1. Haemofiltration for sepsis: burial or resurrection?
Andrew Durward
London 2015
Haemofiltration for sepsis:
burial or resurrection?

2. 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
Cell death
AKI
Severity of
illness
Haemofiltration
Target /Goal
Indication CVVH
Efficiency
Timing CVVH
Complications

3. Haemofiltration in sepsis
Obtain fluid balance
Acid base balance
Electrolyte normalisation
Cyotkine and toxin removal
Oliguria is not good
Titratable fluid loss
Haemodynamic stability
Temperature control
Antibiotic dosing may be modified
Risk anticoagulation / vascular access
Macedo Nephrol Dial Transplant 2010

4. Plasma exchange in meningococcal sepsis
Plasma exchange (3-4 volumes)
Followed by CVVH
n=85 children
Of 23 with CVVH 6 died (26%)

5. Cytokine Peak Concentration Hypothesis
Just need to
Balance the
Cytokine scales
Annu. Rev. Pathol. Mech. Dis :467–96

6. Endotoxin adsorption on haemofilter
Kellum CCM 2004

7. Cytokine removal in sepsis
n=24 adults with sepsis, no AKI
No reduction in cytokines, no clinical benefit
Cole CCM 2002:30, De Vriese Am Soc Nephrol 1999;10:846

8. 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

9. Genetic and inflammatory markers of Sepsis
n=1886 adults pneumonia in 28 US centres
Systemic cytokine activation common, not universal
Cytokines had peaked by ICU admission
No rise in cytokine with the onset of organ dysfunction
Differences between groups with different outcomes were modest
Cytokines remained high even with clinical recovery in some
Mortlaity highest when both pro and anti-inflammatory cytokines are high
Arch Intern Med. 2007;167(15):

10. JAMA. 2011;306(23):

11. 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

12. 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 / %
CVVHD 10/ %
Wald et al. Critical Care 2012, 16:R205

13. CVVH 70ml/kg/hr vs 35ml/kg/hr No difference 28 day mortality
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

14. 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)
Surviving sepsis 5.4% fall in mortality in participating centres over 3 yrs
Giving antibiotics quicker
8% increase death / hour delay. CCM 2006;34:
10% severe sepsis
ARF mortality
55 % (2000) % (2012)

15. Paediatric sepsis 2002 – 2012 (Australia / NZ)
97127 children
2.9% sepsis
2.1% septic shock
Mortality severe sepsis unchanged
19%
15%
Lancet Infect Dis 2015;15: 46–54

16. Untreated AKI without dialysis is not good
29 vs 43% sepsis
Schneider A G et al. Nephrol. Dial. Transplant. 2012;27:

17. Adults vs Children: BFR vs UFR

18. CVVH for fluid overload
N=297 children
Multicentre
3% mortality per 1% increase fluid overload
GET THE
FLUID OFF
Sepsis 25% % %

19. Hyperchloraemia: Survival advantage in children

20. Summary AKI increases mortality in sepsis
CVVH benefit for fluid overload
No evidence immune modulating
Get basic care right first
(eg. surviving sepsis campaign)