Fluid Oter Apia

1
Nat|ona| C||n|ca| Gu|de||ne Centre

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Intravenous f|u|d therapy
Intravenous f|u|d therapy |n adu|ts |n hosp|ta|
cllolcol ColJelloe <cC174>
MetboJs, evlJeoce ooJ tecommeoJotloos
uecembet 201J
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commlsslooeJ by tbe Notloool lostltote fot
neoltb ooJ cote xcelleoce
lnLroducLlon
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lv fluld Lherapy ln adulLs

1

D|sc|a|mer
PealLhcare professlonals are expecLed Lo Lake nlCL cllnlcal guldellnes fully lnLo accounL when
exerclslng Lhelr cllnlcal [udgemenL. Powever, Lhe guldance does noL overrlde Lhe responslblllLy of
healLhcare professlonals Lo make declslons approprlaLe Lo Lhe clrcumsLances of each paLlenL, ln
consulLaLlon wlLh Lhe paLlenL and/or Lhelr guardlan or carer.
Copyr|ght
naLlonal Cllnlcal Culdellne CenLre, 2012. ConfldenLlal.
Iund|ng
naLlonal lnsLlLuLe for PealLh and Care Lxcellence
ConLenLs

naLlonal Cllnlcal Culdellne CenLre-uecember 2013
4
Contents
Contents ...................................................................................................................................... 4
Gu|de||ne deve|opment group members ....................................................................................... 8
Acknow|edgements .................................................................................................................... 9
1 Introduct|on ........................................................................................................................ 10
2 Deve|opment of the gu|de||ne .............................................................................................. 12
2.1 WhaL ls a nlCL cllnlcal guldellne? ....................................................................................... 12
2.2 8emlL ................................................................................................................................... 12
2.3 Who developed Lhls guldellne? .......................................................................................... 13
2.4 WhaL Lhls guldellne covers .................................................................................................. 13
2.3 WhaL Lhls guldellne does noL cover .................................................................................... 14
2.6 8elaLlonshlps beLween Lhe guldellne and oLher nlCL guldance ......................................... 14
3 Methods .............................................................................................................................. 16
3.1 ueveloplng Lhe revlew quesLlons and ouLcomes ................................................................ 16
3.1.1 lssues wlLh evldence relaLed Lo guldellne .............................................................. 20
3.1.2 8evlew sLraLegy ...................................................................................................... 20
3.2 Searchlng for evldence ........................................................................................................ 22
3.2.1 Cllnlcal llLeraLure search ......................................................................................... 22
3.2.2 PealLh economlc llLeraLure search ......................................................................... 22
3.3 Lvldence of effecLlveness .................................................................................................... 23
3.3.1 lncluslon/excluslon ................................................................................................. 23
3.3.2 MeLhods of comblnlng cllnlcal sLudles ................................................................... 24
3.3.3 Appralslng Lhe quallLy of evldence by ouLcomes ................................................... 24
3.3.4 Cradlng Lhe quallLy of cllnlcal evldence ................................................................. 26
3.3.3 SLudy llmlLaLlons..................................................................................................... 26
3.3.6 lnconslsLency .......................................................................................................... 27
3.3.7 lndlrecLness ............................................................................................................ 27
3.3.8 lmpreclslon ............................................................................................................. 28
3.4 Lvldence of cosL-effecLlveness ............................................................................................ 29
3.4.1 LlLeraLure revlew .................................................................................................... 30
3.4.2 underLaklng new healLh economlc analysls .......................................................... 31
3.4.3 CosL-effecLlveness crlLerla ...................................................................................... 32
3.4.4 ln Lhe absence of economlc evldence .................................................................... 32
3.3 ueveloplng recommendaLlons ............................................................................................ 32
3.3.1 8esearch recommendaLlons .................................................................................. 33
3.3.3 lundlng ................................................................................................................... 33
4 Gu|de||ne summary .............................................................................................................. 3S
ConLenLs

3
4.1 key prlorlLles for lmplemenLaLlon ....................................................................................... 33
4.2 lull llsL of recommendaLlons .............................................................................................. 37
4.2.1 AlgorlLhms for lv fluld Lherapy ............................................................................... 42
4.2.2 ulagram of ongolng losses ..................................................................................... 43
4.2.3 Consequences of fluld mlsmanagemenL Lo be reporLed as crlLlcal lncldenLs ........ 44
4.2.4 lv fluld prescrlpLlon (by body welghL) for rouLlne malnLenance over a 24-hour
perlod ..................................................................................................................... 44
4.3 key research recommendaLlons ......................................................................................... 46
S r|nc|p|es and protoco|s for |ntravenous f|u|d therapy .......................................................... 47
3.1 1he prlnclples of fluld prescrlblng ....................................................................................... 48
3.1.1 1he physlology of fluld balance ln healLh ............................................................... 48
3.1.2 aLhophyslologlcal effecLs on fluld balance ........................................................... 32
3.1.3 1he cllnlcal approach Lo assesslng lv fluld needs .................................................. 34
3.1.4 1he properLles of avallable lv flulds ....................................................................... 36
3.1.3 8ecommendaLlons based on fluld prescrlblng prlnclples ...................................... 38
3.2 use of algorlLhms ln lv fluld Lherapy .................................................................................. 60
3.2.1 8evlew quesLlon ..................................................................................................... 60
3.2.2 Cllnlcal evldence ..................................................................................................... 60
3.2.3 Lconomlc evldence ................................................................................................. 63
3.2.4 Lvldence sLaLemenLs .............................................................................................. 66
3.2.3 8ecommendaLlons and llnk Lo evldence ................................................................ 66
3.2.6 AlgorlLhms for lv fluld Lherapy ............................................................................... 68
6 Assessment and mon|tor|ng of pat|ents rece|v|ng |ntravenous f|u|d therapy .......................... 69
6.1 lnLroducLlon ........................................................................................................................ 69
6.2 AssessmenL ......................................................................................................................... 70
6.2.1 8evlew quesLlon: WhaL aspecLs of cllnlcal assessmenL are requlred Lo assess,
monlLor and re-evaluaLe fluld and elecLrolyLe sLaLus? .......................................... 70
6.3 8eassessmenL and monlLorlng ............................................................................................ 72
6.3.1 Serlal measuremenL of body welghL ...................................................................... 72
6.3.2 MeasuremenL of urlnary ouLpuL and recordlng of fluld balance ........................... 73
6.3.3 MeasuremenL of serum chlorlde ........................................................................... 79
6.3.4 AlgorlLhm 1: AssessmenL ........................................................................................ 92
6.4 8esearch recommendaLlons ............................................................................................... 93
7 Intravenous f|u|d therapy for f|u|d resusc|tat|on ................................................................... 94
7.1 lnLroducLlon ........................................................................................................................ 94
7.1.1 lv llulds for resusclLaLlon ....................................................................................... 93
7.2 lnLravenous fluld Lherapy for fluld resusclLaLlon- 1ypes of fluld ........................................ 93
7.2.1 CelaLln .................................................................................................................... 97
7.2.2 1eLrasLarch ........................................................................................................... 102
ConLenLs

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7.2.3 Albumln ................................................................................................................ 108
7.2.4 8uffered/physlologlcal soluLlons .......................................................................... 116
7.3 volumes and Llmlng .......................................................................................................... 117
7.3.1 Cllnlcal evldence: volumes and Llmlng ................................................................. 117
7.3.2 Lconomlc evldence ............................................................................................... 123
7.3.3 Lvldence sLaLemenLs ............................................................................................ 123
7.4 8ecommendaLlons and llnk Lo evldence ........................................................................... 124
7.4.1 AlgorlLhm 2: lluld 8esusclLaLlon .......................................................................... 129
7.3 8esearch recommendaLlons ............................................................................................. 131
8 Intravenous f|u|d therapy for rout|ne ma|ntenance ............................................................. 134
8.1 lnLroducLlon ...................................................................................................................... 134
8.1.1 8ouLlne malnLenance flulds for surglcal paLlenLs ................................................ 134
8.1.2 Cholce of lnLravenous flulds for malnLenance ..................................................... 133
8.2 lluld Lypes, volumes and Llmlngs for lv fluld malnLenance .............................................. 136
8.2.1 Cllnlcal evldence: lluld Lypes ............................................................................... 136
8.2.2 Cllnlcal evldence: volumes of lv flulds for malnLenance ..................................... 137
8.2.3 Cllnlcal evldence: 1lmlng of lv fluld malnLenance ............................................... 140
8.3 Lconomlc evldence ........................................................................................................... 140
8.4 Lvldence sLaLemenLs ......................................................................................................... 141
8.4.1 Cllnlcal .................................................................................................................. 141
8.4.2 Lconomlc .............................................................................................................. 143
8.3.1 AlgorlLhm 3: 8ouLlne malnLenance ...................................................................... 148
9 Intravenous f|u|d therapy for rep|acement and red|str|but|on ............................................. 1S1
9.1 lnLroducLlon ...................................................................................................................... 131
9.1.1 rlnclples of lv fluld prescrlblng for replacemenL of deflclLs or ongolng
abnormal losses .................................................................................................... 131
9.1.2 rlnclples of lv fluld prescrlblng for paLlenLs wlLh fluld
redlsLrlbuLlon/abnormal fluld handllng problems ............................................... 132
9.2 lnLravenous fluld Lherapy for replacemenL and redlsLrlbuLlon ........................................ 133
9.3 1ypes of fluld ..................................................................................................................... 133
9.3.1 Cllnlcal evldence ................................................................................................... 134
9.4 volumes and Llmlng of fluld admlnlsLraLlon ..................................................................... 134
9.4.1 Cllnlcal evldence ................................................................................................... 134
9.3.1 AlgorlLhm 4: 8eplacemenL and redlsLrlbuLlon ..................................................... 136
ConLenLs

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10 1ra|n|ng and educat|on of hea|th care profess|ona|s for management of |ntravenous f|u|d
therapy ............................................................................................................................. 1S9
10.1 lnLroducLlon ...................................................................................................................... 139
10.2 8arrlers faced by healLh care professlonals ...................................................................... 160
10.3 Cllnlcal evldence ................................................................................................................ 161
10.3.1 Summary of flndlngs ............................................................................................ 161
10.4 Lvldence summary ............................................................................................................ 164
10.3 key Lhemes ........................................................................................................................ 164
10.3.1 undersLandlng off fluld physlology and paLhophyslology (whaL you should
know prlor Lo prescrlblng lnLravenous fluld) ....................................................... 164
10.3.2 lnlLlal and ongolng Lralnlng and educaLlon lssues ................................................ 163
10.3.3 AssessmenL of compeLence ln relaLlon Lo prescrlblng and admlnlsLerlng
lnLravenous flulds ................................................................................................. 166
10.3.4 lnLravenous flulds managemenL (proLocol led care and prescrlblng).................. 167
10.3.3 CommunlcaLlon lssues ......................................................................................... 168
10.6 Lconomlc evldence ........................................................................................................... 169
11 keference ||st ..................................................................................................................... 173
12 Acronyms and abbrev|at|ons .............................................................................................. 183
13 G|ossary ............................................................................................................................ 18S

Culdellne developmenL group members

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Gu|de||ne deve|opment group members

Name ko|e
Mlchael SLroud Chalr, ConsulLanL ln CasLro-enLerology and Ceneral (lnLernal) medlclne,
SouLhampLon unlverslLy
8eem Al-!ayyousl ConsulLanL nephrologlsL
aul Cook ConsulLanL ln Chemlcal aLhology
8lchard Leach ConsulLanL ln 8esplraLory and CrlLlcal care
ulleep Lobo rofessor of CasLrolnLesLlnal Surgery
1om McLoughlln-?lp aLlenL and carer member
Mlchael MyLhen rofessor of AnaesLheLlcs and CrlLlcal care (unLll CcLober 2012)
aLrlck nee ConsulLanL ln Lmergency Medlclne and CrlLlcal care medlclne
!erry nolan ConsulLanL ln lnLenslve care and AnaesLheLlcs (from CcLober 2012)
lleur norLh aLlenL and carer member
kaLle Scales ConsulLanL nurse- CrlLlcal care (CuLreach)
8ebecca SherraLL Advanced nurse racLlLloner
nell Sonl ConsulLanL ln lnLenslve care and AnaesLheLlcs
Mark 1omlln ConsulLanL harmaclsL CrlLlcal care
Lxpert adv|sors to the group
Name ko|e
Andrew LewlngLon ConsulLanL nephrologlsL, CuC member from AcuLe kldney ln[ury guldellne
Mlchael MyLhen rofessor of AnaesLheLlcs and CrlLlcal care (from CcLober 2012)
Nat|ona| C||n|ca| Gu|de||ne Centre techn|ca| team
Name ko|e
!oanna Ashe Senlor lnformaLlon SclenLlsL
lan 8ullock Culdellne Lead (from november 2011)
varo klrLhl Co-opLed 1echnlcal 1eam Member
Llllan Ll PealLh LconomlsL
SmlLa adhl Senlor 8esearch lellow and ro[ecL Manager
uavld Wonderllng PealLh Lconomlcs Lead
nlna 8alachander Senlor 8esearch lellow (from March 2013 Lo Aprll 2013)
Serena Carvllle Senlor 8esearch lellow (from lebruary 2013 unLll March 2013)
Lee ?ee Chong Senlor 8esearch lellow (from !uly 2011 unLll november 2012)
!ennlfer Layden Senlor ro[ecL Manager (from !uly 2011 unLll !uly 2012)
!ulle nellson Senlor 8esearch lellow and ro[ecL manager (from uecember 2010 unLll !uly
2011 )
Sara 8uckner 8esearch lellow (from !uly 2011 unLll Aprll 2012 )
Susan LaLchem Culdellne lead/CperaLlons dlrecLor (from uecember 2010 unLll november 2011)

AcknowledgemenLs

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Acknow|edgements
1he developmenL of Lhls guldellne was greaLly asslsLed by Lhe followlng people:
nCCC:
Maggle WesLby, Cllnlcal LffecLlveness Lead, nCCC
PaLl Zorba, ro[ecL Co-ordlnaLor, nCCC
!lll Cobb, lnformaLlon SclenLlsL, nCCC
Sarah Podgklnson, Senlor 8esearch lellow and ro[ecL Manager, nCCC

nlCL ro[ecL Leam:
Sharon Summers-Ma, AssoclaLe ulrecLor
Mark 8aker, Cllnlcal Advlser
Clalre 8ulz, Culdellne Commlsslonlng Manager, nlCL (from May 2013)
Cllfford MlddleLon, Culdellne Commlsslonlng Manager, nlCL (unLll May 2013)
Llalne Clydesdale, Culdellne CoordlnaLor
SLeven 8arnes, 1echnlcal Lead
!asdeep Payre, PealLh LconomlsL
Sarah alombella, Senlor Medlcal LdlLor

lnLroducLlon

10
1 Introduct|on
Many adulL hosplLal lnpaLlenLs need lnLravenous (lv) fluld Lherapy Lo prevenL or correcL problems
wlLh Lhelr fluld and/or elecLrolyLe sLaLus. 1hls may be because Lhey cannoL meeL Lhelr normal needs
Lhrough oral or enLeral rouLes (for example, Lhey have swallowlng problems or gasLrolnLesLlnal
dysfuncLlon) or because Lhey have unusual fluld and/or elecLrolyLe deflclLs or demands caused by
lllness or ln[ury (for example, hlgh gasLrolnLesLlnal or renal losses). uecldlng on Lhe opLlmal amounL
and composlLlon of lv flulds Lo be admlnlsLered and Lhe besL raLe aL whlch Lo glve Lhem can be a
difficult task, and decisions must be based on careful assessment of the patients individual needs.
uesplLe Lhe relaLlve complexlLy of estimating a patients IV fluid needs, assessment and prescription
ls ofLen delegaLed Lo healLhcare professlonals who have recelved llLLle or no speclflc Lralnlng on Lhe
sub[ecL. lndeed, Lhe Lask of prescrlblng lv flulds ls ofLen lefL Lo Lhe mosL [unlor medlcal sLaff, who
frequenLly lack Lhe relevanL experlence. 1hls problem was hlghllghLed by a 1999 naLlonal
ConfldenLlal Lnqulry lnLo erloperaLlve ueaLhs (nCLCu) reporL, whlch found LhaL a slgnlflcanL
number of hosplLallsed paLlenLs were dylng as a resulL of Lhe lnfuslon of Loo much or Loo llLLle fluld.
73

1he reporL Lhen recommended LhaL fluld prescrlblng should be glven Lhe same sLaLus as drug
prescrlblng. unforLunaLely Lhls has noL yeL occurred, and alLhough lnapproprlaLe fluld Lherapy ls
rarely reporLed as belng responslble for paLlenL harm, lL remalns llkely LhaL as many as 1 ln 3 paLlenLs
on lv flulds and elecLrolyLes suffer compllcaLlons or morbldlLy due Lo Lhelr lnapproprlaLe
admlnlsLraLlon.
Lrrors ln prescrlblng lv flulds and elecLrolyLes are parLlcularly llkely ln emergency deparLmenLs, acuLe
admlsslon unlLs, and general medlcal and surglcal wards raLher Lhan ln operaLlng LheaLres and
crlLlcal care unlLs because paLlenLs ln more general areas usually have less cardlovascular monlLorlng
and Lhe sLaff may have less experlence of fluld prescrlblng. lndeed, surveys have shown LhaL many
sLaff who prescrlbe lv flulds ln such areas know nelLher Lhe llkely fluld and elecLrolyLe needs of
lndlvldual paLlenLs, nor Lhe speclflc composlLlon of Lhe many cholces of lv flulds avallable Lo Lhem.
SLandards of recordlng and monlLorlng lv fluld and elecLrolyLe Lherapy may also be poor ln Lhese
settings, and staff may fail to reassess and respond to patients inevitable changes in IV fluid and
elecLrolyLe sLaLus over Llme.
ln addlLlon Lo Lhe problems above, Lhere ls also conslderable debaLe among lv fluld and elecLrolyLe
experLs abouL Lhe besL lv flulds Lo use, parLlcularly for more serlously lll or ln[ured paLlenLs. 1here ls
Lherefore wlde varlaLlon ln cllnlcal pracLlce. Many reasons underlle Lhe ongolng debaLe, buL mosL
revolve around dlfflculLles ln lnLerpreLaLlon of boLh Lrlals evldence and cllnlcal experlence, lncludlng
Lhe followlng facLors:
Many accepLed pracLlces of lv fluld prescrlblng were developed for hlsLorlcal reasons raLher Lhan
Lhrough cllnlcal Lrlals.
1rlals cannoL easlly be lncluded ln meLa-analyses because Lhey examlne varled ouLcome measures
ln heLerogeneous groups, comparlng noL only dlfferenL Lypes of fluld wlLh dlfferenL elecLrolyLe
conLenL, buL also dlfferenL volumes and raLes of admlnlsLraLlon and, ln some cases, Lhe addlLlonal
use of lnoLropes or vasopressors.
MosL Lrlals have been underLaken ln operaLlng LheaLres and crlLlcal care unlLs raLher Lhan
admlsslon unlLs or general and elderly care seLLlngs.
1rlals clalmlng Lo examlne besL early Lherapy for resusclLaLlon have acLually evaluaLed Lherapy
cholces made afLer lnlLlal resusclLaLlon wlLh paLlenLs already ln crlLlcal care or operaLlng LheaLres.
Many Lrlals lnferrlng besL Lherapy for resusclLaLlon afLer acuLe fluld loss have acLually examlned
slLuaLlons of hypovolaemla lnduced by anaesLhesla.
lnLroducLlon

11
ln Lhe llghL of all Lhe above, Lhere ls a clear need for guldance on lv fluld Lherapy for general areas of
hosplLal pracLlce, coverlng boLh Lhe prescrlpLlon and monlLorlng of lv fluld and elecLrolyLe Lherapy,
and Lhe Lralnlng and educaLlonal needs of all hosplLal sLaff lnvolved ln lv fluld managemenL.
1he alm of Lhls nlCL guldellne ls Lherefore Lo help prescrlbers undersLand Lhe:
physlologlcal prlnclples LhaL underpln fluld prescrlblng
paLhophyslologlcal changes LhaL affecL fluld balance ln dlsease sLaLes
lndlcaLlons for lv fluld Lherapy
reasons for Lhe cholce of Lhe varlous flulds avallable and
prlnclples of assesslng fluld balance.

ln developlng Lhe guldellne, however, lL was necessary Lo llmlL Lhe scope by excludlng paLlenL groups
wlLh more speclallsed fluld prescrlblng needs. lL ls lmporLanL Lo emphaslse from Lhe ouLseL LhaL Lhe
recommendaLlons do noL apply Lo paLlenLs under 16 years, pregnanL women, and Lhose wlLh severe
llver or renal dlsease, dlabeLes or burns. 1hey also do noL apply Lo paLlenLs needlng lnoLropes and
Lhose on lnLenslve monlLorlng, and so Lhey have less relevance Lo lnLenslve care seLLlngs and paLlenLs
durlng surglcal anaesLhesla. aLlenLs wlLh LraumaLlc braln ln[ury (lncludlng neurosurglcal paLlenLs)
are also excluded and Lhe recommendaLlons do noL cover Lhe acLual admlnlsLraLlon (as opposed Lo
Lhe prescrlpLlon) of lv flulds.
lL ls hoped LhaL Lhls guldellne wlll lead Lo beLLer fluld prescrlblng ln hosplLallsed paLlenLs, help reduce
boLh morbldlLy and morLallLy, and lead Lo beLLer paLlenL ouLcomes.
SLraLegles for furLher research lnLo Lhe sub[ecL have also been proposed.
uevelopmenL of Lhe guldellne

12
2 Deve|opment of the gu|de||ne
2.1 What |s a NICL c||n|ca| gu|de||ne?
nlCL cllnlcal guldellnes are recommendaLlons for Lhe care of lndlvlduals ln speclflc cllnlcal condlLlons
or clrcumsLances wlLhln Lhe nPS from prevenLlon and self-care Lhrough prlmary and secondary
care Lo more speclallsed servlces. We base our cllnlcal guldellnes on Lhe besL avallable research
evldence, wlLh Lhe alm of lmprovlng Lhe quallLy of healLh care. We use predeLermlned and
sysLemaLlc meLhods Lo ldenLlfy and evaluaLe Lhe evldence relaLlng Lo speclflc revlew quesLlons.
nlCL cllnlcal guldellnes can:
provlde recommendaLlons for Lhe LreaLmenL and care of people by healLh professlonals
be used Lo develop sLandards Lo assess Lhe cllnlcal pracLlce of lndlvldual healLh professlonals
be used ln Lhe educaLlon and Lralnlng of healLh professlonals
help paLlenLs Lo make lnformed declslons
lmprove communlcaLlon beLween paLlenL and healLh professlonal
Whlle guldellnes asslsL Lhe pracLlce of healLhcare professlonals, Lhey do noL replace Lhelr knowledge
and skllls.
We produce our guldellnes uslng Lhe followlng sLeps:
Culdellne Loplc ls referred Lo nlCL from Lhe ueparLmenL of PealLh
SLakeholders reglsLer an lnLeresL ln Lhe guldellne and are consulLed LhroughouL Lhe developmenL
process.
1he scope ls prepared by Lhe naLlonal Cllnlcal Culdellne CenLre (nCCC)
1he nCCC esLabllshes a guldellne developmenL group
A drafL guldellne ls produced afLer Lhe group assesses Lhe avallable evldence and makes
recommendaLlons
1here ls a consulLaLlon on Lhe drafL guldellne.
1he flnal guldellne ls produced.
1he nCCC and nlCL produce a number of verslons of Lhls guldellne:
Lhe full guldellne conLalns all Lhe recommendaLlons, plus deLalls of Lhe meLhods used and Lhe
underplnnlng evldence
Lhe nlCL guldellne llsLs Lhe recommendaLlons
lnformaLlon for Lhe publlc ls wrlLLen uslng sulLable language for people wlLhouL speclallsL medlcal
knowledge
Lhe nlCL paLhway brlngs LogeLher all connecLed nlCL guldance.
1hls verslon ls Lhe full verslon. 1he oLher verslons can be downloaded from nlCL aL www.nlce.org.uk
2.2 kem|t
nlCL recelved Lhe remlL for Lhls guldellne from Lhe ueparLmenL of PealLh. 1hey commlssloned Lhe
nCCC Lo produce Lhe guldellne.
1he remlL for Lhls guldellne ls:
1o produce a cllnlcal guldellne on lnLravenous fluld Lherapy ln hosplLallsed adulL paLlenLs.

13
2.3 Who deve|oped th|s gu|de||ne?
A mulLldlsclpllnary Culdellne uevelopmenL Croup (CuC) comprlslng professlonal group members and
consumer represenLaLlves of Lhe maln sLakeholders developed Lhls guldellne (see secLlon on
Culdellne uevelopmenL Croup Membershlp and acknowledgemenLs).
1he naLlonal lnsLlLuLe for PealLh and Care Lxcellence funds Lhe naLlonal Cllnlcal Culdellne CenLre
(nCCC) and Lhus supporLed Lhe developmenL of Lhls guldellne. 1he CuC was convened by Lhe nCCC
and chalred by Mlchael SLroud ln accordance wlLh guldance from Lhe naLlonal lnsLlLuLe for PealLh
and Care Lxcellence (nlCL).
1he group meL every 3-6 weeks durlng Lhe developmenL of Lhe guldellne. AL Lhe sLarL of Lhe guldellne
developmenL process all CuC members declared lnLeresLs lncludlng consulLancles, fee-pald work,
share-holdlngs, fellowshlps and supporL from Lhe healLhcare lndusLry. AL all subsequenL CuC
meeLlngs, members declared arlslng confllcLs of lnLeresL, whlch were also recorded (Appendlx 8)
Members were elLher requlred Lo wlLhdraw compleLely or for parL of Lhe dlscusslon lf Lhelr declared
lnLeresL made lL approprlaLe. 1he deLalls of declared lnLeresLs and Lhe acLlons Laken are shown ln
Appendlx 8.
SLaff from Lhe nCCC provlded meLhodologlcal supporL and guldance for Lhe developmenL process.
1he Leam worklng on Lhe guldellne lncluded a pro[ecL manager, sysLemaLlc revlewers, healLh
economlsLs and lnformaLlon sclenLlsLs. 1hey underLook sysLemaLlc searches of Lhe llLeraLure,
appralsed Lhe evldence, conducLed meLa-analysls and cosL effecLlveness analysls where approprlaLe
and drafLed Lhe guldellne ln collaboraLlon wlLh Lhe CuC.
2.4 What th|s gu|de||ne covers
1hls guldellne covers Lhe followlng populaLlons:
AdulLs (16 years and older) ln hosplLal recelvlng lnLravenous fluld Lherapy
1he followlng cllnlcal lssues are covered:
1ralnlng and educaLlon ln cllnlcal assessmenL, prescrlblng, monlLorlng, evaluaLlng and
documenLlng lnLravenous fluld Lherapy ln hosplLals.
AssessmenL, monlLorlng and re-evaluaLlon of fluld and elecLrolyLe sLaLus
ApproprlaLe documenLaLlon for cllnlcal assessmenL, prescrlblng, monlLorlng and re-evaluaLlon of
the patients fluid and electrolyte status.
1ypes, volume and Llmlng of flulds and elecLrolyLes Lo resLore fluld balance (resusclLaLlon):
o crysLallolds compared wlLh oLher crysLallolds
o crysLallolds compared wlLh collolds
o collolds compared wlLh oLher collolds.
1ypes, volume and Llmlng of flulds and elecLrolyLes Lo malnLaln fluld balance:
o crysLallolds compared wlLh oLher crysLallolds.
1ypes, volume and Llmlng of flulds and elecLrolyLes Lo replace conLlnulng abnormal fluld losses:
o crysLallolds compared wlLh oLher crysLallolds
o crysLallolds compared wlLh collolds
o collolds compared wlLh oLher collolds.
Speclflc conslderaLlons relaLed Lo lnLravenous fluld Lherapy ln paLlenLs who have:
o acuLe kldney ln[ury, up Lo Lhe polnL of renal replacemenL Lherapy

14
o sepsls
o Lrauma
o congesLlve hearL fallure.
lor furLher deLalls please refer Lo Lhe scope ln Appendlx A and revlew quesLlons ln secLlon 3.1.
2.S What th|s gu|de||ne does not cover
1he guldellne does noL cover Lhe followlng:
opu|at|ons:
eople younger Lhan 16 years.
regnanL women.
aLlenLs wlLh severe (sLage 4 or 3) chronlc kldney dlsease or llver dlsease (Chlld-ugh grade A-C).
aLlenLs wlLh dlabeLes, lncludlng Lhose wlLh dlabeLlc keLoacldosls and hyperosmolar sLaLes.
aLlenLs needlng lnoLropes Lo supporL Lhelr clrculaLlon.
aLlenLs wlLh burns.
aLlenLs wlLh LraumaLlc braln ln[ury or needlng neurosurgery.
key areas:
8ouLe of admlnlsLraLlon and lnLravenous caLheLer-relaLed lssues, such as cholce of caLheLer,
placemenL Lechnlques and caLheLer-relaLed lnfecLlon.
use of blood and blood producLs, excepL albumln.
1he speclflc monlLorlng or prescrlpLlon of elecLrolyLes, mlnerals and Lrace elemenLs oLher Lhan
sodlum, poLasslum and chlorlde, unless Lhelr sLaLus dlrecLly lnfluences sodlum, poLasslum or
chlorlde provlslon (for example, low magneslum prevenLlng correcLlon of hypokalaemla).
use of lnoLropes Lo supporL clrculaLory fallure.
lnvaslve monlLorlng of fluld sLaLus, for example ln crlLlcal care or durlng surglcal anaesLhesla.
arenLeral nuLrlLlon beyond conslderaLlon of fluld and elecLrolyLe conLenL.
Labelllng, preparaLlon and sLorage of boLh sLandard and non-sLandard lnLravenous flulds.
LLhlcal lssues relaLed Lo lnLravenous fluld prescrlpLlon aL Lhe end of llfe.
2.6 ke|at|onsh|ps between the gu|de||ne and other NICL gu|dance
ke|ated NICL nea|th 1echno|ogy Appra|sa|s:
re-hosplLal lnlLlaLlon of fluld replacemenL Lherapy ln Lrauma. nlCL Lechnology appralsal guldance 74
(2004).
ke|ated NICL C||n|ca| Gu|de||nes:
AcuLe kldney ln[ury. nlCL cllnlcal guldellne 169 (2013).
aLlenL experlence ln adulL nPS servlces. nlCL cllnlcal guldellne and quallLy sLandard (2012).
Chronlc kldney ulsease. nlCL cllnlcal guldellne 73 (2008). 1hls guldance ls currenLly belng updaLed.
Medlclnes adherence. nlCL cllnlcal guldellne 76 (2009).
AcuLely lll paLlenLs ln hosplLal. nlCL cllnlcal guldellne 30 (2007).

13
CbeslLy. nlCL cllnlcal guldellne 43 (2006)
nuLrlLlon supporL ln adulLs. nlCL cllnlcal guldellne 32 (2006).
1ype 1 dlabeLes. nlCL cllnlcal guldellne 13 (2004).
ke|ated NICL ub||c nea|th Gu|dance:
revenLlon and conLrol of healLhcare assoclaLed lnfecLlons. nlCL publlc healLh quallLy lmprovemenL
gulde 36 (2011).
NICL ke|ated Gu|dance current|y |n deve|opment:
1ransfuslon. nlCL cllnlcal guldellne. ubllcaLlon expecLed May 2013.
Ma[or Lrauma: AssessmenL and managemenL of ma[or Lrauma. nlCL cllnlcal guldellne. ubllcaLlon
expecLed !une 2013.
lnLravenous fluld Lherapy ln chlldren. nlCL cllnlcal guldellne. ubllcaLlon expecLed november 2013.
1ype 1 ulabeLes (updaLe). nlCL cllnlcal guldellne. ubllcaLlon expecLed AugusL 2013.
MeLhods

16
3 Methods
1hls guldance was developed ln accordance wlLh Lhe meLhods ouLllned ln Lhe nlCL Culdellnes
Manual 2009.
76
An updaLed nlCL Culdellnes Manual was publlshed ln 2012, when Lhls guldellne was
already ln developmenL.
3.1 Deve|op|ng the rev|ew quest|ons and outcomes
8evlew quesLlons were developed ln a lCC framework (paLlenL, lnLervenLlon, comparlson and
ouLcome) for lnLervenLlon revlews. 1hls was Lo gulde Lhe llLeraLure searchlng process and Lo faclllLaLe
Lhe developmenL of recommendaLlons by Lhe guldellne developmenL group (CuC). 1hese were
drafLed by Lhe nCCC Lechnlcal Leam and reflned and valldaLed by Lhe CuC. 1he quesLlons were
based on Lhe key cllnlcal areas ldenLlfled ln Lhe scope (see Appendlx A).
uue Lo Lhe breadLh of Lhe scope and Lhe LargeL populaLlon, Lhe CuC ofLen found LhaL several revlew
quesLlons could be generaLed for a slngle area wlLhln Lhe scope. Powever, only 13 Lo 20 quesLlons
can be reasonably managed wlLhln Lhe usual Llme frame of full cllnlcal guldellne developmenL (18
monLhs). Slnce lL was noL posslble Lo cover all poLenLlally lmporLanL aspecLs, Lhe CuC consldered Lhe
relaLlve lmporLance of Lhese and prlorlLlsed areas for developlng revlew quesLlons
77
. 1hls declslon Lo
prlorlLlse cerLaln areas Look lnLo conslderaLlon facLors such as wheLher Lhe area ls a key cllnlcal lssue
for Lhe nPS, paLlenL safeLy, cosL (Lo Lhe nPS), equallLy and varlaLlons ln pracLlce.
1ab|e 1: kev|ew quest|ons
Chapter kev|ew quest|ons Cutcomes
r|nc|p|es and protoco|s
of |ntravenous f|u|d
therapy
WhaL ls Lhe cllnlcal and cosL effecLlveness
of cllnlcal algorlLhms or deflned proLocols
for Lhe assessmenL, monlLorlng and/or
managemenL of lnLravenous fluld and
elecLrolyLe requlremenL ln hosplLallsed
adulL paLlenLs?
All-cause morLallLy wlLhln 30
days of hosplLallsaLlon
LengLh of sLay ln hosplLal
LengLh of sLay ln lnLenslve care
unlL
CuallLy of llfe
8enal compllcaLlons
ulmonary oedema
Assessment and
mon|tor|ng on
|ntravenous f|u|d
therapy
WhaL aspecLs of cllnlcal assessmenL are
requlred Lo assess, monlLor and re-evaluaLe
fluld and elecLrolyLe sLaLus?
n/A
ln hosplLallsed paLlenLs recelvlng
lnLravenous flulds, whaL ls Lhe cllnlcal and
cosL effecLlveness of measurlng and
recordlng serlal body welghL?
unlL
CuallLy of llfe
8enal compllcaLlons/AcuLe
kldney ln[ury deflned as an
lncrease of 30 or more of
serum creaLlnlne from basellne
8esplraLory compllcaLlons
lncludlng pulmonary oedema,
resplraLory fallure, chesL
lnfecLlon, mechanlcal
venLllaLlon
MorbldlLy measured by SClA
MeLhods

17
(SequenLlal Crgan lallure
AssessmenL) score and MulLlple
Crgan uysfuncLlon Score
(MCuS).
1oLal volume of fluld recelved (lf
boLh groups recelve Lhe same
Lype of fluld).
lnLravenous flulds, whaL ls Lhe cllnlcal and
cosL effecLlveness of measurlng and
recordlng urlne ouLpuL ln addlLlon Lo
recordlng sLandard parameLers sLaLed ln
nLWS (naLlonal Larly Warnlng Score) Lo
deLermlne Lhe need for lnLravenous fluld
admlnlsLraLlon?
unlL
CuallLy of llfe
venLllaLlon
(MCuS).
1oLal volume of fluld recelved (lf
boLh groups recelve Lhe same
Lype of fluld).
lnLravenous flulds, whaL ls Lhe lncldence
and cllnlcal slgnlflcance of hyperchloraemla
and hypochloraemla?
All-cause morLallLy
LengLh of sLay ln hosplLal and/or
lnLenslve care unlL
CuallLy of llfe
kldney ln[ury (Akl) deflned as an
level
(MCuS).
Pyperchloraemla
Pyperchloraemlc acldosls
Pypochloraemla.
Intravenous f|u|d
therapy for
resusc|tat|on
WhaL ls Lhe mosL cllnlcally and cosL
effecLlve lnLravenous fluld for fluld
resusclLaLlon of hosplLallsed paLlenLs?
MeLhods

18
unlL
CuallLy of llfe
lncrease of 30 or more ln
serum creaLlnlne level from
basellne
lnfecLlon and mechanlcal
venLllaLlon
(MCuS).
WhaL ls cllnlcal and cosL effecLlveness of
dlfferenL volumes of lnLravenous fluld
admlnlsLraLlon for fluld resusclLaLlon?

WhaL are Lhe mosL cllnlcally and cosL
effecLlve Llmlng and raLe of admlnlsLraLlon
of lnLravenous flulds for fluld resusclLaLlon?
unlL
CuallLy of llfe
basellne
venLllaLlon
(MCuS).
Intravenous f|u|d
therapy for rout|ne
ma|ntenance

effecLlve lnLravenous fluld for rouLlne
malnLenance ln hosplLallsed paLlenLs?
unlL
CuallLy of llfe
basellne
lncludlng pulmonary oedema ,
MeLhods

19
venLllaLlon
(MCuS).
admlnlsLraLlon for rouLlne malnLenance?

of lnLravenous flulds for rouLlne
malnLenance?
unlL
CuallLy of llfe
basellne
venLllaLlon
(MCuS).
Intravenous f|u|d
therapy for rep|acement
and red|str|but|on
effecLlve lnLravenous fluld for replacemenL
of abnormal ongolng losses ln hosplLallsed
paLlenLs?
unlL
CuallLy of llfe
basellne
venLllaLlon
(MCuS).
admlnlsLraLlon for replacemenL of
MeLhods

20
abnormal ongolng losses?

of lnLravenous flulds for replacemenL of
abnormal ongolng losses?
unlL
CuallLy of llfe
basellne
venLllaLlon
(MCuS).
1ra|n|ng and educat|on
for management of
|ntravenous f|u|d
therapy
WhaL are Lhe barrlers faced by healLhcare
professlonals ln Lhe effecLlve prescrlpLlon
and monlLorlng of lnLravenous flulds ln
hosplLal seLLlngs?
Pealth care professionals views
and experlences.

3.1.1 Issues w|th ev|dence re|ated to gu|de||ne
Larly ln Lhe developmenL of Lhe guldellne lL was ldenLlfled LhaL evldence from mulLlple groups of
paLlenLs would need Lo be consldered due Lo Lhe breadLh of Lhe LargeL populaLlon. Powever, Lhe
evldence from one group of paLlenLs was noL necessarlly appllcable Lo all hosplLallsed paLlenLs as
Lhese groups have dlfferenL fluld requlremenL and responses Lo lnLravenous fluld Lherapy. 1hls was a
recurrlng feaLure wlLh Lhe ma[orlLy of Lhe evldence ldenLlfled for Lhls guldellne.
1he oLher lmporLanL lssues whlch came Lo llghL durlng developmenL were:
Lack of evldence: LxcepL for some areas ln Lhe guldellne, Lhere was a lack of evldence, especlally
hlgh quallLy evldence from randomlsed conLrolled Lrlals (8C1s) and large cohorL sLudles wlLh
respecL Lo lnLravenous fluld Lherapy
lraudulenL research: A large number of Lrlals perLalnlng Lo Lhe Lypes and admlnlsLraLlon of
lnLravenous flulds had been reLracLed durlng Lhe guidelines development period or were under
lnvesLlgaLlon for reLracLlon.
3.1.2 kev|ew strategy
A robusL buL pragmaLlc approach was warranLed ln Lhe absence of hlgh quallLy evldence.
3.1.2.1 Ind|rect ev|dence
When 8C1 evldence was noL avallable, Lhe lnlLlal approach was Lo conslder uslng lndlrecL evldence
from 8C1s ln oLher populaLlons - evldence from one subgroup LhaL could be exLrapolaLed Lo oLhers.
1he CuC members dlscussed Lhe appllcablllLy of Lhe evldence across groups and slLuaLlons where
lndlrecL evldence lnformed declslon maklng and Lhese were expllclLly documenLed.
lor example , Lhe LargeL populaLlon for Lhe revlew on fluld resusclLaLlon was adulLs ln hosplLal who
were recelvlng lnLravenous fluld Lherapy for fluld resusclLaLlon. 1he CuC dlscussed and agreed LhaL lf
MeLhods

21
no evldence ln Lhe LargeL populaLlon was ldenLlfled, Lhe revlew would lnclude lndlrecL evldence ln
Lhe followlng order:
1.paLlenLs ln lnLenslve care unlLs/ hlgh dependency unlLs,
2.emergency servlces, lncludlng paLlenLs fluld resusclLaLlon ln ambulances and emergency servlces
3.lnLra-operaLlve paLlenLs (Lhls would however exclude paLlenLs recelvlng lv flulds for
normovolaemlc hemodlluLlon, lnLraoperaLlve cardlac bypass surgery and preload for splnal
anaesLhesla as Lhese were deemed Lo be Loo lndlrecL or relevanL Lo Lhe LargeL populaLlon)
3.1.2.2 Lv|dence from non-random|sed stud|es
lL was hlghllghLed LhaL evldence from 8C1s was only avallable for selecLed cllnlcal quesLlons, and Lhe
CuC agreed on a conslsLenL approach Lo lnclude non-randomlsed sLudles ln Lhls guldellne.
Powever, Lhe breadLh of populaLlon of Lhe guldellne meanL LhaL Lhe flne balance of lnvesLlng more
resources Lo search and evaluaLe lower quallLy evldence from observaLlonal sLudles was Lo be
carefully evaluaLed agalnsL Lhe addlLlonal value lL broughL Lo Lhe declslon maklng process.
1herefore, Lhe revlew sLraLegy for lncluslon of evldence from 8C1s and non-randomlsed sLudles
followed Lhe followlng prlnclples ln a sLep wlse manner:
Cnly randomlsed conLrolled Lrlals were lncluded, lf evldence was avallable (for revlew quesLlons
relaLlng Lo lnLervenLlons)
rospecLlve cohorL sLudles were lncluded lf Lhe followlng condlLlons were meL:
o no 8C1 evldence avallable
o Lvldence avallable from 8C1s where only llmlLed Lo speclflc populaLlons wlLhln Lhe cllnlcal
quesLlon, and lL was consldered lnapproprlaLe Lo exLrapolaLe Lhe lnformaLlon Lo oLher
subgroups.
o 1here were conLroversles regardlng Lhe besL pracLlce ln Lhe area Lhe CuC were
uncomforLable ln maklng recommendaLlons based on consensus and belleved LhaL even very
low quallLy evldence may provlde relevanL lnformaLlon LhaL lmpacLed Lhelr declslons.
3.1.2.3 Iraudu|ent research
A declslon was Laken by Lhe CuC Lo exclude any sLudy LhaL had been reLracLed or was under
lnvesLlgaLlon. 1he ma[orlLy of Lhese sLudles had conLrlbuLlons by !oachlm 8oldL.
3.1.2.4 Stud|es conducted before 1990
1he CuC dlscussed LhaL Lhere have been conslderable changes ln cllnlcal pracLlce ln Lhe pasL few
decades, wlLh Lhe lmpllcaLlon LhaL older sLudles may noL be appllcable. 1hls was Laken lnLo accounL
when decldlng Lhe revlew proLocols and sLudles publlshed before 1990 were excluded for Lhe
revlews where Lhls would have an lmpacL (fluld resusclLaLlon)
3.1.2.S kecommendat|ons based on consensus
lL was acknowledged LhaL lL was noL posslble Lo underLake cllnlcal evldence revlews for cerLaln areas
of Lhe guldellne. 1wo such areas whlch were excepLlons Lo Lhe normal sysLemaLlc revlew process
were:
sLandard prlnclples of lnLravenous fluld Lherapy
assessmenL and monlLorlng of lnLravenous fluld and elecLrolyLe needs
Pere, Lhe CuC Look lnLo conslderaLlon Lhe prlnclples of physlology and paLhophyslology of
lnLravenous flulds and oLher accepLed sLandard cllnlcal guldance and drafLed recommendaLlons
based on experL consensus ln a formaL lnLended Lo be useful Lo a cllnlclan.
16,93

MeLhods

22
1he naLlonal Larly Warnlng Score (nLWS) ls a ueparLmenL of PealLh lnlLlaLlve whlch was accepLed by
Lhe CuC as a rellable and lnformaLlve scorlng sysLem for assessmenL. 1he CuC based Lhls declslon on
Lhe facL LhaL nLWS has been demonsLraLed Lo be as good as Lhe besL of oLher early warnlng scores ln
dlscrlmlnaLlng rlsk of acuLe morLallLy and ls llkely Lo be more senslLlve Lhan mosL currenLly used
sysLems aL prompLlng an alerL and cllnlcal response Lo acuLe lllness deLerloraLlon.
93

3.2 Search|ng for ev|dence
3.2.1 C||n|ca| ||terature search
SysLemaLlc llLeraLure searches were underLaken Lo ldenLlfy evldence wlLhln publlshed llLeraLure ln
order Lo answer Lhe revlew quesLlons as per 1he Culdellnes Manual [2009].
76
Cllnlcal daLabases were
searched uslng relevanL medlcal sub[ecL headlngs, free-LexL Lerms and sLudy Lype fllLers where
approprlaLe. SLudles publlshed ln languages oLher Lhan Lngllsh were noL revlewed. Where posslble,
searches were resLrlcLed Lo arLlcles publlshed ln Lngllsh language. All searches were conducLed on
core daLabases, MLuLlnL, Lmbase and 1he Cochrane Llbrary. AddlLlonal sub[ecL speclflc daLabases
were used for some quesLlons: ClnAPL for quesLlons on Lralnlng and educaLlon, algorlLhms, urlne
ouLpuL, and dally welghLs, syclnlC for Lhe Lralnlng and educaLlon quesLlon. All searches were
updaLed on 12 March 2013. no papers afLer Lhls daLe were consldered.
Search sLraLegles were checked by looklng aL reference llsLs of relevanL key papers, checklng search
sLraLegles ln oLher sysLemaLlc revlews and asklng Lhe CuC for known sLudles. 1he quesLlons, Lhe
sLudy Lypes applled, Lhe daLabases searched and Lhe years covered can be found ln Appendlx u.
1hls ls a cllnlcal area LhaL presenLed challenges when searchlng for Lhe evldence. 1here was no clear
populaLlon for each quesLlon, as well as a lack of conslsLency ln Lhe Lermlnology used ln Lhe papers
and ln Lhe appllcaLlon of lndex Lerms ln Lhe daLabases. 1hese facLors Lend Lo lead Lo very large
searches wlLh lmpreclse reLrleval. 1here was a need Lo balance Lhls wlLh Lhe resources avallable Lo
slfL Lhrough large reLrlevals wlLhln Lhe Llme alloLLed. lor Lhls reason Lhere was exLra rellance on
flndlng evldence Lhrough meLhods such as checklng reference llsLs or asklng Lhe CuC for known
sLudles, as a supplemenL Lo Lhe llLeraLure searches. 1hls ls ln llne wlLh meLhodology suggesLed by Lhe
Cochrane CollaboraLlon.
2

As an exLra precauLlon, revlewers also checked Lhrough Lhe all sLudles whlch were ordered buL
excluded for relaLed revlews, Lo ensure LhaL no relevanL sLudles were mlssed. lor example, when
looklng for sLudles for Lhe volume and Llmlng of resusclLaLlon revlew, revlewers also checked Lhe
sLudles whlch had been ordered for Lhe algorlLhm quesLlons (Lhere ls a posslblllLy LhaL some
algorlLhms effecLlvely compare early vs. laLe resusclLaLlon) and Lhe fluld Lype quesLlon.
uurlng Lhe scoplng sLage, a search was conducLed for guldellnes and reporLs on Lhe webslLes llsLed
below and on organlsaLlons relevanL Lo Lhe Loplc. Searchlng for grey llLeraLure or unpubllshed
llLeraLure was noL underLaken. All references senL by sLakeholders were consldered.
Culdellnes lnLernaLlonal neLwork daLabase (www.g-l-n.neL)
naLlonal Culdellne Clearlng Pouse (www.guldellne.gov/)
naLlonal lnsLlLuLe for PealLh and Care excellence (nlCL) (www.nlce.org.uk)
naLlonal lnsLlLuLes of PealLh Consensus uevelopmenL rogram (consensus.nlh.gov/)
naLlonal Llbrary for PealLh (www.llbrary.nhs.uk/)
3.2.2 nea|th econom|c ||terature search
SysLemaLlc llLeraLure searches were also underLaken Lo ldenLlfy healLh economlc evldence wlLhln
publlshed llLeraLure relevanL Lo Lhe revlew quesLlons. 1he evldence was ldenLlfled by conducLlng
MeLhods

23
broad searches relaLlng Lo speclflc key areas ln Lhe nPS economlc evaluaLlon daLabase (nPS LLu),
Lhe PealLh Lconomlc LvaluaLlons uaLabase (PLLu) and healLh Lechnology assessmenL (P1A)
daLabases wlLh no daLe resLrlcLlons. AddlLlonally, Lhe searches were run on MLuLlnL and Lmbase,
wlLh a speclflc economlc fllLer Lo ensure publlcaLlons LhaL had noL yeL been lndexed by Lhese
daLabases were ldenLlfled. SLudles publlshed ln languages oLher Lhan Lngllsh were noL revlewed.
Where posslble, searches were resLrlcLed Lo arLlcles publlshed ln Lngllsh language.
1he search sLraLegles for healLh economlcs are lncluded ln Appendlx u. All searches were updaLed on
12 March 2013. no papers publlshed afLer Lhls daLe were consldered.
3.3 Lv|dence of effect|veness
1he 8esearch lellow:
ldenLlfled poLenLlally relevanL sLudles for each revlew quesLlon from Lhe relevanL search resulLs
by revlewlng LlLles and absLracLs full papers were Lhen obLalned.
8evlewed full papers agalnsL pre-speclfled lncluslon / excluslon crlLerla Lo ldenLlfy sLudles LhaL
addressed Lhe revlew quesLlon ln Lhe approprlaLe populaLlon and reporLed on ouLcomes of
lnLeresL (see revlew proLocols ln Appendlx C).
CrlLlcally appralsed relevanL sLudles uslng Lhe approprlaLe checkllsL as speclfled ln 1he Culdellnes
Manual.
77

Extracted key information about the studys methods and results into evidence tables (see
evldence Lables are lncluded ln Appendlx L).
CeneraLed summarles of Lhe evldence by ouLcome (lncluded ln Lhe relevanL chapLer wrlLe-ups):
o 8andomlsed sLudles: meLa analysed, where approprlaLe and reporLed ln C8AuL proflles (for
cllnlcal sLudles) see below for deLalls
o CbservaLlonal sLudles: daLa presenLed as a range of values ln C8AuL proflles
o CuallLaLlve sLudles: each sLudy summarlsed ln a Lable where posslble, oLherwlse presenLed ln a
narraLlve.
3.3.1 Inc|us|on]exc|us|on
Lvldence was searched and assessed accordlng Lo Lhe revlew proLocols for each cllnlcal quesLlon
formed. See Lhe revlew proLocols ln Appendlx C for full deLalls.
A ma[or conslderaLlon ln deLermlnlng Lhe lncluslon and excluslon crlLerla ln Lhe proLocol was Lhe
appllcablllLy of Lhe evldence Lo Lhe guldellne populaLlon. 1he populaLlon wlLhln Lhe scope of Lhe
guldellne ls hosplLallsed adulLs, wlLh Lhe excluslon of cerLaln populaLlons from Lhe scope and Lhls ls
broadly adhered Lo ln mosL revlews. Powever, Lhe CuC dlscussed and declded upon addlLlonal
lncluslon or excluslon crlLerla for each proLocol accordlng Lo Lhe cllnlcal conLexL of Lhe revlew
quesLlon. ln areas where evldence was anLlclpaLed Lo be lacklng, declslons were made Lo conslder
populaLlons or seLLlngs noL lncluded wlLhln Lhls guldellne lf Lhe CuC consldered Lhe evldence as
lndlrecLly appllcable. Some examples of how Lhls was applled lnclude:
paLlenLs who had ma[or cardlac surgery were excluded ln lv fluld lnLervenLlon revlews on Lypes
and volumes of fluld, buL lncluded ln Lhe assessmenL of welghL monlLorlng
sLudles of resusclLaLlon conducLed ln Lhe lCu seLLlng were lncluded ln Lhe resusclLaLlon revlew
1he search for evldence for fluld replacemenL lncluded paLlenLs wlLh dlabeLes melllLus.
More information about Indirectness, is available in 3.3.7
LaboraLory sLudles were excluded because Lhe populaLlons used (healLhy volunLeers, anlmals or lo
vltto) and seLLlngs are arLlflclal and noL comparable Lo Lhe populaLlon we are maklng
MeLhods

24
recommendaLlons for. 1hese sLudles would undoubLedly be of very low quallLy as assessed by C8AuL
and Lherefore 8C1s, cohorL sLudles or CuC consensus oplnlon was consldered preferable.
LlLeraLure revlews, leLLers and edlLorlals, forelgn language publlcaLlons and unpubllshed sLudles were
excluded.
3.3.2 Methods of comb|n|ng c||n|ca| stud|es
Data synthes|s for |ntervent|on rev|ews
Where posslble, meLa-analyses were conducLed Lo comblne Lhe resulLs of sLudles for each revlew
quesLlon uslng Cochrane 8evlew Manager (8evMan3) sofLware. llxed-effecLs (ManLel-Paenszel)
Lechnlques were used Lo calculaLe rlsk raLlos (relaLlve rlsk) for Lhe blnary ouLcomes. 1he conLlnuous
ouLcomes were analysed uslng an lnverse varlance meLhod for poollng welghLed mean dlfferences
and where Lhe sLudles had dlfferenL scales, sLandardlsed mean dlfferences were used.
SLaLlsLlcal heLerogenelLy was assessed by conslderlng Lhe chl-squared LesL for slgnlflcance aL p <0.1
or an l-squared lnconslsLency sLaLlsLlc of >30 Lo lndlcaLe slgnlflcanL heLerogenelLy. Where Lhere was
heLerogenelLy and a sufflclenL number of sLudles, senslLlvlLy analyses were conducLed based on rlsk
of blas and pre-speclfled subgroup analyses were carrled ouL as deflned ln Lhe proLocol. AssessmenLs
of poLenLlal dlfferences ln effecL beLween subgroups were based on Lhe chl-squared LesLs for
heLerogenelLy sLaLlsLlcs beLween subgroups. lf no senslLlvlLy analysls was found Lo compleLely
resolve sLaLlsLlcal heLerogenelLy Lhen a random effecLs (uerSlmonlan and Lalrd) model was employed
Lo provlde a more conservaLlve esLlmaLe of Lhe effecL.
1he means and sLandard devlaLlons of conLlnuous ouLcomes were requlred for meLa-analysls.
Powever, ln cases where sLandard devlaLlons were noL reporLed, Lhe sLandard error was calculaLed lf
Lhe p-values or 93 confldence lnLervals were reporLed and meLa-analysls was underLaken wlLh Lhe
mean dlfference and sLandard error uslng Lhe generlc lnverse varlance meLhod ln Cochrane 8evlew
Manager (RevMan5) software. Where p values were reported as less than, a conservative
approach was undertaken. For example, if p value was reported as p <0.001, the calculations for
sLandard devlaLlons were based on a p value of 0.001. lf Lhese sLaLlsLlcal measures were noL
available then the methods described in section 16.1.3 of the Cochrane Handbook 121 Missing
standard deviations were applied as the last resort.
lor blnary ouLcomes, absoluLe dlfferences ln evenL raLes were also calculaLed uslng Lhe C8AuLpro
software using total event rate in the control arm of the pooled results and presented in the Clinical
Summary of Findings Table.
re-speclfled subgroup analyses were conducLed for populaLlons of lnLeresL. 1hese are groups were
lL had been ldenLlfled LhaL Lhe lnLervenLlons were llkely Lo have dlfferenL effecL (effecL modlflers),
raLher Lhan prognosLlc facLors. AlLhough prognosLlc facLors are usually noL good candldaLes for
subgrouplng ln meLa-analysls, lL ls ofLen lmposslble Lo compleLely predlcL wheLher a poLenLlal
dlfference ln effecL ls due Lo a dlfference ln how Lhe lnLervenLlon may work ln a group, or ln how lL
wlll affecL all ouLcomes, for example acLlve cancer ls a prognosLlc facLor, buL can also posslbly affecL
how anLlcoagulanLs work. When such subgroups are ldenLlfled, sLudles were sub grouped Lo observe
wheLher Lhere mlghL be dlfferences ln effecLs beLween dlfferenL groups of paLlenLs.
3.3.3 Appra|s|ng the qua||ty of ev|dence by outcomes
1he evldence for ouLcomes from Lhe lncluded 8C1 and observaLlonal sLudles were evaluaLed and
presented using an adaptation of the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) toolbox developed by the international GRAuL worklng group
(hLLp://www.gradeworklnggroup.org/). 1he sofLware (C8AuLpro) developed by Lhe C8AuL worklng
MeLhods

23
group was used Lo assess Lhe quallLy of each ouLcome, Laklng lnLo accounL lndlvldual sLudy quallLy
and Lhe meLa-analysls resulLs. 1he Clinical evidence profile tables presented summarise the quality
of evldence and Lhe flndlngs of Lhe revlews ln Lhe guldellne. 1he Lables presenL Lhe pooled ouLcome
daLa (where approprlaLe), an absoluLe measure of lnLervenLlon effecL and Lhe summary of quallLy of
evldence for LhaL ouLcome. ln Lhese Lables, Lhe columns for lnLervenLlon and conLrol lndlcaLe Lhe
sum of Lhe sample slze for conLlnuous ouLcomes. lor blnary ouLcomes such as number of paLlenLs
wlLh an adverse evenL, Lhe evenL raLes (n/n: number of paLlenLs wlLh evenLs dlvlded by sum of
number of paLlenLs) are shown wlLh percenLages. 8eporLlng or publlcaLlon blas was only Laken lnLo
conslderaLlon ln Lhe quallLy assessmenL and lncluded ln Lhe Cllnlcal SLudy CharacLerlsLlcs Lable lf lL
was apparenL.
Lach ouLcome was examlned separaLely for Lhe quallLy elemenLs llsLed and deflned ln 1ab|e 2 and
each graded uslng Lhe quallLy levels llsLed ln 1ab|e 3.1he maln crlLerla consldered ln Lhe raLlng of
Lhese elemenLs are dlscussed below (see secLlon 3.3.4 Cradlng of Lvldence). looLnoLes were used Lo
descrlbe reasons for downgradlng a quallLy elemenL as havlng serlous or very serlous problems. 1he
raLlngs for each componenL were summed Lo obLaln an overall assessmenL for each ouLcome.
1ab|e 2: Descr|pt|on of qua||ty e|ements |n GkADL for |ntervent|on stud|es
ua||ty e|ement Descr|pt|on
LlmlLaLlons LlmlLaLlons ln Lhe sLudy deslgn and lmplemenLaLlon may blas Lhe esLlmaLes of Lhe
LreaLmenL effecL. Ma[or llmlLaLlons ln sLudles decrease Lhe confldence ln Lhe esLlmaLe
of Lhe effecL.
lnconslsLency lnconslsLency refers Lo an unexplalned heLerogenelLy of resulLs.
lndlrecLness lndlrecLness refers Lo dlfferences ln sLudy populaLlon, lnLervenLlon, comparaLor and
ouLcomes beLween Lhe avallable evldence and Lhe revlew quesLlon, or
recommendaLlon made.
lmpreclslon 8esulLs are lmpreclse when sLudles lnclude relaLlvely few paLlenLs and few evenLs and
Lhus have wlde confldence lnLervals around Lhe esLlmaLe of Lhe effecL relaLlve Lo Lhe
cllnlcally lmporLanL Lhreshold.
ubllcaLlon blas ubllcaLlon blas ls a sysLemaLlc underesLlmaLe or an overesLlmaLe of Lhe underlylng
beneflclal or harmful effecL due Lo Lhe selecLlve publlcaLlon of sLudles.

1ab|e 3: Leve|s of qua||ty e|ements |n GkADL
Leve| Descr|pt|on
none 1here are no serlous lssues wlLh Lhe evldence
Serlous 1he lssues are serlous enough Lo downgrade Lhe ouLcome evldence by one level
very serlous 1he lssues are serlous enough Lo downgrade Lhe ouLcome evldence by Lwo levels

1ab|e 4: Cvera|| qua||ty of outcome ev|dence |n GkADL
Leve| Descr|pt|on
Plgh lurLher research ls very unllkely Lo change our confldence ln Lhe esLlmaLe of effecL
ModeraLe lurLher research ls llkely Lo have an lmporLanL lmpacL on our confldence ln Lhe esLlmaLe
of effecL and may change Lhe esLlmaLe
Low lurLher research ls very llkely Lo have an lmporLanL lmpacL on our confldence ln Lhe
esLlmaLe of effecL and ls llkely Lo change Lhe esLlmaLe
very low Any esLlmaLe of effecL ls very uncerLaln

MeLhods

26
3.3.4 Grad|ng the qua||ty of c||n|ca| ev|dence
AfLer resulLs were pooled, Lhe overall quallLy of evldence for each ouLcome was consldered. 1he
followlng procedure was adopLed when uslng C8AuL:
1. A quallLy raLlng was asslgned, based on Lhe sLudy deslgn. 8C1s sLarL PlCP and observaLlonal
sLudles as LCW, unconLrolled case serles as LCW or vL8? LCW.
2. 1he raLlng was Lhen downgraded for Lhe speclfled crlLerla: SLudy llmlLaLlons, lnconslsLency,
lndlrecLness, lmpreclslon and reporLlng blas. 1hese crlLerla are deLalled below. CbservaLlonal sLudles
were upgraded lf Lhere was: a large magnlLude of effecL, dose-response gradlenL, and lf all plauslble
confoundlng would reduce a demonsLraLed effecL or suggesL a spurlous effecL when resulLs showed
no effect. Each quality element considered to have serious or very serious risk of bias was rated
down -1 or -2 polnLs respecLlvely.
3. 1he downgraded/upgraded marks were Lhen summed and Lhe overall quallLy raLlng was revlsed.
lor example, all 8C1s sLarLed as PlCP and Lhe overall quallLy became MCuL8A1L, LCW or vL8? LCW
lf 1, 2 or 3 polnLs were deducLed respecLlvely.
4. 1he reasons or crlLerla used for downgradlng were speclfled ln Lhe fooLnoLes.
1he deLalls of crlLerla used for each of Lhe maln quallLy elemenL are dlscussed furLher ln Lhe followlng
secLlons 3.3.3 Lo 3.3.8 .
3.3.S Study ||m|tat|ons
1he maln llmlLaLlons for randomlsed conLrolled Lrlals are llsLed ln 1ab|e S
1he declslon of downgradlng depends on wheLher meLhodologlcal llmlLaLlons resulLed ln poLenLlally
lmporLanL rlsks of blas for an ouLcome. lor example, lL ls well accepLed LhaL lnvesLlgaLor bllndlng
and/or parLlclpanL bllndlng was lmposslble Lo achleve ln some lnLervenLlons (e.g. paLlenL educaLlon
or monlLorlng). neverLheless, open-label sLudles would sLlll be downgraded lf Lhere ls an lmporLanL
rlsk of blas (for example lf Lhe ouLcome was sub[ecLlve, or lf oLher facLors can affecL Lhe performance
of Lhe lnLervenLlons). 1hls ls lmporLanL Lo malnLaln a conslsLenL approach ln quallLy raLlng across Lhe
guldellne. 1ab|e S llsLed Lhe llmlLaLlons consldered for randomlsed conLrolled Lrlals and 1ab|e 6 llsLs
Lhe lmporLanL llmlLaLlons consldered for observaLlonal sLudles.
1ab|e S: Study ||m|tat|ons of random|sed contro||ed tr|a|s
L|m|tat|on Lxp|anat|on
AllocaLlon concealmenL 1hose enrolllng paLlenLs are aware of Lhe group Lo whlch Lhe nexL enrolled
patient will be allocated (major problem in pseudo or quasi randomised
Lrlals wlLh allocaLlon by day of week, blrLh daLe, charL number, eLc.)
Lack of bllndlng aLlenL, careglvers, Lhose recordlng ouLcomes, Lhose ad[udlcaLlng ouLcomes, or
daLa analysLs are aware of Lhe arm Lo whlch paLlenLs are allocaLed
lncompleLe accounLlng
of paLlenLs and ouLcome
evenLs
Loss Lo follow-up noL accounLed and fallure Lo adhere Lo Lhe lnLenLlon Lo LreaL
prlnclple when lndlcaLed
SelecLlve ouLcome
reporLlng
8eporLlng of some ouLcomes and noL oLhers on Lhe basls of Lhe resulLs
CLher llmlLaLlons lor example:
SLopplng early for beneflL observed ln randomlsed Lrlals, ln parLlcular ln Lhe
absence of adequaLe sLopplng rules
use of unvalldaLed paLlenL-reporLed ouLcomes
Carry-over effecLs ln cross-over Lrlals
MeLhods

27
8ecrulLmenL blas ln clusLer randomlsed Lrlals
1ab|e 6: Study ||m|tat|ons of cohort ]observat|ona| stud|es
lallure Lo develop and apply approprlaLe ellglblllLy
crlLerla (lncluslon of conLrol populaLlon)
under- or over-maLchlng ln case-conLrol sLudles
selecLlon of exposed and unexposed ln cohorL
sLudles from dlfferenL populaLlons
llawed measuremenL of boLh exposure and ouLcome dlfferences ln measuremenL of exposure (e.g.
recall blas ln case- conLrol sLudles)
dlfferenLlal survelllance for ouLcome ln exposed
and unexposed ln cohorL sLudles
lallure Lo adequaLely conLrol confoundlng fallure of accuraLe measuremenL of all known
prognosLlc facLors
fallure Lo maLch for prognosLlc facLors and/or
ad[usLmenL ln sLaLlsLlcal analysls

3.3.6 Incons|stency
lnconslsLency refers Lo an unexplalned heLerogenelLy of resulLs. When esLlmaLes of Lhe LreaLmenL
effecL across sLudles dlffer wldely (l.e. heLerogenelLy or varlablllLy ln resulLs), Lhls suggesLs Lrue
dlfferences ln underlylng LreaLmenL effecL. When heLerogenelLy exlsLs (Chl square p<0.1 or l- squared
lnconslsLency sLaLlsLlc of >30), buL no plauslble explanaLlon can be found, Lhe quallLy of evldence
was downgraded by one or Lwo levels, dependlng on Lhe exLenL of uncerLalnLy Lo Lhe resulLs
conLrlbuLed by Lhe lnconslsLency ln Lhe resulLs. ln addlLlon Lo Lhe l- square and Chl square values, Lhe
declslon for downgradlng was also dependenL on facLors such as wheLher Lhe lnLervenLlon ls
assoclaLed wlLh beneflL ln all oLher ouLcomes or wheLher Lhe uncerLalnLy abouL Lhe magnlLude of
beneflL (or harm) of Lhe ouLcome showlng heLerogenelLy would lnfluence Lhe overall [udgmenL abouL
neL beneflL or harm (across all ouLcomes).
lf lnconslsLency could be explalned based on pre-speclfled subgroup analysls, Lhe CuC Look Lhls lnLo
accounL and consldered wheLher Lo make separaLe recommendaLlons based on Lhe ldenLlfled
explanaLory facLors, l.e. populaLlon and lnLervenLlon. Where subgroup analysls gave a plauslble
explanaLlon of heLerogenelLy, Lhe quallLy of evldence was noL downgraded.
3.3.7 Ind|rectness
ulrecLness refers Lo Lhe exLenL Lo whlch Lhe populaLlons, lnLervenLlon, comparlsons and ouLcome
measures are slmllar Lo Lhose deflned ln Lhe lncluslon crlLerla for Lhe revlews. lndlrecLness ls
lmporLanL when Lhese dlfferences are expecLed Lo conLrlbuLe Lo a dlfference ln effecL slze, or may
affecL Lhe balance of harms and beneflLs consldered for an lnLervenLlon.
ln Lhls guldellne, lndlrecL evldence was an lmporLanL source of lnformaLlon due Lo Lhe breadLh of
populaLlon and Lhe lack of evldence. Lvldence for Lhe LargeL guldellne populaLlon was ofLen noL
avallable and lndlrecL evldence was applled and lnLerpreLed based on Lhe cllnlcal experLlse and
experlence of CuC members.
Lxamples of Lhls lnclude:
lndlrecL populaLlon: evldence from paLlenLs ln crlLlcal care unlLs for revlews on fluld resusclLaLlon
MeLhods

28
lndlrecL ouLcome: pP values were used as surrogaLe ouLcomes for meLabollc acldosls ln Lhe
revlew on measuremenL of serum chlorlde.
Whenever lndlrecL evldence was ldenLlfled and applled, Lhe evldence was downgraded for
lndlrecLness ln C8AuL and also dlscussed ln Lhe secLlons llnklng evldence Lo recommendaLlon ln Lhe
guldellne.
3.3.8 Imprec|s|on
lmpreclslon refers Lo Lhe cerLalnLy ln Lhe effecL for Lhe ouLcome. When resulLs are lmpreclse or very
lmpreclse we are uncerLaln lf Lhere ls an lmporLanL dlfference beLween lnLervenLlons or noL.
1he sample slze, evenL raLes and Lhe resulLlng wldLh of confldence lnLervals were Lhe maln crlLerla
consldered for evaluaLlng lmpreclslon.
1he Lhresholds of lmporLanL beneflLs or harms, or Lhe mlnlmally lmporLanL dlfferences (Mlu) for an
outcome are important considerations for determining whether there is a clinically important
dlfference beLween lnLervenLlon and conLrol groups and ln assesslng lmpreclslon. lor conLlnuous
outcomes, the MID is defined as the smallest difference in score in the outcome of interest that
lnformed paLlenLs or lnformed proxles percelve as lmporLanL, elLher beneflclal or harmful, and LhaL
would lead Lhe paLlenL or cllnlclan Lo consider a change in the management
36,42,98,99
. An effecL
esLlmaLe larger Lhan the MID is considered to be clinically important. For dichotomous outcomes,
Lhe Mlu ls consldered ln Lerms of changes ln boLh relaLlve and absoluLe rlsk.
1he CuC were asked aL Lhe ouLseL of Lhe guldellne lf Lhey were aware of any esLabllshed values for
Mlu, for beLween group dlfferences, for Lhe ouLcomes lncluded ln Lhe revlew. 1here were no
publlshed Mlus for any of Lhe ouLcomes. 1he CuC agreed LhaL Lhe defaulL values sLaLed ln Lhe
C8AuLpro were approprlaLe for Lhe ouLcomes. 1he defaulL Lhresholds suggesLed by C8AuL are a
relaLlve rlsk reducLlon of 23 (relaLlve rlsk of 0.73 for negaLlve ouLcomes) or a relaLlve rlsk lncrease
of 23 (rlsk raLlo 1.23 for poslLlve ouLcomes) for dlchoLomous ouLcomes. lor conLlnuous ouLcomes
Lwo approaches were used. When only one Lrlal was lncluded as Lhe evldence base for an ouLcome,
Lhe mean dlfference was converLed Lo Lhe sLandardlzed mean dlfference (SMu) and checked Lo see lf
Lhe confldence lnLerval crossed 0.3. Powever, Lhe mean dlfference (93 confldence lnLerval) was sLlll
presenLed ln Lhe Crade Lables. lf Lwo or more lncluded Lrlals reporLed a quanLlLaLlve ouLcome Lhen
Lhe defaulL approach of mulLlplylng 0.3 by sLandard devlaLlon (Laken as Lhe medlan of Lhe sLandard
devlaLlons across Lhe meLa-analyzed sLudles) was employed.
Assess|ng c||n|ca| |mportance and |mprec|s|on
1he confldence lnLerval for Lhe pooled or besL esLlmaLe of effecL was consldered ln relaLlon Lo Lhe
Mlus Lo assess lmpreclslon. lf Lhe confldence lnLerval crossed Lhe Mlu Lhreshold, Lhere was
uncerLalnLy ln Lhe effecL esLlmaLe supporLlng our recommendaLlon (because Lhe Cl was conslsLenL
wlLh Lwo declslons) and Lhe effecL esLlmaLe was raLed as havlng serlous lmpreclslon. lf boLh Mlus
were crossed, Lhe effecL esLlmaLe was raLed as havlng very serlous lmpreclslon.
lor Lhe purposes of Lhls guldellne, cllnlcal lmporLance was assessed by comparlng Lhe effecL esLlmaLe
agalnsL Lhe Mlu and revlewlng Lhe absoluLe effecL reporLed ln Lhe C8AuL summary Lable. lor
example, lf Lhe effecL slze was small (less Lhan Lhe Mlu), Lhls flndlng suggesLs LhaL Lhere may noL be
enough dlfference Lo recommend one lnLervenLlon over Lhe oLher based on LhaL ouLcome, unless ln
excepLlonal clrcumsLances, Lhe CuC agreed LhaL Lhe absoluLe effecL was greaL enough Lo reach
cllnlcal lmporLance. An effecL esLlmaLe larger Lhan Lhe Mlu ls consldered Lo be cllnlcally lmporLanL.
Powever, Lhe CuC agreed LhaL assessmenL of cllnlcal lmporLance when evaluaLlng morLallLy would
have Lo be lnLerpreLed Laklng lnLo accounL Lhe absoluLe lncrease ln rlsk of morLallLy.
MeLhods

29
llgure 1 lllusLraLes how Lhe cllnlcal lmporLance of effecL esLlmaLes were consldered along wlLh
lmpreclslon. 1hls ls documenLed ln Lhe evldence sLaLemenLs LhroughouL Lhls guldellne.
I|gure 1: I||ustrat|on of prec|se and |mprec|s|on outcomes based on the conf|dence |nterva| of
outcomes |n a forest p|ot

5ootce. llqote oJopteJ ftom CkAulto softwote.

