the role of acute hemodialysis in pediatric intensive care : new technological advances on line...

Les HôpitauxUniversitairesde STRASBOURG

The role of acute hemodialysis in pediatric intensive care :

new technological advanceson line equipments : tools or toys?

M. Fischbach

Children Dialysis Unit

Strasbourg - France


• Intermittent hemodialysis techniques especially in case of either

major hemodynamic instability or « too shortened » dialysis times

(acute osmotic changes), and overall logistic factors (implication of

the nephrological team), could adversely affect the quality of an

acute intermittent dialysis procedure, therefore continuous

hemodialysis (hemofiltration) are often advocated as « superior ».

• Nevertheless slow low efficiency on line HDF offers a

«nephrological» dialysis prescripiton, with a magnitude of

individually adapted prescription as often needed for a critically ill

patient hemodinamically instable and hypercatabolic (on-line

dialysis tools equipment especially, continuous determination of the

blood volume),

acute hemodialysis: continuous or intermittent ?


Slow low efficiency dialysis : a new gold standard ?

• Today ARF is generally one feature of a multiorgan dysfunction syndrome in critically ill children, usually hemodinamically instable and hypercatabolic

• The choice of renal replacement modality either CVVHD or sustained low efficient hemodialysis, should consider the dual need : * hyghly efficacious elimination of uremic toxins *and concomitant gentle volume removal

Technology insight: tretment of renal failure in the intensive care unit with extended dialysis. D Fliser, Jt Kielstein.Nature Clinical Practice Nephrology.2006:32-9


Slow low efficiency dialysis : a new gold standard ?

• Conventional hemodialysis with a low dialysate flow and a long duration (8 or more hours): « gentle » ultrafiltration and « progressive » osmotic changes

• Easy to perform, available material, discontinuous/intermittent, reasonable team demand

• Slow UF rate per hour (zero balance UF prior dialysis connection) : optimal vascular tolerance

• Low K per hour : optimal osmotic tolerance, but sufficient treatment dose (hypercatabolic patients)

• High Kt/V : good prognostic/outcome factor

• Highly efficient membranes : chance of recovery, biocompatibility

• Dialysate : bicarbonate as buffer, glucose, NaD, K, Ca2+

Technology insight: tretment of renal failure in the intensive care unit with extended dialysis. D Fliser, Jt Kielstein.Nature Clinical Practice Nephrology.2006:32-9


During the past decades many improvement in hemodialysis technology occured :

• Volumetrically control of the ultrafiltration,even the availability of profiled UF/NaD

• Bicarbonate dialysate buffer

• Smaller lines and membranes for infants

• Biocompatible membanes (highly efficient)

• Hemodiafiltration on line with ultrapure dialysate, (reduced continuous inflammation: microCRP)

• And on line equipments…..


On line equipments : power tools for (acute) hemodialysis

• Blood volume monitoring : « vascular refilling capacity »

• Blood thermal monitoring : isothermic dialysis (thermoneutral), cool

temperature dialysis, regional blood flow redistribution risk

managment (vasoconstriction)

• Profiled prescriptions: UF total and rate (continuous/intermittent),

NaD (high or low dialysate concentrations)

• Urea clearance (OCM : on line clearence measurement) and

dialysis dose measurement, dialysis efficiency/osmotic risk


Slow low efficiency on line HDF

• Access : veino veinous, catheter • Membrane biocompatibility: high permeability, chance of recovery• Anticoagulation : low MW, but either free in predilution mode or

citrate Na conducted • Dialysate flow modulable and, base : bicarbonate (+ acetate)• Replacement fluid (pre/postdilution): bicarbonate (+ acetate)• Solute clearance mechanism : diffusion and convection• Duration : 6-12 hours• Tools/ toys : BVM, BTM, UF and Na modelling, predilution (mixed

pre-post), Kt/Vurea on linemeasurement, change from sequential UF, to HF, to HD, to HDF, to pre or/and post dilution (without changing the dialysis set)

• Cost : water quality, membrane, dialysis and replacement fluids


Blood flow and catheter size (diameter)

Radius : 1 mm Blood flow 1

Radius : 0,5 mm Blood flow 1/16

Radius : 0,25 mm Blood flow 1/32

Poiseuille law : QB = x r 4

Flow through a tube varus with the 4th

power of it radius

A single but large lumen catheter offers for small children a better flow compromise than a double small lumen catheter


Dialysis membranes : practical parameters

• Type of membrane : biocompatibility• Initial blood volume need, ie area related, quality

of blood restitution, heparin demand• Molecular permeability : maximal clearance for

urea (osmotic risk) and other uremic toxins, ie phosphate and cytokins+++

• Hydraulic permeability : possibility of use for HF or HDF procedure ; back filtration risk

