Renal replacement therapy in Intensive Care - LearnICU in ICU.ppt · PPT file · Web...
Transcript of Renal replacement therapy in Intensive Care - LearnICU in ICU.ppt · PPT file · Web...
Renal Replacement Renal Replacement Therapies in Critical CareTherapies in Critical Care
Dr. Andrew FergusonDr. Andrew FergusonConsultant in Intensive Care Medicine & AnaesthesiaConsultant in Intensive Care Medicine & Anaesthesia
Craigavon Area Hospital, United KingdomCraigavon Area Hospital, United Kingdom
Where are we - too many questions?
• What therapy should we use?What therapy should we use?• When should we start it?When should we start it?• What are we trying to achieve?What are we trying to achieve?• How much therapy is enough?How much therapy is enough?• When do we stop/switch?When do we stop/switch?• Can we improve outcomes?Can we improve outcomes?
Does the literature help us?Does the literature help us?
Overview
AKI classification systems 1: RIFLE
AKI classification systems 2: AKINStage Creatinine criteria Urine output criteria
1 1.5 - 2 x baseline (or rise > 26.4 mol/L) < 0.5 ml/kg/hour for > 6 hours
2 >2 - 3 x baseline < 0.5 ml/kg/hour for > 12 hours
3 > 3 x baseline (or > 354 mol/L with acute rise > 44 mol/L)
< 0.3 ml/kg/hour for 24 hours or anuria for 12 hours
Patients receiving RRT are Stage 3 regardless of creatinine or urine output
Acute Kidney Injury in the ICU
• AKIis common: 3-35%* of admissions• AKI is associated with increased mortality• “Minor” rises in Cr associated with worse outcome• AKI developing after ICU admission (late) is
associated with worse outcome than AKI at admission (APACHE underestimates RODAPACHE underestimates ROD)
• AKI requiring RRT occurs in about 4-5% of ICU admissions and is associated with worst mortality risk **
* Brivet, FG et al. Crit Care Med 1996; 24: 192-198** Metnitz, PG et al. Crit Care Med 2002; 30: 2051-2058
Mortality by AKI Severity (1)
Clermont, G et al. Kidney International 2002; 62: 986-996
Mortality by AKI Severity (2)
Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409
RRT for Acute Renal Failure• There is some evidence There is some evidence for a relationship
between higher therapy dose and better outcome, at least up to a point
• This is true for IHD* and for CVVH**• There is nono definitive evidence definitive evidence for superiority
of one therapy over another, and wide practice variation exists***
• Accepted indications for RTT vary• No definitive evidence No definitive evidence on timing of RRT
*Schiffl, H et al. NEJM 2002; 346: 305-310 ** Ronco, C et al. Lancet 2000; 355: 26-30*** Uchino, S. Curr Opin Crit Care 2006; 12: 538-543
Therapy Dose in IRRTp = 0.01
p = 0.001
Schiffl, H et al. NEJM 2002; 346: 305-310
Therapy Dose in CVVH
25 ml/kg/hr
35 ml/kg/hr
45 ml/kg/hr
Ronco, C et al. Lancet 2000; 355: 26-30
Outcome with IRRT vs CRRT (1)
• Trial quality low: many non-randomized
• Therapy dosing variable• Illness severity variable
or details missing• Small numbers• Uncontrolled technique,
membrane • Definitive trial would
require 660 patients in each arm!
• Unvalidated instrument for sensitivity analysis
Kellum, J et al. Intensive Care Med 2002; 28: 29-37
“there is insufficient evidence to establish whether CRRT is associated with improved survival in critically ill patients with ARF when compared with IRRT”
Outcome with IRRT vs CRRT (2)
Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885
• No mortality difference between therapies• No renal recovery difference between therapies• Unselected patient populations• Majority of studies were unpublished
Outcome with IRRT vs CRRT (3)
Vinsonneau, S et al. Lancet 2006; 368: 379-385
Proposed Indications for RRT
• Oliguria < 200ml/12 hours• Anuria < 50 ml/12 hours• Hyperkalaemia > 6.5 mmol/L• Severe acidaemia pH < 7.0• Uraemia > 30 mmol/L• Uraemic complications• Dysnatraemias > 155 or < 120 mmol/L• Hyper/(hypo)thermia• Drug overdose with dialysable drug
Lameire, N et al. Lancet 2005; 365: 417-430
Implications of the available data
The Ideal Renal Replacement Therapy
• Allows control of intra/extravascular volume• Corrects acid-base disturbances• Corrects uraemia & effectively clears “toxins”• Promotes renal recovery• Improves survival• Is free of complications• Clears drugs effectively (?)
