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Controversies

Do not drown the patient appropriate1047298uid management in critical illness

Kees H Polderman MD PhD Joseph Varon MD

Department of Critical Care Medicine University of Pittsburgh Medical Center Pittsburgh PA USA

The University of Texas Health Science Center at Houston Houston TX USA

The University of Texas Medical Branch at Galveston Galveston TX USA

University General Hospital Houston TX USA

a b s t r a c ta r t i c l e i n f o

Article history

Received 29 November 2014

Received in revised form 28 January 2015

Accepted 29 January 2015

Available online xxxx

Administering intravenous 1047298uids to support the circulation in critically ill patients has been a mainstay of

emergency medicine and critical care for decades especially (but not exclusively) in patients with distributive

or hypovolemic shock However in recent years this automatic use of large 1047298uid volumes is beginning to be

questioned Analysis from several large trials in severe sepsis andor acute respiratory distress syndrome have

shown independent links between volumes of 1047298uid administered and outcome conservative 1047298uid strategies

have also been associated with lower mortality in trauma patients In addition it is becoming ever more clear

thatcentral venouspressure which is often usedto guide1047298uidadministration is a completely unreliable param-

eter of volume status or 1047298uid responsiveness Furthermore 2 recently published large multicenter trials (ARISE

and ProCESS) have discredited the ldquoearly goal-directed therapyrdquo approach which used prespeci1047297ed targets of

central venous pressure and venous saturation to guide 1047298uid and vasopressor administration This article dis-

cussesthe risks of ldquoiatrogenic submersionrdquo andstrategiesto avoid this riskwhilestillgivingour patients the1047298uids

they need The key lies in combining good clinical judgement awareness of the potential harm from excessive

1047298uid use restraint in re1047298exive administration of 1047298uids and use of data from sophisticated monitoring tools

such as echocardiography and transpulmonary thermodilution Use of smaller volumes to perform 1047298uid

challenges monitoring of extravascular lung water earlier use of norepinephrine and other strategies can help

further reduce morbidity and mortality from severe sepsis

copy 2015 Elsevier Inc All rights reserved

One of the most challenging and controversial areas in the care of

emergent and critically ill patients is the administration of intravenous

1047298uids to support the circulation This does not only apply to hemody-

namically unstable patients In clinical conditions such as subarachnoid

hemorrhage large volumes of 1047298uid are often administered over

prolonged periods to reduce the risk of vasospasm often targeting a

positive 1047298

uid balance or a speci1047297

c central venous pressure (CVP) [1]However especially when a patient presents with a distributive or hy-

povolemic shock rapid administration of 1047298uids is one of the mainstays

of treatment one that has been recommended for decades This applies

to both the initial and later phases of treatment especially in distribu-

tive shock The 2012 ldquoSurviving Sepsis Campaignrdquo guidelines recom-

mend an initial 1047298uid challenge followed by continued 1047298uid

administration if hypotension persists or blood lactate concentration

exceeds 4 mmolL [2] Again CVP is often used to guide 1047298uid volume

this in spite of abundant evidence showing that CVP is completely un-

reliable as a parameter of volume status or 1047298uid responsiveness [2-5]

In 2001 a highly in1047298uential single-center study reported that 1047298uid

and vasopressor administration using prespeci1047297

ed targets including aCVP of 8 to 12 and venous saturation greater than 65 in the 1047297rst

6 hours of sepsis could reduce mortality by 158 [6] This approach

was termed early goal-directed therapy (EGDT ) [6] Recently 2 large

multicentered studies (the ProCESS trial and the ARISE trial) failed to

demonstrate any bene1047297ts of the EGDT approach [78] in spite of this

current guidelines still recommend EGDT and a recent statement on

behalf of the ldquoSurviving Sepsis Campaignrdquo panel put out after publica-

tion of the ProCESS trial suggests that no change in guidelines will be

forthcoming because ldquothe ProCESS trial used protocolized care in all

study groupsrdquo and thus its negative 1047297ndings ldquodo not invalidate the

EGDT approachrdquo [9]

American Journal of Emergency Medicine xxx (2015) xxxndashxxx

Disclosures Neither of the authors has a relevant con1047298ict of interest to declare

Corresponding author at Department of Critical Care Medicine University of Pitts-

burgh Medical Center 3550 Terrace St Scaife Hall6th Floor Pittsburgh PA 15261

E-mail addresses kpoldermantipnl PoldermanKHupmcedu (KH Polderman)