• Cost, need (purification molecular spectrum) , diuresis recovery hope


The dialysate : adaptable, and « ultra »pure

• Dialysate flow : low flow should be available (300ml/min or less)

• Bicarbonate buffered (controlled alkalinisation, concentration flexible)

• Low calcium level (1.25 mmol L-1) becomes the standard for chronic

dalysis, but for acute HD higher concentrations (1. 75 mmol L-1) are

more appropriated (cardiac inotropic impact)

• Adaptable concentration of sodium (132 to 150), kalium (not a too

important blood/dialysate gradient due to the cardiac arythmia risk)

• Glucose concentration at physiological level

• Dialysate quality control is required (germs and endotoxins), if highly

permeable membranes are used (of course in on-line HDF

configuration) : ultrapure dialysate+++


Ultrapure dialysate

• Improved nutritional status (Schefftel H et al. NDT 2001)

• Reduced inflammation, AGE accumulation, amyloidosis (corporel tunnel syndrome) (Gerdeman A et al. NDT 2002)

• Lowered cardiovascular mortality (Lederer SR et al. Nephron 2002)

• Preserved renal residual function Schefftel H et al. NDT 2002) : renal recovery ???


Principles of blood purification

• Diffusive Process (HD) : low MW uremic toxins removal i.e.urea

• Convective mass transport (HF) : middle Mw uremic toxins removal i.e.phosphate

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

HD

HF

HDF


Blood purification dialysis modalities :

diffusion versus convection

Diffusive Process

(hemodialysis)

Membrane area

Mass transport coefficient

Concentration gradient

Blood flow x extraction coefficient ci - co

KHD = QB x ci

i, o : in outlet solute concentrations

Convective mass transport(hemofiltration)

Ultrafiltrate flow (QUF)Hydraulic permeabilityTransmembrane pressure (TMP ; mmHg)Sieving coefficient (S)*

2 CUF

*S = ci+co

CUF : ultrafiltrate solute concentration

KHF = QUF x S (postdilution)

QB x QUF

KHF = x S (predilution) QB - QUF


Simultaneous purification: diffusion process and

convection mass transport i.e. hemodiafiltration

KHDF = KHD + x QUF x 0.46

KHDF = KHD (1 - QUF x S/QB) + KHF (Granger)

with QUF x S = KHF and QB = Kmax

KHD x KHF QHDF = KHD + KHF- Kmax

one minute of dialysis « is equal» to two minutes of purification, one of HD and another one of HF

If KHF is equal to Kmax then QHDF= KHD


HDF versus HD : advantages

• Hemodynamic stability over the session

* increased tolerance to weight loss, and blood pressure

control improvement (hemofiltration effect)

* osmotic stability, compartment preservation,

peripheral vascular resistances, myocardial contractility

• Optimal blood purification capacities both for urea and

inflammatory/catabolic agents

• Optimized hemocompatibility : bicarbonate dialysate, synthetic

membrane, retrofiltration control, ultrapure dialysate

• Individual adaptadive prescription : easy switch from HDF to

HF to HD to sequential « isolated » UF (isoosmotic)


Hemodiafiltration : pre/post dilution

Substitution solution

QB in QBout

pre-dilution post-dilution

Addition of substitution solution in HDF can be made before thefilter , predilution mode, or after the filter , postdilution mode

In HDF addition of substitution solution can be made before the filter called predilution mode, or after the filter, postdilution mode


Hemodiafiltration modalities

• Conventional HDF: :

substitution fluid (bags) with « balanced »

compensation, not more applied (cost)

• High flux hemodialysis i.e. internal HDF : highly

permeable membranes with retrofiltration due to the

high hydraulic permeability coefficient

• On line HDF : substitution fluid produced from the

ultrapure dialysate +++



on line equipments , tools or toys ?

• BVM +++ , relative blood volume variation (reduction), hypotensive riks, dry weight adjustment

• BTM, controlled « cooled » dialysis, reduced thermic dialytic loss

• Modelling of the UF rate and sodium in the dialysate (NaD): individual patients profiles

• Ionic dialysance : on-line KT/V determination, vascular access blood flow measurement

BVM

KT/V


Hypotension : a multifactorial event, dialysis impacted

• Cardiac rythm, and contractility : *dialysate Ca++, *optimal purification (cytokines)

• Vascular resistances : *bicarbonate dialysate, *temperature control…

• Blood volume : *preservation, despite need for weight loss, *ultrafiltration versus plasma refilling from the interstitial space



tools or toys ?





