The Indian Anaesthetists Forum (www.theiaforum.

org) October 2004

Online ISSN 0973-0311

CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)

Dr. Manish Chaturvedi Nephrologist, Dr. S. N. Medical College, Jodhpur It is a mode of renal replacement therapy for hemodynamically unstable, fluid overloaded, catabolic septic patients and finds its application in management of acute renal failure especially in the critical care /intensive care unit setting. The popularity of slow continuous therapies for the treatment of critically ill patients with renal failure is increasing. The techniques most commonly used are slow continuous hemodialysis and hemodiafiltration. Slow continuous hemofiltration and slow continuous ultrafiltration also are commonly used. ARF in the ICU setting is frequent especially secondary to multiple organ dysfunction syndrome; post surgical setting i.e after abdominal surgery; post interventional studies eg. PTCA, PTRA studies in already susceptible individuals. These patients having various co-morbid conditions are on mechanical ventilation and various life supporting modalities which do not merit the dialysis procedure to be carried out in the routine dialysis set up. Being catabolic, they require continuous clearance of waste produced due to ongoing illnesses and an adequate potential for infusion of nutritional and inotropic agents for sustenance of vital parameters which is continuously desired in the management. CRRT has tried to meet these challenges in the ICU settings since its inception and has saved many lives across the globe including critically ill paediatric or geriatric population with renal failure as a co-existent co-morbid illness. The outcome of therapy depends on clearance of waste products achieved with restoration of blood biochemistry; maintenance of fluid, electrolyte and acid base balance; ability to maintain hemodynamic stability during the procedure with minimum side effects during the procedure. GOALS OF CRRT THERAPY The aggressive management in initial hours to counter the derangements in critically ill patients is the cornerstone in the therapy. CRRT initiated for ARF in critically ill patients should serve as a renal replacement therapy mimicking as artificial kidney support. It should enhance recovery of the native kidneys with prevention of hyperkalemia, hyper/hyponatremia, acidosis/alkalosis and rapid correction of pulmonary/peripheral edema by gradual and consistent removal of surplus fluid retained in the body. It should also diffuse the various ongoing smoldering proinflammatory mediators especially in multiple organ dysfunction syndromes. HISTORY It was originally promoted by Kramer and associates for treatment of hypotensive patients. Its efficacy was later proven by Peganini in 1984, who used

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

CRRT in hemodynamically unstable patients rendering improved survival by this modality. INDICATION FOR INIATION OF CRRT: Presence of marked azotemia, fluid overload, or both; maintaining electrolyte, acid-base, and solute homeostasis. Persistent oliguria, hyperkalemia refractory pulmonary edema or fluid overload, pericarditis, hypothermia, hyperthermia, poisonings with a dialyzable toxin and serial rise in blood urea and serum creatinine.

PROCESS a) Hemodialysis

P Out In Dialysate

Blood flow: 250-300ml/min Dialysate flow: 500ml/min Membrane: Cuprophan; Hemophan Mechanism: diffusion Replacement solution: not required This process effectively removes small molecular weight solutes.

b) Hemofiltration: Replacement fluid P P

UF Blood flow: 500ml/min Dialysate flow: nil Membrane: highly permeable; AN-69; Polyamide; Polysulphone Mechanism: convection Replacement fluid: calcium & lactate containing fluid Over 3-4 hours 30 litres of fluid may be taken out.

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

c) Hemodiafiltration Replacement fluid P P P Dialysate out Dialysate in + UF Membrane: Polysulphone; AN-69 Mechanism: diffusion+ convection Replacement fluid: calcium+ bicarbonate

d) High flux dialysis

Membrane: Polysulphone, AN69 Mechanism: diffusion + convection Pressure in dialysate is increased in the setting of both convection and diffusion. Dialysate back filters into the distal part of dialyzer which tends to correct the fluid balance. Thus, use of sterile/ultrapure dialysate is recommended. ACCESS a) Arteriovenous access

Femoral artery

Femoral vein

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

Heparin Infusion Femoral artery

Hemofilter

Replacement fluid

UF Femoral vein

Advantage: No pump is required. The mean arterial pressure drives the blood into the filter /dialyzer. Risks 1. Atheroembolism 2. Ischemia of the limb 3. Hematoma formation 4. Hemorrhage 5. Arterial wall injury 6. Spasm of the artery cannulated ~The patient has to remain in bed till the catheter is in situ. The use of CAVH, even though does not require a pump, is associated with increased risk of bleeding from puncture site in artery and inadvertent disconnection during the procedure are potential risks encountered. The clearance rate of urea and other wastes cannot be enhanced beyond a limit on account of fluctuations in blood pressure during the flow of blood through the dialyzer or hemofilter. Low blood pressure can even decrease the blood perfused in the circuit with recurrent clotting problems in the dialyzer/hemofilter. b) Venovenous access A double lumen cannula is inserted into a large vein. Internal jugular vein is preferred over femoral vein and femoral vein is opted over subclavian vein. This access requires a roller pump as the driving force of mean arterial pressure is not present here. Advantages: This method gives rapid and constant blood flow rate; improved dialyzer performance and decreased line and dialyzer clotting. CVVH with its ease of cannulating a central vein and use of a pump in the circuit is used more frequently as a CRRT procedure in the ICU setting with greater removal of urea, metabolic wastes and surplus fluid by adjusting the pump speed.

