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ESPEN Congress Lisbon 2004
Water and electrolytes
Hyperhydration and hypoalbuminemia. How to proceed?
A Sigtes-Sierra
AlbuminAlbumin andand fluid fluid shiftsshifts
WhatWhat isis albuminalbumin andand whatwhat albuminalbumin isis meantmeant forfor??
•• STRUCTURE STRUCTURE andand KINETICSKINETICS-- Globular Globular proteinprotein (60,000 (60,000 daltondalton MW)MW)-- HalfHalf--lifelife ofof 21 21 daysdays-- IntraIntra (40%) (40%) andand extravascularextravascular (60%) (60%) poolspools-- Total Total albuminalbumin massmass = 250= 250--300 grs.300 grs.-- ReferenceReference valuesvalues forfor [s[s--albalb]: 35]: 35--50 g/L50 g/L
•• FUNCTIONFUNCTION-- Fluid Fluid shiftsshifts acrossacross capillarycapillary membranemembrane-- TransportTransport proteinprotein
AlbuminAlbumin as a as a riskrisk factorfactorShort Short termterm, general , general surgerysurgery
AlbuminAlbumin in in compositecomposite nutritionnutrition indicesindices
SeltzerSeltzer (1979)(1979) SS--albalb + + lymphocyteslymphocytesBuzbyBuzby (1980)(1980) SS--albalb + TSK, + TSK, transferrintransferrin, DHT, DHTDetskyDetsky (1987) (1987) SS--albalb + + subjectivesubjective assessmentassessmentChristouChristou (1989)(1989) SS--albalb + + anergyanergyWindsorWindsor (1988)(1988) SS--albalb + + organorgan failurefailureBuzbyBuzby (1991) (1991) SS--albalb + + weightweight lossloss
AlbuminAlbumin as a as a riskrisk factorfactor
TheThe hypoalbuminaemichypoalbuminaemic patientpatient::a a metabolicmetabolic cripplecripple
•• AlteredAltered bodybody compostioncompostion•• DiminishedDiminished musclemuscle strengthstrength•• HigherHigher APACHE II APACHE II scoresscores•• DerangedDeranged endocrineendocrine responseresponse•• WorseWorse organorgan functionfunction•• ImmunesuppressionImmunesuppression•• ComorbidityComorbidity•• OldOld ageage
AlbuminAlbumin metabolismmetabolism
IntakeIntakeMuscleMuscle
Plasma Plasma aminoacidsaminoacidsNormal Normal metabolicmetabolic pathwayspathways
HepaticHepatic synthesissynthesis (14g/(14g/dayday))
IntravascularIntravascularalbuminalbumin
(120g; 40%)(120g; 40%)
ExtravascularExtravascularalbuminalbumin
(180g; 60%)(180g; 60%)(120g/(120g/dayday))
TissueTissue catabolismcatabolism(12g/(12g/dayday))
LossesLosses:: RenalRenal (0.4g/(0.4g/dayday))IntestinalIntestinal (1.0g/(1.0g/dayday))
((WhicherWhicher, 1987), 1987)
AlbuminAlbumin metabolismmetabolism
IntakeIntakeMuscleMuscle
PathogenesisPathogenesis ofof hypoalbuminaemiahypoalbuminaemia
Plasma Plasma aminoacidsaminoacids
HepaticHepatic synthesissynthesis (14g/(14g/dayday))
IntravascularIntravascularalbuminalbumin
(120g; 40%)(120g; 40%)
ExtravascularExtravascularalbuminalbumin
(180g; 60%)(180g; 60%)(120g/(120g/dayday))
TissueTissue catabolismcatabolism(12g/(12g/dayday))
LossesLosses:: RenalRenal (0.4g/(0.4g/dayday))IntestinalIntestinal (1.0g/(1.0g/dayday))
