1. Continuous Renal-Replacement Therapy CRRT
Kianoush Kashani
5th Anesthesia and Critical Care Conference
Kuwait 2013
test

2. RRT indications (traditional)
Gibney et al. cJASN 3: , 2008.

3. RRT Improve metabolic milieu for
Support pt and effects of complications from MOF
Improve metabolic milieu for
Increasing survival
Recovery of multiple organ systems
Volume overload without oligoanuria or azotemia
CHF
Postoperative
Withhold RRT
If return of renal function is likely
Conservative management likely to succeed

4. MultiOrgan Support Therapy (MOST)

5. Heart

6. MOST: Cardiac Support Uncontrolled studies
 improve myocardial elastance with HF and adequate fluid balance
UNLOAD Trial (Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure)
RCT, multicenter, (N=200) excluded sCR > 3 mg/dL
Improved 48-hours weight loss
↓ re-hospitalization rates and ED visits at 90 days
↑ diuretic responsiveness
No change in mortality, CHF class and QOL
Costanzo et al. J Am Coll Cardiol 49:675–683, 2007

7. Liver

8. Liver extracorporeal support therapies
Non-cell based
RRT (IRRT, CRRT, SLED)
Hemoperfusion, hemoabsorption
Plasma exchange
Plasmaphoresis, Plasma filtration absorption, Selective plasma filtration technology (SEPET)
Albumin based
Molecular adsorbent recirculating system (MARS)
Single pass albumin dialysis (SPAD)
Cell-based  synthetic function
Human hepatocytes
Porcine hepatocytes
Cerda et al. Seminars in Dialysis—Vol 24, No –202

9. Cell-based Liver Purposes Detoxification Provide synthetic
Provide regulatory functions
Cell sources
Primary porcine hepatocytes
Immunologic reactions
Immortalized human cells
Rare source
Loose their liver function by time
Cells derived from hepatic tumors
Fear of tumorgenicity
Small single-center phase I and II trials
Proof of principle
Cerda et al. Seminars in Dialysis—Vol 24, No –202

10. Sepsis

11. Systemic Inflammatory Response Syndrome (SIRS) Vs
Systemic Inflammatory Response Syndrome (SIRS) Vs. Compensatory Anti-inflammatory Response Syndrome (CARS)

12. Sepsis management - MOST
HVHF
High cut-off hemofilters
Hemoadsorption
Non-specific
Charcoal
Resin
Plasma filtration coupled with adsorption (CPFA)
Improved MAP
Decrease the need for norepinephrine
Grootendorst et al.J Crit Care 1992;7:67–75.
Bellomo et al: Intensive CareMed 29:1222–1228, 2003

13. HICOSS trial (High Cut-Off Sepsis study)
N = 120
Septic shock with AKI
Conventional membrane vs. HCO membrane (cut-off of 60 kD)
5 days on CVVHD
Stopped prematurely after 81 patients
No difference in 28-day mortality (31% vs. 33%)
No difference in vasopressor need, MV, or LOS
No difference in albumin levels
Honore et al. Proc 10th WFSCICCM,Florence, Italy, 2009.

14. Sepsis management - MOST
Specific
Polymyxin B
EUPHAS trial (single center_Italy)
Improve MAP/vasopressor use
↑PaO2 ⁄FIO2
↓Mortality and SOFA
EUPHRATES trial (multicenter_US)
Cruz et al. JAMA. 2009;301(23):
Ding et al. ASAIO Journal 2011; 57:426 – 432.

15. Lung

16. Respiratory support Refractory ARDS
TV decreased from 6ml/kg to 4 ml/kg
Terragni et al. Anesthesiology 2009; 111:826–35

17. RRT modalities

18. Hemodyalisis IRRT CRRT Peritoneal dialysis Transplant
Modalities of RRT
Hemodyalisis
IRRT
CRRT
Peritoneal dialysis
Transplant

19. RRT modality and mortality
Bagshaw et al. Crit Care Med 2008 Vol. 36, No. 2

20. Renal recovery Evidence for CRRT benefit on renal recovery
Strong physiologic rationale
Observational studies
Epidemiologic studies (n=3000)
No benefit found in RCTs
All RCTs have significant limitations

21. Cost Mayo Clinic study N= 161, retrospective observational study
Mean adjusted total costs through hospital discharge
$ for IHD
$140,733 for CRRT (P< .001).
Rauf et al. J Intensive Care Med May-Jun;23(3):

22. Anticoagulation

23. Case 65 yo ♀ with PMH of ESLD, DM, HTN Presented with sepsis, DIC, AKI
Started on CVVH for AKI stage III
Qb 200 ml/min
RF 4500 ml/h
Citrate 300 ml/h
22 mEq/L Bicarbonate Prismasate® bath
Her dialyzer clots every four hours
What to do?

