Regional ICM Teaching - Renal Dr Rosie Kalsi

1. Renal Replacement
Therapies in Critical Care
Rosie Kalsi
Regional teaching October2014

2. Where are we - too many questions?
• What therapy should we use?
• When should we start it?
• What are we trying to achieve?
• How much therapy is enough?
• When do we stop/switch?
• Can we improve outcomes?
Does the literature help us?

3. Overview

4. Renal failure of any cause
Many physiologic derangements:
• Homeostasis of water and electrolytes as the
excretion of the daily metabolic load of fixed
hydrogen ions is no longer possible.
• Toxic end-products of nitrogen metabolism (urea,
creatinine, uric acid, among others) accumulate
in blood and tissue.
• Endocrine organ dysfunction and failing
production of erythropoietin and 1,25
dihydroxycholecalciferol (calcitriol).

5. Evaluating ARF
Severity of ARF/AKI should not be estimated
from measurements of blood urea or creatinine
alone .
Cockcroft & Gault equation or MDRD eGFR or
reciprocal creatinine plots should not be used
when the GFR is <30 mL/min or to determine
the need for acute RRT.

6. AKI classification systems 1: RIFLE
Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy
and information technology needs: the second International Consensus Conference of the Acute Dialysis Initiative
(ADQI) group. Crit Care 2004; 8: R204–R212.

7. AKI classification systems 2: AKIN
Stage Creatinine criteria Urine output criteria
1
1.5 - 2 x baseline (or rise > 26.4
mmol/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 mmol/L with
acute rise > 44 mmol/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
Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an
initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.

8. The ‘evolving’ evidence says…
• Early initiation of RRT and utilization of RIFLE criteria.
Minimal dose 35ml/kg/hr (ie for 70kg person
2450ml/hr exchange)(1)
• But results of RENAL and ATN suggest 25mg/kg/hr
• Kidney Disease: Improving Global Outcomes (KDIGO)
Acute Kidney Injury Work Group. KDIGO Clinical
Practice Guideline for Acute Kidney Injury. Kidney Int
2012;2(Suppl):S1-138.
(1)Effects of different doses in CVVH on outcomes of ARF – C. Ronco M.D., R. Bellomo M.D. Lancet 2000;
356:26-30

9. 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 (pericarditis, nausea, vomiting, poor
appetite, hemorrhage, lethargy, malaise, somnolence, stupor,
coma, delirium, asterixis, tremor, seizures)
• Dysnatraemias > 155 or < 120 mmol/L
• Hyper/(hypo)thermia
• Drug overdose with dialysable drug
• Refractory hypertension
Lameire, N et al. Lancet 2005; 365: 417-430

10. “Non-renal” indications
• Substances with higher degrees of protein binding and is
sometimes substances with very long plasma half-lives.
• In general, the size of the molecule and the degree of protein
binding determines the degree to which the substance can be
removed (smaller, nonprotein bound substances are easiest to
remove).
• Techniques such as sorbent hemoperfusion may also be used.
• These substances include drugs, poisons, contrast agents, and
cytokines.

11. Acute Kidney Injury in the ICU
• AKI is 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 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

12. Mortality by AKI Severity (1)
Clermont, G et al. Kidney International 2002; 62: 986-996

13. Mortality by AKI Severity (2)
Bagshaw, S et al. Am J Kidney Dis 2006; 48: 402-409

14. CRRT Treatment Goals
• The concept behind CRRT is to dialyse patients in a more
physiologic way, slowly, over 24 hours, just like the kidney
• Tolerated well by hemodynamically unstable patients
• Maintain fluid, electrolyte, acid/base balance
• Prevent further damage to kidney tissue
• Promote healing and total renal recovery
• Allow other supportive measures; nutritional support

15. Determinants of Outcome
• Initiation of Therapy
– Ronco Study (2000)
– Gettings Study (2000)
– ADQI Consensus Initiative - Rifle Criteria (2004)
• Dose
– Ronco Study (2000)
– Kellum Meta-Analysis (2002)
– Saudan Study (2006)
– RENAL and ATN studies (2007)
– IVOIRE (2013)

