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Andrew Durward
London 2015
Haemofiltration for sepsis:
burial or resurrection?
Is haemofiltration beneficial in sepsis?
• Mortality benefit in
sepsis ?
• With or with
kidney injury ?
• What mechanism ?
• Dialysis dose
benefit ?
Disease
Sepsis
Disease
Modification
OUTCOME
Apoptosis
Severity of
illness
AKI
Cell death
Haemofiltration
Target /Goal
Indication CVVH
Timing
CVVH
Efficiency
Complications
Haemofiltration in sepsis
1.
2.
3.
4.
Obtain fluid balance
Acid base balance
Electrolyte normalisation
Cyotkine and toxin removal
•
•
•
•
•
Titratable fluid loss
Haemodynamic stability
Temperature control
Antibiotic dosing may be modified
Risk anticoagulation / vascular access
Oliguria is not good
Macedo Nephrol Dial Transplant 2010
Plasma exchange in meningococcal sepsis
•
•
•
•
Plasma exchange (3-4 volumes)
Followed by CVVH
n=85 children
Of 23 with CVVH 6 died (26%)
Cytokine Peak Concentration Hypothesis
Just need to
Balance the
Cytokine scales
Annu. Rev. Pathol. Mech. Dis. 2006. 1:467–96
Endotoxin adsorption on haemofilter
Kellum CCM 2004
Cytokine removal in sepsis
n=24 adults with sepsis, no AKI
No reduction in cytokines, no clinical benefit
Cole CCM 2002:30,100-106
De Vriese Am Soc Nephrol 1999;10:846
CVVH may be harmful in sepsis
n=76 adults sepsis . CVVH (35ml/kg/hr) vs standard care
No change cytokines
worse organ failure scores with CVVH
Longer ventilation and inotrope need
Worsening SOFA Score
Time to death
Payen Crit Care Med 2009; 37:803–810
Genetic and inflammatory markers of Sepsis
n=1886 adults pneumonia in 28 US centres
1. Systemic cytokine activation common, not
universal
2. Cytokines had peaked by ICU admission
3. No rise in cytokine with the onset of organ
dysfunction
4. Differences between groups with different
outcomes were modest
5. Cytokines remained high even with clinical
recovery in some
6. Mortlaity highest when both pro and antiinflammatory cytokines are high
Arch Intern Med. 2007;167(15):1655-1663
JAMA. 2011;306(23):2594-2605
Dose dialysis in sepsis: No effect
RENAL study (n=1508) NEJM 2009
CVVHDF 25ml/kg vs 40ml/kg/hr
No difference mortality
Tolwani (n=200) J Am Soc Neph 2008
CVVHDF 20ml/kg vs 35ml/kg/hr
No difference mortality
NIH ATN (n=1124) NEJM 2008
CVVHDF 35ml/kg vs 20ml/kg/hr
No difference mortality
Mode dialysis in sepsis: CVVH vs CVVHD
Acute Kidney Injury (OMAKI) Canadian Trial group
CVVH vs CVVHD n=78 adults (80% sepsis)
Same dialysis dose of 35ml/kg/hr effluent rate
No difference mortality
CVVH 12/35 35%
CVVHD 10/38 27%
Wald et al. Critical Care 2012, 16:R205
15 % absolute reduction in 28-day
mortality (460 patients)
Stopped early before power obtained
n=144 Adults
(96 hrs dialysis)
CVVH 70ml/kg/hr vs 35ml/kg/hr
No difference 28 day mortality
Intensive Care Med (2013) 39:1535–1546
Falling annual mortality with sepsis
Over 1 million patients (171 ICU’s Australia / NZ)
Absolute mortality in severe sepsis decreased
from 35% to 18% in 2012 (1.3% reduction per year)
10% severe sepsis
ARF mortality
55 % (2000)
35% (2012)
Surviving sepsis 5.4% fall in
mortality in participating
centres over 3 yrs
Giving antibiotics quicker
8% increase death / hour
delay. CCM 2006;34:1589-1596
Paediatric sepsis 2002 – 2012 (Australia / NZ)
97127 children
2.9% sepsis
2.1% septic shock
Mortality severe sepsis
unchanged
19% 2002-2007
15% 2008-20012
Lancet Infect Dis 2015;15: 46–54
Untreated AKI without dialysis is not good
29 vs 43% sepsis
Schneider A G et al. Nephrol. Dial. Transplant. 2012;27:947-952
Adults vs Children: BFR vs UFR
CVVH for fluid overload
N=297 children
3% mortality per 1% increase fluid overload
Multicentre
GET THE
FLUID OFF
Sepsis 25%
37%
40%
Hyperchloraemia: Survival advantage in children
Summary
1. AKI increases mortality in sepsis
2. CVVH benefit for fluid overload
3. No evidence immune modulating
4. Get basic care right first
(eg. surviving sepsis campaign)
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