cardiogenic s oc#.E -dministration of do%amine, as com%ared wit

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nore%ine% rine, ma" also +e associated wit ig er rates of deat among %atients wit se%tic s oc#.1> (ence, we no longer recommend

do%a- mine for t e treatment of %atients wit s oc#.

'%ine% rine, w ic is a stronger agent, as %redominantl" L-adrenergic effects at low doses, wit M-adrenergic effects +ecoming more clini- call" signif icant at ig er doses. (owever, e%i- ne% rine administration can +e associated wit an increased rate of 1B,12 arr "t mia and a decrease in

I n o t r o p i c g e n t s

s%lanc nic +lood f low1B and can increase +lood lactate levels, %ro+a+l" +" increasing cellular me- ta+olism.1B,1/ Pros%ective, randomi4ed studies ave not s own an" +enef icial effects of e%ine% rine over nore%ine% rine in 12,1/ se%tic s oc#. Ge re- serve e%ine% rine as a second-line agent for se- vere cases.1@
7 e use of ot er strong vaso%ressor agents as continuous infusions 5e.g., angiotensin or meta- raminol6 as largel" +een a+andoned. Aonselec- tive in i+ition of nitric o,ide as not +een s own to +e +enef icial in %atients wit cardiogenic s oc#18 and is detrimental in

Ge consider do+utamine to +e t e inotro%ic agent of c oice for increasing cardiac out%ut, re- gardless of w et er nore%ine% rine is also +eing given. Git %redominantl" Ladrenergic %ro%er-

%atients wit se%- tic s oc#.;0

Vaso%ressin def icienc" can develo% in %a- tients wit ver" "%er#inetic forms of distri+u- tive s oc#, and t e administration of low-dose vaso%ressin ma" result in su+stantial increases in arterial %ressure. &n t e Vaso%ressin and Se%- tic S oc# 7rial 5V-SS76, investigators found t at t e addition of low-dose vaso%ressin to nore%i- ne% rine in t e treatment of %atients wit se%tic s oc# was safe;1 and ma" ave

+een associated wit a survival +enef it for %atients wit forms of s oc# t at were not severe and for t ose w o also received glucocorticoids.;; Vaso%ressin s ould not +e used at doses ig er t an 0.0E ) %er min- ute and s ould +e administered onl" in %atients wit a ig level of cardiac out%ut.
7erli%ressin, an analogue of vaso%ressin, as a duration of action of several ours, as com- %ared wit minutes for vaso%ressin. For t is reason, we do not +elieve it offers an advantage over vaso%ressin in t e &!). Vaso%ressin deriva- tives wit more selective V1rece%tor activit" are currentl" +eing studied.

ties, do+utamine is less li#el" to induce tac "car- dia t an iso%roterenol. -n initial dose of just a few micrograms %er #ilogram %er minute ma" su+stantiall" increase cardiac out%ut. &ntravenous doses in e,cess of ;0 Ng %er #ilogram %er minute usuall" %rovide little additional +enef it. Do+uta- mine as limited effects on arterial %ressure, al- t oug %ressure ma" increase slig tl" in %atients wit m"ocardial d"sfunction as t e %rimar" a+- normalit" or ma" decrease slig tl" in %atients wit underl"ing "%ovolemia. &nstead of routine administration of a f i,ed dose of do+utamine to increase o,"gen deliver" to su%ranormal, %rede- termined levels, t e dose s ould +e adjusted on an individual +asis to ac ieve ade.uate tissue %erfusion. Do+utamine ma" im%rove ca%illar" %erfusion in %atients wit se%tic s oc#, inde%en- dent of its s"stemic effects.;@ P os% odiesterase t"%e &&& in i+itors, suc as milrinone and eno,imone, com+ine inotro%ic and vasodilating %ro%erties. $" decreasing t e me- ta+olism of c"clic -MP, t ese agents ma" rein- force t e effects of do+utamine. 7 e" ma" also +e useful w en L-adrenergic rece%tors are down- regulated or in %atients recentl" treated wit +eta-+loc#ers. (owever, % os% odiesterase t"%e &&& in i+itors ma" ave unacce%ta+le adverse ef- fects in %atients wit "%otension, and t e long alf-lives of t ese agents

