Transcript Role of CRRT in Sepsis

ROLE OF CRRT IN SEPSIS
Dr Apoorva Jain
Agra
SEPSIS:
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BACKGROUND
Severe Sepsis and Septic Shock are the primary
causes of Multiple Organ Dysfunction Syndrome
(MODS) [of which Acute Renal Failure-is part of]
One of the most common cause of mortality in the
ICU setting
SEPSIS:
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BACKGROUND
Variety of Water soluble mediators with Pro & AntiInflammatory Activities play a strategic role in
Septic Syndrome including (but not limited to):
TNF, IL-6,IL-8 and IL-10, Kinins, Thrombins, heat shock
proteins
SEPSIS:

BACKGROUND
Stimulus –Receptor coupling sets off the signal
transduction cascade resulting in exacerbated
generation of; Platelet activating factor, cytokines,
leukotrienes, Arachidonic acid derivatives etc.) and
activation of the complement cascade and
coagulation pathways.
SEPSIS: Pathophysiology
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Dysfunctional homeostatic balance results in increased
biological activity of sepsis associated mediators and
loss of control over these by specific inhibitors-cell
hypo-responsiveness
This excessive anti-inflammatory counterpart to SIRS
has been coined “CARS- Compensated Antiinflammatory Response Syndrome”

