Basic FluidBasic Fluid--Electrolyte Electrolyte Disorder & TherapyDisorder & Therapy

ศ.พญ. สณุีรตัน ์คงเสรพีงศ์

ภาควิชาวิสญัญีวิทยา

คณะแพทยศาสตรศ์ิรริาชพยาบาล

Fluid Management in Fluid Management in Critically Ill PatientCritically Ill Patient

ศ.พญ. สณุีรตัน ์คงเสรพีงศ์

ภาควิชาวิสญัญีวิทยา

คณะแพทยศาสตรศ์ิรริาชพยาบาล

WhWh II I t tI t t ??WhyWhy IsIs ImportantImportant ??

Most common management & Rx

Most common pitfall & complicationsp p

May make a difference between organ protection & organ failureorgan failure

Others organ protective activities

Indication: replacementIndication: replacementMaintenance

Insensible & sensible lossInsensible & sensible loss

Hemorrhage, sepsis

WhWh II I t tI t t ??WhyWhy IsIs ImportantImportant ??

Influence outcomes– Right time to replace

Right type– Right type

– Right amount

– Right evaluation

BenefitBenefit of fluid replacementof fluid replacement

Maintenance effective circulatory volume

Maintain oxygen perfusion (renal, mesenteric, CNS,

cardiac)cardiac)

Optimize oxygen transport & cellular respirationp yg p p

Better “quality” of recovery

Provide electrolyte replacement

Ri kRi k f fl id lf fl id lRiskRisk of fluid replacementof fluid replacement

Interstitial edema

C t t l dCompartmental syndrome

Impair cellular metabolismp

Poor wound healing

Decrease pulmonary compliance

Left heart failure/overloadLeft heart failure/overload

Delayed return of bowel function

Body Fluid DistributionBody Fluid DistributionBody Fluid Distribution Body Fluid Distribution

ECF (E ll l fl id)ECF (E ll l fl id)ECF (Extracellular fluid)ECF (Extracellular fluid)

Sodium….major cation (140mEq/L), major osmotically active ion in the ECF

T t l b d N t t d t i ECF lTotal body Na content determine ECF volume

ECF (PV + ISF)

PV fi ECF ff i l l– PV …first ECF space …effective plasma volume

• Hypovolemia……decrease effective circulating plasma lvolume

• Increase ECF while decrease PVH t f ilHeart failure

Hypoalbuminemia

Inflammatory capillary leak syndromey p y y

ECF (E ll l fl id)ECF (E ll l fl id)ECF (Extracellular fluid)ECF (Extracellular fluid)

ECF (ISF + PV)

– ISF • …Second ECF space

• … Third space…..edema fluid (cannot be mobilized by diuresis, dialysis, fl id t i ti bili d t l h i fl tior fluid restriction……mobilized spontaneously when inflammation

subsides…….fluid move back to PV…eliminate by normal renal homeostasis

Impact of fluid replacement onImpact of fluid replacement onImpact of fluid replacement on Impact of fluid replacement on ECF compartmentECF compartment

Various fluid solution expand volume of fluid

compartments differentially base oncompartments differentially base on

Water content (osmolarity) of the fluid

Extent of capillary leak

Pre-existing water deficits in the various fluid compartment

HumoralHumoral Factor Affecting Fluid StatusFactor Affecting Fluid Status

Renin-angiotensin-aldosterone axis

Anti-diuretic hormone (ADH)

Atrial natriuretic peptide (ANP)Atrial natriuretic peptide (ANP)

Brain natriuretic peptide (BNP)

C-type natriuretic peptide (CNP)

Capillary endotheliumCapillary endothelium

Water moves freely through vessel wall: water, Na+, K+

Impermeable to larger molecule

AlbuminAlbumin

Semisynthetic colloid eg., gelatin, starches

Perioperative factors :

– Vasoconstriction

– Vasodilatation

Increase capillary permeability eg sepsis– Increase capillary permeability eg., sepsis

Vascular barrierVascular barrier

Rationale for Intravascular FluidRationale for Intravascular Fluid Replacement Therapy