5E to B ours6 %revent minute-to-minute adjustment. (ence, intermit- tent, s ort-term infusions of small doses of % os% odiesterase &&& in i+itors ma" +e %refer- a+le to a continuous infusion in s oc# states. Levosimendan, a more e,%ensive agent, acts %rimaril" +" +inding to cardiac tro%onin ! and increasing t e calcium sensitivit" of m"oc"tes, +ut it also acts as a vasodilator +" o%ening -7Psensitive %otassium c annels in vascular smoot muscle. (owever, t is agent as a alf-life of several da"s, w ic limits t e %racticalit" of its use in acute s oc# states.
Vasodilators

$" reducing ventricular afterload, vasodilating agents ma" increase cardiac out%ut wit out increasing m"ocardial demand for o,"gen. 7 e major limitation of t ese drugs is t e ris# of decreasing arterial %ressure to a level t at com%romises tissue %erfusion. Aevert eless, in some %atients, %rudent use of nitrates and %ossi+l" ot er vasodilators ma" im%rove microvascular %erfusion and cellular function.;E

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Mec

a n i c a l S u %% o rt

Mec anical su%%ort wit intraaortic +alloon counter%ulsation 5&-$!6 can reduce left ventricu- lar afterload and increase coronar" +lood f low. (owever, a recent randomi4ed, controlled trial s owed no +enef icial effect of &-$! in %atients wit cardiogenic s oc#,;> and

its routine use in cardiogenic s oc# is not currentl" recommended. Venoarterial e,tracor%oreal mem+rane o,"genation 5'!MH6 ma" +e used as a tem%orar" lifesaving measure in %atients wit reversi+le cardiogenic s oc# or as a +ridge to eart ;B trans%lantation.
O o a l s o f ( em o d " n a m i c S u %% ort
,rterial 7re++'re

7 e %rimar" goal of resuscitation s ould +e not onl" to restore +lood %ressure +ut also to %rovide ade.uate cellular meta+olism, for w ic t e correction of arterial "%otension is a %rere.uisite. Restoring a mean s"stemic arterial %ressure of B> to 20 mm (g is a good initial goal, +ut t e level s ould +e adjusted to restore tissue %erfusion, assessed on t e +asis of mental status, s#in a%%earance, and urine out%ut, as descri+ed a+ove. &n %atients wit oliguria, in %articular, t e effects of a furt er increase in arterial %ressure on urine out%ut s ould +e assessed regularl", unless acute renal failure is alread" esta+lis ed. !onversel", a mean arterial %ressure lower t an B> to 20 mm (g ma" +e acce%ta+le in a %atient wit acute +leeding w o as no major neurologic %ro+lems, wit t e aim of limiting +lood loss and associated coagulo%at ", until t e +leeding is controlled.
2ardiac O't('t and O9%gen Deli5er%

)ig're 2. &ide+tream Dar1-)ield Image+ $0 &'4ling'al Micr$circ'lati$n in a 6ealt-% #$l'nteer and a 7atient 8it- &e(tic &-$c1. 7 e microcirculation in t e ealt " volunteer is c aracteri4ed +" dense ca%illaries t at are consistentl" %erfused 5Panel -, arrows6, w ereas in t e %atient wit se%tic s oc#, t e densit" of t e ca%illaries is diminis ed, and man" of t e ca%illaries ave sto%%ed or intermittent f low 5Panel $, arrows6.