Mlu = mlnlmal lmporLanL dlfference deLermlned for each ouLcome. 1he Mlus are Lhe Lhreshold for
appreclable beneflLs and harms. 1he confldence lnLervals of Lhe Lop Lhree polnLs of Lhe dlagram were
consldered preclse because Lhe upper and lower llmlLs dld noL cross Lhe Mlu. Conversely, Lhe boLLom
Lhree polnLs of Lhe dlagram were consldered lmpreclse because all of Lhem crossed Lhe Mlu and
reduced our cerLalnLy of Lhe resulLs.
1he confldence lnLerval for Lhe pooled or besL esLlmaLe of effecL was consldered ln relaLlon Lo Lhe
Mlu, as lllusLraLed ln llgure 1. LssenLlally, lf Lhe confldence lnLerval crossed Lhe Mlu Lhreshold, Lhere
was uncerLalnLy ln Lhe effecL esLlmaLe ln supporLlng our recommendaLlons (because Lhe Cl was
conslsLenL wlLh Lwo declslons) and Lhe effecL esLlmaLe was raLed as lmpreclse.
lor Lhe purposes of Lhls guldellne, an lnLervenLlon ls consldered Lo have a cllnlcally lmporLanL effecL
wlLh cerLalnLy lf Lhe whole of Lhe 93 confldence lnLerval descrlbes an effecL of greaLer magnlLude
Lhan Lhe Mlu.
lor morLallLy, Lhe CuC agreed Lo conslder any reducLlon ln morLallLy as a cllnlcally lmporLanL
dlfference for paLlenLs.
vlJeoce stotemeots
Lvldence sLaLemenLs were formed for each ouLcome lndlcaLlng Lhe quanLlLy and quallLy of evldence
avallable, and Lhe ouLcome and populaLlon Lo whlch Lhey relaLe. Where posslble Lhese were drafLed
for each subgroup or by ouLcome. An overall evldence summary for a parLlcular lnLervenLlon was
presenLed, where posslble.
3.4 Lv|dence of cost-effect|veness
1he CuC ls requlred Lo make declslons based on Lhe besL avallable evldence of boLh cllnlcal and cosL
effecLlveness. Culdellne recommendaLlons should be based on Lhe expecLed cosLs of Lhe dlfferenL
options in relation to their expected health benefits (that is, their cost effectiveness) rather than the
LoLal lmplemenLaLlon cosL.
76
1hus, lf Lhe evldence suggesLs LhaL a sLraLegy provldes slgnlflcanL healLh
beneflLs aL an accepLable cosL per paLlenL LreaLed, lL should be recommended even lf lL would be
expenslve Lo lmplemenL across Lhe whole populaLlon.
MeLhods

30
Lvldence on cosL-effecLlveness relaLed Lo Lhe key cllnlcal lssues belng addressed ln Lhe guldellne was
soughL. 1he healLh economlsL underLook:
A sysLemaLlc revlew of Lhe publlshed economlc llLeraLure.
new cosL-effecLlveness analysls ln prlorlLy areas.
3.4.1 L|terature rev|ew
1he healLh economlsL:
ldenLlfled poLenLlally relevanL sLudles for each revlew quesLlon from Lhe economlc search resulLs
by revlewlng LlLles and absLracLs full papers were Lhen obLalned.
8evlewed full papers agalnsL pre-speclfled lncluslon / excluslon crlLerla Lo ldenLlfy relevanL sLudles
(see below for deLalls).
CrlLlcally appralsed relevanL sLudles uslng Lhe economlc evaluaLlons checkllsL as speclfled ln 1he
Culdellnes Manual.
76

Extracted key information about the studies methods and results lnLo evldence Lables (lncluded
ln Appendlx l)
CeneraLed summarles of Lhe evldence ln nlCL economlc evldence proflles (lncluded ln Lhe
relevanL chapLer wrlLe-ups) see below for deLalls.
3.4.1.1 Inc|us|on]exc|us|on
lull economlc evaluaLlons (sLudles comparlng cosLs and healLh consequences of alLernaLlve courses
of acLlon: cosLuLlllLy, cosL-effecLlveness, cosL-beneflL and cosL-consequence analyses) and
comparaLlve cosLlng sLudles LhaL addressed Lhe revlew quesLlon ln Lhe relevanL populaLlon were
consldered poLenLlally lncludable as economlc evldence.
SLudles LhaL only reporLed cosL per hosplLal (noL per paLlenL), or only reporLed average cosL
effecLlveness wlLhouL dlsaggregaLed cosLs and effecLs, were excluded. AbsLracLs, posLers, revlews,
leLLers/edlLorlals, forelgn language publlcaLlons and unpubllshed sLudles were excluded. SLudles
judged to have an applicability rating of not applicable were excluded (this included studies that
Look Lhe perspecLlve of a non-CLCu counLry).
8emalnlng sLudles were prlorlLlsed for lncluslon based on Lhelr relaLlve appllcablllLy Lo Lhe
developmenL of Lhls guldellne and Lhe sLudy llmlLaLlons. lor example, lf a hlgh quallLy, dlrecLly
appllcable uk analysls was avallable oLher less relevanL sLudles may noL have been lncluded. Where
excluslons occurred on Lhls basls, Lhls ls noLed ln Lhe relevanL secLlon.
lor more deLalls abouL Lhe assessmenL of appllcablllLy and meLhodologlcal quallLy see Lhe economlc
evaluaLlon checkllsL (1he Culdellnes Manual),
76
and Lhe healLh economlcs research proLocol ln
Appendlx C.7.
3.4.1.2 NICL econom|c ev|dence prof||es
1he nlCL economlc evldence proflle has been used Lo summarlse cosL and cosL-effecLlveness
esLlmaLes. 1he economlc evldence proflle shows, for each economlc sLudy, an assessmenL of
appllcablllLy and meLhodologlcal quallLy, wlLh fooLnoLes lndlcaLlng Lhe reasons for Lhe assessmenL.
1hese assessmenLs were made by Lhe healLh economlsL uslng Lhe economlc evaluaLlon checkllsL from
1he Culdellnes Manual.
76
. lL also shows lncremenLal cosLs, lncremenLal effecLs (for example, quallLy-
ad[usLed llfe years [CAL?s]) and Lhe lncremenLal cosL-effecLlveness raLlo, as well as lnformaLlon
abouL Lhe assessmenL of uncerLalnLy ln Lhe analysls. See 1ab|e 7 for more deLalls.
MeLhods

31
lf a non-uk sLudy was lncluded ln Lhe proflle, Lhe resulLs were converLed lnLo pounds sLerllng uslng
Lhe approprlaLe purchaslng power parlLy.
80

1ab|e 7: Content of NICL econom|c prof||e
Item Descr|pt|on
SLudy llrsL auLhor name, reference, daLe of sLudy publlcaLlon and counLry perspecLlve.
AppllcablllLy An assessmenL of appllcablllLy of Lhe sLudy Lo Lhe cllnlcal guldellne, Lhe currenL nPS
slLuaLlon and nlCL declslon-maklng*:
ulrecLly appllcable Lhe appllcablllLy crlLerla are meL, or one or more crlLerla are
noL meL buL Lhls ls noL llkely Lo change Lhe concluslons abouL cosL effecLlveness.
arLlally appllcable one or more of Lhe appllcablllLy crlLerla are noL meL, and Lhls
mlghL posslbly change Lhe concluslons abouL cosL effecLlveness.
noL appllcable one or more of Lhe appllcablllLy crlLerla are noL meL, and Lhls ls
llkely Lo change Lhe concluslons abouL cosL effecLlveness.
LlmlLaLlons An assessmenL of meLhodologlcal quallLy of Lhe sLudy*:
Mlnor llmlLaLlons Lhe sLudy meeLs all quallLy crlLerla, or Lhe sLudy falls Lo meeL
one or more quallLy crlLerla, buL Lhls ls unllkely Lo change Lhe concluslons abouL
cosL effecLlveness.
oLenLlally serlous llmlLaLlons Lhe sLudy falls Lo meeL one or more quallLy
crlLerla, and Lhls could change Lhe concluslon abouL cosL effecLlveness
very serlous llmlLaLlons Lhe sLudy falls Lo meeL one or more quallLy crlLerla and
Lhls ls very llkely Lo change Lhe concluslons abouL cosL effecLlveness. SLudles wlLh
very serlous llmlLaLlons would usually be excluded from Lhe economlc proflle
Lable.
CLher commenLs arLlcular lssues LhaL should be consldered when lnLerpreLlng Lhe sLudy.
lncremenLal cosL 1he mean cosL assoclaLed wlLh one sLraLegy mlnus Lhe mean cosL of a comparaLor
sLraLegy.
lncremenLal effecLs 1he mean CAL?s (or oLher selecLed measure of healLh ouLcome) assoclaLed wlLh
one sLraLegy mlnus Lhe mean CAL?s of a comparaLor sLraLegy.
CosL effecLlveness lncremenLal cosL-effecLlveness raLlo (lCL8): Lhe lncremenLal cosL dlvlded by Lhe
lncremenLal effecLs.
uncerLalnLy A summary of Lhe exLenL of uncerLalnLy abouL Lhe lCL8 reflecLlng Lhe resulLs of
deLermlnlsLlc or probablllsLlc senslLlvlLy analyses, or sLochasLlc analyses of Lrlal daLa,
as approprlaLe.
*AppllcablllLy and llmlLaLlons were assessed uslng Lhe economlc evaluaLlon checkllsL from 1he Culdellnes
Manual.
76

3.4.2 Undertak|ng new hea|th econom|c ana|ys|s
As well as revlewlng Lhe publlshed economlc llLeraLure for each revlew quesLlon, as descrlbed above,
new economlc analysls was underLaken by Lhe healLh economlsL ln selecLed areas. rlorlLy areas for
new healLh economlc analysls were agreed by Lhe CuC afLer formaLlon of Lhe revlew quesLlons and
conslderaLlon of Lhe avallable healLh economlc evldence.
1he CuC ldenLlfled monlLorlng, fluld Lype for resusclLaLlon and fluld Lype for malnLenance as Lhe
hlghesL prlorlLy areas for orlglnal economlc modelllng (see secLlons 6.3.1.3, 6.3.2.3 7.2.3.3, 7.3.2,
7.2.4.2).
ln all Lhree areas, Lhe sysLemaLlc revlew dld noL produce sLrong enough evldence Lo evaluaLe cosL-
effecLlveness, so cosL analyses were developed. 1he followlng general prlnclples were adhered Lo:
MeLhods were conslsLenL wlLh Lhe nlCL reference case, where posslble.
74
.
MeLhods

32
1he CuC was lnvolved ln Lhe deslgn of Lhe model, selecLlon of lnpuLs and lnLerpreLaLlon of Lhe
resulLs.
When published daLa was noL avallable CuC experL oplnlon was used Lo populaLe Lhe model.
Model inputs and assumptions were reported fully and transparently.
The results were subject to sensitivity analysis and limitations were discussed.
The model was peer-revlewed by anoLher healLh economlsL aL Lhe nCCC.
lull meLhods for Lhe cosL analyses are descrlbed ln Appendlces L, M and n.
3.4.3 Cost-effect|veness cr|ter|a
NICEs report Social value judgements: principles for the development of NICE guidance sets out the
prlnclples LhaL CuCs should conslder when [udglng wheLher an lnLervenLlon offers good value for
money.
73,76
ln general, an lnLervenLlon was consldered Lo be cosL effecLlve lf elLher of Lhe followlng
crlLerla applled (glven LhaL Lhe esLlmaLe was consldered plauslble):
a. 1he lnLervenLlon domlnaLed oLher relevanL sLraLegles (LhaL ls, lL was boLh less cosLly ln Lerms of
resource use and more cllnlcally effecLlve compared wlLh all Lhe oLher relevanL alLernaLlve
sLraLegles), or
b. 1he lnLervenLlon cosL less Lhan 20,000 per CAL? galned compared wlLh Lhe nexL besL sLraLegy.
lf Lhe CuC recommended an lnLervenLlon LhaL was esLlmaLed Lo cosL more Lhan 20,000 per CAL?
galned, or dld noL recommend one LhaL was esLlmaLed Lo cosL less Lhan 20,000 per CAL? galned,
the reasons for this decision are discussed explicitly in the from evidence to recommendations
secLlon of Lhe relevanL chapLer wlLh reference Lo lssues regardlng Lhe plauslblllLy of Lhe esLlmaLe or
to the factors set out in the Social value judgements: principles for the development of NICE
guidance.
73
lf a sLudy reporLed Lhe cosL per llfe year galned buL noL CAL?s, Lhe cosL per CAL? galned
was esLlmaLed by mulLlplylng by an approprlaLe uLlllLy esLlmaLe Lo ald lnLerpreLaLlon. 1he esLlmaLed
cosL per CAL? galned ls reporLed ln Lhe economlc evldence proflle wlLh a fooLnoLe deLalllng Lhe llfe-
years galned and Lhe uLlllLy value used. When CAL?s or llfe years galned are noL used ln Lhe analysls,
resulLs are dlfflculL Lo lnLerpreL unless one sLraLegy domlnaLes Lhe oLhers wlLh respecL Lo every
relevanL healLh ouLcome and cosL.
3.4.4 In the absence of econom|c ev|dence
When no relevanL publlshed sLudles were found, and a new analysls was noL prlorlLlsed, Lhe CuC
made a quallLaLlve [udgemenL abouL cosL effecLlveness by conslderlng expecLed dlfferences ln
resource use beLween opLlons and relevanL uk nPS unlL cosLs alongslde Lhe resulLs of Lhe cllnlcal
revlew of effecLlveness evldence.
3.S Deve|op|ng recommendat|ons
Cver Lhe course of Lhe guldellne developmenL process, Lhe CuC was presenLed wlLh:
Lvldence Lables of Lhe cllnlcal and economlc evldence revlewed from Lhe llLeraLure. All evldence
Lables are ln Appendlx L (cllnlcal evldence) and Appendlx l (economlc evldence).
Summary of cllnlcal and economlc evldence and quallLy (as presenLed ln chapLers 3-10.)
loresL ploLs and summary 8CC curves (Appendlx C)
A descrlpLlon of Lhe meLhods and resulLs of Lhe cosL-senslLlvlLy analysls underLaken for Lhe
guldellne (Appendlces L, M, n)
8ecommendaLlons were drafLed based on CuC lnLerpreLaLlon of Lhe avallable evldence, Laklng lnLo
accounL Lhe balance of beneflLs and harms and evldence of cosL effecLlveness. When cllnlcal and
MeLhods

33
economlc evldence was of poor quallLy, confllcLlng or absenL, Lhe CuC drafLed recommendaLlons
based on experL oplnlon. 1he conslderaLlons for maklng consensus based recommendaLlons lncluded
Lhe balance beLween poLenLlal harms and beneflLs, economlc or lmpllcaLlons compared Lo Lhe
beneflLs, currenL pracLlces, recommendaLlons made ln oLher relevanL guldellnes, paLlenL preferences
and equallLy lssues. Consensus on recommendaLlons was achleved Lhrough dlscusslons ln Lhe CuC
meeLlngs. 1he CuC also consldered areas where Lhe uncerLalnLy was sufflclenL Lo [usLlfy delaylng
maklng a recommendaLlon Lo awalL furLher research, Laklng lnLo accounL Lhe poLenLlal harm of
falllng Lo make a clear recommendaLlon.
1he maln conslderaLlons speclflc Lo each recommendaLlon are ouLllned ln Lhe Lvldence Lo
8ecommendaLlon SecLlon precedlng Lhe recommendaLlon secLlon.
3.S.1 kesearch recommendat|ons
When areas were ldenLlfled for whlch good evldence was lacklng, Lhe guldellne developmenL group
consldered maklng recommendaLlons for fuLure research. ueclslons abouL lncluslon were based on
facLors such as:
Lhe lmporLance Lo paLlenLs or Lhe populaLlon
naLlonal prlorlLles
poLenLlal lmpacL on Lhe nPS and fuLure nlCL guldance
eLhlcal and Lechnlcal feaslblllLy
lor deLalls of all research recommendaLlons, see Appendlx C.
3.S.2 Va||dat|on process
1he guldance ls sub[ecL Lo a slx week publlc consulLaLlon and feedback as parL of Lhe quallLy
assurance and peer revlew Lhe documenL. All commenLs recelved from reglsLered sLakeholders are
responded Lo ln Lurn and posLed on Lhe nlCL webslLe when Lhe pre-publlcaLlon check of Lhe full
guldellne occurs.
3.S.3 Updat|ng the gu|de||ne
A formal revlew of Lhe need Lo updaLe a guldellne ls usually underLaken by nlCL afLer lLs publlcaLlon.
nlCL wlll conducL a revlew Lo deLermlne wheLher Lhe evldence base has progressed slgnlflcanLly Lo
alLer Lhe guldellne recommendaLlons and warranL an updaLe.
3.S.4 D|sc|a|mer
PealLh care provlders need Lo use cllnlcal [udgemenL, knowledge and experLlse when decldlng
wheLher lL ls approprlaLe Lo apply guldellnes. 1he recommendaLlons clLed here are a gulde and may
noL be approprlaLe for use ln all slLuaLlons. 1he declslon Lo adopL any of Lhe recommendaLlons clLed
here musL be made by Lhe pracLlLloners ln llghL of lndlvldual paLlenL clrcumsLances, Lhe wlshes of Lhe
paLlenL, cllnlcal experLlse and resources.
1he naLlonal Cllnlcal Culdellne CenLre dlsclalms any responslblllLy for damages arlslng ouL of Lhe use
or non-use of Lhese guldellnes and Lhe llLeraLure used ln supporL of Lhese guldellnes.
3.S.S Iund|ng
1he naLlonal Cllnlcal Culdellne CenLre was commlssloned by Lhe naLlonal lnsLlLuLe for PealLh and
Care Lxcellence Lo underLake Lhe work on Lhls guldellne.

MeLhods

34

Culdellne summary

33
4 Gu|de||ne summary
4.1 key pr|or|t|es for |mp|ementat|on
lrom Lhe full seL of recommendaLlons, Lhe CuC selecLed Len key prlorlLles for lmplemenLaLlon. 1he
crlLerla used for selecLlng Lhese recommendaLlons are llsLed ln deLall ln 1he Culdellnes Manual.
77
1he
reasons LhaL each of Lhese recommendaLlons was chosen are shown ln Lhe Lable llnklng Lhe evldence
Lo Lhe recommendaLlon ln Lhe relevanL chapLer. 1he recommendaLlons are llsLed ln Lhe order Lhey
appear ln Lhe guldellne.
r|nc|p|es and protoco| for |ntravenous f|u|d therapy
1. When prescrlblng lv flulds, remember Lhe 3 8s: 8esusclLaLlon, 8ouLlne malnLenance,
8eplacemenL, 8edlsLrlbuLlon and 8eassessmenL.
2. Cffer lv fluld Lherapy as parL of a proLocol (see AlgorlLhms for lv fluld Lherapy):
Assess patients fluid and electrolyte needs following AlgorlLhm 1: AssessmenL.
lf paLlenLs need lv flulds for fluld resusclLaLlon, follow AlgorlLhm 2: lluld resusclLaLlon.
lf paLlenLs need lv flulds for rouLlne malnLenance, follow AlgorlLhm 3: 8ouLlne malnLenance.
lf paLlenLs need lv flulds Lo address exlsLlng deflclLs or excesses, ongolng abnormal losses or
abnormal fluld dlsLrlbuLlon, follow AlgorlLhm 4: 8eplacemenL and redlsLrlbuLlon.
3. aLlenLs should have an lv fluld managemenL plan, whlch should lnclude deLalls of:
Lhe fluld and elecLrolyLe prescrlpLlon over Lhe nexL 24 hours
Lhe assessmenL and monlLorlng plan.
lnlLlally, Lhe lv fluld managemenL plan should be revlewed by an experL dally. lv fluld managemenL
plans for paLlenLs on longer-Lerm lv fluld Lherapy whose condlLlon ls sLable may be revlewed less
frequenLly.
Assessment and mon|tor|ng
4. Assess the patients likely fluid and electrolyte needs from their history, clinical examination,
currenL medlcaLlons, cllnlcal monlLorlng and laboraLory lnvesLlgaLlons:
PlsLory should lnclude any prevlous llmlLed lnLake, LhlrsL, Lhe quanLlLy and composlLlon of
abnormal losses (see ulagram of ongolng losses), and any comorbldlLles, lncludlng paLlenLs who
are malnourlshed and aL rlsk of refeedlng syndrome (see nuLrlLlon supporL ln adulLs [nlCL cllnlcal
guldellne 32]).
Cllnlcal examlnaLlon should lnclude an assessmenL of Lhe paLlenL's fluld sLaLus, lncludlng:
o pulse, blood pressure, caplllary reflll and [ugular venous pressure
o presence of pulmonary or perlpheral oedema
o presence of posLural hypoLenslon.
Cllnlcal monlLorlng should lnclude currenL sLaLus and Lrends ln:
o naLlonal Larly Warnlng Score (nLWS)
o fluld balance charLs
o welghL.
LaboraLory lnvesLlgaLlons should lnclude currenL sLaLus and Lrends ln:
o full blood counL
o urea, creaLlnlne and elecLrolyLes.
Culdellne summary

36
3. All paLlenLs conLlnulng Lo recelve lv flulds need regular monlLorlng. 1hls should lnlLlally lnclude aL
leasL dally reassessmenLs of cllnlcal fluld sLaLus, laboraLory values (urea, creaLlnlne and
elecLrolyLes) and fluld balance charLs, along wlLh welghL measuremenL Lwlce weekly. 8e aware
LhaL:
aLlenLs recelvlng lv fluld Lherapy Lo address replacemenL or redlsLrlbuLlon problems may need
more frequenL monlLorlng.
AddlLlonal monlLorlng of urlnary sodlum may be helpful ln paLlenLs wlLh hlgh-volume
gasLrolnLesLlnal losses. (8educed urlnary sodlum excreLlon [less Lhan 30 mmol/l] may lndlcaLe
LoLal body sodlum depleLlon even lf plasma sodlum levels are normal. urlnary sodlum may also
lndlcaLe Lhe cause of hyponaLraemla, and gulde Lhe achlevemenL of a negaLlve sodlum balance ln
paLlenLs wlLh oedema. Powever, urlnary sodlum values may be mlsleadlng ln Lhe presence of
renal lmpalrmenL or dlureLlc Lherapy.)
aLlenLs on longer-Lerm lv fluld Lherapy whose condlLlon ls sLable may be monlLored less
frequenLly, alLhough declslons Lo reduce monlLorlng frequency should be deLalled ln Lhelr lv fluld
managemenL plan.
6. Clear lncldenLs of fluld mlsmanagemenL (for example, unnecessarlly prolonged dehydraLlon or
lnadverLenL fluld overload due Lo lv fluld Lherapy) should be reporLed Lhrough sLandard crlLlcal
lncldenL reporLlng Lo encourage lmproved Lralnlng and pracLlce (see Consequences of fluld
mlsmanagemenL Lo be reporLed as crlLlcal lncldenLs).
kesusc|tat|on
7. lf paLlenLs need lv fluld resusclLaLlon, use crysLallolds LhaL conLaln sodlum ln Lhe range 130134
mmol/l, wlLh a bolus of 300 ml over less Lhan 13 mlnuLes. (lor more lnformaLlon see Lhe
ComposlLlon of commonly used crysLallolds Lable.)
kout|ne ma|ntenance
8. lf paLlenLs need lv flulds for rouLlne malnLenance alone, resLrlcL Lhe lnlLlal prescrlpLlon Lo:
2330 ml/kg/day of waLer and
approxlmaLely 1 mmol/kg/day of poLasslum, sodlum and chlorlde and
approxlmaLely 30100 g/day of glucose Lo llmlL sLarvaLlon keLosls. (1hls quanLlLy wlll noL address
patients nutritional needs; see nuLrlLlon supporL ln adulLs [nlCL cllnlcal guldellne 32].)
lor more lnformaLlon see lv fluld prescrlpLlon (by body welghL) for rouLlne malnLenance over a 24-
hour perlod.
9. PosplLals should esLabllsh sysLems Lo ensure LhaL all healLhcare professlonals lnvolved ln
prescrlblng and dellverlng lv fluld Lherapy are Lralned on Lhe prlnclples covered ln Lhls guldellne,
and are Lhen formally assessed and reassessed aL regular lnLervals Lo demonsLraLe compeLence
ln:
undersLandlng Lhe physlology of fluld and elecLrolyLe balance ln paLlenLs wlLh normal physlology
and durlng lllness
assessing patients fluid and electrolyte needs (the 5 8s: 8esusclLaLlon, 8ouLlne malnLenance,
8eplacemenL, 8edlsLrlbuLlon and 8eassessmenL)
assesslng Lhe rlsks, beneflLs and harms of lv flulds
prescrlblng and admlnlsLerlng lv flulds
monlLorlng Lhe paLlenL response
evaluaLlng and documenLlng changes and
Culdellne summary

37
Laklng approprlaLe acLlon as requlred.
10. PosplLals should have an lv flulds lead, responslble for Lralnlng, cllnlcal governance, audlL and
revlew of lv fluld prescrlblng and paLlenL ouLcomes.

4.2 Iu|| ||st of recommendat|ons
In this guideline, the term expert refers to a healthcare professional who has core compeLencles Lo
dlagnose and manage acuLe lllness. 1hese compeLencles can be dellvered by a varleLy of models aL a
local level, such as a crlLlcal care ouLreach Leam, a hosplLal-aL-nlghL Leam or a speclallsL Lralnee ln an
acuLe medlcal or surglcal speclalLy. lor more lnformaLlon, see AcuLely lll paLlenLs ln hosplLal (nlCL
cllnlcal guldellne 30).
r|nc|p|es and protoco|s for |ntravenous f|u|d therapy:
The assessment and management of patients fluid and electrolyte needs is fundamental to good
paLlenL care.
1. Assess and manage paLlenLs' fluld and elecLrolyLe needs as parL of every ward revlew. rovlde
lnLravenous (lv) fluld Lherapy only for paLlenLs whose needs cannoL be meL by oral or enLeral
rouLes, and sLop as soon as posslble.
2. Skllled and compeLenL healLhcare professlonals should prescrlbe and admlnlsLer lv flulds, and
assess and monlLor paLlenLs recelvlng lv flulds (see recommendaLlons 2628).
3. When prescrlblng lv flulds, remember Lhe 3 8s: 8esusclLaLlon, 8ouLlne malnLenance,
8eplacemenL, 8edlsLrlbuLlon and 8eassessmenL.
4. Cffer lv fluld Lherapy as parL of a proLocol (see AlgorlLhms for lv fluld Lherapy):
Assess patients fluid and electrolyte needs following AlgorlLhm 1: AssessmenL.
lf paLlenLs need lv flulds for fluld resusclLaLlon, follow AlgorlLhm 2: lluld resusclLaLlon.
lf paLlenLs need lv flulds for rouLlne malnLenance, follow AlgorlLhm 3: 8ouLlne malnLenance.
lf paLlenLs need lv flulds Lo address exlsLlng deflclLs or excesses, ongolng abnormal losses or
abnormal fluld dlsLrlbuLlon, follow AlgorlLhm 4: 8eplacemenL and redlsLrlbuLlon.
3. lnclude Lhe followlng lnformaLlon ln lv fluld prescrlpLlons:
1he Lype of fluld Lo be admlnlsLered.
1he raLe and volume of fluld Lo be admlnlsLered.
6. aLlenLs should have an lv fluld managemenL plan, whlch should lnclude deLalls of:
Lhe fluld and elecLrolyLe prescrlpLlon over Lhe nexL 24 hours
Lhe assessmenL and monlLorlng plan.
lnlLlally, Lhe lv fluld managemenL plan should be revlewed by an experL dally. lv fluld managemenL
plans for paLlenLs on longer-Lerm lv fluld Lherapy whose condlLlon ls sLable may be revlewed less
frequenLly.
7. When prescrlblng lv flulds and elecLrolyLes, Lake lnLo accounL all oLher sources of fluld and
elecLrolyLe lnLake, lncludlng any oral or enLeral lnLake, and lnLake from drugs, lv nuLrlLlon, blood and
blood producLs.
8. aLlenLs have a valuable conLrlbuLlon Lo make Lo Lhelr fluld balance. lf a paLlenL needs lv flulds,
explaln Lhe declslon, and dlscuss Lhe slgns and sympLoms Lhey need Lo look ouL for lf Lhelr fluld
Culdellne summary

38
balance needs ad[usLlng. lf posslble or when asked, provlde wrlLLen lnformaLlon (for example, NICEs
lnformaLlon for Lhe publlc), and involve the patients family members or carers (as appropriate).
Assessment and mon|tor|ng:
In|t|a| assessment
9. Assess wheLher Lhe paLlenL ls hypovolaemlc. lndlcaLors LhaL a paLlenL may need urgenL fluld
resusclLaLlon lnclude:
sysLollc blood pressure ls less Lhan 100 mmPg
hearL raLe ls more Lhan 90 beaLs per mlnuLe
caplllary reflll Llme ls more Lhan 2 seconds or perlpherles are cold Lo Louch
resplraLory raLe ls more Lhan 20 breaLhs per mlnuLe
naLlonal Larly Warnlng Score (nLWS) ls 3 or more
passlve leg ralslng suggesLs fluld responslveness
a
.
10. Assess the patients likely fluid and electrolyte needs from their history, clinical examination,
currenL medlcaLlons, cllnlcal monlLorlng and laboraLory lnvesLlgaLlons:
PlsLory should lnclude any prevlous llmlLed lnLake, LhlrsL, Lhe quanLlLy and composlLlon of
abnormal losses (see ulagram of ongolng losses), and any comorbldlLles, lncludlng paLlenLs who
guldellne 32]).
Cllnlcal examlnaLlon should lnclude an assessmenL of Lhe paLlenL's fluld sLaLus, lncludlng:
o pulse, blood pressure, caplllary reflll and [ugular venous pressure
o presence of pulmonary or perlpheral oedema
o presence of posLural hypoLenslon.
Cllnlcal monlLorlng should lnclude currenL sLaLus and Lrends ln:
o nLWS
o fluld balance charLs
o welghL.
LaboraLory lnvesLlgaLlons should lnclude currenL sLaLus and Lrends ln:
o full blood counL
o urea, creaLlnlne and elecLrolyLes.
keassessment
11. lf paLlenLs are recelvlng lv flulds for resusclLaLlon, reassess Lhe paLlenL uslng Lhe A8CuL approach
(Alrway, 8reaLhlng, ClrculaLlon, ulsablllLy, Lxposure), monlLor Lhelr resplraLory raLe, pulse, blood
pressure and perfuslon conLlnuously, and measure Lhelr venous lacLaLe levels and/or arLerlal pP and
base excess accordlng Lo guldance on advanced llfe supporL (8esusclLaLlon Councll [uk], 2011)
90
.
12. All paLlenLs conLlnulng Lo recelve lv flulds need regular monlLorlng. 1hls should lnlLlally lnclude aL
leasL dally reassessmenLs of cllnlcal fluld sLaLus, laboraLory values (urea, creaLlnlne and elecLrolyLes)
and fluld balance charLs, along wlLh welghL measuremenL Lwlce weekly. 8e aware LhaL:

a asslve leg ralslng ls a bedslde meLhod Lo assess fluld responslveness ln a paLlenL. lL ls besL underLaken wlLh Lhe paLlenL
lnlLlally seml-recumbenL and Lhen LllLlng Lhe enLlre bed Lhrough 43. AlLernaLlvely lL can be done by lylng Lhe paLlenL flaL
and passlvely ralslng Lhelr legs Lo greaLer Lhan 43. lf, aL 3090 seconds, Lhe paLlenL shows slgns of haemodynamlc
lmprovemenL, lL lndlcaLes LhaL volume replacemenL may be requlred. lf Lhe condlLlon of Lhe paLlenL deLerloraLes, ln
parLlcular breaLhlessness, lL lndlcaLes LhaL Lhe paLlenL may be fluld overloaded.
Culdellne summary

39
aLlenLs recelvlng lv fluld Lherapy Lo address replacemenL or redlsLrlbuLlon problems may need
more frequenL monlLorlng.
AddlLlonal monlLorlng of urlnary sodlum may be helpful ln paLlenLs wlLh hlgh-volume
gasLrolnLesLlnal losses. (8educed urlnary sodlum excreLlon [less Lhan 30 mmol/l] may lndlcaLe
LoLal body sodlum depleLlon even lf plasma sodlum levels are normal. urlnary sodlum may also
lndlcaLe Lhe cause of hyponaLraemla, and gulde Lhe achlevemenL of a negaLlve sodlum balance ln
paLlenLs wlLh oedema. Powever, urlnary sodlum values may be mlsleadlng ln Lhe presence of
renal lmpalrmenL or dlureLlc Lherapy.)
aLlenLs on longer-Lerm lv fluld Lherapy whose condlLlon ls sLable may be monlLored less
frequenLly, alLhough declslons Lo reduce monlLorlng frequency should be deLalled ln Lhelr lv fluld
managemenL plan.
13. lf paLlenLs have recelved lv flulds conLalnlng chlorlde concenLraLlons greaLer Lhan 120 mmol/l
(for example, sodlum chlorlde 0.9), monlLor Lhelr serum chlorlde concenLraLlon dally. lf paLlenLs
develop hyperchloraemla or acldaemla, reassess Lhelr lv fluld prescrlpLlon and assess Lhelr acldbase
sLaLus. Conslder less frequenL monlLorlng for paLlenLs who are sLable.
14. Clear lncldenLs of fluld mlsmanagemenL (for example, unnecessarlly prolonged dehydraLlon or
lnadverLenL fluld overload due Lo lv fluld Lherapy) should be reporLed Lhrough sLandard crlLlcal
lncldenL reporLlng Lo encourage lmproved Lralnlng and pracLlce (see Consequences of fluld
mlsmanagemenL Lo be reporLed as crlLlcal lncldenLs).
13. lf paLlenLs are Lransferred Lo a dlfferenL locaLlon, reassess Lhelr fluld sLaLus and lv fluld
managemenL plan on arrlval ln Lhe new seLLlng.
kesusc|tat|on
16. lf paLlenLs need lv fluld resusclLaLlon, use crysLallolds LhaL conLaln sodlum ln Lhe range 130134
mmol/l, wlLh a bolus of 300 ml over less Lhan 13 mlnuLes. (lor more lnformaLlon, see Lhe
ComposlLlon of commonly used crysLallolds Lable.)
17. uo noL use LeLrasLarch for fluld resusclLaLlon.
18. Conslder human albumln soluLlon 43 for fluld resusclLaLlon only ln paLlenLs wlLh severe sepsls.
kout|ne ma|ntenance
19. lf paLlenLs need lv flulds for rouLlne malnLenance alone, resLrlcL Lhe lnlLlal prescrlpLlon Lo:
2330 ml/kg/day of waLer and
approxlmaLely 1 mmol/kg/day of poLasslum, sodlum and chlorlde and
approxlmaLely 30100 g/day of glucose Lo llmlL sLarvaLlon keLosls. (1hls quanLlLy wlll noL address
patients nutritional needs; see nuLrlLlon supporL ln adulLs [nlCL cllnlcal guldellne 32].)
lor more lnformaLlon see Lhe lv fluld prescrlpLlon (by body welghL) for rouLlne malnLenance over a
24-hour perlod.
20. lor paLlenLs who are obese, ad[usL Lhe lv fluld prescrlpLlon Lo Lhelr ldeal body welghL. use lower
range volumes per kg (paLlenLs rarely need more Lhan a LoLal of 3 llLres of fluld per day) and seek
experL help lf Lhelr 8Ml ls more Lhan 40 kg/m
2
.
21. Conslder prescrlblng less fluld (for example, 2023 ml/kg/day fluld) for paLlenLs who:
are older or frall
have renal lmpalrmenL or cardlac fallure
Culdellne summary

40
guldellne 32]).
22. When prescrlblng for rouLlne malnLenance alone, conslder uslng 2330 ml/kg/day sodlum
chlorlde 0.18 ln 4 glucose wlLh 27 mmol/l poLasslum on day 1 (Lhere are oLher reglmens Lo
achleve Lhls). rescrlblng more Lhan 2.3 llLres per day lncreases Lhe rlsk of hyponaLraemla. 1hese are
lnlLlal prescrlpLlons and furLher prescrlpLlons should be gulded by monlLorlng.
23. Conslder dellverlng lv flulds for rouLlne malnLenance durlng dayLlme hours Lo promoLe sleep and
wellbelng.
kep|acement and red|str|but|on
24. Ad[usL Lhe lv prescrlpLlon (add Lo or subLracL from malnLenance needs) Lo accounL for exlsLlng
fluld and/or elecLrolyLe deflclLs or excesses, ongolng losses (see ulagram of ongolng losses) or
abnormal dlsLrlbuLlon.
23. Seek experL help lf paLlenLs have a complex fluld and/or elecLrolyLe redlsLrlbuLlon lssue or
lmbalance, or slgnlflcanL comorbldlLy, for example:
gross oedema
severe sepsls
hyponaLraemla or hypernaLraemla
renal, llver and/or cardlac lmpalrmenL
posL-operaLlve fluld reLenLlon and redlsLrlbuLlon
malnourlshed and refeedlng lssues (see nuLrlLlon supporL ln adulLs [nlCL cllnlcal guldellne 32]).

26. PosplLals should esLabllsh sysLems Lo ensure LhaL all healLhcare professlonals lnvolved ln
prescrlblng and dellverlng lv fluld Lherapy are Lralned on Lhe prlnclples covered ln Lhls guldellne, and
are Lhen formally assessed and reassessed aL regular lnLervals Lo demonsLraLe compeLence ln:
undersLandlng Lhe physlology of fluld and elecLrolyLe balance ln paLlenLs wlLh normal physlology
and durlng lllness
assessing patients fluid and electrolyte needs (the 5 8s: 8esusclLaLlon, 8ouLlne malnLenance,
8eplacemenL, 8edlsLrlbuLlon and 8eassessmenL)
assesslng Lhe rlsks, beneflLs and harms of lv flulds
prescrlblng and admlnlsLerlng lv flulds
monlLorlng Lhe paLlenL response
evaluaLlng and documenLlng changes and
Laklng approprlaLe acLlon as requlred.
27. PealLhcare professlonals should recelve Lralnlng and educaLlon abouL, and be compeLenL ln,
recognlslng, assesslng and prevenLlng consequences of mlsmanaged lv fluld Lherapy, lncludlng:
pulmonary oedema
perlpheral oedema
volume depleLlon and shock.
28. PosplLals should have an lv flulds lead, responslble for Lralnlng, cllnlcal governance, audlL and
revlew of lv fluld prescrlblng and paLlenL ouLcomes.
Culdellne summary

41

Culdellne summary

naLlonal Cllnlcal Culdellne CenLre-uecember 2013 42
4.2.1 A|gor|thms for IV f|u|d therapy

Algorithms for IV fluid therapy

Using an ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach, assess whether the patient is hypovolaemic and needs fluid resuscitation
Assess volume status taking into account clinical examination, trends and context. Indicators that a patient may need fluid resuscitation include: systolic BP <100mmHg; heart rate
>90bpm; capillary refill >2s or peripheries cold to touch; respiratory rate >20 breaths per min; NEWS 5; 45
o
passive leg raising suggests fluid responsiveness.
Can the patient meet their fluid and/or electrolyte needs orally or enterally?

Assess the patients likely fluid and electrolyte needs
History: previous limited intake, thirst, abnormal losses, comorbidities.
Clinical examination: pulse, BP, capillary refill, JVP, oedema (peripheral/pulmonary), postural hypotension.
Clinical monitoring: NEWS, fluid balance charts, weight.
Laboratory assessments: FBC, urea, creatinine and electrolytes.

Does the patient have complex fluid or
electrolyte replacement or abnormal
distribution issues?
Look for existing deficits or excesses, ongoing
abnormal losses, abnormal distribution or other
complex issues.

Reassess the patient using the ABCDE
approach
Does the patient still need fluid
resuscitation? Seek expert help if unsure
Initiate treatment
Identify cause of deficit and respond.
Give a fluid bolus of 500 ml of crystalloid
(containing sodium in the range of
130154 mmol/l) over 15 minutes.
Ongoing abnormal fluid or
electrolyte losses
Check ongoing losses and estimate
amounts. Check for:
vomiting and NG tube loss
biliary drainage loss
high/low volume ileal stoma
loss
diarrhoea/excess colostomy
loss
ongoing blood loss, e.g.
melaena
sweating/fever/dehydration
pancreatic/jejunal fistula/stoma
loss
urinary loss, e.g. post AKI
polyuria.

Algorithm 3: Routine Maintenance

Give maintenance IV fluids
Normal daily fluid and electrolyte requirements:
2530 ml/kg/d water
1 mmol/kg/day sodium, potassium, chloride
50100 g/day glucose (e.g. glucose 5% contains
5 g/100ml).

Reassess and monitor the patient
Stop IV fluids when no longer needed.
Nasogastric fluids or enteral feeding are preferable
when maintenance needs are more than 3 days.
Existing fluid or
electrolyte deficits
or excesses
Check for:
dehydration
fluid overload
hyperkalaemia/
hypokalaemia

Estimate deficits or
excesses.
Redistribution and
other complex issues
Check for:
gross oedema
severe sepsis
hypernatraemia/
hyponatraemia
renal, liver and/or
cardiac impairment.
post-operative fluid
retention and
redistribution
malnourished and
refeeding issues
Seek expert help if
necessary and estimate
requirements.
Give a further fluid bolus of 250500 ml of
crystalloid
>2000 ml
given?
Seek expert help
Algorithm 2: Fluid Resuscitation

Algorithm 4: Replacement and Redistribution

No

Yes
No

Yes
No

Ensure nutrition and fluid needs are met
Also see Nutrition support in adults (NICE
clinical guideline 32).
Yes
Yes
Prescribe by adding to or subtracting from routine maintenance, adjusting for all
other sources of fluid and electrolytes (oral, enteral and drug prescriptions)

Yes
Monitor and reassess fluid and biochemical status by clinical and laboratory
monitoring
Yes
Algorithm 1: Assessment
No

No

No
Does the patient have
signs of shock?

Culdellne summary

43

4.2.2 D|agram of ongo|ng |osses

5ootce. copytlqbt-Notloool cllolcol ColJelloe ceotte

Culdellne summary

44

4.2.3 Consequences of f|u|d m|smanagement to be reported as cr|t|ca| |nc|dents
Consequence of f|u|d
m|smanagement Ident|fy|ng features
1|me frame of
|dent|f|cat|on
Pypovolaemla Patients fluld needs noL meL by oral, enLeral or lv
lnLake and
leaLures of dehydraLlon on cllnlcal examlnaLlon
Low urlne ouLpuL or concenLraLed urlne
8lochemlcal lndlcaLors, such as more Lhan 30
lncrease ln urea or creaLlnlne wlLh no oLher
ldenLlflable cause
8efore and durlng lv
fluld Lherapy
ulmonary oedema
(breaLhlessness durlng
lnfuslon)
no oLher obvlous cause ldenLlfled (for example,
pneumonla, pulmonary embolus or asLhma)
leaLures of pulmonary oedema on cllnlcal
examlnaLlon
leaLures of pulmonary oedema on x-ray
uurlng lv fluld Lherapy or
wlLhln 6 hours of
sLopplng lv flulds
PyponaLraemla Serum sodlum less Lhan 130 mmol/l
no oLher llkely cause of hyponaLraemla ldenLlfled
wlLhln 24 hours of
sLopplng lv flulds
PypernaLraemla Serum sodlum 133 mmol/l or more
8asellne sodlum normal or low
lv fluld reglmen lncluded 0.9 sodlum chlorlde
no oLher llkely cause of hypernaLraemla
ldenLlfled
wlLhln 24 hours of
sLopplng lv flulds
erlpheral oedema lLLlng oedema ln exLremlLles and/or lumbar
sacral area
no oLher obvlous cause ldenLlfled (for example,
nephroLlc syndrome or known cardlac fallure)
wlLhln 24 hours of
sLopplng lv flulds
Pyperkalaemla Serum poLasslum more Lhan 3.3 mmol/l
no oLher obvlous cause ldenLlfled
wlLhln 24 hours of
sLopplng lv flulds
Pypokalaemla Serum poLasslum less Lhan 3.0 mmol/l llkely Lo be
due Lo lnfuslon of flulds wlLhouL adequaLe
poLasslum provlslon
no oLher obvlous cause (for example, poLasslum-
wasLlng dlureLlcs, refeedlng syndrome)
wlLhln 24 hours of
sLopplng lv flulds

4.2.4 IV f|u|d prescr|pt|on (by body we|ght) for rout|ne ma|ntenance over a 24-hour per|od
8ody
we|ght Water
Sod|um, ch|or|de,
potass|um

8ody
we|ght Water
Sod|um, ch|or|de,
potass|um
kg 2S30 m|]kg]day
approx.
1 mmo|]kg]day
of each kg 2S30m|]kg]day
approx.
1 mmo|]kg]day
of each
40 10001200 40 71 17732130 71
41 10231230 41 72 18002160 72
42 10301260 42 73 18232190 73
43 10731290 43 74 18302220 74
Culdellne summary

43
44 11001320 44 73 18732230 73
43 11231330 43 76 19002280 76
46 11301380 46 77 19232310 77
47 11731410 47 78 19302340 78
48 12001440 48 79 19732370 79
49 12231470 49 80 20002400 80
30 12301300 30 81 20232430 81
31 12731330 31 82 20302460 82
32 13001360 32 83 20732490 83
33 13231390 33 84 21002320 84
34 13301620 34 83 21232330 83
33 13731630 33 86 21302380 86
36 14001680 36 87 21732610 87
37 14231710 37 88 22002640 88
38 14301740 38 89 22232670 89
39 14731770 39 90 22302700 90
60 13001800 60 91 22732730 91
61 13231830 61 92 23002760 92
62 13301860 62 93 23232790 93
63 13731890 63 94 23302820 94
64 16001920 64 93 23732830 93
63 16231930 63 96 24002880 96
66 16301980 66 97 24232910 97
67 16732010 67 98 24302940 98
68 17002040 68 99 24732970 99
69 17232070 69 100 23003000 100
70 17302100 70 >100 23003000 100
1. AJJ 50-100 qtoms/Joy qlocose (e.q. qlocose 5X cootolos 5q/100ml).
2. lot speclol cooslJetotloos tefet to tbe tecommeoJotloos fot tootloe moloteoooce.

Culdellne summary

46
4.3 key research recommendat|ons
1. What |s the |nc|dence of comp||cat|ons dur|ng, and as a consequence of, IV f|u|d therapy?
2. Are ba|anced so|ut|ons super|or to sod|um ch|or|de 0.9 for the f|u|d resusc|tat|on of pat|ents
w|th acute hypovo|aem|c shock?
3. Are ba|anced crysta||o|ds super|or to a comb|nat|on of a ba|anced crysta||o|d and a ge|at|n
suspended |n a ba|anced so|ut|on for the f|u|d resusc|tat|on of pat|ents w|th acute
hypovo|aem|c shock?
4. Does a h|gher sod|um content IV f|u|d reg|men for ma|ntenance reduce the r|sk of deve|op|ng
hyponatraem|a and vo|ume dep|et|on w|thout |ncreas|ng the r|sk of vo|ume over|oad |n
hosp|ta||sed adu|ts?
S. Does the |ntroduct|on of hosp|ta| systems that ensure:
a|| hosp|ta| hea|thcare profess|ona|s |nvo|ved |n prescr|b|ng and de||ver|ng IV f|u|d therapy
are appropr|ate|y tra|ned |n the pr|nc|p|es of f|u|d prescr|b|ng, and
a|| IV f|u|d therapy-re|ated comp||cat|ons are reported,
|ead to a reduct|on |n f|u|d-re|ated comp||cat|ons and assoc|ated hea|thcare costs?

rlnclples and proLocols for lnLravenous fluld Lherapy

47
S r|nc|p|es and protoco|s for |ntravenous f|u|d
therapy
PosplLallsed paLlenLs need lnLravenous (lv) fluld and elecLrolyLes for one or more of Lhe followlng
reason (Lhe 48s):
I|u|d resusc|tat|on
lv flulds may need Lo be glven urgenLly Lo resLore clrculaLlon Lo vlLal organs followlng loss of
lnLravascular volume due Lo bleedlng, plasma loss, or excesslve exLernal fluld and elecLrolyLe loss,
usually from Lhe gasLrolnLesLlnal (Cl) LracL, or severe lnLernal losses (e.g. from fluld redlsLrlbuLlon ln
sepsls).
kout|ne ma|ntenance
lv flulds are someLlmes needed for paLlenLs who slmply cannoL meeL Lhelr normal fluld or elecLrolyLe
needs by oral or enLeral rouLes buL who are oLherwlse well ln Lerms of fluld and elecLrolyLe balance
and handllng l.e. Lhey are essenLlally euvolaemlc, wlLh no slgnlflcanL deflclLs, ongolng abnormal
losses or redlsLrlbuLlon lssues. Powever, even when prescrlblng lv flulds for more complex cases,
Lhere ls sLlll a need Lo meeL Lhe patients routine maintenance requirements, adjusting the
malnLenance prescrlpLlon Lo accounL for Lhe more complex fluld or elecLrolyLe problems. LsLlmaLes
of rouLlne malnLenance requlremenLs are Lherefore essenLlal for all paLlenLs on conLlnulng lv fluld
Lherapy.
kep|acement
ln some paLlenLs, lv flulds Lo LreaL losses from lnLravascular and or oLher fluld comparLmenLs, are noL
needed urgenLly for resusclLaLlon, buL are sLlll requlred Lo correcL exlsLlng waLer and/or elecLrolyLe
deflclLs or ongolng exLernal losses. 1hese losses are usually from Lhe Cl or urlnary LracL, alLhough
hlgh lnsenslble losses occur wlLh fever, and burns paLlenLs can lose hlgh volumes of whaL ls
effecLlvely plasma. SomeLlmes, Lhese deflclLs have developed slowly wlLh assoclaLed compensaLory
adapLaLlons of Llssue elecLrolyLe and fluld dlsLrlbuLlon LhaL musL be Laken lnLo accounL ln subsequenL
replacemenL reglmens (e.g. cauLlous, slow replacemenL Lo reduce rlsks of ponLlne demyellnosls).
ked|str|but|on
ln addlLlon Lo exLernal fluld and elecLrolyLe losses, some hosplLal paLlenLs have marked lnLernal fluld
dlsLrlbuLlon changes or abnormal fluld handllng. 1hls Lype of problem ls seen parLlcularly ln Lhose
who are sepLlc, oLherwlse crlLlcally lll, posL-ma[or surgery or Lhose wlLh ma[or cardlac, llver or renal
co-morbldlLy. Many of Lhese paLlenLs develop oedema from sodlum and waLer excess and some
sequesLer flulds ln Lhe Cl LracL or Lhoraclc/perlLoneal cavlLles.
uecldlng on Lhe opLlmal amounL, composlLlon and raLe of admlnlsLraLlon of lv flulds Lo address Lhese
ofLen complex needs ls lnherenLly dlfflculL yeL assessmenL, prescrlblng and monlLorlng of lv flulds ln
general admlsslon and ward areas of hosplLals, ls ofLen lefL Lo [unlor docLors and hard-pressed nurses
who may lack requlred Lralnlng and compeLence.
36,37,86,87,93
Lvldence suggesLs LhaL mlsmanagemenL of
flulds ls common, parLlcularly ln general ward areas wlLh Lhe poLenLlal for adverse ouLcomes
lncludlng excess morbldlLy and morLallLy, prolonged hosplLal sLays and lncreased cosLs.
6,39,73,103,116,117

1here ls, Lherefore, a clear need for guldance on lv fluld prescrlblng appllcable Lo general ward areas
buL slnce mosL randomlzed conLrolled Lrlals of lv fluld Lherapy have examlned narrow cllnlcal
quesLlons ln lnLenslve care or lnLra-operaLlve seLLlngs, many recommendaLlons for more general use

48
musL be based on flrsL prlnclples. All healLh professlonals lnvolved ln prescrlblng and admlnlsLerlng lv
flulds need Lo undersLand Lhese prlnclples lf Lhey are Lo prescrlbe and manage lv fluld Lherapy safely
and effecLlvely.
S.1 1he pr|nc|p|es of f|u|d prescr|b|ng
b

1he knowledge needed Lo underpln safe and effecLlve lv fluld and elecLrolyLe prescrlblng lles ln four
areas:
1he physlology of fluld balance ln healLh,
aLhophyslologlcal effecLs on fluld balance,
Cllnlcal approaches Lo assesslng lv fluld needs,
1he properLles of avallable lv flulds.
S.1.1 1he phys|o|ogy of f|u|d ba|ance |n hea|th
When prlmlLlve marlne unlcellular organlsms evolved lnLo mulLlcellular organlsms and emerged onLo
land, Lhey carrled wlLh Lhem Lhelr own lnLernal sea or exLracellular fluld (LCl), ln whlch Lhelr cells
could baLhe ln a consLanL chemlcal envlronmenL. 1he lrench physlologlsL Claude 8ernard called Lhls
the milieu interieur,
10
an envlronmenL ln whlch Lhe cells reLaln Lhelr energy consumlng capaclLy Lo
pump sodlum ouL and reLaln poLasslum ln order Lo neuLrallse Lhe negaLlve charges of proLelns and
oLher lons.
Whlle fluld balance ls usually consldered as LhaL beLween Lhe body and lLs envlronmenL, l.e. exLernal
balance, dlsease also affecLs Lhe lnLernal balance beLween Lhe varlous body fluld comparLmenLs, e.g.
beLween Lhe lnLravascular and lnLersLlLlal componenLs of Lhe exLracellular fluld comparLmenL (LCl),
beLween Lhe lnLracellular fluld (lCl) and Lhe LCl, and beLween Lhe LCl and Lhe guL and oLher lnLernal
spaces.
38,60
ApproprlaLe lv fluld Lherapy depends on an undersLandlng of Lhe underlylng physlology
and paLhophyslology and a conslderaLlon noL only of exLernal buL lnLernal fluld balance.
38

S.1.1.1 Norma| anatomy and phys|o|ogy
WaLer comprlses approxlmaLely 60 of Lhe body welghL of an average adulL (abouL 40L ln a 70kg
man).
29
1he percenLage ls lower ln obeslLy, slnce adlpose Llssue conLalns less waLer Lhan lean Llssue.
lL ls also lower ln women Lhan ln males because of Lhe relaLlvely greaLer amounL of adlpose Llssue ln
women. 1he LoLal body waLer ls dlvlded funcLlonally lnLo Lhe exLracellular (LCl=20 of body welghL,
abouL 14L ln a 70kg man ) and Lhe lnLracellular fluld spaces (lCl= 40 of body welghL, abouL 28L ln a
70kg man) separaLed by Lhe cell membrane wlLh lLs acLlve sodlum pump, whlch ensures LhaL sodlum
remalns malnly ln Lhe LCl. 1he cell, however, conLalns large anlons such as proLeln and glycogen,
whlch cannoL escape and, Lherefore, draw ln k+ lons Lo malnLaln elecLrlcal neuLrallLy (Clbbs-uonnan
equlllbrlum). 1hese mechanlsms ensure LhaL na+ and lLs balanclng anlons, Cl- and PCC3-, are Lhe
malnsLay of LCl osmolallLy, and k+ has Lhe correspondlng funcLlon ln Lhe lCl. 1he LCl ls furLher
dlvlded lnLo Lhe lnLravascular (wlLhln Lhe clrculaLlon) and Lhe lnLersLlLlal (exLravascular fluld
surroundlng Lhe cells) fluld spaces. 1he lnLravascular space (blood volume = 3-7 of body welghL,
approx. 4 3L) has lLs own lnLracellular componenL ln Lhe form of red (haemaLocrlL = 40-43) and
whlLe cells and an exLracellular elemenL ln Lhe form of plasma (33-60 of LoLal blood volume). 1he
normal dlsLrlbuLlon of flulds ln Lhe dlfferenL body comparLmenLs ls shown ln llgure 2 whlch also
shows Lhe llkely comparLmenLal dlsLrlbuLlon of some dlfferenL Lypes of lv flulds (see secLlon3.1.4).

b
Some secLlons of Lhe LexL ln Lhe lnLroducLlon of Lhls chapLer are wrlLLen by Lwo CuC members who are also co-auLhors of
a LexLbook on lnLravenous fluld Lherapy. 1he LexL book was commlssloned by a pharmaceuLlcal company (8.8raun) who
own Lhe copyrlghL permlsslons. 1he company dld noL have any lnLellecLual or edlLorlal lnpuL lnLo Lhe LexL and Lhe
lnLellecLual conLenL of Lhe LexL ls Lhe properLy of Lhe CuC members. lf Lhe wordlng and senLlmenL of Lhe LexL ls slmllar,
it can be attributed to the GDG members direct involvement in both pieces of work.

49
1he lnLravascular and exLravascular componenLs of Lhe LCl are separaLed by Lhe caplllary
membrane, wlLh lLs mlcropores. 1he lnLravascular volume depends on plasma oncoLlc (collold)
pressure (C) wlLh plasma proLelns reLalnlng waLer ln Lhe clrculaLlon. C ls normally ~3.4ka
(26mmPg) wlLh 73 of Lhe effecL due Lo albumln, 20 haemoglobln and 3 globullns. 1he plasma
albumln concenLraLlon ls ~33-32g/L, LoLal body albumln ls ~270g (120g lnLravascular, 130g lSl) and
llgure 2(see below) illustrates the albumin cycle. A gram of albumin binds ~18mls of water, thus
normal plasma albumin concentrations bind ~2.25L (18mls x 120g) of intravascular plasma water.
normally, Lhe caplllary mlcropores only allow a slow escape raLe of albumln (3/hr, 120g/day), whlch
ls Lhen reLurned Lo Lhe clrculaLlon vla Lhe lymphaLlcs aL Lhe same raLe, malnLalnlng equlllbrlum.
30

Whlle Lhe hydrosLaLlc pressure wlLhln Lhe clrculaLlon drlves fluld ouL, Lhe oncoLlc pressure of Lhe
plasma proLelns, e.g. albumln, draws fluld ln. 1hls malnLalns Lhe relaLlve consLancy of Lhe plasma
volume as a proporLlon of Lhe LCl (SLarllng effecL). 1here ls also a cllnlcally lmporLanL flux of fluld and
elecLrolyLes beLween Lhe LCl and Lhe Cl LracL lnvolvlng acLlve secreLlon and reabsorpLlon of dlgesLlve
[ulces. ln healLh Lhere ls a consLanL flux beLween Lhese varlous spaces and lmporLanL physlologlcal
mechanlsms ensure a consLanL relaLlonshlp beLween Lhem, whlch ls Lermed Lhe lnLernal fluld
balance.
38

I|gure 2: 8ody water compartments and approx|mate d|str|but|on of common|y used IV f|u|ds

5ootce. AJopteJ ftom Jloqtom(copytlqbt obtoloeJ) by ulleep lobo
58

S.1.1.2 I|u|d 8a|ance
1he exLernal fluld and elecLrolyLe balance beLween Lhe body and lLs envlronmenL refers Lo Lhe lnLake
of fluld and elecLrolyLes versus Lhe ouLpuL from kldneys, Cl LracL and Lhe skln and lungs (lnsenslble
loss). 1he normal average dally lnLake and ouLpuL of fluld and elecLrolyLes are shown ln 1able 8 and
1able 9 alLhough Lhese are very approxlmaLe and are modlfled greaLly ln Lhe presence of excesslve
lnsenslble losses e.g. of waLer and sodlum ln hoL cllmaLes.

30
1ab|e 8: Approx|mate da||y water ba|ance |n hea|th
Intake (m|) Cutput (m|)
WaLer from beverages 1200 urlne 1300
WaLer from solld food 1000 lnsenslble losses from
skln and lungs
300 - 1000
MeLabollc waLer from oxldaLlon 300 laeces 100
1ab|e 9: Average da||y |ntake
S2

WaLer 23-33 ml/kg/day
Sodlum Approx.1 mmol/kg/day
oLasslum Approx. 1 mmol/kg/day

S.1.1.3 Intake
under normal clrcumsLances mosL of our fluld lnLake ls ln Lhe form of drlnks buL food also conLalns
fluld and elecLrolyLes, and waLer ls also an end producL of lLs oxldaLlon whlch makes a furLher small
buL slgnlflcanL addlLlonal conLrlbuLlon Lo fluld lnLake. urlnklng ls governed by LhlrsL, whlch ls
Lrlggered when waLer balance ls negaLlve Lhrough lnsufflclenL lnLake or lncreased loss. lL ls also
Lrlggered by hlgh sodlum lnLake, slnce exLra waLer ls Lhen needed Lo keep Lhe LCl sodlum
concenLraLlon ln Lhe normal range.
AlLhough, ln Lhe elderly, LhlrsL may be blunLed, ln general lL ensures LhaL lnLake maLches Lhe bodlly
needs, malnLalnlng zero balance and a sLeady physlologlcal osmolallLy of 280-290mCsm/kg.
Claude 8ernard colned the term volume obligatoire to describe the minimum volume of urine
needed Lo excreLe wasLe producLs, e.g. urea, ln order Lo prevenL accumulaLlon ln Lhe blood. 1hls
concepL lmplles LhaL, lf sufflclenL fluld has been drunk or admlnlsLered Lo balance lnsenslble and
other losses, and to meet the kidneys needs, there is no advantage in giving more. Indeed, excessive
lnLakes of fluld and elecLrolyLes may be hazardous under cerLaln clrcumsLances (see below) slnce
they can overwhelm the kidneys capacity to excreLe Lhe excess and malnLaln normal balance.
Sodlum and waLer excess ln parLlcular can cause oedema, alLhough Lhls only becomes an lssue when
Lhe LCl has been expanded by aL leasL 2-3 llLres.
61

S.1.1.4 Cutput
lnsenslble loss: evaporaLlon of waLer from Lhe lungs and skln occurs all Lhe Llme wlLhouL us belng
aware of lL. ln Lhe uk cllmaLe, Lhe amounL losL ls 0.3-1 llLre/day buL ln hoL cllmaLes, durlng fever or
wlLh exerLlon, losses of several llLres of sweaL can occur, conLalnlng up Lo 30 mmol/l of sodlum.
CasLrolnLesLlnal losses: normally, Lhe lnLesLlne absorbs waLer and elecLrolyLes efflclenLly so LhaL sLool
fluld loss ls as llLLle as 100-130 ml/day. Powever, ln Lhe presence of dlsease Lhls may be greaLly
lncreased (see SecLlon 3.1.2 and secLlon on lnLravenous fluld Lherapy for replacemenL and
redlsLrlbuLlon).
kldneys: 1hese are Lhe maln organs for fluld and elecLrolyLe regulaLlon and excreLlon of wasLe
producLs from meLabollsm, e.g. urea. 1helr acLlvlLy ls conLrolled by pressure and osmoLlc sensors
whlch resulL ln changes ln Lhe secreLlon of hormones. 1he modesL dally flucLuaLlons ln waLer and
sodlum lnLake cause small changes ln plasma osmolallLy whlch Lrlgger osmorecepLors. 1hls ln Lurn
causes changes ln LhlrsL and Lhe renal excreLlon of waLer and sodlum. lf blood or LCl volumes are
sub[ecL Lo abnormal losses, volume recepLors are Lrlggered (see below) whlch overrlde Lhe

31
osmorecepLors. ln Lhe presence of large volume changes, Lherefore, Lhe kldney ls less able Lo ad[usL
osmolallLy. 1hls can be lmporLanL ln some cllnlcal slLuaLlons.
"#$#$#%#$ &'()* *)+,-'(./01
CsmorecepLors whlch sense changes ln plasma osmolallLy, are locaLed ln Lhe hypoLhalamus and
slgnal Lhe plLulLary Lo lncrease or decrease secreLlon of vasopressln or anLldlureLlc hormone (AuP).
ulluLlon of Lhe LCl, lncludlng plasma, by lnLake of waLer or fluld of lower osmolallLy Lhan plasma,
causes AuP secreLlon Lo fall, so LhaL Lhe kldneys excreLe more free waLer and produce a dlluLe urlne).
Conversely, dehydraLlon causes Lhe LCl Lo become more concenLraLed, AuP secreLlon rlses and Lhe
renal Lubules reabsorb more waLer, produclng concenLraLed urlne. ln response Lo dehydraLlon, Lhe
normal kldney can concenLraLe urea ln Lhe urlne up Lo a hundred-fold, so LhaL Lhe normal dally
producLlon of urea relaLed Lo proLeln meLabollsm ln healLh can be excreLed ln as llLLle as 300 ml of
urlne.
ln Lhe presence of waLer deflclL, Lhe urlne Lo plasma urea or osmolallLy raLlo ls, Lherefore, a measure
of the kidneys concentrating capacity. Age and disease can impair the renal concentrating capacity
so LhaL a larger volume of urlne ls requlred ln order Lo excreLe Lhe same amounL of wasLe producLs.
Also lf proLeln caLabollsm lncreases due Lo a hlgh proLeln lnLake or lncreased caLabollsm, a larger
volume of urlne ls needed Lo clear Lhe resulLlng lncrease ln urea producLlon.
1o assess renal funcLlon, Lherefore, measuremenL of boLh urlnary volume and concenLraLlon
(osmolallLy) are lmporLanL, and Lhe underlylng meLabollc clrcumsLances Laken lnLo accounL. lf serum
urea and creaLlnlne concenLraLlons are unchanged and normal, Lhen, urlnary ouLpuL over Lhe
previous 24 hours has been sufficient, fluid intake has been adequate, and the urinary volume
obligatoire has been achieved.

"#$#$#%#2 3/4.,5 67'89 *)+,-'(./01
Slnce Lhe lnLegrlLy of Lhe LCl volume and lLs proporLlon of Lhe LoLal body waLer are largely
dependenL on Lhe osmoLlc effecL of na+ and lLs accompanylng anlons, lL ls lmporLanL LhaL Lhe kldneys
malnLaln na+ balance wlLhln narrow llmlLs. lf sodlum depleLlon occurs, Lhe LCl and plasma volumes
fall. ressure sensors ln Lhe clrculaLlon are Lhen sLlmulaLed and Lhese exclLe renln secreLlon by Lhe
kldney. 1hls, ln Lurn, sLlmulaLes aldosLerone secreLlon by Lhe adrenal gland, whlch acLs on Lhe renal
Lubules, causlng Lhem Lo reabsorb and conserve sodlum.
Conversely, lf Lhe lnLake of na+ ls excesslve, Lhe renln-aldosLerone sysLem ls supressed, allowlng
more na+ Lo be excreLed, unLll normal balance ls resLored. 1he mechanlsm for sodlum conservaLlon
ls exLremely efflclenL and Lhe kldney can reduce Lhe concenLraLlon of na+ ln Lhe urlne Lo <3 mmol/l.
Cn Lhe oLher hand, even ln healLh, we are slow Lo excreLe an excess sodlum load, posslbly because
human physlology evolved ln Lhe conLexL of Lhe hoL, low sodlum envlronmenL of Afrlca and has noL
unLll modern Llmes been exposed Lo excesslve sodlum lnLake. 1he response of aLrlal naLrlureLlc
pepLlde Lo fluld lnfuslons seems Lo be relaLed more Lo volume (sLreLchlng of Lhe rlghL aLrlum) Lhan
sodlum load per se.
1he mechanlsm for malnLalnlng sodlum balance may be dlsLurbed ln dlsease, leadlng Lo na+
deflclency or, more commonly, Lo excesslve sodlum reLenLlon, wlLh consequenL oedema and adverse
cllnlcal ouLcome.
"#$#$#%#: ;/('<<.,5 6=89 *)+,-'(./01
Although only a small proportion of the bodys K+ is in the extracellular space, its concentration has
Lo be malnLalned wlLhln narrow llmlLs (3.3-3.3 mmol/l) Lo avold Lhe rlsk of muscular dysfuncLlon or
poLenLlally faLal cardlac evenLs. 1hls ls achleved by exchange of k+ ln Lhe renal Lubules for na+ or P+,

32
allowlng more or less k+ Lo be excreLed. ln Lhe presence of k+ deflclency, P+ lon reabsorpLlon ls
lmpaired, leading to hypokalaemic alkalosis and a decrease in the kidneys ablllLy Lo excreLe a sodlum
load.