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

j o u r n a l h o m e p a g e w w w e l s e v i e r c o m l o c a t e a j e m

Please cite this article as Polderman KH Varon J Donot drownthepatient appropriate1047298uidmanagement in critical illness Am J Emerg Med(2015) httpdxdoiorg101016jajem201501051

7232019 Fluidos Manejo Apropiado 2015

httpslidepdfcomreaderfullfluidos-manejo-apropiado-2015 23

However in recent years a number of studies in emergency medi-

cine and critical care have raised concerns over the practice of unre-

strained 1047298uid administration that has become so ingrained in daily

practice One of the 1047297rst studies to address this issue was a clinical

trial in children performed in Africa designed to compare 1047298uid bolus

of albumin to normal saline with the hypothesis that albumin adminis-

tration might improve outcome in sepsis [10] Children receiving nor-

mal saline and albumin 1047298uid bolus had similar outcomes but

mortality was signi1047297cantly lower in children who had not receivedany 1047298uid bolus [10] As the study had been performed in poor countries

in Africa there were questions regarding the applicability of these 1047297nd-

ings to industrial countries with modern health care systems The

causes of infection disease course time to medical treatment health

care delivery systems preexisting conditions and many other factors

are very different in Africa compared to Western countries Although

these criticisms are valid other reports support the initial observations

and lend credence to the hypothesis that excessive1047298uid administration

can be detrimental A post hoc analysis of the acute respiratory distress

syndrome network (ARDS-NET) showed that a negative cumulative

1047298uid balance at day 4 was associated with signi1047297cantly lower mortality

independent of other measures of severity of illness including a diagno-

sisof sepsis [11] This observation wascon1047297rmed inanother studyof pa-

tients with acute respiratory distress syndrome (ARDS) secondary toseptic shock [12] In fact in this study patients receiving 1047298uid manage-

ment considered ldquoinadequate but conservativerdquo had better outcomes

than 1047298uid administration considered ldquoadequate but liberalrdquo [12] Simi-

larly in the Vasopressin vs Norepinephrine Infusion in Patients with

Septic Shock trial a more positive 1047298uid balance both early in resuscita-

tion and cumulatively over 4 days was associated with increased risk

of mortality in septic shock corrected for other factors [13]

This does not just apply to sepsis A recent meta-analysis of random-

ized controlled trials and cohort studies and cohort studies found that

conservative 1047298uid strategies were associated with lower mortality in

trauma patients [14] In addition it is not only unrestrained crystalloid

infusion that is being called into question a recent study reported that

transfusion of red blood cells was associated with signi1047297cantly worse

outcomes in patients with traumatic brain injury and no evidence of

shock if the initial hemoglobin was greater than 10 gdL [15] Twenty

years ago Bickell et al [16] challenged the practice of early 1047298uid resusci-

tation in patients with penetrating injuries suggesting that this practice

might be linked to increased bleeding and adverse outcomes This issue

still remains controversial [17]

In this issue of The American Journal of Emergency Medicine Sirvent

[18] reports on the effects of 1047298uid administration at the onset of severe

sepsis and septic shock The author found that the accumulated positive

1047298uidbalance in the1047297rst 48 72 and 96hours wassigni1047297cantly associatedwith increased mortality [18] These results are in keeping with the re-

sults discussed above and remind us again of the risks of ldquoiatrogenic

submersionrdquo How can we avoid this risk while still giving our patients

the 1047298uids that they may need

In our view the key lies in a multipronged approach using clinical

judgment along with sophisticated monitoring tools to guide our treat-

ment The 1047297rst step is awareness and restraint awareness that exces-

sive 1047298uid administration could be harmful and restraint in the

restraint in there1047298exive administration of 1047298uids If a patient does not re-

spond to a bolus of 1047298uid we should think twice before giving yet more

1047298uids or trying yet another 1047298uid challenge instead we might consider

earlier initiation of pressors or perhaps accepting less ambitious target

values Especially we should not target speci1047297c CVPs to guide treat-

ment rather a combination of clinical and biochemical parametersand more sophisticated hemodynamic monitoring (echocardiography