Solute Clearance - Diffusion
• Small (< 500d) molecules cleared efficiently
• Concentration gradient critical
• Gradient achieved by countercurrent flow
• Principal clearance mode of dialysis techniques
Solute Clearance – Ultrafiltration & Convection (Haemofiltration)
• Water movement “drags” solute across membrane
• At high UF rates (> 1L/hour) enough solute is dragged to produce significant clearance
• Convective clearance dehydrates the blood passing through the filter
• If filtration fraction > 30% there is high risk of filter clotting*
• Also clears larger molecular weight substances (e.g. B12, TNF, inulin)
* In post-dilution haemofiltration
Major Renal Replacement TechniquesIntermittent ContinuousHybrid
IHDIHDIntermittent
haemodialysis
IUFIUFIsolated
Ultrafiltration
SLEDDSLEDDSustained (or slow) low efficiency daily
dialysis
SLEDD-FSLEDD-FSustained (or slow) low efficiency daily
dialysis with filtration
CVVHCVVHContinuous veno-venous
haemofiltration
CVVHDCVVHDContinuous veno-venous
haemodialysis
CVVHDFCVVHDFContinuous veno-venous
haemodiafiltration
SCUFSCUFSlow continuous
ultrafiltration
Intermittent Therapies - PRO
Intermittent Therapies - CON
Intradialytic Hypotension: Risk Factors
• LVH with diastolic dysfunction oror LV systolic dysfunction / CHF• Valvular heart disease• Pericardial disease • Poor nutritional status / hypoalbuminaemia• Uraemic neuropathy or autonomic dysfunction• Severe anaemia• High volume ultrafiltration requirements• Predialysis SBP of <100 mm Hg• Age 65 years +• Pressor requirement
Managing Intra-dialytic Hypotension• Dialysate temperature modelling
• Low temperature dialysate
• Dialysate sodium profiling• Hypertonic Na at start decreasing to 135 by end• Prevents plasma volume decrease
• Midodrine if not on pressors• UF profiling• Colloid/crystalloid boluses• Sertraline (longer term HD)
2005 National Kidney Foundation K/DOQI GUIDELINES
Continuous Therapies - PRO
Continuous Therapies - CON
SCUF
• High flux membranes• Up to 24 hrs per day• Objective VOLUME control• NotNot suitable for solute clearance
• Blood flow 50-200 ml/min• UF rate 2-8 ml/min
CA/VVH
• Extended duration up to weeks• High flux membranes• Mainly convectiveconvective clearance• UF > volume control amount• Excess UF replacedreplaced• Replacement pre- or post-filter
• Blood flow 50-200 ml/min• UF rate 10-60 ml/min
CA/VVHD
• Mid/high flux membranes• Extended period up to weeks• DiffusiveDiffusive solute clearance• Countercurrent dialysate• UF for volume control
• Blood flow 50-200 ml/min• UF rate 1-8 ml/min• Dialysate flow 15-60 ml/min
CVVHDF• High flux membranes• Extended period up to weeks• DiffusiveDiffusive & convective & convective solute clearance• Countercurrent dialysate• UF exceeds volume control• ReplacementReplacement fluid as required
• Blood flow 50-200 ml/min• UF rate 10-60 ml/min• Dialysate flow 15-30 ml/min• Replacement 10-30 ml/min
SLED(D) & SLED(D)-F : Hybrid therapy
• Conventional dialysis equipment• Online dialysis fluid preparation• ExcellentExcellent small molecule detoxification• Cardiovascular stability as good as CRRT• Reduced anticoagulation requirement• 11 hrs SLED comparable to 23 hrs CVVH• Decreased costs compared to CRRT• Phosphate supplementation required
Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39 Berbece, AN & Richardson, RMA. Kidney International 2006; 70: 963-968
Kinetic Modelling of Solute ClearanceCVVH (predilution) Daily IHD SLED
Urea TAC (mg/ml) 40.3 64.6 43.4
Urea EKR (ml/min) 33.8 21.1 31.3
Inulin TAC (mg/L) 25.4 55.5 99.4
Inulin EKR (ml/min) 11.8 5.4 3.0
2 microglobulin TAC (mg/L) 9.4 24.2 40.3
2 microglobulin EKR (ml/min) 18.2 7.0 4.2
TAC = time-averaged concentration (from area under concentration-time curve)EKR = equivalent renal clearanceEKR = equivalent renal clearanceInulin represents middle molecule and 2 microglobulin large molecule.