S.1.2 athophys|o|og|ca| effects on f|u|d ba|ance
lllness and ln[ury alLer fluld and elecLrolyLe balance and dlsLrlbuLlon needs ln many ways lncludlng:
non-speclflc meLabollc responses Lo sLress (especlally ln Lhe serlously lll or ln[ured),
Changes ln fluld or elecLrolyLe handllng dlrecLly aLLrlbuLable Lo speclflc organ or sysLem
dysfuncLlon or Lhe effecLs of drugs or oLher lv Lheraples used Lo LreaL such problems,
Changes ln fluld or elecLrolyLe handllng due Lo very resLrlcLed recenL food lnLake or malnuLrlLlon.
S.1.2.1 Non-Spec|f|c responses to |||ness and |n[ury
In the 1930s, Cuthbertson
22
descrlbed Lhe meLabollc changes, whlch occur ln response Lo ln[ury
(lncludlng surgery and sepsls), as an lncrease ln meLabollc raLe and proLeln breakdown Lo meeL Lhe
requlremenLs for heallng. 1hese changes were laLer shown Lo be due Lo neuroendocrlne and cyLoklne
changes and Lo occur ln Lhree phases. 1he ebb or shock phase ls brlef and ls modlfled by
resusclLaLlon. 1hls glves way Lo Lhe flow or caLabollc phase, Lhe lengLh and lnLenslLy of whlch
depends on Lhe severlLy of ln[ury and lLs compllcaLlons. As lnflammaLlon subsldes, Lhe convalescenL
anabollc phase of rehablllLaLlon beglns. ln parallel wlLh Lhese meLabollc changes, Lhere are changes
ln waLer and elecLrolyLe physlology. uurlng Lhe flow phase, Lhere ls an lncrease ln AuP, corLlsol and
aldosLerone secreLlon, especlally lf Lhere has been any reducLlon ln blood or LCl volume. 1hese lead
Lo reLenLlon of sodlum and waLer wlLh loss of poLasslum.
121,122
1he normal, lf somewhaL slugglsh,
ablllLy Lo excreLe an excess of sodlum and waLer load ls Lhen furLher dlmlnlshed, leadlng Lo LCl
expanslon and oedema.
38

1hese non-speclflc responses lmply LhaL a degree of ollgurla ls normal ln Lhe conLexL of serlous lllness
or ln[ury,
110
and hence LhaL Lhe presence of ollgurla does noL necessarlly lndlcaLe a need Lo lncrease
admlnlsLraLlon of sodlum and waLer or plasma expanders unless Lhere are also lndlcaLlons of
lnLravascular volume deflclL, e.g. from posLoperaLlve bleedlng. lndeed, sodlum and waLer reLenLlon
after injury can be seen as natures way of trying to protect the ECF and circulating volume at all
cosLs. lL also explalns why slck paLlenLs can be so easlly overloaded wlLh excesslve lv sodlum and
waLer admlnlsLraLlon durlng Lhe flow phase. Slnce waLer as well as sodlum ls reLalned, lL ls also easy
Lo cause hyponaLraemla by glvlng excess waLer or hypoLonlc fluld. lL ls lmporLanL, Lherefore, Lo
admlnlsLer crysLallolds, noL only ln Lhe correcL volume buL also ln Lhe approprlaLe concenLraLlon
especlally as, ln Lhe presence of Lhese responses Lo lllness or ln[ury, Lhe kldneys are unable Lo correcL
for errors ln prescrlblng, even ln Lhe absence of slgnlflcanL acuLe kldney ln[ury (Akl) or oLher renal
paLhology.
1he convalescenL phase of serlous lllness or ln[ury ls noL only characLerlsed by Lhe reLurn of
anabollsm buL also by a reLurnlng capaclLy Lo excreLe any excess sodlum and waLer load LhaL has
been accumulated. These periods have been termed the sodium retention phase and the sodium
diuresis phase of injury.
1ranscap|||ary escape rate of a|bum|n
1he responses Lo serlous lllness of ln[ury also lncludes an lncrease ln Lhe slze of Lhe pores ln Lhe
caplllary membrane and Lhe Lranscaplllary escape raLe of albumln lncreases by up Lo 300 from
abouL 3/h ln healLh Lo 13-13/h.
30
SubsequenL falls ln plasma albumln Lhen reduce C and
lnLravascular volume, whllsL lncreases ln lSl albumln promoLe oedema. 1hls phenomenon can lasL

33
from several hours Lo days. Albumln and oLher plasma proLelns leak ouL from Lhe lnLravascular
comparLmenL lnLo Lhe lnLersLlLlal space and waLer and sodlum also move lnLo LhaL space. 1hls resulLs
ln a neL conLracLlon of Lhe lnLravascular comparLmenL and expanslon of Lhe lnLersLlLlal space. As Lhe
reLurn of albumln Lo Lhe clrculaLlon vla Lhe lymphaLlcs ls unchanged, Lhe neL resulL ls an lnLravascular
hypovolaemla wlLh oedema .
otass|um
oLasslum losses durlng serlous lllness and ln[ury are noL only secondary Lo lncreased excreLlon from
hlgh corLlsol and aldosLerone levels, buL also Lo proLeln and glycogen caLabollsm. As lnLracellular
proLeln ls broken down and lLs consLlLuenL amlno aclds are released from cells, so lnLracellular
negaLlve charges are losL and k+, wlLh lLs balanclng poslLlve charges, passes ouL lnLo Lhe LCl Lo be
excreLed. ln slLuaLlons where caLabollsm ls exLreme and renal funcLlon ls lmpalred, Lhe ouLflow of k+
from the cells may exceed the kidneys capacity to excrete it, causing dangerous hyperkalaemla.
Conversely, ln Lhe convalescenL phase, as neL lnLracellular proLeln and glycogen anabollsm ls
restored, the cells take up again and the patients K+ intake has to be increased to prevent the
developmenL of hypokalaemla and Lo help wlLh Lhe excreLlon of a llkely LoLal excess ln body sodlum.
MalnuLrlLlon ls common ln hosplLal paLlenLs slnce lL ls boLh a cause and a consequence of lllness and
ln[ury. When presenL, lL can have non-speclflc effecLs on fluld and elecLrolyLe sLaLus and handllng
slnce sLarvaLlon ls accompanled by reducLlons ln cell membrane pumplng, wlLh consequenL
movemenL of more sodlum and waLer lnLo cells Lhan usual, whlle slmulLaneously poLasslum,
magneslum, calclum and phosphaLe move ouL of cells and are excreLed by Lhe kldneys. A
malnourlshed lndlvldual Lherefore Lends Lo have a degree of LoLal body sodlum and waLer overload,
coupled wlLh depleLlon of LoLal body poLasslum, phosphaLe, magneslum and calclum. 1hese changes
are ofLen unrecognlzed as plasma levels may remaln normal. 1he mosL lmporLanL problems caused
by Lhese changes ln relaLlon Lo lv fluld and elecLrolyLe prescrlblng, occur when a malnourlshed
lndlvldual ls fed, even lf LhaL feedlng ls only ln Lhe form of glucose from lv lnfuslons. 1he arrlval of
Lhe glucose, coupled wlLh Lhe release of lnsulln lL Lrlggers, can reverse Lhe depresslon of Lhe
membrane pumps, leadlng Lo cellular upLake of poLasslum, phosphaLe, magneslum and calclum wlLh
poLenLlally dangerous falls ln plasma levels.
104
AL Lhe same Llme, Lhere ls a neL movemenL of sodlum
and waLer ouL of cells lnLo Lhe clrculaLlon, a redlsLrlbuLlon change LhaL ls effecLlvely added Lo any lv
flulds belng admlnlsLered buL ls frequenLly unaccounLed for. Slnce malnourlshed lndlvlduals may
have dlmlnlshed cardlac reserve and/or hldden lnfecLlon wlLh hlgh caplllary escape raLes, Lhe
consequence of all Lhe above may be poLenLlally leLhal fluld overload and cardlac lnsLablllLy. 1hese
problems are known as Lhe refeedlng syndrome and speclflc advlce on Lhe prevenLlon and
managemenL of Lhese problems ls provlded ln Lhe nlCL guldellne on nuLrlLlon SupporL ln adulLs.
S.1.2.2 Lffects of spec|f|c organ or system dysfunct|on
Many specific medical conditions can alter the bodys fluid and electrolyte handling, as can many of
Lhe Lheraples used Lo LreaL such problems. ueLalled dlscusslons of such changes are clearly noL
posslble wlLhln Lhls guldance buL examples of lssues LhaL mlghL lnfluence lv fluld prescrlpLlons are
shown ln 1able 10. 1he organ or sysLem dysfuncLlon may be Lhe elLher Lhe prlmary problem LhaL has
broughL Lhe paLlenL lnLo hosplLal or a slgnlflcanL co-morbldlLy)
1ab|e 10: Issues |nf|uenc|ng IV f|u|d prescr|pt|ons
Crgan]System Cons|derat|ons when prescr|b|ng IV f|u|ds
Cardlac dysfuncLlon lncreased vulnerablllLy Lo fluld and sodlum overload wlLh consequenL
congesLlve fallure. oLenLlal for hypokalaemla from dlureLlcs and
renln/angloLensln/aldosLerone acLlvaLlon, or hyperkalemla from poLasslum
sparlng dlureLlcs. Severe cardlac paLlenLs may also have consequenL renal or
llver lmpalrmenL.

34
Crgan]System Cons|derat|ons when prescr|b|ng IV f|u|ds
8enal dlsease lmpalred clearance or excesslve losses of boLh flulds and elecLrolyLes ln boLh
acuLe and chronlc kldney dlsease. ulsordered calclum and phosphaLe handllng
ln chronlc renal fallure.
CasLrolnLesLlnal problems Plgh losses of boLh fluld and elecLrolyLes are seen ln many Cl problems, and
paLlenLs wlLh lleus can sequesLer large volumes of elecLrolyLe rlch fluld.
Llver dlsease very abnormal fluld and elecLrolyLe handllng wlLh a Lendency for marked
sodlum and waLer reLenLlon due Lo complex paLhophyslologlcal changes
lncludlng hyper-aldosLeronlsm. ModeraLe Lo severe renal lmpalrmenL ls seen ln
many paLlenLs Lhe hepaLo-renal syndrome).
8esplraLory dlsease Plgh resplraLory fluld losses buL many paLlenLs are vulnerable Lo fluld overload.
SlAuP common. Cor-pulmonale makes paLlenLs vulnerable Lo venous
clrculaLory overload, someLlmes wlLh hepaLlc congesLlon and dysfuncLlon.
neurology PypoLhalamlc or plLulLary dlsease can severely damage fluld regulaLory
mechanlsms. Plgh concenLraLlon lv sallne ls someLlme admlnlsLered Lo Lry Lo
reduce lnLracranlal pressure.
uermaLology 8urns and oLher exLenslve skln lnflammaLory problems can lead Lo very hlgh
fluld/plasma loss.
Lndocrlne Problems including diabetes mellitus, Addisons disease and SIADH can
markedly alLer fluld and elecLrolyLe handllng.

S.1.2.3 Lffects due to very restr|cted recent food |ntake or ma|nutr|t|on.
Some degree of sLarvaLlon ls common ln lndlvlduals who are lll or ln[ured, especlally Lhose who mlghL
need lv fluld Lherapy. 8educed or absenL food lnLake leads qulLe swlfLly Lo alLeraLlons ln cell funcLlon
whlch lnclude a reducLlon ln membrane pumplng so LhaL poLasslum leaks ouL of Lhe cells and ls Lhen
losL ln Lhe urlne, whlle sodlum and waLer move lnLo cells. Malnourlshed lndlvlduals, and even Lhose
who are overwelghL buL have a hlsLory of recenL sLarvaLlon, may Lherefore have lower Lhan expecLed
LoLal body poLasslum and hlgher LoLal salL and waLer conLenL. 1hls makes Lhem poLenLlally
vulnerable Lo fluld mlsmanagemenL, especlally slnce malnuLrlLlon can also cause a decrease ln
cardlac reserve, a decrease ln renal capaclLy Lo clear salL and waLer, and deflclencles of speclflc
vlLamlns. lurLhermore. 1hls vulnerablllLy ls furLher enhanced lf slgnlflcanL feedlng ls lnLroduced aL
Lhe same Llme as lv flulds wlLhy Lhe poLenLlal for lnduclng low phosphaLe, poLasslum or magneslum
as parL of Lhe refeedlng syndrome (see Culdance of 8efeedlng syndrome ln nlCL CC32 nuLrlLlon
SupporL ln AdulLs).

S.1.3 1he c||n|ca| approach to assess|ng IV f|u|d needs
1he mosL approprlaLe meLhod of fluld and elecLrolyLe admlnlsLraLlon ls Lhe slmplesL, safesL and
effecLlve. 1he oral rouLe should be used whenever posslble and lv flulds can usually be avolded ln
paLlenLs who are eaLlng and drlnklng. 1he posslblllLy of enLeral Lube admlnlsLraLlon should also be
consldered lf safe oral lnLake ls compromlsed buL Lhere ls enLeral Lube-accesslble Cl funcLlon.
llgure 3 illustrates the 4 Rs that underpin the clinical approach to deciding IV fluid needs:
8esusclLaLlon, 8ouLlne malnLenance, 8eplacemenL and 8edlsLrlbuLlon. 1here ls also a 5th R for
8eassessmenL.

33
I|gure 3: 1he 4 ks - kesusc|tat|on, kout|ne ma|ntenance, kep|acement and ked|str|but|on.
S8
A
Sth k keassessment |s a|so a cr|t|ca| e|ement of care.

5ootce. AJopteJ ftom Jloqtom(copytlqbt obtoloeJ) by ulleep lobo
58

Clinical considerations around the 4Rs can be complex and so decisions on the optimal amount,
composlLlon and raLe of lv fluld admlnlsLraLlon musL be based on careful, lndlvldual paLlenL
assessmenL. Powever, Lhe cllnlcal prlnclples underlylng Lhese declslons can be approached as a
serles of quesLlons.
Does my pat|ent need IV f|u|d resusc|tat|on?
1hls ls Lhe flrsL quesLlon, slnce urgenL lv fluld Lherapy ls a crlLlcal elemenL ln Lhe managemenL of
mosL shocked paLlenLs. lor deLalls on prescrlblng for rouLlne malnLenance see secLlon lnLravenous
fluld Lherapy for fluld resusclLaLlon.
Can my pat|ent meet f|u|d and e|ectro|yte needs by the ora| or entera| route?
1he unnecessary use of lv flulds should be avolded. When Lhey are needed, Lhey should be sLopped
as soon as posslble.
What is my patients current fluid and electrolyte status?
AssessmenL musL be lnformed by all lnformaLlon avallable lncludlng a focussed hlsLory and
examlnaLlon along wlLh resulLs of cllnlcal monlLorlng (e.g. nLWS, fluld balance and body welghL) and
laboraLory resulLs. lor deLalls on assessmenL and monlLorlng, see secLlon AssessmenL and monlLorlng
of paLlenLs recelvlng lnLravenous fluld Lherapy.

36
What are my patients routine maintenance needs for fluid and electrolytes?
1he average person requlres 23-30 ml/kg waLer per day and abouL 1 mmol/kg of na+ and k+. lor
deLalls on prescrlblng for rouLlne malnLenance see secLlon lnLravenous fluld Lherapy for rouLlne
malnLenance.
Does my pat|ent have ex|st|ng f|u|d or e|ectro|yte def|c|ts or abnorma| ongo|ng |osses?
All lv fluld prescrlpLlons should add enough fluld and/or elecLrolyLes Lo correcL any exlsLlng deflclLs or
meeL abnormal ongolng losses, Lo esLlmaLes of rouLlne malnLenance requlremenLs.
8ecommendaLlons and more deLalls on fluld prescrlpLlon for replacemenL are covered ln Lhe secLlon
lnLravenous fluld Lherapy for replacemenL and redlsLrlbuLlon.
Does my pat|ent have prob|ems w|th |nterna| red|str|but|on of f|u|d or other f|u|d hand||ng |ssues
from e|ther the|r pr|mary prob|em or s|gn|f|cant co-morb|d|t|es?
lv fluld prescrlpLlons musL alm Lo accounL for boLh non-speclflc responses Lo lllness or ln[ury
descrlbed ln SecLlon 3.1.2 as well as Lhe more complex problems of fluld dlsLrlbuLlon or handllng
caused by speclflc organ or sysLem dysfuncLlon and/or malnuLrlLlon. 8ecommendaLlons and more
deLalls on Lhese lssues are also covered ln Lhe secLlon lnLravenous fluld Lherapy for replacemenL and
redlsLrlbuLlon.
ConslderaLlon of all quesLlons above allows esLlmaLes of Lhe LoLal volume of lv fluld and amounLs of
elecLrolyLes LhaL should be glven, before decldlng on Lhe besL raLe aL whlch Lo admlnlsLer Lhe flulds.
CfLen, LhaL raLe needs Lo be slow ln order noL Lo overload Lhe clrculaLlon or Lo cause acuLe
elecLrolyLe problems, slnce Llme ls needed for Lransmembrane (l.e. LCl/lCl) physlologlcal
equlllbraLlons Lo occur. 1he besL lv fluld (or mlx of flulds) Lo use can Lhen be chosen alLhough, before
compleLlng Lhe prescrlpLlon, allowance musL be made for any fluld and elecLrolyLes lnLake from oLher
sources. 1hese lnclude any food and drlnks, enLeral Lube provlslon and oLher lv Lheraples. 8lood or
blood producLs, ln parLlcular, conLaln large amounLs of elecLrolyLes as do some lv drugs, especlally
Lhose glven ln larger volume dlluenLs, several Llmes a day. aLlenLs on arLlflclal parenLeral or enLeral
nuLrlLlon usually recelve adequaLe fluld and elecLrolyLes from Lhelr feed Lo meeL aL leasL rouLlne
malnLenance needs and prescrlpLlon of unnecessary addlLlonal lv flulds ln such paLlenLs ls a common
mlsLake.
S.1.4 1he propert|es of ava||ab|e IV f|u|ds
Many dlfferenL crysLallolds, arLlflclal collolds and albumln soluLlons are avallable for lv fluld Lherapy.
1he alm ls Lo meeL esLlmaLes of LoLal fluld and elecLrolyLe requlremenLs. 1here are LheoreLlcal
advanLages Lo glvlng a collold lnsLead of a crysLallold when resusclLaLlng Lhe hypovolaemlc paLlenL
because collold-based flulds generally remaln for longer ln Lhe clrculaLlon. CrysLallolds are dlsLrlbuLed
LhroughouL Lhe LCl and LradlLlonal Leachlng ls LhaL Lhelr lnfuslon has relaLlvely llmlLed and LranslenL
effecLs on plasma volume. Powever, such conslderaLlons are based on daLa derlved from sLudles
underLaken ln euvolaemlc human volunLeers who have no lllness-lnduced abnormallLles ln fluld
dlsLrlbuLlon and caplllary permeablllLy, and ln hypovolaemlc paLlenLs, crysLallolds have much beLLer
lnLravascular reLenLlon Lhan Lhese sLudles have suggesLed. 1he acLual beneflLs, lf any, of collolds over
crysLallolds when lnLravascular volume expanslon ls requlred are Lherefore unclear.
A revlew of all Lhe avallable lv flulds ln Lhe uk ls beyond Lhe remlL of Lhls guldance buL undersLandlng
Lhe composlLlon and properLles of some of Lhose more commonly used provldes much of Lhe
undersLandlng needed Lo prescrlbe any fluld approprlaLely. lurLhermore, lL helps undersLandlng of
Lhe lssues ln fluld prescrlblng whlch are of debaLe ln currenL pracLlce.

37
See Appendlces .1 and .2 for deLalls on Lhe composlLlon of commonly used crysLallolds and collolds
whlch have been revlewed as parL of Lhe evldence for Lhls guldellne. A brlef descrlpLlon of some of
Lhe avallable flulds hlghllghLlng Lhelr properLles and poLenLlal pros and cons of Lhelr usage ls deLalled
below.
Isoton|c sa||ne
Sodlum chlorlde 0.9 wlLh or wlLhouL addlLlonal poLasslum ls one of Lhe mosL commonly used lv
flulds ln uk pracLlce. Powever, quesLlons have been ralsed ln relaLlon Lo lLs approprlaLe use. As wlLh
all crysLallolds, sodlum chlorlde 0.9 ls dlsLrlbuLed LhroughouL Lhe LCl and lnfuslon usually has a
more LranslenL effecL on plasma volume Lhan collolds. 1radlLlonally sodlum chlorlde 0.9 lnfuslon
has been consldered Lo expand blood volume by only a quarLer Lo a Lhlrd of Lhe volume lnfused, Lhe
remalnder belng sequesLered ln Lhe lnLersLlLlal space.
18,39,62,89
ln pracLlce, for Lhe reasons glven
above, lnLravascular reLenLlon of sodlum chlorlde 0.9 ls llkely Lo beLLer Lhan Lhls ln hypovolaemlc
and sLressed paLlenLs. 1heoreLlcally, use of sodlum chlorlde 0.9 for plasma volume expanslon mlghL
cause more oedema Lhan would occur wlLh use of a collold buL such a dlfference ls seldom reallsed ln
pracLlce.
ln addlLlon, lL ls also posslble LhaL a slgnlflcanL albelL lesser degree of unnecessary sodlum and waLer
reLenLlon, ls a problem when sodlum chlorlde 0.9 ls used for rouLlne malnLenance. 1he normal dally
requlremenLs of sodlum are only 70-100mmol buL one llLre of normal sallne conLalns 134mmol, so lL
ls easy Lo glve an excess. 1hls wlll Lhen need Lo be excreLed buL Lhe ablllLy Lo clear a soluLe load ls
llmlLed even ln healLh and may be furLher lmpalred durlng lllness or ln[ury.
AnoLher lssue LhaL ralses quesLlons abouL Lhe wldespread usage of sodlum chlorlde 0.9 ls Lhe facL
LhaL lL produces a degree of hyperchloraemla due Lo lLs hlgh chlorlde conLenL compared wlLh plasma.
1hls ln Lurn could lead Lo slgnlflcanL reducLlons ln renal blood flow and glomerular fllLraLlon
18
as well
as hyperchloraemlc acldosls, gasLrolnLesLlnal mucosal acldosls and lleus.
39

Some Cl fluld losses and occaslonally renal losses are very hlgh ln sodlum chlorlde and hence sodlum
chlorlde 0.9 use may well be approprlaLe ln slLuaLlons where Lhere are ongolng hlgh sodlum losses
or deflclLs of sodlum, chlorlde and waLer from earller losses. lL ls lmporLanL Lo recognlze, however,
LhaL many of Lhese losses wlll be hlgh ln poLasslum, calclum and magneslum and so a balanced
crysLallold mlghL have advanLages over sodlum chlorlde 0.9 wlLh added poLasslum.
8a|anced crysta||o|d so|ut|ons
8alanced crysLallolds are also dlsLrlbuLed LhroughouL Lhe LCl and are Lherefore of slmllar efflcacy Lo
sodlum chlorlde 0.9 ln Lerms of plasma volume expanslon. Powever, Lhey do have LheoreLlcal
advanLages ln LhaL Lhey conLaln somewhaL less sodlum and slgnlflcanLly less chlorlde, and Lhey may
already have some poLasslum, calclum and magneslum conLenL. 1he use of balanced crysLallolds
could Lherefore have advanLages over sodlum chlorlde 0.9 when used for resusclLaLlon or rouLlne
malnLenance and preparaLlons wlLh more specialized resuscitation and maintenance versions, wlLh
conLenL Lallored Lo meeL more closely Lhe LheoreLlcal requlremenLs for Lhese dlfferenL
clrcumsLances, are llkely Lo become lncreaslngly avallable ln fuLure. 8alanced soluLlons conLalnlng
lacLaLe or oLher buffers mlghL also granL advanLages ln slLuaLlons of slgnlflcanL acldosls whlch ls ofLen
seen when resusclLaLlon ls needed.
G|ucose and g|ucose sa||nes
SoluLlons such as 3 glucose and glucose/ sallne wlLh or wlLhouL poLasslum are noL meanL for
resusclLaLlon or replacemenL of elecLrolyLe rlch losses. 1hey are however, useful means of provldlng
free waLer for, once Lhe glucose ls meLabollsed, Lhey are largely dlsLrlbuLed Lhrough LoLal body waLer
wlLh very llmlLed and LranslenL effecLs on blood volume. 1hey should Lherefore be useful ln

38
correcLlng or prevenLlng slmple dehydraLlon, and Lhe admlnlsLraLlon of approprlaLe glucose sallne
wlLh poLasslum soluLlons may provlde a good means of meeLlng rouLlne malnLenance needs.
Powever, Lhe use of Lhese flulds wlll lncrease rlsks of slgnlflcanL hyponaLraemla, especlally lf Loo
much fluld ls glven or Lhe lnfuslon ls glven Loo rapldly. Such rlsks are parLlcularly hlgh ln chlldren, Lhe
elderly, paLlenLs on dlureLlcs and Lhose wlLh SlAuP problems whlch are seen qulLe frequenLly ln
hosplLallzed paLlenLs. lL ls also lmporLanL Lo appreclaLe LhaL Lhe calorle conLenL of 3 glucose ls very
low and provldes llLLle conLrlbuLlon Lo Lhe nuLrlLlon supporL whlch may be needed ln some paLlenLs.
Synthet|c Co||o|ds
SynLheLlc collolds conLaln non-crysLalllne large molecules or ulLramlcroscoplc parLlcles dlspersed
Lhrough a fluld whlch ls usually a crysLallold. 1he colloldal parLlcles are large enough LhaL Lhey should
be reLalned wlLhln Lhe clrculaLlon and so exerL an oncoLlc pressure across caplllary membranes. ln
Lheory, collolds LhaL are lso-oncoLlc wlLh plasma should Lherefore expand blood volume by Lhe
volume lnfused buL ln pracLlce, Lhe volume expanslon achleved ls closer Lo 60-80
7,62
and lL may be
much less ln slcker paLlenLs wlLh hlgh Lranscaplllary escape raLes. 1he acLual advanLages of collolds
over crysLallolds when used for elLher lnLravascular volume expanslon ln paLlenLs requlrlng flulds for
resusclLaLlon or Lo help wlLh Lhe resoluLlon of oedemaLous redlsLrlbuLlon problems are Lherefore
uncerLaln and wlLh some preparaLlons, Lhere have been concerns LhaL any poLenLlal advanLages may
be offseL by problems lncludlng renal dysfuncLlon or dlsLurbed coagulaLlon. lL ls lmporLanL Lo noLe,
LhaL older preparaLlons of hydroxyeLhyl sLarch are suspended ln sodlum chlorlde 0.9 whlle some
newer preparaLlons are suspended ln balanced soluLlons whlch should make Lhem more
physlologlcal. neverLheless, all currenLly avallable seml-synLheLlc collolds conLaln 140-134 mmol
sodlumwhlch could conLrlbuLe Lo poslLlve sodlum balance ln slcker paLlenLs ln Lhe same way as for
sodlum chlorlde 0.9, alLhough collolds do conLaln less chlorlde.
ln Lhe uk, synLheLlc collolds commonly used ln admlsslon and general ward areas lnclude,
hydroxyeLhyl sLarch, succlnylaLed gelaLln, urea-llnked gelaLln , whllsL dexLrans and hlgh molecular
welghL penLa- and hexa-sLarches are used seldom or noL aL all.
A|bum|n so|ut|ons
As wlLh synLheLlc collolds, lnfuslon of albumln soluLlons mlghL LheoreLlcally granL poLenLlal beneflLs
from beLLer lnLravascular volume expanslon alLhough cosLs would be very hlgh. ConcenLraLed (20-
23) sodlum poor albumln could also be valuable ln fluld redlsLrlbuLlon problems especlally when
oedema from LoLal sodlum and waLer overload ls presenL ln posL- severe lllness or ln[ury paLlenLs
who sLlll have low plasma volumes.
3,4,34
Albumln ls also used ln some paLlenLs wlLh hepaLlc fallure and
asclLes alLhough lLs use ln Lhls seLLlng ls beyond Lhe scope of Lhls guldance.
S.1.S kecommendat|ons based on f|u|d prescr|b|ng pr|nc|p|es
kecommendat|ons
1he assessment and management of pat|ents' f|u|d and e|ectro|yte needs
|s fundamenta| to good pat|ent care.
1. Assess and manage pat|ents' f|u|d and e|ectro|yte needs as part of every
ward rev|ew. rov|de |ntravenous (IV) f|u|d therapy on|y for pat|ents
whose needs cannot be met by ora| or entera| routes, and stop as soon
as poss|b|e.
2. Sk|||ed and competent hea|thcare profess|ona|s shou|d prescr|be and
adm|n|ster IV f|u|ds, and assess and mon|tor pat|ents rece|v|ng IV f|u|ds
(see recommendat|ons 26-28).

39
3. When prescr|b|ng IV f|u|ds, remember the S ks: kesusc|tat|on, kout|ne
ma|ntenance, kep|acement, ked|str|but|on and keassessment.
4. Inc|ude the fo||ow|ng |nformat|on |n IV f|u|d prescr|pt|ons:
1he type of f|u|d to be adm|n|stered.
1he rate and vo|ume of f|u|d to be adm|n|stered.
S. at|ents shou|d have an IV f|u|d management p|an, wh|ch shou|d |nc|ude
deta||s of:
the f|u|d and e|ectro|yte prescr|pt|on over the next 24 hours
the assessment and mon|tor|ng p|an.
In|t|a||y, the IV f|u|d management p|an shou|d be rev|ewed by an expert
da||y. IV f|u|d management p|ans for pat|ents on |onger-term IV f|u|d
therapy whose cond|t|on |s stab|e may be rev|ewed |ess frequent|y.
6. When prescr|b|ng IV f|u|ds and e|ectro|ytes, take |nto account a|| other
sources of f|u|d and e|ectro|yte |ntake, |nc|ud|ng any ora| or entera|
|ntake, and |ntake from drugs, IV nutr|t|on, b|ood and b|ood products.
7. at|ents have a va|uab|e contr|but|on to make to the|r f|u|d ba|ance. If a
pat|ent needs IV f|u|ds, exp|a|n the dec|s|on, and d|scuss the s|gns and
symptoms they need to |ook out for |f the|r f|u|d ba|ance needs ad[ust|ng.
If poss|b|e or when asked, prov|de wr|tten |nformat|on (for examp|e,
NICL's Informat|on for the pub||c), and |nvo|ve the pat|ent's fam||y
members or carers (as appropr|ate).

8elaLlve values of
dlfferenL ouLcomes
MorLallLy and morbldlLy were ldenLlfled as Lhe mosL crlLlcal ouLcomes. 1he oLher
ouLcome consldered lmporLanL for declslon maklng was lengLh of sLay ln hosplLal.
1rade-off beLween
cllnlcal beneflLs and
harms
Clven Lhe morbldlLy assoclaLed wlLh ln[udlclous prescrlpLlon of lnLravenous flulds,
parLlcularly Lhe consequences of fluld overload (e.g. pulmonary oedema), Lhe CuC
agreed LhaL emphasls should be placed on careful assessmenL and reassessmenL of
Lhe need for lnLravenous fluld Lherapy.
Lconomlc
conslderaLlons
1here was no cosL-effecLlveness evldence. Powever, Lhe prlnclple of only uslng
lnLravenous flulds when necessary and sLopplng Lhem as early as posslble ls llkely Lo
be hlghly cosL-effecLlve, slnce lL should boLh reduce Lhe cosL of admlnlsLerlng
unnecessary lv flulds and should reduce Lhe cosL of LreaLlng avoldable fluld overload
as well as lmprovlng oLher cllnlcal ouLcomes.
CuallLy of evldence 1he CuC drafLed Lhese recommendaLlons based on physlologlcal, paLhophyslologlcal
and cllnlcal prlnclples uslng consensus.
CLher
conslderaLlons
lL was acknowledged LhaL LhaL lL was noL posslble Lo underLake cllnlcal evldence
revlews for cerLaln areas of Lhe guldellne and Lhe prlnclples of fluld prescrlblng was
one such excepLlon Lo Lhe normal sysLemaLlc revlew process.
Pere, Lhe CuC Look lnLo conslderaLlon Lhe prlnclples of physlology and
paLhophyslology of lnLravenous flulds and oLher accepLed sLandard cllnlcal guldance
and drafLed recommendaLlons based on experL consensus ln a formaL lnLended Lo be
useful Lo a cllnlclan. 1he CuC dlscussed and agreed LhaL as Lhe recommendaLlons
were fundamenLal Lo fluld prescrlblng, Lhe wordlng of Lhe recommendaLlons should
reflecL Lhe sLrengLh of Lhe recommendaLlons.

60
Cllnlcal assessmenL and dlagnosls of Lhe volume sLaLus of Lhe paLlenL was [udged Lo
be key Lo prescrlblng safe, approprlaLe lv fluld Lherapy for a paLlenL. 1he CuC
dlscussed Lhe four sLaLes where lnLravenous fluld was glven, LhaL ls, (l) resusclLaLlon,
(ll) rouLlne malnLenance, lll) replacemenL of exlsLlng deflclLs or abnormal ongolng
losses and lv) complex lssues of redlsLrlbuLlon. 1hey agreed LhaL clear ldenLlflcaLlon of
Lhe reason for glvlng lv fluld Lherapy should always precede admlnlsLraLlon.
8ecommendaLlons 3 and 3 were ldenLlfled as key prlorlLles for lmplemenLaLlon by Lhe
CuC as Lhey have a hlgh lmpacL on ouLcomes LhaL are lmporLanL Lo paLlenLs and have
a hlgh lmpacL ln reduclng varlaLlon ln care and ouLcomes.

S.2 Use of a|gor|thms |n IV f|u|d therapy
An approach Lo lv fluld prescrlblng based on physlologlcal, paLhophyslologlcal and cllnlcal prlnclples
can poLenLlally be descrlbed ln proLocols and algorlLhms. Slnce lL ls well recognlzed LhaL adopLlon of
proLocol- drlven care has lmproved cllnlcal sLandards ln oLher areas, a revlew of Lhe cllnlcal and cosL
effecLlveness of any publlshed cllnlcal algorlLhms or deflned proLocols for assessmenL, monlLorlng
and/or managemenL of lv fluld prescrlpLlons was underLaken.
S.2.1 kev|ew quest|on
What |s the c||n|ca| and cost effect|veness of c||n|ca| a|gor|thms or def|ned protoco|s for the
assessment, mon|tor|ng and]or management of |ntravenous f|u|d and e|ectro|yte requ|rement |n
hosp|ta||sed adu|t pat|ents?
1he ob[ecLlve of Lhls revlew was Lo compare ouLcomes ln hosplLallsed paLlenLs who recelved lv fluld
Lherapy as parL of a proLocol Lo Lhose who recelved lv flulds wlLhouL any proLocol.
lor Lhe revlew proLocol see C.1, Appendlx C.
S.2.2 C||n|ca| ev|dence
We searched for randomlsed conLrolled Lrlals comparlng Lhe effecLlveness of uslng algorlLhms or
deflned proLocols compared Lo no proLocols or usual care for Lhe managemenL of hosplLallsed adulL
paLlenLs on lv fluld Lherapy.
no Cochrane revlews relevanL Lo Lhe revlew quesLlon were ldenLlfled.
Slx randomlsed conLrolled sLudles were ldenLlfled.
9,32,40,33,78,91
1he sLudles lncluded dlfferenL
populaLlons and seLLlngs, for example, surglcal paLlenLs, sepsls paLlenLs, burn paLlenLs and paLlenLs ln
lnLenslve care unlLs. Some of Lhese sLudles dld noL meeL Lhe crlLerla seL ln Lhe proLocol for our LargeL
populaLlon, buL ln vlew of Lhe pauclLy of dlrecLly relevanL llLeraLure daLa, Lhey were sLlll exLracLed
and exLrapolaLed Lo our LargeL groups, wlLh Lhe evldence downgraded for lndlrecLness (see cllnlcal
evldence proflle ln 1able 12).
All 6 sLudles compared proLocol dlrecLed care wlLh no proLocol. 1he componenLs of Lhe proLocols
varled across Lhe sLudles. 1hree sLudles focused on early goal dlrecLed Lherapy.
48,33,91
1able 11 deLalls
Lhe summary characLerlsLlcs of lncluded sLudles.


61
1ab|e 11: Summary of |nc|uded stud|es - rotoco| vs. no protoco|
S1UD CULA1ICN IN1LkVLN1ICN CCMAkISCN CU1CCMLS
8enes eL al.
2010
9

Plgh rlsk paLlenLs
scheduled for
ma[or abdomlnal
surgery
roLocol:
lnLraoperaLlve,
conLlnuous
monlLorlng of
haemodynamlc
sLaLus uslng onllne
analysls of arLerlal
waveform.
erloperaLlve:
monlLorlng of sLroke
volume and cardlac
lndex
no proLocol:
AnaesLheslologlsL
free Lo glve
addlLlonal flulds
(crysLallold or
collold) or use
vasoacLlve
subsLances Lo
malnLaln blood
pressure, dluresls
and cenLral venous
pressure
MorLallLy, lengLh of sLay
ln hosplLal, morbldlLy
and compllcaLlons
(sepsls, renal
compllcaLlons)
Can eL al.
2002
32

aLlenLs
undergolng ma[or
elecLlve surgery
wlLh an
anLlclpaLed blood
loss of >300mL
roLocol-
8oluses of fluld
gulded by algorlLhm
uoppler esLlmaLlons
of sLroke volume.
no proLocol:
SLandard care
LengLh of
sLay(hosplLallsaLlon),
acuLe renal dysfuncLlon,
resplraLory supporL for
>24 hours,
cardlovascular
compllcaLlons
Popklns eL
al. 1983
40

PypoLenslve
adulLs ln surglcal
emergency
deparLmenL
roLocol for Lhe flrsL
hour of resusclLaLlon
of emergency
admlsslons
no proLocol

All cause morLallLy,
lengLh of sLay ln
hosplLal, resusclLaLlon
Llme, lCu days,
compllcaLlons relaLed
Lo shock and
resusclLaLlon
Lln eL al.
2006
33

Sepsls wlLh organ
fallure, shock
Coal dlrecLed
Lherapy:
Cv of 8-12mmPg
Mean arLerlal
pressure 65mmHg
no proLocol:
SLandard Lherapy
ad[usLed by a
physlclan
All cause morLallLy,
LoLal lengLh of sLay,
lengLh of lCu sLay,
duraLlon of mechanlcal
venLllaLlon, sepsls
assoclaLed renal fallure
nobleLL eL al.
2006
78

LlecLlve
colorecLal
resecLlon
lnLra-operaLlve
and posL-
operaLlve care
AddlLlonal flulds
boluses glven Lo
malnLaln
descendlng aorLlc
correcLed flow
Llme > 0.33s
sLroke volume
SLandard care
lluld admlnlsLered
by Lhe anaesLheLlsL
based on
lnLraoperaLlve losses
and sLandard
haemodynamlc
parameLers.
MorLallLy, LoLal posL-
operaLlve sLay, posL-
operaLlve compllcaLlons
requlrlng
pharmacologlcal
managemenL/ surglcal/
endoscoplc/
radlologlcal
lnLervenLlon, llfe
LhreaLenlng
compllcaLlons requlrlng
crlLlcal care
8lvers eL al.
2001
91

aLlenLs wlLh
sepsls
Larly goal dlrecLed
Lherapy
no proLocol:
SLandard Lherapy
All cause morLallLy, 28
day morLallLy, 60 day
morLallLy, lengLh of
sLay, quallLy of llfe,
mean duraLlon of
mechanlcal venLllaLlon.

62
Slnce Lhe evldence came from dlfferenL populaLlons and seLLlngs, poollng of resulLs across all sLudles
was noL consldered Lo be approprlaLe. 1he evldence ls Lherefore presenLed wlLh respecL Lo Lhe
dlfferenL populaLlon sub-groups as ldenLlfled ln Lhe revlew proLocol.
See flow dlagram for cllnlcal arLlcle selecLlon ln !.1, Appendlx ! and economlc arLlcle selecLlon k.1,
Appendlx k, foresL ploLs ln C.1, Appendlx C, cllnlcal evldence Lables ln L.1, Appendlx L, economlc
evldence Lables ln l.1, Appendlx l and excluded sLudles llsL ln P.1, Appendlx, P.

1ab|e 12: C||n|ca| ev|dence prof||e: rotoco| vs. No protoco|
ua||ty assessment No. of pat|ents Lffect s|ze
ua||ty
Importan
ce
No of
stud|e
s Des|gn
k|sk of
b|as Incons|stency
Ind|rect
ness
Imprec|s|
on Cther rotoco| No protoco|
ke|at|ve
effect
(9S CI) Abso|ute effect
Morta||ty
Seps|s pat|ents
S3,91

2 randomlsed
Lrlals
serlous
(a)
no serlous
lnconslsLency
serlous
lndlrecL
ness(b)
no serlous
lmpreclslon

none 94/238
(39.3)
139/249
(33.8)
88 0.71
(0.39 Lo
0.86)
162 fewer per 1000
(from 78 fewer Lo 229
fewer)
LCW C8l1lCAL
Intra-operat|ve pat|ents
9,78

2 randomlsed
Lrlals
serlous
(c)
no serlous
lnconslsLency
serlous
(b)
very serlous (d) none 1/114
(0.9)
3/114
(2.6)
88 0.43
(0.06 Lo
2.83)
13 fewer per 1000 (from
23 fewer Lo 49 more)
vL8?
LCW
C8l1lCAL
1rauma]shock pat|ents
40

1 randomlsed
Lrlals
serlous
(e)
no serlous
lnconslsLency
serlous
lndlrecL
ness(b)
very serlous (d) none 39/212
(18.4)
73/391
(19.2)
88 0.96
(0.68 Lo
1.36)
vL8?
LCW
C8l1lCAL
Length of stay |n hosp|ta|
Seps|s pat|ents
S3,91

2 randomlsed
Lrlals
serlous
(a)
no serlous
lnconslsLency
serlous
lndlrecL
ness(b)
very serlous (d) none 238 249 - Mu 2.09 lower (3.16
lower Lo 0.98 hlgher)
vL8?
LCW
lMC81A
n1
32

1 randomlsed
Lrlals
serlous
(f)
no serlous
lnconslsLency
serlous
lndlrecL
ness(b)
no serlous
lmpreclslon
none 30 30 - Mu 2 lower (3.18 Lo 0.82
lower)
LCW lMC81A
n1
ost-operat|ve pat|ents
48

1 randomlsed
Lrlals
very
serlous
(g)
no serlous
lnconslsLency
serlous
lndlrecL
ness(b)
no serlous
lmpreclslon
none 13 13 - Mu 3 lower (4.22 Lo 1.78
lower)
vL8?
LCW
lMC81A
n1
1rauma]Shock pat|ents
40

1 randomlsed
Lrlals
serlous
(e)
no serlous
lnconslsLency
serlous
lndlrecL
very serlous (d) none 173 316 - Mu 1 lower (4 lower Lo 2
hlgher)
vL8?
LCW
lMC81A
n1

ua||ty assessment No. of pat|ents Lffect s|ze
ua||ty
Importan
ce
No of
stud|e
s Des|gn
k|sk of
b|as Incons|stency
Ind|rect
ness
Imprec|s|
on Cther rotoco| No protoco|
ke|at|ve
effect
(9S CI) Abso|ute effect
ness(b)
Length of stay |n |ntens|ve care un|t
1rauma]Shock pat|ents
40

1 randomlsed
Lrlals
serlous
(e)
no serlous
lnconslsLency
serlous
lndlrecLness(b)
very
serlous
(d)
none 173 316 - Mu 0 hlgher (1.81 lower
Lo 1.81 hlgher)
vL8?
LCW
lMC81A
n1
48

1 randomlsed
Lrlals
very
serlous
(g)
no serlous
lnconslsLency
serlous
lndlrecLness(b)
no
serlous
lmprecls
lon
none 13 13 - Mu 2.3 lower (3.32 Lo
1.28 lower)
vL8?
LCW
lMC81A
n1
kena| comp||cat|ons
Seps|s pat|ents
S3

1 randomlsed
Lrlals
serlous
(a)
no serlous
lnconslsLency
serlous
lndlrecLness(b)
serlous
(h)
none 42/108
(38.9)
64/116(33.2
)
88 0.70
(0.33 Lo
0.94)
166 fewer per 1000
fewer)
vL8?
LCW
lMC81A
n1
9,32

2 randomlsed
Lrlals
serlous
(c, f)
no serlous
lnconslsLency
serlous
lndlrecLness(b)
very
serlous
(d)
none 3/110
(4.3)
3/117
(2.7)
88 1.67 (0.41
Lo 6.73)
18 more per 1000 (from
vL8?
LCW
lMC81A
n1
48

1 randomlsed
Lrlals
very
serlous
(g)
no serlous
lnconslsLency
serlous
lndlrecLness(b
)
very
serlous (d)
none 1/13
(6.7)
1/13
(6.7)
88 1 (0.07 Lo
14.33)
vL8?
LCW
lMC81A
n1
(o) Ooe stoJy wos oo opeo lobel stoJy
5J
ooJ tbe follow op lo tbe secooJ stoJy wos oocleot
91
, Also tbls stoJy boJ >10X Jtopoot tote.
(b) 5toJles wete lo loJltect popolotloos wblcb moy oot be tepteseototlve of oll popolotloos oJJtesseJ lo tbe qolJelloe.
(c) Ooe stoJy wos pottlolly blloJeJ ooJ boJ >10X Jtopoot tote
9
ooJ lo tbe secooJ stoJy, tooJomlsotloo ooJ ollocotloo cooceolmeot wete oocleot(Noblett2006)
(J) cooflJeoce lotetvol ctosses botb Mlus
(e) 1be stoJy pottlclpoots JlJ oot oJbete to tbe ptotocol ot oll tlmes, l11 ooolysls oot cottleJ oot, leoqtb of follow op oot stoteJ
40

(f) Aooestbetlst oot blloJeJ, lotleots lo ptotocol qtoop tecelveJ slqolflcootly mote 6Xn5 tboo tbe stooJotJ cote qtoop, ulffeteot types of flolJ oJmlolsteteJ lo botb qtoops
J2

(q) 5moll somple slze, ooblloJeJ stoJy, oo l11 ooolysls
48

(b) cooflJeoce lotetvol ctosses ooe Mlu
.

63
S.2.3 Lconom|c ev|dence
1hree sLudles were lncluded LhaL made relevanL comparlsons. 1hese are summarlsed ln Lhe
economlc evldence proflle below (1ab|e 13 and 1ab|e 14)
See also Lhe full sLudy evldence Lable ln l.1, Appendlx l.
1ab|e 13: rotoco| vs No rotoco| Lconom|c Lv|dence
Study App||cab|||ty L|m|tat|ons Cther comments
!ones
46

arLlally Appllcable
(a)
oLenLlally Serlous
LlmlLaLlons (b)
Analysls conducLed from a uS
perspecLlve
Shorr
101

arLlally
Appllcable(a)
oLenLlally Serlous
LlmlLaLlons(c)
perspecLlve
1almor
107

arLlally Appllcable(a,
d)
oLenLlally Serlous
LlmlLaLlons(e)
perspecLlve
(o) uolteJ 5totes settloq.
(b)Ootcomes JlJ oot locloJe oll flolJ teloteJ oJvetse eveots, Obsetvotloool evlJeoce wblcb ls sobject to coofoooJloq,
ptotocol JlJ oot excloslvely moooqe lv flolJ tbetopy, looq tetm costs oot occoooteJ fot becoose potleots wete oot followeJ
beyooJ bospltol Jlscbotqe, oocettoloty lo compooeots of ooo ptotocollseJ cote wblcb mokes lotetptetotloo of tesolts
Jlfflcolt.
(c)Obsetvotloool evlJeoce wblcb ls sobject to coofoooJloq, Ootcomes JlJ oot locloJe oll flolJ teloteJ oJvetse eveot, looq
tetm costs oot occoooteJ fot Joe to lock of Joto , ptotocol JlJ oot excloslvely moooqe lv flolJ tbetopy, oocettoloty lo
compooeots of ooo ptotocollseJ cote wblcb mokes lotetptetotloo of tesolts Jlfflcolt.
(J)ltotocol JlJ oot excloslvely moooqe lv flolJ tbetopy,
(e)Ootcomes JlJ oot locloJe oll flolJ teloteJ oJvetse eveots, moooqemeot ptotocol oot speclflc to lottoveooos flolJ tbetopy,
looq tetm costs oot occoooteJ fot becoose potleots wete oot followeJ beyooJ bospltol Jlscbotqe, Obsetvotloool evlJeoce
wblcb ls sobject to coofoooJloq, oocettoloty lo compooeots of ooo ptotocollseJ cote wblcb mokes lotetptetotloo of tesolts
Jlfflcolt.
1ab|e 14: rotoco| vs. No rotoco| -- Lconom|c summary of f|nd|ngs
Study
Incrementa|
cost

Incrementa| effects

ICLk Uncerta|nty
!ones
46
4,407
a

1.3 CAL?s galned

3,384 per
CAL? galned

8esulLs were noL senslLlve
Lo uLlllLy of survlvors or
dlscounL raLe.

robablllLy of cosL-
effecLlveness was 97 aL a
Lhreshold of 20,000 per
CAL? galned.

Shorr
101
-3,742
b
-18 morLallLy

roLocol
domlnaLes (ls
less cosLly
wlLh lower
morLallLy)
noL consldered.

1almor
107
3,368
c

0.340 CAL?s galned

10,312 per
CAL? galned

lf uLlllLy of survlvors <0.4
d

Lhen Lhe lCL8 ls >20,000
and ls noL cosL effecLlve
(base case=0.69)

o) coovetteJ to ukIftom u55 osloq 2006 potcbosloq powet potltles (see AppeoJlx l fot foll Jetolls)
b) coovetteJ to ukIftom u55 osloq 2005 potcbosloq powet potltles (see AppeoJlx l fot foll Jetolls)
c) coovetteJ to ukI ftom u55 osloq 2004 potcbosloq powet potltles (see AppeoJlx l fot foll Jetolls)

66
J) 0.4 ls opptoxlmote sloce lt wos teoJ off o qtopb (ooJ tbeo coovetteJ to ukI).

S.2.4 Lv|dence statements
C||n|ca| ev|dence
lotleots wltb sepsls
Lvldence from Lwo sLudles ln paLlenLs wlLh sepsls suggesLed LhaL paLlenLs recelvlng lv fluld
Lherapy as parL of a proLocollsed care package had less morLallLy, decreased lengLh of hosplLal
sLay, and fewer renal compllcaLlons compared Lo paLlenLs who recelved lv flulds noL as parL of
any proLocol. 1he quallLy of evldence was of low Lo very low quallLy.
lotto-opetotlve potleots
Lvldence from Lwo sLudles ln lnLra-operaLlve paLlenLs suggesLed LhaL paLlenLs recelvlng lv fluld
Lherapy as parL of a proLocollsed care package may have decreased morLallLy and decreased
lengLh of sLay ln hosplLal compared Lo paLlenLs who recelved lv flulds noL as parL of any proLocol.
1he evldence was of very low quallLy.
lost-opetotlve potleots
Lvldence from one sLudy ln posL-operaLlve paLlenLs showed LhaL paLlenLs recelvlng lv fluld
Lherapy as parL of a proLocollsed care package have decreased lengLh of sLay ln hosplLal and
lnLenslve care unlL compared Lo Lhose recelvlng lv flulds noL as parL of any proLocol. Powever,
Lhere was no dlfference wlLh respecL Lo number of renal compllcaLlons beLween Lhe Lwo groups.
1toomo/sbock potleots
Lvldence from one sLudy ln paLlenLs wlLh Lrauma or shock suggesLed LhaL Lhere was no dlfference
wlLh respecL Lo morLallLy, lengLh of sLay ln hosplLal and lengLh of sLay ln lnLenslve care unlL when
comparlng paLlenLs recelvlng lv fluld Lherapy as parL of a proLocollsed care package wlLh Lhose
who recelve lv flulds noL as parL of any proLocol. 1he evldence was of very low quallLy.
Lconom|c ev|dence
1hree sLudles found LhaL compared Lo convenLlonal, non- proLocollsed care, lv fluld Lherapy as
parL of a proLocollsed care package for paLlenLs presenLlng wlLh sepsls and sepLlc shock was cosL
effecLlve (from cosL savlng up Lo 10,312 per CAL? galned). 1hls analysls was assessed as
parLlally appllcable wlLh poLenLlally serlous llmlLaLlons.
S.2.S kecommendat|ons and ||nk to ev|dence
kecommendat|ons
8. Cffer IV f|u|d therapy as part of a protoco| (see A|gor|thms for IV f|u|d
therapy):
Assess patients fluid and electrolyte needs fo||ow|ng A|gor|thm 1:
Assessment.
If pat|ents need IV f|u|ds for f|u|d resusc|tat|on, fo||ow A|gor|thm 2:
I|u|d kesusc|tat|on.
If pat|ents need IV f|u|ds for rout|ne ma|ntenance, fo||ow A|gor|thm
3: kout|ne ma|ntenance.
If pat|ents need IV f|u|ds to address ex|st|ng def|c|ts or excesses,
ongo|ng abnorma| |osses or abnorma| f|u|d d|str|but|on, fo||ow
A|gor|thm 4: kep|acement and red|str|but|on.

67
8elaLlve values of
dlfferenL ouLcomes
MorLallLy and morbldlLy were ldenLlfled as Lhe mosL crlLlcal ouLcomes. LengLh of
sLay ln hosplLal was also consldered lmporLanL for declslon maklng was.
1rade-off beLween
harms
1he cllnlcal evldence revlew found LhaL on Lhe whole, ouLcomes, lncludlng survlval
were more favourable ln paLlenLs recelvlng lv flulds as parL of a proLocol-based care
package, lrrespecLlve of dlfferenL paLlenL populaLlon groups, LhaL ls, paLlenLs wlLh
sepsls or lnLra/posL-operaLlve paLlenLs. lL was recognlsed LhaL componenLs of
lndlvldual proLocols lnfluence ouLcomes dlfferenLly ln dlfferenL populaLlons and Lhls
should be kepL ln mlnd when followlng any parLlcular proLocol. 1he CuC agreed LhaL
emphasls should be placed on accuraLe assessmenL and reassessmenL of volume
and elecLrolyLe sLaLus when admlnlsLerlng lv fluld Lherapy Lo any paLlenL.
Lconomlc
conslderaLlons
ln paLlenLs wlLh sepsls, lv fluld Lherapy as parL of a proLocollsed care package was
found Lo be cosL-effecLlve for sepsls paLlenLs ln Lwo sLudles and cosL savlng ln a Lhlrd
sLudy.
1here was no cosL-effecLlveness evldence for paLlenLs wlLhouL sepsls. Powever,
glven LhaL Lhe healLh lmprovemenLs observed ln Lhe revlew of cllnlcal effecLlveness
evldence were [usL as pronounced for lnLra-operaLlve care Lhe CuC felL LhaL Lhe
economlc beneflLs of proLocols are very llkely Lo be achlevable across all seLLlngs.
Powever, Lhere were lssues of appllcablllLy and quallLy see below.
CuallLy of evldence 1he quallLy of Lhe cllnlcal evldence varled from low Lo very low. 1he sLudles
lncluded ln Lhe cllnlcal evldence revlew have several llmlLaLlons and are aL rlsk of
blas. Slnce our LargeL populaLlon ls all hosplLallsed paLlenLs, Lhe cllnlcal evldence
avallable from Lhe sLudles found for speclflc populaLlon groups has llmlLed
appllcablllLy and Lhe evldence has been downgraded for lndlrecLness.
1he Lhree cosL-effecLlveness evldence sLudles were all ln a uS seLLlng and Lherefore
may noL be Lransferable Lo a uk nPS seLLlng slnce cllnlcal pracLlce resource use and
unlL cosLs are all llkely Lo be dlfferenL. ln addlLlon Lhere were some poLenLlally
serlous llmlLaLlons. lor example, noL all healLh and cosL ouLcomes of lnLeresL were
lncluded and unllke Lhe cllnlcal evldence revlewed above all Lhree were based on
observaLlonal evldence.
CLher conslderaLlons

1he CuC dlscussed LhaL evldence was only avallable for speclflc populaLlon groups
whlch may noL appllcable Lo all hosplLallsed paLlenLs, parLlcularly older paLlenLs wlLh
mulLlple co-morbld chronlc dlseases. 1he CuC also dlscussed Lhe exLreme
heLerogeneous naLure of Lhe LargeL populaLlon and agreed LhaL lL would noL be
meanlngful Lo pool Lhe evldence across dlfferenL populaLlon groups. 8esulLs are
Lherefore presenLed separaLely. neverLheless, Lhe evldence favoured Lhe use of
proLocollsed care when glvlng lv flulds, lrrespecLlve of Lhe populaLlon group, and
Lhe CuC were noL only aware LhaL followlng of proLocols has been shown Lo be of
value ln several oLher areas of complex declslon maklng ln healLhcare, buL felL LhaL
algorlLhms were Lhe besL way for Lhe guldance Lo be lmplemenLed across hosplLal
seLLlngs. 1he CuC Lherefore made a consensus declslon Lo advocaLe Lhe use of
algorlLhms for lv fluld Lherapy.
ln vlew of Lhe above, Lhe CuC drafLed four algorlLhms Lo be used for managemenL
of lv fluld Lherapy ln hosplLallsed paLlenLs coverlng: assessmenL (algorlLhm 1), fluld
resusclLaLlon (algorlLhm 2), rouLlne malnLenance (algorlLhm 3), and replacemenL
and redlsLrlbuLlon (algorlLhm 4). Avallable evldence and dlscusslon underplnnlng
sLeps ln each of Lhe lndlvldual algorlLhm ls presenLed ln Lhe relevanL secLlons.
1hls recommendaLlon was ldenLlfled as a key prlorlLy for lmplemenLaLlon by Lhe
CuC.


S.2.6 A|gor|thms for IV f|u|d therapy

Algorithms for IV fluid therapy

Using an ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach, assess whether the patient is hypovolaemic and needs fluid resuscitation
Assess volume status taking into account clinical examination, trends and context. Indicators that a patient may need fluid resuscitation include: systolic BP <100mmHg; heart rate
>90bpm; capillary refill >2s or peripheries cold to touch; respiratory rate >20 breaths per min; NEWS 5; 45
o

Clinical examination: pulse, BP, capillary refill, JVP, oedema (peripheral/pulmonary), postural hypotension.

Does the patient have complex fluid or
electrolyte replacement or abnormal
distribution issues?
Look for existing deficits or excesses, ongoing
abnormal losses, abnormal distribution or other
complex issues.

Reassess the patient using the ABCDE
approach
Does the patient still need fluid
resuscitation? Seek expert help if unsure
Initiate treatment
Identify cause of deficit and respond.
Give a fluid bolus of 500 ml of crystalloid
(containing sodium in the range of
130154 mmol/l) over 15 minutes.
Ongoing abnormal fluid or
electrolyte losses
Check ongoing losses and estimate
amounts. Check for:
vomiting and NG tube loss
biliary drainage loss
high/low volume ileal stoma
loss
diarrhoea/excess colostomy
loss
ongoing blood loss, e.g.
melaena
sweating/fever/dehydration
pancreatic/jejunal fistula/stoma
loss
urinary loss, e.g. post AKI
polyuria.


2530 ml/kg/d water
50100 g/day glucose (e.g. glucose 5% contains
5 g/100ml).

Reassess and monitor the patient
Stop IV fluids when no longer needed.
when maintenance needs are more than 3 days.
Existing fluid or
electrolyte deficits
or excesses
Check for:
dehydration
fluid overload
hyperkalaemia/
hypokalaemia

Estimate deficits or
excesses.
Redistribution and
other complex issues
Check for:
gross oedema
severe sepsis
hypernatraemia/
hyponatraemia
renal, liver and/or
cardiac impairment.
post-operative fluid
retention and
redistribution
malnourished and
refeeding issues
Seek expert help if
necessary and estimate
requirements.
Give a further fluid bolus of 250500 ml of
crystalloid
>2000 ml
given?
Seek expert help
Algorithm 2: Fluid Resuscitation

Algorithm 4: Replacement and Redistribution

No

Yes
No

Yes
No

Ensure nutrition and fluid needs are met
Also see Nutrition support in adults (NICE
clinical guideline 32).
Yes
Yes
Prescribe by adding to or subtracting from routine maintenance, adjusting for all
other sources of fluid and electrolytes (oral, enteral and drug prescriptions)

Yes
Monitor and reassess fluid and biochemical status by clinical and laboratory
monitoring
Yes
No

No

No
Does the patient have
signs of shock?

AssessmenL and monlLorlng of paLlenLs recelvlng lnLravenous fluld Lherapy

69
6 Assessment and mon|tor|ng of pat|ents rece|v|ng
|ntravenous f|u|d therapy
6.1 Introduct|on
PosplLal paLlenLs needlng lv flulds are very varlable ln Lerms of Lhelr currenL fluld and elecLrolyLe
sLaLus and Lhelr llkely physlologlcal responses Lo lv fluld Lherapy. 1hey Lherefore need a full
assessmenL by a compeLenL cllnlclan of Lhe besL conLenL, volume and raLe of lv flulds Lo be glven ln
order Lo mlnlmlze rlsks of:
under- or over-provlslon of fluld and
LlecLrolyLe abnormallLles such as hypo- or hyper-naLraemla, hypo- or hyper-kalaemla and hyper-
chloraemlc acldosls.
Slnce Lhese Lypes of compllcaLlons ofLen lead Lo lncreased morbldlLy and morLallLy (e.g. pulmonary
oedema lncreases rlsks of subsequenL pneumonla whllsL perlpheral oedema lncreases rlsks of
deblllLaLlng ulceraLlon), careful assessmenLs should also reduce lengLh of sLay and dlscomforL Lo
paLlenLs.
AssessmenLs should be based on Lhe prlnclples ouLllned ln 3.1.2.3. 1he cllnlcal approach Lo assesslng
lv fluld needs. 1hese lnclude a focussed hlsLory, cllnlcal examlnaLlon, lnspecLlon of monlLorlng charLs
and conslderaLlon of laboraLory lndlces ln Lerms of boLh currenL values and prevlous Lrends. Slnce lL
ls noL posslble fully Lo predlcL how each paLlenL wlll handle lv flulds when lnlLlaLlng Lherapy, Lhe
same elemenLs need reassessmenL on a regular basls so LhaL Lhe lv fluld prescrlpLlon can be alLered
as approprlaLe and sLopped as soon as posslble. 1he lmporLance of Lhls reassessmenL ls hlghllghLed
ln Lhe recommendaLlons as Lhe 3Lh 8 ln Lhe 38 prlnclple of lv fluld prescrlblng.
underLaklng assessmenLs of lv fluld and elecLrolyLe needs ls noL always sLralghLforward and
sLandards of pracLlce are very varlable ln hosplLal admlsslon and general ward areas. Lven senlor
cllnlclans someLlmes need guldance ln Lhe assessmenL of more complex paLlenLs e.g. Lhose wlLh
slgnlflcanL oedema or abnormal gasLrolnLesLlnal losses, yeL desplLe Lhe complexlLy of Lhe process, lL
ls ofLen delegaLed Lo Lhe mosL [unlor medlcal sLaff wlLh no esLabllshed process for senlor revlew.
Many of Lhose [unlors have also recelved llLLle Lralnlng ln assessmenL of lv fluld needs and
mlslnLerpreLaLlon of lndlces whlch lnform lv fluld prescrlpLlon ls common. lor example, low serum
sodlum may lead an lnexperlenced docLor Lo prescrlbe a hlgher sodlum conLalnlng fluld, even ln Lhe
presence of volume overload when whole body sodlum conLenL ls llkely Lo be hlgh. lndeed, Lhe need
for conLlnulng lv flulds ls noL always quesLloned wlLh some [unlors lncllned slmply Lo repeaL Lhe
previous days IV fluld prescrlpLlon raLher Lhan properly reassess Lhe paLlenL or seek advlce from a
senlor colleague. lurLhermore, Lhe daLa LhaL cllnlclans rely on Lo ald prescrlblng declslons, such as
measures of urlne ouLpuL, oLher losses, oral lnpuL, flulds admlnlsLered (lncludlng Lhose wlLh lv
drugs), body welghL and laboraLory resulLs, are ofLen lncompleLe.
1hls chapLer examlnes Lhe dlfferenL componenLs of cllnlcal and laboraLory assessmenL Lo Lry Lo
deLermlne whlch are Lhe mosL lmporLanL Lo ensure safe and effecLlve lv fluld Lherapy. An algorlLhm
Lo supporL declslon-maklng ls also suggesLed.

70
6.2 Assessment
6.2.1 kev|ew quest|on: What aspects of c||n|ca| assessment are requ|red to assess, mon|tor
and re-eva|uate f|u|d and e|ectro|yte status?
1he CuC agreed LhaL a formal cllnlcal evldence approach Lo Lhls quesLlon was noL approprlaLe as Lhe
raLlonale and [usLlflcaLlon for each aspecL of cllnlcal assessmenL was embedded ln Lhe prlnclples and
proLocols for lnLravenous fluld Lherapy and could noL be answered by a speclflc revlew quesLlon.
lurLhermore, Lhere ls evldence based guldance from nlCL on Lhe dlfferenL aspecLs Lo be consldered
when assessing and monitoring patients (NICE guideline on Acutely ill patients in hospital and the
CuC.
16
1he CuC drew upon Lhls guldance when drafLlng Lhe recommendaLlons for Lhls secLlon.1he
CuC agreed LhaL no llLeraLure search would be underLaken and Lhe guldance would be based on
consensus uslng Lhe experL oplnlon of CuC members and Lhe prlnclples of fluld prescrlblng as
descrlbed ln Lhe secLlon on rlnclples and proLocols for lnLravenous fluld Lherapy, along wlLh
reference Lo nlCL guldellne on Acutely lll paLlenLs ln hospital
16
whlch ldenLlfles Lhe maln areas of
cllnlcal assessmenL and physlcal examlnaLlon LhaL are lmporLanL Lo lv fluld managemenL.
1he guldance would also Lake lnLo accounL Lhe naLlonal Larly Warnlng Score (nLWS).
93
1he naLlonal
Larly Warnlng Score (nLWS) ls a ueparLmenL of PealLh lnlLlaLlve whlch was accepLed by Lhe CuC as a
rellable and lnformaLlve scorlng sysLem for assessmenL. nLWS has been demonsLraLed Lo be as good
as Lhe besL of oLher early warnlng scores ln dlscrlmlnaLlng rlsk of acuLe morLallLy and ls llkely Lo be
more senslLlve Lhan mosL currenLly used sysLems aL prompLlng an alerL and cllnlcal response Lo acuLe
lllness deLerloraLlon.
93

Powever, Lhe CuC dld ldenLlfy a number of revlew quesLlons on speclflc lssues of laboraLory or ward-
based assessmenLs, perLlnenL Lo assessmenL and monlLorlng and Lhree of Lhese were felL Lo be ln
areas where Lhere was hlgh varlaLlon ln pracLlce and a lack of clear guldance. 1hese were Lherefore
prlorlLlsed by Lhe CuC for formal cllnlcal evldence revlews Lo lnform declslon-maklng. 1he Lhree
areas were:
Serlal measuremenL of body welghL
MeasuremenL of urlnary ouLpuL and recordlng fluld balance
MeasuremenL of serum chlorlde levels
A revlew conducLed earller ln Lhe guldellne whlch evaluaLed Lhe cllnlcal and cosL effecLlveness of
uslng an algorlLhm Lo gulde care, found evldence Lo supporL Lhe use of algorlLhms and Lhe CuC have
Lherefore suggesLed an algorlLhmlc approach Lo Lhe assessmenL and monlLorlng of paLlenLs recelvlng
lv flulds (see secLlon 3.2)

kecommendat|ons
9. Assess whether the pat|ent |s hypovo|aem|c. Ind|cators that a
pat|ent may need urgent f|u|d resusc|tat|on |nc|ude:
systo||c b|ood pressure |s |ess than 100 mmng
heart rate |s more than 90 beats per m|nute
cap|||ary ref||| t|me |s more than 2 seconds or per|pher|es are
co|d to touch
resp|ratory rate |s more than 20 breaths per m|nute

71
Nat|ona| Lar|y Warn|ng Score (NLWS) |s S or more
pass|ve |eg ra|s|ng suggests f|u|d respons|veness
c
.
10. Assess the patients likely fluid and electrolyte needs from their
h|story, c||n|ca| exam|nat|on, current med|cat|ons, c||n|ca|
mon|tor|ng and |aboratory |nvest|gat|ons:
n|story shou|d |nc|ude any prev|ous ||m|ted |ntake, th|rst, the
quant|ty and compos|t|on of abnorma| |osses (see D|agram of
ongo|ng |osses), and any comorb|d|t|es, |nc|ud|ng pat|ents who
are ma|nour|shed and at r|sk of refeed|ng syndrome (see
Nutr|t|on support |n adu|ts [NICL c||n|ca| gu|de||ne 32]).
C||n|ca| exam|nat|on shou|d |nc|ude an assessment of the
pat|ent's f|u|d status, |nc|ud|ng:
pulse, blood pressure, caplllary reflll and [ugular venous
pressure
presence of pulmonary or perlpheral oedema
presence of posLural hypoLenslon.
C||n|ca| mon|tor|ng shou|d |nc|ude current status and trends |n:
nLWS
fluld balance charLs
welghL.
Laboratory |nvest|gat|ons shou|d |nc|ude current status and
trends |n:
full blood counL
urea, creaLlnlne and elecLrolyLes.
8elaLlve value of dlfferenL
ouLcomes
Slx physlologlcal parameLers are rouLlnely monlLored ln hosplLal (l) resplraLory
raLe, (ll) oxygen saLuraLlons, (lll) LemperaLure, (lv) sysLollc blood pressure, (v)
pulse raLe and (vl) level of consclousness. 1hese form Lhe basls of Lhe naLlonal
Larly Warnlng Score (nLWS) upon whlch Lhe CuC has based lLs
recommendaLlons.
93

AssessmenL of volume sLaLus also requlres addlLlonal assessmenLs or
measuremenLs of body welghL, fluld balance, [ugular venous pressure and Lhe
presence or absence of fluld-relaLed compllcaLlons, as well as laboraLory
measures of l8C, urea, creaLlnlne and elecLrolyLes. 1he CuC agreed LhaL serlal,
accuraLe assessmenL or measuremenL of all Lhese addlLlonal parameLers
provldes lmporLanL lnformaLlon for assesslng volume sLaLus and esLlmaLlng Lhe
need for fluld and elecLrolyLes.
1rade-off beLween
beneflLs and harms
8ouLlne laboraLory assessmenL of paLlenLs on lnLravenous Lherapy may requlre
addlLlonal blood LesLs Lo be Laken from Lhe paLlenL. Powever, Lhe CuC agreed
LhaL serlal measuremenL of blochemlcal markers can provlde lmporLanL
addlLlonal lnformaLlon on renal funcLlon and poLenLlal compllcaLlons of fluld
Lherapy (e.g. chlorlde load).
Lconomlc evldence 1lme and resources spenL on monlLorlng fluld sLaLus are cruclal Lo good paLlenL
care and are llkely Lo be more Lhan offseL by healLh galns and poLenLlal cosL

c asslve leg ralslng ls a bedslde meLhod Lo assess fluld responslveness ln a paLlenL. lL ls besL underLaken wlLh Lhe paLlenL
lnlLlally seml-recumbenL and Lhen LllLlng Lhe enLlre bed Lhrough 43. AlLernaLlvely lL can be done by lylng Lhe paLlenL flaL
and passlvely ralslng Lhelr legs Lo greaLer Lhan 43. lf, aL 3090 seconds, Lhe paLlenL shows slgns of haemodynamlc
lmprovemenL, lL lndlcaLes LhaL volume replacemenL may be requlred. lf Lhe condlLlon of Lhe paLlenL deLerloraLes, ln
parLlcular breaLhlessness, lL lndlcaLes LhaL Lhe paLlenL may be fluld overloaded.