16. RRT for Acute Renal Failure
• Newer evidence from RENAL and ATN trials
suggest no difference between higher therapy
CRRT dose and better outcome
• There is no definitive evidence for superiority
of one therapy over another, and wide
practice variation exists
• Accepted indications for RTT vary
• No definitive evidence on timing of RRT

17. 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

18. ATN
(2007)
large numbers
mixed RRT
20 vs 35ml/kg/hr
60 days

19. RENAL (2007)
Large numbers
20 vs 40ml/kg/hr
CVVHDF
90 days

20. 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”

21. 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

22. Outcome with IRRT vs CRRT (3)
Vinsonneau, S et al. Lancet 2006; 368: 379-385

23. Outcome with high vs low dose CRRT (1)
Min Jun et al. Intensities of Renal Replacement Therapy in Acute Kidney Injury: A Systematic Review and Meta-
Analysis. Clin J Am Soc Nephrol. Jun 2010; 5(6): 956–963.

24. Outcome with high vs low dose CRRT (2)

25. Implications of the available data
ARF is not an innocent bystander in ICU
We must ensure adequate dosing of RRT
Choice of RRT mode may not be critical
Septic ARF may be a different beast
We must strive to avert acute renal failure

26. 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 (?)

27. Intermittent Therapies - PROS
(Relatively) Inexpensive
Flexible timing allows for mobility/transport
Rapid correction of fluid overload
Rapid removal of dialyzable drugs
Rapid correction of acidosis & electrolyte abnormality
Minimises anticoagulant exposure

28. Intermittent Therapies - CONS
Hypotension 30-60%
Cerebral oedema
Limited therapy duration
Renal injury & ischaemia
Gut/coronary ischaemia

29. Intradialytic Hypotension: Risk Factors
• LVH with diastolic dysfunction or 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

30. 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

31. Continuous Therapies - PROS
Haemodynamic stability => ?? better renal recovery
Stable and predictable volume control
Stable and predictable control of chemistry
Stable intracranial pressure
Disease modification by cytokine removal (CVVH)?

32. Continuous Therapies - CONS
Anticoagulation requirements
Higher potential for filter clotting
Expense – fluids etc.
Immobility & Transport issues
Increased bleeding risk
High heparin exposure

33. Comparison of IHD and CVVH
John, S & Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464

34. PrismaFlex
Basic CRRT Principles

35. Continuous Renal Replacement
Therapy (CRRT)
““Any extracorporeal blood purification therapy
intended to substitute for impaired renal function over
an extended period of time and applied for or aimed at
being applied for 24 hours/day.”
Bellomo R., Ronco C., Mehta R, Nomenclature for Continuous Renal
Replacement Therapies, AJKD, Vol 28, No. 5, Suppl 3, Nov 1996

36. Anatomy of a Haemofilter
• 4 External ports
– blood and dialysis fluid
• Potting material
– support structure
• Hollow fibers
– Semi-permeable
membrane
• Outer casing

37. Semi-permeable Membranes
• Semi-permeable membranes are the basis of all
blood purification therapies.
• They allow water and some solutes to pass through
the membrane, while cellular components and other
solutes remain behind.
• The water and solutes that pass through the
membrane are called ultrafiltrate.
• The membrane and its housing are referred to as the
filter.

38. RRT Molecular Transport Mechanisms
• Ultrafiltration
• Diffusion
• Convection
• Adsorption
Fluid Transport
Solute Transport
}

39. Ultrafiltration
• Ultrafiltration is the passage of fluid through a
membrane under a pressure gradient.
• Pressures that drive ultrafiltration can be positive, that is
the pressure pushes fluid through the filter.
• They can also be negative, there may be suction applied
that pulls the fluid to the other side of the filter.
• Also osmotic pressure from non-permeable solutes.
• The rate of UF will depend upon the pressures applied to
the filter and on the rate at which the blood passes
through the filter.
• Higher pressures and faster flows increase the rate of
ultrafiltration.
• Lower pressures and slower flows decrease the rate of
ultrafiltration.

