1. RENAL REPLACEMENT THERAPY IN THE ICU
Dr. Kondamudi Sai Kiran Internal Medicine & Critical Care
20th April, 2016

2. INTRODUCTION
One third of patients admitted to ICU have acute kidney injury.
Five to ten percent of those require some form of renal replacement therapy.
Mortality for patients with AKI needing RRT is as high as 60%.

3. INITIAL MANAGEMENT Treat underlying cause Stop nephrotoxic drugs
Maintain euvolemia
Maintain adequate MAP

4. INDICATIONS Acute Kidney Injury with : No universally accepted levels
Fluid overload (refractory to diuretics)
Hyperkalemia (K+ > 6.5)
Severe metabolic acidosis (pH < 7.1)
Rapidly climbing urea/creatinine (or urea > 30 mmol/L)
Symptomatic uremia: encephalopathy, pericarditis, bleeding, nausea, pruritus
Oliguria / anuria
No universally accepted levels
Rate of change of renal parameters and overall clinical status

5. INDICATIONS (cont.)
2. Overdose with a dialyzable drug or toxin

6. Rimmelé and Kellum Critical Care 2011, 15:205
INDICATIONS (cont.)
3. Sepsis:
High Volume Ultrafiltration
Hemadsorption
Plasmapheresis
Coupled Plasma Filtration Adsorption
High adsorption Hemofiltration and high cut-off membranes
Rimmelé and Kellum Critical Care 2011, 15:205

7. “In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI”.

8. Major Renal Replacement Techniques
Intermittent
Hybrid
Continuous
IHD
Intermittent haemodialysis
SLEDD
Sustained (or slow) low efficiency daily dialysis
CVVH
Continuous veno-venous haemofiltration
IUF
Isolated Ultrafiltration
CVVHD
Continuous veno-venous haemodialysis
SLEDD-F
Sustained (or slow) low efficiency daily dialysis with filtration
CVVHDF
Continuous veno-venous haemodiafiltration
SCUF
Slow continuous ultrafiltration

9. Intermittent Therapies - PRO
(Relatively) Inexpensive
Flexible timing allows for mobility/transport
Rapid correction of fluid overload
Rapid removal of dialyzable drugs
Rapid correction of acidosis & electrolyte abnormality
Minimises anticoagulant exposure

10. Intermittent Therapies - CON
Hypotension 30-60%
Cerebral oedema
Limited therapy duration
Renal injury & ischaemia
Gut/coronary ischaemia

11. Continuous Therapies - PRO
Haemodynamic stability => ??? better renal recovery
Stable and predictable volume control
Stable and predictable control of chemistry
Stable intracranial pressure
Disease modification by cytokine removal (CVVH)?

12. Continuous Therapies - CON
Anticoagulation requirements
Higher potential for filter clotting
Expense – fluids etc.
Immobility & Transport issues
Increased bleeding risk
High heparin exposure

13. SLED(D) & SLED(D)-F : Hybrid therapy
Conventional dialysis equipment
Online dialysis fluid preparation
Excellent small molecule detoxification
Cardiovascular stability as good as CRRT
Reduced anticoagulation requirement
11 hrs SLED comparable to 23 hrs CVVH
Decreased costs compared to CRRT
Phosphate supplementation required
Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39
Berbece, AN & Richardson, RMA. Kidney International 2006; 70:

14. SOLUTE CLEARANCE - DIFFUSION
Small (< 500d) molecules cleared efficiently
Concentration gradient critical
Gradient achieved by countercurrent flow
Principal clearance mode of dialysis techniques

15. SOLUTE CLEARANCE - ULTRAFILTRATION
Water movement “drags” solute across membrane
At high UF rates (> 1L/hour) enough solute is dragged to produce significant clearance
Convective clearance dehydrates the blood passing through the filter
If filtration fraction > 30% there is high risk of filter clotting*
Also clears larger molecular weight substances (e.g. B12, TNF, inulin)
* In post-dilution haemofiltration

16. “ These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.”

17. ACCESS FOR HD
Venovenous RRT requires a double lumen vascular catheter placed in a central vein.
IVC for femoral lines, SVC from IJV/SC
Catheter made of polyurethane or silicone
Each lumen at least 11 french gauge
Good flow through catheter is crucial to prevent stasis of blood in circuit and clotting of filter.