72
savlngs from compllcaLlons averLed. 1he monlLorlng sLraLegles recommended
here are commonly pracLlced ln Lhe nPS.
CuallLy of evldence 8ecommendaLlons were drafLed based on prlnclples of fluld prescrlblng, nlCL
guidance CG50 Acutely ill patients ln hospital
16
, Lhe nLW score
93
and
consensus experL oplnlon of Lhe CuC members. nLWS has been demonsLraLed
Lo be as good as Lhe besL of oLher early warnlng scores ln dlscrlmlnaLlng rlsk of
acuLe morLallLy and ls llkely Lo be more senslLlve Lhan mosL currenLly used
sysLems aL prompLlng an alerL and cllnlcal response Lo acuLe lllness
deLerloraLlon.
93
. 1he recommendaLlons ln Lhe nlCL guldellne on acuLely lll
paLlenLs ln hosplLal were based on sysLemaLlc llLeraLure revlews of Lhe
evldence and consensus oplnlon of Lhe CuC members of LhaL guldellne, lf no
evldence was ldenLlfled.
16

CLher conslderaLlons ln conslderlng Lhe quesLlon of opLlmal assessmenL and reassessmenL Lhe CuC
almed for recommendaLlons LhaL ensure lv fluld Lherapy dellvers lLs
LherapeuLlc purpose whllsL compllcaLlons are prevenLed or ldenLlfled as soon
as posslble. 1he CuC dlscussed Lhe facL LhaL lnLerpreLaLlon of commonly used
assessmenL Lools (e.g serum sodlum and poLasslum levels) ls poor amongsL
[unlor medlcal sLaff and can lead Lo poor lv fluld prescrlblng. 1hey Lherefore
concluded LhaL assessmenL lssues musL also be lncluded ln Lhe Lralnlng and
educaLlon arm of Lhls guldance (see secLlon on 1ralnlng and educaLlon of
healLh care professlonals for managemenL of lnLravenous fluld Lherapy)
1he CuC acknowledged LhaL Lhere are slgnlflcanL pracLlcal challenges ln
measurlng cerLaln cllnlcal parameLers. lor example, serlal assessmenL of body
welghL ln obese or bedbound paLlenLs requlres addlLlonal resources of Llme
and sLaff. Slmllarly, Lhe CuC agreed LhaL recordlng of fluld lnLake and ouLpuL ls
ofLen lncompleLe or lnaccuraLe on fluld balance charLs. uesplLe Lhese
challenges, Lhe CuC felL lL lmporLanL Lo emphaslse Lhe value of serlal body
welghLs and accuraLe fluld balance records ln monlLorlng response Lo
lnLravenous fluld Lherapy and ldenLlflcaLlon of poLenLlal harm, speclflcally fluld
overload. 1he CuC agreed LhaL recommendaLlon 9 was a key prlorlLy for
lmplemenLaLlon.
6.3 keassessment and mon|tor|ng
Lvldence revlews were underLaken ln Lhe Lhree areas prlorlLlsed by Lhe CuC:
Serlal measuremenL of body welghL
MeasuremenL of urlnary ouLpuL and recordlng fluld balance
MeasuremenL of serum chlorlde levels
6.3.1 Ser|a| measurement of body we|ght
Regular, accurate measurement of the patients weight can be a useful indicator of inadequate or
excesslve volume replacemenL. Powever, even wlLh modern equlpmenL, documenLlng accuraLe
welghL changes can be dlfflculL. 1here are parLlcular dlfflculLles wlLh non-ambulanL and obese
paLlenLs and posL-operaLlve paLlenLs wlLh paln conLrol lssues and numerous llnes and dralns. 8asellne
welghLs are rarely accuraLe and Lhe measuremenLs are sub[ecL Lo numerous confounders, such as Lhe
exLernal losses lnLo dralns and dresslngs, and poLenLlally huge volumes of fluld can be redlsLrlbuLed
ln oedema or sequesLered wlLhln a non-funcLlonlng guL or Lhe naLural body cavlLles. 1he CuC
examlned Lhe publlshed llLeraLure Lo deLermlne wheLher Lhere was any evldence Lo supporL Lhe need
for repeaLed body welghL measuremenLs ln paLlenLs ln general, as well as ln speclflc hlgh rlsk groups
such as Lhose wlLh chronlc kldney dlsease or hearL fallure.

73
6.3.1.1 kev|ew quest|on
In hosp|ta||sed pat|ents rece|v|ng IV f|u|ds, what |s the c||n|ca| and cost effect|veness of measur|ng
and record|ng ser|a| body we|ght?
We searched for sysLemaLlc revlews, randomlsed conLrolled Lrlals and cohorL sLudles comparlng Lhe
effecLlveness of Lhe cllnlcal and cosL effecLlveness for measurlng and recordlng serlal welghLs
compared Lo any one or more of Lhe followlng:
usual care (l.e. where Lhere ls no speclflc proLocol Lo measure and record welghL )
fluld balance charL
welghL measuremenL plus fluld balance charL
cllnlcal assessmenL.
1he CuC had ldenLlfled paLlenLs wlLh chronlc renal lmpalrmenL or congesLlve hearL fallure as speclflc
subgroups who would beneflL more from welghlng due Lo paLhophyslologlcal changes ln Lhelr fluld
handllng.
lor more deLalls see revlew proLocol ln C.2.1, Appendlx C.
6.3.1.2 C||n|ca| ev|dence
no sLudles were found on Lhe use of serlal welghL measuremenL Lo lnform Lhe cllnlcal monlLorlng of
lv fluld admlnlsLraLlon ln hosplLallsed paLlenLs.
lor deLalls on excluded sLudles, see secLlon P.2, Appendlx P.
6.3.1.3 Lconom|c ev|dence
no publlshed sLudles of cosL-effecLlveness were found. 1he CuC consldered monlLorlng Lo be a hlgh
prlorlLy for de novo economlc modelllng. Powever, Lhe cllnlcal revlew dld noL flnd evldence of cllnlcal
effecLlveness, so a slmple cosL analysls was conducLed wlLh a Lhreshold senslLlvlLy analysls around
Lhe number of compllcaLlons averLed, see Appendlx L. We consldered dlfferenL sLraLegles LhaL were
dlfferenLlaLed by Lhe frequency of welghlng paLlenLs and Lhe presence or absence of fluld charL use.
lL was assumed LhaL welghlng would be predomlnanLly done by healLh care asslsLanLs whereas fluld
balance would predomlnanLly be done by nurses. 1he cosL of welghlng a paLlenL was esLlmaLed Lo be
11 each Llme (ranglng from 2 for a moblle paLlenL Lo 23 for a compleLely lmmoblle paLlenL) and
Lhe cosL of rouLlnely compleLlng a fluld balance charL was esLlmaLed Lo cosL 20 per paLlenL per 24hr
day (34 mlnuLes per paLlenL).
1he cosL of a ma[or fluld-relaLed compllcaLlon (see 4.2.3) was esLlmaLed uslng nPS reference cosLs Lo
be 1868 (or 3,000 lncludlng a crlLlcal care eplsode).
1he cosL of each monlLorlng sLraLegy ls shown ln 1able 13 along wlLh Lhe number of compllcaLlons
LhaL would need Lo be averLed Lo make each sLraLegy cosL neuLral.
1hls analysls can be consldered as parLlally appllcable (slnce nPS unlL cosLs were used buL CAL?s
were noL esLlmaLed) buL lL has poLenLlally serlous llmlLaLlons slnce Lhe resource use was based on
experL oplnlon. lurLhermore, concluslons abouL cosL-effecLlveness or cosL neuLrallLy are noL posslble
wlLhouL evldence of Lhe number of compllcaLlons averLed due Lo monlLorlng.

74
1ab|e 1S: 1he cost of mon|tor|ng
Strategy
1ota| costs for each
mon|tor|ng strategy per
week ()
Number of extra ma[or
comp||cat|ons that
wou|d have to be
avo|ded per 1000
pat|ents (d) to make
strategy cost neutra|
compared to no
mon|tor|ng (|nc|ud|ng
cost of cr|t|ca| care)
WelghL I|u|d 8a|ance Chart
none no fluld charL 0 ---
Lwlce a week no fluld charL 16 8 (3)
dally no fluld charL 33 30 (18)
none fluld charL 102 34 (34)
Lwlce a day no fluld charL 111 39 (37)
Lwlce a week fluld charL 118 63 (39)
dally fluld charL 137 84 (32)
Lwlce a day fluld charL 213 114 (71)
(o) lotleots bospltollseJ fot flve Joys
6.3.1.4 Lv|dence statements
C||n|ca|
no sLudles were found comparlng Lhe cllnlcal and cosL effecLlveness of measurlng and recordlng
serlal bodywelghLs compared Lo usual care, lncludlng no proLocol Lo measure and record welghL,
fluld balance charL, welghL measuremenL plus fluld balance charL or cllnlcal assessmenL Lo lnform Lhe
cllnlcal monlLorlng of lv fluld admlnlsLraLlon ln hosplLallsed paLlenLs.
Lconom|c
An orlglnal comparaLlve cosL analysls showed LhaL, lf a sLraLegy of welghlng paLlenLs Lwlce a week
prevenLs 3-8 ma[or compllcaLlons per 1000 paLlenLs, Lhen lL would be cosL neuLral compared wlLh no
monlLorlng. 1hls analysls was assessed as parLlally appllcable wlLh poLenLlally serlous llmlLaLlons.
1he same orlglnal comparaLlve cosL analysls showed LhaL, lf a sLraLegy of welghlng paLlenLs dally
prevenLs 18-30 ma[or compllcaLlons per 1000 paLlenLs, Lhen lL would be cosL neuLral compared wlLh
no monlLorlng. 1hls analysls was assessed as parLlally appllcable wlLh poLenLlally serlous llmlLaLlons.
6.3.1.S kecommendat|ons and ||nk to ev|dence
1he assessmenL and monlLorlng of body welghL ls closely lnLerllnked Lo Lhe measuremenL of urlnary
ouLpuL (as recorded by malnLalnlng fluld balance charLs). 1herefore, revlews on boLh of Lhese Loplcs
have been consldered LogeLher and recommendaLlons on boLh Lhese aspecLs are comblned, and
presenLed aL Lhe end of Lhe revlew on measuremenL of urlnary ouLpuL (see secLlon 6.3.2.3)


73
6.3.2 Measurement of ur|nary output and record|ng of f|u|d ba|ance
8egular, accuraLe monlLorlng of urlne ouLpuL ls consldered a sLandard of care for all paLlenLs
recelvlng lnLravenous volume replacemenL alLhough lL ls noL one of Lhe parameLers measured as parL
of Lhe nLWS scorlng sysLem.
82
As wlLh Lhe assessmenL of body welghL (see above), varlaLlon ln urlne
ouLpuL requlres lnLerpreLaLlon wlLhln Lhe cllnlcal conLexL, ollgurla may noL lndlcaLe hypovolaemla
whlle polyurla may be seen regardless of Lhe sLaLe of Lhe lnLravascular space.
32,30,68,71,78,103,112,113
1he
CuC examlned Lhe evldence for regular measuremenL of urlne ouLpuL, ln addlLlon Lo Lhe sLandard
parameLers of Lhe nLWS scorlng sysLem, and lLs lnfluence on ouLcome measures.
93

In hosp|ta||sed pat|ents rece|v|ng |ntravenous f|u|ds, what |s the c||n|ca| and cost effect|veness of
measur|ng and record|ng ur|ne output |n add|t|on to record|ng standard parameters stated |n
NLWS to determ|ne the need for |ntravenous f|u|d adm|n|strat|on?
We searched for sysLemaLlc revlews, randomlsed conLrolled Lrlals and cohorL sLudles comparlng Lhe
cllnlcal and cosL effecLlveness of measurlng and recordlng urlne ouLpuL ln addlLlon Lo recordlng
sLandard parameLers sLaLed ln nLWS Lo deLermlne Lhe need for lv fluld admlnlsLraLlon.
1he CuC ldenLlfled LhaL achlevlng sLable fluld balance may be more challenglng ln cerLaln groups of
paLlenLs namely lndlvlduals wlLh chronlc renal lmpalrmenL and Lhose aL rlsk of acuLe kldney ln[ury,
Lhose wlLh congesLlve cardlac fallure, older people and perl-operaLlve paLlenLs. 1hese were
Lherefore ldenLlfled as speclflc subgroups ln whom addlLlonal beneflL may be derlved from havlng
Lhelr urlne ouLpuL measured.
lor more deLalls see revlew proLocol ln secLlon C.2.2 ln Appendlx C.
no sLudles were found on use of urlnary ouLpuL Lo lnform Lhe cllnlcal need for lv fluld admlnlsLraLlon
ln hosplLallsed paLlenLs.
lor deLalls on cllnlcal arLlcle selecLlon and excluded sLudles, see secLlon !.2 (Appendlx !) and secLlon
P.2 (Appendlx P) respecLlvely.
no publlshed economlc evldence was found on Lhls quesLlon. A de novo comparaLlve cosLlng analysls
was conducLed comparlng dlfferenL monlLorlng sLraLegles (see secLlon 6.3.1.3).
C||n|ca|
no sLudles were found comparlng Lhe cllnlcal and cosL effecLlveness of measurlng and recordlng
urlnary ouLpuL ln addlLlon Lo recordlng sLandard parameLers sLaLed ln nLWS Lo lnform Lhe cllnlcal
need for lv fluld admlnlsLraLlon ln hosplLallsed paLlenLs.
Lconom|c
An orlglnal comparaLlve cosL analysls showed LhaL, lf sysLemaLlcally compleLlng a fluld balance charL
prevenLs 34-34 ma[or compllcaLlons per 1000 paLlenLs, Lhen lL would be cosL neuLral compared wlLh
no monlLorlng. 1hls analysls was assessed as parLlally appllcable wlLh poLenLlally serlous llmlLaLlons.

76
kecommendat|ons
11. If pat|ents are rece|v|ng IV f|u|ds for resusc|tat|on, reassess the
pat|ent us|ng the A8CDL approach (A|rway, 8reath|ng, C|rcu|at|on,
D|sab|||ty, Lxposure), mon|tor the|r resp|ratory rate, pu|se, b|ood
pressure and perfus|on cont|nuous|y, and measure the|r venous
|actate |eve|s and]or arter|a| pn and base excess accord|ng to
gu|dance on advanced ||fe support (kesusc|tat|on Counc|| [Uk],
2011)
90
.
8elaLlve value of
dlfferenL ouLcomes
1he CuC agreed LhaL all-cause morLallLy was Lhe mosL crlLlcal ouLcome. CLher
ouLcomes such as morbldlLy (as measured by SClA scores and MCu scores) were
also lmporLanL Lo declslon maklng.
1rade-off beLween
beneflLs and harms
1he CuC consldered LhaL Lhere were only beneflLs Lo monlLorlng and LhaL Lhls ls
parL of sLandard care.
Lconomlc
conslderaLlons
Slnce paLlenLs requlrlng resusclLaLlon are serlously lll, Llme spenL carefully
monlLorlng ls llkely Lo be offseL conslderably by healLh galns and poLenLlal cosL
savlngs from compllcaLlons belng averLed.
CuallLy of evldence 8ecommendaLlons were drafLed based on Lhe nLW score, nlCL guldance on
managemenL of crlLlcally lll paLlenLs ln hosplLal and consensus experL oplnlon of
Lhe CuC members.
16,93

CLher conslderaLlons 1he assessmenL of paLlenLs recelvlng lv fluld for resusclLaLlon was consldered
separaLely as lL was agreed by Lhe CuC Lhls ls a shorL-Lerm assessmenL proLocol
wlLh a hlgh degree of urgency requlred. 1he A8CuL approach Lo resusclLaLlon ls
based on sLandard prlnclples of resusclLaLlon.
MeasuremenL of venous and/or arLerlal lacLaLe was dlscussed by Lhe CuC and lL
was agreed LhaL Lhls ls now wldely avallable ln acuLe seLLlngs and parL of Advanced
Llfe SupporL and Advanced 1rauma Llfe SupporL proLocols and can gulde lv fluld
Lherapy declslons.
3

kecommendat|ons
12. A|| pat|ents cont|nu|ng to rece|ve IV f|u|ds need regu|ar mon|tor|ng.
1h|s shou|d |n|t|a||y |nc|ude at |east da||y reassessments of c||n|ca|
f|u|d status, |aboratory va|ues (urea, creat|n|ne and e|ectro|ytes)
and f|u|d ba|ance charts, a|ong w|th we|ght measurement tw|ce
week|y. 8e aware that:
at|ents rece|v|ng IV f|u|d therapy to address rep|acement or
red|str|but|on prob|ems may need more frequent mon|tor|ng.
Add|t|ona| mon|tor|ng of ur|nary sod|um may be he|pfu| |n
pat|ents w|th h|gh-vo|ume gastro|ntest|na| |osses. (keduced
ur|nary sod|um excret|on [|ess than 30 mmo|]|] may |nd|cate
tota| body sod|um dep|et|on even |f p|asma sod|um |eve|s are
norma|. Ur|nary sod|um may a|so |nd|cate the cause of
hyponatraem|a, and gu|de the ach|evement of a negat|ve
sod|um ba|ance |n pat|ents w|th oedema. nowever, ur|nary
sod|um va|ues may be m|s|ead|ng |n the presence of rena|
|mpa|rment or d|uret|c therapy.)
at|ents on |onger-term IV f|u|d therapy whose cond|t|on |s

77
stab|e may be mon|tored |ess frequent|y, a|though dec|s|ons to
reduce mon|tor|ng frequency shou|d be deta||ed |n the|r IV f|u|d
management p|an.
13. C|ear |nc|dents of f|u|d m|smanagement (for examp|e,
unnecessar||y pro|onged dehydrat|on or |nadvertent f|u|d over|oad
due to IV f|u|d therapy) shou|d be reported through standard
cr|t|ca| |nc|dent report|ng to encourage |mproved tra|n|ng and
pract|ce (see Consequences of f|u|d m|smanagement to be
reported as cr|t|ca| |nc|dents).
14. If pat|ents are transferred to a d|fferent |ocat|on, reassess the|r
f|u|d status and IV f|u|d management p|an on arr|va| |n the new
sett|ng.
8elaLlve values of dlfferenL
ouLcomes
1he CuC agreed LhaL Lhe mosL lmporLanL ouLcomes are reducLlon of morLallLy
and morbldlLy from fluld overload or dehydraLlon from recelvlng lnsufflclenL
fluld. CLher lmporLanL ouLcomes lncluded reducLlons ln resplraLory or renal
compllcaLlons, lengLh of hosplLallsaLlon and quallLy of llfe for Lhe paLlenL.
1hese ouLcomes can be affected by the patients fluid balance and serial
welghL changes are an lndlcaLor of Lhls. urlnary ouLpuL ls an lmporLanL
elemenL ln Lhe assessmenL of fluld balance and Lhe adequacy of fluld provlslon.
Powever, no evldence was found reporLlng Lhese ouLcomes.
1rade-off beLween cllnlcal
beneflLs and harms
no sLudles were ldenLlfled LhaL lnvesLlgaLed Lhe addlLlonal beneflL of
measurlng dally welghL.
ually welghL ls an lndlcaLor of fluld accumulaLlon or depleLlon and provldes an
lndlcaLor of wheLher a person ls dehydraLed or has recelved excesslve flulds
(overload), boLh of Lhese sLaLes are assoclaLed wlLh lncreased morbldlLy.
Measurlng dally welghL lmproves Lhe quallLy of paLlenL care and poLenLlally
reduces morbldlLy and morLallLy ln paLlenLs requlrlng lv flulds.
no sLudles were ldenLlfled LhaL lnvesLlgaLed Lhe addlLlonal beneflL of
measurlng urlnary ouLpuL.
urlnary ouLpuL ls a key componenL of fluld balance ln a person and provldes an
lndlcaLor of wheLher a person ls dehydraLed or has recelved Loo much fluld
(overload), boLh of Lhese sLaLes are assoclaLed wlLh morbldlLy and morLallLy.
MeasuremenL of urlnary ouLpuL lmproves Lhe quallLy of paLlenL care and
poLenLlally reduces morbldlLy and morLallLy ln paLlenLs requlrlng lv flulds.
MeasuremenL of spoL urlnary sodlum can be useful ln deLermlnlng wheLher
paLlenLs wlLh poLenLlally hlgh sodlum losses e.g. Lhose wlLh excesslve upper Cl
losses from vomlLlng or hlgh ouLpuL sLomas, may have whole body sodlum
depleLlon. When lL wlll usually be very low (<30 mmol/L) whllsL plasma sodlum
levels may be malnLalned. 8esulLs however, can be mlsleadlng ln Lhe presence
of slgnlflcanL renal lmpalrmenL.
urlnary sodlum measuremenLs, comblned wlLh measures of urlnary volume
and esLlmaLes of Lhe sodlum conLenL of all oLher abnormal losses, can also be
of value ln assesslng neL sodlum balance ln oedemaLous paLlenLs when
achlevemenL of neL negaLlve balance ls ofLen Lhe alm.
1he CuC dlscussed LhaL Lhere may be dlfflculLles ln welghlng paLlenLs who are
lmmoblle and Lhe rlsks assoclaLed wlLh Lhls.
Lconomlc conslderaLlons 1here was no exlsLlng economlc evldence and lL was lnapproprlaLe Lo model
glven Lhe lack of evldence of cllnlcal effecLlveness. 8oLh serlal welghL
measuremenL and compleLlon of fluld balance charLs add Lo Lhe workload for
nurslng sLaff and healLhcare asslsLanLs.
An orlglnal cosL Lhreshold analysls lndlcaLed LhaL, Lo be cosL neuLral, Lwlce
weekly welghlng would only need Lo prevenL 3-8 ma[or compllcaLlons per 1000

78
paLlenLs, whlch seemed plauslble Lo Lhe CuC. ually welghLs would need Lo
prevenL 18-30 ma[or compllcaLlons per 1000 paLlenLs, Lhls seemed less llkely Lo
Lhe CuC, especlally ln Lhe conLexL of sysLemaLlc compleLlon of fluld balance
charLs. 1wlce weekly welghlng ls belleved Lo be common pracLlce ln Lhe nPS
and ls used Lo assess nuLrlLlonal sLaLus as well as fluld sLaLus. More frequenL
welghlng could noL be [usLlfled.
8ased on Lhelr collecLlve experlence, Lhe CuC consldered lL very llkely LhaL
sysLemaLlc compleLlon of fluld balance charLs ls cosL-effecLlve. lor example
Lhey can be used Lo ldenLlfy renal lmpalrmenL as well as calculaLe fluld balance.

1hey noLed LhaL Lhe cosL of monlLorlng paLlenLs recelvlng lv flulds seemed
small relaLlve Lo Lhe cosL of an lnpaLlenL sLay, as a whole.

Cverall Lhese recommendaLlons reflecL currenL pracLlce. 1here was no
evldence for lncreaslng Lhe lnLenslLy of monlLorlng buL nor was Lhere evldence
Lo reduce lnLenslLy.
CuallLy of evldence Serlal welghL: no sLudles were found whlch were relevanL Lo Lhls revlew
proLocol. 1he recommendaLlons were based on Lhe consensus oplnlon of Lhe
CuC members.
urlnary ouLpuL: no 8C1 or cohorL sLudles lnvesLlgaLlng Lhe cllnlcal beneflL of
measurlng urlnary ouLpuL among paLlenLs on lv fluld was found. 1he
recommendaLlons were based on Lhe consensus oplnlon of Lhe CuC members
CLher conslderaLlons Serlal welghLs and measuremenL of urlne ouLpuL: 1he cllnlcal revlew dld noL
flnd any sLudles whlch dlrecLly meL Lhe crlLerla pre-speclfled ln Lhe revlew
proLocol. Powever, durlng Lhe course of Lhe revlew, several papers were
hlghllghLed whlch Lhe CuC felL were parLlcularly useful Lo ald Lhem ln
developlng recommendaLlons based on consensus. Some of Lhese sLudles were
lncluded for Lhe revlews on fluld Lype or volume and Llmlng.. 1he CuC noLed
Lhe followlng flndlngs from Lhese sLudles:
Cne sLudy whlch recorded cumulaLlve lnLake and ouLpuL among paLlenLs found
LhaL Lhese correlaLed wlLh dally welghLs. Powever, fluld balance daLa were less
rellable and accuraLe Lhan dally welghL. 1he sLudy recommended uslng dally
welghL for all paLlenLs who dld noL have acuLe kldney ln[ury.
123

CumulaLlve welghL change also correlaLed wlLh cumulaLlve fluld balance ln
anoLher sLudy
94
and a slmllar Lrend was noLlced for boLh fluld balance and
welghL change for paLlenL undergolng cardlac surgery.
28
WelghL galns were
larger and of slmllar magnlLude of Lhe exLra volumes of fluld glven Lo Lhe
liberal arm in a study comparing restricted versus liberal fluid for
perloperaLlve colon resecLlon paLlenLs.
33
Cne sLudy evaluaLed Lhe feaslblllLy of
use of beds wlLh bullL ln elecLronlc welghlng scales ln Lhe lCu and correlaLed
Lhe fluld balance esLlmaLed by Lhls meLhod wlLh fluld balance esLlmaLed by
regular charLlng of fluld lnpuL and ouLpuL.
97
As wlLh oLher sLudles, Lhls sLudy
reporLed weak correlaLlon beLween boLh Lhese measuremenLs and found LhaL
changes ln body welghL and fluld balance had wlde llmlLs of agreemenL. 1he
sLudy concluded LhaL even wlLh modern Lechnology- based welghlng beds and
Lralned sLaff, obLalnlng rellable welghLs ln lCu paLlenLs ls dlfflculL. Cne sLudy
whlch looked aL accuracy of documenLaLlon of nLWS crlLerla prlor Lo
emergency admlsslons Lo lnLenslve care unlL found urlnary ouLpuL was Lhe
second worsL documenLed crlLerlon only documenLed ln 42 of paLlenLs.
47

1he CuC also dlscussed Lhe pracLlcallLy and feaslblllLy of welghL measuremenLs
ln hosplLals and Lhelr opLlmal frequency, wlLh speclflc dlscusslon ln relaLlon Lo
Lhe dlfflculLy ln measurlng welghLs ln speclflc populaLlon groups such as obese
paLlenLs and paLlenLs who were bed-bound. uesplLe Lhe lack of 8C1 evldence
and Lhe conslderable pracLlcal dlfflculLles Lhe CuC felL LhaL Lhe
recommendaLlon of Lwlce weekly welghL measuremenL and dally fluld balance

79
charLs for paLlenLs recelvlng lv flulds should be parL of assessmenL and
reassessmenL Lo ald declslon maklng when prescrlblng lv flulds and Lo brlng
paLlenLs aL rlsk of compllcaLlons of lv fluld Lherapy Lo Lhe aLLenLlon of Lhe
cllnlcal sLaff as early as posslble. lL ls expecLed LhaL welghL measuremenLs wlll
be underLaken by scales LhaL have been sub[ecLed Lo callbraLlon proLocols and
are sLandardlsed across Lhe hosplLal. 1he CuC agreed LhaL recommendaLlons
12 and 13 were key prlorlLles for lmplemenLaLlon.
1he CuC also dlscussed LhaL Lhe recommended frequency of at least daily
reassessmenL of cllnlcal fluld sLaLus, laboraLory values (urea, creaLlnlne and
elecLrolyLes) and fluld balance charLs was Lhe mlnlmal baslc sLandard Lo be
expecLed ln monlLorlng of paLlenLs. 1hls does noL replace cllnlcal [udgemenL
and declslon maklng where Lhls frequency may be lncreased dependlng on Lhe
cllnlcal condlLlon of Lhe paLlenL.
1he CuC dlscussed Lhe currenL lack of emphasls on reporLlng of adverse
ouLcomes occurrlng as a resulL of mlsmanagemenL of lv fluld Lherapy. lL was
belleved LhaL parL of Lhe reason for Lhls was Lhe facL LhaL Lhe compllcaLlons
have noL been dlrecLly aLLrlbuLed Lo mlsmanagemenL of lv fluld Lherapy and
Lhere ls a lack of undersLandlng on how Lo how Lo dlagnose Lhese ln Lhe
conLexL of lv fluld managemenL. 1he CuC recommended LhaL compllcaLlons
occurrlng as a resulL of mlsmanagemenL should be reporLed as crlLlcal
lncldenLs. lL was agreed LhaL Lhls recommendaLlon would be supporLed by
provldlng a framework on how Lo dlagnose Lhese compllcaLlons ln Lhe conLexL
of lv fluld managemenL and Lhe CuC drafLed a Lable Lhrough consensus
deLalllng Lhese Lo supporL Lhe recommendaLlon (see Consequences of fluld
mlsmanagemenL Lo be reporLed as crlLlcal lncldenLs).uue Lo Lhe pauclLy of
evldence ln relaLlon Lo reporLlng of compllcaLlons relaLed Lo lnLravenous fluld
Lherapy, Lhe CuC also prlorlLlsed a research recommendaLlon ln Lhls Loplc area
(see secLlon 6.4)

6.3.3 Measurement of serum ch|or|de
Pyperchloraemla ls a recognlsed consequence of Lhe lnLravenous fluld Lherapy and Lhere ls some
evldence ln Lhe llLeraLure suggesLlng LhaL lL may be assoclaLed wlLh hlgher levels of morLallLy and
morbldlLy due Lo developmenL of hyperchloraemlc acldosls or reduced renal perfuslon and
glomerular fllLraLlon raLes. AdmlnlsLraLlon of lnLravenous flulds wlLh concenLraLlons of chlorlde
hlgher Lhan normal plasma levels wlll clearly predlspose lndlvlduals Lo hyperchloraemla whllsL,
conversely, lnadequaLe lnLravenous provlslon of chlorlde ln paLlenLs wlLh hlgh Cl losses may be
assoclaLed wlLh Lhe developmenL of hypochloraemla and hypochloraemlc alkalosls. 1he
measuremenL of plasma chlorlde concenLraLlon underlles Lhe dlagnosls of elLher hyperchloraemla or
hypochloraemla buL Lhere are wlde varlaLlons ln pracLlce as Lo wheLher Lhls LesL ls underLaken.
In hosp|ta||sed pat|ents rece|v|ng |ntravenous f|u|ds, what |s the |nc|dence and c||n|ca| s|gn|f|cance
of hyperch|oraem|a and hypoch|oraem|a?
1he evldence revlew almed Lo evaluaLe Lhe lncldence of hyperchloraemla, hyperchloraemlc acldosls
and hypochloraemla ln people recelvlng lnLravenous fluld Lherapy and Lhe cllnlcal slgnlflcance of
Lhese problems, parLlcularly Lhelr assoclaLlon wlLh morLallLy and morbldlLy. 1he focus of Lhe revlew
was Lo address ouLcomes relaLed Lo paLlenL safeLy and Lhe consequences of mlsmanagemenL of
lnLravenous fluld Lherapy raLher Lhan on core cllnlcal effecLlveness ouLcomes.

80
1he measuremenL of serum chlorlde ls Lhe gold sLandard ln dlagnosls of any abnormallLy ln serum
chlorlde level, buL lL was lmporLanL Lo ascerLaln Lhe cllnlcal conLexL ln whlch Lhls measuremenL ls
essenLlal ln addlLlon Lo measuremenL of oLher blochemlcal parameLers ln paLlenLs recelvlng
lnLravenous fluld Lherapy. lL was recognlsed LhaL all Lhe relevanL evldence ln Lhls Loplc area would
noL lend lLself Lo mosL Lypes of revlew proLocol, for example, a dlagnosLlc revlew, an lnLervenLlon
revlew or a prognosLlc revlew.
A Lwo parL approach was underLaken Lo address Lhe ob[ecLlves of Lhls revlew and lnclude allavallable
relevanL llLeraLure.
1he flrsL secLlon evaluaLed Lhe lncldence of hyperchloraemla or hyperchloraemlc acldosls ln
paLlenLs recelvlng flulds conLalnlng dlfferenL concenLraLlons of chlorlde. 8andomlsed conLrolled
Lrlals were ldenLlfled Lo be Lhe mosL approprlaLe Lype of sLudy deslgn for Lhls revlew. Powever, lL
was recognlsed LhaL Lhe evldence from 8C1s wlll malnly be for shorL Lerm ouLcomes. 1herefore,
evldence from cohorL sLudles and case conLrol sLudles was revlewed for Lhls secLlon only lf long
Lerm ouLcomes were noL presenLed ln 8C1s and Lhe observaLlonal sLudles reporLed Lhese
ouLcomes. A summary of Lhe sLudles presenLed ln Lhls secLlon ls presenLed ln 1able 16
1he second secLlon evaluaLed Lhe cllnlcal slgnlflcance of abnormal chlorlde levels by looklng aL Lhe
developmenL of morLallLy and oLher compllcaLlons ln paLlenLs who were dlagnosed wlLh abnormal
chloraemlc sLaLes, even Lhough Lhe CuC recognlzed LhaL Lhe developmenL of abnormal
chloraemlc sLaLes may noL always have been due solely to the patients lnLravenous fluld
Lherapy. 1he mosL approprlaLe deslgn for Lhls secLlon was ldenLlfled Lo be cohorL or case-conLrol
sLudles ln adulL, hosplLallsed paLlenLs for areas wlLhln Lhe scope of Lhe guldellne. A summary of
Lhe key characLerlsLlcs of sLudles lncluded ln Lhls secLlon ls presenLed ln 1able 17
1ab|e 16: Summary of stud|es eva|uat|ng the deve|opment of hyperch|oraem|a]hyperch|oraem|c
ac|dos|s.
Study Des|gn opu|at|on
Intervent|on
(I|u|ds w|th
ch|or|de
concentrat|on>
120mmmo|]|)
Compar|son
(I|u|ds w|th
ch|or|de
concentrat|ons <
120mmo|]L) Cutcomes
Schelngrabe
r eL al.
1999
96

8C1 aLlenLs
undergolng
ma[or lnLra-
abdomlnal
gynaecologlc
surgery
Sodlum chlorlde
0.9
LacLaLed 8lnger's
soluLlon
MeLabollc acldosls
wlLh
hyperchloraemla
Shaw eL al.
2012
100

8eLrosp
ecLlve
cohorL
sLudy
aLlenLs who
recelved lv
crysLallolds
durlng surgery
Sodlum chlorlde
0.9
AlLernaLe
8alanced SoluLlon
MorbldlLy and
morLallLy, LCS,
elecLrolyLe
lmbalances
WaLers eL al.
2001
118

8C1 aLlenLs
undergolng aorLlc
reconsLrucLlve
surgery
Sodlum chlorlde
0.9
LacLaLed rlnger's
soluLlon
Pyperchloraemla,
lCu sLay, hosplLal
lengLh of sLay,
morLallLy
Mclarlane
eL al. 1994
67

8C1 aLlenLs
scheduled Lo
undergo elecLlve
ma[or
hepaLoblllary or
pancreaLlc
surgery
Sodlum chlorlde
0.9
AlLernaLe
8alanced SoluLlon
Chlorlde levels aL
end of surgery
and 24 hours
posL- surgery
1akll eL al. 8C1 aLlenLs Sodlum chlorlde LacLaLed 8lnger's Chlorlde levels

81
Study Des|gn opu|at|on
Intervent|on
(I|u|ds w|th
ch|or|de
concentrat|on>
120mmmo|]|)
Compar|son
(I|u|ds w|th
ch|or|de
concentrat|ons <
120mmo|]L) Cutcomes
2002
106
undergolng
elecLlve ma[or
splne surgery
0.9 soluLlon lnLra operaLlvely
and up Lo 12
hours posL-
operaLlvely
?unos eL al.
2012
126

rospe
cLlve
cohorL
sLudy
aLlenLs
admlLLed Lo lCu
Chlorlde llberal
flulds:
Sodlum chlorlde
0.9, 4
succlnylaLed
gelaLlne soluLlon,
4 albumln ln
sodlum chlorlde
Chlorlde
resLrlcLlve flulds:
Hartmanns
soluLlon, lasma-
LyLe 148, 20
albumln soluLlon

Akl, morLallLy,
lengLh of sLay ln
lCu and hosplLal

1ab|e 17: Summary of stud|es eva|uat|ng the assoc|at|on of hyperch|oraem|a or hypoch|oraem|a
w|th morta||ty
Study Des|gn opu|at|on Lxposure Non-exposure Cutcomes Comments
8onlaLLl
eL al.
2011
12

rospec
Llve
cohorL
sLudy
aLlenLs ln
lCu
n=212
Pyperchlor
aemla
normo/Pypoc
hloraemla
MorLallLy,
AACPL ll
score
LvaluaLes correlaLlon
beLween chlorlde levels
and morLallLy and
morbldlLy,
no menLlon of whaL
flulds were glven
Sllva eL
al.
2009
102

rospec
Llve
cohorL
sLudy
aLlenLs
undergolng
surgery and
subsequenLl
y admlLLed
Lo lCu
n=393
Pyperchlor
aemla aL
end of
surgery
normochlorae
mla
MorLallLy
LCS ln lCu
LCS ln
hosplLal
8oLh groups recelved
Sodlum chlorlde 0.9
buL dlfferenL volumes
1anl eL
al.
2012
109

8eLrosp
ecLlve
cohorL
sLudy
CrlLlcally lll
paLlenLs ln
surglcal lCu
n=488
Pyperchlor
aemla
normochlorae
mla and
Pypochloraem
la
lCu sLay,
PosplLal
sLay,
lCu
morLallLy ,
PosplLal
morLallLy
LvaluaLes correlaLlon
beLween chlorlde levels
and morLallLy and
lengLh of sLay,
no menLlon of whaL
flulds were glven

lor full deLalls on revlew proLocol, see secLlon C.2.3 ln Appendlx C.
We searched for randomlsed conLrolled Lrlals and observaLlonal sLudles for boLh secLlons of Lhe
revlew.
1he CuC ldenLlfled paLlenLs wlLh chronlc renal lmpalrmenL or AcuLe kldney ln[ury (Akl), older people
and paLlenLs wlLh congesLlve hearL fallure as groups who could parLlcularly beneflL more from havlng

82
serum chlorlde measured as Lhey may be aL hlgher rlsk of hyperchloraemla and assoclaLed meLabollc
acldosls or hypochloraemla and alkalosls.
1he flrsL parL of Lhe revlew compared paLlenLs who recelved lnLravenous flulds wlLh chlorlde
concenLraLlons greaLer Lhan 120mmol/l wlLh Lhose recelvlng lnLravenous flulds wlLh chlorlde
concenLraLlons less Lhan 120mmmol/l. Slx sLudles were found.
67,96,100,106,118
Lvldence for Lhls secLlon
ls summarlsed ln Lhe cllnlcal C8AuL evldence proflle below (see 1able 18 and 1able 19)
All sLudles were ln paLlenLs undergolng surgery. lour sLudles were 8C1s
67,96,106,118
, one was a
prospecLlve cohorL sLudy
126
and one was a reLrospecLlve cohorL sLudy.
100
1hree sLudles compared
0.9% sodium chloride solution to lactated Ringers solution.
96,106,118
1wo sLudles compared 0.9
sodlum chlorlde soluLlon Lo and alLernaLe balanced soluLlon (as deflned ln glossary, also see secLlon
.1, Appendlx ) .
67,100
Cne sLudy compared ouLcomes ln paLlenLs recelvlng lnLravenous flulds based
on a chlorlde resLrlcLlve sLraLegy Lo Lhose ln paLlenLs on a chlorlde llberal lnLravenous sLraLegy.
126

1he second parL of Lhe revlew examlned Lhe assoclaLlon beLween abnormal chlorlde levels, prlmarlly
hyperchloraemla, wlLh morLallLy and morbldlLy. 1hree sLudles were ldenLlfled.
12,102,109
1hese sLudles
compared Lwo groups of paLlenLs- one wlLh hyperchloraemla and Lhe oLher wlLh normochloraemla or
hypochloraemla and evaluaLed Lhe assoclaLlon of chloraemlc sLaLe wlLh morLallLy. Powever, lL was
unclear wheLher Lhose paLlenLs wlLh hyperchloraemla had developed lL as a consequence of
lnLravenous fluld Lherapy, and Lhe flndlngs from Lhls seL of sLudles were Lherefore downgraded for
lndlrecLness, a declslon acknowledged ln Lhe secLlon llnklng evldence Lo recommendaLlons. 1he
flndlngs from Lhese sLudles are presenLed separaLely (see 1able 20). Where Lhe relaLlve or absoluLe
effecLs were noL esLlmable and oLher measures of effecL were reporLed ln Lhe sLudy, such as co-
relaLlon eLc., Lhese have been hlghllghLed as noL esLlmable and explalned ln fooLnoLes.
1here were dlfferences beLween Lhe sLudles wlLh respecL Lo Lhe raLe and volumes of admlnlsLraLlon
of flulds and hence, Lhe LoLal volume of fluld admlnlsLered dlffers beLween sLudles. 1hls would have
had an effecL on serum chlorlde levels and so Lhe resulLs were noL pooled across sLudles.
no evldence was ldenLlfled ln relaLlon Lo Lhe speclflc subgroups ldenLlfled ln Lhe revlew proLocol.
See also Lhe sLudy selecLlon flow charL ln !.2 (Appendlx !), sLudy evldence Lables ln L.2.1 (Appendlx L),
and excluslon llsL ln P.2 (Appendlx P).



1ab|e 18: C||n|ca| ev|dence prof||e: I|u|ds w|th ch|or|de concentrat|on |ess than 120 mmo|]L vs I|u|ds w|th ch|or|de concentrat|on greater than 120
mmo|]L D|chotomous outcomes
ua||ty assessment No of pat|ents Lffect s|ze
ua||ty
Importan
ce Study |d. Des|gn
k|sk of
b|as
Incons|st
ency
Ind|rectn
ess Imprec|s|on
I|u|ds w|th
ch|or|de
<120
mmo|]L
I|u|ds
w|th
ch|or|de >
120
mmo|]L
ke|at|ve
effect(k|sk
rat|o (kk) or
Cdds rat|o
(Ck) Abso|ute effect
Morta||ty
WaLers eL
al. 2001
118

randomlse
d Lrlal
serlous (a,
b)
no serlous
lnconslsLe
ncy
serlous
lndlrecLne
ss (c)
no serlous
lmpreclson
33 33 88:
1.00(0.07,
13.33)
LCW C8l1lCAL
Shaw eL
al. 2012
100

reLrospecL
lve cohorL
926 2778 C8:
0.769(0.484,
1.220)
17 fewer Lo 7 more)
?unos eL
al. 2012
126

prospecLlv
e cohorL
773 760 88: 0.90(0.70,
1.13)
Morb|d|ty (ma[or comp||cat|on |ndex)
Shaw eL
al. 2012
100

reLrospecL
lve cohorL
serlous (b) no serlous
lnconslsLe
ncy
serlous
lndlrecLne
ss (c)
serlous
lmpreclson (d)
926 2778 C8:
0.798(0.636,
0.970)
6 fewer Lo 72 fewer)
vL8? LCW lMC81A
n1
L|ectro|yte d|sturbances
Shaw eL
al. 2012
100

reLrospecL
lve cohorL
serlous (b) no serlous
lnconslsLe
ncy
serlous
lndlrecLne
ss (c)
serlous
lmpreclson (d)
926 2778 C8:
0.733(0.371,
0.994)
vL8? LCW C8l1lCAL
kena| |nsuff|c|ency]AkI
WaLers eL
al. 2001
118

randomlse
d Lrlal
serlous (a,
b)
no serlous
lnconslsLe
ncy
serlous
lndlrecLne
ss (c)
serlous
lmpreclson (d)
33 33 88:
0.80 (0.24,
2.72)
vL8? LCW lMC81A
n1
Shaw eL
al. 2012
100

reLrospecL
lve cohorL
926 2778 C8:
0.431(0.160,
3 fewer per 1000 (from 7
fewer Lo 2 more)

ua||ty assessment No of pat|ents Lffect s|ze
ua||ty
Importan
ce Study |d. Des|gn
k|sk of
b|as
Incons|st
ency
Ind|rectn
ess Imprec|s|on
I|u|ds w|th
ch|or|de
<120
mmo|]L
I|u|ds
w|th
ch|or|de >
120
mmo|]L
ke|at|ve
effect(k|sk
rat|o (kk) or
Cdds rat|o
(Ck) Abso|ute effect
1.273)
?unos eL
al. 2012
126

prospecLlv
e cohorL
773 760 C8: 0.32 (0.37-
0.73)
(o) lo tbe kc1 (wotets et ol 2001), ollocotloo cooceolmeot wos oot tepotteJ, somple slze wos too low, ooJ stoJy solotloos wete oot qlveo excloslvely,
(b) 1be obsetvotloool stoJy (5bow et ol. 2012) wos o tettospectlve Jotobose boseJ stoJy wblcb oseJ coJes fot ootcomes wblcb moy oot be occotote. Also, tbete wete lotqe Jlffeteoces lo
boselloe cbotoctetlstlcs betweeo qtoops.
(c) 1be stoJles wete cooJocteJ lo potleots ooJetqoloq sotqety ot oJmltteJ to lcu wblcb ls loJltect to tbe totqet popolotloo, electtolyte Jlstotbooces ls oo loJltect ootcome os lt ls oot o
cllolcol ootcome
(J) cooflJeoce lotetvol(s) ctosseJ Mlus
1ab|e 19: C||n|ca| ev|dence prof||e: I|u|ds w|th ch|or|de concentrat|on |ess than 120 mmo|]L vs f|u|ds w|th ch|or|de concentrat|on greater than 120
mmo|]L - Cont|nuous outcomes
ua||ty assessment No of pat|ents
Lffect s|ze
Mean D|fference ua||ty Importance Study |d Des|gn
k|sk
of
b|as Incons|stency Ind|rectness Imprec|s|on
I|u|ds w|th
ch|or|de <120
mmo|]|
I|u|ds w|th
ch|or|de >
120 mmo|]|
Ac|dos|s (reported as pn |eve|s at d|fferent t|me po|nts)-better |nd|cated by h|gher pn va|ues
Schelngraber 1999( 2
hours)
96

randomls
ed Lrlals
serlou
s(a)
no serlous
lnconslsLency
serlous
lndlrecLness
(b)
no serlous
lmpreclslon

12 12 noL esLlmable(e) vL8?
LCW
C8l1lCAL
1akll 2002 (2 hours)
106
13 13 0.09 (0.06, 0.12)
1akll 2002 (12
hours)
106

13 13
0.01(-0.01, 0.03)
WaLers 2001
(aL admlsslon Lo
surglcal lCu afLer
surgery )
118

33 33 0.03( 0.01, 0.09)
nyperch|oraem|a (reported as ch|or|de |eve|s |n mLq]L)-better |nd|cated by |ower va|ues
Schelngraber 1999(2
hours)
96

randomls
ed Lrlals
serlou
s(a)
no serlous
lnconslsLency
serlous
lndlrecLness
no serlous
lmpreclslon
12 12 noL esLlmable(e) vL8?
LCW
C8l1lCAL

ua||ty assessment No of pat|ents
Lffect s|ze
Mean D|fference ua||ty Importance Study |d Des|gn
k|sk
of
b|as Incons|stency Ind|rectness Imprec|s|on
I|u|ds w|th
ch|or|de <120
mmo|]|
I|u|ds w|th
ch|or|de >
120 mmo|]|
Mclarlane1994
(reporLs lncrease ln Cl-
level)(2 hours)
67

(b) 13 13 -6.3 (-7.61, -4.99)
1akll 2002(2 hours)
106
13 13 -3.00(-8.24, -1.76)
1akll 2002(12 hours)
106
13 13 -6.00 (-10.33, -1.63)
WaLers 2001(aL
admlsslon Lo surglcal
lCu afLer surgery )
118

33 33 -7.00(-9.46, -4.34)
Length of stay |n ICU |n hours-better |nd|cated by |ower va|ues
1akll 2002
106
randomls
ed Lrlals
serlous
(c)
no serlous
lnconslsLency
serlous
lndlrecLness
(d)
no serlous
lmpreclslon
13 13 3.00(-9.78, 19.78) vL8?
LCW
lMC81An1
?unos 2002
126
prospecLl
ve
cohorL
773 760 noL esLlmable(e)
Length of stay |n hosp|ta| |n days-better |nd|cated by |ower va|ues
1akll 2002
106
randomls
ed Lrlals
serlous
(c)
no serlous
lnconslsLency
serlous
lndlrecLness
(d)
no serlous
lmpreclslon
13 13 1.00( -0.43, 2.43) vL8?
LCW
lMC81An1
Shaw 2012
100
8eLrospe
cLlve
cohorL
sLudy
926 2778 0.30 (0.13, 0.83)
?unos 2002
126
prospecLl
ve
cohorL
773 760 noL esLlmable(e)
(o) MetboJ of tooJomlsotloo ooJ ollocotloo cooceolmeot oot tepotteJ lo most stoJles, Jetolls of blloJloq oot tepotteJ, stoJles boJ vety smoll somple slzes.
(b) 8otb ootcomes ote loJltect, os pn voloes ooJ cblotlJe levels ote tepotteJ losteoJ of well JefloeJ cllolcol ootcomes, Also, tbe meosotemeot of setom cblotlJe levels ls Jooe ot less tboo
24 boots lo oll stoJles ooJ lt ls oocleot lf tbls ls o ttoosleot pbeoomeooo ooJ tbetefote less televoot, Also, tbe stoJles wete cooJocteJ lo potleots ooJetqoloq sotqety wblcb ls loJltect
to tbe totqet popolotloo
(c) Ooe stoJy tepotteJ ootcomes ot less tboo 24 boots (1okll 2002)ooJ ooe wos o ooo tooJomlseJ obsetvotloool stoJy(ooos 2012).
(J) 1be stoJles wete cooJocteJ lo potleots ooJetqoloq sotqety ot oJmltteJ to lcu wblcb ls loJltect to tbe totqet popolotloo.
(e) No stooJotJ Jevlotloos tepotteJ fot pn ooJ cblotlJe levels,

l) 5cbeloqtobet 1999- pn lo lotetveotloo qtoop (cl-< 120 mmol/l)=7.41 ooJ lo coottol qtoop(cl->120 mmol/l)=7.28, cblotlJe level lo lotetveotloo qtoop(cl-< 120 mmol/l)=
106mmol/l ooJ lo coottol qtoop (cl->120 mmol/l)= 115mmol/l.
ll)ooos 2012- kepotteJ lo meJloo ooJ lOk, leoqtb of stoy lo lcu lo boots lo lotetveotloo qtoop=42.8 boots(lOk, 21.8-90.5) ooJ lo coottol qtoop=42.9boots(21.1-88.6), leoqtb of stoy
lo bospltol lo Joys lo lotetveotloo qtoop=11 Joys(lOk, 7-22) ooJ coottol qtoop= 11 Joys(lOk, 7-21)
1ab|e 20: C||n|ca| ev|dence prof||e: nyperch|oraem|a vs Normo]nypoch|oraem|a
ua||ty assessment Number of pat|ents Lffect s|ze ua||ty
Important
Study |d Des|gn k|sk of
b|as
Incons|stenc
y
Ind|rectness Imprec|s|o
n
nyperch|or
aem|a
nypo]n
ormoch|
oraem|a
ke|at|ve
effect
Abso|ute
effect]Mean
d|fference

D|chotomous outcomes
Morta||ty
8onlaLLl
eL al.
2011
12

prospecLl
ve cohorL
sLudy
very
serlous
(a)
no serlous
lnconslsLenc
y
very serlous
lndlrecLness (b)
no serlous
lmpreclslon
n8 n8 Cdds raLlo:
1.063
(1.013,
1.118)
noL esLlmable vL8? LCW C8l1lCAL
Sllva eL
al.
2009
102

prospecLl
ve cohorL
sLudy
124 269 8lsk raLlo:
2.60 (1.30,
4.33)
119 more per
1000(from 37
more Lo 262
more)
nosp|ta| morta||ty
nyper Normo vL8? LCW C8l1lCAL
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous l
(a)
no serlous
lnconslsLenc
y
very serlous
lndlrecLness (b)
no serlous
lmpreclslon

81

364 8lsk raLlo:
0.96(0.28,
3.27)
2 fewer per
1000(from 28
fewer Lo 87
more)
nyper nypo
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous
(a)
no serlous
lnconslsLenc
y
very serlous
lndlrecLness (b)
no serlous
lmpreclslon
81

43 8lsk raLlo:
0.16(0.03
0.33)
193 fewer per
1000(from
103 fewer Lo
221 fewer)
Morb|d|ty- AACnL II score
8onlaLLl prospecLl very no serlous very serlous noL n8 n8 noL vL8? LCW lMC81An

ua||ty assessment Number of pat|ents Lffect s|ze ua||ty Important
eL al.
2011
12

ve cohorL
sLudy
serlous
(a)
lnconslsLenc
y
lndlrecLness (b) esLlmable esLlmable(c) 1
1anl eL
al.
2012
109

reLrospec
Llve sLudy
noL
esLlmable(c)

Cont|nuous outcomes
Length of stay |n ICU |n days- better |nd|cated by |ower va|ues
Sllva eL
al.
2009
102

prospecLl
ve cohorL
sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
noL
esLlmable
124 269 noL
esLlmable(d)
vL8? LCW lMC81An
1
nyper Normo
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
no serlous
lmpreclslon
81 364 Mu:
-2.90 (-4.03, -
1.77)
nyper nypo
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
no serlous
lmpreclslon
81 43 Mu:
-9.90(-13.91, -
3.89)

Length of stay |n hosp|ta| |n days- better |nd|cated by |ower va|ues
Sllva eL
al.
2009
102

prospecLl
ve cohorL
sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
noL
esLlmable
124 269 noL
esLlmable(d)
vL8? LCW lMC81An
1
nyper Normo
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
no serlous
lmpreclslon
81 364 Mu:
-13.10(-18.72,
-7.28)
nyper nypo

ua||ty assessment Number of pat|ents Lffect s|ze ua||ty Important
1anl eL
al.
2012
109

reLrospec
Llve sLudy
very
serlous
(a)
no serlous
lnconslsLency
very
serlous
lndlrecLnes
s (b)
no serlous
lmpreclslon
81 43 Mu:
-42.10(-62.19,
-22.01)
(o) 5toJles wete ooo- tooJomlseJ obsetvotloool stoJles wltb smoll somple slzes. 1be flolJ tesoscltotloo sttoteqles ptlot to ooJ Jotloq sotqety ote oot tepotteJ, tbetefote, lt ls oocleot lf tbe
effects of bypetcblotoemlo ote Joe to flolJ tesoscltotloo.
(b) 1be stoJles ote cooJocteJ lo sotqlcol potleots ot l1u potleots ooJ moy oot be tepteseototlve of oll potleots tecelvloq lottoveooos flolJs, tbetefote loJltect to tbe totqet popolotloo. lt ls
oocleot lf oll potleots tecelveJ lv flolJs ooJ wbetbet tbe obootmollty lo cblotlJe levels wos o coosepoeoce of lottoveooos flolJ tbetopy, tbetefote loJltect to tbe lotetveotloo.
(c) (c) No tow Joto ot tlsk totlos tepotteJ, lo 8oolottl et ol. 2011- tesolts tepotteJ os oo cottelotloo betweeo cblotlJe levels ooJ sevetlty of Jlseose occotJloq to tbe AlAcn ll scote, bowevet,
lo 1ool et ol. 2012, cblotlJe level wos ossocloteJ wltb tbe sevetlty of Jlseose occotJloq to AlAcn ll scote- tbe sevetlty of cooJltloos wos qteotet lo bypocblotoemlc potleots lo ctltlcol cote
settloq.
(J) Meoo Jlffeteoces wete oot estlmoble os voloes tepotteJ ote meJloo ooJ tooqes (25
tb
-75
tb
petceotlles), lo 5llvo et ol. 2009, leoqtb of stoy lo lcu lo Joys wos 2.0 (1.0- J.0) lo botb qtoops ooJ
leoqtb of stoy lo bospltol lo Joys lo tbe qtoop wltb bypetcblotoemlo wos 1J.0(8.0-19.5)ooJ 10.0(6.0-18.0)lo qtoop wltb ootmo/bypocblotoemlo.


89

no relevanL economlc evaluaLlons for Lhe cosL effecLlveness of measurlng serum chlorlde
concenLraLlons for Lhe purpose of recognlslng poLenLlal problems from hyperchloraemla ln people ln
hosplLal who requlre lv flulds were ldenLlfled.
C||n|ca|
Compar|son: I|u|ds w|th ch|or|de concentrat|on > 120mmo|]L vs. I|u|ds w|th ch|or|de
concentrat|on< 12ommo|]L
Cverall, mosL 8C1s and observaLlonal sLudles suggesL LhaL Lhe provlslon of lnLravenous flulds
conLalnlng less Lhan 120 mmol/l of chlorlde ls assoclaLed wlLh lower morLallLy and morbldlLy Lhan Lhe
provlslon of flulds conLalnlng more Lhan 120 mmol/l of chlorlde, alLhough all evldence was very low
quallLy. lndlvldual sLudles lncluded Lhe followlng effecLs:
Cne randomlsed conLrolled Lrlal wlLh 66 paLlenLs and Lwo observaLlonal sLudles wlLh 3237
paLlenLs suggesLed LhaL paLlenLs recelvlng lnLravenous flulds wlLh chlorlde concenLraLlon less Lhan
120 mmol/l may have less acuLe ln[ury and lower morLallLy ln comparlson Lo paLlenLs recelvlng
lnLravenous flulds wlLh chlorlde concenLraLlon greaLer Lhan 120 mmol/l.[very low quallLy]
Cne observaLlonal sLudy wlLh 3704 paLlenLs suggesLed LhaL paLlenLs recelvlng lnLravenous flulds
wlLh chlorlde concenLraLlon less Lhan 120 mmol/l may have less morbldlLy and less elecLrolyLe
dlsLurbances ln comparlson Lo paLlenLs recelvlng lnLravenous flulds wlLh chlorlde concenLraLlon
greaLer Lhan 120 mmol/l.[very low quallLy]
1hree randomlsed conLrolled Lrlals wlLh 126 paLlenLs suggesLed LhaL LhaL paLlenLs recelvlng
lnLravenous flulds wlLh chlorlde concenLraLlon less Lhan 120 mmol/l may have less acldosls and
less hyperchloremla compared Lo paLlenLs recelvlng lnLravenous flulds wlLh chlorlde
concenLraLlon greaLer Lhan 120 mmol/l. [very low quallLy]
Cne randomlsed conLrolled Lrlal wlLh 30 paLlenLs suggesLed LhaL paLlenLs recelvlng lnLravenous
flulds wlLh chlorlde concenLraLlon greaLer Lhan 120 mmol/l for lnLravenous fluld Lherapy may
have shorLer lengLh of sLay ln lCu as compared Lo paLlenLs recelvlng lnLravenous flulds wlLh
chlorlde concenLraLlon less Lhan 120 mmol/l buL Lhe sLudy was very small wlLh wlde varlaLlon ln
lCu lengLhs of sLay and consequenLly exLremely wlde confldence lnLervals whlch dld noL allow any
real concluslons Lo be drawn. [very low quallLy]
Cne randomlsed conLrolled Lrlal wlLh 30 paLlenLs and one observaLlonal sLudy wlLh 3704 paLlenLs
suggesLed LhaL paLlenLs recelvlng lnLravenous flulds wlLh chlorlde concenLraLlon greaLer Lhan 120
mmol/l for lnLravenous fluld Lherapy may have shorLer lengLh of sLay ln hosplLal as compared Lo
paLlenLs recelvlng lnLravenous flulds wlLh chlorlde concenLraLlon less Lhan 120 mmol/l. [very low
quallLy]
Compar|son: nyperch|oraem|a vs Normo]nypoch|oraem|a
Cverall, Lhe assoclaLlons beLween serum chlorlde level and cllnlcal ouLcomes were dlfflculL Lo
lnLerpreL, wlLh some sLudles suggesLlng worse cllnlcal ouLcomes wlLh hyperchloraemla compared Lo
normal or low chlorlde levels, whereas oLhers suggesLed LhaL Lhe worsL ouLcomes were ln paLlenLs
who were hypochloraemlc. lurLhermore, lL was noL posslble Lo deLermlne wheLher abnormal serum
chlorlde ln elLher dlrecLlon was predomlnanLly a reflecLlon of lnapproprlaLe lv fluld prescrlblng raLher
Lhan underlylng dlsease sLaLes. lndlvldual sLudles lncluded Lhe followlng effecLs:

90
1wo prospecLlve cohorL sLudles wlLh 602 paLlenLs suggesLed LhaL paLlenLs wlLh hyperchloraemla
have a hlgher rlsk of morLallLy compared Lo paLlenLs wlLh normo/hypo-chloraemla, and chlorlde
level was lndependenLly assoclaLed wlLh morLallLy ln a mulLlple regresslon model. Powever,
evldence from anoLher reLrospecLlve cohorL sLudy wlLh 488 paLlenLs suggesLed LhaL paLlenLs wlLh
hypochloraemla had Lhe greaLesL hosplLal morLallLy followed by paLlenLs wlLh normochloraemla
and Lhen followed by paLlenLs wlLh hyperchloraemla. [very low quallLy]
Cne prospecLlve cohorL sLudy wlLh 212 paLlenLs suggesLed LhaL Lhere was no correlaLlon beLween
chlorlde level and Lhe severlLy of dlsease accordlng Lo Lhe AACPL ll score. Powever, anoLher
reLrospecLlve cohorL sLudy wlLh 488 paLlenLs suggesLed LhaL chlorlde level was assoclaLed wlLh Lhe
severlLy of dlsease and Lhe severlLy of dlsease was hlghesL ln paLlenLs wlLh hypochloraemla. [very
low quallLy]
Cne prospecLlve cohorL sLudy wlLh 393 paLlenLs showed LhaL Lhere was no dlfference ln lengLh of
sLay ln lCu beLween paLlenLs wlLh hyperchloraemla as compared Lo Lhose wlLh
hypo/normochloraemla. Powever, one reLrospecLlve cohorL sLudy wlLh 488 paLlenLs suggesLed
LhaL paLlenLs wlLh hypochloraemla had Lhe greaLesL lengLh of sLay ln hosplLal and lCu followed by
paLlenLs wlLh normochloraemla and Lhen followed by paLlenLs wlLh hyperchloraemla. [very low
quallLy]
Lconom|c
no relevanL economlc evaluaLlons were ldenLlfled.
kecommendat|ons
1S. If pat|ents have rece|ved IV f|u|ds conta|n|ng ch|or|de concentrat|ons
greater than 120 mmo|]| (for examp|e, sod|um ch|or|de 0.9), mon|tor
the|r serum ch|or|de concentrat|on da||y. If pat|ents deve|op
hyperch|oraem|a or ac|daem|a, reassess the|r IV f|u|d prescr|pt|on and
assess the|r ac|dbase status. Cons|der |ess frequent mon|tor|ng for
pat|ents who are stab|e.
8elaLlve values of
dlfferenL ouLcomes
1he mosL lmporLanL ouLcomes were agreed by Lhe CuC as Lhe developmenL of
susLalned hyperchloraemla and hyperchloraemlc acldosls whlch are llkely Lo be
dlrecL consequences of recelvlng lnLravenous flulds wlLh hlgh concenLraLlons of
serum chlorlde. MorLallLy and morbldlLy were also consldered lmporLanL ouLcomes.
1he presence of hypochloraemla ls also lmporLanL buL ls ofLen caused by underlylng
dlsease sLaLes wlLh hlgh chlorlde losses or excess waLer reLenLlon raLher Lhan by
lnapproprlaLe lv fluld prescrlblng alone.
1rade-off beLween
harms
MeasuremenL of serum chlorlde concenLraLlon helps ln Lhe early ldenLlflcaLlon of
hyperchloraemla, hyperchloraemlc acldosls and hypochloraemla whlch could be
slgnlflcanL ln decreaslng assoclaLed morbldlLy and morLallLy. AlLhough Lhe wlder use
of chlorlde measuremenL would lncrease Lhe raLe of lnvaslve monlLorlng lf no oLher
LesLs were belng underLaken, lL ls very unllkely LhaL Lhls would ever occur ln reallLy
slnce paLlenLs recelvlng lv flulds also requlre oLher laboraLory monlLorlng.
Lconomlc
conslderaLlons
no evldence of cosL-effecLlveness was found.
Some analysers wlll rouLlnely measure serum chlorlde concenLraLlon, even lf Lhe LesL
resulL ls noL revealed Lo Lhe orderlng cllnlclan unless speclflcally requesLed. ln Lhls
case Lhere wlll be no lncremenLal cosL assoclaLed wlLh orderlng Lhe LesL. ln oLher
hosplLals, however, Lhere wlll be an lncreased cosL assoclaLed wlLh lnLroduclng wlder
chlorlde measuremenL alLhough Lhls should noL amounL Lo more Lhan a few pence
per LesL. 1he CuC expecLs Lhls modesL lncrease ln cosL Lo be offseL by cosL savlngs
from averLlng compllcaLlons ln addlLlon Lo assoclaLed lmprovemenLs ln healLh
ouLcome.
CuallLy of evldence Cverall, mosL 8C1s and observaLlonal sLudles suggesL LhaL Lhe provlslon of

91
lnLravenous flulds conLalnlng <120 mmol/l ls assoclaLed wlLh lower morLallLy and
morbldlLy Lhan Lhe provlslon of flulds conLalnlng >120 mmol/l. lour 8C1s and one
observaLlonal sLudy conLrlbuLed Lo Lhe evldence whlch was of very low quallLy.
Cverall, Lhe assoclaLlons beLween chloraemlc sLaLe and cllnlcal ouLcomes were very
dlfflculL Lo lnLerpreL, wlLh some sLudles suggesLlng worse cllnlcal ouLcomes wlLh
hyperchloraemla compared Lo normal or low chlorlde levels, whereas oLhers
suggesLed LhaL Lhe worsL ouLcomes were ln paLlenLs who were hypochloraemlc.
Lvldence was derlved from Lhree cohorL sLudles and was of very low quallLy and
furLhermore, lL was noL posslble Lo deLermlne wheLher abnormal serum chlorlde
level elLher hlgh or low was predomlnanLly a reflecLlon of lnapproprlaLe lv fluld
prescrlblng raLher Lhan underlylng dlsease sLaLes.
CLher conslderaLlons 1he revlew quesLlon was addressed ln Lwo secLlons. 1he flrsL secLlon evaluaLed Lhe
developmenL of hyperchloraemla ln paLlenLs recelvlng lv flulds wlLh chlorlde
concenLraLlons greaLer Lhan 120mmmol/l. Powever, all Lhe sLudles reporLed
ouLcomes aL less Lhan 24 hours afLer lnfuslon and lL was unclear lf Lhe
hyperchloraemla was susLalned beyond Lhls and was relevanL.
1he second secLlon presenLed evldence from sLudles whlch evaluaLed assoclaLlon of
abnormal chlorlde levels wlLh morLallLy and morbldlLy. A ma[or drawback of Lhls
evldence ls LhaL lL was unclear lf Lhe paLlenLs had recelved lnLravenous flulds ln Lhe
sLudles and Lhe hyperchloraemla was a consequence of Lhls. 1he evldence has been
downgraded for lndlrecLness on Lhls accounL and Lhe CuC agreed LhaL lL overall, Lhe
flndlngs could noL acLually conLrlbuLe Lo declslon maklng.
1he lack of hlgh quallLy evldence demonsLraLlng an assoclaLlon beLween serum
chlorlde and cllnlcal ouLcomes was acknowledged by Lhe CuC and Lherefore
recommendaLlons were based on Lhe evldence revlewed and Lhe consensus experL
oplnlon of Lhe CuC members. 1he CuC also dlscussed Lhe lmporLance of llnklng Lhls
recommendaLlon wlLh Lralnlng and educaLlon abouL how Lo lnLerpreL serum chlorlde
level and how Lo use lL as an assessmenL Lool raLher Lhan Lo slmply change Lhe lv
fluld prescrlbed as a resulL of a slngle serum chlorlde measuremenL.


92
6.3.4 A|gor|thm 1: Assessment

1h|s sect|on ||nks the ev|dence to A|gor|thm 1 and recommendat|on bu||et spec|f|c to assessment.
kecommendat|ons
Cffer IV f|u|d therapy as part of a protoco| (see A|gor|thms for IV f|u|d
therapy):
Assess patients fluid and electrolyte needs following
A|gor|thm 1: Assessment.
If pat|ents need IV f|u|ds for f|u|d resusc|tat|on, fo||ow
A|gor|thm 2: I|u|d resusc|tat|on.
If pat|ents need IV f|u|ds for rout|ne ma|ntenance, fo||ow
A|gor|thm 3: kout|ne ma|ntenance.
If pat|ents need IV f|u|ds to address ex|st|ng def|c|ts or
excesses, ongo|ng abnorma| |osses or abnorma| d|str|but|on,
fo||ow A|gor|thm 4: kep|acement and red|str|but|on.
ouLcomes
1he CuC were lnLeresLed ln all cause morLallLy, lengLh of hosplLal sLay,
compllcaLlons lncludlng renal and resplraLory problems, and morbldlLy as
measured by SClA or MCuS scores.
1rade-off beLween cllnlcal
beneflLs and harms
roLocols are by deslgn creaLed Lo supporL cllnlcal declslon maklng, and are noL
meanL Lo replace cllnlcal [udgemenL aL Lhe bedslde.
Lconomlc conslderaLlons ln chapLer 1 lL was noLed LhaL for paLlenLs wlLh sepsls, proLocollsed care was
found Lo be cosL-effecLlve for sepsls paLlenLs ln Lwo sLudles and cosL savlng ln a
Lhlrd sLudy. 1hls evldence was consldered Lo be parLlally appllcable and wlLh
Using an ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach,
assess whether the patient is hypovolaemic and needs fluid resuscitation
Assess volume status taking into account clinical examination, trends and context.
Indicators that a patient may need fluid resuscitation include: systolic BP <100mmHg;
heart rate >90bpm; capillary refill >2s or peripheries cold to touch; respiratory rate >20
breaths per min; NEWS 5; 45
o
Can the patient meet their fluid and/or electrolyte needs orally or
enterally?

Clinical examination: pulse, BP, capillary refill, JVP, oedema (peripheral/pulmonary), postural
hypotension.

Does the patient have complex fluid or electrolyte replacement
or abnormal distribution issues?
Look for existing deficits or excesses, ongoing abnormal losses,
abnormal distribution or other complex issues.

Algorithm 3: Routine
Maintenance

Algorithm 2:
Fluid
Resuscitation

Algorithm 4:
Replacement and
Redistribution

No

Ensure nutrition and fluid
needs are met
Also see Nutrition support in
adults (NICE clinical
guideline 32).
Yes
Yes
Yes
No

No

93
poLenLlally serlous llmlLaLlons.
1here was no cosL-effecLlveness evldence for paLlenLs wlLhouL sepsls.
Powever, glven LhaL Lhe healLh lmprovemenLs observed ln Lhe revlew of
cllnlcal effecLlveness evldence were [usL as pronounced for lnLra-operaLlve care
Lhe CuC felL LhaL Lhe economlc beneflLs of proLocols are very llkely Lo be
achlevable across all seLLlngs.
CuallLy of evldence 1he algorlLhm was based on esLabllshed guldance (nLWS, Advanced Llfe
SupporL guldance, nlCL CC30), consensus oplnlon of Lhe CuC members and
flndlngs from Lhe sysLemaLlc revlew on cllnlcal effecLlveness of proLocollsed
care.
CuallLy of evldence for ouLcomes analysed ln Lhe sysLemaLlc revlew was very
low. lor deLalls on quallLy of evldence for lndlvldual revlews, cllnlcal evldence
proflles ln secLlons.
CLher conslderaLlons uesplLe Lhe pauclLy of evldence on Lhe use of proLocols for lv fluld
admlnlsLraLlon, Lhe CuC felL LhaL proLocollsed care ln general achleves beLLer
ouLcomes for paLlenLs and Lherefore declded LhaL an algorlLhmlc approach Lo
assessmenL of fluld and elecLrolyLe sLaLus ls approprlaLe ln Lhls conLexL. ln
deslgnlng Lhe algorlLhm, Lhe CuC placed parLlcular emphasls on developlng
recommendaLlons LhaL a foundaLlon year docLor could follow.
1he CuC agreed LhaL recognlLlon of Lhe serlously lll paLlenL wlLh a nLWS score
of 3 or more should prompL seeklng of experL help, alongslde Lhe lnlLlaLlon of
resuscitation. The GDG consensus on expert help is deflned by nlCL CC30.
1hls recommendaLlon was ldenLlfled as a key prlorlLy for lmplemenLaLlon by
Lhe CuC.

