Andrew DurwardLondon 2015

Haemofiltration for sepsis:burial or resurrection?

DiseaseSepsis

DiseaseModification

OUTCOME

Haemofiltration

AKI

Apoptosis

Cell death

Indication CVVH

Timing CVVH

Efficiency

Complications

Target /Goal

Severity of illness

Is haemofiltration beneficial in sepsis?

• Mortality benefit in sepsis ?• With or with

kidney injury ?• What mechanism ?• Dialysis dose

benefit ?

Haemofiltration in sepsis1. Obtain fluid balance2. Acid base balance3. Electrolyte normalisation4. Cyotkine and toxin removal

• Titratable fluid loss• Haemodynamic stability• Temperature control• Antibiotic dosing may be modified• Risk anticoagulation / vascular access

Macedo Nephrol Dial Transplant 2010

Oliguria is not good

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

Plasma exchange in meningococcal sepsis

Cytokine Peak Concentration Hypothesis

Annu. Rev. Pathol. Mech. Dis. 2006. 1:467–96

Just need toBalance the Cytokine scales

Kellum CCM 2004

Endotoxin adsorption on haemofilter

Cytokine removal in sepsisn=24 adults with sepsis, no AKINo reduction in cytokines, no clinical benefit

Cole CCM 2002:30,100-106 De Vriese Am Soc Nephrol 1999;10:846

n=76 adults sepsis . CVVH (35ml/kg/hr) vs standard careNo change cytokinesworse organ failure scores with CVVHLonger ventilation and inotrope need

Payen Crit Care Med 2009; 37:803–810

CVVH may be harmful in sepsis

Worsening SOFA Score Time to death

Arch Intern Med. 2007;167(15):1655-1663

1. Systemic cytokine activation common, not universal

2. Cytokines had peaked by ICU admission3. No rise in cytokine with the onset of organ

dysfunction4. Differences between groups with different

outcomes were modest5. Cytokines remained high even with clinical

recovery in some6. Mortlaity highest when both pro and anti-

inflammatory cytokines are high

Genetic and inflammatory markers of Sepsisn=1886 adults pneumonia in 28 US centres

JAMA. 2011;306(23):2594-2605

RENAL study (n=1508) NEJM 2009CVVHDF 25ml/kg vs 40ml/kg/hrNo difference mortality

Tolwani (n=200) J Am Soc Neph 2008CVVHDF 20ml/kg vs 35ml/kg/hrNo difference mortality

NIH ATN (n=1124) NEJM 2008CVVHDF 35ml/kg vs 20ml/kg/hrNo difference mortality

Dose dialysis in sepsis: No effect

Wald et al. Critical Care 2012, 16:R205

Acute Kidney Injury (OMAKI) Canadian Trial groupCVVH vs CVVHD n=78 adults (80% sepsis) Same dialysis dose of 35ml/kg/hr effluent rate

Mode dialysis in sepsis: CVVH vs CVVHD

No difference mortalityCVVH 12/35 35% CVVHD 10/38 27%

Intensive Care Med (2013) 39:1535–1546

n=144 Adults

(96 hrs dialysis)

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

Falling annual mortality with sepsis

ARF mortality 55 % (2000) 35% (2012)

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 quicker8% increase death / hour delay. CCM 2006;34:1589-1596

10% severe sepsis

Lancet Infect Dis 2015;15: 46–54

97127 children

2.9% sepsis

2.1% septic shock

Mortality severe sepsis

unchanged

19% 2002-2007

15% 2008-20012

Paediatric sepsis 2002 – 2012 (Australia / NZ)

Schneider A G et al. Nephrol. Dial. Transplant. 2012;27:947-952

Untreated AKI without dialysis is not good

29 vs 43% sepsis

Adults vs Children: BFR vs UFR

Sepsis 25% 37% 40%

3% mortality per 1% increase fluid overload N=297 children

Multicentre

GET THE FLUID OFF

CVVH for fluid overload

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)