18. SITE OF ACCESS

19. TIMING OF INITIATION Based on clinical assessment
“In critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression”

20. “In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes”

21. WHICH FORM OF RRT Aim of removal Cardiovascular status
Available resources
Clinician’s experience
Other specific considerations
CRRT can aid feeding regimens
CRRT may be associated with better cerebral perfusion

22. AIM OF REMOVAL

23. OPTIMAL FLOW RATE / DOSE OF RRT
Flow rate refers to the ultrafiltrate produced by the filtration process as well as any effluent dialysis flow.
Marker of solute clearance
Urea kinetic modelling (URR , Kt/V)
Solute removal index

24. “In critically ill patients with acute kidney injury, treatment with higher intensity (40 ml/kg/hr) continuous renal replacement therapy did not reduce mortality at 90 days”

25. “Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function or reduce the rate of non-renal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and crrt at 20 ml/kg/hour”

26. ANTICOAGULATION
Extracorporeal circuit will activate coagulation pathways
Premature clotting off of a filter is a common problem
May result in significant blood loss

27. ANTICOAGULATION (cont.)
Unfractionated heparin –
40 to 70 IU/kg bolus f/b pre-filter infusion at 5 to 10 IU/Kg/Hr. Monitor aPTT. Reversed by protamine sulfate.
LMWH –
Dose adjustment guided by anti factor Xa levels ( IU/ml). Longer half life. Partial reversibility with protamine.
Prostaglandins –
Inhibit platelet function. Synergistic effect. Short half life. Hypoxemia. Expensive.
Regional citrate anticoagulation –
Sodium citrate infused into circuit pre-filter which chelates calcium and inhibits clot formation. Calcium infusion post filter. Metabolic derangements.

28. FILTERS Cellulose based or synthetic (polysulphone and polyamide)
Biocompatibility – patient’s inflammatory and coagulation pathways
Flux – permeability
Adsorption – clears mid sized molecules
Thickness – thin membranes allow greater movement
Surface area – greater the area, more diffusion and ultrafiltration
CRRT: synthetic, high flux membranes with surface area of m2 and a pore size allowing the passage of molecules up to 50,000 Daltons

29. REPLACEMENT FLUID
Balanced salt solutions with either lactate or bicarbonate buffer
Lactate based solutions are stable, cheaper and more practical. But may not be favourable in certain conditions.
Bicarbonate based replacement solutions have a more reliable buffering capacity but need to be prepared just prior to use.
No evidence to suggest one better over the other.
Can be added pre or post filter

30. PHARMACOKINETICS Associated factors – Protein binding
Size of drug molecule and mode of RRT
Timing of RRT
Dose of RRT
Membrane permeability
Residual GFR

31. COMPLICATIONS OF HD Related to catheter Haemodynamic instability
Air emboli
Platelet consumption
Blood loss
Electrolyte imbalances
Hypothermia
Effects of anticoagulation

32. Managing Intra-dialytic Hypotension
Dialysate temperature modelling
Low temperature dialysate / 0.5 degrees C below pt’s
Dialysate sodium profiling
Hypertonic Na at start decreasing to 135 by end
Prevents plasma volume decrease
Dosing Anti-hypertensives
Avoid oral food or glucose
Midodrine if not on pressors
UF profiling
Colloid/crystalloid boluses
Sertraline (longer term HD)
2005 National Kidney Foundation K/DOQI GUIDELINES

33. DIALYSIS DISEQUILIBRIUM SYNDROME
Set of systemic and neurologic symptoms
Associated with characteristic EEG findings
Can occur during or after dialysis
Early – Nausea, vomiting, restlessness, headache
Serious – seizures, obtundation, coma
Cause – acute increase in brain water content, changes in pH of CSF
Minor – treat symptomatically
Major – stop HD. AED. Mannitol. Recovers in 24 hours
Prevention – URR < 40%, adjust dialysate sodium

34. THE FUTURE REDY (Recycled Dialysis System) Alliant HD system WAKPD
RAD (Renal Assist Device)

35. THANK YOU !