6.4 kesearch recommendat|ons
1. What |s the |nc|dence of comp||cat|ons dur|ng, and as a consequence of, IV f|u|d therapy?

Why th|s |s |mportant
1hls ls almosL cerLalnly under-reporLed ln Lhe ward seLLlng wlLh slgnlflcanL lmpllcaLlons for paLlenLs,
predomlnanLly morbldlLy Lhrough Lo morLallLy. lL ls probable LhaL compllcaLlons of fluld Lherapy are
frequenL and may be assoclaLed wlLh lncreased cllnlcal needs, such as crlLlcal care and, on occaslon,
may necesslLaLe resusclLaLlon. Lack of a seL of clearly deflned feaLures of Lhe compllcaLlons of fluld
mlsmanagemenL compounds Lhe problem. lL ls lmporLanL Lo deflne Lhese feaLures and Lhen
underLake an observaLlonal sLudy ln a hosplLal seLLlng Lo deLermlne Lhe epldemlology of Lhese
compllcaLlons. Such a sLudy would hlghllghL Lhe prevalence of fluld relaLed compllcaLlons and lnform
Lhe developmenL of prevenLlve measures.
lnLravenous fluld Lherapy for fluld resusclLaLlon

94
7 Intravenous f|u|d therapy for f|u|d resusc|tat|on
7.1 Introduct|on
urgenL fluld resusclLaLlon ls needed lf a paLlenL has losL enough fluld elLher acuLely or chronlcally Lo
sLarL showlng slgns of decompensaLlon. SympaLheLlc responses aLLempL Lo compensaLe for Lhe
decrease ln lnLravascular volume by prlorlLlslng blood flow Lo vlLal organs. 1he hearL raLe ls usually
lncreased (Lachycardla) and perlpheral vasoconsLrlcLlon lncreases dlasLollc blood pressure. and Lhe
LoLal effecLlve lnLravascular volume ls reduced by vasoconsLrlcLlon. 1he Lachycardla and reduced
perlpheral perfuslon ls followed by a marked decrease ln sysLollc blood pressure when more Lhan 30-
40 of Lhe lnLravascular volume has been losL. 1he changes are Lherefore manlfesL by Lachycardla
and reduced perlpheral perfuslon and as Lhe volume deflclL lncreases, an lncreaslngly marked fall ln
blood pressure wlLh dysfuncLlon of mosL organ sysLems. CenLral nervous sysLem depresslon causes
aglLaLlon, confuslon or decreased level of consclousness, renal hypo-perfuslon causes ollgurla and
general Llssue hypo-perfuslon causes acldosls, ofLen wlLh compensaLory Lachypnoea.
Shock is defined as a life threatening condition with generalized maldistribution of blood flow
causing failure to deliver and/or utilize adequate amounts of oxygen, leading to tissue dysoxia. . It is
always beLLer Lo prevenL shock and prevenL any slgns of end organ fallure.
1he presence of Lwo or more of Lhe followlng ls llkely Lo lndlcaLe shock.
ulse raLe > 20 bpm above basellne
SysLollc 8 20 mmPg less Lhan normal
Caplllary reflll greaLer Lhan 2 seconds
8esplraLory raLe > 20 per mlnuLe
urlne ouLpuL less Lhan 0.3 ml/kg/h
1he presence of organ dysfuncLlon ls also suggesLed by meLabollc acldosls, lncreased plasma lacLaLe
values and a cenLral venous oxygen saLuraLlon of <70.
1here ls a wlde range ln Lhe ablllLy of paLlenLs Lo compensaLe for fluld loss. aLlenLs wlLh slgnlflcanL
co-morbldlLles and Lhose Laklng cardlovascular drugs, for example, may decompensaLe wlLh
relaLlvely llLLle fluld loss. ?oung, very flL paLlenLs wlll compensaLe for much greaLer loss of
lnLravascular volume and Lhelr sysLollc blood pressure may be preserved unLll severe shock has
ensued.
ln Lhe uk, Lhe recenL adopLlon of Lhe naLlonal Larly Warnlng Score (nLWS) provldes a baslc unlversal
meLhod Lo ldenLlfy Lhe slgns of physlologlcal decompensaLlon.
93
nLWS ls derlved from slx
physlologlcal parameLers: resplraLory raLe, arLerlal blood oxygen saLuraLlon, LemperaLure, sysLollc
blood pressure, pulse raLe and level of consclousness, an ad[usLmenL ls made for paLlenLs recelvlng
oxygen Lherapy. 1he aggregaLe score Lrlggers a response from nurslng and/or medlcal sLaff
dependlng on Lhe Lhresholds seL by local pollcy.
1reaLmenL of shock requlres urgenL lnLravenous fluld lnfuslon Lo resLore lnLravascular volume,
reverse decompensaLlon and resLore organ perfuslon. CLher lmmedlaLe measures may also be
needed, lncludlng hlgh-flow oxygen, leg ralslng/head down LllL, Lhe use of lnoLropes and speclflc
measures Lo LreaL Lhe orlglnal cause of hypovolaemla, buL Lhese are beyond Lhe scope of Lhls
guldance.

93
AlLhough lL ls crlLlcal LhaL adequaLe fluld ls glven Lo resLore and Lhen malnLaln lnLravascular volume,
lL ls lmporLanL Lo avold fluld and/or elecLrolyLe overload. Modlfylng and monlLorlng Lhe lnLravascular
volume ls relaLlvely easy buL Lhls ls much more dlfflculL for Lhe lnLersLlLlal and lnLracellular fluld
comparLmenLs. 1he amounL of fluld needed for resusclLaLlon ls exLremely varlable and so frequenL
reassessmenL ls needed. 1he llLeraLure revlew alms Lo esLabllsh Lhe besL Lype of fluld(s) for
resusclLaLlon and Lhe opLlmum Llmlng and volume of admlnlsLraLlon.
7.1.1 IV I|u|ds for resusc|tat|on
A varleLy of crysLallolds, arLlflclal collolds and human albumln soluLlons have been used for fluld
resusclLaLlon and Lhere has been conslderable debaLe for more Lhan 30 years abouL Lhe besL Lype of
fluld Lo use and Lhe opLlmal volume and raLes of dellvery. SoluLlons such as glucose 3 and glucose
sallne are noL sulLable for fluld resusclLaLlon because Lhey lead Lo rapld dlluLlon of plasma sodlum
and only modesL lncreases ln clrculaLory volume because of Lhelr Lendency Lo dlsLrlbuLe rapldly
across all fluld comparLmenLs.
1here has been conslderable debaLe over 30 years or more ln relaLlon Lo Lhe besL Lype of fluld Lo use
for fluld resusclLaLlon, as well as Lhe opLlmal volume and raLe of dellvery. 1hese debaLes have
revolved around Lhe followlng:
SynLheLlc collolds as well as albumln soluLlons have LheoreLlcal advanLages over crysLallolds ln
Lerms of Lhelr ablllLy Lo expand lnLravascular volume raLher Lhan Lhe lnLersLlLlal space buL ln
recenL years lL has become clear LhaL Lhey are less effecLlve ln Lerms of lnLravascular volume
expanslon and reLenLlon Lhan orlglnally LhoughL, especlally ln paLhophyslologlcal sLaLes when, ln
Lhe presence of hypovolaemla and hlgh caplllary escape raLes, all lv flulds have very dlfferenL
posL-lnfuslon dlsLrlbuLlons Lhan ln healLh. Collolds are also more expenslve Lhan crysLallolds.
1he synLheLlc collolds avallable vary conslderably ln slze and sLrucLure and Lherefore have
dlfferenL dlsLrlbuLlons and capaclLy Lo expand plasma volume, as well as oLher dlfferlng properLles
lncludlng half-llfe and poLenLlal LoxlclLy. Plgh (430 ku) and medlum molecular welghL (200 ku)
hydroxyeLhyl sLarches have also been shown Lo have adverse effecLs and as a resulL are now
rarely used ln Lhe uk, especlally ln admlsslon unlLs or general ward seLLlngs. lor Lhls reason, Lhe
hlgh and medlum molecular welghL sLarches were noL lncluded ln our revlew.
8alanced soluLlons, elLher balanced crysLallolds per se or collolds made up ln a balanced
crysLallold base, have LheoreLlcal advanLages over sodlum chlorlde 0.9 or collolds made up ln
sodlum chlorlde 0.9 slnce lnfuslon of more sodlum may lead Lo lncreased posL-resusclLaLlon
lnLersLlLlal sodlum and waLer reLenLlon and lnfuslon of more chlorlde mlghL cause
hyperchloraemla wlLh posslble assoclaLed adverse effecLs such as acldosls and decreases ln renal
perfuslon and glomerular fllLraLlon.
18,79

uesplLe Lhe years of debaLe, uncerLalnLy remalns abouL Lhe besL fluld Lo use and many declslons are
acLually based on personal preferences.
1he lnLenLlon of Lhls chapLer ls Lo examlne Lhe evldence avallable on lv fluld Lherapy for fluld
resusclLaLlon. 1hls evldence wlll lnform baslc guldance on when Lo use lv fluld resusclLaLlon, as well
as Lhe Lype, volume and raLe of lnfuslon of fluld. 1he guldance applles Lo hosplLal paLlenLs ln
admlsslon and general ward areas belng LreaLed by healLhcare professlonals who are noL experLs ln
fluld resusclLaLlon.
7.2 Intravenous f|u|d therapy for f|u|d resusc|tat|on- 1ypes of f|u|d
1he ob[ecLlve of Lhe formal cllnlcal evldence revlew was Lo ldenLlfy Lhe mosL cllnlcally and cosL
effecLlve Lypes of fluld Lo be used for resusclLaLlon ln general hosplLal admlsslon unlLs and ward
seLLlngs.

96
kev|ew quest|on: What |s the most c||n|ca| and cost effect|ve |ntravenous f|u|d for resusc|tat|on of
hosp|ta||sed pat|ents?
We searched for randomlsed conLrolled Lrlals (8C1) comparlng Lhe effecLlveness for lmprovlng
ouLcomes of gelaLln, hydroxyeLhylsLarch (LeLrasLarch), sodlum chlorlde 0.9 soluLlon, balanced
solutions (Ringers lactate/acetate, Hartmanns solution) and albumin (all compared to each other) as
lnLervenLlons ln hosplLal paLlenLs requlrlng lv fluld resusclLaLlon.
1he guldance conLalned ln Lhls documenL ls focussed on prescrlblng lv flulds ln hosplLal admlsslon
unlLs and general wards, Lherefore, Lhe evldence revlew dld noL lnclude large penLa- or hexa-sLarches
nor hyper-oncoLlc crysLallolds or collolds as comparaLors because Lhese fluld Lypes are rarely lf ever
used ln such seLLlngs.
8evlew sLraLegy:
1he LargeL populaLlon for Lhls revlew was adulLs ln hosplLal who were recelvlng lnLravenous fluld
Lherapy for fluld resusclLaLlon. 1he CuC dlscussed and agreed LhaL lf no evldence ln Lhe LargeL
populaLlon was ldenLlfled, Lhe revlew would lnclude lndlrecL evldence ln Lhe followlng order:
1.paLlenLs ln lnLenslve care unlLs/ hlgh dependency unlLs,
2.emergency servlces, lncludlng paLlenLs fluld resusclLaLlon ln ambulances and emergency servlces
3.lnLra-operaLlve paLlenLs (Lhls would however exclude paLlenLs recelvlng lv flulds for
normovolaemlc hemodlluLlon, lnLraoperaLlve cardlac bypass surgery and preload for splnal
anaesLhesla as Lhese were deemed Lo be Loo lndlrecL or relevanL Lo Lhe LargeL populaLlon)
lor more deLalls on Lhe revlew proLocol, see secLlon C.3.1, Appendlx C.
Cne Cochrane revlew was ldenLlfled comparlng crysLallolds wlLh collolds ln crlLlcally lll paLlenLs
83
.
AlLhough Lhls was parLlally relevanL Lo our revlew quesLlon, lL was noL lncluded as Lhe proLocol for
Lhls revlew dlffered from LhaL of Lhe Cochrane revlew ln Lhe followlng respecLs:
1he Cochrane revlew
83
lncluded sLudles on paLlenLs wlLh burns and LraumaLlc braln ln[ury LhaL
were ouL of Lhe scope of Lhls guldellne.
1he Cochrane revlew lncluded penLasLarches, hexasLarches and hyper-oncoLlc crysLallolds and
collolds.
1he Cochrane revlew lncluded sLudles conducLed before 1990 whllsL Lhe CuC felL LhaL LhaL slnce
pracLlce ln fluld resusclLaLlon has evolved over Llme, sLudles prlor Lo 1990 may noL be relevanL
and Lhey were Lherefore excluded.
A number of oLher Cochrane revlews were also ldenLlfled whlch evaluaLed some of Lhe lnLervenLlons
lncluded ln Lhls revlew.
13,23,26,31,66,88,111
1hese were even less relevanL Lo Lhe revlew proLocol and
Lherefore noL lncluded. lor reasons of excluslon, see Lhe excluded sLudles llsL ln secLlon P.2,
Appendlx P).

8elow ls a maLrlx showlng where evldence was ldenLlfled. A box fllled wlLh a number represenLs Lhe
number of sLudles found for LhaL comparlson and subsequenLly revlewed ln Lhls chapLer. 1here ls no
dlscusslon ln Lhe chapLer on comparlsons where no sLudles were ldenLlfled.
1ab|e 21: Matr|x of treatment compar|sons
Ge|at|n Sod|um ch|or|de 0.9
8a|anced
so|ut|ons A|bum|n
1etrastarch 3 4 1 0

97
Ge|at|n Sod|um ch|or|de 0.9
8a|anced
so|ut|ons A|bum|n
Ge|at|n 1 3 0
Sod|um ch|or|de 0.9 0 1
8a|anced so|ut|ons 0
A|bum|n
1be oombet lo eocb box loJlcotes tbe oombet of stoJles lJeotlfleJ fot tbot compotlsoo.
7.2.1 Ge|at|n
Comparisons: Gelatin vs hydroxyethylstarch, sodium chloride 0.9%, balanced solutions (Ringers
lactate/ acetate, Hartmanns solution) and albumin.
Seven 8C1s were ldenLlfled as relevanL Lo Lhls revlew quesLlon.
33,34,41,43,64,113,123

llve 8C1s compared CelaLln wlLh LeLrasLarches
33,34,43,64,113,123

Three RCTs compared Gelatin with lactated Ringers solution
34,41,123

Cne 8C1 compared CelaLln wlLh sodlum chlorlde 0.9 soluLlon
113

Cf Lhe slx sLudles comparlng gelaLln Lo LeLrasLarches, Lhree were Lhree-armed Lrlals wlLh
physlologlcal lacLaLed soluLlons as Lhe Lhlrd comparaLor.
34,43,123
Cne furLher Lrlal was also Lhree-
armed wlLh sodlum chlorlde 0.9 as Lhe addlLlonal comparaLor.
113

1he populaLlons lncluded ln Lhe sLudles varled:
Cne was on paLlenLs undergolng gasLrecLomy
43
.
Cne lncluded paLlenLs undergolng orLhopaedlc surgery
41
,
1wo were on people who had open aorLlc aneurysm surgery
33,64

1wo were on posLoperaLlve paLlenLs, one sLudy had a populaLlon of hypovolaemlc posLoperaLlve
paLlenLs
34
and one sLudy had a populaLlon of posLoperaLlve cardlac and vascular surgery paLlenLs
113

Cne was on Lrauma paLlenLs
123

1here was heLerogenelLy ln Lhe lnLervenLlons of Lhe lncluded sLudles:
1he lnLervenLlon fluld admlnlsLered Lo Lhe sLudy groups was flxed (elLher by volume of fluld, or by
proLocol of fluld admlnlsLraLlon) ln 3 sLudles
33,34,43,113,123
, and was varled accordlng Lo whlch fluld
was recelved ln one sLudles
41
1wo sLudles dld noL reporL Lhe proLocol for fluld admlnlsLraLlon.
64,123

Some studies reported median values for the outcomes amount of study fluid received
113
, lengLh of
sLay ln lCu
33,34
and length of stay in hospital
33
, Lhese ouLcomes could noL be meLa-analysed.
1he flndlngs are summarlsed ln Lhe cllnlcal C8AuL evldence proflle below (see 1able 22, 1able 23 and
1able 24). See also Lhe full sLudy evldence Lables ln secLlon L.3.1, Appendlx L and foresL ploLs ln
secLlon C.3.1, Appendlx C. lor deLalls on excluded sLudles, see secLlon P.2, Appendlx P.


1ab|e 22: C||n|ca| ev|dence prof||e: Ge|at|n vs tetrastarch
ua||ty assessment No of pat|ents Lffect
ua||ty
Importa
nce
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|
on
Cther GLLA1IN nLS ke|at|ve
(9S CI)
Abso|ute
Morta||ty
33,34,64,113

4 randomlsed
Lrlals
Serlous(a) Serlous(b) very
serlous(c)
no serlous
lmpreclslo
n
none 21/119
(17.6)
17/120
(14.2)
88 1.24
(0.70 Lo
2.18)
vL8?
LCW
C8l1lCAL
Morta||ty ostoperat|ve
34,113

2 randomlsed
Lrlals
Serlous(a) no serlous
lnconslsLency
very
serlous(c)
no serlous
lmpreclslo
n
none 13/66
(19.7)
14/67
(20.9)
88 0.93
(0.49 Lo
1.78)
vL8?
LCW
C8l1lCAL
Morta||ty - Aort|c aneurysm
33,64

2 randomlsed
Lrlals
lnconslsLency
very
serlous(c)
no serlous
lmpreclslo
n
none 8/33
(13.1)
3/33
(3.7)
88 2.70
(0.76 Lo
9.36)
vL8?
LCW
C8l1lCAL
Vo|ume of study f|u|d adm|n|stered (8etter |nd|cated by |ower va|ues)
33,41,4S,64

4 randomlsed
Lrlals
Serlous(d) no serlous
lnconslsLency
Serlous(e) very
serlous(f)
none 83 83 - Mu 103.28 hlgher (96.10
vL8?
LCW
lMC81
An1
Vo|ume of study f|u|d adm|n|stered - Intraoperat|ve (8etter |nd|cated by |ower va|ues)
41,4S

2 randomlsed
Lrlals
lnconslsLency
Serlous(e) very
serlous(f)
none 32 32 - Mu 120.16 hlgher (93.3
vL8?
LCW
lMC81
An1
Vo|ume of study f|u|d adm|n|stered - Aort|c aneurysm (8etter |nd|cated by |ower va|ues)
33,64

2 randomlsed
Lrlals
lnconslsLency
Serlous(e) very
serlous(f)
none 33 33 - Mu 2.66 hlgher (323.46
vL8?
LCW
lMC81
An1
1ota| vo|ume of f|u|d adm|n|stered (8etter |nd|cated by |ower va|ues)
41

1 randomlsed
Lrlals
Serlous(g) no serlous
lnconslsLency
Serlous(h) very
serlous(f)
none 20 20 - Mu 193 hlgher (99.23
vL8?
LCW
lMC81
An1
(o)Allocotloo cooceolmeot oot tepotteJ lo ooe stoJy (CooJos 2010), televoot boselloe ctltetlo oot tepotteJ lo most of tbe stoJles
(b) l2 voloe 70.9X

(c)Ooe stoJy wos cooJocteJ lo post-opetotlve potleots wbo moy olteoJy bove beeo boemoJyoomlcolly stoble (CooJos 2010) ooJ two stoJles wete lo potleots wltb obJomlool oottlc ooeotysm
sotqety wblcb wos oqteeJ to be o blqbly loJltect popolotloo (CoJet 2008, MobmooJ 2009)
(J) kelevoot boselloe cbotoctetlstlcs oot tepotteJ lo most of tbe stoJles, ollocotloo cooceolmeot oot tepotteJ lo 2 stoJles(looetbofet 2002, Ilo 2001), Jetolls of blloJloq oot tepotteJ lo two
stoJles(CoJet 2008, MobmooJ 2009)
(e) 1wo stoJles wete cooJocteJ lo lottoopetotlve potleots (looetbofet 2002, Ilo 2001) ooJ two stoJles lo potleots ooJetqoloq obJomlool oottlc ooeotysm sotqety(CoJet 2008, MobmooJ 2009)
ooJ floJloqs moy oot be qeoetollsoble to oll potleots tecelvloq flolJ tesoscltotloo
(f) cooflJeoce lotetvol ctosses botb Mlus
(q) kelovoot boselloe cbotoctetlstlcs oot tepotteJ, Jetolls of ollocotloo cooceolmeot oot tepotteJ
(b) 5toJy cooJocteJ lo lottoopetotlve potleots ooJ floJloqs moy oot be qeoetollsoble to oll potleots tecelvloq flolJ tesoscltotloo (loooetbofet 2002)

1ab|e 23: C||n|ca| ev|dence prof||e: Ge|at|n vs |actated Ringers solution
ua||t
y
Importa
nce
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|on Cther GLLA1
IN
kINGLk'S
LAC1A1L
ke|at|ve
(9S CI)
Abso|ute
Morta||ty
34,12S

2 randomlsed
Lrlals
Serlous
(a)
no serlous
lnconslsLency
Serlous(b) no serlous
lmpreclslon
none 14/68
(20.6
)
18/66
(27.3)
88 0.76
(0.42 Lo
1.4)
63 fewer per 1000
(from 138 fewer Lo
109 more)
LCW C8l1lCAL
Morta||ty 1rauma
12S

1 randomlsed
Lrlals
Serlous
(a)
no serlous
lnconslsLency
lmpreclslon
none 2/18
(11.1
)
3/16
(18.8)
88 0.39
(0.11 Lo
3.11)
77 fewer per 1000
(from 167 fewer Lo
396 more)
LCW C8l1lCAL
Morta||ty ostoperat|ve
34

1 randomlsed
Lrlals
Serlous
(a)
no serlous
lnconslsLency
lmpreclslon
none 12/30
(24)
13/30
(30)
88 0.8
(0.42 Lo
1.33)
60 fewer per 1000
(from 174 fewer Lo
139 more)
LCW C8l1lCAL
Vo|ume of study f|u|d adm|n|stered (8etter |nd|cated by |ower va|ues)
41,4S

2 randomlsed
Lrlals
very
serlous
(c)
no serlous
lnconslsLency
lmpreclslon
none 32 32 - SMu 3.38 lower (4.41
Lo 2.76 lower)
vL8?
LCW
lMC81
An1
1ota| vo|ume of f|u|d adm|n|stered (8etter |nd|cated by |ower va|ues)
41

1 randomlsed
Lrlals
very
serlous
no serlous
lnconslsLency
lmpreclslon
none 20 20 - Mu 1396 lower
(1986.93 Lo 803.03
lower)
vL8?
LCW
lMC81
An1

ua||t
y
Importa
nce
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|on Cther GLLA1
IN
kINGLk'S
LAC1A1L
ke|at|ve
(9S CI)
Abso|ute
(c)
(o) kelevoot boselloe cbotoctetlstlcs oot tepotteJ lo botb stoJles, Jetolls of ollocotloo cooceolmeot oot tepotteJ lo botb stoJles(wo 2001, CooJos 2010), Jetolls of tooJomlsotloo oot tepotteJ
lo ooe stoJy(wo 2001)
(b)Ooe stoJy wos lo post-opetotlve potelots wbo moy olteoJy bove beeo boemoJyoomlcolly stoble (CooJos 2010) ooJ tbe otbet stoJy wos lo ttoomo potleots (wo 2001),floJloqs ftom botb
moy oot be qeoetollsoble to oll potleots tecelvloq flolJ tesoscltotloo
(c) kelevoot boselloe cbotoctetlstlcs oot tepotteJ, Jetolls of ollocotloo cooceolmeot oot tepotteJ ooJ bllolJloq of pottlclpoots ooJ lovestlqotots wos oocleot.
(J)5toJy cooJocteJ lo lottoopetotlve potleots ooJ floJloqs moy oot be qeoetollsoble to oll potelots tecelvloq flolJ tesoscltotloo
1ab|e 24: C||n|ca| ev|dence prof||e: Ge|at|n vs. Sod|um ch|or|de 0.9
ua||ty
Import
ance
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectn
ess
Imprec|s|
on
Cther
cons|derat|ons
Ge|a
t|n
Sod|um
ch|or|d
e 0.9
ke|at|ve
(9S CI)
Abso|ute
Morta||ty
113

1 randomlsed
Lrlals
Serlous
(a)
no serlous
lnconslsLency
very
serlous(b)
no
serlous
lmpreclsl
on
none 1/16
(6.3)
1/1
6
(6.3
)
88 1 (0.07
Lo 14.64)
vL8?
LCW
C8l1lCAL
(o)uetolls of ollocotloo cooceolmeot oot tepotteJ, oo lofotmotloo ptovlJeJ oo flolJ composltloo
(b) 5toJy cooJocteJ lo post-opetotlve cotJloc ooJ voscolot sotqety potleots ooJ floJloqs moy oot be qeoetollsoble to oll potleots tecelvloq flolJ tesoscltotloo (vetbelj 2006)


101
no economlc sLudles were ldenLlfled on Lhe cosL-effecLlveness of gelaLln vs. hydroxyeLhylsLarch for
lnLravenous fluld resusclLaLlon of hosplLallsed paLlenLs.
An orlglnal cosL analysls was developed Lo compare gelaLln, hydroxyeLhylsLarch (LeLrasLarch),
albumln and crysLallolds - see secLlon 7.2.3.2
C||n|ca|
CelaLln vs LeLrasLarch
1he revlew of Lhe use of gelaLln compared wlLh LeLrasLarch for fluld resusclLaLlon showed no
conslsLenL advanLage or dlsadvanLage wlLh Lhe use of gelaLln ln Lerms of morLallLy or Lhe volume of
fluld LhaL needed Lo be lnfused.
1here was also no clear evldence LhaL Lhe use of gelaLln for fluld resusclLaLlon granLed any slgnlflcanL
advantage or disadvantage over the use of either Ringers lactate or 0.9% sodium chloride in terms of
morLallLy.
no sLudles reporLed morbldlLy, resplraLory compllcaLlons, renal compllcaLlons or lengLh of sLay ln
hosplLal or lCu.
CuLcome: MorLallLy
lour sLudles wlLh 239 paLlenLs from a mlxed populaLlon (posL-operaLlve paLlenLs, aorLlc aneurysm
surgery) suggesLed LhaL Lhere may be no dlfference ln morLallLy beLween paLlenLs recelvlng gelaLln or
LeLrasLarch for fluld resusclLaLlon. Cf Lhese, Lwo sLudles wlLh posL-operaLlve paLlenLs showed no
dlfference ln morLallLy beLween paLlenLs recelvlng gelaLln or LeLrasLarch. 1wo sLudles wlLh 106
paLlenLs who had undergone surgery for aorLlc aneurysm suggesLed lower morLallLy wlLh LeLrasLarch
Lhan gelaLln buL Lhere was some uncerLalnLy. All Lhe evldence was of very low quallLy.
CuLcome: volume of sLudy fluld recelved
lour sLudles wlLh 170 paLlenLs from a mlxed populaLlon (lnLraoperaLlve, aorLlc aneurysm surgery)
suggesLed LhaL paLlenLs recelvlng LeLrasLarch requlred lower volumes of fluld for resusclLaLlon. 1hls
effecL was lndependenLly observed ln Lwo sLudles wlLh 64 lnLraoperaLlve paLlenLs buL Lhere was
conslderable uncerLalnLy. 1wo sLudles ln 106 aorLlc aneurysm surgery paLlenLs suggesLed no
dlfference ln volumes of fluld requlred for fluld resusclLaLlon, buL Lhere was conslderable uncerLalnLy.
All of Lhe evldence was of very low quallLy.
CelaLln vs balanced crysLallold soluLlons
CuLcome: MorLallLy
1wo sLudles wlLh 134 paLlenLs from mlxed populaLlons (Lrauma, posLoperaLlve) suggesLed LhaL Lhere
was no difference in mortality between patients receiving gelatin or lactated Ringers solution for
fluld resusclLaLlon, buL Lhere was conslderable uncerLalnLy. 1hls effecL was also observed
lndependenLly ln boLh Lrauma and posL-operaLlve paLlenLs, buL Lhere was conslderable uncerLalnLy.
CuLcome: volume of sLudy fluld recelved

102
1wo sLudles wlLh 64 lnLraoperaLlve paLlenLs showed LhaL paLlenLs recelvlng gelaLln requlred lower
volumes for fluid resuscitation compared to those receiving lactated Ringers solution. The evidence
was of very low quallLy.
CelaLln vs sodlum chlorlde 0.9
Cne sLudy wlLh 32 paLlenLs suggesLed LhaL Lhere was no dlfference ln morLallLy beLween paLlenLs
recelvlng gelaLln or sodlum chlorlde 0.9 for fluld resusclLaLlon, buL Lhere was conslderable
uncerLalnLy. 1he evldence was of very low quallLy.
Lconom|c
7.2.1.4 See 7.2.3.3
See recommendaLlons and llnk Lo evldence ln secLlon7.4
7.2.2 1etrastarch
llve 8C1s were ldenLlfled relevanL Lo Lhls revlew quesLlon.
23,38,43,70,84
1hree sLudles were ln sepsls
paLlenLs,
23,38,84
one was ln crlLlcally ln[ured paLlenLs
43
and one sLudy was conducLed ln all paLlenLs
admlLLed Lo lnLenslve care unlLs and lncluded Lhose wlLh sepsls and Lrauma.
70

1he CuC prlorlLlsed evaluaLlon of Lhe effecLs of LeLrasLarches for Lhe purposes of Lhls revlew as Lhese
were consldered Lo be mosL wldely used ln admlsslon and general ward seLLlngs. lour of Lhe sLudles
compared 6 hydroxyeLhylsLarch 130/0.4 Lo sodlum chlorlde 0.9
23,38,43,70
and one sLudy compared
6 hydroxyeLhylsLarch 130/0.42 to Ringers acetate solution
84
.
1he ouLcomes reporLed across sLudles lncluded morLallLy aL 30 and 90 days, SClA scores, renal
ouLcomes, and lengLh of sLay ln hosplLal and lnLenslve care unlLs. no sLudles reporLed any quallLy of
llfe ouLcomes.
1he evldence ls summarlsed ln Lhe cllnlcal C8AuL evldence proflle below (see 1able 23 and 1able 26)
See also Lhe flow dlagram for sLudy selecLlon ln secLlon !.3, Appendlx !, evldence Lables ln secLlon
L.3.2, Appendlx L, foresL ploLs ln secLlon C.3.2 ln Appendlx C and excluded sLudles llsL ln secLlon P.3,
Appendlx P.



1ab|e 2S: C||n|ca| ev|dence prof||e: 1etrastarch compared to Sod|um ch|or|de 0.9 for f|u|d resusc|tat|on
ua||ty Importance
No of
stud|e
s
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|on Cther 1etrastarc
h
Sod|um
Ch|or|de
0.9
ke|at|ve
(9S CI)
Abso|ute
A|| cause morta||ty (90 days)
38,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 637/3414
(18.7)
398/343
1
(17.4)
88 1.07
(0.97 Lo
1.18)
12 more per 1000 (from 3
fewer Lo 31 more)
MCuL8
A1L
C8l1lCAL
38,43,70

3 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 301/3469
(14.4)
467/347
9
(13.4)
88 1.07
(0.96 Lo
1.21)
fewer Lo 28 more)
MCuL8
A1L
C8l1lCAL
A|| cause morta||ty (30 days) 1rauma
43

1 randomlsed
Lrlals
Serlous(
b)
no serlous
lnconslsLency
no serlous
lndlrecLness
no serlous
lmpreclslon
none 12/36
(21.4)
6/33
(11.3)
88 1.89
(0.77 Lo
4.68)
MCuL8
A1L
C8l1lCAL
A|| cause morta||ty (30 days) Seps|s
38,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
no serlous
lndlrecLness
no serlous
lmpreclslon
none 489/3413
(14.3)
461/342
6
(13.3)
88 1.06
(0.94 Lo
1.2)
fewer Lo 27 more)
PlCP C8l1lCAL
Length of stay |n ICU (8etter |nd|cated by |ower va|ues)
38,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
Serlous(c) Serlous(a)1 very
serlous(d)
none 3441 3463 - Mu 1.31 lower (6.43
vL8?
LCW
lMC81An1

ua||ty Importance
No of
stud|e
s
Des|gn k|sk of
b|as
h
Sod|um
Ch|or|de
0.9
ke|at|ve
(9S CI)
Abso|ute
Length of stay |n hosp|ta| (8etter |nd|cated by |ower va|ues)
38,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 3441 3463 - Mu 0.2 hlgher (0.19 Lo
0.21 hlgher)
MCuL8
A1L
lMC81An1
New organ fa||ure (Card|ovascu|ar- SOFA score3)
70

1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 663/1813
(36.3)
722/180
8
(39.9)
88 0.91
(0.84 Lo
0.99)
MCuL8
A1L
lMC81An1
New organ fa||ure(kesp|ratory)
70

1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 340/2062
(26.2)
324/209
4
(23)
88 1.03
(0.94 Lo
1.16)
MCuL8
A1L
lMC81An1
AkI- kIILL- k|sk
43,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 1796/336
3
(33.4)
1924/33
89
(36.8)
88 0.94
(0.9 Lo
0.98)
MCuL8
A1L
lMC81An1
AkI- kIILL- k|sk 1rauma (subgroup)
43

1 randomlsed
Lrlals
Serlous(
b)
no serlous
lnconslsLency
no serlous
lndlrecLness
very
serlous(d)
none 8/36
(14.3)
12/34
(22.2)
88 0.64
(0.29 Lo
1.43)
vL8?
LCW
lMC81An1
AkI- kIILL- k|sk Seps|s (subgroup)
70

1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
no serlous
lndlrecLness
no serlous
lmpreclslon
none 1788/330
9
(34)
1912/33
33
(37.3)
88 0.94
(0.9 Lo
0.98)
PlCP lMC81An1

ua||ty Importance
No of
stud|e
s
Des|gn k|sk of
b|as
h
Sod|um
Ch|or|de
0.9
ke|at|ve
(9S CI)
Abso|ute
AkI- kIILL-In[ury
43,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
lmpreclslon
none 1134/332
1
(34.1)
1261/33
34
(37.6)
88 0.91
(0.83 Lo
0.97)
MCuL8
A1L
lMC81An1
AkI- kIILL-In[ury 1rauma (subgroup)
43

1 randomlsed
Lrlals
Serlous(
b)
no serlous
lnconslsLency
no serlous
lndlrecLness
very
serlous(d)
none 4/36
(7.1)
8/34
(14.8)
88 0.48
(0.13 Lo
1.31)
vL8?
LCW
lMC81An1
AkI- kIILL-In[ury Seps|s (subgroup)
70

1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
no serlous
lndlrecLness
no serlous
lmpreclslon
none 1130/326
3
(34.6)
1233/33
00
(38)
88 0.91
(0.83 Lo
0.97)
PlCP lMC81An1
AkI- kIILL-Ia||ure
70

1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
Serlous(a) Serlous(e) none 336/3243
(10.4)
301/326
3
(9.2)
88 1.12
(0.97 Lo
1.3)
fewer Lo 28 more)
LCW lMC81An1
Use of rena| rep|acement therapy
43,70

2 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
Serlous(a) Serlous(e) none 237/3408
(7)
199/342
9
(3.8)
88 1.2 (1
Lo 1.44)
more Lo 26 more)
LCW lMC81An1
Use of rena| rep|acement therapy 1rauma (subgroup)
43

1 randomlsed
Lrlals
Serlous(
b)
no serlous
lnconslsLency
no serlous
lndlrecLness
very
serlous(d)
none 2/36
(3.6)
3/34
(3.6)
88 0.64
(0.11 Lo
3.7)
vL8?
LCW
lMC81An1
Use of rena| rep|acement therapy Seps|s (subgroup)
70


ua||ty Importance
No of
stud|e
s
Des|gn k|sk of
b|as
h
Sod|um
Ch|or|de
0.9
ke|at|ve
(9S CI)
Abso|ute
1 randomlsed
Lrlals
no
serlous
rlsk of
blas
no serlous
lnconslsLency
no serlous
lndlrecLness
Serlous(e) none 233/3332
(7)
196/337
3
(3.8)
88 1.21 (1
Lo 1.43)
more Lo 26 more)
PlCP lMC81An1
(o) 5toJy (Mybotqb 2012) cooJocteJ lo potleots lo lcu ooJ moy oot be qeoetollsoble to otbet potleots tecelvloq flolJ tesoscltotloo ootslJe of lcu. Otbet stoJles wete cooJocteJ lo potleots wltb
sepsls ColJet2012) ot ttoomo (Iomes 2011) ooJ moy oot be qeoetollsoble to oll potleots tecelvloq flolJ tesoscltotloo.
(b) ulffeteoce lo boselloe cbotoctetlstlcs of two qtoops- lojoty sevetlty wos qteotet lo potleots wltb bloot ttoomo wbo tecelveJ 6X n5 os compoteJ to soJlom cblotlJe 0.9X, oocleot lf
ollocotloo cooceolmeot cottleJ oot ot lf lovestlqotots blloJeJ.
(c) l2 voloe=74X, ooexploloeJ betetoqeoelty os botb stoJles locloJeJ sepsls potleots, tooJom effects ooolysls ooJettokeo.
(J) cooflJeoce lotetvol ctosses botb Mlus
(e) cooflJeoce lotetvol ctosses ooe Mlu.

1ab|e 26: C||n|ca| ev|dence prof||e: 1etrastarch compared to Ringers acetate solution for fluid resuscitation
ua||ty
Importan
ce
No of
stud|es
Des|gn k|sk of b|as Incons|stency Ind|rectne
ss
Imprec|s|on Cther 1etrsratch k|nger's
acetate
ke|at|ve
(9S CI)
Abso|ute
84

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
lmpreclslon
none 134/398
(38.7)
144/400
(36)
88 1.07 (0.9
Lo 1.29)
MCuL8
A1L
C8l1lCAL
84

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
lmpreclslon
none 201/398
(30.3)
172/400
(43)
88 1.17
(1.01 Lo
1.36)
more Lo 133 more)
MCuL8
A1L
C8l1lCAL
AkI- doub||ng of serum creat|n|ne |eve|
84

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
Serlous(a) Serlous(b) none 148/398
(37.2)
127/400
(31.8)
88 1.17
(0.97 Lo
1.42)
fewer Lo 133 more)
LCW lMC81A
n1

ua||ty
Importan
ce
No of
stud|es
Des|gn k|sk of b|as Incons|stency Ind|rectne
ss
Imprec|s|on Cther 1etrsratch k|nger's
acetate
ke|at|ve
(9S CI)
Abso|ute
Use of mechan|ca| vent||at|on
84

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
lmpreclslon
none 323/398
(81.7)
321/400
(80.3)
88 1.02
(0.93 Lo
1.09)
fewer Lo 72 more)
MCuL8
A1L
lMC81A
n1
(o)5toJy (letoet 2012) wos cooJocteJ lo potleots wltb sevete sepsls ooJ floJloqs moy oot be qeoetollsoble to oll potleots tecelvloq lottoveooos flolJs fot flolJ tesoscltotloo.
(b) ctosses ooe Mlu.


108
no economlc sLudles were ldenLlfled on Lhe cosL-effecLlveness of hydroxyeLhylsLarch vs sodlum
chlorlde 0.9 for lnLravenous fluld resusclLaLlon of hosplLallsed paLlenLs.
An orlglnal cosL analysls was developed Lo compare gelaLln, hydroxyeLhylsLarch (LeLrasLarch),
albumln and crysLallolds - see secLlon 7.2.3.2.
C||n|ca|
1wo sLudles wlLh 6827 paLlenLs ln crlLlcal care seLLlngs suggesLed LhaL Lhere may be no dlfference ln
all cause morLallLy aL 30 days or aL 90 days wlLh Lhe use of LeLrasLarch over sodlum chlorlde 0.9.
1he evldence was of moderaLe quallLy. Powever, Lwo sLudles wlLh 6837 paLlenLs showed LhaL
paLlenLs recelvlng LeLrasLarch were more llkely Lo recelve renal replacemenL Lherapy as compared Lo
paLlenLs who had recelved sodlum chlorlde 0.9 for fluld resusclLaLlon. Powever, Lhe same Lwo
sLudles also showed LhaL fewer paLlenLs ln Lhe LeLrasLarch group meL Lhe 8llLL crlLerla for 8lsk and
ln[ury. 1he evldence ranged from very low Lo moderaLe quallLy.
Cne study w|th 798 seps|s pat|ents showed that there may be an |ncrease |n morta||ty at 90 days
with the use of tetrastarch over lactated Ringers solution. 1he ev|dence a|so showed that pat|ents
rece|v|ng tetrastarch may have an |ncrease |n acute k|dney |n[ury as compared to pat|ents rece|v|ng
lactated Ringers solution. The evidence was of moderate qua||ty.Lconom|c
See secLlon 7.2.3.3
7.2.2.4 kecommendat|ons and ||nk to ev|dence
See recommendaLlons and llnk Lo evldence ln secLlon 7.4
7.2.3 A|bum|n
A Cochrane revlew
92
and one 8C1 were lncluded ln Lhe revlew.
37
Lvldence from Lhese are
summarlsed ln Lhe cllnlcal C8AuL evldence proflle below. See also Lhe foresL ploLs ln secLlon C.3.3,
Appendlx C, sLudy evldence Lables ln L.3.3, Appendlx L and excluslon llsL ln secLlon P.3, Appendlx P.


1ab|e 27: C||n|ca| ev|dence prof||e: A|bum|n vs. Sod|um ch|or|de 0.9: Inc|uded stud|es for morta||ty outcome on|y (Irom Cochrane rev|ew)
92

ua||ty
Importan
ce
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|on Cther A|bum|n Sod|um
ch|or|de
0.9
ke|at|ve
(9S CI)
Abso|ute
Morta||ty A|| stud|es ava||ab|e
1,124

2 randomlse
d Lrlals
no
serlous
rlsk of
blas (a)
no serlous
lnconslsLency
no serlous
lndlrecLness
no serlous
lmpreclslon
none 727/331
0
(20.7)
729/3492
(20.9)
C8 0.99
(0.88 Lo
1.11)
2 fewer per 1000
(from 20 fewer Lo
18 more)
PlCP C8l1lCAL
(o) 1bete wete lmpottoot Jlffeteoces lo boselloe tlsk octoss stoJles. Most of tbe lofotmotloo wos ftom o lotqe kc1 lo loteoslve cote potleots

1ab|e 28: C||n|ca| ev|dence prof||e: A|bum|n compared to sod|um ch|or|de 0.9
ua||ty
Importa
nce
No
of
stu
d|es
Des|gn k|sk of b|as Incons|sten
cy
Ind|rectness Imprec|s|
on
Cthe
r
A|bum|n
4
Sod|um
ch|or|de
0.9
SAIL
study
ke|at|ve
(9S CI)
Abso|ute
A|| cause morta||ty - 28 days - A|| pat|ents
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
serlous
lndlrecLness
(a)
no
serlous
lmpreclsl
on
none 726/3473
(20.9)
729/346
0
(21.1)
88 0.99
(0.91 Lo
1.09)
2 fewer per 1000
(from 19 fewer Lo
19 more)
MCuL8
A1L
C8l1lCAL
A|| cause morta||ty - 28 days 1rauma subgroup
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 81/396
(13.6)
39/390
(10)
88 1.36
(0.99 Lo
1.86)
36 more per 1000
(from 1 fewer Lo 86
more)
PlCP C8l1lCAL
A|| cause morta||ty - 28 days - Severe Seps|s subgroup
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 183/603
(30.7)
217/613
(33.3)
88 0.87
(0.74 Lo
1.02)
46 fewer per 1000
(from 92 fewer Lo 7
more)
PlCP C8l1lCAL
A|| cause morta||ty - 28 days AkDS (Acute kesp|ratory D|stress Syndrome) subgroup
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 24/61
(39.3)
28/66
(42.4)
88 0.93
(0.61 Lo
1.41)
30 fewer per 1000
(from 163 fewer Lo
174 more)
PlCP C8l1lCAL
Morb|d|ty (assessed w|th: New organ fa||ure - SCIA score 3 or 4)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 1232/26
49
(47.3)
1249/26
73
(46.7)
88 1.01
(0.96 Lo
1.07)
3 more per 1000
(from 19 fewer Lo
33 more)
PlCP C8l1lCAL

ua||ty
Importa
nce
No
of
stu
d|es
cy
on
Cthe
r
A|bum|n
4
Sod|um
ch|or|de
0.9
SAIL
study
ke|at|ve
(9S CI)
Abso|ute
kesp|ratory fa||ure (measured w|th: Days w|th mechan|ca| vent||at|on, 8etter |nd|cated by |ower va|ues)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3473 3460 - Mu 0.19 hlgher
(0.08 lower Lo 0.47
hlgher)
PlCP C8l1lCAL
AkI (measured w|th: Durat|on of rena| rep|acement therapy, 8etter |nd|cated by |ower va|ues)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3473 3460 - Mu 0.09 hlgher (0
Lo 0.19 hlgher)
PlCP C8l1lCAL
Vo|ume of f|u|ds used |n m| - Study f|u|d - Day 1 (8etter |nd|cated by |ower va|ues)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3410 3460 - Mu 381.4 lower
(442.13 Lo 320.67
lower)
PlCP lMC81
An1
Vo|ume of f|u|ds used |n m| - Non study f|u|d- Day 1 (8etter |nd|cated by |ower va|ues)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3392 3403 - Mu 46.2 lower
(104.17 lower Lo
11.77 hlgher)
PlCP C8l1lCAL
Length of Stay |n days- nosp|ta||sat|on (8etter |nd|cated by |ower va|ues)
1

1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3473 3460 - mean 0 hlgher
(0.70 lower Lo 0.21
hlgher)
PlCP C8l1lCAL
Length of Stay |n days - ICU (8etter |nd|cated by |ower va|ues)
1


ua||ty
Importa
nce
No
of
stu
d|es
cy
on
Cthe
r
A|bum|n
4
Sod|um
ch|or|de
0.9
SAIL
study
ke|at|ve
(9S CI)
Abso|ute
1 randomls
ed Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLen
cy
no serlous
lndlrecLness
no
serlous
lmpreclsl
on
none 3473 3460 - Mu 0.24 hlgher
(0.06 Lo 0.34
hlgher)
PlCP C8l1lCAL
(o) 5toJy wos cooJocteJ lo potleots wltb sepsls, ttoomo ooJ tbese floJloqs ftom tbese qtoops moy oot be oppllcoble to oll bospltollseJ potleots.


113
ub||shed ||terature
Cne cosL-effecLlveness analysls was ldenLlfled assesslng Lhe cosLs and effecLlveness of Lwo Lypes of
fluld used for fluld supporL. ln one sLraLegy, paLlenLs were glven sodlum chlorlde 0.9 whlle ln Lhe
second, Lhey were prescrlbed lnLravenous albumln 4.
37
1hls ls summarlsed ln Lhe economlc
evldence proflle below (1able 29). See also Lhe sLudy selecLlon flow charL ln secLlon !.3, ln Appendlx !
and economlc evldence Lable ln secLlon l.3, Appendlx l
llve sLudles LhaL were noL relevanL Lo Lhe cllnlcal quesLlon were noL lncluded. 1hese are llsLed ln
secLlon l.1, Appendlx l wlLh reasons for excluslon glven.



1ab|e 29: Lconom|c ev|dence prof||e: A|bum|n 4 vs. Sod|um ch|or|de 0.9
Study App||cab|||ty L|m|tat|ons Cther comments
Incrementa|
cost
Incrementa|
effects
Cost
effect|veness Uncerta|nty
CuldeL
37

arLlally
Appllcable
(a)

oLenLlally
Serlous
LlmlLaLlons
(b)

Analysls developed from a lrench
naLlonal PealLh Servlces
perspecLlve of paLlenLs wlLh
severe sepsls for fluld supporL
191
(c)

0.43 llfe
years galned

423 per llfe
year galned

lf Lhe morLallLy dlfference ls only
1 Lhen Lhe lCL8=400 of Lhe
base case scenarlo (4.6).
lf Lhere ls no morLallLy dlfference
Lhen sallne lnfuslon domlnaLes.

lf quanLlLy of albumln 4.3L, lCL8=
200 base case scenarlo (2.23L).
(o) 5ome oocettoloty oboot tbe oppllcoblllty of lteocb lv flolJ costs to uk Nn5 settloq.
(b) cost Jlffeteoce betweeo lotetveotloos boseJ oo oJJltloool cost of olbomlo ooJ otbet oolJeotlfleJ costs. lo-bospltol costs ossomeJ to be slmllot fot botb lotetveotloos
(c) 2005 otos pteseoteJ bete os 2005 uk poooJs

113
New cost ana|ys|s
1he CuC consldered Lhe cholce of resusclLaLlon fluld Lo be a hlgh prlorlLy for de novo economlc
modelllng. Powever, Lhe cllnlcal revlew found llLLle evldence of Lhe relaLlve cllnlcal effecLlveness of
dlfferenL fluld Lypes, so a slmple cosL analysls was conducLed wlLh a Lhreshold senslLlvlLy analysls
around Lhe number of compllcaLlons averLed, see Appendlx M.
lL was assumed LhaL admlnlsLraLlon cosLs would be slmllar for each fluld and Lherefore only fluld
cosLs and compllcaLlon cosLs were lncluded. lluld cosLs were provlded by Lhe nPS Commerclal
Medlclnes unlL1he cosL of a ma[or fluld-relaLed compllcaLlon (see 4.2.3) was esLlmaLed uslng nPS
reference cosLs Lo be 1,868 (or 3,000 lncludlng a crlLlcal care eplsode).
1he cosL of each fluld ls shown ln 1able 30 along wlLh Lhe number of compllcaLlons LhaL would need
Lo be averLed Lo make each fluld cosL neuLral. 1he lowesL cosL fluld was 0.9 Sodlum chlorlde aL
1.40 per paLlenL see 1able.
1he mosL expenslve fluld, Albumln 4.3 cosL 136.24 and would need Lo averL 43-72 ma[or
compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
1he analysls dld noL Lake accounL of fluld volume. ln Lhe cllnlcal evldence Lhere was llLLle evldence of
a dlfference ln fluld volume, excepL ln Lhe case of albumln vs naCl. 8uL even here lL ls doubLful LhaL
Lhls dlfference ls large enough LhaL a fewer number of bags could be used. lurLhermore, lf one less
bag was requlred Lhen albumln would sLlll be Lhe mosL cosLly fluld ln Lerms of acqulslLlon cosL and
thats not even considering the additional costs associated with storing and administering albumin.
1hls analysls can be consldered as parLlally appllcable (slnce nPS unlL cosLs were used buL CAL?s
were noL esLlmaLed. lurLhermore, concluslons abouL cosL-effecLlveness or cosL neuLrallLy are noL
posslble wlLhouL evldence of Lhe number of compllcaLlons averLed.
1ab|e 30: Cost of f|u|ds for resusc|tat|on
kesusc|tat|on f|u|d reg|men (|n
order of cost of f|u|d per pat|ent)

Cost of f|u|d for
resusc|tat|on
(2000m|)
(a)
Number of extra ma[or comp||cat|ons per
1000 pat|ents that must be avo|ded for f|u|d
to be cost neutra| compared w|th 0.9
Sod|um ch|or|de (|nc|ud|ng cr|t|ca| care costs)
0.9 Sodlum chlorlde 1.40 -
ParLmanns soluLlon 1.70 <1
lasma-LyLe M 1.84 <1
8lngers LacLaLe 3.00 2 (1)
volplex 7.60 3 (2)
lsoplex 7.80 3 (2)
Celofuslne/Celaspan 4 9.60 4 (3)
Celoplasma 10.00 3 (3)
6 venofundln 23.20 13 (8)
6 1eLraspan 26.00 13 (8)
6 voluven 30.00 13 (10)
6 volulyLe 30.60 16 (10)
10 1eLraspan 39.60 20 (13)
3 Albumln 122.08 63 (40)
4.3 Albumln 136.24 72 (43)
(o)1otol cost fot flolJ tesoscltotloo boseJ oo oolt costs of 250ml ot 500ml boqs ooly wbeo oolt costs fot 1000 ml boqs wete
oot ovolloble. lt ls ooteJ tbot oo o locol coottoct, tbe ovolloblllty of boq slze moy Jlffet.

116

C||n|ca|
Cverall, Lhere were no cllnlcally lmporLanL dlfferences ln any of Lhe ouLcomes (all cause morLallLy,
morbldlLy, Akl, resplraLory fallure, lengLh of sLay ln lCu and overall lengLh of sLay ln hosplLal)
ldenLlfled for Lhe comparlson of albumln 4 vs sodlum chlorlde 0.9.
Powever, when morLallLy daLa of Lhe SAlL study were analysed according to the studys pre-
speclfled subgroup, Lhere may be a cllnlcally lmporLanL reducLlon ln morLallLy ln Lhe sepsls subgroup
ln Lhe albumln LreaLmenL arm compared wlLh Lhe sodlum chlorlde 0.9 LreaLmenL arm. ln Lhe
Lrauma subgroup, Lhere may be an lncrease ln morLallLy ln Lhe albumln LreaLmenL arm compared Lo
Lhe sodlum chlorlde 0.9 LreaLmenL arm. nelLher of Lhese dlfferences ln Lhese subgroups reached
sLaLlsLlcally slgnlflcance even wlLhouL correcLlon for mulLlple LesLlng. lurLher analysls of Lhe Lrauma
subgroup showed LhaL vlrLually all Lhe excess morLallLy ln Lhe albumln group was among paLlenLs
wlLh severe LraumaLlc braln ln[ury.
69
1he quallLy of evldence was hlgh for all of Lhe ouLcomes excepL
for morLallLy whre Lhe evldence was of moderaLe quallLy.
Lconom|c
Cne cosLeffecLlveness analysls found LhaL albumln 4 was cosL effecLlve compared Lo sodlum
chlorlde 0.9 for fluld resusclLaLlon ln paLlenLs wlLh severe sepsls (lCL8: 423 per llfe-year galned).
1hls analysls was assessed as parLlally appllcable wlLh poLenLlally serlous llmlLaLlons.
An orlglnal comparaLlve cosL analysls showed LhaL:
Sodlum Chlorlde 0.9 was Lhe cheapesL fluld for resusclLaLlon.
8alanced physlologlcal soluLlons would need Lo averL up Lo 2 compllcaLlons per 1000 paLlenLs
Lo be cosL neuLral.
CelaLln would need Lo averL 2-3 compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
1eLrasLarches would need Lo averL 8-20 compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
Albumln would need Lo averL 40-72 compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
7.2.3.4 kecommendat|ons and ||nk to ev|dence
See recommendaLlons and llnk Lo evldence ln secLlon 7.4
7.2.4 8uffered]phys|o|og|ca| so|ut|ons
Comparlsons: 8uffered/physlologlcal soluLlons vs. sodlum chlorlde 0.9 soluLlon.
no 8C1 was ldenLlfled for Lhe followlng comparlsons:
balanced physlologlcal soluLlons vs. sodlum chlorlde 0.9
collolds ln balanced physlologlcal soluLlons vs. collolds ln sodlum chlorlde 0.9
Cne Cochrane revlew was ldenLlfled whlch appeared Lo be relevanL Lo Lhls revlew quesLlon.
14

Powever, Lhls was excluded as:

117

Lhe analysls of ouLcomes of lnLeresL was from sLudles wlLh populaLlons or lnLervenLlons LhaL were
ouL of scope of Lhls guldance or were Loo lndlrecL Lo Lhe revlew populaLlon
o lnLra-operaLlve cardlac surgery paLlenLs
8

o use of heLasLarches
31

o 8enal LransplanL paLlenLs
79

CuLcomes were assessed aL dlfferenL Llme frames Lo LhaL of Lhe revlew proLocol (morLallLy was
assessed for all Llme frames)
1he llsL of excluded sLudles and reasons for excluslons are shown ln secLlon P.3, Appendlx P.
no economlc sLudles were ldenLlfled on Lhe cosL-effecLlveness of buffered/physlologlcal soluLlons vs.
sodlum chlorlde 0.9 for lnLravenous fluld resusclLaLlon of hosplLallsed paLlenLs. An orlglnal cosL
analysls was developed Lo compare gelaLln, hydroxyeLhylsLarch (LeLrasLarch), albumln and
crysLallolds (see secLlon 7.2.3.2)
C||n|ca|
No studies comparing balanced physiological solution such as Ringers lactated solution vs Sodlum
chlorlde 0.9 for paLlenLs requlrlng lv fluld resusclLaLlon were found.
Lconom|c
See secLlon 7.2.3.3.
7.3 Vo|umes and t|m|ng
1he ob[ecLlve of Lhls revlew was Lo flnd ouL wheLher facLors such as when fluld should be lnlLlaLed,
raLe of admlnlsLraLlon (ml/kg/hour), LoLal volume (ml/kg/day) and admlnlsLerlng flulds conLlnuously
over 24 hours vs. lnLermlLLenLly, affecL Lhe safeLy and efflcacy of fluld resusclLaLlon managemenL.
kev|ew quest|ons:
What are the most c||n|ca||y and cost effect|ve t|m|ngs and rate of adm|n|strat|on of |ntravenous
f|u|ds |n f|u|d resusc|tat|on?
What |s c||n|ca| and cost effect|veness of d|fferent vo|umes of f|u|d adm|n|strat|on |n pat|ents
requ|r|ng f|u|d resusc|tat|on?
We searched for 8C1s comparlng Lhe effecLlveness of varylng volumes, Llmlng and/or raLe of fluld
admlnlsLraLlon beLween LreaLmenL arms. Cnly Lhose flulds found Lo be cllnlcally and cosL- effecLlve
ln Lhe revlews reporLed ln secLlon 7.2 of Lypes of fluld for resusclLaLlon were lncluded ln Lhls revlew.
lor more deLalls see revlew proLocol ln secLlon C.3 ln Appendlx C.
7.3.1 C||n|ca| ev|dence: Vo|umes and t|m|ng
We found 6 8C1s lnvesLlgaLlng Lhe effecLs of volume and Llmlng
27,33,63,91,120
:

118
1lmlng of fluld resusclLaLlon (early vs. delayed/conLrol group): 3 sLudles, 1 sLudy ln peneLraLlng
Lrauma paLlenLs(8lckell1994
11
), 2 ln sepsls paLlenLs (8lvers2001
91
, Lln2006
33
)
8aLe of fluld admlnlsLraLlon: 1 sLudy ln acuLe pancreaLlLls paLlenLs(Mao 2009
63
)
Low volume (conservaLlve Lherapy) vs. hlgh volume (llberal): 2 sLudles, 1 ln acuLe lung ln[ury
paLlenLs (Wledemann
120
), 1 ln Lrauma paLlenLs (uuLLon2002
27
)
All Lhese sLudles were underLaken ln very speclflc paLlenL groups, Lhe resulLs may noL Lherefore be
appllcable Lo Lhe general paLlenLs ln hosplLal. See evldence Lable ln secLlon L.3.4 ln Appendlx L for
more deLalls on populaLlons and lnLervenLlons.
See also sLudy excluslon llsL ln secLlon P.3, ln Appendlx P


1ab|e 31: C||n|ca| ev|dence prof||e: Lar|y vs de|ayed f|u|d resusc|tat|on
ua||ty Importance
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectnes
s
Imprec|s|on Cther Lar|y Contro| ke|at|ve
(9S CI)
Abso|ute
A|| cause morta||ty
11

Subgroup of trauma pat|ents (haemorrhage)
1 randomlsed
Lrlals
serlous(
a)
no serlous
lnconslsLency
very
serlous(b)
no serlous
lmpreclslon
none 116/309
(37.3)
86/289
(29.8)
88 1.26 (1
Lo 1.38)
0 more Lo 173 more)
vL8?
LCW
C8l1lCAL
Subgroup of seps|s pat|ents
S3,91

2 randomlsed
Lrlals
serlous(
a)
no serlous
lnconslsLency
serlous(b) no serlous
lmpreclslon
none 98/238
(41.2)
144/249
(38.7)
88 0.72
(0.60 Lo
0.86)
164 fewer per 1000
fewer)

LCW
C8l1lCAL
kena| Ia||ure(e)
Subgroup of trauma pat|ents (haemorrhage)
11

1 randomlsed
Lrlals
serlous(
a)
no serlous
lnconslsLency
very
serlous(b)
serlous(c) none 8/227
(3.3)
3/360
(1.2)
883.3(0.8
2, 11.38)
2 fewer Lo 123 more )

vL8?
LCW
lMC81An1
S3

1 randomlsed
Lrlals
serlous(
a)
no serlous
lnconslsLency
serlous(b) serlous(c) none 42/108
(38.9)
64/116
(33.2)
88 0.7
(0.33 Lo
0.94)
166 fewer per 1000
fewer)

vL8?
LCW
lMC81An1
kesp|ratory fa||ure- Durat|on of mechan|ca| vent||at|on (days) (8etter |nd|cated by |ower va|ues)
11,S3

2 randomlsed
Lrlals
serlous(
a)
no serlous
lnconslsLency
serlous(b) serlous(c) none 180 210 - Mu 2.93 lower (8.73

vL8?
LCW
lMC81An1
Length of hosp|ta||sat|on (days) (8etter |nd|cated by |ower va|ues)(f)
11,S3,91

3 randomlsed
Lrlals
serlous(
a),(d)
no serlous
lnconslsLency
serlous(b) serlous(c) none 463 487 - Mu 1.38 hlgher (0.76

vL8?
LCW
lMC81An1
Length of hosp|ta||sat|on among pat|ents who surv|ved unt|| d|scharge (days) (8etter |nd|cated by |ower va|ues)(f)
11

Subgroup of Lrauma paLlenLs (haemorrhage)

ua||ty Importance
No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectnes
s
Imprec|s|on Cther Lar|y Contro| ke|at|ve
(9S CI)
Abso|ute
1 randomlsed
Lrlals
serlous(
a),(d)
no serlous
lnconslsLency
serlous(b) serlous(c) none 227 238 - Mu 3 hlgher (0.93
vL8?
LCW
lMC81An1
91

1 randomlsed
Lrlals
serlous(
a),(d)
no serlous
lnconslsLency
lower Lo 0.72 hlgher
vL8?
LCW
lMC81An1
Length of ICU stay (days) (8etter |nd|cated by |ower va|ues)
11,S3

2 randomlsed
Lrlals
serlous(
a),(d)
no serlous
lnconslsLency

vL8?
LCW
lMC81An1
Morb|d|ty not reported
ua||ty of ||fe not reported
(o) 5etloos llmltotloos Joe to lock of Jesctlptloo tooJomlsotloo, ollocotloo cooceolmeot ooJ blloJloq metboJs. 8lckell1994 ls o poosl tooJomlseJ stoJy
11
5toJles lo of eotly qool JltecteJ
tbetopy
5J,91
bove o ptotocol fot tbe lotetveotloo qtoop, bot lock o ptotocol fot tbe coottol qtoop. 1bls pteseoce of o ptotocol vs lock of ptotocol coolJ offect otbet oteos of lotetveotloo.
(b) 5toJles wete cooJocteJ lo speclflc qtoops of potleots (boemottboqlc sbock lo peoettotloq ttoomo potleots
11
, sepsls
5J,91
, ocote looq lojoty
120
), wltb oocettolo oppllcoblllty to tbe mojotlty of
potleots lo tbe qolJelloe.
(c) cooflJeoce lotetvols wlJe, ctossloq tbe Mlus.
(J) Ooe stoJy, llo2006
5J
tepotteJ ovetoqe lO5 fot oll potleots eotolleJ. 8lckell1994
11
tepotteJ ovetoqe of potleots wbo sotvlveJ, 1be somple slze oseJ fot colcolotloo lo ooe stoJy wos oocleot
(klvets2001
91
), most llkely boJ oseJ ovetoqe of oll potleots eotolleJ fot lO5 (bospltollsotloo), bot lO5 of ooly potleots wbo sotvlveJ ootll Jlscbotqe lo lO5 (bospltollsotloo) of sotvlvots (Joto
ooolyseJ lo tbe seosltlvlty ooolysls).
(e) 8lckell1994
11
ooly tepotteJ Joto fot potleots wbo sotvlveJ tbe opetotloo.llo2006
5J
tepotteJ Joto fot tbe wbole cobott.
(f) 5eosltlvlty ooolysls of leoqtb of stoy Joto fot wbole cobott ooJ sotvlvots ooly cooJocteJ

1ab|e 32: C||n|ca| ev|dence prof||e: Iast vs. contro||ed rate of f|u|d resusc|tat|on
ua||ty Importance
No of
stud|es
Des|gn k|sk of
b|as
Incons|stenc
y
Ind|rectn
ess
Imprec|s|
on
Cther Iast Contro||ed ke|at|ve
(9S CI)
Abso|ute
A|| cause morta||ty
6S


ua||ty Importance
No of
stud|es
Des|gn k|sk of
b|as
Incons|stenc
y
Ind|rectn
ess
Imprec|s|
on
Cther Iast Contro||ed ke|at|ve
(9S CI)
Abso|ute
1 randomlsed
Lrlals
serlous(a) no serlous
lnconslsLency
serlous(b) no
serlous
lmpreclsl
on
none 11/36
(30.6)
4/40
(10)
88 3.06
(1.07 Lo
8.73)
206 more per 1000
(from 7 more Lo
773 more)
LCW C8l1lCAL
Morb|d|ty (AACnL score) (8etter |nd|cated by |ower va|ues)
6S

1 randomlsed
Lrlals
serlous(a) no serlous
lnconslsLency
serlous(b) serlous(c) none 36 40 - Mu 3.3 hlgher (0.66
Lo 3.94 hlgher)

vL8?
LCW
C8l1lCAL
kesp|ratory fa||ure - not reported
kena| fa||ure not reported
Length of hosp|ta|]ICU stay not reported
(o)5etloos llmltotloos Joe to lock of Jesctlptloo tooJomlsotloo, ollocotloo cooceolmeot ooJ blloJloq metboJs.
(b)5toJy wos cooJocteJ lo potleots wltb ocote poocteotltls, oocleot lts oppllcoblllty to tbe qeoetol qolJelloe popolotloo.
(c)wlJe cooflJeoce lotetvols ctossloq Mlu. 5moll somple slze

1ab|e 33: C||n|ca| ev|dence prof||e: n|gh vs |ow vo|ume f|u|d resusc|tat|on
ua||ty assessment No of pat|ents Lffect ua||ty Importance

No of
stud|es
Des|gn k|sk of
b|as
Incons|stency Ind|rectness Imprec|s|on Cther Low n|gh
vo|ume
ke|at|ve
(9S CI)
Abso|ute
A|| cause morta||ty
27,120

2 randomlsed
Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
serlous no serlous
lmpreclslon
none 132/33
8
(23.7)
26.3 88 0.9
(0.73 Lo
1.1)
26 fewer per
1000 (from 71
fewer Lo 26
more)

MCuL8
A1L
C8l1lCAL
kena| Ia||ure, rece|v|ng rena| rep|acement therapy
120

1 randomlsed
Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
serlous(a) serlous(b) none 30/303
(9.9)
14.1 88 0.71
(0.3 Lo
0.99)
42 fewer per
1000 (from 1
fewer Lo 71
fewer)

LCW
C8l1lCAL
kesp|ratory fa||ure, measured by vent||ator free days ( w|th|n f|rst 28 days) (8etter |nd|cated by h|gher va|ues)
120

1 randomlsed
Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
serlous(a) serlous(b) none 303 497 - Mu 2.3 hlgher
(1.11 Lo 3.89
hlgher)

LCW
C8l1lCAL
ICU free days ( w|th|n f|rst 28 days) (8etter |nd|cated by h|gher va|ues)
120

1 randomlsed
Lrlals
no serlous
rlsk of blas
no serlous
lnconslsLency
serlous(a) serlous(b) none 303 497 - Mu 2.2 hlgher
(1.09 Lo 3.31
hlgher)

LCW
lMC81An1
Length of hosp|ta| stay not reported
(a) Both studies were conducted in specific groups of patients; Dutton 2002 was conducted in trauma patients, Wiedemann2006 were conducted in intubated acute lung injury patients. Applicability to
guideline population unclear
(b) Confidence intervals crossed MIDs


123

7.3.2 Lconom|c ev|dence
no economlc sLudles were ldenLlfled on Lhe cosL-effecLlveness of dlfferenL volumes of fluld
admlnlsLraLlon for lnLravenous fluld resusclLaLlon of hosplLallsed paLlenLs.
no economlc sLudles were ldenLlfled on Lhe cosL-effecLlveness of dlfferenL Llmlngs for Lhe
admlnlsLraLlon of lnLravenous fluld resusclLaLlon of hosplLallsed paLlenLs.

7.3.3 Lv|dence statements
C||n|ca|
otly vs. lote oJmlolsttotloo of lv flolJ fot tesoscltotloo
1here was a poLenLlal cllnlcally lmporLanL lncrease ln all-cause morLallLy, lengLh of hosplLallsaLlon for
survlvors, and renal fallure ln Lhe group recelvlng early LreaLmenL compared Lo delayed LreaLmenL for
paLlenLs wlLh Lrauma, buL a cllnlcally lmporLanL decrease ln Lhese parameLers ln paLlenLs recelvlng early
lv fluld resusclLaLlon for sepsls, alLhough evldence ln all Lhe sLudles was very low quallLy.
1here was a decrease ln resplraLory fallure for paLlenLs recelvlng early admlnlsLraLlon of lv fluld, buL
alLhough Lwo sLudles suggesLed LhaL Lhere may be abouL a 1 day savlng ln lengLh of lCu sLay, Lhere was
conslderable uncerLalnLy and Lhe evldence was of very low quallLy.
no sLudles reporLed morbldlLy and quallLy of llfe ouLcomes.
lost vs. coottolleJ tote of flolJ tesoscltotloo
1here was cllnlcally lmporLanL lncrease ln all cause morLallLy and morbldlLy among acuLe pancreaLlLls
paLlenLs recelvlng fasLer raLe of fluld admlnlsLraLlon as compared Lo Lhose recelvlng conLrolled raLes of
lv fluld admlnlsLraLlon. 1he evldence was low quallLy for all cause morLallLy and of very low quallLy for
morbldlLy.
no sLudles reporLed quallLy of llfe, acuLe kldney ln[ury, resplraLory fallure, lengLh of hosplLallsaLlon or
lCu sLay.
nlqb vs low volome flolJ tesoscltotloo
1here were no cllnlcally lmporLanL dlfferences ln all cause morLallLy for paLlenLs recelvlng hlgher or
lower fluld volume. 1he evldence ranged from moderaLe (only for all cause morLallLy) Lo low quallLy.
1here may be cllnlcally lmporLanL decrease ln renal fallure, resplraLory fallure and lengLh of lCu sLay
among paLlenLs recelvlng lower fluld volume.
no sLudles reporLed quallLy of llfe and lengLh of hosplLallsaLlon.

