Treatment of Acute Renal Failure

Bad Homburg

Treatment of ARFAcute renal failureIndications Diffusion and convectionPossible treatment modesIntermittent or continuous? Dose of renal replacement therapyAnticoagulationLactate or bicarbonate?

Patients With ARFSpecific problems (compared to chronic renal failure)More co-morbid conditionsMore problems with hypotension Often additional organ failures which require, e.g.,Mechanical ventilation, Infusion of catecholamine's

Therapeutic consequencesEarly start of therapyProlonged or continuous treatmentsIntensified renal replacement therapy

Sylvester W et al.Crit Care Med 29:1910-1915, 2001Severe ARF = renal replacement therapy clinically required Aetiology of Severe ARF

Diagramm1

35.4

7

45.2

5

1.3

6.1

main cause of ARF

patients [%]

Tabelle1

ischaemia / low blood pressuresepsissepticshockrhabdo-myolysisnephro-toxinsother

35.4745.251.36.1

Liao F et al.Kidney Int Suppl 66:S16-24, 1998 MOF: Multi-organ failureMortality of Patients with ARF

Long-term Results After ARF Therapy979 ICU-patients with ARF needing CRRT, 301 surviving to dischargeQuestionnaire sent to surviving patients, response rate: 89%Survival rate77 % surviving patients after 6 month67 % surviving patients after 12 month50 % surviving patients after approx. 5 yearsPost discharge quality of lifeMost patients self-sustaining, physically active, and psychologically balancedMorgera S et al.Am J Kidney Dis 40:275-279, 2002=> Effort justified!

Indications to Start Renal Replacement TherapyAbsolute indicationsHyperkalemia (> 6,5 mmol/l)Acidosis (pH < 7,20 7,25; BE < - 8)Unmanageable hypervolemiaSigns of uraemiaPericarditisNeurological symptomsPeritonitisBleeding tendencyRelative indicationsElectrolyte disturbances HyponatremiaHyperkalemiaOliguria / AnuriaAzotemia Urea > 100 mg/dlFast rise of creatinine > 100 mol/l (1 mg/dl) per dayIf possible start of therapy prior to obvious signs of uraemia!

When to start?Gettings LG et al. Intensive Care Med 25:805-813, 1999BUN at start > 60 mg/dl (ca. 130 mg/dl urea)Late start, after 19,4 days of hospitalization, n=59 20.3 % survivalBUN at start < 60 mg/dl (ca. 130 mg/dl urea)Early start, after 10.5 days of hospitalization, n=41 39.0 % survivalonly patients with post-traumatic ARF

Physical MechanismsSemi-permeable MembraneA very fine sieveDiffusionConcentration equilibrate over time UltrafiltrationFiltration of Water due to a pressure gradientConvection (solvent drag)Solved substances are transported with the filtered water

middle molecules, e.g. cytokineswater passes the membrane easilyerythrocyte, red blood cellleukocyte, white blood celllarge proteins, e.g. albuminsmall molecules, e.g. ureaCells are not drawn at scale, in fact they are much larger than the pores.Semi-permeable Membrane

Microscopic Structure of a Capillarysymmetric: pore size blood side = pore size dialysate sidee.g. Cuprophan, AN69asymmetric: pore size blood side < pore size dialysate sidee.g. Fresenius Polysulfone

start:different concentrations of solutesend:concentrations of solutes on both sides of the membrane equilibrateddriving force: random movement of all molecules (Browns molecular movement)Note: Diffusion is faster for smaller molecules!timeDiffusion

Are we able to regulate diffusion?We want, e.g.:- eliminate a lot of urea from the blood- lower plasma potassium a little bit- keep plasma sodium approx. constantHo do we achieve these goals?Question

Peritoneal dialysise.g. small children, no vascular accessVarious forms of blood purificationDominantly used approachDistinguished by mode of application intermittent or continuousDistinguished by vascular access arterio-venous or veno-venousDistinguished by location of fluid application without, pre-filter, into the filter, post-filter or combinationsSCUFCVVHCAVHCVVHDFCVVHDiHD CRRTPDCAPDPre-dilutionPost-dilutionRenal Replacement Therapies used with ARF