Correction of circulating ECF volumeCorrection of circulating ECF volume

Maintenance of cardiac output & organ perfusionMaintenance of cardiac output & organ perfusion

C ti f i t ll l t d fi itC ti f i t ll l t d fi itCorrection of intracellular water deficitCorrection of intracellular water deficit

Treatment of electrolyte abnormalitiesTreatment of electrolyte abnormalitiesyy

Nutrition Nutrition

Current Controversies of Fluid & Volume Current Controversies of Fluid & Volume Management

oo Amount of Fluid ReplacementAmount of Fluid Replacement

oo Type of Fluid ReplacementType of Fluid Replacement

Monitoring of fluid responsiveness & adequacy of Monitoring of fluid responsiveness & adequacy of oo Monitoring of fluid responsiveness & adequacy of Monitoring of fluid responsiveness & adequacy of fluid replacementfluid replacement

A t f Fl id R l tAmount of Fluid Replacement

Controversies:Controversies:–– Liberal fluid resuscitation Liberal fluid resuscitation

–– Restricted fluid resuscitationRestricted fluid resuscitation

–– Optimal fluid resuscitation: Goal direct therapyOptimal fluid resuscitation: Goal direct therapy

Amount of Fluid ReplacementAmount of Fluid Replacement

Liberate fluid resuscitation Liberate fluid resuscitation

Pro Pro : Maximal tissue perfusion, good urine flow: Maximal tissue perfusion, good urine flowp , gp , g

Need to replace third space lossNeed to replace third space loss

Replace crystalloid Replace crystalloid 3 3 times of blood losstimes of blood lossp yp y

Con : Con : Fluid overloadFluid overload

Tissue edemaTissue edema

»» Poor microcirculation flow/perfusionPoor microcirculation flow/perfusion

»» Poor oxygenation/ventilationPoor oxygenation/ventilation

Increase close space volume/pressureIncrease close space volume/pressure

Degrade endothelial Degrade endothelial glycocalyxglycocalyx (increase ANP)(increase ANP)

Most common cause of iatrogenic hypervolemia

Very little fluid lost as third space during surgery (eg., 0.5-1 ml/kg instead of 10 ml/Kg)

Jacob M, et, 2009

Amount of Fluid ReplacementAmount of Fluid Replacement

Restricted fluid resuscitation Restricted fluid resuscitation

•• Prevent tissue edema/injury: Major traumatic /conditionPrevent tissue edema/injury: Major traumatic /condition–– TraumaTrauma

–– BurnsBurns

–– SurgerySurgerySurgerySurgery

–– Ischemia Ischemia

–– Good outcome in colonic surgeryGood outcome in colonic surgery

•• How much of the restriction ?How much of the restriction ?–– Low/poor perfusionLow/poor perfusion

–– Low microcirculatory flowLow microcirculatory flowLow microcirculatory flowLow microcirculatory flow

–– Mislead with Mislead with vasopressorvasopressor

Amount of Fluid ReplacementAmount of Fluid Replacement

Optimal fluid resuscitation Optimal fluid resuscitation

• Goal direct therapy as per patients/conditions needpy p p

• Maintain intravasal normovolemia

• Most recommend• Most recommend

• Most difficult to do

• How much optimum?

•• Good monitoring/assessment Good monitoring/assessment

•• Goal directed therapyGoal directed therapy

Type of Fluid ResuscitationType of Fluid Resuscitation

Controversies: Controversies: C t ll id C ll idCrystalloid vs Colloid

Crystalloid : Isotonic vs hypertonic

Colloid : Iso-oncotic vs hyperoncotic

What/When should we use?