Bone et al. Chest 112:235-43, 1997
Goals of Treatment are hemodynamic and
relate to outcome
Early Goal-Directed Therapy in the treatment of Severe
Sepsis and Septic Shock. Rivers E, N Engl J Med
2001;345:1368-1377.
RCT
Results:
130 adults randomized to aggressive care In First few hours
In Hospital Mortality 30.5% vs 46.5% in Controls
Early goal directed therapy improves shock outcome (Han Y.
2000 Pediat Res 47:108a. Ceneviva G. Pediatrics 1998;102:e19.)
OUTLINE
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1 CRRT for Sepsis - associated AKI
2. CRRT as Immunomodulatory therapy
CRRT for Sepsis-associated AKI
CRRT for Sepsis-associated AKI
• Role & Indications
• Dosing
• Alternative therapies
CRRT for Sepsis-associated AKI
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Dialysis allows:
– Correction of acid-base status
– Correction of electrolyte abnormalities
– Clearance of toxins
– Control of fluid balance
CRRT for Sepsis-associated AKI
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Advantages of using CRRT
 Suitable
for use in hemodynamically unstable patients
 Precise, adaptable, volume control
 Very effective control of uremia, PO4, K
 Rapid control of metabolic acidosis
 Improved nutritional support (full protein diet)
 Available 24 hours a day
 May have an effect as an adjuvant therapy in sepsis
CRRT for Sepsis-associated AKI
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Disadvantages of using CRRT
 Expense
– more than IHD, due to fluids
 Continuous anticoagulation may be required
 Risk of line disconnection
 Hypothermia
 Severe depletion of electrolytes (K and PO4), nutrients
CRRT for Sepsis-associated AKI
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Dosing of dialysis in AKI
 425
patients randomized
 Post-dilution CVVH mode
 only 12% had sepsis
Ronco et al, Lancet 2000; 355: 26
CRRT for Sepsis-associated AKI
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Modes of CRRT
CRRT for Sepsis-associated AKI
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Modes of CRRT
CRRT for Sepsis-associated AKI
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Modes of CRRT
CRRT for Sepsis-associated AKI
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Dosing of dialysis in AKI
 206
patients randomized
 60% sepsis
 CVVH versus
CVVH + added D
Saudan et al, Kidney Int 2006; 70:1312
CRRT for Sepsis-associated AKI
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Negative dosing studies
 200
patients
 CVVHDF
20 v 35 ml/kg/hr
 No difference
Tolwani et al J Am Soc Nephrol 2008; 19:1233
 1124
patients, multicentred (NIH ATN study)
 Intensified
(35ml/kg, 6x/wk IHD) versus
 Standard (20ml/kg, 3x/wk IHD)
 No difference
Palevsky et al N Engl J Med 2008; 359:7.
CRRT for Sepsis-associated AKI
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Reasons for differences
 Delayed
initiation of RRT in Tolwani and ATN studies: 6
to 8 days
 No clear separation of dose delivered when combining
CRRT and IHD dosing (ATN study)
 Majority (65%) enrolled after initial dialysis
 Dosing was not actually achieved in the ATN study
CRRT for Sepsis-associated AKI
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RENAL study
 1508
patients, approx 50% sepsis
 48-54 hr in ICU before randomisation
 Prescribed dose achieved: 84 – 88%
 CVVHDF, postdilution (1:1 dialysate:filtration)
 Low
intensity: 25 ml/kg/hr
 High intensity: 40 ml/kg/hr
 No
difference in mortality
N Engl J Med Oct 22nd, 2009.
CRRT for Sepsis-associated AKI
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Alternative therapies
IHD
 mortality
higher in many CRRT studies
 5 RCT’s: no difference in mortality
 7 meta-analyses: no differences
CRRT for Sepsis-associated AKI
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Alternative therapies
Kellum et al. Intensive Care Med 2002; 28:29
CRRT for Sepsis-associated AKI
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Alternative therapies
Bagshaw et al, Crit Care Med 2008; 36:610
CRRT for Sepsis-associated AKI
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Alternative therapies
IHD
 mortality
higher in many CRRT studies
 5 RCT’s: no difference in mortality
 7 meta-analyses: no differences
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SLED: sustained low efficiency dialysis
 safe,
effective, cheaper than CRRT
 limited comparative data
Berbece & Richardson, Kidney Int 2006; 70:963
Epidemiology of AKI
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BEST Kidney study:
 23
countries, over 30,000 patients, 2001
 1738 developed acute renal failure
 Dialysis
CVVH 53%
 CRRT
80% -- IHD 17%
 SLED/PD 3%
 Hospital
CVVHD 13%
CVVHDF 34%
mortality 60%
Uchino et al, JAMA 2005; 294:813
Uchino et al, Intensive Care Med, 2007 33:1563
CRRT as Immunomodulatory therapy
CRRT as Immunomodulatory therapy
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Background & rationale
Studies supporting this hypothesis
Clinical studies
Variations on standard CRRT
CRRT as Immunomodulatory therapy
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Rationale – Removal of “Bad Humours”
CRRT as Immunomodulatory therapy
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Rationale – Removal of “Bad Humours”
CRRT as Immunomodulatory therapy
CRRT as Immunomodulatory therapy
Ronco et al. Artif organs 2003; 27:792
CRRT as Immunomodulatory therapy
Ronco et al. Artif organs 2003; 27:792
CRRT as Immunomodulatory therapy
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Mechanism of cytokine removal
 Convective
 High
flux membranes cut-off 30 – 40 kD
 Should remove many cytokines (17 – 30 kD)
 Is removal rate significant given high production?
 Adsorption
 Filter
dependent: higher with polyacrylonitrile (AN69) than
with polysulfone membranes
CRRT as Immunomodulatory therapy
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Convective therapy can:
 Remove
cytokines
 In
some, but not all studies
 Adsorption important
 Frequent filter changes
 Plasma levels unchanged
 Improve
hemodynamics
 In
animal studies
 In open clinical studies
Heering et al Intensive Care Med. 1997;23:288
CRRT as Immunomodulatory therapy
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15 pts, sepsis, AKI
 first
24 hr hemofiltration
 AN69 filter
De Vriese et al. J Am Soc Nephrol 1999;10:846-853
CRRT as Immunomodulatory therapy
Morgera et al. Crit Care Med 2006; 34:2099
CRRT as Immunomodulatory therapy
Morgera et al. Crit Care Med 2006; 34:2099
CRRT as Immunomodulatory therapy
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Outcome studies
CRRT as Immunomodulatory therapy
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Ronco study
Ronco et al, Lancet 2000; 355: 26
CRRT as Immunomodulatory therapy
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RENAL study
CRRT as Immunomodulatory therapy
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CRRT without AKI
 Sepsis,
no renal failure
 CVVH, 2L/hr, AN69 filter
 No
significant reduction in
cytokines
 No
clinical benefit
Cole et al, Crit Care Med 2002; 30:100
CRRT as Immunomodulatory therapy
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Outcome studies
 80
patients, early CVVH 25ml/kg/hr or control
 High flux polysulfone filter
Payen et al Crit Care Med 2009; 37:803
CRRT as Immunomodulatory therapy
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Outcome studies
 80
patients, early CVVH 25ml/kg/hr or control
 High flux polysulfone filter
 No benefit, deleterious?
Payen et al Crit Care Med 2009; 37:803
CRRT as Immunomodulatory therapy
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Outcome studies
 80
patients, early CVVH 25ml/kg/hr or control
 High flux polysulfone filter
 No benefit, deleterious?
Payen et al Crit Care Med 2009; 37:803
CRRT as Immunomodulatory therapy
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Outcome studies
 80
patients, early CVVH 25ml/kg/hr or control
 High flux polysulfone filter
 No benefit, deleterious?
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Can’t expect a mortality benefit
with the wrong intervention in the
wrong dose
Payen et al Crit Care Med 2009; 37:803
Variations on standard CRRT
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High volume hemofiltration
High cutoff hemofiltration
Plasmafiltration
Cascade filtration
Coupled plasma filtration adsorption