Lconom|c
no economlc evldence was found on Lhls quesLlon

124

7.4 kecommendat|ons and ||nk to ev|dence
kecommendat|ons
16. If pat|ents need IV f|u|d resusc|tat|on, use crysta||o|ds that conta|n
sod|um |n the range 1301S4 mmo|]|, w|th a bo|us of S00 m| over
|ess than 1S m|nutes. (Ior more |nformat|on see the Compos|t|on
of common|y used crysta||o|ds tab|e.)
17. Do not use tetrastarch for f|u|d resusc|tat|on.
18. Cons|der human a|bum|n so|ut|on 4S for f|u|d resusc|tat|on on|y
|n pat|ents w|th severe seps|s.
ouLcomes
measured by SClA or MCuS scores.
All cause morLallLy was consldered Lo be Lhe crlLlcal ouLcome for declslon-
maklng, alLhough all oLher ouLcomes were deemed as lmporLanL for lnformlng
recommendaLlons. MorLallLy aL 30 days was consldered Lo be Lhe mosL crlLlcal
ouLcome relevanL Lo paLlenLs recelvlng lv flulds for resusclLaLlon ln admlsslon
or general ward seLLlngs buL Lhe CuC also consldered morLallLy aL 90 days for
declslon maklng.
MorbldlLy and developmenL of compllcaLlons, acuLe kldney ln[ury and lengLh of
sLay ln lCu and hosplLal were consldered as lmporLanL ouLcomes. 1hey were
also lnLeresLed ln Lhe volumes of fluld lnfused for sLudles comparlng dlfferenL
fluld Lypes for resusclLaLlon, as success wlLh fluld resusclLaLlon achleved wlLh a
lower volume, lmplles LhaL Lhe fluld used mlghL have beLLer lnLravascular
expandlng properLles.
1rade off beLween cllnlcal
beneflLs and harms
Summary of Lhe evldence:
1he revlews on Lhe use of dlfferenL fluld Lypes for resusclLaLlon lndlcaLed Lhe
followlng:
no conslsLenL advanLage or dlsadvanLage for Lhe use of gelaLln compared
wlLh LeLrasLarch ln Lerms of morLallLy, Lhe volume of fluld needed Lo be
lnfused for fluld resusclLaLlon
no clear evldence LhaL Lhe use of gelaLln granLed slgnlflcanL advanLage or
disadvantage over the use of either Ringers lactate or 0.9% sodium chloride
ln Lerms of morLallLy.
no evldence of cllnlcal beneflL wlLh Lhe use of sLarches over crysLallolds for
fluld resusclLaLlon. 1he cllnlcal evldence revlew found no dlfference ln all
cause morLallLy wlLh Lhe use of LeLrasLarches over sodlum chlorlde 0.9 aL
30 days (88 1.07 [0.96 Lo 1.21]) and aL 90 days (88 1.07 [0.97 Lo 1.18]. Cn
comparison of tetrastarches with lactated Ringers solution, agaln Lhere was
no dlfference ln morLallLy aL 30 days (88 1.07 [0.9 Lo 1.29]).
1here was an lncrease ln 90-day morLallLy wlLh LeLrasLarch compared wlLh
Ringers acetate in paLlenLs wlLh sepsls (88 1.17 [1.01 Lo 1.36]). 1here was an
lncrease of 8 ln Lhe absoluLe rlsk of morLallLy wlLh Lhe use of LeLrasLarches
over Ringers acetate.
Cverall, Lhere were no cllnlcally lmporLanL dlfferences ln ouLcomes ln Lhe

123
sLudles LhaL compared albumln 4 wlLh sodlum chlorlde 0.9 for fluld
resusclLaLlon ln Lerms of all cause morLallLy, morbldlLy, Akl, resplraLory fallure,
lengLh of sLay ln lCu and overall lengLh of sLay ln hosplLal.
1here was evldence of cllnlcal beneflL wlLh Lhe use of albumln ln paLlenLs wlLh
severe sepsls. MorLallLy daLa from Lhe SAlL sLudy suggesLed LhaL Lhere may be
a cllnlcally lmporLanL reducLlon ln morLallLy ln sepsls when albumln ls used
compared Lo 0.9 sodlum chlorlde, whllsL ln Lhe Lrauma subgroup, Lhere may
be an lncrease ln morLallLy when albumln ls used compared Lo 0.9 sodlum
chlorlde.
no cllnlcal evldence was ldenLlfled for Lhe followlng comparlsons:
gelaLln or hydroxyeLhylsLarch vs. Hartmanns
balanced physlologlcal soluLlons vs. sodlum chlorlde 0.9
collolds ln balanced physlologlcal soluLlons vs. collolds ln sodlum chlorlde
0.9
1herefore Lhe CuC prlorlLlsed research recommendaLlons evaluaLlng Lhese
comparlsons(see secLlon 7.3)
1he revlews on Lhe volumes and Llmlngs of flulds for fluld resusclLaLlon
lndlcaLed Lhe followlng:
otly vs. lote oJmlolsttotloo of lv flolJ fot flolJ tesoscltotloo
1here was a poLenLlally cllnlcally lmporLanL lncrease ln all-cause morLallLy,
lengLh of hosplLallsaLlon for survlvors, and renal fallure ln a group recelvlng
early lv fluld resusclLaLlon compared Lo delayed LreaLmenL for paLlenLs wlLh
Lrauma. Conversely, however, Lhere was a cllnlcally lmporLanL decrease ln
Lhese parameLers ln paLlenLs recelvlng early lv fluld resusclLaLlon for sepsls,
alLhough evldence ln all Lhe sLudles was very low quallLy.
1here was a poLenLlally a cllnlcally lmporLanL decrease ln resplraLory fallure for
paLlenLs recelvlng early admlnlsLraLlon of lv fluld buL, alLhough Lwo sLudles
suggesLed LhaL Lhere may also be abouL a 1 day savlng ln lengLh of lCu sLay
wlLh early admlnlsLraLlon, Lhere was conslderable uncerLalnLy and Lhe
evldence was of very low quallLy.
no sLudles of early vs. laLe admlnlsLraLlon of lv flulds for resusclLaLlon reporLed
morbldlLy and quallLy of llfe ouLcomes.
lost vs. coottolleJ tote of flolJ tesoscltotloo
1here were cllnlcally lmporLanL lncrease ln all cause morLallLy and morbldlLy
among acuLe pancreaLlLls paLlenLs recelvlng fasL vs. conLrolled raLes of lv fluld
admlnlsLraLlon.
no sLudles reporLed quallLy of llfe, acuLe kldney ln[ury, resplraLory fallure,
lengLh of hosplLallsaLlon or lCu sLay.
nlqb vs. low volome flolJ tesoscltotloo
Cverall, Lhere were no cllnlcally lmporLanL dlfferences ln all cause morLallLy for
paLlenLs recelvlng hlgher or lower fluld volumes buL Lhere may be cllnlcally
lmporLanL decreases ln renal fallure, resplraLory fallure and lengLh of lCu sLay
for paLlenLs who recelve lower fluld volumes.
no sLudles reporLed quallLy of llfe and lengLh of hosplLallsaLlon.

Lconomlc conslderaLlons A slmple cosL analysls was conducLed. ln Lhe absence of evldence of
dlfferences ln compllcaLlons, crysLallolds were Lhe lowesL cosL flulds followed
by gelaLln and Lhen LeLrasLarches, albumln was Lhe hlghesL cosL.
CrysLallolds: Slnce Lhey are Lhe cheapesL and aL no apparenL cllnlcal
dlsadvanLage, crysLallolds appear Lo be Lhe mosL cosL-effecLlve fluld for mosL

126
paLlenLs. Pence ln mosL clrcumsLances a move from collolds Lo crysLallolds
would be expecLed Lo lead Lo cosL savlng as well as leadlng Lo lmprovemenL (or
aL leasL no deLrlmenL) Lo healLh ouLcome.
Slnce LeLrasLarches are more cosLly and were assoclaLed wlLh an lncrease ln
morLallLy,lL ls unllkely LhaL Lhey could be cosL-effecLlve. unless evldence of
clear beneflL ls forLhcomlng ln oLher paLlenL groups, Lhe CuC recommend LhaL
LeLrasLarch ls noL used ouLslde of cllnlcal Lrlals.
CelaLln ls more cosLly Lhan crysLallolds and Lhere was no evldence of a cllnlcal
beneflL wlLh lLs use over crysLallolds and Lherefore lLs cosL-effecLlveness ls
unproven see research recommendaLlon.
Albumln: lor paLlenLs wlLh severe sepsls, Lhe use of albumln lnfuslon for fluld
supporL was found by a lrench economlc evaluaLlon Lo be cosL-effecLlve
compared wlLh 0.9 sodlum chlorlde based on Lhe sepsls subgroup from Lhe
SAlL sLudy. Albumln 4 cosLs more buL Lhls was ouLwelghed by Lhe survlval
beneflL.
CuallLy of evldence 1he quallLy of evldence on Lhe use of dlfferenL Lypes of flulds for resusclLaLlon
ranged from very low Lo hlgh quallLy.
Lvldence on Lhe use of gelaLln for fluld resusclLaLlon was malnly of very low
quallLy for ma[orlLy of Lhe ouLcomes.
1here was evldence of lack of effecLlveness and some evldence of harm
(lncrease ln morLallLy) wlLh Lhe use of LeLrasLarches for fluld resusclLaLlon ln
paLlenLs wlLh sepsls. 1he evldence for Lhe crlLlcal ouLcome (morLallLy) when
comparlng LeLrasLarches Lo crysLallolds was of moderaLe quallLy (downgraded
due Lo lndlrecLness). CuallLy of evldence for oLher lmporLanL ouLcomes
lncludlng morbldlLy, lengLh of sLay ln hosplLal and lCu ranged from moderaLe
Lo low quallLy.
1he evldence of effecLlveness for Lhe use of albumln ln paLlenLs wlLh sepsls
was of moderaLe Lo hlgh quallLy.
CLher Lhan LhaL perLalnlng Lo Lhe use of albumln and LeLrasLarches for fluld
resusclLaLlon, much of Lhe evldence ln Lhe revlews presenLed ln Lhls chapLer on
Lhe besL Lype of fluld Lo use and Lhe opLlmal volume, Llmlng and raLe of lLs
admlnlsLraLlon was of low or very low quallLy, wlLh ma[or llmlLaLlons ln Lhe
deslgn of sLudles whlch lncrease Lhe rlsk of blas.
A ma[or lssue wlLh Lhls revlew (and oLher revlews ln Lhls guldellne) has been
Lhe breadLh of Lhe LargeL populaLlon, whlch lncludes all hosplLallsed paLlenLs.
As a resulL, evldence found ln relaLlon Lo speclflc groups of paLlenLs (as was
mosLly Lhe case) was [udged Lo be lndlrecL Lo Lhe whole LargeL populaLlon and
Lhe evldence was downgraded for Lhls. 1he evldence from Lhe Lrlals ldenLlfled
may have llmlLed appllcablllLy Lo Lhe slLuaLlon where baslc guldance for lv fluld
resusclLaLlon ln hosplLal admlsslon unlLs and general ward areas ls needed for
cllnlclans wlLh relaLlvely llmlLed experlence. MosL Lrlals were carrled ouL ln
elLher:
operaLlng sulLes - where much of the need for fluld resuscitation for
sub[ecLs llkely Lo be ellglble for a Lrlal relaLes Lo Lhe need Lo malnLaln
lnLravascular volume ln Lhe face of anaesLheLlc lnduced vasodllaLaLlon, or
lnLenslve care seLLlngs - where many cases needing IV fluid resuscitation
are effectively in second line situations rather than the first line therapy
slLuaLlon when fluld resusclLaLlon ls needed ln admlsslon or general ward
areas
1he lncluslon of dlfferenL groups and dlfferenL lnLeracLlon of Lhe lnLervenLlons
ln Lhese speclflc groups creaLed conslderable heLerogenelLy - Lhls was
consldered when assesslng Lhe quallLy of evldence.

127
. 1he evldence from Lrlals on fluld resusclLaLlon was dlfflculL Lo analyse
(comblne for a meLa-analysls) because Lhe Lypes and volumes of fluld, Llmlng
of lnlLlaLlon and raLes of admlnlsLraLlon varled conslderably. Some Lrlals also
lncluded Lhe use of dlfferenL lnoLropes.
CuallLy of evldence for sLudles on volume and Llmlng of flulds for resusclLaLlon
was low Lo very low for all crlLlcal ouLcomes. 1here are ma[or llmlLaLlons ln Lhe
deslgn of sLudles, whlch lncrease Lhe rlsk of blas.
1he sLudles on early vs. laLe admlnlsLraLlon of lv fluld resusclLaLlon were
conducLed ln speclflc populaLlons (e.g. peneLraLlng Lrauma, sepLlc shock, acuLe
lung ln[ury paLlenLs) LhaL may well noL be represenLaLlve of Lhe more general
hosplLal populaLlons who are Lhe focus of Lhls guldellne. aLlenLs wlLh
peneLraLlng Lrauma ln parLlcular, may respond dlfferenLly (as suggesLed by
subgroup evldence) slnce early fluld resusclLaLlon (before surgery) may
lncrease blood pressure and dlluLe coagulaLlon facLors, lncreaslng Lhe rlsk of
furLher bleedlng. 1here ls also a concern LhaL Lhe sLudy populaLlons were
relaLlvely young and LhaL elderly paLlenLs may noL be able Lo LoleraLe fasL and
hlgh volume fluld resusclLaLlon as well as younger paLlenLs. lor Lhese reasons,
Lhe evldence was downgraded for lndlrecLness.
1he cosL-effecLlveness analysls of albumln was assessed as parLlally appllcable,
slnce lL was conducLed from a lrench healLh care perspecLlve and Lherefore
Lhe resource use and cosL may noL be enLlrely Lransferable Lo a uk nPS seLLlng.
lL was also assessed as havlng poLenLlally serlous llmlLaLlons as Lhe non-drug
cosLs were noL adequaLely descrlbed.
CLher conslderaLlons 1he CuC consldered Lhe flndlngs from Lhe evldence revlews on Lypes, volumes
and Llmlngs of fluld admlnlsLraLlon when drafLlng Lhe recommendaLlons for
Lhls revlew.
An updaLed Cochrane revlew comparlng crysLallolds Lo collolds for fluld
resusclLaLlon ln crlLlcally lll paLlenLs publlshed ln lebruary 2013
83
was also
dlscussed by Lhe CuC. AlLhough dlfferenL ln many aspecLs wlLh respecL Lo Lhe
revlew proLocol and Lherefore noL lncluded ln Lhls guldellne (Lhe Cochrane
revlew lncluded sLudles on paLlenLs wlLh burns and LraumaLlc braln ln[ury LhaL
were ouL of Lhe scope of Lhls guldellne, lncluded penLasLarches, hexasLarches
and hyper-oncoLlc crysLallolds and collolds as comparaLors and also lncluded
sLudles conducLed before 1990), Lhe revlew lncluded cerLaln populaLlons and
lnLervenLlons whlch were relevanL Lo Lhls revlew. llndlngs from Lhls Cochrane
revlew echo Lhe flndlngs of Lhls cllnlcal evldence revlew wlLh respecL Lo effecL
slzes of morLallLy when comparlng crysLallolds Lo collolds. 1he CuC Look Lhls
lnLo conslderaLlon as slgnlflcanL addlLlonal evldence when maklng Lhe
recommendaLlons.
1he CuC consldered Lhe absoluLe lncrease ln morLallLy when maklng Lhe
recommendaLlons. uefaulL values of Lhe mlnlmal cllnlcally lmporLanL
dlfferences (0.73- 1.23) when assesslng Lhe relaLlve rlsk were agreed Lo be
lnapproprlaLe when decldlng upon Lhe cllnlcal lmporLance of morLallLy as an
ouLcome and Lhe declslon of Lhe CuC was based on effecL slze of Lhe absoluLe
rlsk dlfference ln morLallLy.
1he recommendaLlon for Lhe use of crysLallolds for fluld resusclLaLlon was
based on moderaLe quallLy cllnlcal evldence and Lhe evldence for cosL-
effecLlveness of crysLallolds. 1hls recommendaLlon was agreed Lo be a key
prlorlLy for lmplemenLaLlon. 1he recommendaLlon for noLuslng LeLrasLarch for
fluld resusclLaLlon was based on Lhe evldence of an lncrease ln morLallLy ln Lhe
long Lerm (morLallLy aL 90 days). AlLhough Lhls evldence was from paLlenLs
wlLh sepsls and was downgraded for lndlrecLness, Lhe CuC consldered LhaL lL
sLlll was appllcable Lo all paLlenLs recelvlng fluld resusclLaLlon as a slgnlflcanL

128
proporLlon may have underlylng sepsls.
1he recommendaLlon of Lhe use of human albumln soluLlon for fluld
resusclLaLlon of paLlenLs wlLh sepsls ls based on Lhe evldence from Lhe revlews
presenLed lncludlng Lhe economlc analysls whlch supporLed lLs use. Powever,
Lhe CuC recognlzed LhaL Lhere were conslderable pracLlcal/supply lssues LhaL
would llmlL lLs wldespread usage ln non-speclallsL seLLlngs. 8ecommendaLlon
16 was ldenLlfled as a key prlorlLy for lmplemenLaLlon.
1he CuC consldered Lhe exLenL Lo whlch Lhls recommendaLlon mlghL change
pracLlce and whaL was needed Lo lmplemenL Lhls. 1he CuC agreed LhaL lL was
lmporLanL LhaL Lhls recommendaLlon was consldered ln accordance wlLh Lhe
algorlLhm ouLllned for fluld resusclLaLlon (refer recommendaLlon 4 and
algorlLhm 2).
noLe: uurlng Lhe perlod of sLakeholder consulLaLlon on Lhls guldellne (on 27Lh
!une, 2013), a Class 2 urug AlerL was lssued by Lhe Medlclnes and PealLh
8egulaLory AuLhorlLy (MP8A), uk recalllng all unexplred sLock of hydroxyeLhyl
sLarches. 1he alerL was based on flndlngs of large 8C1s whlch reporLed an
lncreased rlsk of renal dysfuncLlon and morLallLy ln crlLlcally lll or sepLlc
paLlenLs who recelved hydroxyeLhyl sLarch compared wlLh Lhose who recelved
crysLallolds.
1he CuC also consldered Lhls declslon of Lhe MP8A and lLs lmpllcaLlons whlle
drafLlng Lhe recommendaLlon Lo noL use LeLrasLarches for fluld resusclLaLlon.
The GDG discussed the findings and its relevance to early on ward fluid
resusclLaLlon wlLh collold soluLlons and agreed LhaL Lhe evldence on Lhls was
sLlll lnconcluslve and drafLed a recommendaLlon for furLher research whlch
alms Lo compare Lhe effecLlveness of balanced crysLallolds wlLh a comblnaLlon
of a balanced crysLallold and a gelaLln suspended ln a balanced soluLlon for
fluld resusclLaLlon of paLlenLs wlLh acuLe hypovolaemlc shock (see research
recommendaLlon 3, also see research recommendaLlon proLocol ln Appendlx
C).


129
7.4.1 A|gor|thm 2: I|u|d kesusc|tat|on


130
1h|s sect|on ||nks the ev|dence to A|gor|thm 2 and the recommendat|on bu||et spec|f|c to
resusc|tat|on.
kecommendat|ons
Cffer IV f|u|d therapy as part of a protoco| (see A|gor|thms for IV
f|u|d therapy):
Assess patients fluid and electrolyte needs following Algorithm
1: Assessment.
If pat|ents need IV f|u|ds for f|u|d resusc|tat|on, fo||ow A|gor|thm
2: I|u|d resusc|tat|on.
ouLcomes
measured by SequenLlal Crgan lallure AssessmenL (SClA) scores.
All cause morLallLy was consldered Lo be Lhe mosL lmporLanL ouLcome for
declslon maklng, alLhough all oLher ouLcomes were deemed as lmporLanL for
lnformlng recommendaLlons.
beneflLs and harms
1he algorlLhm for fluld resusclLaLlon was based on:
evldence based on Lhe prlnclples of fluld prescrlblng as descrlbed ln secLlon
3.1
Lhe revlews of Lhe use of algorlLhms ln fluld prescrlblng descrlbed ln
secLlon 3.2
guldance on Lhe assessmenL of paLlenLs accordlng Lo Lhe nLWS score
93

guldance on Lhe non-fluld based elemenLs recommended for resusclLaLlon
conLalned currenL Advanced Llfe SupporL guldance
3

Lhe evldence revlews lnformlng Lhe Lype, volume and Llmlng of fluld
admlnlsLraLlon for resusclLaLlon (see secLlon 7.3)
1hls approach allowed Lhe CuC Lo develop Lhe compleLe resusclLaLlon
algorlLhm as well as some speclflc recommendaLlons on lv fluld Lherapy for
resusclLaLlon.
AssessmenL of Lhe need for fluld resusclLaLlon was based on naLlonal Larly
Warnlng Score (nLWS) crlLerla and nlCL CC30.
16,93
lrom Lhe slx rouLlnely
monlLored physlologlcal parameLers, Lhe CuC ldenLlfled pulse, blood
pressure and resplraLory raLe as Lhe key cllnlcal markers of Lhe sympaLheLlc
response Lo physlologlcal decompensaLlon.
ln addlLlon Lhe CuC agreed LhaL prolonged caplllary reflll Llme and cool
perlpherles were lmporLanL slgns of reduced Llssue perfuslon secondary Lo
Lhe sympaLheLlc response Lo shock LhaL should be ldenLlfled on lnlLlal
assessmenL of need for fluld resusclLaLlon.
Lconomlc conslderaLlons ln secLlon 3.2.3 lL was noLed LhaL for paLlenLs wlLh sepsls, proLocollsed care
was found Lo be cosL-effecLlve for sepsls paLlenLs ln Lwo sLudles and cosL
savlng ln a Lhlrd sLudy. 1hls evldence was consldered Lo be parLlally
appllcable and wlLh poLenLlally serlous llmlLaLlons.


131
cllnlcal effecLlveness evldence were [usL as pronounced for lnLra-operaLlve
care Lhe CuC felL LhaL Lhe economlc beneflLs of proLocols are very llkely Lo
be achlevable across all seLLlngs.
CuallLy of evldence 1he algorlLhm was based on esLabllshed guldance (nLWS, ALS guldance),
consensus oplnlon of Lhe CuC members and flndlngs from Lhe sysLemaLlc
revlews underLaken for deLermlnlng Lhe mosL cllnlcal and cosL-effecLlve Lype,
volume and Llmlng of flulds Lo be used for resusclLaLlon and Lhe revlew on
cllnlcal effecLlveness of proLocollsed care.
CuallLy of evldence for ouLcomes analysed ln Lhe sysLemaLlc revlews ranged
from very low Lo hlgh. lor deLalls on quallLy of evldence for lndlvldual
revlews, refer secLlons 3.2, 7.2 and 7.3.
admlnlsLraLlon (see secLlon 3.2), Lhe CuC felL LhaL proLocollsed care ln
general achleves beLLer ouLcomes for paLlenLs and Lherefore declded LhaL an
algorlLhmlc approach Lo fluld resusclLaLlon ls approprlaLe ln Lhls conLexL. ln
recommendaLlons LhaL a foundaLlon year docLor could follow vla Lhe
proLocol Lo lnlLlaLe approprlaLe resusclLaLlon LreaLmenL as a flrsL responder.
1he recommendaLlons and proLocol conLalned wlLhln Lhe algorlLhm on Lhe
Lype, volume, Llmlng and raLe of lv fluld use for resusclLaLlon are based on:
the principles of fluid prescribing described ln secLlon 3.1
the reviews of evidence related to the use of algorithms in fluid prescribing
descrlbed ln secLlon 3.2
the evidence reviews on fluid type, volume, rate and timing presented here;
and
the consensus expert views of the GDG.
1he non-fluld prescrlpLlon elemenLs lncorporaLed ln Lhe algorlLhm lncludlng
Lhose on assessmenL for resusclLaLlon and Lhe non-fluld urgenL LreaLmenLs
such as hlgh-flow oxygen and securlng lnLravenous access are ln llne wlLh
Advanced Llfe SupporL (ALS) guldance
90
.
AdmlnlsLraLlon of fluld boluses accordlng Lo body welghL was recommended
by Lhe CuC as a safe and effecLlve approach Lo fluld resusclLaLlon, alLhough
as wlLh oLher approaches regular reassessmenL of Lhe paLlenL ls needed. 1he
use of 300 ml of fluld bolus for fluld resusclLaLlon was based on CuC
consensus.
1he CuC agreed LhaL recognlLlon of Lhe serlously lll paLlenL wlLh a nLWS
score of 3 or more should prompL seeklng of experL help, alongslde Lhe
lnlLlaLlon of resusclLaLlon. The GDG consensus on senior input was as
deflned by nlCL CC30.
16

7.S kesearch recommendat|ons
2. Are ba|anced so|ut|ons super|or to sod|um ch|or|de 0.9 for the f|u|d resusc|tat|on of pat|ents w|th
acute hypovo|aem|c shock?


132
hyslologlcal sLudles, large cohorL sLudles and small randomlsed sLudles have shown LhaL balanced
crysLallolds may be superlor Lo sodlum chlorlde 0.9 for Lhe LreaLmenL of surglcal paLlenLs. Powever,
Lhe quallLy of Lhe evldence ls poor. 1hese sLudles have shown LhaL, when compared wlLh sodlum
chlorlde 0.9, Lhere ls less dlsLurbance ln acldbase balance (hyperchloraemlc acldosls), acuLe kldney
ln[ury, Lhe need for renal replacemenL Lherapy, blood loss and overall compllcaLlon raLes wlLh balanced
crysLallolds. Powever, large randomlsed Lrlals have shown LhaL crysLallolds are superlor Lo collolds for
resusclLaLlon. ln Lhese sLudles collolds were glven for prolonged perlods of Llme and Lhe groups of
paLlenLs lncluded were heLerogenous. 1he proposed Lrlal wlll help valldaLe wheLher Lhe daLa gaLhered
from physlologlcal sLudles and cohorL sLudles LhaL compared sodlum chlorlde 0.9 wlLh balanced
crysLallolds LranslaLe lnLo relevanL cllnlcal beneflL ln paLlenLs needlng acuLe fluld resusclLaLlon, and wlll
be a valuable gulde Lo cllnlcal pracLlce.
3. Are ba|anced crysta||o|ds super|or to a comb|nat|on of a ba|anced crysta||o|d and a ge|at|n
suspended |n a ba|anced so|ut|on for the f|u|d resusc|tat|on of pat|ents w|th acute hypovo|aem|c
shock?

8ecenL large randomlsed conLrolled Lrlals suggesL LhaL crysLallolds (sodlum chlorlde 0.9 or balanced
soluLlons) are superlor Lo 6 hydroxyeLhyl sLarch for resusclLaLlon. MorLallLy and compllcaLlon raLes,
especlally renal compllcaLlons, may be lncreased wlLh 6 hydroxyeLhyl sLarch. Powever, Lhere ls a lack
of good-quallLy evldence on Lhe use of gelaLln for resusclLaLlon. Some randomlsed conLrolled Lrlals have
shown LhaL when collolds are used for resusclLaLlon, volumes of fluld requlred may be less Lhan wlLh
crysLallolds. lL musL be remembered LhaL collolds cannoL be used excluslvely for resusclLaLlon and LhaL
some free waLer musL be provlded, and Lhere are llmlLed daLa on Lhe use of gelaLlns for resusclLaLlon.
1he proposed Lrlal wlll help lnform wheLher a comblnaLlon of gelaLln and crysLallold ls superlor Lo
crysLallold alone for Lhe resusclLaLlon of paLlenLs wlLh acuLe shock.
4. When undertak|ng per|operat|ve goa|-d|rected f|u|d therapy, does the cho|ce of f|u|d affect
comp||cat|ons and hosp|ta| |ength of stay?
Several sLudles have shown reduced lengLhs of sLay and reduced compllcaLlons afLer a varleLy of surglcal
procedures when fluld Lherapy ls opLlmlsed by LargeLlng varlous haemodynamlc goals (goal-dlrecLed
Lherapy [Cu1]). 1he mosL common haemodynamlc goal has been opLlmal sLroke volume, as measured
by oesophageal doppler or an alLernaLlve non-lnvaslve Lechnlque .MosL sLudles have used collolds
(hydroxyeLhyl sLarch or gelaLlne), alLhough some have used crysLallold.
Collolds are more expenslve Lhan crysLallolds and recenL daLa lndlcaLe LhaL hydroxyeLhyl sLarch ls
assoclaLed wlLh an lncreased rlsk of acuLe kldney ln[ury ln paLlenLs wlLh sepsls. lf collolds are Lo be used
as Lhe defaulL fluld for perloperaLlve Cu1, Lhere should be clear evldence for Lhelr beneflL over
crysLallolds.
1here ls evldence showlng beneflL of physlologlcal (or balanced) flulds compared wlLh sallne-based
flulds, Lherefore, lL would seem approprlaLe Lo underLake a bllnded, randomlsed conLrolled Lrlal of
collold ln balanced soluLlon compared wlLh a balanced crysLallold soluLlon for perloperaLlve Cu1. lf
morLallLy ls Lo be Lhe prlmary end polnL for such a sLudy, Lhen prohlblLlvely large numbers of paLlenLs
would need Lo be enrolled. CLher achlevable ouLcomes lnclude hosplLal lengLh of sLay, recovery of guL
funcLlon (for gasLrolnLesLlnal surgery) and compllcaLlons such as renal lmpalrmenL, lnfecLlon, pulmonary

133
oedema and myocardlal lnfarcLlon. Such a sLudy should be deslgned Lo show non-lnferlorlLy for
crysLallold versus collold.

lnLravenous fluld Lherapy for rouLlne malnLenance

134
8 Intravenous f|u|d therapy for rout|ne ma|ntenance
8.1 Introduct|on
lnLravenous fluld Lherapy for rouLlne malnLenance refers Lo Lhe provlslon of lv flulds and elecLrolyLes for
paLlenLs who cannoL meeL Lhelr needs by oral or enLeral rouLes, yeL are oLherwlse well ln Lerms of fluld
and elecLrolyLe balance and handllng (l.e. Lhey are essenLlally euvolaemlc wlLh no slgnlflcanL elecLrolyLe
deflclLs, ongolng abnormal losses or complex lnLernal redlsLrlbuLlon lssues). Powever, even when
prescrlblng lv flulds for more complex cases, there is still a need to account for patients routine
malnLenance requlremenLs, provldlng lv fluld malnLenance prescrlpLlons LhaL are Lhen ad[usLed Lo
accounL for Lhelr more complex fluld or elecLrolyLe problems. LsLlmaLes of rouLlne malnLenance
requlremenLs are Lherefore essenLlal for any paLlenL on conLlnulng lv fluld Lherapy.
1he use of lv flulds for purely rouLlne malnLenance purposes ls relaLlvely unusual. Lxamples lnclude
paLlenLs followlng a dysphaglc sLroke, paLlenLs wlLh Cl obsLrucLlon before surgery, and oLher pre-
operaLlve paLlenLs who need Lo be nll-by-mouLh. Cccaslonally lv flulds may also be needed for paLlenLs
who are unable Lo access drlnks because of physlcal deblllLy, reduced menLal capaclLy or dlmlnlshed
level of consclousness buL ln many of Lhese cases, and lndeed ln some of Lhe oLher lnsLances menLloned
above, lL ls ofLen posslble Lo meeL fluld and elecLrolyLe needs vla enLeral Lubes or, occaslonally, by uslng
sub-cuLaneous flulds.
8.1.1 kout|ne ma|ntenance f|u|ds for surg|ca| pat|ents
Cne group LhaL frequenLly recelves lv flulds whlch are essenLlally for routine malnLenance ls posL-
operaLlve paLlenLs, alLhough early afLer surgery many such paLlenLs have fluld redlsLrlbuLlon lssues and
elLher deflclLs or more frequenLly excesses consequenL Lo lmbalances ln fluld and elecLrolyLe loss vs.
provlslon durlng Lhe operaLlon lLself. Advances ln surgery, anaesLhesla and perl-operaLlve care,
however, have reduced Lhe lengLh of Llme LhaL paLlenLs need Lo be nll by mouLh (n8M) boLh prlor Lo
and followlng surgery and so even afLer ma[or abdomlnal operaLlons, gasLrolnLesLlnal funcLlon reLurns
rapldly. Larly posL-operaLlve oral lnLake ls ofLen Lherefore posslble and Lhe absence of bowel sounds
per se does noL mean LhaL food and drlnk wlll noL be LoleraLed. Cenerally, nasogasLrlc (nC) Lubes are
only lndlcaLed for dralnage ln Lhe presence of Lrue lleus or gasLrlc dysfuncLlon (e.g. delayed gasLrlc
empLylng afLer pancreaLlc surgery) and lndeed, ln many cases, morbldlLy from nC Lubes may exceed
beneflL. CerLalnly, ln Lhe pasL, a comblnaLlon of nC Lubes and excess lv flulds may well have caused
unnecessary delay ln re-esLabllshlng oral lnLake and consequenL prolonged lengLh of sLay and, even
Loday, prolonged and ofLen excesslve posL-operaLlve lv malnLenance flulds conLlnue Lo be glven ln some
hosplLals.
1he alm when glvlng rouLlne malnLenance flulds ls Lo provlde enough fluld and elecLrolyLes Lo meeL
lnsenslble losses (300-1000 ml), malnLaln normal sLaLus of body fluld comparLmenLs and enable renal
excreLlon of wasLe producLs (300-1300 ml.). 8ouLlne malnLenance provlslon should nearly always be a
shorL-Lerm measure slnce lnapproprlaLe Lherapy rlsks volume overload and elecLrolyLe and acld-base
dlsLurbance parLlcularly hyponaLraemla. 1here may also be problems relaLed Lo prolonged venous
access.
!unlor medlcal sLaff are more llkely Lhan senlor sLaff Lo conLlnue lv malnLenance Lherapy when no
longer requlred, raLher Lhan re-lnsLlgaLlng oral lnLake. 1hey are also less llkely Lo lnlLlaLe nC or
parenLeral feedlng whlch help wlLh rlsks of malnuLrlLlon as well as lv fluld problems. More senlor
lnvolvemenL ln lv fluld prescrlblng and feedlng declslons ls Lherefore needed.

133
8.1.2 Cho|ce of |ntravenous f|u|ds for ma|ntenance
A varleLy of flulds can be used Lo meeL rouLlne malnLenance needs alLhough Lhere ls conslderable
debaLe abouL Lhe opLlmal ones Lo use. See 1able .1 ln Appendlx for Lhe composlLlon of some
crysLallolds commonly used ln Lhe uk.
PealLhcare professlonals lnvolved ln lv fluld prescrlblng should be famlllar wlLh Lhe composlLlon of Lhe
flulds Lhey use, and lL ls Lhe dlfferlng composlLlon of Lhese flulds (and Lhelr consequenL dlfferlng
properLles) LhaL underlle Lhe debaLes abouL Lhe besL Lype of fluld Lo use and hence Lhe evldence revlews
underLaken for Lhls ChapLer.
lsoLonlc sallne
Sodlum chlorlde 0.9, wlLh or wlLhouL addlLlonal poLasslum, ls one of Lhe mosL commonly used lv flulds
ln uk pracLlce. lL ls dlsLrlbuLed LhroughouL Lhe exLracellular fluld comparLmenL (LCl) wlLh perhaps only
23 of Lhe lnfused volume remalnlng ln Lhe lnLravascular comparLmenL. ln recenL years, quesLlons have
been ralsed as Lo wheLher lL ls sulLable for rouLlne malnLenance purposes slnce Lhe hlgh sodlum conLenL
could promoLe a degree of unnecessary sodlum and waLer reLenLlon and Lhe hlgh chlorlde conLenL wlll
promoLe some degree of hyperchloraemla. 1hls may Lhen lead Lo hyperchloraemlc acldosls and/or
slgnlflcanL reducLlons ln renal blood flow and glomerular fllLraLlon raLe as well as gasLrolnLesLlnal
mucosal acldosls and lleus . 1he use of 0.9 sodlum chlorlde mlghL Lherefore be beLLer conflned Lo
resusclLaLlon (Lhls quesLlon ls examlned ln chapLer 4) or replacemenL of speclflc Cl fluld or renal losses
hlgh ln sodlum chlorlde (examlned ln ChapLer 3).
Clucose 3 soluLlon
Clucose 3 soluLlon provldes a useful means of glvlng free waLer for, once Lhe glucose ls meLabollsed,
Lhe fluld ls dlsLrlbuLed LhroughouL LoLal body waLer. lL ls Lherefore a poLenLlally useful means of
correcLlng or prevenLlng slmple dehydraLlon and Lhe glucose conLenL wlll also help Lo prevenL sLarvaLlon
keLosls, alLhough lL ls lmporLanL Lo recognlze LhaL lL wlll noL make much of a conLrlbuLlon Lo coverlng a
paLlenLs overall nuLrlLlonal needs. 1he use of 3 glucose, , wlll lncrease rlsks of slgnlflcanL
hyponaLraemla, parLlcularly ln chlldren, Lhe elderly, paLlenLs on dlureLlcs and Lhose wlLh excess AuP due
Lo osmoLlc and non osmoLlc sLlmull (a problem seen qulLe frequenLly ln hosplLallzed paLlenLs).
neverLheless, hyponaLremla ls llkely Lo be avolded by noL exceedlng recommended volumes of
maintenance IV fluids and by careful monitoring of patients clinical volume status and electrolyte
measuremenLs. use of glucose conLalnlng soluLlons may also lead Lo hyperglycaemla ln paLlenLs who are
glucose lnLoleranL, alLhough Lhls can be avolded or LreaLed lf paLlenLs are monlLored approprlaLely.
Clucose sallnes
1here are many dlfferenL lv flulds conLalnlng glucose and sallne ln dlfferenL concenLraLlons buL Lhe Lwo
mosL commonly used ln general areas of uk hosplLal pracLlce are glucose 4 wlLh sodlum chlorlde
(elLher 0.18 or 0.43) . 8oLh are avallable wlLh or wlLhouL poLasslum aL varlous concenLraLlons). 1he
use of glucose 4 wlLh sodlum chlorlde 0.18 or even glucose 4 wlLh sodlum chlorlde 0.43 wlll
promoLe hyponaLraemla lf glven rapldly or ln excess, alLhough boLh are less llkely Lo cause Lhls Lhan
glucose 3 alone.
8alanced crysLallold soluLlons
8alanced crysLallolds are dlsLrlbuLed LhroughouL Lhe LCl and Lherefore have slmllar properLles Lo
sodlum chlorlde 0.9 ln Lerms of plasma volume expanslon and overall fluld dlsLrlbuLlon. Powever, Lhey
have LheoreLlcal advanLages over sodlum chlorlde 0.9 ln LhaL Lhey conLaln somewhaL less sodlum and

136
slgnlflcanLly less chlorlde. 1hey may Lherefore cause less sodlum and waLer reLenLlon Lhan 0.9 sodlum
chlorlde as well as less hyperchloraemla and Lhey do already conLaln oLher elecLrolyLes ln amounLs
whlch may meeL overall malnLenance needs.
A number of newer balanced crysLallold soluLlons are llkely Lo appear on Lhe markeL, beLLer Lallored Lo
meeL Lhe LheoreLlcal requlremenLs for malnLenance. When prescrlblng Lhese flulds lL wlll be ls essenLlal
to specify the Maintenance version where appropriate since there may be oLher verslons of Lhe flulds
deslgned for 8esusclLaLlon of 8eplacemenL. 1he facL LhaL some balanced soluLlons conLaln lacLaLe or
oLher buffers ls noL llkely Lo alLer Lhelr usefulness for rouLlne malnLenance.
1he evldence revlews descrlbed below examlne Lhe lssues relaLed Lo dlfferenL Lypes of poLenLlal rouLlne
malnLenance flulds as well lssues of Lhe opLlmal volumes and Llmlngs Lo use. Powever, even before LhaL
evldence was explored, Lhe CuC were aware LhaL lL would be dlfflculL Lo lnLerpreL slnce mosL sLudles ln
Lhls area vary aL leasL Lwo of Lhese parameLers slmulLaneously l.e. sLudy arms ln many 8C1s dlffer ln
boLh volume glven as well as Lype of fluld provlded.
1he CuC were also aware LhaL mosL sLudles would be ln posL-surglcal paLlenLs who ln many ways are
noL a slmple lv malnLenance group. Many posL-operaLlve paLlenLs sLarL wlLh some degree of sodlum and
waLer excess due Lo lnLra-operaLlve lv fluld provlslon when vasodllaLaLlon from anaesLhesla, coupled
wlLh lncreased Lranscaplllary escape from Lhe sLress responses Lo surgery (see secLlon 3.1.2.3), ofLen
demands Lhe lnfuslon of conslderable fluld volumes Lo malnLaln lnLravascular fllllng. Much of Lhls fluld
Lhen mlgraLes Lo Lhe lnLersLlLlal space and needs Lo be excreLed durlng Lhe early days afLer Lhe
operaLlon and, furLhermore, Lhe sLress responses Lrlggered by Lhe surgery are ofLen sLlll presenL Lo some
degree durlng LhaL perlod. Lvldence from posL-surglcal sLudles may Lherefore have llmlLed appllcablllLy
Lo non-surgical pure maintenance paLlenLs (ln whom lL ls unllkely LhaL sLudles have been performed)
and sLudles commenced or underLaken before, durlng or very shorLly afLer surgery are llkely Lo be
lnappllcable.
8.2 I|u|d types, vo|umes and t|m|ngs for IV f|u|d ma|ntenance
1he CuC were lnLeresLed ln explorlng any evldence whlch would ldenLlfy Lhe mosL cllnlcal and cosL
effecLlve fluld Lypes for meeLlng rouLlne fluld malnLenance needs, as well as Lhe besL volumes, lnfuslon
raLes and Llmlng of dellvery of Lhose flulds.
8.2.1 C||n|ca| ev|dence: I|u|d types
kev|ew quest|on: What |s the most c||n|ca| and cost effect|ve f|u|d to be used for |ntravenous f|u|d
therapy for rout|ne ma|ntenance |n hosp|ta||sed pat|ents?
We searched for randomlsed conLrolled Lrlals comparlng Lhe effecLlveness of glvlng equal volumes of
dlfferenL crysLallolds for lmprovlng ouLcomes ln hosplLallsed paLlenLs prescrlbed lv flulds for
predomlnanLly malnLenance purposes. We looked for sLudles LhaL compared Lhe effecLlveness of any of
Lhe followlng crysLallolds, elLher alone or ln comblnaLlon: sodlum chlorlde 0.9, buffered or
physlologlcal soluLlons, sodlum chlorlde 0.43 ln glucose 3, sodlum chlorlde 0.18 ln glucose 4,
alLernaLe balanced soluLlons (see secLlon 13 for deflnlLlon) and glucose 3.
lor full deLalls see revlew proLocol ln secLlon C.4, Appendlx C.
no 8C1s were found comparlng Lhe same volumes of Lhese dlfferenL flulds for malnLenance reglmens ln
hosplLallsed paLlenLs.

137
See secLlon 8.3 for llnklng evldence Lo recommendaLlons
8.2.2 C||n|ca| ev|dence: Vo|umes of IV f|u|ds for ma|ntenance
kev|ew quest|on: What |s c||n|ca| and cost effect|veness of d|fferent vo|umes of f|u|d adm|n|strat|on |n
pat|ents requ|r|ng |ntravenous f|u|ds for rout|ne ma|ntenance?
1he ob[ecLlve of Lhls revlew was Lo flnd ouL wheLher facLors such as LoLal volume (ml/kg/day) and
wheLher glvlng flulds conLlnuously over 24 hours vs. lnLermlLLenLly affecL Lhe safeLy and efflcacy of
malnLenance fluld managemenL.
We searched for 8C1s comparlng Lhe effecLlveness of varylng dlfferenL volumes beLween LreaLmenL
arms, alLhough ln dolng so lL was lnevlLable LhaL Lhe resulLlng fluld reglmens ln dlfferenL arms would also
vary ln elecLrolyLe dellvery as well as volume. Slnce paLhophyslologlcal changes durlng surgery mean
LhaL Lhe lnLraoperaLlve fluld ls noL really belng glven for malnLenance alone, we only lncluded sLudles
where allocaLlon Lo dlfferenL lv fluld LreaLmenL arms commenced afLer operaLlon. lor more deLalls see
revlew proLocol ln secLlon C.4, Appendlx C. lour 8C1s
33,33,63,114
comparlng Lhe safeLy and efflcacy of
resLrlcLed versus sLandard or llberal fluld managemenL afLer surgery were ldenLlfled. no 8C1s ln medlcal
(non-surglcal) populaLlons were found. Slnce Lhe four lncluded sLudles varled ln Lerms of Lhe sLudy
populaLlons and fluld sLraLegles, Lhey could noL be pooled for analysls. 1able 34 summarlses Lhe key
populaLlon and lnLervenLlon characLerlsLlcs for each sLudy. lor furLher deLalls of Lhe lncluded sLudles,
see Lhe evldence Lables ln secLlon L. 4, Appendlx L.
1he llsL of excluded sLudles and reasons for excluslons are shown ln secLlon P.4, Appendlx P.
1ab|e 34: Summary of key popu|at|ons and |ntervent|on character|st|cs
Study ID opu|at|on kestr|cted Standard Cther |nformat|on
CCnZALLZ
-lA!A8uC
2009
33

Cpen abdomlnal
vascular surgery
24 hours posL-
operaLlvely
n=40
Sodlum chlorlde
0.9, 1.3 llLres

1.3 llLres of sodlum
chlorlde 0.9 and 1
llLre of
Clucose 3

Cral flulds sLarLed on 3rd
day
AbouL 6 llLres excess
durlng operaLlon/lCu
40mmol poLasslum/day
LC8C
2002
33

Peml-colecLomles
& slgmold
colecLomles for
cancer
n=20
2L IV fluid, 0.5 litre
of sodlum chlorlde
0.9 and 1.3 llLres
of glucose 3
Cr
2 llLres of Clucose
4 / sodlum
chlorlde 0.18
(27ml/kg/day)
3 litres IV fluid, 1
llLre of sodlum
chlorlde 0.9
And 2 llLres of
glucose 3
(43ml/kg/day)
Cral flulds encouraged
posL-surgery
More oral flulds lnLake
recorded ln resLrlcLed
group
40-60mmol poLasslum/day
MACkA?
2006
63

ColorecLal surgery
wlLh prlmary
anasLomosls
n=80
2 llLres of glucose
4 / sodlum
chlorlde 0.18
2 llLres of glucose 3
and 1 llLre of sodlum
chlorlde 0.9
Cral flulds encouraged
posL surgery
lv fluld unLll day 3
vL8MLuL
Ln2009
114

Ceneral
abdomlnal
surgery
n=62
0.3 llLre of glucose
3 and 1 llLre of
sodlum chlorlde
0.9 (21ml/kg/day)
1 llLre of glucose 3
and 1.3 llLres of
sodlum chlorlde 0.9
(33ml/kg/day )
lmmedlaLely posL surgery,
1.3 llLres and 2.3 llLres /24
hour for resLrlcLed and
sLandard group

1ab|e 3S: C||n|ca| ev|dence prof||e: kestr|cted versus standard vo|umes of |ntravenous ma|ntenance f|u|ds
ua||ty assessment Number of pat|ents Lffect
ua||ty Importance
No of
stud|es Des|gn
k|sk of
b|as Incons|stency Ind|rectness Imprec|s|on Cther
kestr|cted
vo|ume
Standard
vo|ume
ke|at|ve
(9S CI) Abso|ute
A|| cause morta||ty (up to 30 days) (fo||ow-up 30 days)
3S,SS,63,114

4 8C1s no serlous
rlsk of blas
Serlous(a) Serlous(b) no serlous
lmpreclslon
none 99 103

noL pooled- See 1able 36

LCW C8l1lCAL
kesp|ratory fa||ure (fo||ow-up 30 days)
3S,SS,63,114

4 8C1s Serlous(c) Serlous(a) Serlous(b) very
serlous(d)
none 99 103

noL pooled See 1able 37 vL8? LCW lMC81An1
Deve|opment of rena| fa||ure]AkI (fo||ow-up 30 days)
3S,63,114

3 8C1s Serlous(c) Serlous(a) Serlous(b) very
serlous(d)
none 89 93

noL pooled See 1able 38

vL8? LCW lMC81An1
ua||ty of ||fe (measured w|th SI 36, at 3 months)
63

1 8C1s Serlous(e) none Serlous(b) very serlous(f) none 23 36 no slgnlflcanL dlfference (f) vL8? LCW lMC81An1
Length of hosp|ta| stay (post operat|ve)
3S,SS,63,114

4 8C1s Serlous(e) Serlous(a) Serlous(b) Serlous(g) none 99 103 noL pooled- See 1able 39 vL8? LCW lMC81An1
Morb|d|ty (SCIA score) not reported
(a) There was important clinical heterogeneity between studies, including; different volumes of fluids used in liberal and restricted arms, patients fluid status at the start of study (patients
lo ooe stoJy boJ sevete ovetlooJ17), potleot popolotloos, and magnitude of difference in between liberal and restricted strategies. Direction of effect dependent of whether flulJ sttoteqy
promotes fluid balance in the studies, rather than liberal or restricted. Direction of effect different between stuJles. kesolts oot pooleJ.
(b) 1be evlJeoce wete ftom obJomlool sotqlcol potleots wltb testtlcteJ vs stooJotJ volomes stotteJ lmmeJlotely post sotqety, except fot ooe stoJy, wblcb tectolteJ post obJomlool voscolot
sotqety potleots 17. lt ls oocleot lf tbls evlJeoce ls Jltectly oppllcoble to moloteoooce potleots - tbe flolJ booJlloq lo tbese potleots moy be Jlffeteot ftom tbe qeoetol (meJlcol) potleot.
(c) Ootcomes wete oot cleotly JefloeJ fot Jevelopmeot of teool follote lo stoJles. votlotloos lo tepottloq of respiratory problems, ranging from respiratory failure to infection.
(J) veot totes wete low ooJ ovetoll pooleJ oombet of pottlclpoots wos low. cooflJeoce lotetvols wete wlJe ooJ ctosseJ Mlus.
(e) Ooly ooe stoJy wos Jooble blloJeJ bot boJ o blqb tote of ooblloJloq ot Jevlotloo ftom ptotocol4. Ooe stoJy wos opeo lobel octool lv flolJ ptesctlptloo wete JepeoJeot oo lovestlqotot (fot
stoJy otm) ooJ sotqlcol teom membets (fot coottol otm) 2. 1be otbet stoJles wete obsetvet blloJeJ 1,J. .
(f) 5omple slze moy oot be poweteJ to Jetect o Jlffeteoce. Actool voloes oot tepotteJ.
(q) Ooe stoJy fovooteJ stooJotJ, wblle tbe otbets fovoot testtlcteJ, ot sboweJ oo Jlffeteoce. kesolts oot pooleJ Joe to Jlffeteot popolotloos


139
1ab|e 36: A|| cause morta||ty
Study ID
kestr|cted vo|ume
Lvents]tota| ()
Standard vo|ume
Lvents]tota| () ke|at|ve r|sk (9S CI)
CCnZALLZ-lA!A8uC2009
33
0/20 (0) 1/20 (3) 0.33 [0.01, 7.72]
LC8C2002
33
0/10 (0) 1/10 (10) 0.33 [0.02, 7.32]
MACkA?2006
63
1/39 (2.6) 1/41 (2.4) 1.03 [0.07, 16.23]
vL8MLuLLn2009
114
1/30 (3.3) 1/32 (3.1) 1.07 [0.07, 16.30]
1ab|e 37: Deve|opment of resp|ratory comp||cat|ons
Study ID
kestr|cted vo|ume
Lvents]tota| ()
Standard vo|ume
33
0/20 (0) 1/20 (3)
(pulmonary oedema)
0.33 [0.01, 7.72]
LC8C2002
33
0/10 (0) 2/10 (20)
(resplraLory lnfecLlon)
0.20 [0.01, 3.70]
MACkA?2006
63
unclear(a) unclear(a) noL esLlmable
vL8MLuLLn2009
114
1/30 (3.3)
(resplraLory dlsorder or
lnfecLlon)
0/32 (0) 3.19 [0.14, 73.49]
(o) 5toJy stotes tbot ooe petsoo JleJ of tespltototy follote. uoes oot stote wblcb qtoop. AlteoJy occoooteJ fot lo oll-coose
mottollty ooolysls.
1ab|e 38: Deve|opment of rena| fa||ure or AkI
Study ID
kestr|cted vo|ume
Lvents]tota| ()
Standard vo|ume
33
0/20 (0) 0/20 (0) noL esLlmable
MACkA?2006
63
0/39 (0) 0/41 (0) noL esLlmable
vL8MLuLLn2009
114
0/30 (0) 0/32 (0) noL esLlmable
1ab|e 39: Length of hosp|ta| stay (days)
Study ID kestr|cted vo|ume Standard vo|ume p va|ue ] effect s|ze
CCnZALLZ-
lA!A8uC2009
33

osL-operaLlve sLay lncludlng
lCu: Mean 8.4 (93 Cl: 7.6 -
9.1 ) n=20
osL-operaLlve sLay lncludlng
lCu: Mean 12.4 (93Cl: 8.7 -
16.1) n=20
0.003 (reporLed, unclear
whlch LesL used)
LC8C2002
33
osL-operaLlve sLay: Medlan
6.0 (lC8 3.070) n=10
osL-operaLlve sLay: Medlan
9.0 (lC8 7.8-14.3) n=10
0.001 (reporLed, uslng
Mann WhlLney u LesL)
MACkA?2006
63
Medlan 7.2 (lC8 61110)
n=39
Medlan 7.2 (lC8 61112)
n=41
0.902 (reporLed, log rank
LesL)
Pazard raLlo: 1.03 (0.66,
1.61)
vL8MLuLLn200
9
114

Medlan 9.0 (lC8 6.8 -11.3)
n=30 [Mean 12.3 (Su 12.7)]

Medlan 7.0(lC8 6.0-9.8)
n=32 [Mean 8.3 (Su 4.3)]

0.049 (reporLed, Mann
WhlLney u LesL)

140
8.2.3 C||n|ca| ev|dence: 1|m|ng of IV f|u|d ma|ntenance
kev|ew quest|on: What are the most c||n|ca| and cost effect|ve t|m|ngs of adm|n|strat|on of
|ntravenous f|u|ds |n pat|ents requ|r|ng |ntravenous f|u|ds for rout|ne ma|ntenance?
1he ob[ecLlve of Lhls revlew was Lo flnd ouL wheLher facLors such as when fluld should be lnlLlaLed or
raLe of admlnlsLraLlon (ml/kg/hour) would affecL Lhe safeLy and efflcacy of malnLenance fluld
managemenL.
We searched for 8C1s comparlng Lhe effecLlveness of varylng Llmlngs or raLe of fluld admlnlsLraLlon
beLween LreaLmenL arms. lor more deLalls see revlew proLocol ln secLlon C.4, Appendlx C.
no evldence was found comparlng dlfferenL Llmlngs or raLes of lv fluld malnLenance admlnlsLraLlon.
8.3 Lconom|c ev|dence
no publlshed sLudles of cosL-effecLlveness were found. 1he CuC consldered Lhe cholce of malnLenance
Lherapy Lo be a hlgh prlorlLy for de novo economlc modelllng. Powever, Lhe cllnlcal revlew dld noL flnd
evldence of Lhe relaLlve cllnlcal effecLlveness of dlfferenL fluld Lypes, so a slmple cosL analysls was
conducLed wlLh a Lhreshold senslLlvlLy analysls around Lhe number of compllcaLlons averLed, see
Appendlx n.
lL was assumed LhaL admlnlsLraLlon cosLs would be slmllar for each fluld and Lherefore only fluld cosLs
and compllcaLlon cosLs were lncluded. lluld cosLs were provlded by Lhe nPS Commerclal Medlclnes unlL
(CMu), where posslble. lor a few flulds, a cosL was noL avallable from Lhe CMu, so Lhese were provlded
by Lhe 1rusLs of lndlvldual CuC members.
1he cosL of a ma[or fluld-relaLed compllcaLlon (see 4.2.3) was esLlmaLed uslng nPS reference cosLs Lo be
1,868 (or 3,000 lncludlng a crlLlcal care eplsode).
1he cosL of each fluld ls shown ln 1able 40 along wlLh Lhe number of compllcaLlons LhaL would need Lo
be averLed Lo make each fluld cosL neuLral. 1he cheapesL flulds cosL 7.00 per paLlenL over 3 days see
1able. 1he lowesL cosL LreaLmenL LhaL meL bodlly fluld requlremenLs (see 3.1, especlally 1able 9), was
Sodlum chlorlde 0.18 ln 4 glucose + oLasslum (2C/27mmol, 0.2 concenLraLlon)aL 12.30 per
paLlenL, whlch would have Lo averL only 2-3 ma[or compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
1he mosL expenslve fluld cosL 108 and would need Lo averL 34-34 compllcaLlons per 1000 paLlenLs Lo
be cosL neuLral.
1hls analysls can be consldered as parLlally appllcable (slnce nPS unlL cosLs were used buL CAL?s were
noL esLlmaLed) buL lL has poLenLlally serlous llmlLaLlons slnce some of Lhe fluld cosLs were Laken from an
individual Trust and therefore arent necessarily generalizable. Furthermore, conclusions about cost-
effecLlveness or cosL neuLrallLy are noL posslble wlLhouL evldence of Lhe number of compllcaLlons
averLed due Lo monlLorlng.

141
1ab|e 40: Cost of ma|ntenance f|u|ds
IV f|u|d type (|n order of cost of f|u|d per pat|ent)
(2)
Cost of f|u|d per
70kg pat|ent
(2000m| per day
for S days)
(1)
Number of extra
comp||cat|ons per 1000
pat|ents that wou|d need to
be averted for f|u|d to the
|owest cost f|u|d (|nc|ud|ng
cr|t|ca| care)
0.9 sodlum chlorlde 7.00 -
Sodlum chlorlde 0.18 ln 4 glucose 7.00 -
3 Clucose 7.00 -
1Lx 0.9 sodlum chlorlde Lo 2Lx 3 glucose 7.00 -
ParLmann's SoluLlon 8.30 1 (1)
AlLernaLe 8alanced SoluLlon 9.00 1 (1)
1Lx ParLmann's Lo 1.3Lx 3 Clucose wlLh
oLasslum (3C/40mmol) 9.88 2 (1)
Sodlum chlorlde 0.18 ln 4 glucose + oLasslum
(2C/27mmol) 12.30 3 (2)
3 Clucose wlLh poLasslum (2C/27mmol) 14.64 4 (3)
1Lx 0.9 sodlum chlorlde Lo 2Lx 3 Clucose wlLh
oLasslum (2C/27mmol) 14.78 4 (3)
0.9 Sodlum Chlorlde wlLh poLasslum(2C/27mmol) 13.12 4 (3)
1Lx 8lngers Lo 1.3Lx 3 Clucose wlLh oLasslum
(3C/40mmol) 16.48 3 (3)
0.43 Sodlum Chlorlde ln 3 glucose 24.00 9 (6)
8lngers LacLaLe 23.00 10 (6)
2Lx 0.43 sodlum chlorlde ln 3 Clucose wlLh
poLasslum Lo 0.3Lx 0.43 sodlum chlorlde ln 3
Clucose 108.16 34 (34)

8.4 Lv|dence statements
8.4.1 C||n|ca|
8.4.1.1 I|u|d types for ma|ntenance
no sLudles were found comparlng Lhe effecLlveness of Lhe same volumes of dlfferenL crysLallolds for
hosplLal paLlenLs needlng lv flulds for rouLlne malnLenance.

142
8.4.1.2 I|u|d vo|umes for ma|ntenance - narrat|ve summary
lour 8C1s were found LhaL compared Lhe safeLy and effectiveness of a restricted vs standard (or
liberal) fluid strategy in 202 people undergoing surgery.
Cr|t|ca| outcomes:
A|| cause morta||ty
1wo 8C1s suggesLed LhaL resLrlcLed fluld reglmens may be assoclaLed wlLh lower all cause morLallLy
compared Lo llberal lnLravenous fluld sLraLegles, alLhough Lhe resLrlcLed reglmens also dellvered less
elecLrolyLes parLlcularly less sodlum chlorlde. 1wo furLher 8C1s suggesLed LhaL Lhere ls no dlfference ln
all cause morLallLy beLween groups, alLhough ln all sLudles, Lhe dlrecLlon of effecL ls uncerLaln slnce
evenL raLes were low. All evldence ls of very low quallLy.
Important outcomes:
Deve|opment of resp|ratory comp||cat|ons
1he dlrecLlon of effecL ln Lerms of developlng resplraLory compllcaLlons ls unclear. 1wo 8C1s suggesLed
LhaL resLrlcLed fluld reglmens may be assoclaLed wlLh lower resplraLory compllcaLlons (ln people
undergolng abdomlnal vascular surgery and colon resecLlons) buL one 8C1 suggesLed LhaL sLandard
volume reglmens may have lower raLes of resplraLory compllcaLlons. A furLher 8C1 menLloned
occurrence of resplraLory fallure buL dld noL sLaLe ln whlch group. 1he evenL raLes were low for all
sLudles and all evldence ls of very low quallLy.
Deve|opment of rena| fa||ure or acute k|dney |n[ury
All four 8C1s suggesLed LhaL Lhere was no cllnlcally lmporLanL dlfference ln Lhe rlsks of developlng renal
fallure or acuLe kldney ln[ury when comparlng paLlenLs recelvlng resLrlcLed lv flulds compared Lo Lhose
recelvlng sLandard fluld volumes wlLh no reporLs of renal fallure or acuLe kldney ln[ury ln elLher group
for any of Lhe sLudles. All evldence ls of very low quallLy.
Cutcome: ua||ty of ||fe
ln Lerms of quallLy of llfe assessed by Sl-36, one 8C1 lndlcaLes Lhere ls no dlfference beLween sLandard
or resLrlcLed lv fluld admlnlsLraLlon aL 3 monLhs. Powever Lhe effecL slze could noL be deLermlned and
no clear lnLerpreLaLlon can be made from Lhls evldence whlch was very low quallLy.
Cutcome: Length of hosp|ta| stay
1he dlrecLlon of effecL on lengLhs of hosplLal sLay were varlable. 1wo 8C1s suggesLed LhaL resLrlcLed fluld
reglmens may be assoclaLed wlLh shorLer hosplLal sLays (ln people undergolng abdomlnal vascular
surgery and colon resecLlons) buL one 8C1 suggesLed LhaL resLrlcLed volume may lead Lo longer hosplLal
sLays, and anoLher reporLed no dlfference beLween groups. 1he overall effecL ls Lherefore uncerLaln
especlally as resulLs could noL be pooled buL Lhe dlfferences ln Lhe dlrecLlon of effecL can be explalned
by varlaLlon ln Lhe degree of fluld resLrlcLlon lmposed ln dlfferenL sLudles (see secLlon 8.3 below). All
evldence ls of very low quallLy.

143
Cutcome: Morb|d|ty
no sLudles reporLlng morbldlLy daLa as measured by SClA scores were found.
8.4.1.3 I|u|d t|m|ngs
no sLudles were found comparlng Lhe effecLlveness of any of Lhe crysLallolds for use ln lnLravenous
malnLenance reglmens ln hosplLallsed paLlenLs.
8.4.2 Lconom|c
An orlglnal comparaLlve cosL analysls showed LhaL:
1he lowesL cosL flulds were sodlum chlorlde 0.9, sodlum chlorlde 0.18 ln glucose 4, glucose 3
aL 7.00 per paLlenL over 3 days.
Sodlum chlorlde 0.18 ln glucose 4 + oLasslum (2C/27mmol, 0.2 concenLraLlon)aL 12.30 per
paLlenL, would have Lo averL only 1-2 ma[or compllcaLlon per 1000 paLlenLs Lo be cosL neuLral
compared wlLh Lhe lowesL cosL flulds.
1he mosL expenslve fluld cosL 108 and would need Lo averL 34-34 compllcaLlons per 1000 paLlenLs
Lo be cosL neuLral.
CLher flulds would have Lo averL up Lo 10 compllcaLlons per 1000 paLlenLs Lo be cosL neuLral.
8.S kecommendat|ons and ||nk to ev|dence
kecommendat|ons
19. If pat|ents need IV f|u|ds for rout|ne ma|ntenance a|one, restr|ct the
|n|t|a| prescr|pt|on to:
2S30 m|]kg]day of water and
approx|mate|y 1 mmo|]kg]day of potass|um, sod|um and ch|or|de
and
approx|mate|y S0100 g]day of g|ucose to ||m|t starvat|on ketos|s.
(1his quantity will not address patients nutritional needs; see
Nutr|t|on support |n adu|ts [NICL c||n|ca| gu|de||ne 32].)
Ior more |nformat|on see IV f|u|d prescr|pt|on (by body we|ght) for
rout|ne ma|ntenance over a 24-hour per|od.
20. Ior pat|ents who are obese, ad[ust the IV f|u|d prescr|pt|on to the|r |dea|
body we|ght. Use |ower range vo|umes per kg (pat|ents rare|y need
more than a tota| of 3 ||tres of f|u|d per day) and seek expert he|p |f the|r
8MI |s more than 40 kg]m
2
.
21. Cons|der prescr|b|ng |ess f|u|d (for examp|e, 202S m|]kg]day f|u|d) for
pat|ents who:
are o|der or fra||
have rena| |mpa|rment or card|ac fa||ure
are ma|nour|shed and at r|sk of refeed|ng syndrome (see Nutr|t|on

144
support |n adu|ts [NICL c||n|ca| gu|de||ne 32]).

22. Cons|der de||ver|ng IV f|u|ds for rout|ne ma|ntenance dur|ng dayt|me
hours to promote s|eep and we||be|ng.
8elaLlve values of
dlfferenL ouLcomes
1he CuC were lnLeresLed ln all cause morLallLy, lengLh of hosplLal sLay and
compllcaLlons lncludlng renal, resplraLory and morbldlLy as measured by SClA or
MCuS scores.
All cause morLallLy was consldered Lo be Lhe mosL lmporLanL ouLcome for declslon
maklng, alLhough all oLher ouLcomes were deemed as lmporLanL for lnformlng
recommendaLlons.
1rade off beLween
harms
lL ls unclear from Lhe cllnlcal evldence wheLher morLallLy or morbldlLy ln Lerms of
resplraLory problems, Akl or any scorlng sysLems are lmproved by resLrlcLed fluld
volumes compared Lo sLandard volumes. , Powever, Lhere dld appear Lo be
slgnlflcanL effecLs on lengLh of hosplLal sLay ln Lhree ouL of four of Lhe sLudles
alLhough Lwo suggesLed reducLlons when resLrlcLed volume reglmens were used
compared Lo sLandard volumes whllsL one suggesLed Lhe reverse. Powever, Lhe
dlfferences ln dlrecLlon of Lhe effecL can probably be explalned by Lhe dlfferenL
degree of fluld resLrlcLlon ln Lhe dlfferenL sLudles (see CuallLy of Lvldence below).