C t ll id C t ll id C ll id it ti f th C iti ll Ill tiC ll id it ti f th C iti ll Ill tiCrystalloid Crystalloid vsvs Colloid resuscitation for the Critically Ill patieColloid resuscitation for the Critically Ill patie

Crystalloid: Type: Isotonic Type: Isotonic

NSSNSS....non balance solution, non balance solution, hyperchloremichyperchloremic metabolic acidosismetabolic acidosis..Effect on renal function & coagulation..Effect on renal function & coagulation

LRSLRS balance lactic acidosis metabolic alkalosisbalance lactic acidosis metabolic alkalosisLRS LRS ....balance, lactic acidosis, metabolic alkalosisbalance, lactic acidosis, metabolic alkalosis:: HypertonicHypertonic33%, %, 77..55% NSS% NSS……high high osmolalityosmolality, shift fluid from interstitial to intravascular, shift fluid from interstitial to intravascular

…increase plasma volume …increase plasma volume 55--8 8 cc/cccc/cc……HypernatremiaHypernatremia, cellular dehydration, cellular dehydration…Depress immune response…Depress immune response

Pro: Pro: Clean, easily use, less allergy, less accumulation, good urine flowClean, easily use, less allergy, less accumulation, good urine flowCon: Con: Need more amount , less stay in intravascular, more tissue edemaNeed more amount , less stay in intravascular, more tissue edema

C t ll id C t ll id C ll id it ti f th C iti ll Ill tiC ll id it ti f th C iti ll Ill tiCrystalloid Crystalloid vsvs Colloid resuscitation for the Critically Ill patieColloid resuscitation for the Critically Ill patie

Colloid: Type: Natural: Type: Natural: Blood, blood component, albuminBlood, blood component, albuminypyp , p ,, p ,

Synthetic starch: Synthetic starch: Gelatin, Gelatin, HydroxyHydroxy Ethyl Starch (HES)Ethyl Starch (HES)Pro: Pro: Stay in the intravascular longerStay in the intravascular longer

AntiAnti--inflammatory propertyinflammatory propertyCon: Con: AllergyAllergy

AccumulationAccumulationAccumulationAccumulationRenal effectRenal effectHematological problemHematological problem

Hypertonic Lactate Saline resuscitation Reduced the risk of AbdomHypertonic Lactate Saline resuscitation Reduced the risk of Abdom

Compartment Syndrome in Severely Burned PatientsCompartment Syndrome in Severely Burned Patients. . OdaOda J. J Trauma, J. J Trauma, 20062006

Patients admitted to our burn unit between 2002 and 2004 with burns > or =40% of the total body surface area without severe inhalation injury were entered into afluid resuscitation protocol using HLS (n = 14) or lactated Ringer's solution (n = 22).

HLS resuscitation could reduce the risk of secondary abdominal

compartment syndrome with lower fluid load in burn shock patients

Blood Transfusion

T f i T iTransfusion Trigger

Controversy in blood transfusionPPro:

increase oxygen carrying capacityyg y g p y

especially in the patient with territory of organ f i i bl diperfusion or ongoing bleeding

optimal Hb concentration to maintain systemic oxygen delivery in critically ill patient is 10 gram ????????

T f i T iTransfusion Trigger

Con:Cell mediated transfusion immunosuppression tumorCell-mediated transfusion immunosuppression, tumor recurrence, postoperative infectionEarly transfusion is a strong independent risk factor ofEarly transfusion is a strong independent risk factor of multiple organ failureStore red cell ….decrease deformability on ymicrocirculation

Alb iAlbumin5% albumin20%, 25% albumin

hyperoncotic..1c.c. increase 18 ml.Natural MW 66 000 daltonNatural , MW 66,000 dalton

> 90% stay in 2 hoursAnaphylactoid, anphylaxis .003-1.53%No problem with coagulation

AlbuminAlbumin

•• Natural colloid, Natural colloid, 585 585 amino acid, amino acid, MWMW 6666 kDkDa a (renal threshold (renal threshold 4545--55 55 kDakDa))

•• Ellipsoid molecule, nonEllipsoid molecule, non--viscous, very flexible, help preserve the structure of RBCviscous, very flexible, help preserve the structure of RBC

•• Minimal problem with coagulationMinimal problem with coagulation, , AnaphylactoidAnaphylactoid//anphylaxisanphylaxis 00..003003--11..5353%%

•• Synthesis in liver (Synthesis in liver (3030% of total) can compensate % of total) can compensate 22--5 5 time to compensate albumin loss; time to compensate albumin loss;

synthesis depend on synthesis depend on

-- Nutritional status with availability of amino acids and caloriesNutritional status with availability of amino acids and calories