CVVH has marked effects on middle and large molecule clearance not seen with IHD/SLEDSLED and CVVH have equivalent small molecule clearanceDaily IHD has acceptable small molecule clearance
Liao, Z et al. Artificial Organs 2003; 27: 802-807
Uraemia Control
Liao, Z et al. Artificial Organs 2003; 27: 802-807
Large molecule clearance
Liao, Z et al. Artificial Organs 2003; 27: 802-807
Comparison of IHD and CVVH
John, S & Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464
Beyond renalrenal replacement…RRT as blood purification blood purification
therapytherapy
Extracorporeal Blood Purification Therapy (EBT)
Intermittent Continuous
TPETPETherapeutic plasma
exchange
HVHFHigh volume
haemofiltration
UHVHFUHVHFUltra-high volume
haemofiltration
PHVHFPHVHFPulsed high volume
haemofiltration
CPFACPFACoupled plasma
filtration and adsorption
Peak Concentration Hypothesis
• Removes cytokines from blood compartment during pro-inflammatory phase of sepsis
• Assumes blood cytokine level needs to fallAssumes blood cytokine level needs to fall• Assumes reduced “free” cytokine levels leads to
decreased tissue effects and organ failure• Favours therapy such as HVHF, UHVHF, CPFA• But tissue/interstitial cytokine levels unknownunknown
Ronco, C & Bellomo, R. Artificial Organs 2003; 27: 792-801
Threshold Immunomodulation Hypothesis
• More dynamic view of cytokine system• Mediators and pro-mediators removed from
blood to alter tissue cytokine levels but blood but blood level does not need to falllevel does not need to fall
• ? pro-inflammatory processes halted when cytokines fall to “threshold” level
• We don’t know when such a point is reached
Honore, PM & Matson, JR. Critical Care Medicine 2004; 32: 896-897
Mediator Delivery Hypothesis
• HVHF with high incoming fluid volumes (3-6 L/hour) increases lymph flow 20-40 times
• “Drag” of mediators and cytokines with lymph• Pulls cytokines from tissues to blood for
removal and tissue levels fall• High fluid exchange is key
Di Carlo, JV & Alexander, SR. Int J Artif Organs 2005; 28: 777-786
High Volume Hemofiltration• May reduce unboundunbound fraction of cytokines• Removes
– endothelinendothelin-II (causes early pulm hypertension in sepsis)– endogenous cannabinoids endogenous cannabinoids (vasoplegic in sepsis)– myodepressant factormyodepressant factor– PAI-IPAI-I so may eventually reduce DIC
• Reduces post-sepsis immunoparalysis (CARS)• Reduces inflammatory cell apoptosis• Human trials probably using too low a dose too low a dose (40
ml/kg/hour vs 100+ ml/kg/hour in animals)
CRRT, Haemodynamics & Outcome• 114 unstable (pressors or MAP < 60) patients• 55 stable (no pressors or MAP > 60) patients• Responders = 20% fall in NA requirement or 20%
rise in MAP (without change in NA)• Overall responder mortality 30%, non-responder
mortality 74.7% (p < 0.001)• In unstable patients responder mortality 30% vs
non-responder mortality 87% (p < 0.001)• Haemodynamic improvement after 24 hours CRRT
is a strong predictor of outcomeHerrera-Gutierrez, ME et al. ASAIO Journal 2006; 52: 670-676
Common Antibiotics and CRRT
These effects will be even more dramatic with HVHF
Honore, PM et al. Int J Artif Organs 2006; 29: 649-659
Towards Targeted Therapy?Non-septic ARF Septic ARF
Cathecholamine resistant septic
shock
Daily IHD
Daily SLEDD
CVVHD/F ? dose
CVVH >> 35ml/kg/hour
? 50-70 ml/kg/hour
CVVH @ 35ml/kg/hour
Daily IHD?
Daily SLEDD?
HVHF 60-120 ml/kg/hourfor 96 hours
PHVHF 60-120 ml/kg/hour
for 6-8 hours then CVVH >> 35
ml/kg/hour
EBTEBT
Honore, PM et al. Int J Artif Organs 2006; 29: 649-659
Cerebral oedema
“You should listen to your heart, and not the voices in your head”
Marge Simpson