Since circulator" s oc# re%resents an im+alance +etween o,"gen su%%l" and o,"gen re.uirements, maintaining ade.uate o,"gen deliver" to t e tis- sues is essential, +ut all t e strategies to ac ieve t is goal ave limitations. -fter correction of "- %o,emia and severe anemia, cardiac out%ut is t e %rinci%al determinant of o,"gen deliver", +ut t e o%timal cardiac out%ut is diff icult to def ine. !ar- diac out%ut can +e measured +" means of various tec ni.ues, eac of w ic as its own +enef

-+solute measures of cardiac out%ut are less im%ortant t an monitoring trends in res%onse to interventions suc as a f luid c al- lenge. 7 e targeting of a %redef ined cardiac out- %ut is not advisa+le, since t e cardiac out%ut t at
its and

draw+ac#s.B

is needed will var" among %atients and in t e same %atient over time. Measurements of mi,ed venous o,"gen satu- ration 5SvH;6 ma" +e el%ful in

assessing t e ade.uac" of t e +alance +etween o,"gen de- mand and su%%l"C SvH; measurements are also ver" useful in t e inter%retation of cardiac

out- %ut.;2 SvH; is t"%icall" decreased in %atients wit low-f low states or anemia +ut is normal or ig in t ose wit distri+utive s oc#. &ts surrogate, central venous o,"gen saturation 5ScvH;6, w ic is measured in t e su%erior vena cava +" means of a central venous cat eter, ref lects t e o,"gen saturation of t e venous +lood from t e u%%er alf of t e +od" onl". )nder normal circumstances, ScvH; is slig tl" less t an SvH;, +ut in criticall" ill %atients it is often greater. Rivers et al.;/ found
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Micr$circ'lat$r% #aria4le+
&al5age O(timi:ati$n &ta4ili:ati$n De-e+calati$n

7 e develo%ment of and eld devices for ort og- onal %olari4ation s%ectral 5HPS6 imaging and its successor, sidestream dar#-f ield 5SDF6 imaging, is %roviding new means of directl" visuali4ing t e microcirculation and evaluating t e effects of interventions on microcirculator" f low in easil" accessi+le surfaces, suc as t e su+lingual area.@0 Microcirculator" c anges, including decreased ca%illar" densit", a reduced %ro%ortion of %erfused ca%illaries, and increased eterogeneit" of +lood f low, ave +een identified in various t"%es of circu- lator" s oc# 5Fig. ;6, and t e %ersistence of t ese alterations is associated wit worse outcomes.@1 Aear-infrared s%ectrosco%" is a tec ni.ue t at uses near-infrared lig t to determine tissue o,"- gen saturation from t e fractions of o," emo- glo+in and deo," emoglo+in. -nal"sis of t e c anges in tissue o,"gen saturation during a +rief e%isode of forearm isc emia can +e used to .uantif" microvascular d"sfunction@;C suc

H+tain a minimal acce%ta+le 7 +lood %ressure Perform e lifesaving measures

a +

Provide ade.uate o,"gen availa+ilit" H%timi4e cardiac out%ut,

Provide organ su%%ort

Gean from vasoactive agents

Minimi4e com%lications

, lactate
SvH
;

-c ieve a negative fluid +alance

)ig're 3. )$'r 7-a+e+ in t-e /reatment $0 &-$c1. 7 e salvage % ase focuses on ac ieving a +lood %ressure and cardiac out%ut com%ati+le wit immediate survival and %erforming lifesaving %rocedures to treat t e underl"ing cause of s oc#. 7 e o%timi4ation % ase focuses on %romoting cellular o,"gen availa+ilit" and monitoring cardiac out%ut, mi,ed venous o,"gen saturation 5SvH;6,

and lactate levels. 7 e sta+ili4ation % ase focuses on %reventing organ d"sfunction, even after emod"namic sta+ilit" as +een ac ieved. 7 e de-escalation % ase focuses on weaning
t e %atient from vasoactive agents and %roviding treatments to el% ac ieve a negative f luid +alance.

alterat at in %atients %resenting to t e emergenc" de%artment wit se%tic s oc#, a treatment algorit m targeting an ScvH; of at least 20D

during t e f irst B ours was associated wit decreased rates of deat . 7 e ro+ustness of t is f inding is currentl" +eing evaluated in t ree multicenter trials. 5!linical7rials.gov num+ers, A!70082>28@ and A!700>10/@>C and !urrent !ontrolled 7rials num+er, &SR!7A@B@02E286.
.l$$d ;actate ;e5el