Liao F et al,Kidney Int, 50:811-818 (1996)data from Madrid (Spain) 10/91-6/92Preferred TreatmentICU vs. non-ICU

Tabelle1

ICUnon-ICU

iHD23%89%

CRRT72%7%

PD5%4%

%

CVVHDCVVHD: continuous veno-venous haemodialysisapplication of the solution within the filtersimilar effectivity for small uraemic toxins (e.g. urea, potassium) as post-dilution CVVH (if identical volumes are used)for larger toxins (e.g. cytokines, mediators) effectivity comparable with pre-dilution CVVH

Postdilution CVVHDFCVVHDF: continuous veno-venous Haemodiafiltrationapplication of solution within and after the filterenables further increase of effectivity, if the exchange volume with post-dilution CVVH cannot (or shall not) be further increased, e.g. because of haemoconcentration

daily, intermittent haemodialysiscontinuous haemodialysisTherapy:Continuous or Intermittent?

CVVH Avoids Hypotensive EpisodesRonco C et alKidney Int 56 [Suppl 72]: S-8-S-14, 1999

Anticoagulation with CRRTHeparinStandard for systemic anticoagulation(in combination with Protamin regional anticoagulation possible, but reduction of bleeding risk with this approach not shown)ProstacyclinInhibition of platelet aggregationUsed alone or in combination with systemic anticoagulantsDanaparoid (Orgaran), Hirudin, ArgatrobanAlso systemic anticoagulationOften used in patients with Heparin Induced Thrombocytopenia (HIT), specifically type II (HIT II) CitrateRegional anticoagulation, established in some centres (often locally established device combinations)Without anticoagulationSometimes possible in patients with a high bleeding risk

Anticoagulation for CRRTUnfractionated HeparinStandard approach, exceptions are heparin contraindications, e.g.:heparin induced thrombocytopenia type II (HIT II)high risk of bleedingAnti-thrombin III required, sometimes need for substitution

Best comprise between long filter life time and risk of bleeding with an aPTT between 35s and 45s

Target range 60-80 s

No consensus in the literatureAbramson S & Niles JLCurr Opin Nephrol Hypertens 8:710-707, 1999Reeves JH et alCrit Care Med 27:2224-2228, 1999

Recommendations for Anticoagulation during CVVHKozeck-Langenecker SAAnaesthetist 51:210-217, 2002Bleeding risk: platelets < 60 G/l, aPTT > 60 s, disseminated intravascular coagulation, or spontaneous bleedingPriming: anticoagulant plus saline for 15 30 min, thereafter rinse with saline for 15 30 min

Standard heparin, unfractionatedRisk of thromboembolismNo riskBleeding riskPriming with 5,000-10,000 IU/liv-bolus prior to CVVH [IU/kg]30 70 15 25 0 10 Continuous infusion during CVVH [IU/kg/h] 10 20 5 15 5 10 Prolongation of activated clotting time (ACT) aimed for [%]1005025

Renal Regeneration of Bicarbonate BufferMetabolismFixed AcidBicarbonate Acid-anion Carbonic Acid (removed by ventilation)Acid-anion (excreted in the urine; together with a cation, e.g., NH4+)Buffer consumptionBuffer regenerationExcretion of the acid-anion-

Which Buffer Basein HF solutions?Direct buffer base: bicarbonateOptimal, physiological bufferStability of bicarbonate solutionsPotential problem: precipitations after loss of CO2 Technical solution: double chamber bag and mixing directly before useIndirect buffer bases: lactate, acetate, citrateAnions of organic acids Metabolism of these anions removes acid equivalentsRemoval of acid equivalents = Conversion to bicarbonateMetabolism requires sufficient oxygen supplyLactate most frequently used (high lactate levels during physical exercise physiological)

Treatment of ARF SummarySeverely ill patientsDifferent renal replacement therapies possibleTransport through the membrane: Diffusion and convection Continuous renal replacement therapies (CRRT)Post dilution CVVHDF as generally suitable treatment mode, other CRRT Modes for specific situationsStandard anticoagulation with heparinPresent dose recommendation: 1.5 2.5 L/h, with severely ill patients also higher dosesReduced hepatic function / cardiac aetiology of ARF: Bicarbonate advantageous

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