BVM


Non-invasive monitoring of Hematocrit (NIVM) : principle

• Red cell volume « remains constant » during dialysis

changes (bleeding ?)

• Hematocrit and intravascular volume changes are

inversely proportional

Hct0 x BV0 = Hctx x BVx 5% Hct = 15% BV Δ BV % = 100 x (BV0 - BVx/BV0) = 100 x (Hctx - Hct0)/ Hct0


Should relative blood volume (RBV) changes be routinely measured during dialysis session ?

Basile C. Nephrol Dial Transplant 2001; 16:10-22

The answer is definitively yes, at least obviously in the case of

hypotension prone patients for the following reasons :

• Hypotensive episode occurrence decreases

• Non invasive method, and relatively inexpensive

• Possibility of further developments : automatic retrocontrol

biofeedback technology, information about real hematocrite?

• BV decrease should be limited (?) to less than 15% ( 5% Ht

increase ) per dialysis session

• BV refilling capacity should be analysed, to optimize ultrafiltration

prescription


0

5

10

15

0 60 120 180 240

TD (min)

1

3

4

2

BV % Routine use of NIVM for

chronic dialysis:

• helps to achieve the target dry

weight,

• reduces both the risk of chronic fluid overload and the

need for antihypertensive medication,

• lead to decrease the intradialytic symptomatology,

• And perhaps, allows better residual diuresis preservation

Blood volume monitoring to achieve target weight in pediatric hemodialysis patients

Michael M, Brewer ED, Goldstein SL.Pediatr Nephrol 2004; 19:432-7


Non-invasive intravascular monitoring (Ht) in the pediatric

population Jain SR et al. Pediatr Nephrol 2001; 16:15-18

• UFR with BV change < 8 % per hour is safe in the 1st hour and

4 % thereafter (NaD 140 mmol/L ; no profile neither NaD nor UF)

• no more than 12 % over a whole session :

*time for plasma refilling occurence ,

*recruitment of the « interstitial » water,

*preservation from cellular water shift

• dBV/Dt = UFR – PRR

0

5

10

15

0 60 120 180 240

TD (min)

1

3

4

2

BV %


« Blood volume, Ht » monitoring allows an on line assessment of the

balance between

• ultafiltrate rate and volume

• vascular refilling capacity

• cellular water shift

d BV/dt = UFR – PRR

if PRR is able to compensate UFR,

vascular compartment will be preserved


vascular : oncotic (proteins) pressure

extracellular : osmotic (Na) pressure

intracellular : osmotic gradient (urea dysequilibrium)


compartment « water »shifts :

vascular

ultrafiltration

UF rate,volume

urea


Compartment shitfs , water and solutes, extracellular (vascular, interstitial) and cellular

compartments : multifactorial

Pressures : hydrostatic ; osmotic crystalloid (Na , urea , glucose) ; osmotic colloid(proteins)

Wall permeability : membranes vessels , cells

Regional blood flow : *cardiac flow , *peripheral vascular resistances (hypovolemia, acidosis, cooled dialysate….) *extra/intra cellular functional compartments


Ultrafiltration tolerance : rate(ml/h) more than total

amount(ml/session)BV preservation,hemoconcentration : osmotic colloid pressure enhancement (proteins,Na,nutrition…)PRR,water shift from the interstitial to the vascular compartment facilitated by : *low/intermittent UF ; *oncotic vascular pressure ; *degree of interstitial repletion (water/Na overload);

*Na(dialysate/blood/interstitial)Water shift from the cells to the extracellular compartment due to the osmotic «cristalloid »gradient ( urea , Na , ,glucose , PVR )Patient whole condition : cardiac output, nutrition,catabolism…


factors affecting plasma refilling capacity: dBV/Dt = UFR – PRR

• Individual state of hydratation (interstitial compliance, water and Na)

• Dialysate sodium concentration (osmotic)

• Plasma protein concentration (oncotic)

• Capillary permeability, cardiovascular reactivity, dialysate composition and temperature, urea reduction rate...