((WhicherWhicher. 1987). 1987)
AlbuminAlbumin metabolismmetabolism
IntakeIntakeMuscleMuscle
PathogenesisPathogenesis ofof hypoalbuminaemiahypoalbuminaemia
Plasma Plasma aminoacidsaminoacids
HepaticHepatic synthesissynthesis (14g/(14g/dayday))
IntravascularIntravascularalbuminalbumin
(120g; 40%)(120g; 40%)
ExtravascularExtravascularalbuminalbumin
(180g; 60%)(180g; 60%)(120g/(120g/dayday))
TissueTissue catabolismcatabolism(12g/(12g/dayday))
LossesLosses:: RenalRenal (0.4g/(0.4g/dayday))IntestinalIntestinal (1.0g/(1.0g/dayday))
((WhicherWhicher. 1987). 1987)
AlbuminAlbumin distributiondistribution
45 (g/L)45 (g/L)
VascularVascularspacespace
InterstitialInterstitialspacespace
ExcludedExcludedspacespace
AvailableAvailablespacespace
AlbuminAlbumin in in thethe ExtracellularExtracellular WaterWater CompartmentCompartmentPhysiologyPhysiology
AlbuminAlbumin andand fluid fluid shiftsshiftsPhysiologyPhysiology
StarlingStarling’s Law’s Law
Net Net filtrationfiltration = = Lp*SLp*S ((∆∆ OncoticOncotic PP -- ∆∆ hydraulichydraulic P)P)
Net Net filtrationfiltration = = Lp*SLp*S ((σ σ ((ΠΠcc--ΠΠii) ) -- ((PPcc--PPii))))σ σ = = reflectionreflection coefficientcoefficient (0(0--1, 1, permeabilitypermeability toto proteinsproteins))
RoseRose & Post, 5th & Post, 5th EditionEdition
AlbuminAlbumin distributiondistribution
45 (g/L)45 (g/L)PathophysiologyPathophysiology
29 (g/L)29 (g/L)
ECWECW ECWECW
VascularVascularspacespace
InterstitialInterstitialSpaceSpace
((hyaluronanhyaluronan gelgelmatrixmatrix))
ExcludedExcludedspacespace
AvailableAvailablespacespace
ProbablyProbably allall hypoalbuminaemichypoalbuminaemic patientspatients havehave ECW ECW expansionexpansion
66
88
1010
1212
1414
HaemoglobinHaemoglobin(g/dL)(g/dL)
p =0.02p =0.02
NonNon--expandedexpandedECW < 25 % wECW < 25 % w
(n=20)(n=20)
ExpandedExpandedECW ECW ≥≥ 25% w25% w
(n=30)(n=30)
ØØ Tumor*Tumor*(mm)(mm)
3030
4040
5050
6060
7070 p =0.002p =0.002
3030
3232
3434
3636
3838
4040 p =0.02p =0.02
AlbuminAlbumin(g/L)(g/L)
*n=23*n=23 n=12n=12
AlbuminAlbumin andand ECW in ECW in cancercancer patientspatients
DistributionalDistributional hypoalbuminaemiahypoalbuminaemiaPathophysiologyPathophysiology
29 (g/L)29 (g/L)
HighHigh/Normal//Normal/LowLow plasma plasma volumevolume
ExpandedExpanded interstitialinterstitial volumevolumeIncreasedIncreased availableavailable spacespace
ReducedReduced excludedexcluded spacespace
ECWECW
ECW ECW increaseincreaseA. A. InterstitialInterstitial illnessillness
B. B. CapillaryCapillary leakleaksyndromesyndrome
PlasmaPlasmacompartmentcompartment
……albumin shiftsalbumin shifts
AvailableAvailableinterstitiuminterstitium
HyaluronanHyaluronangellygelly matrixmatrix
……oedema developsoedema develops
……albumin shiftsalbumin shifts
PlasmaPlasmacompartmentcompartment
AvailableAvailableinterstitiuminterstitium
HyaluronanHyaluronangellygelly matrixmatrix