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

Disadvantages: Air embolism; hemorrhage due to inadvertent disconnection; longer blood lines used in extra corporeal circuit which are more liable to clot; central vein thrombosis and stenosis risk; and addition of gadgets in the circuit like, air bubble trap, alarms etc. NOMENCLATURE: CONTINUOUS + ACCESS Continuous ArterioVenous

+ METHOD HemoDiafiltration

-------- CAVHD

scuf Arteriovenous(AV) Or AV or VV Venovenous(VV) Blood flow(ml/min) Dialysate flow(ml/min) Clearance(L/24hr) Ultrafiltration rate (ml/min) Blood filter 50-100

continuous hemofiltration AV/VV

continuous continuous hemodialysis hemodiafiltration AV/VV AV/VV

50-200

50-200

50-200

2-5 Highly permeable filter

12-36 8-25 Highly permeable filter

10-20 14-36

10-20 20-40 8-12 High permeability dialyzer with countercurrent flow through dialyzer compartment In excess of patients weight loss; solute clearance by both diffusion and convection. Yes; to achieve fluid balance to Extends from small to large molecules

Ultrafiltrate

2-4 Low permeability dialyzer with countercurrent flow through dialyzer compartment Corresponds Replaced in Corresponds exactly to part or to weight loss; patients completely solute weight loss to achieve clearance by purification diffusion and volume control none yes none

Replacement fluid

Efficiency

Used only for fluid control in overhydrated states

Clearance Limited for all small solutes molecules equals ultrafiltration

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

Continuous high flux dialysis Blood flow 50-200 ml/min Dialysate flow 50-200 ml/min Ultrafiltration rate 2-8 ml/min Blood is driven through a highly permeable dialyzer and a countercurrent flow of dialysis solution is delivered in single pass or re-circulation mode. The ultrafiltration production is controlled by a couple of pumps and regulated by gravimetric control. Replacement fluid is not required since fine regulation of filtration and back filtration achieves fluid balance. In this mode convection and diffusion are combined and optimized. Continuous Plasma Filtration-adsorption In this technique blood is driven through a highly permeable plasma filter. The plasma filtrate is then circulated in a bed of adsorptive substance (carbon/resins) in order to obtain selective removal of molecules by adsorption. Fluid balance is maintained and no replacement fluid is needed .It can be coupled with continuous hemofiltration /hemodialysis. It is indicated for treatment/removal of mediators of sepsis pro-inflammatory agents. V P V

PF

Mechanism of fluid and solute removal Diffusion is the process where movement of solutes occurs across a semi-permeable membrane depending on the concentration gradient of the solute, its molecular weight, velocity size. Ultrafiltration involves movement of water by hydrostatic or an osmotic force across a semi-permeable membrane with concomitant solute "drag even if the concentration of the solutes is close to their original concentration. If hydrostatic pressure is the determinant, then the transmembrane pressure (calculated as the pressure difference across the membrane) is significant. Increased ultrafiltration can be achieved by increasing the transmembrane pressure. In CRRT, the transmembrane pressure can be increased by lowering the dialysate drain bag/applying suction to the dialysate drain line (which increases the negative pressure in the dialysate compartment.) or by increasing positive pressure in the blood compartment by increasing blood flow rate by adjusting prefilter blood pump or by increasing the venous resistance by decreasing venous return.

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

Predilution of the blood prior to its entry in the dialyzer with replacement fluid can lead to decreased requirement of anticoagulation and also by maintaining the concentration gradient. Dialysate characteristics: Usually the dialysate does not come in contact with blood except during high flux dialysis where dialysate can backleak into the blood compartment leading to permeation of bacterial endotoxins. Glucose rich solutions can lead to hyperglycemia. Lactate is commonly used as buffer. In conditions where inadequate lactate metabolism takes place (eg. in liver failure) the bicarbonate based dialysate is preferred. A. Dialysate A solution-contains 4.5 litres of electrolyte solution with calcium, magnesium lactic acid which increases carbondioxide which prevents precipitation of calcium and magnesium. B. Dialysate B solution contains 8.4% bicarbonate. Replacement fluids contain normal saline with calcium chloride; normal saline with magnesium sulphate; half normal saline; half normal saline with sodium bicarbonate. Anticoagulation The major disadvantage of CRRT is the need for continuous anticoagulation leading to increased risk of bleeding, thrombocytopenia. Patients having impaired liver functions and having thrombocytopenia (50,000/mm3) anticoagulation is not required. Procedure The filter is primed with 1-2 litres of heparnized saline @400-800 IU/hr with monitoring of Clotting time (1.5-2 times normal) or PTTK. Low molecular weight heparin can also be used with monitoring of anti Xa activity (0.3-0.6 times anti Xa activity) Prostacyclin with low dose heparin; citrate; protamine can be used in patients with high risk of bleeding. ADVANTAGES OF CRRT 1. CRRT by its lower rate of fluid removal can lead to steady state fluid equilibrium in hemodynamically unstable, critically ill patients with associated comorbid conditions eg. M.I, ARDS, septicemia, bleeding disorders. 2. It provides excellent control of azotemia, electrolytes and acid base balance. These patients are catabolic thus, removal of urea is mandatory to effectively control azotemia. 3. It is efficacious in removing fluid in special circumstances post surgery pulmonary edema; ARDS etc.