-- Hormonal environment : growth hormone, Hormonal environment : growth hormone, adrenocorticotropicadrenocorticotropic hormones, insulin, hormones, insulin,

testosteronetestosterone

•• Depress albumin synthesisDepress albumin synthesis•• Depress albumin synthesisDepress albumin synthesis

-- Inflammatory state, with inflammatory cytokine Inflammatory state, with inflammatory cytokine egeg. TNF, IL. TNF, IL--66, reduce the availability of , reduce the availability of albumin messenger RNA, decrease albumin synthesisalbumin messenger RNA, decrease albumin synthesis

Vascular barrier

Hypoalbuminemia & Critically Ill PatientHypoalbuminemia & Critically Ill Patient

o Vincent JL, et al. 2003

Meta-analysis ….hypoalbuminemia as an outcome predictor in acutely ill patient

o Hypoalbuminemia was a dose dependant predictor of poor outcome

o Each 1 g/dl decrease in serum albumin increase the odds of mortalityo Each 1 g/dl decrease in serum albumin increase the odds of mortality 137%, morbidity 89%, prolonged ICU stay by 28%

o Independent of patient’s nutritional status & inflammatory statuso Gibb J, 1999

NationalVeterans Administration Surgical Risk Study of 54,215 major noncardiac surgery cases, preoperative serum albumin concentrations g y , p pwere the strongest predictor of surgical mortality and morbidity

HypoalbuminemiaHypoalbuminemia

Question???Question???

--HypoalbuminemiaHypoalbuminemia causes the worse outcome: causes the worse outcome: provide exogenous albuminprovide exogenous albumin

--Is the simple marker of more serious disease: Is the simple marker of more serious disease: improve albumin concentration may have no effectimprove albumin concentration may have no effect

Vincent JL, BMJ Vincent JL, BMJ 20062006

--The aim of the study was to show that albumin administration is safe or notThe aim of the study was to show that albumin administration is safe or notThe aim of the study was to show that albumin administration is safe or notThe aim of the study was to show that albumin administration is safe or not

--All patient who needed a fluid challenge for what All patient who needed a fluid challenge for what evereevere reason were include, reason were include, regardlessregardless of the underlying conditionof the underlying condition

--It is therefore unreasonable to expect the study to show the benefit of albumin It is therefore unreasonable to expect the study to show the benefit of albumin administrationadministration

The question that we need to answer is which subgroup of patient are likely toThe question that we need to answer is which subgroup of patient are likely to--The question that we need to answer is which subgroup of patient are likely to The question that we need to answer is which subgroup of patient are likely to benefit from albumin administrationbenefit from albumin administration

1212//1818//5252 Update fluid mangement for critically ill surgical ptsUpdate fluid mangement for critically ill surgical pts

AA furtherfurther analysisanalysis ofof thethe SAFESAFE studystudy assessesassesses whetherwhether outcomesoutcomesstudystudy assessesassesses whetherwhether outcomesoutcomesofof resuscitationresuscitation withwith salinesaline oror albuminalbumin areare relatedrelated toto baselinebaseline serumserum albuminalbumin concentrationsconcentrations, , predefinedpredefined asas serumserum albuminlessalbuminless thanthan oror greatergreater thanthan 22..5 5 g/l.g/l.

. Gelatin• Polygelin, Succinylte gelatin

MW 30 000 40 000 dalton• MW 30,000-40,000 dalton• Good clear• Length 3-4 hour• No renal or coagulation problemg p• Anaphylaxis or anaphylactoid

Dilution effect• Dilution effect

G l iGelatins

Hydrolysis of bovine collagen

Risks associated between new-variant Creutzfeldt-Jakob disease & bovineCreutzfeldt Jakob disease & bovine spongiform encephalitis (BSE)

D t 40 70Dextran 40, 70

• Clearance is dependant on MW

• Dextrans molecule < 50-55000 Da are freely filtered at the renal glomerulusfreely filtered at the renal glomerulus

