1. ARF in ICU
Andy Slack

2. ARF definition in critically ill.
RIFLE Classification.
Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group
Rinaldo Bellomo1, Claudio Ronco2 et al
Separate criteria for SCr and urine output, patients can fulfill either criteria.
Criteria leading to worse classification should be used.
Criteria for changes in SCr and UO or both.
RIFLE-Fc = acute on chronic with SCr >350 or >4mg/dl in setting of an acute SCr rise 0.5mg/dl or 44mmol/l.
RIFLE-Fo = ARF with oliguria
If no previous Cr known use MDRD Calculation for estimate GFR. (Modification of diet in renal disease)

3. ARF – RIFLE definition

4. Epidemiology ARF 1-25% ICU patients and ICU bed occupancy up to 10%.
High mortality rate 28-90%
Separate independent effect on mortality.
Predictors of poor prognosis for pts with ARF in ICU include; oliguria, CPR, mechanical ventilation and LOS>7day prior to admission to ICU.

5. Pathophysiology
Pathogenesis is an immune or toxic state rather than simply a hemodynamic condition.
Acute apoptosis; growing evidence of a role for apoptosis in organ injury during sepsis.
Haemodynamic disease causing kidney ischemia
High CO, low SVR state seen in human sepsis has been poorly reproduced in animal models.
Curr Opin Crit Care Dec;9(6): The pathogenesis of septic acute renal failure. Wan L, Bellomo R, Di Giantomasso D, Ronco C.
Renal perfusion remains important. Beneficial effect of increasing MAP with fluid/NA without a reduction CO.
ARF causes loss of autoregulation and sepsis is associated with BP below autoregulatory threshold
Blood purification 2002;20(3) Vasopressors and the kidney Schetz M

6. ARF and Sepsis Severe sepsis is primary cause of MOD
Infectious sepsis and non-infectious response syndrome SIRS.
Sepsis is no longer simply pro-inflammatory.
Hyporesponsive seen in monocytes and whole blood with increased IL-10 and PGE2
Both are potent inhibitors of inflammatory cytokines.

7. ARF and Sepsis
Severe sepsis SIRS and CARS (compensated anti-inflammatory response syndrome) may coexist.
Inducing either shock or immune depression in different compartments.
In parallel (parallel theory) or in sequence (serial theory).
SIRS predominates in inflammed tissues Bone et al
CARS in systemic blood leucocytes, which show hyporeactivity. Cavaillon et al

8. ARF and Sepsis

9. ARF and Sepsis 80% ARF associated MODS.
Pro and inhibitory inflammatory mediators circulate in blood.
MOST=Multi organ support therapy
Concept that all organs are in contact with blood and all extracorporeal therapies treat blood.

10. ARF and Sepsis Blood purification includes HD, CVVHF and CPFA.
Inflammatory mediators are of molecular size 5-70,000 Daltons and act at low concentrations.
RRTs are able to filter blood and remove these undesirable molecules(~20KDalton.)
Growing evidence that global and non selective elimination of cytokine peaks confer prognostic benefit.
The peak concentration hypothesis.

11. The Peak concentration hypothesis

12. Haemodialysis Semipermeable membrane
Concentration gradient with diffusion of molecules according to size
Urea 60D faster than Creatinine 116D and PO4 very little
Dialysate used to normalise plasma and has [Na+] physiological and [K+] lower. Urea and Cr zero.
Dialysate flows in opposite direction to blood.
TMP to remove salt and water.

13. Haemofiltration Highly permeable membrane
Water and molecules up to 20K Daltons pass through by convective flow.
Urea/Cr/PO4/Heparin/Vanco cleared at similar rate.
Unlike human kidney ultrafiltrate is discarded and replacement fluid required.
Replacement fluid is physiological with a buffer, either lactate or HCO3-.

14. ARF and RRT
Venous therapy possible now there are blood pumps on the machines.
Anticoagulation required heparin or citrate.
Intensive Care Medicine 2004;30: Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P.
Dialysis dose – depends on the clinical situation.
Catabolic septic patients have improved outcomes with higher dialysis doses i.e. UF/24hrs.

15. Randomized control trial 425 pt with different UF doses
Randomized control trial 425 pt with different UF doses. >35ml/kg/hr is best.

16. ARF and RRT Only 6 randomized controlled trials performed to date.
No statistical difference between HD and CVVHF.
Evidence to support CVVHF over HD includes;
Fluid management - unsuccessful in critically ill on HD, Mehta et al Kidney international 2001
Efficacy/tolerance - >85% receive prescribed dose with CVVHF Ronco Lancet 2000.
Delivery Kt/V <25% of prescribed Kt/V with HD – Schiff et al

17. Newer RRT modes Coupled plasma – filtration absorption - CPFA
Clinical benefit with low dose CVVHF is poor.
Lastest techniques target elimination of sepsis mediators.
Cytokines have high sieving coefficients and thus plamsa filters have been developed which have a high absorbing capacity.

18. Coupled plasma-filtration adsorption

19. CPFA and sepsis
Sepsis study CPFA vs CVVHF (San Bortolo Hosptial) study
Increased CI/SVR and reduction NA dose but no change MAP.
Now Sepsis study CPFA vs CVVHF San Bortolo Hosptial study planned but only CFPA for 4hrs!
Magic shield against inflammatory mediators in sepsis – immunomodulation.

20. ARF and Diuretics Am J Kidney Dis. 2004 Sep;44(3):402-9.
High-dose furosemide for established ARF: a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Cantarovich F, Rangoonwala B, Lorenz H, Verho M, Esnault VL; High-Dose Flurosemide in Acute Renal Failure Study Group.
338 pts with ARF requiring HD randomised to placebo, frusemide - IV 25mg/kg/d vs PO 35mg/kg/d.
High-dose furosemide helps maintain urinary output.
No impact on the survival and renal recovery rate of patients with established ARF.

21. ARF and diurectics J Nephrol. 2002 May-Jun;15(3):213-9.
Diuretics and dopamine for the prevention and treatment of acute renal failure: a critical reappraisal. Gambaro G, Bertaglia G, Puma G, D'Angelo A.
Very few well controlled, large trials testing these agents in different ARF settings, with either a preventive or a curative goal.
Most rule out favourable effects of diuretics, mannitol, atrial natriuretic peptides, and dopamine.

22. The End!! BUT: Useful to understand how to clinically estimate CO.
CO is pivotal in maintaining BP (organ perfusion) (BP=CO X SVR) and oxygen delivery.
Vascular resistance is given by the relationship.
CO is pivotal in maintaining BP (BP=CO X SVR) and oxygen delivery.
CO = (pressure difference across vascular beds) MAP - CVP Systemic vascular resistance SVR
Expression is analogous to electrical resistance given by V=IR.
V=potential difference, I=Current (Flow) and R=resistance.

23. Approximation of CO.
SVR is estimated feeling the point of change in temperature in the limbs.
Stroke volume, correlates with the clinically observed pulse volume.
SV x HR = CO
Normal = 60mls, Low = 30mls High = 80mls
Can estimate CO using both methods.
Always fluid challenge if not clinically overloaded and then decide on CO state.
High CO -> vasopressor
Low CO -> inotrope SVR low (dilator) high (constrictor).