-n increase in t e +lood lactate level ref lects a+- normal cellular function. &n low-f low states, t e %rimar" mec anism of "%erlactatemia is tissue "%o,ia wit develo%ment of anaero+ic meta+o- lism, +ut in distri+utive s oc#, t e %at o% "siol- og" is more com%le, and ma" also involve increased gl"col"sis and in i+ition of %"ruvate de "drogenase. &n all cases, alterations in clearance can +e due to im%aired liver function. 7 e value of serial lactate measurements in t e management of s oc# as +een ;8 recogni4ed for @0 "ears. -lt oug c anges

c anges in s"stemic arterial %ressure or cardiac out%ut, t e +lood lactate level s ould decrease over a %eriod of ours wit effective t era%". &n %atients wit s oc# and a +lood lactate level of more t an @ mmol %er liter, Jansen et al.;E found t at targeting a decrease of at least ;0D in t e +lood lactate level over a
;- our %eriod seemed to +e associated wit re- duced inos%ital mortalit".

in lactate ta#e %lace more slowl" t an

Vari- ous t era%eutic interventions ave +een s own to ave an effect on t ese microcirculator" vari- a+les, +ut w et er t era%" t at is guided +" monitoring or targeting t e microcirculation can im%rove outcomes re.uires furt er stud" and cannot +e recommended at t is time.
tions are associated wit

worse outcomes.@@

e r a %e u t ic Pr io r i t i e s a n d O o al s

neededC in most cases, invasive monitoring can +e restricted to arterial and cen- tral venous cat eters. Lifesaving %rocedures 5e.g., surger" for trauma, %ericardial drainage, revasculari4ation for acute m"ocardial infarction, and anti- +iotics for se%sis6 are needed to treat t e under- l"ing cause. &n t e second 5o%timi4ation6 % ase, t e goal is to increase cellular o,"gen availa+ilit", and t ere is a narrow window of o%%ortunit" for inter- ventions targeting emod"namic status.;/ -de- .uate

7 ere are essentiall" four % ases in t e treatment of s oc#, and t era%eutic goals and monitoring need to +e ada%ted to eac % ase 5Fig. @6. &n t e first 5salvage6 % ase, t e goal of t era%" is to ac ieve a minimum +lood %ressure and cardiac out%ut com%ati+le wit immediate survival. Mini- mal monitoring is
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emod"namic resuscitation reduces inf lammation, mitoc ondrial d"sfunction, and cas%ase activation.@E,@> Measurements of SvH; and lactate levels ma" el% guide t era%", and monitoring of cardiac out%ut s ould +e considered. &n t e t ird

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!r itic a l ! a r e Medicine

5sta+ili4ation6 % ase, t e goal is to %revent organ d"sfunction, even after emod"namic sta+ilit" as +een ac ieved. H,"gen su%%l" to t e tissues is no longer t e #e" %ro+lem, and organ su%%ort +e- comes more relevant. Finall", in t e fourt 5de- escalation6 % ase, t e goal is to wean t e %atient from vasoactive agents and %romote s%ontaneous %ol"uria or %rovo#e f luid elimination t roug t e use of diuretics or ultrafiltration to ac ieve a neg- ative f luid +alance.

sential so t at aggressive management can +e started. -%%ro%riate treatment is +ased on a good understanding of t e underl"ing %at o% "siolog- ical mec anisms. 7reatment s ould include cor- rection of t e cause of s oc# and emod"namic sta+ili4ation, %rimaril" t roug f luid infusion and administration of vasoactive agents. 7 e %a- tientKs res%onse can +e monitored +" means of careful clinical evaluation and +lood lactate mea- surementsC microvascular evaluation ma" +e fea- si+le in t e future.
Ao %otential conf lict of interest relevant to t is article was re%orted. Disclosure forms %rovided +" t e aut ors are availa+le wit t e full te,t of t is article at A'JM.org.

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