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Renal disorders are important causes of morbidity and mortality in the dog and cat. Since, one of the primary functions of the kidney is the removal of the waste products of metabolism, any severe disturbance in the function of this organ will result in an abnormal accumulation of toxic products. The milder forms of renal disease may go unnoticed, since the kidneys, like most other organs, have great compensatory powers. However, when the limits of compensation are exceeded and the kidneys are no longer able to assure a proper chemical balance in the body, uraemia results.
Management of chronic renal failure (1) with dietary restriction and acute renal failure with diuresis and fluid administration becomes ineffective as renal function declines. Peritoneal dialysis can be done in such cases but it has certain disadvantages because the removal of toxic waste products is very slow and there will be some loss of protein. The procedure cannot be performed immediately following abdominal surgery and there is always a possibility of peritonitis. These drawbacks are overcome by the use of haemodialysis. In human uremic patients, renal function is replaced by haemodialysis, while in veterinary practice the use of haemodialysis was limited due to the technical aspects of the procedure. However, modern machines have removed these constraints.
Haemodialysis is the therapeutic application of diffusion and ultrafilteration to promote removal of toxic solute and normalization of the volume and composition of body fluids disrupted by the loss of renal function.
Thomas Graham laid the foundation of haemodialysis with the recognition of ‘osmotic membrane’ in 1854. Haemodialysis was first performed in 1913 by Abel, Rowtree and Turner (2) on experimental dogs with an ‘artificial kidney’ composed of celloidin tubes. The first human haemodialysis was performed in 1924 by George Hass. Willem Kolff in 1943 invented the rotating drum
dialyzer.
Veterinary application of haemodialysis was described first by Butler in 1968 (3). The first clinical application of haemodialysis in dogs was reported from the University of California and Purdue University in the early 1980s (4). The first clinical dialysis programme started with establishment of the Companion Animal Haemodialysis Unit at the University of California in 1990. Feline haemodialysis was initiated in 1993 (5).
Principles governing haemodialysis
To perform haemodialysis, blood is exposed to a contrived solution, the dialysate, formulated to transfer solutes across a transposed semipermeable membrane. The factors governing the efficacy of solute transfer (6) are:-
a. The diffusion gradients across the membrane.
b. The diffusion properties of the solutes.
c. The permeability and surface area of the membrane.
d. The volume of blood exposed to the membrane.
e. The volume of ultrafilteration.
In diffusion dialysis, the solutes move across the semipermeable membrane due to the difference in the concentration gradient of the solutes across the membrane. In ultrafilteration dialysis, there is movement of water across the membrane due to the difference in hydrostatic pressure of blood and dialysate. Along with water the solutes dissolved in water also move across the membrane.
Indications of haemodialysis in dogs and cats
1. Acute renal failure: Acute renal failure which may occur due to toxicant induced injury to the kidney as in case of heavy metals like lead, mercury, cadmium, arsenic, organic compounds like ethylene glycol, nephrotoxic drugs like aminoglycosides and tetracyclines or over dose of iatragenically administered toxic drugs or injury due to ischemia as in case of renal vessel thrombosis. The major infectious diseases which necessitate haemodialysis are leptospirosis and infectious canine hepatitis. Severe endotoxaemias which lead to acute renal failure also warrant haemodialysis. The criteria for performing haemodialysis in acute renal failure are:-
a) Uncontrolled biochemical or clinical manifestation of uraemia.
b) Failure to induce an effective diuresis (severe oliguria or anuria).
c) Life threatening electrolyte disturbances (hyperkalemia, hyponatremia, hypernatremia).
d) Life threatening fluid overload (pulmonary oedema, congestive heart failure, severe systemic hypertension).
e) Severe azotemia (blood urea nitrogen more than 100 mg/dl, serum creatinine more than 10 mg/dl).
f) Non-responsive clinical course (12-24 hours).
2. Chronic renal failure:
The criteria for performing haemodialysis in chronic renal failure are:-
a) Refractory azotemia (BUN more than 100 mg/dl, creatinine more than 8 mg/dl).
b) Intractable uremic signs.
c) Preoperative conditioning for renal transplantation.
d) Finite extension of life without overt manifestation of uremia to permit owner adjustment and acceptance of diagnosis and prognosis.
3. Fluid overload / excessive fluid administration:
a) Fulminant congestive heart failure or pulmonary oedema.
b) Iatrogenic fluid administration.
c) Parentral nutrition in oliguric/anuric animals.