1he sLudles lncluded ln Lhe revlew welghed paLlenLs dally and paLlenLs recelvlng
hlgher volumes of flulds showed welghL galn, whlch ls llkely Lo be assoclaLed wlLh
excesslve fluld provlslon.
Lconomlc
conslderaLlons
no publlshed healLh economlc evldence was ldenLlfled. Powever, Lhe CuC would
expecL LhaL resLrlcLlng fluld lnLake would be cosL savlng as well as healLh lmprovlng,
slnce noL only wlll less fluld cosL less buL Lhere would be lower LreaLmenL cosLs from
Lhe cosLs of LreaLlng Lhe compllcaLlons assoclaLed wlLh fluld overload. As noLed
above Lhe lmpacL of resLrlcLlng flulds on lengLh of sLay ls uncerLaln.
CuallLy of evldence no 8C1 evldence was found comparlng Lhe fluld malnLenance Lypes of lnLeresL Lo Lhe
CuC.
no sLudles comparlng Lhe effecL of dlfferenL Llmlngs of sLarLlng, sLopplng or duraLlon
of lv fluld admlnlsLraLlon were found.
1he CuC dlscussed Lhe followlng ln relaLlon Lo Lhe quallLy of Lhe evldence relaLed Lo
Lhe opLlmal volume of lnfuslon for rouLlne malnLenance :
1he sLudles found had small sample slzes (lmpreclslon).
1here were llmlLaLlons ln sLudy deslgn and conducL whlch led Lo rlsk of blas and
downgradlng wlLhln Lhe C8AuL quallLy crlLerla.
1he sLudles lncluded had posL-operaLlve paLlenL samples (abdomlnal surgery or
abdomlnal vascular sLudy) wlLh none found relaLlng Lo medlcal paLlenLs. 1he CuC
Lherefore dlscussed Lhe exLenL Lo whlch flndlngs could be exLrapolaLed Lo all
paLlenLs requlrlng malnLenance Lherapy. 1he populaLlon ln Lhe sLudy was lndlrecL
Lo Lhe LargeL revlew populaLlon.
osL surglcal paLlenLs are noL LhoughL Lo be Lyplcal of Lhose paLlenLs recelvlng
malnLenance flulds. 1hls ls because surglcal paLlenLs do ofLen have excess fluld loads
and Lhe naLure of Lhe procedure means LhaL Lhey reLaln flulds.
82

1here was wlde varlaLlon ln sLudy proLocols and Lhe degree of dlfference beLween
whaL was consldered Lo be resLrlcLed and sLandard provlslon. lor example, ln Lhe
Mackay sLudy, Lhe dlfferences ln fluld volumes beLween Lhe Lwo reglmens were
noL cllnlcally slgnlflcanL and Lhe dlfferences ln welghL galn observed beLween Lhe
sLandard and resLrlcLed groups was less Lhan 1kg, whlch would noL be consldered

143
cllnlcally slgnlflcanL. lL was noLed LhaL noL only Lhe fluld volume buL Lhe sodlum
chlorlde provlslon was very dlfferenL across Lhe four sLudles ldenLlfled whlch
prevenLed meanlngful meLa-analysls. 1he resLrlcLed groups were glven fluld
volumes ranglng from 1.3L Lo 2.3 L wlLh sodlum chlorlde provlslon ranglng from 62
mmols Lo 231 mmols, whlle Lhe sLandard reglmen groups ln Lhe sLudles recelved
fluld volumes beLween 2L and more Lhan 4 L of fluld wlLh sodlum chlorlde
provlslon ranglng from 134 mmol Lo and 231 mmol. CuC felL LhaL Lhese
dlfferences mlghL explaln Lhe dlfferences ln Lhe resulLs wlLh poLenLlally adverse
ouLcomes seen wlLh elLher Loo much or Loo llLLle fluld and sodlum chlorlde and
LhaL Lhls would be loglcal ln Lerms of fluld prescrlblng prlnclples.
CLher conslderaLlons 1he CuC Look lnLo conslderaLlon many oLher sLudles, whlch dld noL meeL Lhe crlLerla
of Lhe revlew buL whlch had been used Lo lnform cllnlcal oplnlon over many years.
I|u|d type
no separaLe evldence was found relaLlng Lo Lhe besL Lype of fluld for Lhe
managemenL of people requlrlng fluld malnLenance buL all of Lhe sLudles revlewed
used elLher glucose 4, sodlum chlorlde 0.18 or a comblnaLlon of glucose 3 and
sodlum chlorlde 0.9.A consensus recommendaLlon was Lherefore made based on
CuC oplnlon and experlence.
1he CuC noLed LhaL Lhe use of glucose sallne, parLlcularly Sodlum chlorlde
0.18/4 glucose could predlspose Lo Lhe developmenL of hyponaLraemla buL
Lhey agreed LhaL Lhe cause of Lhls compllcaLlon ls mulLlfacLorlal and ls parLlcularly
a consequence of of admlnlsLerlng excesslve volumes especlally when Lhere are
oLher sources of waLer provlslon (e.g. from lv medlcaLlon or oral rouLes) or Lhe
presence excess anLl dlureLlc hormone (AuP) due Lo non osmoLlc sLlmull whlch
does occur ln some hosplLal paLlenLs. 1he compllcaLlon should Lherefore be
avolded lf only moderaLe volumes of lv flulds are prescrlbed for malnLenance and
paLlenLs are adequaLely monlLored, wlLh Lhe developmenL of hyponaLraemla
prompLlng a cllnlcal revlew of volume sLaLus and a change ln lnfuslon flulds
(alLhough hyponaLraemla ln Lhe conLexL of oedema should prompL senlor revlew
slnce many of Lhese paLlenLs have boLh sodlum and waLer overload and Lhe besL
LreaLmenL ls fluld resLrlcLlon raLher Lhan addlLlonal sodlum chlorlde
admlnlsLraLlon. 1he use of glucose conLalnlng soluLlons may lead Lo hyperglycemla
ln paLlenLs who are glucose lnLoleranL. 8lood glucose monlLorlng should be parL of
assessmenLs of paLlenLs recelvlng glucose conLalnlng flulds ln general. aLlenLs
wlLh dlabeLes are ouLslde Lhe scope of Lhls guldellne).
Commencement of ora| or entera| f|u|ds
1he CuC were lnLeresLed ln ldenLlfylng Lhe besL Llme Lo cease lv fluld managemenL
slnce Lhey were aware, from Lhelr cllnlcal experlence, LhaL prolonged lv fluld
managemenL can lead Lo slgnlflcanL problems and lncreased hosplLal sLay. no dlrecL
evldence was found Lo answer Lhls quesLlon buL Lhere have been Cochrane revlews
looklng aL oral and enLeral feedlng whlch compare early commencemenL of feeds Lo
delayed commencemenL. 1hese revlews conclude LhaL paLlenLs recelvlng early oral
or enLeral feedlng have reduced lengLhs of sLay. 1he CuC surmlsed LhaL lf paLlenLs
can LoleraLe food, Lhey are able Lo LoleraLe oral flulds and hence LhaL Lhese flndlngs
supporL Lhe consensus recommendaLlon LhaL lv flulds should be sLopped as soon as
a paLlenLs can LoleraLe flulds by oLher rouLes.
kestr|cted compared to standard vo|umes
1he CuC consldered Lhe volume of flulds Lo be a cenLral aspecL ln fluld malnLenance
managemenL. Adverse evenLs from fluld managemenL are relaLed Lo paLlenLs belng
glven lnapproprlaLe amounLs of flulds and elecLrolyLes (elLher Loo much or Loo llLLle.
1he CuC agreed LhaL lL was dlfflculL Lo lnLerpreL Lhe resulLs based on Lhe llmlLaLlons
of Lhe sLudles and varlaLlon ln effecL (see above). As such, Lhey agreed on an

146
approprlaLe range LhaL should be glven (lncludlng Lhe amounL of sodlum, poLasslum
and chlorlde).
1he CuC also consldered LhaL Lhere are groups of paLlenLs who should recelve lower
volumes ln Lhe ranges recommended. lor example, obese lndlvlduals do noL have
Lhe same meLabollc or muscle mass as people wlLh lean body mass. CedemaLous
paLlenLs requlre speclal conslderaLlon also, ln LhaL Lhe addlLlonal fluld musL be Laken
lnLo accounL before prescrlblng Lhe volume.
lL was hlghllghLed LhaL whllsL Lhe recommendaLlon ls Lo measure fluld volume
requlred ln Lerms of mllllllLre per kllogram of body welghL, fluld bags are prescrlbed
by Lhe llLre. See secLlon .4, Appendlx for Lable Lo ald rapld calculaLlon of
suggesLed volumes.
I|u|d prescr|b|ng dur|ng dayt|me hours
1he CuC dlscussed LhaL adequaLe sleep aL nlghL ls cruclal Lo paLlenL recovery.
Whlle lL was acknowledged LhaL Lhere may be lnsLances where lnLravenous fluld
Lherapy for rouLlne malnLenance may have Lo be glven aL nlghL due Lo compeLlng
demands durlng Lhe day, Lhe alm should be Lo promoLe sleep and well-belng for a
compleLe recovery. 1he CuC also consldered Lhe lmpllcaLlons of Lhls
recommendaLlon Lo Lhe effecL of docLors requlrlng a cllnlcal lndlcaLlon Lo resLarL
Lhe flulds whlch wlll lead Lo reduced lnapproprlaLe lv fluld prescrlblng, reduced
work for nurslng sLaff aL nlghL and lmproved paLlenL moblllLy due Lo noL belng Lled
Lo a drlp.
Cther cons|derat|ons
Cllnlcal evaluaLlon and conLlnued monlLorlng ls lmporLanL Lo ensure LhaL paLlenLs
are recelvlng Lhe correcL volume and Lype of fluld.
1he CuC dlscussed how body welghL ls deflned l.e. acLual or lean
8esearch recommendaLlons Lhe CuC agreed LhaL Lhere ls a need for research
relaLed Lo lv fluld rouLlne malnLenance provlslon ln medlcal paLlenLs buL
recognlsed LhaL Lhere could be dlfflculLles ln deslgnlng such a Lrlal.
8ecommendaLlon 22 was ldenLlfled as a key prlorlLy for lmplemenLaLlon by Lhe
CuC.

kecommendat|ons
23. When prescr|b|ng for rout|ne ma|ntenance a|one, cons|der us|ng 2S30
m|]kg]day sod|um ch|or|de 0.18 |n 4 g|ucose w|th 27 mmo|]|
potass|um on day 1 (there are other reg|mens to ach|eve th|s).
rescr|b|ng more than 2.S ||tres per day |ncreases the r|sk of
hyponatraem|a. 1hese are |n|t|a| prescr|pt|ons and further prescr|pt|ons
shou|d be gu|ded by mon|tor|ng.
8elaLlve values of
dlfferenL ouLcomes
1he CuC consldered all cause morLallLy Lo be Lhe mosL lmporLanL ouLcome. CLher
ouLcome consldered lmporLanL for declslon maklng lncluded developmenL of renal
compllcaLlons and resplraLory compllcaLlons. Powever, no evldence was ldenLlfled
for any of Lhese ouLcomes.
1rade off beLween
harms
use of sodlum chlorlde 0.18 ln Clucose 4 was agreed Lo be a slmple and effecLlve
reglmen for rouLlne malnLenance. Powever lL was recognlsed LhaL Lhere ls a rlsk of
hyponaLremla and hyperglycemla and Lhls should be kepL ln mlnd when prescrlblng.
Lconomlc
conslderaLlons
1here were no publlshed cosL-effecLlveness sLudles found. An orlglnal cosL analysls
compared a number of dlfferenL fluld sLraLegles, some of whlch lncluded poLasslum
and oLhers dld noL.
1he lowesL cosL flulds were 0.9 sodlum chlorlde, Sodlum chlorlde 0.18 ln 4

147
glucose, 3 glucose aL 7.00 per paLlenL over 3 days. Powever, Lhe CuC do noL
belleve LhaL Lhls sLraLegy would effecLlvely meeL bodlly requlremenLs. 1he lowesL
cosL LreaLmenL sLraLegy LhaL would meeL bodlly malnLenance fluld requlremenLs
was found Lo be Sodlum chlorlde 0.18 ln 4 glucose + poLasslum (2C/27mmol, 0.2
concenLraLlon). AL a cosL of 12.30 per paLlenL, lL would have Lo averL only 2-3
ma[or compllcaLlons per 1000 paLlenLs Lo be cosL neuLral compared wlLh Lhe lowesL
cosL fluld, whlch Lhe CuC consldered plauslble.
1he CuC dld noL wanL Lo be Loo prescrlpLlve abouL Lhe Lype of fluld used on Lhe
basls LhaL:
Lhe prlce of flulds varles conslderably accordlng Lo local conLracLs and volumes
purchased,
manufacLurers may declde Lo lnLroduce new brands of flulds as a resulL of Lhls
guldellne. lf Lhls guldellne leads Lo a sLandardlsaLlon of pracLlce Lhen Lhe cosL of
such flulds are llkely Lo come down.
1rusLs should purchase for malnLenance Lhe lowesL cosL fluld LhaL meeLs Lhe dally
requlremenLs recommended ln Lhls guldellne.
CuallLy of evldence no 8C1 evldence was found comparlng Lhe dlfferenL Lypes of fluld for rouLlne
malnLenance. 1he recommendaLlons are Lherefore based on Lhe consensus oplnlon
of Lhe CuC members.
CLher conslderaLlons 1he CuC dlscussed LhaL Lhe commonly used malnLenance reglmens were noL
approprlaLe and alLhough Lhese were lncluded ln Lhe comparaLors, Lhey were noL
accepLable.
1he CuC dlscussed LhaL for slmpllclLy of admlnlsLraLlon, Lhe lv fluld reglmens
conLalnlng only one fluld (LhaL ls Sodlum chlorlde 0.9 or Clucose 3) were mosL
accepLable and Lhe cosL of each would also have Lo be Laken lnLo accounL. 1he CuC
dlscussed recommendlng Sodlum chlorlde 0.18 ln Clucose 4 as a malnLenance
reglmen. lL was hlghllghLed LhaL a recenL MP8A warnlng had been lssued agalnsL
Lhe use of Lhls fluld ln chlldren under 16 years due Lo resulLlng faLal hyponaLremla.
1he CuC agreed LhaL Lhe recommendaLlon should acknowledge Lhls warnlng, buL
equally, lL was Lo be made clear LhaL Lhls recommendaLlon was for malnLenance use
and noL for use durlng resusclLaLlon or ln paedlaLrlc paLlenLs. lL was also declded
LhaL a warnlng should accompany Lhls recommendaLlon sLaLlng LhaL cauLlon was
needed ln paLlenLs wlLh low sodlum levels and hyponaLremla should be checked for
ln all cases wlLh ad[usLmenL of Lhe prescrlpLlon accordlngly. 1he recommendaLlon
above ls for Lhe lnlLlal prescrlpLlon.
1he CuC also dlscussed LhaL Lhls recommendaLlon would have Lo be pracLlced ln
con[uncLlon wlLh approprlaLe assessmenL and monlLorlng as Lhls was essenLlal lf Lhe
beneflLs were Lo be observed.
uue Lo Lhe pauclLy of evldence ln Lhls Loplc area, Lhe CuC prlorlLlsed a research
recommendaLlon evaluaLlng Lhe reducLlon ln rlsk of hyponaLraemla wlLh hlgher
sodlum conLalnlng lv fluld reglmens for malnLenance (see secLlon 8.6).

148
8.S.1 A|gor|thm 3: kout|ne ma|ntenance

Using an ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach, assess whether the patient is hypovolaemic and
needs fluid resuscitation
Assess volume status taking into account clinical examination, trends and context. Indicators that a patient may need fluid resuscitation
include: systolic BP <100mmHg; heart rate >90bpm; capillary refill >2s or peripheries cold to touch; respiratory rate >20 breaths per min;
NEWS 5; 45o passive leg raising suggests fluid responsiveness.
Clinical examination: pulse, BP, capillary refill, JVP, oedema (peripheral/
pulmonary), postural hypotension.

Does the patient have complex fluid or electrolyte
replacement or abnormal distribution issues?
Look for: existing deficits or excesses, ongoing losses,
abnormal distribution or other complex issues.


2530 ml/kg/d water
50100 g/day glucose (e.g dextrose 5% contains
5g/100ml).

Monitor and reassess the patient
Stop IV fluids when no longer an appropriate indication.
when maintenance needs are >3 days
Algorithm 2: Fluid
Resuscitation

Algorithm 4:
Replacement and
redistribution

No
No
No
Ensure nutrition
and fluid needs
are met. Also see
Nutrition support
in adults (NICE
clinical guideline
32).
Yes
Yes
Yes

149
1h|s sect|on ||nks the ev|dence to A|gor|thm 3 and the recommendat|on bu||et spec|f|c to rout|ne
ma|ntenance.
kecommendat|ons
Cffer IV f|u|d therapy as part of a protoco| (see A|gor|thms for IV
f|u|d therapy):
Assess patients fluid and electrolyte needs following A|gor|thm
1: Assessment.
If pat|ents need IV f|u|ds for f|u|d resusc|tat|on, fo||ow A|gor|thm
2: I|u|d resusc|tat|on.
ouLcomes
measured by SequenLlal Crgan lallure AssessmenL (SClA) scores.
All cause morLallLy was consldered Lo be Lhe mosL lmporLanL ouLcome for
declslon maklng, alLhough all oLher ouLcomes were deemed as lmporLanL for
lnformlng recommendaLlons.
beneflLs and harms
1he algorlLhm for rouLlne malnLenance was based on:
evldence based on Lhe prlnclples of fluld prescrlblng as descrlbed ln secLlon
3.1
Lhe revlews of Lhe use of algorlLhms ln fluld prescrlblng descrlbed ln
secLlon 3.2
guldance on Lhe assessmenL of paLlenLs accordlng Lo Lhe nLWS score
93

guldance on Lhe non-fluld based elemenLs recommended for resusclLaLlon
conLalned currenL Advanced Llfe SupporL guldance
3

Lhe evldence revlews lnformlng Lhe Lype, volume and Llmlng of fluld
admlnlsLraLlon for rouLlne malnLenance (see secLlon 8.2)
1hls approach allowed Lhe CuC Lo develop Lhe compleLe rouLlne
malnLenance algorlLhm as well as some speclflc recommendaLlons on lv fluld
Lherapy for rouLlne malnLenance.
Lconomlc conslderaLlons ln secLlon 3.2.3 lL was noLed LhaL for paLlenLs wlLh sepsls, proLocollsed care
was found Lo be cosL-effecLlve for sepsls paLlenLs ln Lwo sLudles and cosL
savlng ln a Lhlrd sLudy. 1hlrd evldence was consldered Lo be parLlally
appllcable and wlLh poLenLlally serlous llmlLaLlons.
cllnlcal effecLlveness evldence were [usL as pronounced for lnLra-operaLlve
care Lhe CuC felL LhaL Lhe economlc beneflLs of proLocols are very llkely Lo
be achlevable across all seLLlngs.
CuallLy of evldence 1he algorlLhm was based on esLabllshed guldance (nLWS, ALS guldance),
consensus oplnlon of Lhe CuC members and flndlngs from Lhe sysLemaLlc
revlews underLaken for deLermlnlng Lhe mosL cllnlcal and cosL-effecLlve Lype,
volume and Llmlng of flulds Lo be used for rouLlne malnLenance and Lhe
revlew on cllnlcal effecLlveness of proLocollsed care.
CuallLy of evldence for ouLcomes analysed ln Lhe sysLemaLlc revlews ranged

130
from very low Lo hlgh.
admlnlsLraLlon (see secLlon 3.2), Lhe CuC felL LhaL proLocollsed care ln
general achleves beLLer ouLcomes for paLlenLs and Lherefore declded LhaL an
algorlLhmlc approach Lo fluld resusclLaLlon ls approprlaLe ln Lhls conLexL. ln
recommendaLlons LhaL a foundaLlon year docLor could follow vla Lhe
proLocol Lo lnlLlaLe approprlaLe resusclLaLlon LreaLmenL as a flrsL responder.
1he recommendaLlons and proLocol conLalned wlLhln Lhe algorlLhm on Lhe
Lype, volume, Llmlng and raLe of lv fluld use for rouLlne malnLenance are
based on:
the principles of fluid prescribing described in section 3.1
the reviews of evidence related to the use of algorithms in fluid prescriblng
descrlbed ln secLlon 3.2
the evidence reviews on fluid type, volume, rate and timing presented here;
and
the consensus experL vlews of Lhe CuC.
1he CuC dlscussed Lhe lmporLance of sLopplng lv flulds as soon as posslble
wlLh reference Lo Lhe nlCL guldance on nuLrlLlon supporL.
72
lL was agreed
LhaL proper assessmenL and monlLorlng was and lnLegral parL of Lhls
algorlLhm and was essenLlal lf Lhe beneflLs were Lo be observed.
1he cholce of Lype of fluld was deLermlned by Lhe sysLemaLlc revlews
underLaken for Lype, volume and Llmlng of rouLlne malnLenance.
1hls recommendaLlon was ldenLlfled as a key prlorlLy for lmplemenLaLlon by
Lhe CuC.

S. Does a h|gher sod|um content IV f|u|d reg|men for ma|ntenance reduce the r|sk of deve|op|ng
hyponatraem|a and vo|ume dep|et|on w|thout |ncreas|ng the r|sk of vo|ume over|oad |n
hosp|ta||sed adu|ts?
aLlenLs who cannoL meeL Lhelr dally needs of flulds and elecLrolyLes Lhrough oral or enLeral rouLes buL
are oLherwlse euvolaemlc ofLen need lv fluld Lherapy for malnLenance. 1he mosL common
compllcaLlons of Lhls Lherapy are hyponaLraemla (lf excesslve lv waLer ls admlnlsLered), volume
overload (lf excesslve sodlum and waLer are admlnlsLered) and volume depleLlon and/or acuLe kldney
ln[ury (lf lnadequaLe sodlum and waLer are admlnlsLered). 1here are no publlshed Lrlals conslderlng
whaL Lhe opLlmal lv fluld reglmen for malnLenance ls.
A randomlsed conLrolled Lrlal ls needed Lo compare lv fluld malnLenance reglmens wlLh dlfferenL
sodlum concenLraLlons (for example, comparlson beLween sodlum chlorlde 0.18 ln glucose 4 and
sodlum chlorlde 0.43 ln glucose 4 soluLlons) ln Lerms of Lhe above deLalled compllcaLlon raLes, cosL
and oLher cllnlcal ouLcomes (for example, lengLh of sLay). 1he paLlenL group wlll be heLerogeneous, and
analysls should conslder subgroups of both medical and surgical patients.
lnLravenous fluld Lherapy for replacemenL and redlsLrlbuLlon

131
9 Intravenous f|u|d therapy for rep|acement and
red|str|but|on
9.1 Introduct|on
Many paLlenLs who need lnLravenous flulds have speclflc needs Lo cover replacemenL of exlsLlng deflclLs
or ongolng losses of fluld or elecLrolyLes and/or problems of lnLernal redlsLrlbuLlon of fluld and
elecLrolyLes whlch musL be accounLed for when decldlng on Lhe opLlmal lv fluld prescrlpLlon.
9.1.1 r|nc|p|es of IV f|u|d prescr|b|ng for rep|acement of def|c|ts or ongo|ng abnorma| |osses
8eplacemenL lnLravenous fluld and elecLrolyLes are needed Lo LreaL exlsLlng deflclLs or ongolng
abnormal exLernal losses, usually from Lhe Cl LracL (e.g. lleosLomles, flsLulae, nC dralnage and surglcal
dralns) or urlnary LracL (e.g. when recoverlng from acuLe kldney ln[ury). Plgh lnsenslble losses may also
occur ln paLlenLs wlLh fever, and burns paLlenLs can lose enormous amounLs of whaL can be effecLlvely
plasma. lf paLlenLs do need lnLravenous flulds for replacemenL purposes, lL ls lmporLanL Lo recognlze
LhaL Lhese wlll usually be ln addlLlon Lo flulds LhaL meeL Lhelr rouLlne malnLenance requlremenLs.
Abnormal exLernal fluld losses are seen ln many clrcumsLances as lllusLraLed ln Lhe dlagram of ongolng
losses (see secLlon 4.2.2) ln general, lv fluld Lherapy prescrlbed for replacemenL should alm Lo meeL Lhe
exLra requlremenLs for fluld and elecLrolyLes as well as malnLenance needs, so LhaL homeosLasls ls
resLored and malnLalned. As usual, all sources of fluld and elecLrolyLe lnLake musL be allowed for (e.g.
oral lnLake, enLeral Lube provlslon and flulds glven wlLh drugs) ln Lallorlng Lhe lv fluld prescrlpLlon.
AlLhough lL ls someLlmes posslble Lo measure boLh fluld volumes and elecLrolyLe conLenL of abnormal
losses accuraLely (e.g. wlLh hlgh urlnary loss), lL ls ofLen only posslble Lo esLlmaLe volumes and
elecLrolyLe conLenLs, uslng Lhe llkely composlLlon of dlfferenL losses LhaL are shown ln Lhe dlagram of
ongolng losses. Slnce Lhese esLlmaLes may well be sub[ecL Lo wlde errors, parLlcularly close cllnlcal and
laboraLory monlLorlng wlll be needed.
9.1.1.1 Cho|ce of f|u|ds |n pat|ents w|th rep|acement needs
AlLhough beyond Lhe scope of Lhls guldance, replacemenL for blood loss ls generally by Lhe use of 0.9
sodlum chlorlde, balanced crysLallolds or sulLable collolds (wlLh packed red cells as necessary). 1he
replacemenL for oLher losses e.g. Cl or urlnary, wlll usually depend on esLlmaLes of Lhelr composlLlon
buL 0.9 sodlum chlorlde, glucose 3 and glucose wlLh sallne soluLlons are all used (wlLh or wlLhouL
addlLlonal poLasslum as approprlaLe) as are balanced crysLallold soluLlons. Collolds are noL generally
used ln Lhese paLlenLs unless Lhelr deflclLs are such LhaL Lhey need urgenL resusclLaLlon.
9.1.1.2 kates of IV f|u|d |nfus|on for pat|ents w|th rep|acement needs
lf paLlenLs wlLh abnormal fluld or elecLrolyLe losses develop slgnlflcanL deflclLs over prolonged perlods,
physlologlcal adapLaLlons and changes ln LCl/lCl dlsLrlbuLlon may occur whlch allow Lhe paLlenL Lo
funcLlon moderaLely well. Sudden correcLlon of Lhese abnormallLles can Lhen be assoclaLed wlLh
profound and even serlously damaglng consequences (e.g. cenLral ponLlne demyellnolysls when
hyponaLramla ls correcLed Loo swlfLly). lL ls Lherefore besL Lo reverse deflcLs cauLlously over several days
ln slLuaLlons where Lhey have developed over days or weeks, unless Lhere ls a llfe LhreaLenlng need for

132
fluld resusclLaLlon or an urgenL reason Lo correcL plasma elecLrolyLe values e.g. severe hypo- or
hyperkalaemla.
9.1.2 r|nc|p|es of IV f|u|d prescr|b|ng for pat|ents w|th f|u|d red|str|but|on]abnorma| f|u|d
hand||ng prob|ems
ln addlLlon Lo exLernal losses, some hosplLal paLlenLs have slgnlflcanL lnLernal redlsLrlbuLlon of flulds
especlally Lhose who are crlLlcally lll, Lhose wlLh sepsls, posL-operaLlve paLlenLs, paLlenLs wlLh severe
renal, llver or cardlac problems, and paLlenLs who are malnourlshed. Such paLlenLs ofLen develop
sodlum and waLer excess (leadlng Lo pulmonary and perlpheral oedema, welghL galn, comparLmenL
syndrome and poor wound heallng), whlch frequenLly occurs ln Lhe conLexL of low lnLravascular volume
(and assoclaLed low urlne ouLpuLs) due Lo hlgh Lrans-caplllary escape. lurLhermore, some paLlenLs
sequesLer flulds ln Lhe lnLesLlnal LracL, chesL or perlLoneal cavlLy.
rescrlblng approprlaLe lv flulds for paLlenLs wlLh redlsLrlbuLlon Lype problems ls parLlcularly dlfflculL
slnce Loo llLLle leads Lo lnLravascular hypovolaemla, low blood pressure, poor urlne ouLpuL and poor
Llssue perfuslon, whllsL Loo much may promoLe more oedema. lurLhermore, as such paLlenLs geL
beLLer, Lrans-caplllary leakage wlll decrease and Lhe redlsLrlbuLlon problems may effecLlvely operaLe ln
reverse. lL may Lherefore lmporLanL Lo reduce overall lv fluld and elecLrolyLe provlslon Lo permlL a neL
negaLlve sodlum and waLer balance, ln order Lo ald oedema resoluLlon.
ln vlew of Lhe above, prescrlblng lv flulds for oedemaLous paLlenLs wlLh fluld dlsLrlbuLlon abnormallLles
needs experlence and early senlor revlew. Powever, Lhe overall approach ls usually Lo LreaL any
lnLravascular hypovolaemla as one would for resusclLaLlon, buL alm for a negaLlve overall fluld and
sodlum balance as soon as posslble. ln severe cases, balance can be assessed by comparlng LoLal sodlum
lnLake (accounLlng for all sources lncludlng oLher lv flulds, lv drugs and Lhelr dlluenLs) wlLh LoLal losses
from urlnary measuremenLs and esLlmaLes of sodlum ln oLher exLernal losses. LxcreLlon should exceed
lnLake.
lL ls also lmporLanL Lo correcL any poLasslum depleLlon ln order Lo maxlmlze sodlum exchange, bearlng
ln mlnd LhaL plasma poLasslum ls a poor marker of whole body sLaLus slnce lL ls prlmarlly lnLracellular.
Powever, when glvlng relaLlvely generous poLasslum, careful monlLorlng for hyperkalaemla ls needed,
especlally as many of Lhese paLlenLs have some a degree of renal lmpalrmenL and caLabollc paLlenLs also
have high endogenous potassium supplies from lean tissue breakdown. Hyperchloraemia should also
be avolded as lL may make moblllzaLlon of oedema more dlfflculL by reduclng renal perfuslon .
18

ulureLlcs are generally used wlLh cauLlon slnce Lhey may reduce clrculaLlng blood volume and
conslderaLlon should always be glven as Lo wheLher Lhe same neL effecL on fluld balance mlghL noL be
achleved Lhrough reducLlon of lv flulds, parLlcularly a reducLlon ln Lhe provlslon of 0.9 sodlum
chlorlde. 1wlce weekly welghlng, when posslble, ln addlLlon Lo rouLlne dally cllnlcalexamlnaLlon allows
oedema moblllzaLlon Lo be assessed .
9.1.2.1 Cho|ce of f|u|ds |n pat|ents w|th red|str|but|on prob|ems
A varleLy of lv fluld Lypes can be used when prescrlblng for paLlenLs wlLh lnLernal redlsLrlbuLlon lssues.
1hese lnclude crysLallolds, synLheLlc collolds and albumln, wlLh Lhe laLLer Lwo cholces havlng Lhe
LheoreLlcal advanLage of greaLer and more perslsLenL lnLravascular volume expanslon wlLh less
promoLlon of furLher lnLersLlLlal oedema Lhan crysLallolds. Powever, as wlLh synLheLlc collold and
albumln use for resusclLaLlon (see chapLer 4), Lhese LheoreLlcal advanLage may noL be reallzed ln
pracLlce ln paLlenLs wlLh lnLravascular hypovolaemla and hlgh raLes of Lrans-caplllary exLravasaLlon.

133
As wlLh boLh malnLenance and resusclLaLlon prescrlblng, Lhere ls Lhe posslblllLy LhaL uslng 0.9 sodlum
chlorlde mlghL promoLe more sodlum and waLer reLenLlon Lhan balanced soluLlons as well lncreaslng
any rlsks from hyperchloraemla. Powever, many paLlenLs wlLh redlsLrlbuLlon lssues also have a degree
of renal lmpalrmenL and Lhe use of some balanced soluLlons may be llmlLed by Lhelr exlsLlng poLasslum
conLenL eLc.. ConcenLraLed (20-23) sodlum poor albumln has also been used ln paLlenLs wlLh
redlsLrlbuLlon problems who are oedemaLous due Lo sodlum and waLer overload buL who sLlll have a
plasma volume deflclL(44), almlng Lo draw fluld from Lhe lnLersLlLlal space lnLo Lhe lnLravascular space
and so promoLe renal perfuslon and excreLlon of Lhe excess sodlum and waLer. Powever, Lhls use ls
hlghly speclallzed and declslons on Lhe use of Lhls expenslve preparaLlon ln Lhese slLuaLlons ls usually
conflned Lo senlor cllnlclans.
9.2 Intravenous f|u|d therapy for rep|acement and red|str|but|on
1he ob[ecLlves of Lhe cllnlcal evldence revlews for Lhls chapLer were Lo ldenLlfy Lhe mosL effecLlve Lype,
volumes and Llmlngs of lnLravenous fluld Lo use for replacemenL of deflclLs or ongolng fluld losses ln
paLlenLs who cannoL meeL Lhelr fluld and elecLrolyLe needs by oral or enLeral rouLes. 1hree evldence
revlews were underLaken for Lhls purpose, as deLalled ln secLlons 1.2 (Lypes of fluld) and 1.3 (volume
and Llmlngs) below.
1he CuC were aware LhaL Lhe complexlLy and heLerogenelLy of mosL paLlenLs wlLh slgnlflcanL
redlsLrlbuLlon lssues was such LhaL Lhey could noL be enLered lnLo Lrlals and no evldence revlews were
underLaken ln relaLlon Lo Lhls group.
9.3 1ypes of f|u|d
kev|ew quest|on: What |s the most c||n|ca| and cost effect|ve f|u|d for |ntravenous f|u|d rep|acement |n
hosp|ta||sed pat|ents?
We searched for randomlsed conLrolled Lrlals, sysLemaLlc revlews and cohorL sLudles comparlng Lhe
lnLravenous flulds LhaL mlghL be used for replacemenL of deflclLs or ongolng losses ln admlsslon of
general ward areas of uk hosplLals. 1hese are deLalled ln Lhe LreaLmenL maLrlx below wlLh a Llck
lndlcaLlng Lhe comparlsons LhaL would be lncluded lf ldenLlfled.
1ab|e 41: Matr|x of treatment compar|sons

8uffered]
phys|o|og|ca|
0.4S NaC| |n
S g|ucose
Sod|um
ch|or|de 0.18
|n 4 g|ucose
A|ternate
8a|anced
So|ut|on S G|ucose
Sodlum chlorlde
0.9

8uffered/
physlologlcal

0.43 naCl ln 3
glucose

Sodlum chlorlde
0.18 ln 4
glucose

AlLernaLe
8alanced SoluLlon


134

8uffered]
phys|o|og|ca|
0.4S NaC| |n
S g|ucose
Sod|um
ch|or|de 0.18
|n 4 g|ucose
A|ternate
8a|anced
So|ut|on S G|ucose
M
3 Clucose
lor full deLalls of Lhe revlew proLocol, see secLlon C.3 ln Appendlx C.
9.3.1 C||n|ca| ev|dence
no sLudles meeLlng Lhe revlew proLocol were ldenLlfled. See Lhe sLudy selecLlon flow charL ln secLlon !.3,
Appendlx !.
no economlc evldence was ldenLlfled for Lhls revlew.
9.4 Vo|umes and t|m|ng of f|u|d adm|n|strat|on
kev|ew quest|ons: What |s c||n|ca| and cost effect|veness of d|fferent vo|umes of f|u|d adm|n|strat|on
|n pat|ents requ|r|ng f|u|d rep|acement for ongo|ng |osses?
What are the most c||n|ca| and cost effect|ve t|m|ngs for the adm|n|strat|on of IV f|u|d rep|acement for
ongo|ng |osses?
We searched for randomlsed conLrolled Lrlals, sysLemaLlc revlews and cohorL sLudles comparlng Lhe
lnLravenous flulds deLalled ln Lhe same LreaLmenL maLrlx as used ln 1able 41.
lor more deLalls see revlew proLocols ln secLlon C.3, Appendlx C.
9.4.1 C||n|ca| ev|dence
no sLudles were ldenLlfled relevanL Lo elLher of Lhe revlew quesLlons.
See also Lhe sLudy selecLlon flow charL ln secLlon !.3, Appendlx ! and excluded sLudles llsL ln secLlon P.3,
Appendlx P.
9.S kecommendat|ons and ||nk to ev|dence
kecommendat|ons
24. Ad[ust the IV prescr|pt|on (add to or subtract from ma|ntenance needs) to
account for ex|st|ng f|u|d and]or e|ectro|yte def|c|ts or excesses, ongo|ng
|osses (see D|agram of ongo|ng |osses) or abnorma| d|str|but|on.
2S. Seek expert he|p |f pat|ents have a comp|ex f|u|d and]or e|ectro|yte
red|str|but|on |ssue or |mba|ance, or s|gn|f|cant comorb|d|ty, for examp|e:

133
gross oedema
severe seps|s
hyponatraem|a or hypernatraem|a
rena|, ||ver and]or card|ac |mpa|rment
post-operat|ve f|u|d retent|on and red|str|but|on
ma|nour|shed and refeed|ng |ssues (see Nutr|t|on support |n adu|ts
[NICL c||n|ca| gu|de||ne 32]).
8elaLlve values of
dlfferenL ouLcomes
1he CuC were lnLeresLed ln all cause morLallLy, lengLh of hosplLal sLay and
compllcaLlons lncludlng renal, resplraLory and morbldlLy as measured by SClA or MCuS
scores. All cause morLallLy was consldered Lo be Lhe mosL lmporLanL ouLcome for
declslon maklng, alLhough all oLher ouLcomes were deemed as lmporLanL for lnformlng
recommendaLlons.
1rade off beLween
harms
1he cllnlcal revlews ldenLlfled no sLudles LhaL addressed Lhe besL Lype, volume, Llmlng
or raLe of fluld Lo use for lnLravenous replacemenL of exlsLlng deflclLs or ongolng
abnormal fluld and elecLrolyLe losses.
no cllnlcal revlews were underLaken of Lhe besL Lype, volume, Llmlng or raLe of fluld Lo
use lnLravenously for paLlenLs wlLh lnLernal fluld redlsLrlbuLlon lssues slnce Lhe CuC felL
LhaL Lhese paLlenLs were Loo heLerogenous and complex Lo have been enLered ln Lrlals
LhaL would speclflcally examlne Lhese lssues ln a non-resusclLaLlon conLexL.
Lconomlc
conslderaLlons
CuallLy of evldence no evldence was avallable. 1he CuC had ldenLlfled early on LhaL lL may noL be posslble
Lo flnd 8C1s ln Lhls Loplc area. 1hls ls because each Lype of loss would have Lo be
replaced by a Lype of fluld whlch addressed Lhe fluld and elecLrolyLe requlremenLs and
Lhus Lhe naLure of Lhe lnLervenLlon does noL lend lLself Lo a 8C1 sLudy deslgn. 1he
recommendaLlons are Lherefore based on Lhe sLandard prlnclples of fluld prescrlblng
and Lhe consensus experL oplnlon of Lhe CuC members.
CLher conslderaLlons 1he recommendaLlons for lv fluld use for replacemenL and redlsLrlbuLlon are based on:
Lhe prlnclples of fluld prescrlblng descrlbed ln secLlon 3.1
Lhe consensus experL vlews of Lhe CuC.
no research recommendaLlons were made ln Lhls Loplc area.
1he CuC agreed LhaL each Lype of abnormal ongolng loss would have Lo be evaluaLed
and replaced wlLh approprlaLe flulds and elecLrolyLes. A dlagram hlghllghLlng Lhe
dlfferenL Lypes of abnormal ongolng losses wlLh Lhelr consLlLuenLs was agreed Lo be
useful for purposes of educaLlon (see dlagram of ongolng losses ln secLlon 4.2.2)
1he CuC dlscussed Lhe complexlLy of assesslng fluld requlremenLs ln paLlenLs who have
redlsLrlbuLlon lssues. 1here was dlscusslon LhaL Lhls was an area where [unlor docLors
were mosL llkely Lo make errors ln [udgemenL and Lherefore senlor revlew ln such
paLlenLs was cruclal.
no research recommendaLlon was prlorlLlsed ln Lhls Loplc area.


136
9.S.1 A|gor|thm 4: kep|acement and red|str|but|on


137

1h|s sect|on ||nks the ev|dence to A|gor|thm 4 and the recommendat|on bu||et spec|f|c to rep|acement
and red|str|but|on.
kecommendat|ons
Cffer IV f|u|d therapy as part of a protoco| (see A|gor|thms for IV f|u|d therapy):
Assess patients fluid and electrolyte needs fo||ow|ng A|gor|thm 1:
Assessment.
If pat|ents need IV f|u|ds for f|u|d resusc|tat|on, fo||ow A|gor|thm 2: I|u|d
resusc|tat|on.
If pat|ents need IV f|u|ds for rout|ne ma|ntenance, fo||ow A|gor|thm 3:
kout|ne ma|ntenance.
If pat|ents need IV f|u|ds to address ex|st|ng def|c|ts or excesses, or ongo|ng
abnorma| |osses or abnorma| f|u|d d|str|but|on, fo||ow A|gor|thm 4:
kep|acement and red|str|but|on.
8elaLlve values of
dlfferenL ouLcomes
1he CuC were lnLeresLed ln all cause morLallLy, lengLh of hosplLal sLay and compllcaLlons
lncludlng renal, resplraLory and morbldlLy as measured by SClA or MCuS scores. All
cause morLallLy was consldered Lo be Lhe mosL lmporLanL ouLcome for declslon maklng,
alLhough all oLher ouLcomes were deemed as lmporLanL for lnformlng recommendaLlons.
1rade off beLween
harms
1he cllnlcal revlews ldenLlfled no sLudles LhaL addressed Lhe besL Lype, volume, Llmlng or
raLe of fluld Lo use for lnLravenous replacemenL of exlsLlng deflclLs or ongolng abnormal
fluld and elecLrolyLe losses.
no cllnlcal revlews were underLaken of Lhe besL Lype, volume, Llmlng or raLe of fluld Lo
use lnLravenously for paLlenLs wlLh lnLernal fluld redlsLrlbuLlon lssues slnce Lhe CuC felL
LhaL Lhese paLlenLs were Loo heLeregenous and complex Lo have been enLered ln Lrlals
LhaL would speclflcally examlne Lhese lssues ln a non-resusclLaLlon conLexL.
Lconomlc
conslderaLlons
ln secLlon 3.2.4, lL was noLed LhaL for paLlenLs wlLh sepsls, proLocollsed care was found Lo
be cosL-effecLlve for sepsls paLlenLs ln Lwo sLudles and cosL savlng ln a Lhlrd sLudy. 1hlrd
evldence was consldered Lo be parLlally appllcable and wlLh poLenLlally serlous
llmlLaLlons. 1here was no cosL-effecLlveness evldence for paLlenLs wlLhouL sepsls.
Powever, glven LhaL Lhe healLh lmprovemenLs observed ln Lhe revlew of cllnlcal
effecLlveness evldence were [usL as pronounced for lnLra-operaLlve care Lhe CuC felL LhaL
Lhe economlc beneflLs of proLocols are very llkely Lo be achlevable across all seLLlngs
CuallLy of evldence no evldence was avallable. 1he recommendaLlons are based on Lhe sLandard prlnclples of
fluld prescrlblng and Lhe consensus experL oplnlon of Lhe CuC members.
CLher
conslderaLlons
uesplLe Lhe pauclLy of evldence on Lhe use of proLocols for lv fluld admlnlsLraLlon, Lhe
CuC felL LhaL proLocollsed care ln general achleves beLLer ouLcomes for paLlenLs and
Lherefore declded LhaL an algorlLhmlc approach Lo fluld use for replacemenL and
redlsLrlbuLlon was approprlaLe. ln deslgnlng Lhe algorlLhm, Lhe CuC placed parLlcular
emphasls on developlng recommendaLlons LhaL a foundaLlon year docLor could follow vla
Lhe proLocol Lo lnlLlaLe approprlaLe LreaLmenL where posslble or Lo call for senlor
asslsLance where necessary. AlLhough Lhe algorlLhm ls LargeLed aL [unlor docLors, Lhere ls
an expecLaLlon LhaL declslon maklng ln Lhese paLlenLs ls revlewed by senlors.
1he recommendaLlons and proLocol conLalned wlLhln Lhe algorlLhm on Lhe Lype, volume,
Llmlng and raLe of lv fluld use for replacemenL and redlsLrlbuLlon are based on:
Lhe prlnclples of fluld prescrlblng descrlbed ln secLlon 3.1
Lhe revlews of evldence relaLed Lo Lhe use of algorlLhms ln fluld prescrlblng descrlbed

138
ln secLlon 3.2
Lhe consensus experL vlews of Lhe CuC.
1hls approach allowed Lhe CuC Lo develop Lhe compleLe replacemenL and redlsLrlbuLlon
algorlLhm as well as some speclflc recommendaLlons on lv fluld Lherapy for replacemenL
and redlsLrlbuLlon.
1ralnlng and educaLlon of healLh care professlonals for managemenL of lnLravenous fluld Lherapy

139
10 1ra|n|ng and educat|on of hea|th care profess|ona|s
for management of |ntravenous f|u|d therapy
10.1 Introduct|on
lluld assessmenL, prescrlpLlon and admlnlsLraLlon are essenLlal dally Lasks on mosL medlcal and surglcal
wards. 1hese are complex responslblllLles LhaL enLall careful cllnlcal and blochemlcal assessmenL, good
undersLandlng of Lhe prlnclples of fluld physlology ln healLh and dlsease, and approprlaLe supervlslon
and Lralnlng.
unforLunaLely, problems of boLh under and over hydraLlon are common and many senlor cllnlclans are
aware LhaL Lhere ls slgnlflcanL morbldlLy and morLallLy assoclaLed wlLh lnapproprlaLe fluld managemenL
ln hosplLals. 1he exLenL of Lhe problem ls dlfflculL Lo quanLlfy as lL ls ofLen mulLlfacLorlal and under-
reporLed. Powever, posLoperaLlve over-hydraLlon has been reporLed ln 17-34 of paLlenLs and has been
shown Lo prolong hosplLal sLay, Lo lncrease morbldlLy (e.g. pulmonary oedema) and Lo conLrlbuLe Lo
abouL 9000 deaLhs annually ln Lhe uSA. up Lo 30 of paLlenLs, especlally older people, have also been
reporLed Lo develop aL leasL one fluld-relaLed compllcaLlon due Lo posL-operaLlve over-hydraLlon.
lour key lssues, relaLed Lo fallures ln educaLlon and Lralnlng, conLrlbuLe Lo poor fluld managemenL:
1. ;//* ,04)*<('04.0+ /> (?) @'<.A B*.0A.B-)< /> >-,.4 @'-'0A) '04 ' -'AC /> C0/D-)4+) '@/,( >-,.4
5'0'+)5)0(.
AlLhough mosL medlcal schools address Lhe physlologlcal prlnclples of fluld homeosLasls ln Lhelr
undergraduaLe currlcula, Lhese are rarely lnLegraLed lnLo pracLlcal cllnlcal guldellnes Lo lnform fluld
prescrlpLlon by [unlor docLors ln cllnlcal seLLlngs. 8ecenL audlLs reporL LhaL mosL [unlor docLors do
noL feel adequaLely prepared Lo wrlLe Lhe fluld prescrlpLlons expecLed of Lhem aL Lhe ouLseL of Lhelr
cllnlcal careers. 1he subsequenL poor performance has been documenLed ln sLudles demonsLraLlng
no relaLlonshlp beLween Lhe fluld balance lnformaLlon avallable (e.g. serum elecLrolyLe daLa,
lnpuL/ouLpuL charLs and dally welghLs) and Lhe subsequenL fluld prescrlpLlon. 1here are also daLa Lo
suggesL LhaL less Lhan half of [unlor docLors know Lhe sodlum conLenL of normal sallne, and even
fewer, Lhe baslc dally elecLrolyLe requlremenLs.
1hese undergraduaLe educaLlon lssues are furLher compounded by a lack of coordlnaLed
postgraduate training. This may be partly attributed to the predominance of specialty-requlrements
ln mosL Lralnlng programmes. 1hese ofLen fall Lo focus on, or assess, baslc medlcal compeLencles llke
fluld managemenL, nuLrlLlon and paln-conLrol, a problem, recenLly ralsed by Lhe 8oyal College of
hyslclans. nurslng and paramedlcal Lralnees face slmllar lssues and audlL suggesLs LhaL many lack
confldence ln fluld managemenL. ln addlLlon Lo Lhls lack of formal undergraduaLe and posLgraduaLe
Lralnlng, [unlor cllnlclans and nurses are rarely glven guldellnes on fluld/elecLrolyLe prescrlblng or
approprlaLe lnducLlon Lralnlng by Lhelr employers.
2. ;//* >-,.4 @'-'0A) 6A?'*(9 4/A,5)0('(./0#
1he naLlonal ConfldenLlal Lnqulry lnLo erloperaLlve ueaLhs (nCLCu) ln 1999 reporLed LhaL poor
documenLaLlon of fluld balance conLrlbuLed Lo boLh morbldlLy and morLallLy.
73
lurLher sLudles
demonsLraLed LhaL less Lhan half of fluld balance sheeLs were compleLed (l.e. no record of oral lnLake
or urlne ouLpuL) and LhaL lnLravenous flulds were ofLen admlnlsLered aL lncorrecL raLes (whlch was

160
ofLen consldered Lo be unlmporLanL)! ln addlLlon, less Lhan 10 of sLaff were aware of Lhe value of
monlLorlng body welghL ln fluld balance monlLorlng.
3. ;//* .0()*B*)('(./0 /> -'@/*'(/*E *)<,-(<
1he lnLerpreLaLlon of laboraLory resulLs requlres conslderable experLlse wlLh approprlaLe accounL made
for lssues such as Lhe Lrend ln changes of elecLrolyLe levels and Lhe cllnlcal sLaLus of Lhe paLlenL. lor
example Lhe developmenL of hyponaLraemla ln a paLlenL on lv flulds may reflecL whole body sodlum
depleLlon from lnadequaLe provlslon of sodlum, parLlcularly ln Lhe conLexL of abnormally hlgh sodlum
losses from Lhre gasLrolnLesLlnal LracL, buL ls more ofLen seen ln oedemaLous paLlenLs where LoLal body
sodlum ls acLually hlgh and Lhe low plasma levels reflecL waLer dlluLlon.

4. F0'4)G,'() .0H/-H)5)0( /> <)0./* A-.0.A.'0< .0 >-,.4 5'0'+)5)0( '04 4)-)+'(./0 /> >-,.4
B*)<A*.B(./0 (/ I,0./* 5)5@)*< /> (?) ()'5.
lluld prescrlpLlon ls ofLen delegaLed Lo Lhe leasL experlenced members of Lhe medlcal Leam wlLh [unlor
sLaff responslble for 80 of perl-operaLlve fluld prescrlpLlons. 1he nCLCu reporL ascrlbed many of Lhe
errors ln fluld and elecLrolyLe managemenL Lo lnadequaLe knowledge and Lralnlng of [unlor medlcal
sLaff.
73
lL may also lndlcaLe LhaL senlor cllnlclans lack confldence ln Lhls area, parLlcularly lf Lhey dld noL
recelve formal fluld managemenL Lralnlng, and need furLher educaLlon. ln Lhe llghL of Lhe above, lL ls
clear LhaL lmprovemenLs ln educaLlon and Lralnlng relaLed Lo lnLravenous fluld Lherapy are needed and
Lhls ChapLer seeks Lo clarlfy how Lhls mlghL besL be achleved.
10.2 8arr|ers faced by hea|th care profess|ona|s
kev|ew quest|on
What are the barr|ers faced by hea|thcare profess|ona|s |n the effect|ve prescr|pt|on and mon|tor|ng of
|ntravenous f|u|ds |n hosp|ta| sett|ngs?
lor full deLalls see revlew proLocol ln secLlon C.6, Appendlx C.
1he beneflLs of a sysLemaLlc narraLlve revlew of cllnlcal evldence ln Lhe absence of relevanL sLudles LhaL
would show Lhe effecL of Lralnlng and educaLlon as a slngle measurable ouLcome are hlghllghLed by
Cxman and colleagues.
81
1hls approach has been used prevlously ln naLlonal cllnlcal guldellne
developmenL Lo greaL effecL (see dlagnosls secLlon of nlCL Cllnlcal Culdellne 61, lrrlLable 8owel
Syndrome). Applylng Lhe quallLy assurance prlnclples advocaLed by Cxman (1994), a valld revlew arLlcle
can, ln Lhe absence of lnLervenLlonal cllnlcal evldence, provlde Lhe besL posslble source of lnformaLlon
LhaL can lay a foundaLlon for cllnlcal declslons Lo be made. WlLh regard Lo Lhls revlew, Lhe Lechnlcal
Leam searched broadly for relevanL evldence LhaL would enable Lhe CuC Lo undersLand whaL Lhe maln
lssues are wlLh regard Lo Lralnlng and educaLlon and Lo lnform Lhelr lnLerpreLaLlon of Lhls evldence when
maklng dlrecLlve recommendaLlons. 1he purpose of whlch ls Lo sLandardlse cllnlcal pracLlce and
opLlmlse Lhe experlence of paLlenLs recelvlng lnLravenous flulds Lhrough effecLlve Lralnlng and ongolng
educaLlon. A sLrong academlc argumenL can be made LhaL Lhe only way for lndlvldual ouLcomes such as
barriers faced by healthcare professionals in relation to education and training to be fully explored and
evaluaLed ls Lhrough a mlxed meLhod approach ln Lhe synLhesls of avallable evldence. lL ls Lhls synLhesls
LhaL deLermlnes boLh Lhe quallLy and avallablllLy of relevanL evldence and provldes Lhe CuC wlLh a
reallsLlc conLexL for relevanL recommendaLlons for cllnlcal pracLlce Lo be made.

161
ln summary, Lhe absence of randomlsed sLudles deLermlnes a wlder search and yleld of relevanL
llLeraLure Lo provlde Lhe besL posslble source of lnformaLlon for Lhe CuC, for lnLerpreLaLlon and
declslons Lo be made. 1hls focused narraLlve revlew for lndlvldual ouLcomes as broad as training and
education enables an appreclaLlon of relevanL llLeraLure Lo be esLabllshed ls more llkely Lo provlde valld
resulLs, wlLh Cxman eL al (1994)
81
sLaLlng LhaL lL ls more useful for cllnlclan lnLerpreLaLlon.
10.3 C||n|ca| ev|dence
We searched for randomlsed Lrlals comparlng Lhe effecLlveness of educaLlon and Lralnlng on end paLlenL
ouLcomes ln relaLlon Lo lv fluld managemenL. no Lrlals were ldenLlfled. 1he search sLraLegy was
therefore purposefully broad, looking at mixed research methods literature relating to in-hosplLal
settings published from 1990 onwards. 1en sLudles were lncluded ln Lhls revlew and are summarlsed ln
Lhe evldence grouplng below. 1he dlfflculLy of deLermlnlng robusL evldence ln Lhls revlew ls noL
dlsslmllar Lo oLher revlews wlLhln Lhe guldellne, ln LhaL Lhe non-cllnlcal seLLlng speclflc focus of Lhe
guideline and the all populations in in-hospital settings focus often determines an implausible
approach Lo normal lCC approaches. WhaL Lhe sysLemaLlc (by search sLraLegy) narraLlve revlew allows
ls for us Lo look aL Lhe relevanL yleld and brlng evldence summary poslLlons LogeLher uLlllslng Lhe mlxed
research meLhods publlshed ln Lhls relevanL area.
1ypes of study |ncorporated |n th|s rev|ew:
Survey research (Coombes eL al, 2008, kelly eL al, 2011, Chung eL al, 2002, !ensen, 2009)
19,21,44,49

knowledge assessmenL research (Welsgerber eL al, 2007)
119

LvaluaLlon of Lralnlng and educaLlon research (uauger eL al, 2008, oLLs eL al,1999, Casserly eL al,
2011)
13,24,83

rospecLlve cohorL sLudy (1ang and Lee, 2010)
108

AcLlon research (Cook, 2003).
20

10.3.1 Summary of f|nd|ngs
1he evldence from Lhe dlfferenL sLudy deslgns ls presenLed below wlLh key flndlngs:
10.3.1.1 Survey kesearch:
Coombes et a|, 2008.
21
AL Lhe end of medlcal Lralnlng, new docLors felL unprepared for fluld prescrlblng
and were concerned abouL error blame (n=101). 1hls flndlng supporLs Lhe CuC consensus of currenL
pracLlce.
key flndlngs: Lack of adequaLe cllnlclan preparaLlon wlLh assoclaLed poLenLlal for lncreased cllnlcal
rlsk and harm.
ke||y et a|, 2011.
49
lnLerns felL underprepared and lacked confldence ln lv fluld managemenL on
commencemenL of Lhelr cllnlcal roles (n=32). 1hls agaln ls supporLlve of CuC consensus of how lll
prepared [unlor docLors are ln Lhls lmporLanL aspecL of Lhelr role.
key flndlngs: Lack of adequaLe cllnlclan preparaLlon wlLh assoclaLed poLenLlal for lncreased cllnlcal
rlsk and harm.
Chung et a|, 2002.
19
8eLrospecLlve revlew of fluld balance charLs (n=230) demonsLraLed large
dlscrepancy ln quallLy and quanLlLy of fluld balance deLall wlLh no clear responslblllLy across professlons

162
for ownershlp and LermlnaLlon or recordlng. 1hls meanL LhaL Lhere was no percelved value ln relaLlon Lo
beneflL and accuracy Lo lnform ongolng declslons. SLudy parLlclpanLs also ralsed concerns abouL Lhe
deslgn of fluld balance charLs.
key flndlngs: oor fluld balance monlLorlng wlLh assoclaLed poLenLlal for lncreased cllnlcal rlsk and
harm.
Iensen, 2009.
44
Survey of nurslng graduaLes followlng relevanL Lralnlng and educaLlon prlor Lo Lhelr
lnvolvemenL ln lnLravenous fluld managemenL demonsLraLed lncreased confldence and compeLence ln
Lhls aspecL of Lhelr role and care.
key flndlngs: lncreased confldence ln relaLlon Lo lv flulds managemenL followlng Lralnlng
lnLervenLlon.
10.3.1.2 know|edge assessment:
We|sgerber et a|, 2007
119
1hls sLudy was deslgned Lo measure compeLency of fluld managemenL of
medical students (M3s) and is illustrative of the concern amongst the GDG. The study was established
as an effecLlve knowledge assessmenL Lhrough a comblnaLlon of mulLlple cholce quesLlons LesLlng
cognitive know how and clinical vignette testing the know that aspects of knowledge that support
cllnlcal declslon maklng and lnLerpreLaLlon of lnformaLlon. 1he sLudy was consldered Lo be ln relevanL
populaLlons and was reasonably large (n=187). llndlngs were LhaL Lhe ma[orlLy of M3s lacked adequaLe
knowledge of fluld managemenL and normal elecLrolyLe physlology. 1hls ls lnLerpreLed by Lhe CuC as
dangerous and could lead to harm rather than benefit in relation to IV fluids management. The
recommendaLlon from Lhls sLudy was for a greaLer emphasls on pracLlce based Leachlng wlLh lmmedlaLe
feedback and increased formal training to ensure that M3s had the right levels of knowledge and
compeLence when underLaklng lv fluld managemenL.
key flndlngs: oLenLlal for harm or lncreased cllnlcal rlsk due Lo poor knowledge.
10.3.1.3 Lva|uat|on of tra|n|ng and educat|on:
Dauger et a|, 2008.
24
Large prospective before and after cohort study (8, 496 as the before
comparison and 8,891 patients as after comparison) following introduction of a hypovolaemia
proLocol. 1he sLudy demonsLraLed lmproved compllance wlLh evldence based hypovolaemla proLocol
care. WhllsL compllance was demonsLraLed by Lhe sLudy, a lack of follow up daLa means LhaL we are noL
able Lo esLabllsh wheLher lnlLlal behavlour change was susLalned and proLocol led care malnLalned. Cf
interest, as this was indirect evidence based in a paedlaLrlc populaLlon, was LhaL daLa demonsLraLed
reduced fluld challenge duraLlon compared Lo sLandard care (posslbly prevenLlng addlLlonal problems of
fluld overload aL a laLer sLage) and Lhe cessaLlon of collold use ln LreaLlng Lhe cllnlcal condlLlon of
hypovolaemla.
key flndlngs: oslLlve lmpacL of Lralnlng lnLervenLlon on cllnlclan compllance wlLh proLocol led care.
otts et a|,1999.
83
CohorL analyLlc sLudy assessmenL of Lralnlng Lype ln 3
rd
year medlcal sLudenLs wlLh no
prevlous lv fluld managemenL experlence (n=89). 1he prlmary ouLcome supporLed Lhe use of compuLer
based Lralnlng as an effecLlve meLhod Lo lmprove knowledge of prescrlblng and managemenL of lv
fluids. This was again identified as of interest to the GDG but it is noted that it is indirect evidence
(paedlaLrlc populaLlon).
key flndlngs: Benefit to focussed training strategy, in this case computer assisted.

163
Casser|y et a|, 2011.
1S
rospecLlve cohorL sLudy (n=106 paLlenLs) focussed on lmplemenLaLlon of sepsls
care from admlsslon Lo Lhe emergency deparLmenL (Lu), sLablllsaLlon (lncludlng as a key cllnlcal
lnLervenLlon lv flulds prescrlblng and managemenL) and Lransfer Lo Lhe lnLenslve care unlL (lCu).
1ralnlng lnLervenLlons supporLed: reducLlon ln Llme Lo fluld admlnlsLraLlon, vasopressor admlnlsLraLlon
(surrogaLe marker for volume balance) and Llme Lo Lransfer. lurLher analysls of Lhe prlmary ouLcome
daLa showed conLlnued lmprovemenL ln Lhe processes of care managemenL, reducLlon ln Llme ln Lhe Lu
prlor Lo Lransfer Lo lCu. 1ralnlng was LargeLed aL all key sLaff over a Lhree monLh perlod. 1he daLa
showed LhaL ln Lhe lasL Lhree monLhs of Lhe sLudy, LhaL Lhere was a sLaLlsLlcally slgnlflcanL reducLlon ln
Llme Lo admlnlsLraLlon of Lhe lnlLlal flulds recommended ln Lhe proLocol and Llme Lo caLheLer lnserLlon.
Secondary ouLcomes showed no change Lo reduclng morLallLy or LoLal lengLh of sLay ln hosplLal, Lhls ls
mosL llkely Lo be due Lo Lhe small sLudy populaLlon whlch was noL calculaLed Lo Lry and deLecL Lhls
effecL.
key flndlngs: oslLlve lmpacL of Lralnlng lnLervenLlon on cllnlclan compllance wlLh proLocol led care.
10.3.1.4 rospect|ve cohort study
1ang and Lee, 2010
108

1hls was a small sLudy wlLh 23 surglcal speclallLy Lralnees (12 speclallsL Lralnees and 13 foundaLlon year
trainees). The aim was to evaluate, in controlled conditions, the junior doctors ability to accurately
assess fluld balance, and by assoclaLlon undersLand Lhe fluld needs of lndlvldual paLlenLs. lluld balance
managemenL was assessed uslng LoLal lnpuL and LoLal ouLpuL calculaLlons across 13 charLs, leadlng Lo a
LoLal of 323 daLa measures. 1here was no slgnlflcanL dlfference across Lhe Lwo groups of docLors.
Powever, Lhe sLudy shows alarmlng resulLs wlLh cause for concern, LhaL surglcal Lralnee calculaLlons are
hugely varied and this has an associated potential for harm. This is reported by the authors
acknowledglng Lhe llmlLaLlons of Lhe sLudy as a cllnlcal rlsk lssue LhaL needs Lo be addressed. 1hey
reporL LhaL Lhe fundamenLal lssue ls Lhe lack of relevanL educaLlon and lnconslsLenL poor
documenLaLlon.
key flndlngs: oor knowledge, poor daLa collecLlon and documenLaLlon.
10.3.1.S Act|on research
Cook, 200S
20

1hls sLudy was seeklng Lo explore Lhe relaLlonshlp of role (nurslng) Lo fluld admlnlsLraLlon and
managemenL. lL was lLeraLlve by naLure as Lhe Lechnlque used was a focus group dlscusslon wlLh
feedback lnvolvlng nurses on 2 neurosurglcal wards. CuLcome of Lhe research helped provlde greaLer
deflnlLlon Lo Lhe role of Lhe nurse and greaLer cerLalnLy wlLh fluld admlnlsLraLlon and managemenL. 1he
research process ln lLself lmproved knowledge and cerLalnLy. 1he roles (Lhemes) LhaL nurses ldenLlfled,
emerglng from focus group dlscusslons were:
1. AdmlnlsLraLlon of fluld
2. AssessmenL of Lhe paLlenL and raLlonale for LreaLmenL (lv flulds)
3. AccuraLe documenLaLlon
4. LvaluaLlon of Lherapy
3. Appralsal wlLh medlcal sLaff ln relaLlon Lo beneflL and harm of lv flulds

164
6. Safe and effecLlve managemenL (safe pracLlce).
key flndlngs: lmproved knowledge led Lo lmproved confldence ln lv fluld managemenL.
10.4 Lv|dence summary
key ev|dence f|nd|ngs were:
Lack of adequaLe cllnlclan preparaLlon ls assoclaLed wlLh poLenLlal for lncreased cllnlcal rlsk and
harm.
oor fluld balance monlLorlng ls assoclaLed wlLh poLenLlal for lncreased cllnlcal rlsk and harm.
Low confldence ln relaLlon Lo lv flulds managemenL ls sub opLlmal ln relaLlon Lo cllnlclan preparaLlon.
oor knowledge ls assoclaLed Lo lncreased poLenLlal for harm or lncreased cllnlcal rlsk.
oslLlve lmpacL of Lralnlng lnLervenLlon on cllnlclan compllance wlLh proLocol led care.
Benefit to focussed training strategy, in this case computer assisted.
lmproved knowledge led Lo lmproved confldence ln lv fluld managemenL.
1he followlng Lhemes were ldenLlfled from Lhe llLeraLure revlew:
undersLandlng of physlology (whaL you should know prlor Lo prescrlblng lnLravenous fluld)
lnlLlal and ongolng Lralnlng and educaLlon lssues
AssessmenL of compeLence ln relaLlon Lo prescrlblng and admlnlsLerlng lnLravenous flulds
lnLravenous flulds managemenL (proLocol led care and prescrlblng)
CommunlcaLlon lssues.
10.S key themes
10.S.1 Understand|ng off f|u|d phys|o|ogy and pathophys|o|ogy (what you shou|d know pr|or to
prescr|b|ng |ntravenous f|u|d)
1he assessmenL, prescrlpLlon and admlnlsLraLlon of lv flulds requlres an undersLandlng of Lhe baslc
physlology of fluld and elecLrolyLe homeosLasls and Lhe changes LhaL occur wlLh lllness or ln[ury..
AlLhough Lhese lssues are always parL of undergraduaLe currlcula, Lhere ls ofLen fallure Lo lnLegraLe
LheoreLlcal knowledge lnLo pracLlcal guldellnes whlch lnform safe and approprlaLe lv fluld
admlnlsLraLlon. An undersLandlng of Lhe followlng baslc concepLs ls requlred:
J-,.4 '04 )-)A(*/-E() A/5B'*(5)0(<1 lncludlng Lhe volumes of lndlvldual comparLmenLs, Lhe
dlsLrlbuLlon and movemenL of elecLrolyLes beLween comparLmenLs and Lhe lmporLance of osmoLlc
pressure and membrane funcLlon ln healLh and dlsease.
F0(*'H'<A,-'* H/-,5)1 lL ls essenLlal Lo undersLand Lhe deLermlnanLs of lnLravascular volume and Lhe
roles of and lnLeracLlons beLween many facLors lncludlng: oncotic pressure from large molecular
welghL (MW), non-dlffuslble vascular plasma proLelns (e.g. albumln), the permeability (leakiness) of
Lhe blood vessels, and clrculaLory hydrosLaLlc pressure dlcLaLed by cardlac funcLlon and fluld sLaLus.
Of particular importance is an understanding of the normal albumin cycle and caplllary permeablllLy
and Lhelr responses Lo acuLe paLhologlcal condlLlons and subsequenL recovery.
7/*5'- 4'.-E >-,.4 -/<<)< '04 *)0'- >,0A(./0 '04 (?) A/0<)G,)0A)< /> 4.<)'<)1 normal dally fluld and
elecLrolyLe losses should be core knowledge, as should be Lhe ablllLy Lo assess and formulaLe a

163
replacemenL plan for Lhe fluld and elecLrolyLe consequences of dlsease. 1hls requlres a good
undersLandlng of Lhe physlologlcal processes conLrolllng fluld and elecLrolyLe homeosLasls ln healLh
and dlsease. ln parLlcular, Lhe kldneys ablllLy Lo excreLe soluLe and elecLrolyLe loads durlng
resusclLaLlon ln acuLe lllness musL be clear.
K)<B/0<) (/ <(*)<<1 lncludlng Lhe endocrlne, meLabollc and renal responses Lo acuLe lllness or ln[ury
and Lhelr effecL on salL and waLer handllng should be known and Lhe approprlaLe managemenL
responses Lo subsequenL salL and waLer reLenLlon.
;?E<./-/+.A'- A/0<)G,)0A)< /> A?*/0.A 4.<)'<) 6)#+# A'*4.'AL *)0'-L )04/A*.0)9 /0 >-,.4 '04
)-)A(*/-E() 5'0'+)5)0(1 changes ln cardlac or urlne ouLpuL, varlable ablllLy Lo excreLe soluLes and
changes ln meLabollc wasLe producLlon may have slgnlflcanL effecLs on fluld managemenL dependlng
on Lhe assoclaLed fluld and elecLrolyLe losses, physlologlcal adapLaLlons (e.g. neurohormonal
responses) and meLabollc effecLs.
M?) A-.0.A'- 'BB*/'A?)< 0))4)4 (/ '<<)<< >-,.4 '04 )-)A(*/-E() 0))4< >/* *)<,<A.('(./0L */,(.0)
5'.0()0'0A)L *)B-'A)5)0( /> 4)>.A(<N /0+/.0+ -/<<)< '04 *)4.<(*.@,(./0 .<<,)<L '04 (?) .5B/*('0A)
/> *)'<<)<<5)0( '04 5/0.(/*.0+ M?) A/5B/<.(./0 '04 B*/B)*(.)< /> A/55/0-E '45.0.<()*)4
.0(*'H)0/,< >-,.4<
LducaLors and cllnlclans need Lo work LogeLher Lo asslsL Lralnees and pracLlclng cllnlclans Lo address and
undersLand Lhe complex physlologlcal responses LhaL occur durlng dlsease processes and how Lhese
alLer fluld and elecLrolyLe requlremenLs ln a cllnlcally relevanL problem-solvlng based approach wlLh
approprlaLe assessmenL and feed-back.
10.S.2 In|t|a| and ongo|ng tra|n|ng and educat|on |ssues
lnadequaLe knowledge, fallure Lo recognlse Lhe lmporLance of fluld managemenL ln paLlenL care and a
relucLance Lo Lake Lhls lssue serlously are ma[or facLors ln poor fluld managemenL. 1he causes of Lhls
lack of engagemenL are mulLlfacLorlal, buL poor educaLlon, Lralnlng and supervlslon are ma[or
conLrlbuLors:
AlLhough medlcal and nurslng undergraduaLe currlcula address mosL aspecLs of fluld and elecLrolyLe
homeosLasls, Lhere ls fallure Lo lnLegraLe and assess Lhls knowledge ln a cllnlcally relevanL formaL.
lluld managemenL Leachlng ls lncluded ln mosL loundaLlon and Core Medlcal 1ralnlng programmes
buL ls ofLen unsLrucLured, wlLhouL a deflned currlculum or sLaLed mlnlmum compeLencles.
knowledge ls rarely formally assessed ln Lerms of practical prescription competency (e.g. uCS) or
Membershlp (e.g. M8C, l8CS) examlnaLlons. Plgher speclalLy programmes Lend Lo focus on Lhe
acquisition of specialty skills rather than core medical competencies like fluid management,
nuLrlLlon and paln managemenL, desplLe Lhese core compeLencles havlng profound effecLs on
speclallsL ouLcomes.
lluld prescrlpLlon ls ofLen percelved Lo be less lmporLanL Lhan oLher aspecLs of medlcal care by [unlor
cllnlclans and Lhe wlder medlcal Leam because senlor docLors and nurses fall Lo Lake responslblllLy,
appear dlslnLeresLed ln, and Lend Lo delegaLe Lhls role Lo less senlor members of Lhe Leam wlLhouL
supervlslon or revlew.
Much of Lhe daLa collecLlon Lo lnform hlgh quallLy prescrlpLlon (e.g. fluld lnpuL/ouLpuL charLs, dally
welghLs eLc.) ls lgnored by prescrlbers and resulLs ln dlsllluslonmenL of Lhose Lasked wlLh Lhls daLa
collecLlon (l.e. Lhe nurslng sLaff). 1hls leads Lo poor compllance wlLh Lhe daLa collecLlon whlch ls
subsequenLly of llLLle value ln Lhe fluld sLaLus assessmenL.

166
1he lack of lmporLance aLLrlbuLed Lo fluld managemenL ls reflecLed ln Lhe lack of adequaLe research
ln Lhls fleld. oor fundlng resulLs ln lnadequaLe daLa collecLlon, conLradlcLory flndlngs and confllcLs of
oplnlon. ConsequenLly many cllnlclans are lefL wlLh Lhe lmpresslon LhaL any sLraLegy wlll do. ln Lhe
absence of consensus Lhe need for carefully managed research and cllnlcal guldance ls even greaLer
and should be a naLlonal prlorlLy.
1here ls a lack of publlshed guldance or naLlonal sLandard seLLlng Lo lnform fluld balance assessmenL
(l.e. lnpuL/ouLpuL charL, elecLrolyLe monlLorlng) and subsequenL fluld prescrlpLlon (parLlcularly ln Lhe
absence of clear research flndlngs). As a consequence sLandards are noL revlewed or LesLed as for
oLher guldellnes.
MorbldlLy and morLallLy relaLed Lo fluld prescrlpLlon ls lnadequaLely monlLored or revlewed as lL ls
deemed too difficult to do accurately. Although doctors and nurses are aware of the morbldlLy
assoclaLed wlLh over- or under-hydraLlon, lL ls rarely, lf ever, reporLed as a cllnlcal lncldenL.
LducaLlon and Lralnlng lmprove cllnlcal assessmenL, undersLandlng of monlLored daLa (e.g. serum
elecLrolyLes, lnpuL/ouLpuL charLs), approprlaLe fluld cholce (e.g. crysLallold, collold) and knowledge of
Lhe currenL llLeraLure and can be demonsLraLed Lo lmprove fluld managemenL and paLlenL ouLcomes.
lor example, educaLlon abouL Lhe value of conservaLlve (resLrlcLed) fluld admlnlsLraLlon ln acuLe lung
ln[ury, many posL-operaLlve slLuaLlons and Lhe recovery phase of crlLlcal lllness, alLhough sLlll largely
unrecognlsed desplLe good daLa demonsLraLlng lmproved ouLcomes, has clear beneflL. Senlor cllnlclans
and nurses musL be seen Lo Lake fluld managemenL serlously and Lo provlde approprlaLe leadershlp and
supervlslon for [unlor medlcal colleagues. Senlor cllnlclan refresher courses ln fluld managemenL should
be avallable.
10.S.3 Assessment of competence |n re|at|on to prescr|b|ng and adm|n|ster|ng |ntravenous f|u|ds
lluld managemenL compeLency should be assessed and revlewed LhroughouL Lralnlng and as parL of
sLandard medlcal cllnlcal governance revlews and Lhe revalldaLlon process.
Undergraduate training should include formal assessment of a trainees knowledge of baslc fluld and
elecLrolyLe physlology and Lhe response Lo dlsease, Lhe normal dally fluld and elecLrolyLe
requlremenLs ln rouLlne medlcal and posL-operaLlve surglcal paLlenLs and Lhe ablllLy Lo communlcaLe
and prescrlbe a 24 hour malnLenance fluld reglme. 8esusclLaLlon fluld reglmes and Lhe baslc
prlnclples underlylng ad[usLmenL of malnLenance reglmes for ongolng or addlLlonal fluld and
elecLrolyLe losses or compllcaLlng facLors should be known. 1ralnees should be able Lo demonsLraLe
an ablllLy Lo collaLe and lnLerpreL monlLored daLa, Lo recommend an approprlaLe fluld reglme and Lo
compleLe an approprlaLe prescrlpLlon lncludlng daLes, slgnaLures (and deslgnaLlons), selecLlon of
approprlaLe fluld Lypes, raLe of lnfuslon and elecLrolyLe supplemenLs.
uurlng early medlcal or nurslng Lralnlng (e.g. loundaLlon and Core 1ralnlng rogrammes) core
generic skills developed during undergraduate training should be fine-tuned and formally assessed
in terms of the required practical essential knowledge and practical problem solving prescription
compeLency (e.g. dlrecLly observed pracLlcal skllls, case based dlscusslons). 8eflnemenL of Lhe ablllLy
Lo dellver resusclLaLlon fluld reglme wlLhouL assoclaLed developmenL of compllcaLlons (e.g.
pulmonary oedema) and ad[usLmenL of malnLenance reglmes for ongolng losses or compllcaLlng
facLors should be developed. 1ralnees plannlng speclallsL Lralnlng should be encouraged Lo develop
and demonsLraLe fluld managemenL compeLencles approprlaLe Lo Lhelr chosen speclalLy lor example
medlcal Lralnees would be expecLed Lo be famlllar wlLh guldellnes for fluld managemenL of common
acuLe medlcal emergencles (e.g. dlabeLlc keLoacldosls, llver fallure, acuLe kldney ln[ury) and surglcal
Lralnees wlLh posL-operaLlve fluld reglmes and ad[usLmenLs requlred for ongolng losses (e.g.