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

4. CRRT can help in administration of parenteral nutrition and obligatory I.V medications like pressors & inotropes by creating an unlimited space by virtue of continuous ultrafiltration. 5. Hemofiltration modality is effective in lowering intracranial tension v/s routine intermittent hemodialysis which can sometimes raise intracranial tension. 6. Proinflammtory mediators of inflammation are also shown to have been removed by this modality eg.IL-1, IL-6, IL-8, TNF-a. DISADVANTAGES This mode of therapy requires regular monitoring of hemodynamic status and fluid balance (ultrafiltration rate, replacement fluid); regular infusion of dialysate; continuous anticoagulation; ongoing alarms and an expensive mode of therapy above all. COMPLICATIONS A.Technical-1.vascular access malformation 2.Air embolism 3.circuit blood clotting and decreased blood flow 4.Fluid and electrolyte imbalance. B.Clinical-1.Bleeding 2.Thrombosis 3.Infection/sepsis 4.Bioincompatibility of membranes 5.Hypothermia 6.Nutrient losses. INDICATIONS OF CRRT a. RENAL CAUSES 1. ARF with cardiovascular instability 2. ARF with septicemia 3. ARF with septicemia and ARDS. 4. ARF with cerebral edema b. NONRENAL CAUSES 1. Systemic inflammatory response syndrome 2. Crush syndrome 3. Lactic acidosis 4. C.H.F DIALYSIS MODALITIES FOR ACUTE RENAL FAILURE Intermittent therapies Hemodialysis Hemodiafiltration Ultrafiltration Extended daily dialysis Slow continuous dialysis Continuous therapies Peritoneal dialysis Slow continuous ultrafiltration Hemofiltration (CAVH, CVVH) Hemodialysis (CAVHD, CVVHD) Hemodiafiltration (CAVHDF, CVVHDF)

Acute renal failure in the ICU is a clinically diverse entity. Consequently, the indications for initiation of dialysis therapy are varied. Usually, the indications are solute control, volume control, or both. A variety of dialysis modalities are available; however, there is no consensus as to the optimal modality for any

Chaturvedi M: Continuous Renal Replacement Therapy

The Indian Anaesthetists Forum (www.theiaforum.org) October 2004

Online ISSN 0973-0311

particular group of patients. A careful understanding of the particular benefits, limitations and potential complications of each modality coupled with a thorough assessment of the individual patients need formulate the basis for the dialysis modality selection. In certain circumstances, the more conventional intermittent therapies are sufficient, whereas in other settings, CRRT techniques are advantageous. The impact of modality selection on outcome remains an area of significant controversy. Future newer therapies aimed at more optimal and more specific blood purification may prove promising in the management of complex critically ill patients with ARF and other co-morbid conditions. Of note in this regard is the experimental technique by David Hume et al who have created a bioartificial kidney which incorporates a hemofilter (analogous to a glomerular unit) with tubular cell lines laid on hollow tubes of less immunogenic nature ; where the ultrafiltrate produced removes the excess of fluid, and circulation through the tubular cell lines causes resorption of essential nutrients (glucose, amino acids etc.) and various electrolytes like sodium, calcium may be achieved. It also serves the endocrinal function by synthesizing active form of vitamin D.

REFERANCES: 1. Bellomo R, Ronco C. Continuous renal replacement therapy in the intensive care unit. Intensive Care Med 1999;25:781-789. 2. Abdeen O, Mehta R.L. Dialysis modality in the intensive care unit. Crit Care Clin 2002;18:2;223-247. 3. Bellomo R,Ronco C. Indications and criteria for initiating renal replacement therapy in the intensive care unit. Kidney Int 1998,Vol.53,Suppl.66:S-106-109. 4. Burchardi H. History and development of continuous renal replacement techniques.Kidney Int1998, Vol.53, Suppl.66:S120-124. 5. Manns M, Sigler M, Teehan BP. Continuous renal replacement therapy:an update. Am J Kidney Dis 1998,32:185-207.

Chaturvedi M: Continuous Renal Replacement Therapy