Continuous blood volume monitoring and ultrafiltration control

Lopot et al, Hemodial Int 2000; 4:8-14

Type 1 constant BV, flat line throughout

the whole dialysis

Type 2 constant BV during a first part of

dialysis followed by a roughly linear

decrease

Type 3 linear decrease of BV from

dialysis start until the end with a

constant declining slope

Type 4 linear decrease of BV with a

variable declining slope

0

5

10

15

0 60 120 180 240

TD (min)

1

3

4

2

BV %




Type 1 : constant BV throughout

the whole dialysis or nearly flat

line or « BV water gain »

• PRR is able to fully compensate

UFR

• Fluid overload in the interstitial

space

• Dry weight adjustment need

(inferior vena cava diameter)

0

5

10

15

0 60 120 180 240

TD (min)

1

3

4

2

BV %




Type 3 or 4 : linear decrease of BV

with an individually variable slope

• Avoid a whole session decrease of

more than 15% BV (Ht 5%) high risk

for clinical intolerance

• Don ’t change DW without adapted

dialysis prescription (UFR, NaD, TD)

0

5

10

15

0 60 120 180 240

TD (min)

1

3

4

2

BV %



• if PRR is able to compensate UFR there will be no

change in BV, low hypotensive risk , «adequate»

tissular perfusion

• BV behavior gives more informations on the

appropriatness of the «UF rate» than on the «total UF

volume» achieved

• BV changes over time allows to test the plasma

refilling capacity, that is the BV profile induced by

UF=0,the water shift capacity from the interstitium to

the vascular or to the cellular space



Normal decrease of BV, at dialysis initiation, usually 5 to 8 % during a « short » time i.e. 5 to 30 minutes, this phenomena could be « controlled » and limited if needed :

• Fill the patient before filling the extracorporeal space• Limit the extracorporeal blood space• Fill the extracorporeal space with « blood » before patient connection, or better don’t flush the extracorporeal space before connection to the patient

Dialysis start : BV usually decrease


• UFR induces BV change : dBV/Dt = UFR – PRR

• In case of a to important decrease of BV ( change of 8 % or more in the 1st hour ), the ability of plasma refilling occurrence should be tested (stop UF, note BV behavior)

• In case of plasma refilling occurence, that is water transfer

from the interstitial space to the vascular space, UF can be prolonged, no or low risk of hypotension episode


Plasma refilling rate is influenced by :

• changes in UF : rate, profile (intermittent+++)• NaD increase : water shift from the interstitial to the vascular compartment ( transiet effect and, sodium « charge »risk) • Dialysate cooling (vasoconstriction, balanced by compartment purification)• Urea clearance reduction (less intracellular water shift)


UF reserve capacity

• overloaded patient, • excess of compensatory factors for BV preservation, to high NaD ?


• BVM over the dialysis session should be performed routinely in almost all children (each session)

• BVM allows an objective perception of compartment water recruitment for ultrafiltration (vascular refilling)

• BVM gives more information on UF rate than on UF total amount tolerance

• BVM could help for a more objective dialysis prescription

- session duration, -NaD,TD,

-UFprofile , - URR , dry weight goal



tools or toys ?

• BVM +++ , relative blood volume variation (reduction), hypotensive riks, dry weight




BVM

KT/V


Blood thermal monitoring

• Thermal balance control : isothermic dialysis,

thermoneutral dialysis (catabolism)

• Cool temperature dialysis, warmed dialysis :

– Blood pressure preservation, vasoconstriction

– Regional blood flow redistibution, share of compartmental

purification/limitation


Total body water: urea « mere » container, pools of

distribution• Intracellular 2/3 ; extracellular 1/3 : notion of

two body compartments (cellular wall)

• Skin, muscle, osseous tissues accounts for

80% TBW, despite receiving only 20% cardiac

blood outflow : notion of two circulatory

compartments (regional blood flow )


Dialysate temperature modelling in children on hemodiafiltration : conflicting impacts on

hemodynamic stability versus dialysis efficiencyM. Fischbach et al. J Am Soc Nephrol 2001; 12:A2317

• There is a beneficial role of cooled dialysate in

promoting hemodynamic stability

• Cooling induces vasoconstriction i.e. a

potential factor of thermally induced decrease

in regional blood flow with compartmental

disequilibrium ; conversely a warmed dialysate

should optimized regional blood flow

improving urea removal (regional blood flow

theory, Schneditz)


Haemodiafiltration with standard temperature dialysate (37°C) in children induces an energy loss

M. Fischbach et al. J Am Soc Nephrol 2001; 12:A1687

Begin End

Tcentral 36.90.18* 37.30.24*

Tax 36.10.22** 35.40.15**

Energy transfer

KJ (kilojoules)

ND -12431

The usually prescribed dialysate temperature of 37°C didn ’t allowed for children thermoneutral haemodiafiltration


URR%

TD profiled TD fixed (37°C)

first hour

Session

49+12

736

35+9*

638**

Energy transfer per session

KJ

- 6724

-124131***

TD profiled : first hour 38°C (TD) second hour ET = 0 (TD) third hour 36°5 C

M. Fischbach et al. J Am Soc Nephrol 2001; 12:A2317

Effect of profiled dialysate temperarure



tools or toys ?





