RENAL REPLACEMENT THERAPY Dr Jyoti Khare FCCCM, Part II PSRI Hospital, New Delhi

Introduction It is estimated that a third of patients in the critical care setting have an AKI and approximately 5% will require renal replacement therapy. The hospital mortality in patients with an AKI requiring RRT is as high as 60% No specific treatments have been shown to reverse the course of AKI, so RRT forms the basis of further management.

Proposed Indications for RRT Oliguria < 200ml/12 hours Anuria < 50 ml/12 hours Hyperkalaemia > 6.5 mmol/L Severe acidaemia pH < 7.0 Uraemia > 30 mmol/L Uraemic complications Dysnatraemias > 155 or < 120 mmol/L Hyper/(hypo)thermia Drug overdose with dialysable drug

The Ideal Renal Replacement Therapy Allows control of intra/extravascular volume Corrects acid-base disturbances Corrects uraemia & effectively clears “toxins” Promotes renal recovery Improves survival Is free of complications Clears drugs effectively (?)

Types of Dialysis Dialysis is a way to clean blood of wastes, fluids and salts that build up in the body when the kidney fail. There are 2 kinds of Dialysis: Peritoneal Dialysis: Uses the peritoneal membrane as the filter. The membrane covers the abdominal organs and lines the abdominal wall. This takes place inside the body and requires placement of a catheter in the peritoneal cavity to allow fluid to be instilled and drained out. Hemodialysis: Uses a dialyzer or artificial kidney to filter the blood. This takes place outside the body and requires some form of access to the circulatory system. Accomplished with the use

Hemodialysis Blood is circulated through an artificial kidney which has two compartments: Blood & Dialysate, separated by a thin semi-permeable membrane. Waste and excess water pass from the blood side to the dialysate side and is discarded in the drain. The cleaned blood is returned to the patient. It is diffusion-based mass transfer (BUN, Creat, lytes) & Pressure - driven water removal (ultrafiltration) Usually done 3x/week ~ 4 hrs M-W or T-Th-Sat

Dialysis Therapy Extracorporeal: Intracorporeal: Intermittent Hemodialysis Slow Low Efficiency Dialysis (SLED) Continuous Hemofiltration CAVH SCUF CVVH CAVHDF CVVHDF Intracorporeal: Peritoneal Dialysis

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

Solute Clearance - Diffusion Small (< 500d) molecules cleared efficiently Concentration gradient critical Gradient achieved by countercurrent flow Principal clearance mode of dialysis techniques

Solute Clearance – Ultrafiltration & Convection (Haemofiltration) 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)

Dialysate Fluid Bicarbonate buffer solutions is used in IHD to replenish serum bicarbonate levels and neutralise metabolic acids that are usually present in patients with renal failure. Acetate buffer solutions present the body with a large acetate load to be metabolised by the skeletal muscle. In critically ill patients the acetate levels rise due to decreased skeletal muscle metabolism. Increased acetate levels have been associated with hypotension and hypoxia due to its negative inotrope effect and vasodilatation. Lactate buffer solutions

Hemodialysis Requires access to the blood stream Arterio – venous fistula Arterio – venous graft Temporary catheter Long – term catheter

Temporary Hemodialysis Catheter

Hemodialysis ~ Graft

Complications of AVF and AVG Thrombosis Infection (10% for AVG, 5% for transposed AVF, 2% for non-transposed AVF) Seromas Steal (6% of B-C AVF, 1% of R-C AVF) Aneurysms and pseudoaneurysms (3% of AVF, 5% of AVG) Venous hypertension (usually 2/2 central venous stenosis) Heart failure (Avoid AVFs in pts with severely depressed LVEF) Local bleeding

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

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

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

Continuous Renal Replacement Therapy: Based on principles of Hemofiltration Subsitute for impaired renal function over an extended period of time and applied for 24 hours a day.

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)?