167
nasogasLrlc, flsLula). AssessmenL and demonsLraLlon of compeLency should be requlred prlor Lo
progresslon Lo speclalLy Lralnlng.
SpeclallsL Lralnees and speclalLy consulLanLs should be able Lo demonsLraLe conLlnulng core fluld
managemenL compeLencles. 1ralnees and consulLanLs lnvolved ln acuLe, general or lnLenslve care
medlclne or surgery and anaesLheLlsLs would be expecLed Lo develop furLher compeLency ln Lhe
managemenL of Lhe crlLlcally compromlsed clrculaLlon and complex fluld balance problems. Some
speclallsLs would be expecLed Lo develop experLlse and demonsLraLe proflclency ln Lhe managemenL
of complex losses (e.g. hlgh ouLpuL lleal flsLulae) or meLabollc derangemenLs.
8esponslblllLy for Lhe dellvery, assessmenL and compeLency revlew should lle wlLh Medlcal School
ueans, Ceneral and SpeclalLy 1ralnlng rogramme Currlculum CommlLLees, Lhe Ceneral Medlcal Councll
(as parL of revalldaLlon) and nurslng Councll.
10.S.4 Intravenous f|u|ds management (protoco| |ed care and prescr|b|ng)
1hls parL of Lhe revlew ls for mlnlmal guldance only. lease refer Lo Lhe sysLemaLlc revlew and
assoclaLed recommendaLlons on proLocol led care for lnLravenous flulds managemenL and Lhe four
assoclaLed algorlLhms cenLral Lo Lhls guldellne.
CbservaLlons from Lhe revlew of evldence are Lo deLermlne wheLher an lnLravenous fluld ls necessary aL
all, a baslc quesLlon LhaL needs Lo be asked as oral or nasogasLrlc flulds are usually always preferable.
lnLravenous fluld admlnlsLraLlon ls lndlcaLed ln paLlenLs who are:
acuLely unwell and requlrlng large quanLlLles of fluld for resusclLaLlon
unable Lo drlnk (e.g. unconsclous, unsafe swallow (e.g. followlng sLrokes, faclo-maxlllary ln[ury)
unable Lo absorb adequaLe quanLlLles of waLer (e.g. vomlLlng, paralyLlc lleus, dlarrhoea)
loslng excesslve quanLlLles of fluld (e.g. dlarrhoea, haemorrhage, burns)
1he bas|c pr|nc|p|es of f|u|d adm|n|strat|on are to:
8eplace normal fluld and elecLrolyLe losses.
8eplenlsh subsLanLlal deflclLs or ongolng losses.
rovlde addlLlonal resusclLaLlon flulds Lo correcL for Lhe effecLs of underlylng paLhology.
MalnLaln an adequaLe cardlac ouLpuL, blood pressure and subsequenL perlpheral blood
flow/dlsLrlbuLlon of oxygen and oLher nuLrlenLs Lo saLlsfy Lhe meLabollc needs of body Llssues and
organs, ald LemperaLure regulaLlon (e.g. sweaLlng) and ensure approprlaLe removal of carbon dloxlde
and meLabollc wasLe from Lhe body.
Lnsure a sLable cellular and exLracellular mllleu Lo preserve cellular Lransmembrane poLenLlals and
normal cellular LransporL mechanlsms for essenLlal lons, resplraLory gases, soluLes and wasLe
producLs.
Avold excesslve oedema whlch may lmpalr cellular oxygen and nuLrlenL dellvery by lncreaslng
caplllary-Lo-cell dlffuslon dlsLances, especlally durlng hypoxaemla.
rescrlpLlon of an lnLravenous fluld should follow a careful cllnlcal assessmenL, blochemlcal revlew and
avallable fluld balance daLa (e.g. lnpuL/ouLpuL charLs, welghLs). 1oLal fluld and elecLrolyLe requlremenLs,
resusclLaLlon needs and oLher compllcaLlng facLors should be deLermlned and Lhe mosL approprlaLe fluld
Lo provlde Lhese requlremenLs deLermlned. CrysLallold and collold requlremenLs should be prescrlbed
dally and ad[usLed lf enLeral feedlng ls noL successful. 1he Lype of fluld (l.e. 3 dexLrose for waLer

168
replacemenL), elecLrolyLe addlLlves (e.g. poLasslum) , rouLe and raLe of lnfuslon should be prescrlbed
wlLh Lhe daLe and slgnaLure of Lhe lssulng physlclan.
1yplcally fluld selecLlon ls gulded by Lhe underlylng condlLlon, exLracellular fluld sLaLus (e.g. oedema),
fluld losses (e.g. dlarrhoea), renal funcLlon, fluld balance (welghL) and elecLrolyLe concenLraLlons. ln Lhe
absence of normal homeosLaLlc mechanlsms, Lhe fluld prescrlpLlon should address:
8aslc malnLenance flulds Lo replace normal dally waLer and elecLrolyLe losses (see regular
malnLenance fluld algorlLhm).
AddlLlonal resusclLaLlon flulds Lo replenlsh poLenLlal fluld deflclLs and Lo compensaLe for Lhe
underlylng paLhology and malnLaln an adequaLe clrculaLlon (see resusclLaLlon algorlLhm).
1he raLe of fluld admlnlsLraLlon and Lhe Llme course over whlch poLenLlal fluld and elecLrolyLe deflclLs
should be correcLed. 1hls should Lake lnLo accounL Lhe raLe of developmenL of fluld and elecLrolyLe
abnormallLles (e.g. esLabllshed hypo or hypernaLraemla should be correcLed slowly Lo avold poLenLlal
neurologlcal sequelae llke cenLral ponLlne demyellnoslysls).
oLenLlal compllcaLlng facLors lncludlng renal, cardlac, hepaLlc and endocrlne funcLlon, complex
losses (e.g. lleal flsLulae), hypoalbumlnaemla and perlpheral oedema should be addressed (see
redlsLrlbuLlon fluld algorlLhm).
ln general, Lhe fluld LhaL ls losL ls replaced. 1hus blood ls mosL approprlaLe for haemorrhaglc loss.
8eplacemenL flulds should maLch normal dally losses. Powever ln more complex slLuaLlons, lL may noL
be approprlaLe for Lhe replacemenL fluld Lo maLch Lhe percelved deflclL (see below). 1hus, ln acuLely
unwell paLlenLs (e.g. sepsls) and Lhose wlLh renal lmpalrmenL or complex fluld losses (e.g. burns,
flsLulae) selecLlon of replacemenL fluld (e.g. crysLallold, collold) should be dlcLaLed by speclalLy
guldellnes (e.g. dlabeLlc keLoacldosls).
10.S.S Commun|cat|on |ssues
aLlenLs should be lnformed as Lo why Lhey requlre lnLravenous flulds, how long Lhey wlll requlre Lhem,
Llmlng (l.e. can lnLravenous lnfuslons be sLopped aL nlghL Lo allow beLLer sleep) and poLenLlal
compllcaLlons (e.g. phleblLls due Lo fluld addlLlves llke poLasslum chlorlde). 1hey should be glven Lhe
opporLunlLy Lo relaLe any relevanL lnformaLlon and Lo dlscuss Lhelr concerns.
Senlor healLhcare professlonals across all dlsclpllnes musL Lake responslblllLy for Lhe assessmenL of fluld
requlremenLs and prescrlpLlon. !unlor colleagues musL be adequaLely supervlsed, Lhelr pracLlce assessed
and poor pracLlce challenged Lo demonsLraLe LhaL Lhls ls an lmporLanL cllnlcal lssue wlLh slgnlflcanL
lmpllcaLlons for paLlenL ouLcome. !unlor cllnlclans should be encouraged Lo dlscuss Lhe fluld
managemenL of Lhelr paLlenLs wlLh senlor colleagues.
All paLlenLs on lnLravenous fluld requlre monlLorlng (e.g. blochemlsLry, lnpuL/ouLpuL charLs, welghlng).
1hls daLa should always be revlewed as lL enhances fluld managemenL and demonsLraLes Lo Lhe Leam
collecLlng Lhls lnformaLlon LhaL Lhls daLa ls lmporLanL Lo paLlenLs care. ually fluld and elecLrolyLe
requlremenLs should be carefully assessed and clearly prescrlbed. lluld prescrlpLlons wrlLLen by ouL-of
hours Leams who are noL famlllar wlLh Lhe paLlenL are llkely Lo be lnferlor and should noL be LoleraLed.
racLlce should be audlLed and presenLed Lo Lhe wlder Leam Lo hlghllghL poLenLlal problems and ad[usL
pracLlce.
CommunlcaLlon wlLh Lhe nurslng Leam ls essenLlal. As Lhe prlmary carers for lnLravenous fluld
admlnlsLraLlon/monlLorlng, wlLh conslderable experLlse, Lhey should have Lhe opporLunlLy Lo ralse
concerns or lssues relaLed Lo fluld managemenL. ApproprlaLe lnLravenous access should be avallable. lf
an lnLravenous llne ls noL expecLed Lo lasL Lhe 24 hour perlod lL should be replaced durlng dayLlme hours

169
Lo avold dlsLurblng Lhe paLlenLs sleep and as ouL-of-hours nlghL-Llme docLors are ofLen over-sLreLched
rlsklng poor lnfecLlon conLrol pracLlces.
10.6 Lconom|c ev|dence
no economlc evldence was found for Lhls quesLlon.
10.7 kecommendat|ons and ||nk to ev|dence
kecommendat|ons
26. nosp|ta|s shou|d estab||sh systems to ensure that a|| hea|thcare
profess|ona|s |nvo|ved |n prescr|b|ng and de||ver|ng IV f|u|d therapy are
tra|ned on the pr|nc|p|es covered |n th|s gu|de||ne, and are then forma||y
assessed and reassessed at regu|ar |nterva|s to demonstrate competence
|n:
understand|ng the phys|o|ogy of f|u|d and e|ectro|yte ba|ance |n
pat|ents w|th norma| phys|o|ogy and dur|ng |||ness
assessing patients fluid and electrolyte needs (the 5 ks: kesusc|tat|on,
kout|ne ma|ntenance, kep|acement, ked|str|but|on and keassessment)
assess|ng the r|sks, benef|ts and harms of IV f|u|ds
prescr|b|ng and adm|n|ster|ng IV f|u|ds
mon|tor|ng the pat|ent response
eva|uat|ng and document|ng changes and
tak|ng appropr|ate act|on as requ|red.
27. nea|thcare profess|ona|s shou|d rece|ve tra|n|ng and educat|on about, and
be competent |n, recogn|s|ng, assess|ng and prevent|ng consequences of
m|smanaged IV f|u|d therapy, |nc|ud|ng:
pu|monary oedema
per|phera| oedema
vo|ume dep|et|on and shock.
28. nosp|ta|s shou|d have an IV f|u|ds |ead, respons|b|e for tra|n|ng, c||n|ca|
governance, aud|t and rev|ew of IV f|u|d prescr|b|ng and pat|ent outcomes.
8elaLlve values of
dlfferenL ouLcomes
Several sLudles reporLed LhaL medlcal and nurslng sLaff lack lmporLanL knowledge
essenLlal for hlgh quallLy fluld managemenL. ln response Lo Lhese flndlngs and obvlous
safeLy lmpllcaLlons, Lhere ls lncreaslng daLa Lo demonsLraLe Lhe effecLlveness of a
varleLy of Leachlng meLhods and programmes Lo lmprove fluld managemenL knowledge
and cllnlcal performance ln boLh medlcal and nurslng pracLlce, noL leasL Lhe beneflLs of
proLocol led care (see relevanL chapLer). ln parLlcular slmulaLlon Lralnlng ls lncreaslngly
recognlsed as an effecLlve Leachlng Lechnlque LhaL can be comblned wlLh compeLency
assessmenL ln a mulLldlsclpllnary seLLlng. 1here ls also evldence from revlews of oLher
areas of poor cllnlcal pracLlce (e.g. nuLrlLlon) LhaL seLLlng sLandards can lmprove
ouLcomes and lL ls hoped LhaL Lhls guldellne wlll sLarL Lhls process.
1he recognlLlon LhaL all medlcal and nurslng graduaLes need mlnlmum levels of
compeLence ln fluld managemenL, wlLh some becomlng experLs ln Lhese flelds, ls long
overdue. 1ralnlng ln fluld managemenL musL also be embedded ln boLh general and

170
speclalLy Lralnlng programmes wlLh clear currlculum based Leachlng ob[ecLlves and
dellneaLlon of mlnlmum sLandards of cllnlcal compeLency and knowledge for each sLage
of Lralnlng and cllnlcal dellvery. 8ecognlLlon and managemenL of Lhe cllnlcal
compllcaLlons of fluld managemenL should also be consldered.
1rade-off beLween
harms
key evldence flndlngs were:
Lack of adequaLe cllnlclan preparaLlon ls assoclaLed wlLh poLenLlal for lncreased cllnlcal
rlsk and harm. CuC lnLerpreLaLlon Lo emphaslse Lhe lmporLance of normaLlve educaLlve
acLlvlLy aL Lhe undergraduaLe, posL graduaLe and conLlnulng professlonal developmenL
levels.
oor fluld balance monlLorlng ls assoclaLed wlLh poLenLlal for lncreased cllnlcal rlsk and
harm. CuC lnLerpreLaLlon ls for renewed emphasls on Lhe lmporLance of malnLalnlng
accuraLe fluld measuremenL.
Low confldence ln relaLlon Lo lv flulds managemenL ls sub opLlmal ln relaLlon Lo
cllnlclan preparaLlon. CuC lnLerpreLaLlon ls lncreased emphasls on Lhe value placed on
all training and education supporting clinicians to be fit for purpose in relation to
assesslng, prescrlblng, managlng and evaluaLlng Lhe efflcacy of lv fluld supporL.
oor knowledge ls assoclaLed Lo lncreased poLenLlal for harm or lncreased cllnlcal rlsk.
CuC lnLerpreLaLlon ls LhaL Lhls evldence supporLs Lhelr experlence of pracLlce and musL
be Laken serlously as poLenLlal adverse effecLs of fluld mlsmanagemenL.
oslLlve lmpacL of Lralnlng lnLervenLlon on cllnlclan compllance wlLh proLocol led care.
CuC recognlse Lhe value of sysLems supporLlng educaLlon and Lralnlng acLlvlLy Lo
opLlmlse paLlenL ouLcome from lv fluld admlnlsLraLlon.
1here is some benefit to focussed training strategy (computer assisted).
lmproved knowledge leads Lo lmproved confldence ln lv fluld managemenL
Lconomlc
conslderaLlons
1here was no cosL-effecLlveness evldence for Lhls Loplc. 1hese recommendaLlons should
be lmplemenLed Lhrough Lralnlng and quallLy assurance mechanlsms already ln place.
ln Lhe medlum Lo longer Lerm Lhe Lralnlng should be prlmarlly Lhrough undergraduaLe
Lralnlng.

ln Lhe shorL-Lerm Lhere wlll be some cosLs lncurred ln Lralnlng currenL sLaff Lo Lhe
requlred sLandard. CosLlng Lhls ls noL sLralghLforward because
1) A course could be dellvered by many dlfferenL means (lncludlng e-learnlng), some of
whlch mlghL noL Lake much sLaff Llme.
2) 1he cosLs may poLenLlally be offseL by cosL savlngs Lhrough lmprovlng pracLlce, whlch
are dlfflculL Lo esLlmaLe (e.g. by prevenLlng compllcaLlons). 1herefore Lhere ls an
lnLeracLlon beLween Lralnlng and all Lhe oLher recommendaLlons ln Lhe guldellne.

1he nlCL lmplemenLaLlon Leam are developlng an e-learnlng Lool for Lhls guldellne and
Lherefore Lhe Lralnlng could be dellvered Lhrough Lhls rouLe wlLhouL Lhe cosL of experLs
and wlLh a small amounL of Llme from Lhe sLaff Lhemselves.

AlLhough dlfflculL Lo quanLlfy, Lhe ouLcome of Lhls guldellne should be boLh subsLanLlal
healLh galn and cosL savlngs slnce Lhe followlng are recommended:
a) Lhe lowesL cosL fluld for resusclLaLlon
b) Cne of Lhe lowesL cosL flulds for malnLenance buL one LhaL more closely meeLs Lhe
paLlenLs dally physlologlcal requlremenLs
c) Lhe sLopplng of lv flulds for paLlenLs LhaL are able Lo Lake oral fluld
d) lower volumes of fluld Lhan ls currenLly pracLlced
e) cllnlclans prescrlbe lv fluld lnLake Lo meeL Lhe needs of lndlvldual paLlenLs so as Lo
reduce adverse evenLs

171
f) ldenLlflcaLlon and reporLlng of Lhe adverse evenLs of mls-prescrlblng.
CuallLy of evldence 1he quallLy of evldence ls varlable LhroughouL Lhls sysLemaLlc narraLlve revlew,
acknowledglng LhaL Lhere ls no randomlsed evldence supporLlng Lhls lmporLanL aspecL
of Lralnlng and developmenL. 1hls ls noL aLyplcal and cerLalnly ls noL unlque Lo Lhe
conLexL of lv lluld Lherapy. 1he value of blendlng a number of research meLhods
Lhrough narraLlve revlew ls well documenLed, and lmporLanLly supporLed Lhe CuC Lo
dlscuss Lhe value placed on Lralnlng and educaLlon acLlvlLy ln Lhree maln areas, Lhese
are:
1he lmporLance of embeddlng Lhls guldance lnLo Lhe undergraduaLe currlculum and
ensure LhaL lL feaLures ln exam processes
1he lmporLance of embeddlng Lhls guldance lnLo speclallsL Lralnlng programmes and
ensure LhaL lL feaLures ln exam processes
1he lmporLance of embeddlng Lhls guldance ln on-golng supporL Lo quallfled and
senlor cllnlclans who carry professlonal and governance responslblllLy for opLlmal lv
fluld Lherapy pracLlce and ouLcomes.
CLher conslderaLlons 1he CuC recognlsed LhaL Lhere ls a presslng need Lo relnforce boLh Lhe prlnclples and
key aspecLs of knowledge relaLlng Lo fluld managemenL ln all healLhcare currlcula
1he CuC recognlse LhaL many aspecLs of Lhls guldellne are abouL culLure shlfL, and do
noL underesLlmaLe Lhe plannlng LhaL needs Lo supporL Lhls shlfL.
1he CuC felL sLrongly abouL Lhe lmporLance of Lhe role of Lhe lv flulds lead. 1here ls
sLrong evldence of mlsmanagemenL ln order Lo supporL Lhls recommendaLlon. 1he
recommendaLlon reflecLs CuC experL vlew- LhaL Lhls role ls posslble Lo esLabllsh wlLhln
exlsLlng workforce modelllng, and would promoLe Lhe guldance, besL pracLlce across
Lhe 1rusL Lhey are employed by and to review learning from near miss and critical
lncldenL reporLlng. 1hls ls cruclal ln opLlmlslng lv fluld Lherapy as a managemenL
lnLervenLlon.
aLlenL vlews are conslsLenLly sLrong on Lhe lmporLance of effecLlve engagemenL of Lhe
paLlenL ln relaLlon Lo fluld managemenL needs. WlLh encouragemenL for Lhe mulLl-
dlsclpllnary Leam Lo dlscuss and clearly communlcaLe Lhe lv fluld managemenL plan
8ecommendaLlons 23 and 27 were ldenLlfled as key prlorlLles for lmplemenLaLlon by
Lhe CuC.
uue Lo Lhe pauclLy of evldence ln Lhls area, Lhe CuC prlorlLlsed a research
recommendaLlon ln Lhls area evaluaLlng Lhe effecLlveness of hosplLal sysLems LhaL
ensure Lralnlng and educaLlon and proper reporLlng of compllcaLlons of fluld
mlsmanagemenL (see secLlon 10.8)

6. Does the |ntroduct|on of hosp|ta| systems that ensure:
a|| hosp|ta| hea|thcare profess|ona|s |nvo|ved |n prescr|b|ng and de||ver|ng IV f|u|d therapy are
appropr|ate|y tra|ned |n the pr|nc|p|es of f|u|d prescr|b|ng, and
a|| IV f|u|d therapy-re|ated comp||cat|ons are reported,
|ead to a reduct|on |n f|u|d-re|ated comp||cat|ons and assoc|ated hea|thcare costs?

172
Why th|s |s |mportant?
uesplLe the fact that assessment of a patients IV fluid needs and prescription of an appropriate IV fluid
reglmen can be complex, Lhe [ob ls ofLen delegaLed Lo healLhcare professlonals wlLh llmlLed experlence
and llLLle or no relevanL Lralnlng. Lrrors ln prescrlblng lv flulds and elecLrolyLes are LhoughL Lo be
common and assoclaLed wlLh unnecessary morbldlLy, morLallLy and lncreased healLhcare cosLs. 1he
problems are mosL llkely Lo occur ln emergency deparLmenLs, acuLe admlsslon unlLs and medlcal and
surglcal wards raLher Lhan operaLlng LheaLres and crlLlcal care unlLs, slnce Lhe sLaff ln more general
hosplLal areas have less relevanL experLlse, and sLandards of recordlng and monlLorlng of lv fluld and
elecLrolyLe Lherapy can be poor. ln addlLlon, Lhe consequences of lv fluld mlsmanagemenL are noL
wldely reporLed. lL would be useful Lo underLake Lhls sLudy Lo evaluaLe and audlL Lhe effecLs of
lnLroduclng Lralnlng and governance lnlLlaLlves ln Lhe nPS.

8eference llsL

173
11 keference ||st
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2 Plgglns !, Creen S (edlLors). Cochrane Pandbook for SysLemaLlc 8evlews of lnLervenLlons 3.0.2
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4 Alllson S, Lobo un, SLanga Z. 1he LreaLmenL of hypoalbumlnaemla. Cllnlcal nuLrlLlon. 2001,
20(3):273-279. (ColJelloe kef lu Alll5ON2001)
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8eference llsL

174
13 Casserly 8, 8aram M, Walsh , Sucov A, Ward nS, Levy MM. lmplemenLlng a collaboraLlve
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8eference llsL

173
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31 Can 1!, 8enneLL-Cuerrero L, hllllps-8uLe 8, Wakellng P, MoskowlLz uM, Clufolabl ? eL al.
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107 1almor u, Creenberg u, Powell Mu, Llsbon A, novack v, Shaplro n. 1he cosLs and cosL-
effecLlveness of an lnLegraLed sepsls LreaLmenL proLocol. CrlLlcal Care Medlclne. 2008,
36(4):1168-1174. (ColJelloe kef lu 1AlMOk2008)
108 1ang vC?, Lee LW?. lluld balance charL: do we undersLand lL? Cllnlcal 8lsk. 2010, 16(1):10-13.
(ColJelloe kef lu 1ANC2010)
109 1anl M, MorlmaLsu P, 1akaLsu l, MorlLa k. 1he lncldence and prognosLlc value of hypochloremla
ln crlLlcally lll paLlenLs. 1heSclenLlflcWorld!ournal. 2012, 2012:474183. (ColJelloe kef lu
1ANl2012)
110 1lndall Sl, Clark 8C. 1he lnfluence of hlgh and low sodlum lnLakes on posL-operaLlve anLldluresls.
8rlLlsh !ournal of Surgery. 1981, 68(9):639-644. (ColJelloe kef lu 1lNuAll1981)
111 1oomLong , Suksompong S. lnLravenous flulds for abdomlnal aorLlc surgery. Cochrane uaLabase
of SysLemaLlc 8evlews. 2010, lssue 1:Cu000991. (ColJelloe kef lu 1OOM1ONC2010)
112 venn 8, SLeele A, 8lchardson , olonleckl !, Crounds M, newman . 8andomlzed conLrolled Lrlal
Lo lnvesLlgaLe lnfluence of Lhe fluld challenge on duraLlon of hosplLal sLay and perloperaLlve
morbldlLy ln paLlenLs wlLh hlp fracLures. 8rlLlsh !ournal of AnaesLhesla. Lngland 2002, 88(1):63-
71. (ColJelloe kef lu vNN2002)
113 verhel[ !, van Llngen A, 8elshulzen A, ChrlsLlaans PM, de !ong !8, Clrbes A8 eL al. Cardlac
response ls greaLer for collold Lhan sallne fluld loadlng afLer cardlac or vascular surgery. lnLenslve
Care Medlclne. 2006, 32(7):1030-1038. (ColJelloe kef lu vknlI2006)
114 vermeulen P, Pofland !, LegemaLe uA, ubblnk u1. lnLravenous fluld resLrlcLlon afLer ma[or
abdomlnal surgery: a randomlzed bllnded cllnlcal Lrlal. 1rlals. 2009, 10:30. (ColJelloe kef lu
vkMulN2009)
113 Wakellng PC, Mclall M8, !enklns CS, Woods WCA, Mlles WlA, 8arclay C8 eL al. lnLraoperaLlve
oesophageal uoppler gulded fluld managemenL shorLens posLoperaLlve hosplLal sLay afLer ma[or
bowel surgery. 8rlLlsh !ournal of AnaesLhesla. 2003, 93(3):634-642. (ColJelloe kef lu
wAkllNC2005)
116 Walsh S8, Cook L!, 8enLley 8, larooq n, Cardner-1horpe !, 1ang 1 eL al. erloperaLlve fluld
managemenL: prospecLlve audlL. lnLernaLlonal !ournal of Cllnlcal racLlce. 2008, 62(3):492-497.
(ColJelloe kef lu wAl5n2008)
117 Walsh S8, Walsh C!. lnLravenous fluld-assoclaLed morbldlLy ln posLoperaLlve paLlenLs. Annals of
Lhe 8oyal College of Surgeons of Lngland. 2003, 87(2):126-130. (ColJelloe kef lu wAl5n2005)
118 WaLers !P, CoLLlleb A, Schoenwald , opovlch M!, Sprung !, nelson u8. normal sallne versus
lacLaLed 8lnger's soluLlon for lnLraoperaLlve fluld managemenL ln paLlenLs undergolng abdomlnal
aorLlc aneurysm repalr: an ouLcome sLudy. AnesLhesla and Analgesla. 2001, 93(4):817-822.
(ColJelloe kef lu wA1k52001)
119 Welsgerber M, llores C, omeranz A, Creenbaum L, PurlbuL , 8ragg u. SLudenL compeLence ln
fluld and elecLrolyLe managemenL: Lhe lmpacL of varlous Leachlng meLhods. AmbulaLory
edlaLrlcs. 2007, 7(3):220-223. (ColJelloe kef lu wl5Ck8k2007)
8eference llsL

182
120 Wledemann P, Wheeler A, 8ernard C8, 1hompson 81, Payden u, de8olsblanc 8 eL al.
Comparlson of Lwo fluld-managemenL sLraLegles ln acuLe lung ln[ury. new Lngland !ournal of
Medlclne. 2006, 334(24):2364-2373. (ColJelloe kef lu wluMANN2006A)
121 Wllklnson AW, 8llllng 8P, . LxcreLlon of chlorlde and sodlum afLer surglcal operaLlons. LanceL.
1949, 1(6333):640-644. (ColJelloe kef lu wllklN5ON1949)
122 Wllklnson AW, 8llllng 8P, nagy C, SLewarL C. LxcreLlon of poLasslum afLer parLlal gasLrecLomy.
LanceL. 1930, 2(6621):133-137. (ColJelloe kef lu wllklN5ON1950)
123 Wlse LC, Mersch !, 8acloppl !, Crosler !, 1hompson C. LvaluaLlng Lhe rellablllLy and uLlllLy of
cumulaLlve lnLake and ouLpuL. !ournal of nurslng Care CuallLy. 2000, 14(3):37-42. (ColJelloe kef
lu wl52000)
124 Woods MS, kelley P. CncoLlc pressure, albumln and lleus: Lhe effecL of albumln replacemenL on
posLoperaLlve lleus. Amerlcan Surgeon. 1993, 39(11):738-763. (ColJelloe kef lu wOOu5199J)
123 Wu !!, Puang MS, 1ang C!, kao Wl, Shlh PC, Su CP eL al. Pemodynamlc response of modlfled
fluld gelaLln compared wlLh lacLaLed rlnger's soluLlon for volume expanslon ln emergency
resusclLaLlon of hypovolemlc shock paLlenLs: prellmlnary reporL of a prospecLlve, randomlzed
Lrlal. World !ournal of Surgery. 2001, 23(3):398-602. (ColJelloe kef lu wu2001)
126 ?unos n, 8ellomo 8, PegarLy C, SLory u, Po L, 8alley M. AssoclaLlon beLween a chlorlde-llberal vs
chlorlde-resLrlcLlve lnLravenous fluld admlnlsLraLlon sLraLegy and kldney ln[ury ln crlLlcally lll
adulLs. !AMA: 1he !ournal of Lhe Amerlcan Medlcal AssoclaLlon. 2012, 308(13):1366-1372.
(ColJelloe kef lu uNO52012)

Acronyms and abbrevlaLlons

183
12 Acronyms and abbrev|at|ons

AAA Abdomlnal aorLlc aneurysm
Akl AcuLe kldney ln[ury
AACPL AcuLe physlology and chronlc healLh evaluaLlon ll
A8uS AcuLe resplraLory dlsLress syndrome
Ca Calclum
CA8C Coronary arLery bypass grafL (surgery)
CAu ConLlnuous ambulaLory perlLoneal dlalysls
CCA CosL-consequences analysls
CLA CosL-effecLlveness analysls
CPl CongesLlve hearL fallure
Cl Confldence lnLerval
Cl Chlorlde
CCu Chronlc obsLrucLlve pulmonary dlsease
C81 Caplllary reflll Llme
Cv CenLral venous pressure
u8 ulasLollc blood pressure
LCl LxLracellular flulds
LCC LffecLlve cardlac ouLpuL
LC-3u LuroCol-3u
llnLSS lluld resusclLaLlon ln Lhe managemenL of early sepLlc shock
ll8S1 llulds ln resusclLaLlon of severe Lrauma
CuC Culdellne developmenL group
C8AuL Cradlng of recommendaLlons assessmenL, developmenL and evaluaLlon
PLS PydroxyeLhyl sLarch
P8 PearL raLe
P8CoL PealLh-relaLed quallLy of llfe
P1A PealLh Lechnology assessmenL or appralsal
lCL8 lncremenLal cosL-effecLlveness raLlo
lCl lnLracellular fluld
ln8 lncremenLal neL beneflL
lSl lnLersLlLlal fluld
lSS ln[ury severlLy score
l18vl lnLra-Lhoraclc blood volume lndex
l11 lnLenLlon-Lo-LreaL analysls
lv lnLravenous
!v !ugular venous pressure
k oLasslum
kCl oLasslum chlorlde
LL18 Llnklng evldence Lo recommendaLlons
Lvl LefL venLrlcular fallure
Acronyms and abbrevlaLlons

184

MA Mean arLerlal pressure
Mlu Mlnlmal lmporLanL dlfference
Mmol Mllllmole(s)
MCuS MulLlple organ dysfuncLlon score
MorbldlLy ulseased condlLlon or sLaLe
MorLallLy erlod of llfe/Llme
n number of paLlenLs randomlsed
nA noL appllcable
naCl Sodlum chlorlde
nC nasogasLrlc
nCCC naLlonal Cllnlcal Culdellne CenLre
nLWS naLlonal Larly Warnlng Score
nlCL naLlonal lnsLlLuLe for PealLh and Care Lxcellence
nlSS new ln[ury severlLy score
nn1 numbers needed Lo LreaL
nSA naLlonal aLlenL SafeLy Agency
n8 noL reporLed
nS noL slgnlflcanL
lCC aLlenL, lnLervenLlon, comparlson, ouLcome
Cnv osL-operaLlve nausea and vomlLlng
CAL? CuallLy-ad[usLed llfe year
CoL CuallLy of llfe
8C1 8andomlsed conLrolled Lrlal
88 8elaLlve rlsk
SA SenslLlvlLy analysls
SAlL sLudy Sallne versus albumln fluld evaluaLlon
SA Severe acuLe pancreaLlLls
S8 SysLollc blood pressure
ScvC2 CenLral venous oxygen saLuraLlon
Su SLandard devlaLlon
SL SLandard error
SClA score SequenLlal organ fallure assessmenL score
1A 1echnology appralsal
18l 1raumaLlc braln ln[ury
v8C venous blood gas
ulP unfracLlonaLed heparln
unC undersLandlng nlCL guldance
v8C venous blood gases
vlSL Lfflcacy of volume subsLlLuLlon and lnsulln Lherapy ln severe sepsls

Clossary

183
13 G|ossary

AbsLracL Summary of a sLudy, whlch may be publlshed alone or as an lnLroducLlon Lo a
full sclenLlflc paper.
Acldosls AccumulaLlon (lncrease) of acld wlLhln Lhe blood and oLher body Llssues.
Cccurs when pP less Lhan 7.33.
Albumln WaLer soluble proLeln ln Lhe blood
AlgorlLhm (ln guldellnes) A flow charL of Lhe cllnlcal declslon paLhway descrlbed ln Lhe guldellne, where
declslon polnLs are represenLed wlLh boxes, llnked wlLh arrows.
AllocaLlon concealmenL 1he process used Lo prevenL advance knowledge of group asslgnmenL ln a
8C1. 1he allocaLlon process should be lmpervlous Lo any lnfluence by Lhe
lndlvldual maklng Lhe allocaLlon, by belng admlnlsLered by someone who ls
noL responslble for recrulLlng parLlclpanLs.
AlLernaLe balanced
soluLlons
AlLernaLe balanced soluLlons aresoluLlons havlng a pP of 4.3, osmolarlLy of
284 mCsm/l and Lhe followlng composlLlon of elecLrolyLes (ln mmol/l)
Sodlum: 31, Chlorlde: 31, Calclum: 0, oLasslum: 0 8lcarbonaLe: 0 Magneslum:
0, Clucose: 222mmol/l.
1hese are avallable commerclally under dlfferenL brand names.
Anurla Absence of urlne producLlon or ouLpuL less Lhan 100ml per day. Anurla may be
caused by a fallure or kldney dysfuncLlon, a decllne ln blood pressure below
LhaL requlred Lo malnLaln fllLraLlon pressure ln Lhe kldney, or an obsLrucLlon ln
Lhe urlnary passages.
AppllcablllLy 1he degree Lo whlch Lhe resulLs of an observaLlon, sLudy or revlew are llkely Lo
hold Lrue ln a parLlcular cllnlcal pracLlce seLLlng.
Arm (of a cllnlcal sLudy) Sub-secLlon of lndlvlduals wlLhln a sLudy who recelve one parLlcular
lnLervenLlon, for example placebo arm
AssoclaLlon SLaLlsLlcal relaLlonshlp beLween Lwo or more evenLs, characLerlsLlcs or oLher
varlables. 1he relaLlonshlp may or may noL be causal.
8asellne 1he lnlLlal seL of measuremenLs aL Lhe beglnnlng of a sLudy (afLer run-ln perlod
where appllcable), wlLh whlch subsequenL resulLs are compared.
8efore-and-afLer sLudy A sLudy LhaL lnvesLlgaLes Lhe effecLs of an lnLervenLlon by measurlng parLlcular
characLerlsLlcs of a populaLlon boLh before and afLer Laklng Lhe lnLervenLlon,
and assesslng any change LhaL occurs.
8las SysLemaLlc (as opposed Lo random) devlaLlon of Lhe resulLs of a sLudy from
the true results that is caused by the way the study is designed or conducted.
8lcarbonaLe An alkallne molecule, generaLed ln Lhe body from carbon dloxlde, and
funcLlonlng as a reservolr Lo ad[usL for lncreases ln acldlLy from meLabollc
acLlvlLy. lL prevenLs Lhe blood from becomlng Loo acldlc.
8llndlng keeplng Lhe sLudy parLlclpanLs, careglvers, researchers and ouLcome assessors
unaware abouL Lhe lnLervenLlons Lo whlch Lhe parLlclpanLs have been
allocaLed ln a sLudy.
Carer (careglver) Someone oLher Lhan a healLh professlonal who ls lnvolved ln carlng for a
person wlLh a medlcal condlLlon.
Case-conLrol sLudy ComparaLlve observaLlonal sLudy ln whlch Lhe lnvesLlgaLor selecLs lndlvlduals
who have experlenced an evenL (lor example, developed a dlsease) and
oLhers who have noL (conLrols), and Lhen collecLs daLa Lo deLermlne prevlous
exposure Lo a posslble cause.
Case-serles 8eporL of a number of cases of a glven dlsease, usually coverlng Lhe course of
Lhe dlsease and Lhe response Lo LreaLmenL. 1here ls no comparlson (conLrol)
group of paLlenLs.
Clossary

186

Cllnlcal efflcacy 1he exLenL Lo whlch an lnLervenLlon ls acLlve when sLudled under conLrolled
research condlLlons.
Cllnlcal effecLlveness 1he exLenL Lo whlch an lnLervenLlon produces an overall healLh beneflL ln
rouLlne cllnlcal pracLlce.
Cllnlclan A healLhcare professlonal provldlng dlrecL paLlenL care, for example docLor,
nurse or physloLheraplsL.
Cochrane 8evlew 1he Cochrane Llbrary conslsLs of a regularly updaLed collecLlon of evldence-
based medlclne daLabases lncludlng Lhe Cochrane uaLabase of SysLemaLlc
8evlews (revlews of randomlsed conLrolled Lrlals prepared by Lhe Cochrane
CollaboraLlon).
CohorL sLudy A reLrospecLlve or prospecLlve follow-up sLudy. Croups of lndlvlduals Lo be
followed up are deflned on Lhe basls of presence or absence of exposure Lo a
suspecLed rlsk facLor or lnLervenLlon. A cohorL sLudy can be comparaLlve, ln
whlch case Lwo or more groups are selecLed on Lhe basls of dlfferences ln
Lhelr exposure Lo Lhe agenL of lnLeresL.
Collolds A soluLlon whlch ls admlnlsLered lnLravenously and acLs as a volume expander.
lL ls composed of parLlcles whlch are noL capable of passlng Lhrough a
semlpermeable membrane. Lxamples of collolds lnclude albumln, sLarches
and gelaLln.
ComorbldlLy Co-exlsLence of more Lhan one dlsease or an addlLlonal dlsease (oLher Lhan
LhaL belng sLudled or LreaLed) ln an lndlvldual.
ComparablllLy SlmllarlLy of Lhe groups ln characLerlsLlcs llkely Lo affecL Lhe sLudy resulLs (such
as healLh sLaLus or age).
CompensaLe (shock) llrsL sLage of shock, characLerlsed by low blood flow and perfuslon.
Concordance 1hls ls a recenL Lerm whose meanlng has changed. lL was lnlLlally applled Lo
Lhe consulLaLlon process ln whlch docLor and paLlenL agree LherapeuLlc
declslons LhaL lncorporaLe Lhelr respecLlve vlews, buL now lncludes paLlenL
supporL ln medlclne Laklng as well as prescrlblng communlcaLlon.
Concordance reflecLs soclal values buL does noL address medlclne-Laklng and
may noL lead Lo lmproved adherence.
Confldence lnLerval (Cl) A range of values for an unknown populaLlon parameLer wlLh a sLaLed
confidence (conventionally 95) LhaL lL conLalns Lhe Lrue value. 1he lnLerval
ls calculaLed from sample daLa, and generally sLraddles Lhe sample esLlmaLe.
The confidence value means that if the method used to calculate the interval
ls repeaLed many Llmes, Lhen LhaL proporLlon of lnLervals wlll acLually conLaln
Lhe Lrue value.
Confoundlng ln a sLudy, confoundlng occurs when Lhe effecL of an lnLervenLlon on an
ouLcome ls dlsLorLed as a resulL of an assoclaLlon beLween Lhe populaLlon or
lnLervenLlon or ouLcome and anoLher facLor (Lhe confounding variable) that
can lnfluence Lhe ouLcome lndependenLly of Lhe lnLervenLlon under sLudy.
CongesLlve hearL fallure 1he lnablllLy of Lhe hearL Lo supply sufflclenL blood flow Lo meeL needs.
Consensus meLhods 1echnlques LhaL alm Lo reach an agreemenL on a parLlcular lssue. Consensus
meLhods may used when Lhere ls a lack of sLrong evldence on a parLlcular
Loplc.
ConLrol group A group of paLlenLs recrulLed lnLo a sLudy LhaL recelves no LreaLmenL, a
LreaLmenL of known effecL, or a placebo (dummy LreaLmenL) - ln order Lo
provlde a comparlson for a group recelvlng an experlmenLal LreaLmenL, such
as a new drug.
CosL beneflL analysls A Lype of economlc evaluaLlon where boLh cosLs and beneflLs of healLhcare
LreaLmenL are measured ln Lhe same moneLary unlLs. lf beneflLs exceed cosLs,
Lhe evaluaLlon would recommend provldlng Lhe LreaLmenL.
Clossary

187

CosL-consequences
analysls (CCA)
A Lype of economlc evaluaLlon where varlous healLh ouLcomes are reporLed ln
addlLlon Lo cosL for each lnLervenLlon, buL Lhere ls no overall measure of
healLh galn.
CosL-effecLlveness analysls
(CLA)
An economlc sLudy deslgn ln whlch consequences of dlfferenL lnLervenLlons
are measured using a single outcome, usually in natural units (For example,
llfe-years galned, deaLhs avolded, hearL aLLacks avolded, cases deLecLed).
AlLernaLlve lnLervenLlons are Lhen compared ln Lerms of cosL per unlL of
effecLlveness.
CosL-effecLlveness model An expllclL maLhemaLlcal framework, whlch ls used Lo represenL cllnlcal
declslon problems and lncorporaLe evldence from a varleLy of sources ln order
Lo esLlmaLe Lhe cosLs and healLh ouLcomes.
CosL-uLlllLy analysls (CuA) A form of cosL-effecLlveness analysls ln whlch Lhe unlLs of effecLlveness are
quallLy-ad[usLed llfe-years (CAL?s).
CreaLlnlne A wasLe producL produced by Lhe body durlng muscle meLabollsm and
normally excreLed ln urlne. lf Lhe creaLlnlne level lncreases ln Lhe blood, Lhls
may lndlcaLe decreased kldney funcLlon
Credlble lnLerval 1he 8ayeslan equlvalenL of a confldence lnLerval.
CrysLallolds A soluLlon whlch ls admlnlsLered lnLravenously and acLs as a volume expander.
lL ls composed of parLlcles whlch are capable of passlng Lhrough a
semlpermeable membrane. Lxamples of crysLallolds lnclude sodlum chlorlde
0.9% and lactated Ringers soluLlon.
ueclslon analysls An expllclL quanLlLaLlve approach Lo declslon maklng under uncerLalnLy, based
on evldence from research. 1hls evldence ls LranslaLed lnLo probablllLles, and
Lhen lnLo dlagrams or declslon Lrees whlch dlrecL Lhe cllnlclan Lhrough a
successlon of posslble scenarlos, acLlons and ouLcomes.
uehydraLlon Loss of body waLer (pure waLer wlLh no sodlum or soluLes), ls always
accompanled by hlgh sodlum concenLraLlon ln Lhe blood (hypernaLremla),
LreaLmenL ls waLer.
ulscounLlng CosLs and perhaps beneflLs lncurred Loday have a hlgher value Lhan cosLs and
beneflLs occurrlng ln Lhe fuLure. ulscounLlng healLh beneflLs reflecLs lndlvldual
preference for beneflLs Lo be experlenced ln Lhe presenL raLher Lhan Lhe
fuLure. ulscounLlng cosLs reflecLs lndlvldual preference for cosLs Lo be
experlenced ln Lhe fuLure raLher Lhan Lhe presenL.
uomlnance An lnLervenLlon ls sald Lo be domlnanL lf Lhere ls an alLernaLlve lnLervenLlon
LhaL ls boLh less cosLly and more effecLlve.
urop-ouL A parLlclpanL who wlLhdraws from a Lrlal before Lhe end of Lrlal.
Lconomlc evaluaLlon ComparaLlve analysls of alLernaLlve healLh sLraLegles (lnLervenLlons or
programmes) ln Lerms of boLh Lhelr cosLs and consequences.
LffecL (as ln effecL
measure, LreaLmenL effecL,
esLlmaLe of effecL, effecL
slze)
1he observed assoclaLlon beLween lnLervenLlons and ouLcomes or a sLaLlsLlc
Lo summarlse Lhe sLrengLh of Lhe observed assoclaLlon.
LffecLlveness See Clinical effectiveness.
Lfflcacy See Clinical efficacy.
LlecLrolyLe lons ln soluLlon LhaL acqulre Lhe capaclLy Lo conducL elecLrlclLy, ln Lhe conLexL
of Lhls guldance Lhe elecLrolyLes evaluaLed refer Lo sodlum, poLasslum and
chlorlde.
LnLeral AbsorpLlon Lhrough gasLrolnLesLlnal LracL (nose (nC), sLomach or lnLesLlne)
Lpldemlologlcal sLudy 1he sLudy of a dlsease wlLhln a populaLlon, deflnlng lLs lncldence and
prevalence and examlnlng Lhe roles of exLernal lnfluences (for example,
Clossary

188

lnfecLlon, dleL) and lnLervenLlons.
LC-3u (LuroCol-3u) A sLandardlsed lnsLrumenL used Lo measure a healLh ouLcome. lL provldes a
slngle lndex value for healLh sLaLus.
Luvolemla 1erm lmplylng LhaL Lhe lndlvldual descrlbed appears Lo have a normal
clrculaLory or blood fluld volume wlLhln Lhelr body
Lvldence lnformaLlon on whlch a declslon or guldance ls based. Lvldence ls obLalned
from a range of sources lncludlng randomlsed conLrolled Lrlals, observaLlonal
sLudles, experL oplnlon (of cllnlcal professlonals and/or paLlenLs).
Lxcluslon crlLerla
(llLeraLure revlew)
LxpllclL sLandards used Lo declde whlch sLudles should be excluded from
conslderaLlon as poLenLlal sources of evldence.
Lxcluslon crlLerla (cllnlcal
sLudy)
CrlLerla LhaL deflne who ls noL ellglble Lo parLlclpaLe ln a cllnlcal sLudy.
LxperL In this guideline, the term expert refers to a healthcare professional who has
core compeLencles Lo dlagnose and manage acuLe lllness. 1hese compeLencles
can be dellvered by a varleLy of models aL a local level, such as a crlLlcal care
ouLreach Leam, a hosplLal-aL-nlghL Leam or a speclallsL Lralnee ln an acuLe
medlcal or surglcal speclalLy. lor more lnformaLlon, see AcuLely lll paLlenLs ln
hosplLal (nlCL cllnlcal guldellne 30).
LxLended domlnance lf CpLlon A ls boLh more cllnlcally effecLlve Lhan CpLlon 8 and has a lower cosL
per unlL of effecL, when boLh are compared wlLh a do-noLhlng alLernaLlve Lhen
CpLlon A ls sald Lo have exLended domlnance over CpLlon 8. CpLlon A ls
Lherefore more efflclenL and should be preferred, oLher Lhlngs remalnlng
equal.
LxLrapolaLlon ln daLa analysls, predlcLlng Lhe value of a parameLer ouLslde Lhe range of
observed values.
llsLulae ermanenL abnormal passageway beLween Lwo organs ln Lhe body.
lollow-up CbservaLlon over a perlod of Llme of an lndlvldual, group or lnlLlally deflned
populaLlon whose approprlaLe characLerlsLlcs have been assessed ln order Lo
observe changes ln healLh sLaLus or healLh-relaLed varlables.
CenerallsablllLy 1he exLenL Lo whlch Lhe resulLs of a sLudy based on measuremenL ln a
parLlcular paLlenL populaLlon and/or a speclflc conLexL hold Lrue for anoLher
populaLlon and/or ln a dlfferenL conLexL. ln Lhls lnsLance, Lhls ls Lhe degree Lo
whlch Lhe guldellne recommendaLlon ls appllcable across boLh geographlcal
and conLexLual seLLlngs. lor lnsLance, guldellnes LhaL suggesL subsLlLuLlng one
form of labour for anoLher should acknowledge LhaL Lhese cosLs mlghL vary
across Lhe counLry.
Cold sLandard . See Reference standard
C8AuL / C8AuL proflle A sysLem developed by Lhe C8AuL Worklng Croup Lo address Lhe
shorLcomlngs of presenL gradlng sysLems ln healLhcare. 1he C8AuL sysLem
uses a common, senslble and LransparenL approach Lo gradlng Lhe quallLy of
evldence. 1he resulLs of applylng Lhe C8AuL sysLem Lo cllnlcal Lrlal daLa are
dlsplayed ln a Lable known as a C8AuL proflle.
Paemodynamlc 8elaLed Lo clrculaLlon of blood ln Lhe body
Parms Adverse effecLs of an lnLervenLlon.
PealLh economlcs 1he sLudy of Lhe allocaLlon of scarce resources among alLernaLlve healLhcare
LreaLmenLs. PealLh economlsLs are concerned wlLh boLh lncreaslng Lhe
average level of healLh ln Lhe populaLlon and lmprovlng Lhe dlsLrlbuLlon of
healLh.
PealLh-relaLed quallLy of
llfe (P8CoL)
A combination of an individuals physical, mental and social well-belng, noL
merely Lhe absence of dlsease.
PeLerogenelLy Cr lack of 1he Lerm ls used ln meLa-analyses and sysLemaLlc revlews when Lhe resulLs or
Clossary

189

homogenelLy. esLlmaLes of effecLs of LreaLmenL from separaLe sLudles seem Lo be very
dlfferenL ln Lerms of Lhe slze of LreaLmenL effecLs or even Lo Lhe exLenL LhaL
some lndlcaLe beneflclal and oLhers suggesL adverse LreaLmenL effecLs. Such
resulLs may occur as a resulL of dlfferences beLween sLudles ln Lerms of Lhe
paLlenL populaLlons, ouLcome measures, deflnlLlon of varlables or duraLlon of
follow-up.
Pypercalcaemla lncreased calclum level ln blood
Pyperchloraemla lncreased chlorlde level ln blood
Pyperkalaemla lncreased poLasslum level ln blood
PypernaLraemla lncreased sodlum level ln blood
Pyperperfuslon lncreased blood flow Lhrough an organ
Pypervolaemla 1erm lmplylng LhaL Lhe lndlvldual descrlbed appears Lo have lncreased
clrculaLory or blood fluld volume wlLhln Lhelr body
Pypoperfuslon uecreased blood flow Lhrough an organ
Pypocalcaemla uecreased calclum level ln blood
Pypochloraemla uecreased chlorlde level ln blood
Pypokalaemla uecreased poLasslum level ln blood
PyponaLraemla uecreased sodlum level ln blood
lleal flsLula Abnormal communlcaLlon beLween Lhe lleum and anoLher organ or cavlLy.
lleus lnLesLlnal obsLrucLlon, maybe characLerlsed by sudden paln, consLlpaLlon,
abdomlnal dlsLenslon, perslsLenL faecal vomlLlng and collapse.
lmpreclslon 8esulLs are lmpreclse when sLudles lnclude relaLlvely few paLlenLs and few
evenLs and Lhus have wlde confldence lnLervals around Lhe esLlmaLe of effecL.
lncluslon crlLerla (llLeraLure
revlew)
LxpllclL crlLerla used Lo declde whlch sLudles should be consldered as poLenLlal
sources of evldence.
lncremenLal analysls 1he analysls of addlLlonal cosLs and addlLlonal cllnlcal ouLcomes wlLh dlfferenL
lnLervenLlons.
lncremenLal cosL 1he mean cosL per paLlenL assoclaLed wlLh an lnLervenLlon mlnus Lhe mean
cosL per paLlenL assoclaLed wlLh a comparaLor lnLervenLlon.
lncremenLal cosL
effecLlveness raLlo (lCL8)
1he dlfference ln Lhe mean cosLs ln Lhe populaLlon of lnLeresL dlvlded by Lhe
dlfferences ln Lhe mean ouLcomes ln Lhe populaLlon of lnLeresL for one
LreaLmenL compared wlLh anoLher.
lncremenLal neL beneflL
(ln8)
1he value (usually ln moneLary Lerms) of an lnLervenLlon neL of lLs cosL
compared wlLh a comparaLor lnLervenLlon. 1he ln8 can be calculaLed for a
glven cosL-effecLlveness (wllllngness Lo pay) Lhreshold. lf Lhe Lhreshold ls
20,000 per CAL? galned Lhen Lhe ln8 ls calculaLed as: (20,000 x CAL?s
galned) lncremenLal cosL.
lndlrecLness 1he avallable evldence ls dlfferenL Lo Lhe revlew quesLlon belng addressed, ln
Lerms of lCC (populaLlon, lnLervenLlon, comparlson and ouLcome).
lnoLropes urugs affecLlng muscle conLracLlon, especlally hearL muscle
lnsenslble (waLer) loss 1he amounL of fluld losL on a dally basls from Lhe lungs, skln, resplraLory LracL,
and waLer excreLed ln Lhe faeces.
lnLenLlon Lo LreaL analysls
(l11)
A sLraLegy for analyslng daLa from a randomlsed conLrolled Lrlal. All
parLlclpanLs are lncluded ln Lhe arm Lo whlch Lhey were allocaLed, wheLher or
noL Lhey recelved (or compleLed) Lhe lnLervenLlon glven Lo LhaL arm.
lnLenLlon-Lo-LreaL analysls prevenLs blas caused by Lhe loss of parLlclpanLs,
whlch may dlsrupL Lhe basellne equlvalence esLabllshed by randomlsaLlon and
whlch may reflecL non-adherence Lo Lhe proLocol.
lnLercellular Space beLween cells
Clossary

190

lnLersLlLlal Lylng ln beLween or placed wlLhln an organ or Llssue.
lnLervenLlon PealLhcare acLlon lnLended Lo beneflL Lhe paLlenL, for example, drug
LreaLmenL, surglcal procedure, psychologlcal Lherapy.
kappa sLaLlsLlc A sLaLlsLlcal measure of lnLer-raLer agreemenL LhaL Lakes lnLo accounL Lhe
agreemenL occurrlng by chance.
LacLlc acldosls AccumulaLlon of lacLlc acld ln Lhe blood, lacLlc acld ls formed ln Lhe body
durlng muscular acLlvlLy by breakdown of glycogen and may be formed aL a
fasLer raLe when Lhere ls lnadequaLe oxygenaLlon of Llssues (for example, ln
sepsls or shock). 1hls ls usually esLlmaLed by Lhe measuremenL of lacLaLe
levels ln venous blood (venous lacLaLe).
LengLh of sLay 1he LoLal number of days a paLlenL sLays ln hosplLal.
Llcence See Product licence.
Llfe-years galned Mean average years of llfe galned per person as a resulL of Lhe lnLervenLlon
compared wlLh an alLernaLlve lnLervenLlon.
Llkellhood raLlo 1he llkellhood raLlo comblnes lnformaLlon abouL Lhe senslLlvlLy and speclflclLy.
lL Lells you how much a poslLlve or negaLlve resulL changes Lhe llkellhood LhaL
a paLlenL would have Lhe dlsease. 1he llkellhood raLlo of a poslLlve LesL resulL
(L8+) ls senslLlvlLy dlvlded by 1- speclflclLy.
Long-Lerm care 8esldenLlal care ln a home LhaL may lnclude skllled nurslng care and help wlLh
everyday acLlvlLles. 1hls lncludes nurslng homes and resldenLlal homes.
Markov model A meLhod for esLlmaLlng long-Lerm cosLs and effecLs for recurrenL or chronlc
condlLlons, based on healLh sLaLes and Lhe probablllLy of LranslLlon beLween
Lhem wlLhln a glven Llme perlod (cycle).
MeLa-analysls A sLaLlsLlcal Lechnlque for comblnlng (poollng) Lhe resulLs of a number of
sLudles LhaL address Lhe same quesLlon and reporL on Lhe same ouLcomes Lo
produce a summary resulL. 1he alm ls Lo derlve more preclse and clear
lnformaLlon from a large daLa pool. lL ls generally more rellably llkely Lo
conflrm or refuLe a hypoLhesls Lhan Lhe lndlvldual Lrlals.
MulLlvarlaLe model A sLaLlsLlcal model for analysls of Lhe relaLlonshlp beLween Lwo or more
predlcLor (lndependenL) varlables and Lhe ouLcome (dependenL) varlable.
number needed Lo LreaL
(nn1)
1he number of paLlenLs LhaL who on average musL be LreaLed Lo prevenL a
slngle occurrence of Lhe ouLcome of lnLeresL.
CbservaLlonal sLudy 8eLrospecLlve or prospecLlve sLudy ln whlch Lhe lnvesLlgaLor observes Lhe
naLural course of evenLs wlLh or wlLhouL conLrol groups, for example, cohorL
sLudles and caseconLrol sLudles.
Cdds raLlo A measure of LreaLmenL effecLlveness. 1he odds of an evenL happenlng ln Lhe
LreaLmenL group, expressed as a proporLlon of Lhe odds of lL happenlng ln Lhe
conLrol group. 1he 'odds' ls Lhe raLlo of evenLs Lo non-evenLs.
Cedema Lxcesslve fluld ln/around cells
Cllgurla 8educed secreLlon of urlne
CpporLunlLy cosL 1he loss of oLher healLh care programmes dlsplaced by lnvesLmenL ln or
lnLroducLlon of anoLher lnLervenLlon. 1hls may be besL measured by Lhe
healLh beneflLs LhaL could have been achleved had Lhe money been spenL on
Lhe nexL besL alLernaLlve healLhcare lnLervenLlon.
CuLcome Measure of Lhe posslble resulLs LhaL may sLem from exposure Lo a prevenLlve
or LherapeuLlc lnLervenLlon. CuLcome measures may be lnLermedlaLe
endpoints or they can be final endpoints. See Intermediate outcome.
-value 1he probablllLy LhaL an observed dlfference could have occurred by chance,
assumlng LhaL Lhere ls ln facL no underlylng dlfference beLween Lhe means of
Lhe observaLlons. lf Lhe probablllLy ls less Lhan 1 ln 20, Lhe value ls less Lhan
Clossary

191

0.03, a resulL wlLh a value of less Lhan 0.03 ls convenLlonally consldered Lo
be statistically significant.
arenLeral uenoLes any medlcaLlon rouLe oLher Lhan Lhrough Lhe allmenLary canal, such
as lnLravenous, subcuLaneous, lnLramuscular or mucosal. arenLeral nuLrlLlon
refers Lo Lhe provlslon of calorlc needs of a paLlenL by lnLravenous rouLe who
ls unable Lo Lake food orally.
asslve leg ralslng asslve leg ralslng ls a bedslde meLhod Lo assess fluld responslveness ln a
paLlenL. lL ls underLaken by lylng Lhe paLlenL flaL and passlvely ralslng Lhelr
legs Lo greaLer Lhan 43 degrees. lf, aL 30-90 seconds, Lhe paLlenL shows slgns
of haemodynamlc lmprovemenL, lL lndlcaLes LhaL volume replacemenL may be
requlred. lf Lhe condlLlon of Lhe paLlenL deLerloraLes, ln parLlcular
breaLhlessness, lL lndlcaLes LhaL Lhe paLlenL may be fluld over loaded.
erfuslon assage of fluld Lhrough organs or spaces.
erloperaLlve 1he perlod from admlsslon Lhrough surgery unLll dlscharge, encompasslng Lhe
pre-operaLlve and posL-operaLlve perlods
pP 1he acld-alkallne balance
lacebo An lnacLlve and physlcally ldenLlcal medlcaLlon or procedure used as a
comparaLor ln conLrolled cllnlcal Lrlals
olypharmacy 1he use or prescrlpLlon of mulLlple medlcaLlons
olyurla Lxcesslve secreLlon and dlscharge of urlne
onLlne demyellnosls 8raln cell dysfuncLlon caused by Lhe desLrucLlon of Lhe myelln layer coverlng
nerve cells ln Lhe mlddle of Lhe bralnsLem (pons).
osLoperaLlve erLalnlng Lo Lhe perlod afLer paLlenLs leave Lhe operaLlng LheaLre, followlng
surgery
ower (sLaLlsLlcal) 1he ablllLy Lo demonsLraLe an assoclaLlon when one exlsLs. ower ls relaLed Lo
sample slze, Lhe larger Lhe sample slze, Lhe greaLer Lhe power and Lhe lower
Lhe rlsk LhaL a posslble assoclaLlon could be mlssed.
reoperaLlve 1he perlod before surgery commences.
rlmary care PealLhcare dellvered Lo paLlenLs ouLslde hosplLals. rlmary care covers a range
of servlces provlded by general pracLlLloners, nurses, denLlsLs, pharmaclsLs,
opLlclans and oLher healLhcare professlonals.
rlmary ouLcome 1he ouLcome of greaLesL lmporLance, usually Lhe one ln a sLudy LhaL Lhe
power calculaLlon ls based on.
roducL llcence An auLhorlsaLlon from Lhe MP8A Lo markeL a medlclnal producL.
rognosls A probable course or ouLcome of a dlsease. rognosLlc facLors are paLlenL or
dlsease characLerlsLlcs LhaL lnfluence Lhe course. Cood prognosls ls assoclaLed
wlLh low raLe of undeslrable ouLcomes, poor prognosls ls assoclaLed wlLh a
hlgh raLe of undeslrable ouLcomes.
rospecLlve sLudy A sLudy ln whlch people are enLered lnLo Lhe research and Lhen followed up
over a perlod of Llme wlLh fuLure evenLs recorded as Lhey happen. 1hls
conLrasLs wlLh sLudles LhaL are reLrospecLlve.
roLocol A pre-deflned seL of meLhods or procedures usually lncludlng a LreaLmenL
plan.
ubllcaLlon blas Also known as reporLlng blas. A blas caused by only a subseL of all Lhe relevanL
daLa belng avallable. 1he publlcaLlon of research can depend on Lhe naLure
and dlrecLlon of Lhe sLudy resulLs. SLudles ln whlch an lnLervenLlon ls noL
found Lo be effecLlve are someLlmes noL publlshed. 8ecause of Lhls,
sysLemaLlc revlews LhaL fall Lo lnclude unpubllshed sLudles may overesLlmaLe
Lhe Lrue effecL of an lnLervenLlon. ln addlLlon, a publlshed reporL mlghL
presenL a blased seL of resulLs (e.g. only ouLcomes or sub-groups where a
Clossary

192

sLaLlsLlcally slgnlflcanL dlfference was found.
CuallLy of llfe See Health-relaLed quallLy of life.
CuallLy-ad[usLed llfe year
(CAL?)

An index of survival that is adjusted to account for the patients quality of life
durlng Lhls Llme. CAL?s have Lhe advanLage of lncorporaLlng changes ln boLh
quanLlLy (longevlLy/morLallLy) and quallLy (morbldlLy, psychologlcal,
funcLlonal, soclal and oLher facLors) of llfe. used Lo measure beneflLs ln cosL-
uLlllLy analysls. 1he CAL?s galned are Lhe mean CAL?s assoclaLed wlLh one
LreaLmenL mlnus Lhe mean CAL?s assoclaLed wlLh an alLernaLlve LreaLmenL.
8andomlsaLlon AllocaLlon of parLlclpanLs ln a research sLudy Lo Lwo or more alLernaLlve
groups uslng a chance procedure, such as compuLer-generaLed random
numbers. 1hls approach ls used ln an aLLempL Lo ensure Lhere ls an even
dlsLrlbuLlon of parLlclpanLs wlLh dlfferenL characLerlsLlcs beLween groups and
Lhus reduce sources of blas.
8andomlsed conLrolled
Lrlal (8C1)
A comparaLlve sLudy ln whlch parLlclpanLs are randomly allocaLed Lo
lnLervenLlon and conLrol groups and followed up Lo examlne dlfferences ln
ouLcomes beLween Lhe groups.
8C1 See Randomised controlled trial.
8ecelver operaLed
characLerlsLlc (8CC) curve
A graphlcal meLhod of assesslng Lhe accuracy of a dlagnosLlc LesL. SenslLlvlLy ls
ploLLed agalnsL 1-speclflclLy. A perfecL LesL wlll have a poslLlve, verLlcal llnear
slope sLarLlng aL Lhe orlgln. A good LesL wlll be somewhere close Lo Lhls ldeal.
8eference sLandard 1he LesL LhaL ls consldered Lo be Lhe besL avallable meLhod Lo esLabllsh Lhe
presence or absence of Lhe ouLcome Lhls may noL be Lhe one LhaL ls
rouLlnely used ln pracLlce.
8elaLlve rlsk (88) 1he number of Llmes more llkely or less llkely an evenL ls Lo happen ln one
group compared wlLh anoLher (calculaLed as Lhe rlsk of Lhe evenL ln group
A/Lhe rlsk of Lhe evenL ln group 8).
8eporLlng blas See publlcaLlon blas.
8esource lmpllcaLlon 1he llkely lmpacL ln Lerms of flnance, workforce or oLher nPS resources.
8eLrospecLlve sLudy A reLrospecLlve sLudy deals wlLh Lhe presenL/ pasL and does noL lnvolve
sLudylng fuLure evenLs. 1hls conLrasLs wlLh sLudles LhaL are prospecLlve.
8evlew quesLlon ln guldellne developmenL, Lhls Lerm refers Lo Lhe quesLlons abouL LreaLmenL
and care LhaL are formulaLed Lo gulde Lhe developmenL of evldence-based
recommendaLlons.
Secondary ouLcome An ouLcome used Lo evaluaLe addlLlonal effecLs of Lhe lnLervenLlon deemed a
prlorl as belng less lmporLanL Lhan Lhe prlmary ouLcomes.
SelecLlon blas A sysLemaLlc blas ln selecLlng parLlclpanLs for sLudy groups, so LhaL Lhe groups
have dlfferences ln prognosls and/or LherapeuLlc senslLlvlLles aL basellne.
8andomlsaLlon (wlLh concealed allocaLlon) of paLlenLs proLecLs agalnsL Lhls
blas.
Sepsls A severe lllness caused by paLhogenlc organlsms or Lhelr Loxlns.
SenslLlvlLy SenslLlvlLy or recall raLe ls Lhe proporLlon of Lrue poslLlves whlch are correcLly
ldenLlfled as such. lor example ln dlagnosLlc LesLlng lL ls Lhe proporLlon of Lrue
cases LhaL Lhe LesL deLecLs.
See the related term Specificity
SenslLlvlLy analysls A means of represenLlng uncerLalnLy ln Lhe resulLs of economlc evaluaLlons.
uncerLalnLy may arlse from mlsslng daLa, lmpreclse esLlmaLes or
meLhodologlcal conLroversy. SenslLlvlLy analysls also allows for explorlng Lhe
generallsablllLy of resulLs Lo oLher seLLlngs. 1he analysls ls repeaLed uslng
dlfferenL assumpLlons Lo examlne Lhe effecL on Lhe resulLs.
Cne-way slmple senslLlvlLy analysls (unlvarlaLe analysls): each parameLer ls
varled lndlvldually ln order Lo lsolaLe Lhe consequences of each parameLer on
Clossary

193

Lhe resulLs of Lhe sLudy.
MulLl-way slmple senslLlvlLy analysls (scenarlo analysls): Lwo or more
parameLers are varled aL Lhe same Llme and Lhe overall effecL on Lhe resulLs ls
evaluaLed.
1hreshold senslLlvlLy analysls: Lhe crlLlcal value of parameLers above or below
whlch Lhe concluslons of Lhe sLudy wlll change are ldenLlfled.
robablllsLlc senslLlvlLy analysls: probablllLy dlsLrlbuLlons are asslgned Lo Lhe
uncerLaln parameLers and are lncorporaLed lnLo evaluaLlon models based on
declslon analyLlcal Lechnlques (lor example, MonLe Carlo slmulaLlon).
Shock A medlcal emergency ln whlch Lhe organs and Llssues are noL recelvlng an
adequaLe flow of blood. 1hls deprlves Lhe organs and Llssues of oxygen and
allows Lhe bulld up of wasLe producLs, shock can resulL ln serlous damage or
even deaLh.
Slgnlflcance (sLaLlsLlcal) A resulL ls deemed sLaLlsLlcally slgnlflcanL lf Lhe probablllLy of Lhe resulL
occurrlng by chance ls less Lhan 1 ln 20 (p <0.03).
Skln Lurgor An abnormality in the skins ability to change shape and reLurn Lo normal
SpeclflclLy 1he proporLlon of Lrue negaLlves LhaL a correcLly ldenLlfled as such. lor
example ln dlagnosLlc LesLlng Lhe speclflclLy ls Lhe proporLlon of non-cases
lncorrecLly dlagnosed as cases.
See related term Sensitivity.
ln Lerms of llLeraLure searchlng a hlghly speclflc search ls generally narrow and
almed aL plcklng up Lhe key papers ln a fleld and avoldlng a wlde range of
papers.
SLakeholder 1hose wlLh an lnLeresL ln Lhe use of Lhe guldellne. SLakeholders lnclude
manufacLurers, sponsors, healLhcare professlonals, and paLlenL and carer
groups.
SLoma An openlng elLher naLural or surglcal whlch connecLs a porLlon of Lhe body
cavlLy Lo Lhe ouLslde.
SubcuLaneous lor ln[ecLlon, refers Lo beneaLh Lhe skln.
SysLemaLlc revlew 8esearch LhaL summarlses Lhe evldence on a clearly formulaLed quesLlon
accordlng Lo a pre-deflned proLocol uslng sysLemaLlc and expllclL meLhods Lo
ldenLlfy, selecL and appralse relevanL sLudles, and Lo exLracL, collaLe and
reporL Lhelr flndlngs. lL may or may noL use sLaLlsLlcal meLa-analysls.
SysLemlc clrculaLlon ClrculaLlon Lo Lhe whole body
1achycardla lncreased hearL raLe
1achypnoea 8apld breaLhlng l.e. more Lhan 20 breaLhs per mlnuLe (normal raLe ls 12-20
per mlnuLe).
1lme horlzon 1he Llme span over whlch cosLs and healLh ouLcomes are consldered ln a
declslon analysls or economlc evaluaLlon.
1reaLmenL allocaLlon Asslgnlng a parLlclpanL Lo a parLlcular arm of Lhe Lrlal.
unlvarlaLe Analysls whlch separaLely explores each varlable ln a daLa seL.
uLlllLy A measure of the strength of an individuals preference for a specific health
sLaLe ln relaLlon Lo alLernaLlve healLh sLaLes. 1he uLlllLy scale asslgns numerlcal
values on a scale from 0 (death) to 1 (optimal or perfect health). Health
sLaLes can be consldered worse Lhan deaLh and Lhus have a negaLlve value.
volume depleLlon SLaLe of vascular lnsLablllLy characLerlzed by decreased sodlum and waLer ln
Lhe exLracellular space, causes lnclude vomlLlng, excesslve sweaLlng,
dlarrhoea, burns, dlureLlc use and kldney fallure.

Clossary

194

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