……oedema developsoedema developsEndotoxinEndotoxin / / CytokinesCytokines
DistributionalDistributional hypoalbuminaemiahypoalbuminaemia
ConvectiveConvective transporttransport ofof albuminalbumin(Fluid ((Fluid (over)loadsover)loads))
Fluid loadFluid load
……oedema developsoedema develops ……albumin shiftsalbumin shifts
MullinsRJMullinsRJ 19891989
DistributionalDistributional hypoalbuminaemiahypoalbuminaemia
ConvectiveConvective transporttransport ofof albuminalbumin(2L/1h fluid load in normal (2L/1h fluid load in normal volounteersvolounteers))
0 1 2 3 4 5 675
80
85
90
95
100
105
Time (hours)
% c
hang
e in
ser
umal
bum
inP=0.002
SalineDextrose
Lobo et al., Clin Sci 2001
DistributionalDistributional hypoalbuminaemiahypoalbuminaemia
ConvectiveConvective transporttransport ofof albuminalbumin(2L/1h fluid load in normal (2L/1h fluid load in normal volounteersvolounteers))
0 1 2 3 4 5 690
92
94
96
98
100
102
Time (hours)
% c
hang
e in
haem
atoc
ritP=0.01
SalineDextrose
Lobo et al., Clin Sci 2001
HypoalbuminaemiaHypoalbuminaemia
TherapeuticTherapeutic approachesapproaches
•• TreatTreat fundamental fundamental illnessillness•• NegativeNegative ECW balanceECW balance
•• DiureticsDiuretics•• WaterWater andand NaNa restrictionrestriction
•• CombinationCombination therapytherapy•• NutritionNutrition supportsupport ifif malnutritionmalnutrition•• Human Human serumserum albuminalbumin??
HypoalbuminaemiaHypoalbuminaemia
TherapeuticTherapeutic approachesapproaches in in differentdifferent scenariosscenarios
•• ElectiveElective cancercancer surgerysurgery•• ObstructiveObstructive jaundicejaundice•• AcuteAcute injuryinjury::
•• PolytraumaPolytrauma•• BurnsBurns•• InfectiousInfectious diseasedisease
•• PostoperativePostoperative complicationscomplications•• MalabsorptionMalabsorption/SBS/SBS
HypoalbuminaemiaHypoalbuminaemia in in gastricgastric cancercancer
A A patientpatient withwith gastricgastric cancercancer
•• 76 76 yryr. . oldold malemale withwith epigastricepigastric painpain•• GastricGastric adenocarcinomaadenocarcinoma ((bodybody))•• WeightWeight lossloss ofof 16%16%•• SS--albalb 28 g/L28 g/L•• HbHb 9 g/dl 9 g/dl •• CandidateCandidate forfor total total gastrectomygastrectomy
HypoalbuminaemiaHypoalbuminaemia in in gastricgastric cancercancer
A A patientpatient withwith gastricgastric cancercancer
•• ECW ECW measurementmeasurement ((bioimpedancebioimpedance))•• Oral/Oral/EnteralEnteral refeedingrefeeding•• IronIron//BloodBlood transfusiontransfusion•• OmeprazolOmeprazol•• PhysiotherapyPhysiotherapy•• FurosemideFurosemide (10(10--40 40 mgmg//dayday) )
HypoalbuminaemiaHypoalbuminaemia in in obstructiveobstructive jaundicejaundice
A A patientpatient withwith obstructiveobstructive jaundicejaundice