40. Blood Out
Blood Into waste
(to patient)
(From patient)
HIGH PRESSLOW PRESS
Fluid Volume
Reduction
Ultrafiltration

41. Diffusion
• Diffusion is the movement of a solute across a
membrane via a concentration gradient.
• For diffusion to occur, another fluid must flow on the
opposite side of the semi-permeable membrane. In
blood purification this fluid is called dialysate.
• Solutes always diffuse across a membrane from an
area of higher concentration to an area of lower
concentration until equilibration.

42. Haemodialysis: Diffusion
Dialysate In
Dialysate Out
(to waste)
Blood Out
Blood In
(to patient)
(from patient)
HIGH CONCLOW CONC

43. Convection
• Convection is the movement of solutes through a
membrane by the force of water (“solvent drag”).
• Convection is able to move very large molecules if the
flow of fluid through the membrane is fast enough.
• In CRRT this property is maximized by using replacement
fluids.
• Replacement fluids are crystalloid fluids administered at a
fast rate just before or just after the blood enters the
filter.

44. to waste
HIGH PRESSLOW PRESS
Repl.
Solution
Haemofiltration: Convection
Blood Out
Blood In
(to patient)
(from patient)

45. Adsorption
• Adsorption is the removal of solutes from the
blood because they cling to the membrane.
• In blood purification. High levels of
solute/molecule adsorption can cause filters
to clog and become ineffective.

46. Adsorption
• Molecular adherence to the surface or interior of the
membrane.

47. Molecular WeightsDaltons
 Inflammatory Mediators (1,200-40,000)
“small”
“middle”
“large”

48. Kinetic Modelling of Solute Clearance
CVVH (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
b2 microglobulin TAC (mg/L) 9.4 24.2 40.3
b2 microglobulin EKR (ml/min) 18.2 7.0 4.2
TAC = time-averaged concentration (from area under concentration-time curve)
EKR = equivalent renal clearance
Inulin represents middle molecule and b2 microglobulin large molecule.
CVVH has marked effects on middle and large molecule clearance not seen with IHD/SLED
SLED and CVVH have equivalent small molecule clearance
Daily IHD has acceptable small molecule clearance
Liao, Z et al. Artificial Organs 2003; 27: 802-807

49. 0
20
40
60
80
100
Clearancein%
35.000 55.00020.0005.0002.500
Urea
(60)
Albumin
(66.000)
Myoglobin
(17.000)
65.000
Creatinine
(113)
Kidney
Convection
Diffusion
Small vs. Large Molecules Clearance

50. Uraemia Control
Liao, Z et al. Artificial Organs 2003; 27: 802-807

51. Large molecule clearance
Liao, Z et al. Artificial Organs 2003; 27: 802-807

52. Major Renal Replacement Techniques
Intermittent ContinuousHybrid
IHD
Intermittent
haemodialysis
IUF
Isolated
Ultrafiltration
SLEDD
Sustained (or slow)
low efficiency daily
dialysis
SLEDD-F
Sustained (or slow)
low efficiency daily
dialysis with
filtration
CVVH
Continuous veno-venous
haemofiltration
CVVHD
Continuous veno-venous
haemodialysis
CVVHDF
Continuous veno-venous
haemodiafiltration
SCUF
Slow continuous
ultrafiltration

53. CRRT Modes of Therapy
• SCUF - Slow Continuous Ultrafiltration
• CVVH - Continuous Veno-Venous Hemofiltration
• CVVHD - Continuous Veno-Venous HemoDialysis
• CVVHDF - Continuous Veno-Venous HemoDiaFiltration

54. Vascular Access and the Extracorporeal
Circuit
• There are two options for vascular access for
CRRT, venovenous and arteriovenous.
• Venovenous access is by far the most
commonly used in the modern ICU.

55. Electrolytes & pH Balance
• Another primary goal for CRRT, specifically:
– Sodium
– Potassium
– Calcium
– Glucose
– Phosphate
– Bicarbonate or lactate buffer
• Dialysate and replacement solutions are used in
CRRT to attain this goal.