• 70% of dextran 40 will be excrete into 0% o de t a 0 be e c ete tourine within 24 hours

Hydroxyethyl StarchsHydroxyethyl Starchs

Has greater volume expansionHas greater volume expansion

Longer intravascular persistence than crystalloidsLonger intravascular persistence than crystalloids

DecreaseDecrease microvascularmicrovascular permeability & capillarypermeability & capillaryDecrease Decrease microvascularmicrovascular permeability & capillary permeability & capillary

leakage by biophysically leakage by biophysically pulggingpulgging endothelial leaksendothelial leaks

Exerting an antiExerting an anti--inflammatory effectinflammatory effect

D i ti ti f d th li l llD i ti ti f d th li l llDecreasing activation of endothelial cellsDecreasing activation of endothelial cells

Hydroxyethyl StarchsHydroxyethyl Starchs

Question aboutQuestion about

–– SafetySafety

–– Side effectSide effectSide effectSide effect

–– Clinical use Clinical use

HydroxyethylHydroxyethyl StarchsStarchs (HES) (HES) : : y y yy y y ( )( )Different Products Different Products -- Different Effects. Different Effects. WestphalWestphal M.M. Anesthesiology Anesthesiology 20092009..

• Concentration , Molecular weight, Molar substitution (MS), CConcentration , Molecular weight, Molar substitution (MS), C22/C/C6 6 g ( )g ( ) 22 6 6 RatioRatio

• Concentration: Concentration: The higher concentration (The higher concentration (egeg. . 66%, %, 1010%), the more volume expansion effect%), the more volume expansion effect

•• CC22/C/C6 6 RatioRatio•• Molecular weight Molecular weight (MW)(MW)CC22/C/C6 6 RatioRatio (MW)(MW)

•• The higher molecular weight, theThe higher molecular weight, theHigher CHigher C22/C/C6 6 Ratio difficult to destroy by Ratio difficult to destroy by alpha amylasealpha amylase The higher molecular weight, the The higher molecular weight, the

longer stay in the intravascular, the longer stay in the intravascular, the more accumulationmore accumulation•• PolydispersePolydisperse colloidcolloid

p yp y-- Corn (Waxy maize) starch Corn (Waxy maize) starch

(C(C22/C/C6 6 Ratio Ratio 00..9797))-- Potato starch Potato starch yy

•• MW MW 4545--60 60 KDA rapidly excrete KDA rapidly excrete via kidneyvia kidney••OncoticOncotic pressure depend on pressure depend on amount of moleculeamount of molecule

(C(C22/C/C6 6 Ratio Ratio 00..4242))

amount of molecule amount of molecule

Molar substitution (MSMolar substitution (MS((Higher difficult to destroy by alpha amylase

- Heta starch (MS 0.6) 1st generation

- Penta starch (MS 0.5) 2nd generation

- Tetrastarch 3rd generation

(Voluven® Volulyte ® MS 0 4(Voluven®, Volulyte ®, MS 0.4

Tetraspan ® 0.42-0.45 )

••Lehnann G, 2007

Corn & Potato derive HES solution are not bioequivalent, study using one type may not q , y g yp ybe valid for another

Sommermeyer et al

P t t d i HES h hi h i t i iPotato derive HES has a higher intrinsic viscosity than Corn derived HES

Pharmacokinetic &Pharmacokinetic &Pharmacokinetic & Pharmacokinetic & Plasma ConcentrationPlasma Concentration

1st ti

HES Different Generation

1st generation Hexastarch (MS 0.6)

2nd generation2 generationPentastarch (MS 0.5)

33rdrd generationgeneration33 generationgenerationTetrastarchTetrastarch

VoluvenVoluven® MS ® MS 00..4 4 VolulyteVolulyte ®,®, TetraspanTetraspan ®® 00..4242--00..4545VolulyteVolulyte ®, ®, TetraspanTetraspan ® ® 00..4242 00..45 45

*Enhance degradation, *Enhance degradation, *Minimize *Minimize

-- Retention in the circulation & tissueRetention in the circulation & tissue-- Renal & coagulation effectRenal & coagulation effect

HES & AntiinflammationHES & Antiinflammation

HydroxyethylHydroxyethyl starch starch 130130//00 4 4 augments healing of colonic augments healing of colonic HydroxyethylHydroxyethyl starch starch 130130//00..4 4 augments healing of colonic augments healing of colonic anastomosisanastomosis in a rat model of peritonitisin a rat model of peritonitis. . Wang P, Gong G, Li Y, Li J. Am J Surg. 2010 Feb;199(2):232-9.