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

Comparison of IHD and CVVH Intermittent hemodialysis Continuous hemofiltration No osmotic cellular shift/ cerebral edema - +++ Hemodynamic tolerance ++ 24 hr volume and electrolyte balance Nutritional support + RRT dose/ adequate uremia control (+) high ultra filtration volume necessary Anticoagulation/ bleeding disorders Patient’s mobility Loss of nutrients, vitamins, trace elements Drug/ antibiotic dosage - No clear data on many drugs, different ultrafiltration rates! Filter down times! Cost Ootcome/ mortality ?

Intradialytic Hypotension: Risk Factors LVH with diastolic dysfunction or LV systolic dysfunction / CHF Valvular heart disease Pericardial disease Poor nutritional status / hypoalbuminaemia Uraemic neuropathy or autonomic dysfunction Severe anaemia High volume ultrafiltration requirements Predialysis SBP of <100 mm Hg Age 65 years + Pressor requirement

Peritoneal Dialysis Uses the peritoneal membrane as the filter. The membrane covers the abdominal organs and lines the abdominal wall. The membrane size is 1 – 2 m2 and approximates the body surface area. Uses the following principles: Diffusion: movement of solutes across the peritoneal membrane from an area of higher concentration to an area of lower concentration. Osmosis: movement of water across the peritoneal membrane from an area of lower solute concentration to an area of higher solute concentration. Ultrafiltration: water removal related to an osmotic pressure gradient with the use of various concentrations of dialysate fluid.

Indications Complications Bleeding tendency Hypotension Diabetic nephropathy Complications Peritonitis Injury of viscus Abdominal hernia Leakage of dialysate into pleural cavity or scrotom

Peritoneal Dialysis Patients Must have a clean room to perform exchanges and a large enough area to store all supplies. No pets allowed in the room. Must learn to monitor their own weight and blood pressure. Must be able to follow important instructions to prevent infection in the peritoneum. Must also be able to determine the choice of dialysate fluid and when to use it.

Guidelines for Anticoagulation Extracorporeal circuit will activate coagulation pathways and the premature clotting of a filter is a common problem. Even a small amount of clot formation will reduce filter performance. NON-PHARMACOLOGICAL MEASURES Adequate central venous pressure. Optimising vascular access. Adding a proportion of the replacement fluid to the patients’ blood before it passes through the haemofilter (this is predilution)

Guidelines for no Anticoagulation There is already a degree of coagulopathy. INR > 2-2.5 APTT > 60 seconds Platelet Count < 60 x 103 mm3 There is a high risk of bleeding The patient is receiving activated protein C

Care of patients receiving hemodialysis Variable Goals Dialysis dine Urea kinetics model Fluid balance Individualised. Intradialytic weight gain should be less than 5% of IBW Quality Measure endotoxin and bacteria in the dialysate water Anemia Target a Hb of 10-12 gms%. Avoid high dose erythropoietin Vascular access Monitoring. To establish AV access rather than indwelling catheters Bone & Mineral Calcium levels between 8.4 – 9.5 and a PO4 3.5 -5.5 mg/dl Blood pressure Optimum targets & strategies not well defined LDL cholesterol < 100mg/dl Quality of life indices Support from the medical social worker

CRRT, Haemodynamics & Outcome 114 unstable (pressors or MAP < 60) patients 55 stable (no pressors or MAP > 60) patients Responders = 20% fall in NA requirement or 20% rise in MAP (without change in NA) Overall responder mortality 30%, non-responder mortality 74.7% (p < 0.001) In unstable patients responder mortality 30% vs non-responder mortality 87% (p < 0.001) Haemodynamic improvement after 24 hours CRRT is a strong predictor of outcome

Towards Targeted Therapy? Non-septic ARF Septic ARF Cathecholamine resistant septic shock Daily IHD Daily IHD? HVHF 60-120 ml/kg/hour for 96 hours Daily SLEDD Daily SLEDD? CVVHD/F ? dose EBT PHVHF 60-120 ml/kg/hour for 6-8 hours then CVVH > 35 ml/kg/hour CVVH @ 35ml/kg/hour CVVH > 35ml/kg/hour ? 50-70 ml/kg/hour Cerebral oedema

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