•• 68 68 yryr. . malemale withwith malignantmalignant obstructiveobstructive jaundicejaundice•• CholangiocarcinomaCholangiocarcinoma (distal 1/3 CBD)(distal 1/3 CBD)•• WeightWeight lossloss 18%18%•• SS--albalb 31 g/L31 g/L•• No No clinicalclinical signssigns ofof cholangitischolangitis•• PotentialPotential candidatecandidate toto pancreaticoduodenectomypancreaticoduodenectomy
HypoalbuminaemiaHypoalbuminaemia & & jaundicejaundice
BenignBenign MalignantMalignant PP
Ideal Ideal bodybody weightweight 97±1197±11 88±1588±15 .03.03BilirubinBilirubin mgmg/dl/dl 9±69±6 15±915±9 .04.04AlkAlk PhosPhos U/LU/L 366±330 366±330 1068±9101068±910 .003.003EndotoxinEndotoxin (EU/ml)(EU/ml) 17±1017±10 10±910±9 NSNSTNFTNF--αα ((pgpg/ml)/ml) 32±2632±26 87±6787±67 .01.01CCK (CCK (pmolpmol/L)/L) 2.5±22.5±2 3.9±1.43.9±1.4 .05.05SS--albuminalbumin (g/L)(g/L) 35±335±3 30±430±4 0.0050.005
PadilloPadillo J et al., World J J et al., World J SurgSurg 20012001
HypoalbuminaemiaHypoalbuminaemia & g.i. & g.i. cancercancerHypoalbuminaemiaHypoalbuminaemia in in obstructiveobstructive jaundicejaundice
ImprovedImproved foodfood intakeintake afterafter internalinternal biliarybiliary drainagedrainage
800
900
1000
1100
1200
1300
1400
1500
1600
1700
0 2 3 4 5 6
BenignMalignant
** ** **
** **
PadilloPadillo FJ et al, 2001FJ et al, 2001
HypoalbuminaemiaHypoalbuminaemia afterafter resuscitationresuscitation
•• 69 69 yryr. . femalefemale withwith postoperativepostoperative peritonitisperitonitis•• BP 90/50 BP 90/50 mmHgmmHg, , metabolicmetabolic acidosis, oliguriaacidosis, oliguria•• ResuscitationResuscitation: : fluidsfluids, , antibioticsantibiotics, , surgerysurgery•• DayDay 3: S3: S--albalb 21 g/dl, 21 g/dl, dependentdependent oedemaoedema•• PostoperativePostoperative coursecourse: BP : BP unstableunstable, oliguria, oliguria•• VentilatorVentilator andand dopaminedopamine requiredrequired
ProblemsProblems afterafter anan anterior anterior resectionresection forfor rectal rectal cancercancer
HypoalbuminaemiaHypoalbuminaemia afterafter resuscitationresuscitation
Do Do notnot use use albuminalbumin forfor resuscitationresuscitationNegativeNegative oror incocnlusiveincocnlusive datadata
Human Human albuminalbumin solutionsolution forfor resuscitationresuscitation andand volumevolume expansionexpansion in in criticallycritically illillpatientspatients. . AldersonAlderson P et al. P et al. CochraneCochrane DatabaseDatabase SystSyst RevRev 2002; (1):CD001208.2002; (1):CD001208.
HypoalbuminemiaHypoalbuminemia in in acuteacute illnessillness: : isis therethere a a rationalerationale forfor interventionintervention? A meta? A meta--analysisanalysis ofof cohortcohort studiesstudies andand controlledcontrolled trialstrials. . VincentVincent JL et al. JL et al. AnnAnn SurgSurg 2003; 237:3192003; 237:319--34.34.
A A comparisoncomparison ofof albuminalbumin andand salinesaline forfor fluid fluid resuscitationresuscitationSAFE SAFE GroupGroup. N . N EnglEngl J J MedMed 2004; 350:22472004; 350:2247--56.56.