56. Dialysate Solutions
• Dialysate is a crystalloid solution containing various
amounts of electrolytes, glucose, buffers and other solutes.
• Flows counter-current to blood flow between 600 –
1800mL/hour
• Remains separated by a semi-permeable membrane
• Drives diffusive transport
– dependent on concentration gradient and flow rate
• Facilitates removal of small solutes
• Contains physiologic electrolyte levels
• Components adjusted to meet patient needs

57. Replacement Solutions
• Infused directly into the blood at points along the
blood pathway
• Replacement fluids are used to increase the amount
of convective solute removal in CRRT
• Facilitates the removal of small middle and large
solutes
• Contains electrolytes at physiological levels
• Important to understand that despite their name,
Replacement fluids do not replace anything.

58. Effluent Flow Rate
Effluent = Total Fluid Volume:
• Patient Fluid Removal
• Dialysate Flow
• Replacement Flow
• Pre-Blood Pump Flow

59. Anticoagulation & CRRT
• Anticoagulation is needed as the clotting
cascades are activated when the blood
touches the non-endothelial surfaces of
the tubing and filter.
• CRRT can be run without anticoagulation

60. SCUF
Slow Continuous Ultra-Filtration
Primary therapeutic goal:
– Safe and effective management of fluid removal from the
patient
• No dialysate or replacement fluid is used
• Primary indication is fluid overload without uremia or
significant electrolyte imbalance.
• Removes water from the bloodstream through ultrafiltration.
• The amount of fluid in the effluent bag is the same as the
amount removed from the patient.
• Fluid removal rates are typically closer to 100-300 mL/hour.

61. SCUF
• High flux membranes
• Up to 24 hrs per day
• Objective VOLUME control
• Not suitable for solute clearance
• Blood flow 50-200 ml/min
• UF rate 2-8 ml/min

62. SCUF
Slow Continuous UltraFiltration
Effluent
Pump
Infusion or
Anticoagulant
Blood Pump
PBP
Pump
Effluent
Access
Return

63. CVVH
Continuous VV Hemofiltration
• Primary Therapeutic Goal:
- Removal of small, middle and large sized solutes
- Safe fluid volume management
• Blood is run through the filter with a replacement fluid added
either before or after the filter.
• No dialysate is used.
• Extremely effective method of solute removal and is indicated
for uremia or severe pH or electrolyte imbalance with or
without fluid overload.
• Removes solutes via convection, and is particularly good at
removal of large molecules.
• Ideal in severe renal impairment combined with a need to
maintain or increase fluid volume status.
• The amount of fluid in the effluent bag is equal to the amount
of fluid removed from the patient plus the volume of
replacement fluids administered.

64. CA/VVH
• Extended duration up to weeks
• High flux membranes
• Mainly convective clearance
• UF > volume control amount
• Excess UF replaced
• Replacement pre- or post-filter
• Blood flow 50-200 ml/min
• UF rate 10-60 ml/min

65. CVVH
Continuous VV Hemofiltration
Effluent
Pump
Blood
Pump
Effluent
Access
Return
Replacement
Pump 1
Replacement
Pump 2
Replacement 1Replacement 2 Infusion or
Anticoagulant
PBP
Pump

66. Pre-Dilution Replacement Solution
• Decreases risk of
clotting
• Higher UF capabilities
• Decreases Hct
Hemofilter
Effluent
Pump
Blood
Pump
PBP
Pump
Effluent
Access
Return
Replacement
Pump
Replacement
Fluid
Infusion or
Anticoagulant

67. Post-Dilution Replacement Solution
• Consider lowering
replacement rates
(filtration %)
• Higher BFR (filtration
%)
• Higher
anticoagulation
• More efficient
clearance (>15%)
Hemofilter
Effluent
Pump
Blood
Pump
Effluent
Access
Return
Replacement
Pump
Replacement
Fluid
Replacement
Pump
Replacement
Fluid
PBP
Pump
Infusion or
Anticoagulant

68. CVVHD
Continuous VV HemoDialysis
• Primary therapeutic goal:
– Small solute removal by diffusion
– Safe fluid volume management
• Dialysate is run on the opposite side of the filter, no
replacement fluid is used.
• Similar to traditional hemodialysis, and is effective for removal
of small to medium sized molecules.
• Solute removal due to diffusion
• Dialysate can be tailored to promote diffusion of specific
molecules.
• CVVHD can be configured to allow a positive or zero fluid
balance, it is more difficult than with CVVH because the rate
of solute removal is dependent upon the rate of fluid removal
from the patient.
• The amount of fluid in the effluent bag is equal to the amount
of fluid removed from the patient plus the dialysate.