24. CVVH -predilution Partial loss of delivered RF by HF
↓ need for anticoagulation
Replacement fluid
Access
Return UF
Flow

25. CVVH -postdilution Higher clearance ↑ chance of clotting
Replacement fluid
Access
Return UF
Flow

26. Effect of filtration on CVVH
Hematocrit
60%
Hematocrit
30%
Maintain filtration fraction at 25%

27. Filtration fraction = [Quf (ml/min) / Qb (ml/min)] X 100
Case
Filtration fraction = [Quf (ml/min) / Qb (ml/min)] X 100
Quf = 4500 ml/hour = 4500/60 = 75 ml/min
Qb = 200 ml/min
Current FF = (75/200) X 100 = 37.5%
Decrease Quf to 3000 ml/hour (50 ml/min)
Increase Qb to 300 ml/min
 FF = 50/200 X 100 = 25%
 FF = 75/300 X 100 = 25%

28. Anticoagulation: Options
No Heparin protocols
Heparin
Unfractionated
LMWH
Citrate
Others
Prostacyclin
Danaparoid
Hirudin/argatroban
Nafamostate mesylate
Our options for anticoagulation during CRRT are quite limited. There is NO gold standard. Every technique is associated with risks / benefits and complications.
It is essential to correct any technical imperfections in the circuit prior to commencing any treatment. Particularly important is the positioning of the cannulae, and ensuring that there is good free flow from both lumen of the DLC. These cannulae are a frequent source of problems in babies as they tend to kink at the skin entrance.
The main advantage that I see with pre-dilution is not prolonging the life of a filter and circuit but enhancing clearance. The other options of NOT anticoagulating are really temporizing in individual cases and can only be recommended for short term use. They do NOT address the more common problems of preventing clot in the greater majority of patients.
That leaves us with either systemic or regional anticoagulation. I am only going to deal with the more common techniques used. NEXT SLIDE

29. Citrate No Heparin Systemically Heparinized
In addition, heparin damages platelets, as can be demonstrated in this slide.
Thanks to Dr. Gail Annich in Ann Arbor at University of Michigan for allowing me to use this slide.
The slide represents scanning electron microscopy of the surface of extracorporeal circuits from an animal study. The right side of each image is a x 5 magnification of the area selected.
Figure A = a circuit that was not heparinized. Note the clumping of platelets and fibrin strands.
Figure B = represents a heparinized circuit - note the shape of the platelets
Figure C = a circuit where the clotting was prevented by a special circuit material that Dr. Annich and her colleagues have been working on, and heparin was NOT used - note the shape of the platelets now.
Citrate
Gail Annich, University of Michigan

30. Citrate Vs. Heparin Filter life span Risk of bleeding
Zhang et al. Intensive Care Med (2012) 38:20–28

31. CRRT dosing

32. Meta-analysis Mortality
Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010.

33. Meta-analysis Renal recovery
Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010.

34. CRRT Timing

35. Early versus late RRT (Mortality)
Abstract
Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy
(RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI).
Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science
and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July Eligible studies
selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI.
Results: We identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494
citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a
significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There
was significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patient
population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was
no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute
Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall
summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported
greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies
showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however,
significantly affect the odds of dialysis dependence beyond hospitalization (OR to 1.13, I2 = 69.6%).
Conclusions: Earlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However,
this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of
new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.
Karvellas et al. Critical Care 2011, 15:R72

36. Early versus late RRT (Mortality)
Karvellas et al. Critical Care 2011, 15:R72

37. Early versus late RRT (RRT independence)
Karvellas et al. Critical Care 2011, 15:R72

38. شكراً
“The best interest of the patient is the only interest to be considered”

39. Questions & Discussion