Aim: Aim: IInvestigate the role of hydroxyethyl starch (HES) 130/0.4 on the wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis

Results: MResults: Moderate doses (15 mL/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced impaired anastomotic healing of the left colon. This beneficial effect of HES 130/0.4 can be mainly attributed to its anti-yinflammatory and antioxidant properties and beneficial effects of modulating endothelial-associated coagulopathy.

HES Effect on Coagulation & Platelet FunctionHES Effect on Coagulation & Platelet FunctionHES….. Effect on Coagulation & Platelet FunctionHES….. Effect on Coagulation & Platelet Function

Kozek-Langenecker S, 2005

–– HES macromolecule interact with platelet and coagulation cascadeHES macromolecule interact with platelet and coagulation cascade

–– Decrease in factors such as Factor VIII and von Decrease in factors such as Factor VIII and von WillebrandWillebrand FactorFactor

TreibTreib J, J, 19961996

–– The higher MS the more effect with coagulation cascade & platelet functionThe higher MS the more effect with coagulation cascade & platelet function

–– More effect with higher dose & more More effect with higher dose & more hemodilutionhemodilution

ElggerElgger B, B, 20062006

–– Least with rapid degrade HES Least with rapid degrade HES egeg, , tetrastarchtetrastarch even with high dose even with high dose 70 70

ml/kg in severe hear injuryml/kg in severe hear injury

–– Least effect in Least effect in 6 6 daysdays

Colloid molecule inhibit platelet function (in carrier solutions without calcium)Colloid molecule inhibit platelet function (in carrier solutions without calcium)

DextranDextran >> HetastarchHetastarch > > PentastarchPentastarch > Gelatin > Gelatin >> TetrastarchTetrastarch, , AlbuminAlbumin

Colloid molecule decrease Colloid molecule decrease vWFvWF and factor VIII: and factor VIII: DextranDextran >> HetastarchHetastarch > > PentastarchPentastarch > Gelatin > > Gelatin > TetrastarchTetrastarch, , AlbuminAlbumin

Colloid molecule induce Colloid molecule induce hypocoagulabilityhypocoagulability and decrease fibrin polymerizationand decrease fibrin polymerization

DextranDextran >> HetastarchHetastarch >> PentastarchPentastarch >> TetrastarchTetrastarch > Gelatin > Albumin> Gelatin > AlbuminDextranDextran > > HetastarchHetastarch > > PentastarchPentastarch > > TetrastarchTetrastarch > Gelatin > Albumin> Gelatin > Albumin

Effect of colloid molecule on blood loss:Effect of colloid molecule on blood loss:

DextranDextran > > HetastarchHetastarch > > PentastarchPentastarch > Gelatin, > Gelatin, TetrastarchTetrastarch, , AlbuminAlbumin

HES….. Effect on Plasma HES….. Effect on Plasma BilirubinBilirubin

• Non of the report of corn derived starch associated with deterioration of liver Non of the report of corn derived starch associated with deterioration of liver function compared to controlfunction compared to control

••Sander O, Sander O, 20032003

C d i d HES (C d i d HES (130130// 4242) & HES) & HES 200200//00•• Compare potato derived HES (Compare potato derived HES (130130/./.4242) & HES ) & HES 200200//00..55

•• Mild to moderate Mild to moderate hyperbilirubinemiahyperbilirubinemia was a significant adverse events was a significant adverse events found in potato derived starchfound in potato derived starchpp

•• impair excretion of bile or increase impair excretion of bile or increase bilirubinbilirubin from fragment erythrocytefrom fragment erythrocyte