Components of haemodialysis
Haemodialyzer (Artificial kidney)
The hollow fiber dialyzers consist of a bundle of small diameter capillary fibers encased in a plastic housing. Blood is channeled through the centre of the fibers while the dialysate is distributed around the fiber bundle in opposite direction which facilitates movement of molecules across the membrane. These dialyzers are available with effective surface area between 0.22 and 2.50 m2. Pediatric hollow fiber dialyzers have blood compartment volumes between 18 and 60 ml which are well suited for animal haemodialysis (7).
The parallel plate dialyzer design consists of multiple layered (stacked) sheets of semi permeable membrane sandwiched between plastic supports that disperse blood and dialysate over opposing sides of the membrane. Parallel plate dialyzers were among the first to be designed, but their popularity has reduced since 1960.
Conventional (cellulosic) dialyzers are composed of chemically modified cellulose membrane (cuprophan, regenerated cellulose, cellulose acetate, cellulose triacetate haemophan). These dialyzers have good diffusion characteristics for low molecular weight solutes (<500 d), but are less effective for medium sized molecules. Due to the low cost, disposability and adequate solute removal, cellulose dialyzers have remained the standard for animal dialysis. High efficiency and high flux dialyzers use synthetic polymer membranes (polycarbomate, polyacrylonitrite, polysurface) that have superior diffusion and ultrafilteration characteristics, greater mechanical strength, lower thrombogenicity and better biocompatibility than the cellulosic dialyzers, but these are costlier than the cellulosic dialyzers.
Dialysis delivery system
It performs the following functions:-
Proportionally dilutes the dialysate by mixing highly purified water and regulates its flow to the dialyzer; continuously monitors the composition, temperature and pH of the final fluid; controls and monitors extracorporeal flow of blood; regulates the rate of ultrafilteration; maintains delivery of anticoagulant to prevent clotting in blood circuit.
Purified water system
Water is abundantly required for dilution of dialysate. During a single dialysis session, the animal is exposed to approximately 150 L of water. The water need not be sterile. The impurities tolerated in drinking water, pose no threat to dialysis patient. However, it is ideal to use deionsed water. Water can be channelized to the machine through a deioniser.
The extracorporeal circuit
It consists of the blood tubings, which route the patient’s blood to and from the dialyzer via the vascular access. The extracorporeal circuit should not contain more than 10% of the patient’s blood volume unless the circuit is primed with compatible blood or volume expanders. A typical pediatric circuit may contain 110 to 130 ml of blood, which would be safe for a dog larger than 14 kg. The volume of typical neonatal circuits is 50 to 60 ml, which is appropriate for dogs larger than 7 kg.
Ultrafilteration control system
It regulates the rate and volume of ultrafilteration during dialysis. The dialysate can be formulated with either acetate or carbonate buffer. Dialysate is not a sterile solution. The dialysate flow rate is 500 ml/min. It can be either prepared or bought as it is commercially available.
The material required for haemodialysis includes a scalp vein set, needles, syringes, tranquilizer e.g. triflupromazine, sedative e.g. xylazine HCL, general anaesthetic e.g. pentothal sodium, local anesthetic e.g. lignocaine HCL, razor for shaving hair, BP blade, normal saline, whole blood in case of severely anaemic patient, heparine, dexamethasone, doxopram, adrenaline and vasofix 16x18G depending upon the size of the dog or a duel lumen catheter from a human pediatric set.
Haemodialysis equipment
This comprises a haemodialyzer, dialysis delivery system (8) (tubing) and purified water delivery system with storage tank and pump if necessary depending upon the pressure of flow of water.
Monitoring equipment
Blood pressure monitoring, ECG, pulse oximeter, serum chemistry analyzer and coagulation monitor.
Haemodialysis procedure
The patient can be restrained either with a sedative or a general anaesthetic. However, in most of the uremic animals it is not required as patient will be either recumbent or in coma.
Vascular access
Ready and repeatable access to the animal’s vasculature to deliver blood to the dialyzer and to return the dialyzed blood to the animal is fundamental for dialysis. The vascular access can be obtained by any one of the following ways (9):
a) An arteriovenous shunt composed of exteriorized Solstice tubes connected to teflon vessel cannulas that are surgically inserted in a peripheral artery and vein. Arteriovenous shunts are generally placed between the femoral artery and veins or carotid and external jugular vein. For haemodialysis treatments, the arterial units of the shunt supplies blood to the dialyzer and the dialyzed blood is returned to the patient via the venous canula. In the interdialysis period the free ends of the silicon tubes are reconnected to establish a free flowing arteriovenous circuit or shunt.
b) Transcutaneous method: The animal is placed on lateral recumbency. The left jugular furrow of the dog is neatly shaved and surgically prepared with povidone iodine. The skin at the catheter insertion site is anaesthetized with 2% lignocaine and 10 ml of heparinized saline solution is taken in syringe with introducer needle. The needle is introduced into the left external jugular vein through percutaneous method. A small quantity of blood is aspirated to ensure proper positioning of the needle in the vein. The heparinized saline solution is administered into the jugular vein to prevent clotting of blood in the introducer needle. Then the syringe is disconnected from the introducer needle. The flexible J end of the guide wire is immediately threaded through the needle hub and is advanced down the vein until the vascular portal is located in the right atrium or cranial vena cava. After placement of the guide wire, the introduced needle is removed, leaving the guide wire in that position. The catheter is flushed with heparinized saline. The clamp on the arterial line (red) is closed.