cardiac output extravascular lung water [EVLW] and stroke volume

variation) can be used to better tailor our therapeutic approach (see

Table) Fluid responsiveness can be assessed with smaller volumes

(100-250 mL administered rapidly rather than 500-1000 mL as is com-

mon practice) Monitoring of EVLW may be a valuable safety parameter

to prevent 1047298uid overload A recent study in ARDS patients suggests that

high EVLW is an independent risk factor for mortality in ARDS [19] This

approach may also apply to less sick patients to take the earlier exam-

ple of subarachnoid hemorrhage a recent randomized controlled trial

reported signi1047297cantly improved outcomes using preload volume and

cardiac output (monitored by transpulmonary thermodilution) to

guide treatments compared to patients where ldquotraditionalrdquo parameters

such as 1047298uidbalance and CVP were used [20] Noninvasive devices such

Table

Diagnostic tools and methods to determine volume status and predict 1047298uid responsiveness

Clinical assessment Devices needed Comments

Blood pressure Blood pressure cuffarterial line Cheap easy to obtain should be the basis of our

assessments However supplemental information

is often needed in more severely ill patients

especially in cases of shock with multiple causes

Heart rate Electrocardiogramarterial line

Urinary output Urinary catheter

Capillary re1047297ll NA

Peripheral temperature Temperature probe

Neurological examination NA

Biochemical parameters

Base excess Laboratory equipment (in laboratory or

as point-of-care equipment)

Allows assessment of changes over time periods

of several hours Changes in lactate levels (or lack

thereof) have been shown to correlate with

outcome Chlorine can be used to assess metabolic

acidosischlorine overload

Serial lactate

Serum creatinineurea

Serum chlorine

Hemodynamic monitoring

CVP Central venous catheter Poor prediction of volume status

Cardiac output PA catheter PiCCO LidCO FloTrac

echocardiography USCOM

Fair prediction of volume status Some devices

(eg FloTrac) are less reliable in patients with

more severe critical illness

Stroke volume variation Arterial line PiCCO LidCO FloTrac Fair to good prediction of volume status

Venous saturation Central venous and PA catheters Fair prediction of volume status

Mixed venous saturation PA catheter Good prediction of volume status Invasive catheter

must be removed within 96 h

Blood volume PiCCO LidCO Fair to good prediction of volume status

EVLW PiCCO Good safety parameter for volume overload

Intrathoracic blood volume PiCCO Fair to good prediction of volume status

Systolicdiastolic function TEETTE PiCCO LidCO Good prediction of volume status

FloTrac is a proprietaryarterial waveform analysisand cardiac outputmonitoring systemAbbreviations PA pulmonary arteryPiCCO pulse contour cardiac output LidCO lithiumdilution

cardiac output TEE transesophageal echocardiography TTE transthoracic echocardiography USCOM ultrasound cardiac output monitoring

2 KH Polderman J Varon American Journal of Emergency Medicine xxx (2015) xxxndash xxx

Please cite this article as Polderman KH Varon J Donot drownthepatient appropriate1047298uidmanagement in critical illness Am J Emerg Med(2015) httpdxdoiorg101016jajem201501051

7232019 Fluidos Manejo Apropiado 2015

httpslidepdfcomreaderfullfluidos-manejo-apropiado-2015 33

as continuous wave Doppler ultrasound cardiac output monitoring may

also have a useful role in cardiac output monitoring [2122]

Mortality was signi1047297cantly lower in all arms of the ProCESStrial than

in the initial EGDT study [67] In the EGDT arm of the ProCESS trial the

use of vasopressors in the1047297rst 6 hours wasdouble (549 vs 274) and

thevolume infused in the1047297rst 72 hourshalf(722 vs 1344 L) compared

to theEGDT studyThis suggests that more restrictive1047298uid management

is feasible even when using a judicious EGDT approach We urge the

readers to take to heart the important lessons of Sirvent and from previ-

ous trials and not to use too much of a good thing

References

[1] Meyer R Deem S Yanez ND Souter M Lam A Treggiari MM Current practices of triple-H prophylaxis and therapy in patients with subarachnoid hemorrhageNeurocrit Care 20111424ndash36

[2] Dellinger RP Levy MM Rhodes A et al Surviving Sepsis Campaign internationalguidelines for management of severe sepsis and septic shock 2012 Crit Care Med201341580ndash637

[3] Shippy CR Appel PL Shoemaker WC Reliability of clinical monitoring to assessblood volume in critically ill patients Crit Care Med 198412107ndash12