••Potato derived HES is the only Potato derived HES is the only tetrastarchtetrastarch to be absolute contraindicated in to be absolute contraindicated in yypatients with severe hepatic impairmentpatients with severe hepatic impairment

HES….. Effect on Renal functionHES….. Effect on Renal function

HES Eff t R l f tiHES Eff t R l f tiHES….. Effect on Renal functionHES….. Effect on Renal function

More with high MS HESMore with high MS HESMore with More with hyperoncotichyperoncotic HESHESMore with high doseMore with high doseLeast with Least with tetrastarchtetrastarch

Intensive Insulin Therapy and PentastarchpyResuscitation in Severe Sepsis. BrunkhorstBrunkhorst F, et al. N F, et al. N EnglEngl J Med, J Med, 20082008

oo Aim: Aim: study role of intensive insulin therapy & study role of intensive insulin therapy & study choice of fluid study choice of fluid resuscitation in severe sepsis either crystalloid or colloidresuscitation in severe sepsis either crystalloid or colloid

oo Method: Method: MuticenterMuticenter, Multidisciplinary ICU, Randomized, , Multidisciplinary ICU, Randomized, 537 537 severe sepsis patients, receivingsevere sepsis patients, receivingoo Intensi e ins lin therap to maintainIntensi e ins lin therap to maintain e gl cemiae gl cemia ss con entionalcon entionaloo Intensive insulin therapy to maintain Intensive insulin therapy to maintain euglycemiaeuglycemia vsvs conventional conventional

insulin therapyinsulin therapy

oo 1010% % pentastarchpentastarch ((200200//00..55) or modified Ringer’s lactate solution for ) or modified Ringer’s lactate solution for fluid resuscitation (keep CVP fluid resuscitation (keep CVP >> 8 8 mmHg)mmHg)

oo Outcome : Death at Outcome : Death at 28 28 days, mean score for organ failuredays, mean score for organ failure

RESULTS: RESULTS: Electron microscopic tubular injury score was highest in sheepElectron microscopic tubular injury score was highest in sheep

treated with 10% HES 200/0.5 (P < 0.001 vs. 6% HES 130/0.4).

CONCLUSIONSCONCLUSIONS: In ovine endotoxemic shock, saline-based 10% HES 200/0.5 was linked to impaired renal function and more pronounced tubular epithelial injury when compared with 6% HES 130/0 4 and balancedepithelial injury when compared with 6% HES 130/0.4 and balanced crystalloids

Renal Problem with Colloid

• DextransHyperoncotic problem ?• Hyperoncotic problem ?

• Hyperoncotic reanl failure h d li filt ti…hydraulic filtration

• Dextrans, 10% HES, 20% albumin

PRO: PRO: HydroxyethylHydroxyethyl starch can be safely uses in the starch can be safely uses in the intensive care patientintensive care patient--the renal debate. the renal debate. BoldtBoldt J. Intensive Care Med J. Intensive Care Med 2009 2009

• HyperoncoticHyperoncotic HES should not be used in patients who HES should not be used in patients who HyperoncoticHyperoncotic HES should not be used in patients who HES should not be used in patients who

are at risk of developing kidney dysfunctionare at risk of developing kidney dysfunction

••In patient without preexisting kidney dysfunction, there In patient without preexisting kidney dysfunction, there

seem to be negative effects of modern HES preparationseem to be negative effects of modern HES preparation

••In septic patients with reduce kidney function (Cr > In septic patients with reduce kidney function (Cr > 22..5 5

mg/mg/dLdL) HES should be used cautiously ) HES should be used cautiously mg/mg/dLdL) HES should be used cautiously ) HES should be used cautiously

Carrier SolutionCarrier Solution

••Non balance solution : Na Non balance solution : Na 154 154 mEqmEq/L, /L, ClCl 154 154 mEqmEq/L/L

•• Balance solution : Balance solution :

*Na *Na 140 140 mEqmEq/L, K /L, K 4 4 mEqmEq/L, /L, Ca Ca 22..5 5 mEqmEq/L, /L, Mg Mg 1 1 mEqmEq/L, /L,