HypoalbuminaemiaHypoalbuminaemia afterafter resuscitationresuscitation
ProblemsProblems afterafter anan anterior anterior resectionresection forfor rectal rectal cancercancer
GuiraoGuirao et al., J et al., J SurgSurg Res 1995Res 1995
rr22= 0.87= 0.87p= 0.0007p= 0.0007
2020
1010
00
--1010--3030 --2525 --2020 --1515 --1010 --55 00
AlbuminAlbumin decreasedecrease prepre--TPN (g/l)TPN (g/l)
NaNa balance balance 00--3d TPN3d TPN((mEqmEq/3d)/3d)
HypoalbuminaemiaHypoalbuminaemia afterafter resuscitationresuscitation
ProblemsProblems afterafter anan anterior anterior resectionresection forfor rectal rectal cancercancer
GuiraoGuirao et al., J et al., J SurgSurg Res 1995Res 1995
rr22= 0.9= 0.9p= 0.0001p= 0.0001
400400
350350
300300
250250
200200--3030 --2525 --2020 --1515 --1010 --55 00
AlbuminAlbumin decreasedecrease prepre--TPN (g/l)TPN (g/l)
ECW / ECW / kgkg endend TPNTPN(ml/(ml/kgkg))
HypoalbuminaemiaHypoalbuminaemia afterafter resuscitationresuscitation
ProblemsProblems afterafter anan anterior anterior resectionresection forfor rectal rectal cancercancerManagementManagement ofof hypoalbuminaemiahypoalbuminaemia
•• ImproveImprove haemodynamicshaemodynamics•• EnhanceEnhance diuresisdiuresis•• PromotePromote a a negativenegative ECW balanceECW balance•• StartStart TPN in a TPN in a stablestable patientpatient•• LowLow sodiumsodium//waterwater TPNTPN
HypoalbuminaemiaHypoalbuminaemia in in malabsorptionmalabsorption
•• 54 54 yryr. . malemale withwith massivemassive SB SB resectionresection•• VenousVenous thrombosisthrombosis. 45 cm. SB . 45 cm. SB withwith coloncolon•• PostoperativePostoperative diarrheadiarrhea. TPN . TPN forfor 2 2 mosmos..•• 2 2 mosmos. . afterafter weaningweaning: : ankleankle oedemaoedema, 15% , 15% weightweight lossloss, , paresthesiaeparesthesiae, s, s--albalb: 22 g/L. : 22 g/L. CaCa: 6.5 : 6.5 mgmg/dl. /dl. MgMg: 0.5 : 0.5 mgmg/dl/dl•• AdmittedAdmitted forfor lobarlobar pneumoniapneumonia
Short Short bowelbowel syndromesyndrome
HypoalbuminaemiaHypoalbuminaemia & TPN& TPN
HypoalbuminaemiaHypoalbuminaemia duringduring i.v. i.v. refeedingrefeeding
NonNon--respondersrespondersRespondersResponders
∆ Weight∆ Weight-3-3-2-2-1-1001122
--1.51.5--11
--0.50.500
111.51.522
∆ Albumin∆ Albuminlbslbs g/Lg/L StarkerStarker et al. et al. AnnAnn SurgSurg 19831983
HypoalbuminaemiaHypoalbuminaemia & TPN& TPN
HypoalbuminaemiaHypoalbuminaemia duringduring i.vi.v. . refeedingrefeeding∆∆
in a
lbum
in (g
/l)in
alb
umin
(g/l)
-5
0
5
10
15
20 R=R=--0.61 0.61 PP=0.003=0.003
-25 -20 -15 -10 -5 0
∆∆ in weight (kg)in weight (kg)Lobo et al., Lobo et al., ClinClin NutrNutr 19991999
HypoalbuminaemiaHypoalbuminaemia & TPN& TPN
HypoalbuminaemiaHypoalbuminaemia duringduring i.vi.v. . refeedingrefeedingPreoperativePreoperative malnutritonmalnutriton. TPN . TPN forfor 10 10 daysdays
Standard Diet Low NaStandard Diet Low Na--water diet Pwater diet Pn =19 n =22n =19 n =22
________________________________________________________________________________________________________________
SS--albumin (g/L)albumin (g/L) 31.731.7±±4.14.1 35.335.3±±3.83.8 0.0080.008∆∆ SS--albumin (g/L)albumin (g/L) --0.70.7±±2.82.8 2.32.3±±3.53.5 0.0060.006∆∆ Weight (Kg)Weight (Kg) 0.80.8±±0.90.9 --1.51.5±±1.11.1 0.00010.0001Daily Daily diuresisdiuresis ((mLmL)) 1,2301,230±±310310 959959±±245245 0.0030.003Water balance (10 d)Water balance (10 d) 478478±±11341134 --10911091±±12561256 0.0010.001Na balance (Na balance (mEqmEq/day)/day) 4040±±33 --2727±±1818 0.00010.0001Urea (mg/dL)Urea (mg/dL) 4141±±1212 6161±±3434 0.020.02
Gil J et al. Gil J et al. NutritionNutrition 19971997