[4] Osman D Ridel C Ray P Monnet X Anguel N Richard C et al Cardiac 1047297lling pres-sures are not appropriate to predict hemodynamic response to volume challengeCrit Care Med 20073564ndash8

[5] Marik PE Cavallazzi R Does the central venous pressure predict 1047298uid responsive-

ness An updated meta-analysis and a plea for some common sense Crit CareMed 2013411774ndash81

[6] Rivers E Nguyen B Havstad S et al Early goal-directed therapy in the treatment of severe sepsis and septic shock N Engl J Med 20013451368ndash77

[7] The ProCESS Investigators A randomized trial of protocol-based care for early septicshock N Engl J Med 20143701683ndash93

[8] ARISE Investigators ANZICS Clinical Trials Group Peake SL Delaney A Bailey MBellomo R et al Goal-directed resuscitation for patients with early septic shock NEngl J Med 20143711496ndash506

[9] Surviving Sepsis Campaign Surviving Sepsis Campaign responds to ProCESS trialUpdated May 19 2014 httpwwwsurvivingsepsisorgSiteCollectionDocuments SSC-RespondsProcess-Trialpdf [Accessed November 28 2014]

[10] Maitland K Kiguli S Opoka RO et al Mortality after 1047298uid bolus in African childrenwith severe infection N Engl J Med 20113642483ndash95

[11] Rosenberg ALDechert REPark PKBartlett RHNIH NHLBI ARDS Network Review of a large clinical series association of cumulative 1047298uid balance on outcome in acutelung injury a retrospective review of the ARDSnet tidal volume study cohort J In-tensive Care Med 20092435ndash46

[12] Murphy CV Schramm GE Doherty JA ReichleyRM Gajic O Afessa B et al The importanceof 1047298uid managementin acute lung injury secondary to septic shockChest 2009136102ndash9

[13] Boyd JH Forbes J Nakada TA Walley KR Russell JA Fluid resuscitation in septicshock a positive 1047298uid balance and elevated central venous pressure are associatedwith increased mortality Crit Care Med 201139259ndash65

[14] Wang CH Hsieh WH Chou HC Huang YS Shen JH Yeo YH et al Liberal versus re-stricted 1047298uid resuscitation strategies in trauma patients a systematic review andmeta-analysis of randomized controlled trials and observational studies Crit CareMed 201442954ndash62

[15] Elterman J Brasel K Brown S et al Transfusion of red blood cells in patients with aprehospital Glasgow Coma Scale score of 8 or less and no evidence of shock is asso-ciated with worse outcomes J Trauma Acute Care Surg 2013758ndash14

[16] Bickell WH Wall Jr MJ Pepe PE et al Immediate versus delayed 1047298uid resuscitation forhypotensive patients with penetrating torso injuries N Engl J Med 19943311105ndash9

[17] Kwan I Bunn F Chinnock P Roberts I Timing and volume of 1047298uid administration forpatients with bleeding Cochrane Database Syst Rev 20143CD002245

[18] Sirvent JM Fluid balance in sepsis and septic shock as a determining factor of mor-tality Am J Emerg Med 2015

[19] Jozwiak M Silva S Persichini R et al Extravascular lung water is an independentprognostic factor in patients with acute respiratory distress syndrome Crit CareMed 201341472ndash80

[20] Mutoh T Kazumata K Terasaka S Taki Y Suzuki A Ishikawa T Early intensive versusminimally invasive approach to postoperative hemodynamic management aftersubarachnoid hemorrhage Stroke 2014451280ndash4

[21] Udy AA Altukroni M Jarrett P Roberts JA Lipman J A comparison of pulse contourwave analysis and ultrasonic cardiac output monitoring in the critically ill AnaesthIntensive Care 201240631ndash7

[22] Chong SW PeytonPJ A meta-analysisof theaccuracy and precision of theultrasoniccardiac output monitor (USCOM) Udy AA1 Altukroni M Jarrett P Roberts JALipman J Anaesthesia 2012671266ndash71

3KH Polderman J Varon American Journal of Emergency Medicine xxx (2015) xxxndash xxx

Please cite this article as Polderman KH Varon J Donot drownthepatient appropriate1047298uidmanagement in critical illness Am J Emerg Med(2015) httpdxdoiorg101016jajem201501051