ClCl 118 118 mEqmEq/L, Acetate /L, Acetate 24 24 mEqmEq/L, /L, MalateMalate 5 5 mEqmEq/L/L

*Na *Na 137 137 mEqmEq/L, K /L, K 4 4 mEqmEq/L, Mg /L, Mg 11..5 5 mEqmEq/L, /L, ClCl 110 110 mEqmEq/L,/L,

Acetate Acetate 34 34 mEqmEq/L/L

* More benefit for renal & coagulation* More benefit for renal & coagulation

The Influence of balanced volume concept on inflammation, d th li l ti ti d kid i t it i ld l diendothelial activation, and kidney integrity in elderly cardiac

surgical patients Boldt et al, Intensive Care Med, 2009

oo Aim: Aim: study the benefit study the benefit balanced fluid balanced fluid replacement regimen for correcting replacement regimen for correcting hypovolemiahypovolemia

M th dM th d R d i dR d i d 5050 ld l (ld l ( 7575 ) di i i) di i ioo Method: Method: Randomized, Randomized, 50 50 elderly (>elderly (>75 75 years), cardiac surgery, receivingyears), cardiac surgery, receivingoo Balance Balance 66% HES % HES 130130//44..2 2 plus a balance crystalloid solution plus a balance crystalloid solution (n=(n=2525))

oo NonNon--balance balance 66% HES % HES 130130//44..0 0 in NSS plus saline solution in NSS plus saline solution (n=(n=2525))

oo To keep PCWP/CVP To keep PCWP/CVP 1212--14 14 mmHgmmHg

oo Studied: Studied:

oo AcidAcid base status inflammation endothelial activationbase status inflammation endothelial activation (soluble intercellular adhesion(soluble intercellular adhesionoo Acid Acid ––base status, inflammation, endothelial activation base status, inflammation, endothelial activation (soluble intercellular adhesion (soluble intercellular adhesion moleculemolecule--11), ), kidney integrity kidney integrity (kidney(kidney--specific proteins glutathione specific proteins glutathione transferasetransferase--alpha: alpha: neutrophilneutrophilgelatinasegelatinase--associated associated lipocalinlipocalin) ) 5 5 hours after induction of anesthesia, hours after induction of anesthesia, 5 5 hours after hours after surgery, surgery, 1 1 and and 2 2 days thereafter.days thereafter.

oo Serum Serum creatininecreatinine ((sCrsCr) was measured approximately ) was measured approximately 60 60 days after dischargedays after discharge

The Influence of balanced volume concept on inflammationThe Influence of balanced volume concept on inflammation, endothelial activation, and kidney integrity in elderly cardiac surgical patients Boldt et al, Intensive Care Med, 2009

C l iC l i A t t l b l d lConclusion: Conclusion: A total balanced volume replacement strategy including a balance HES & a balance crystalloid solution resulted in moderate beneficial effects on acid basein moderate beneficial effects on acid-base status, inflammation, endothelial activation, and kidney integrity compared to a conventional unbalanced volume replacementconventional unbalanced volume replacement regimen.

BACKGROUND AND OBJECTIVE: Haemostasis appears to be less altered with balanced than with unbalanced

h d th l t h (HES) tihydroxyethylstarch (HES) preparations.

METHODS: Blood from 12 healthy young male volunteers was diluted by 10, 30 and 50% byBlood from 12 healthy young male volunteers was diluted by 10, 30 and 50% by

using either a balanced 6% HES 130/0.42 or a nonbalanced 6% HES 130/0.4.

Rotation thrombelastometry was used to assess changes in coagulation

RESULTS: extreme haemodilution with HES 130/0.42 dissolved in a balanced solution

containing calcium was associated with less negative effects on thrombelastometry and platelet aggregation than HES 130/0.4 prepared in a nonbalanced solution without calcium. Gelatin prepared in a nonbalanced solution showed similar effects on coagulation to balanced HES without calcium.

How to Give Fluid

• Early, fast adequateFrequent evaluation• Frequent evaluation

• Peripheral IV.• Bolus• Avoid central line• Frequent evaluation of response

Evaluation of Fluid Responsiveness