69. CA/VVHD
• Mid/high flux membranes
• Extended period up to weeks
• Diffusive 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

70. CVVHD
Continuous VV HemoDialysis
Hemofilter
Effluent
Pump
Effluent
Access
Return
Dialysate
Pump
Dialysate
Fluid
Blood
Pump
Infusion or
Anticoagulant
PBP
Pump

71. CVVHDF
Continuous VV HemoDiaFiltration
• Primary therapeutic goal:
– Solute removal by diffusion and convection
– Safe fluid volume management
– Efficient removal of small, middle and large molecules
• Dialysate and replacement fluid either before or after the
filter.
• Combines the benefits of diffusion and convection for solute
removal.
• The amount of fluid in the effluent bag equals the fluid
removed from the patient plus the dialysate and the
replacement fluid.

72. CVVHDF
• High flux membranes
• Extended period up to weeks
• Diffusive & convective solute
clearance
• Countercurrent dialysate
• UF exceeds volume control
• Replacement 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

73. CVVHDF
Continuous VV HemoDiaFiltration
Effluent
Pump
Effluent
Access
Return
Dialysate
Pump
Dialysate
Fluid
Blood
Pump
Replacement
Pump
Replacement
Fluid
PBP
Pump
Infusion or
Anticoagulant

74. SLED(D) & SLED(D)-F : Hybrid therapy
• Conventional dialysis equipment
• Online dialysis fluid preparation
• Excellent 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

75. Complications of CRRT
• Bleeding
• Hypothermia
• Electrolyte Imbalances
• Acid-Base Imbalances
• Infection
• Appropriate Dosing of Medications

76. 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 outcome
Herrera-Gutierrez, ME et al. ASAIO Journal 2006; 52: 670-676

77. 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

78. Beyond renal replacement…
RRT as blood purification
therapy

79. Extracorporeal Blood Purification Therapy
(EBT)
Intermittent Continuous
TPE
Therapeutic plasma
exchange
HVHF
High volume
haemofiltration
UHVHF
Ultra-high volume
haemofiltration
PHVHF
Pulsed high volume
haemofiltration
CPFA
Coupled plasma
filtration and
adsorption

80. Peak Concentration Hypothesis
• Removes cytokines from blood compartment
during pro-inflammatory phase of sepsis
• Assumes 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 unknown
Ronco, C & Bellomo, R. Artificial Organs 2003; 27: 792-801

81. Threshold Immunomodulation Hypothesis
• More dynamic view of cytokine system
• Mediators and pro-mediators removed from
blood to alter tissue cytokine levels but blood
level 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

82. 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

83. High Volume Haemofiltration
• May reduce unbound fraction of cytokines
• Removes
– endothelin-I (causes early pulm hypertension in sepsis)
– endogenous cannabinoids (vasoplegic in sepsis)
– myodepressant factor
– PAI-I so may eventually reduce DIC
• Reduces post-sepsis immunoparalysis (CARS)
• Reduces inflammatory cell apoptosis
• Human trials probably using too low a dose (40
ml/kg/hour vs 100+ ml/kg/hour in animals)

84. High-volume versus standard-volume
haemofiltration for septic shock patients with
acute kidney injury (IVOIRE study): a
multicentre randomized controlled trial
Intensive Care Med. 2013 Sep;39(9):1535-46.
No evidence that HVHF at 70 mL/kg/h, when compared
with contemporary SVHF at 35 mL/kg/h, leads to a
reduction of 28-day mortality or contributes to early
improvements in haemodynamic profile or organ
function. HVHF, as applied in this trial, cannot be
recommended for treatment of septic shock
complicated by AKI

85. Towards Targeted Therapy
Honore, PM et al. Int J Artif Organs 206; 29: 649-659
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/hour
for 96 hours
PHVHF 60-120
ml/kg/hour
for 6-8 hours
then CVVH >
35 ml/kg/hour
EBT
Cerebral oedema