BVM

KT/V


Sodium of the dialysateDiffusion, high NaD : - from dialysate to vascular , then to the interstitial compartment, with a « transiet » gradient between the vascular/interstitial compartments : potential « vascular water shift » -but Na «storage» in the interstitial space, with induction of interstitial oedema, and extra/intra cellular osmotic gradient (preservation from celluar « oedema »)

Convection, high interstitial Na: (cellular wall impermeability) generates water shift (intra to extra ; free Na water) and solute shift (convective cellular wash out), « counterbalanced » by intracellular urea « retention »


Ultrafiltration and sodium modeling : an efficacious trick, but could be at risk

• Able to limit dialysis morbidity, vascular instability

• Allow optimized ultrafiltration, in case of hypotension despite fluid

overload : intermittent UF should be appied +++ (refiling time)

• Risk of enhanced interdialytic weight gain, positive sodium balance

with interstitial oedema in case of too high, inadapted NaD

• Impact on purification : tissue perfusion, cellular washout

• 144 mmol/l is the « normal » plasma Na concentration :

NaD should be adapted to the evolutive, individual patient needs



tools or toys ?





BVM

KT/V


Urea dialysis dose : Kt x Vurea

• K : blood flow, dialyzer membrane capacity

• t : uremic toxins kinetics, single or double pool (intra-extra

cellular ; regional blood flow), multicompartmental : diffusibility

of the toxins

• Vurea :

– Urea pool

– Total body water : hydratation and nutrition

– V, is the volume of distribution of urea, total body water calculated

from gender specific normograms, it is also a surrogate of nutrition


Estimating TBW in children on the basis of height and weight : a reevaluation of the formulars of Mellits and CheekMorgenstern B, Mahoney D, Warady B, JASN 2002; 13:1884-8

• Infants 0 to 3 m (n = 71) : 0.887 x (Wt)0.83

• Gender specific normograms :

–Children 3 mo to 13 yr (n =167) : TBW = 0.0846 x 0.95[if female] x (Ht xWt)0.65

–Children > 13 yr (n = 99) : TBW = 0.0758 x 0.84[if female] x (Ht x Wt)0.6

Anthropometric prediction of TBW in children on PD Morgenstern B, Wuhl E, Sreekumaran NK, Warady B, Schaefer F.JASN 2005

• Gender specific normograms:

–Males : TBW=0.086x(heightxweight)0.680-0.21xweight

–Females : TBW=0. 112x(heightxweight)0.658_-0. 328xweight


Urea dialysis dose : Kt x Vurea

• Urea « osmotic » clearance has a direct impact on intracellular water shift (osmotic sydrome), be not too fast : vascular stability, neurological tolerance

• Kt x Vurea of 0.15 per hour , is sufficient to reach a

dialysis dose of 1.5 over a 10 hours dialysis session

• Potassium clearance is nearly 80% of Kt x Vurea

• Effect of time per se on final outcome : intermittent is not necessary too short dialysis time, it should be strongly influenced by the need to optimize vascular volume status and to preserve cellular space


On line equipments : power tools for acute hemodialysis

not too tricky tricks• Blood volume continuous monitoring (BVM) : refilling capacity test, secured

and optimized UF

• Blood thermal monitoring (BTM) : vascular stability, regional blood flow

potential impact

• HDF procedure : allowed sequential UF, HF, HD, adapted to the individual

patient needs, and evolution; on-line HDF provide for the restitution-

hemofiltration fluid (possibility for adapted sodim concentration)

• Profiled prescriptions: UFrate at the best intermittent (refilling time), NaD not

too high (interstitial storage,oedema)

• Clearance and dialysis dose measurement, dialysis efficiency: slow (urea

osmotic tolerance) but controlled purification (potassium gradient)


Steep wise initial prescription : massive fluid overload with interstitial

oedema, coma• HDF predilution, QUF2/3 of QB (osmotic « stability »),• Osmotic gradients :

* plasma oncotic pressure (maintain « albuminemia »), * cristalloid gradient (NaD but will move in the interstitium)

• UF rate (weight loss about 0.5 to 1% BW per hour in the acute phase) under BVM control, BV reduction limited to 10/15%

• Vascular instability or preservation of BV : * reduce dialysate temperature, * limit « urea » osmotic clearance, * profile intermittent UF, but limit interstitial sodium « charge » (NaD)


• Slow low efficiency dialysis : a new gold standard • On line equipments : power tools for acute hemodialysis

MERCI