A slight incision is made at the skin line using a 11 size BP blade to facilitate tissue dilution. The dilator is introduced into the exposed end of the guide wire with a rotating motion. It is advanced through the skin and soft tissue until it is found within the vein. Then the dilator alone is removed leaving the guide wire in that position. The duel lumen catheter is introduced into the exposed end of the guide wire until the tip of the catheter is located in the right atrium or cranial vena cava. The guide wire is removed from the venous lumen and immediately clamped. Potency is verified by aspirating blood through each lumen of the catheter. The incision is closed with a single stitch. Between dialysis treatments, both the lumen of the catheter are filled with heparin to prevent clotting (Heplock). The cutaneous exit is treated with povidone iodine ointment and entire catheter is protected in a bandage after dialysis. Catheter is clamped at all times except when not connected to a syringe or during treatment. Catheters are replaced if they become physically damaged, occluded or infected. In most cases replacing catheter in the opposite jugular vein rather than the previous access site is preferable.
Priming the dialysis unit and the patient
The dialysis unit (comprising of blood tubing and the dialyser) has to be primed with normal saline. Heparin is given as an intravenous loading dose at 50 to 100 U/kg and is continued as a constant infusion (200 to 1200 U/h). For animals at severe risk of life threatening haemorrhage, no heparin procedures can be performed, but preventing clotting in the dialyzer is very difficult. Heparin management may be problematic for animals with bleeding tendencies. If bleeding persists after discontinuing dialysis, heparin can be antagonized continuously with protamin sulphate at 1 mg per 100 U of estimated residual heparin. In case of severe anaemia, whole blood should be administered at 20 ml/kg body weight before starting dialysis.
Before starting the dialysis, the blood tubings are connected and the dialysis unit is switched on. During dialysis the dialysate flow can be at the rate of 200-500 ml/min. About 150 L of purified water is required for each dialysis.
Acute dialysis
Blood flow rate
Extra corporeal blood flow should be restricted to 3 to 5 ml/kg/min for initial treatment to prevent excessive urea clearance and dialysis disequilibrium. For second and third sessions blood flow can be increased progressively to 10 to 15 ml/kg/min. For more intensive dialysis, treatment is largely determined by the blood flow rate and the length of dialysis. These parameters should be selected to achieve a urea reduction ratio (1-(postdialysis / predialysis) BUN mg/dl) not greater than 0.5. When the predialysis BUN is less than 100 mg/dl subsequent treatments in both dogs and cats can be extended to 180 to 300 minutes and can incorporate faster blood flow rates to achieve urea reduction ratio greater than 0.9. The dialysate used can be either acetate based or bicarbonate based. However, the acetate based dialysate is commonly used (10).
Ultrafilteration
An ultrafilteration volume and rate is selected to lessen the pre-existing fluid burden, correct pulmonary oedema and vascular congestion, compensate for fluids administered during dialysis sessions and facilitate ongoing fluid therapies like parenteral nutrition and blood or plasma transfusions. Eliminating large fluid loads during the first dialysis session is usually unnecessary and dangerous. However, a rate of 5 to 10 ml/kg of ultrafilteration is suitable for most cases.
Chronic intermittent dialysis
This is done every 2 to 4 days to supplement the residual excretory capacity of chronically diseased kidneys. Blood flow, rates should be between 8 and 12 ml/kg/min in bicarbonate dialysate and 5 ml/kg/min in acetate dialysate. For high efficiency dialysis the rate could be 15 to 20 ml/kg/min with continuous monitoring of blood pressure and pulse rate. Duration of dialysis should be 240 to 300 minutes. A twice weekly schedule is required for animals with serum creatinine concentration, between 8 and 10 mg/dl and thrice weekly schedule is required for those with serum creatinine concentration greater than 10 mg/dl.
Animals with end stage renal disease or decompensated chronic renal failure should be treated initially with an acute dialysis prescription until the predialysis BUN is less than 100 mg/dl. This usually requires 2 to 3 dialysis sessions. After this the animal can go on a more intensive maintenance.
Dialysis schedule
Dialysis in case of acute intoxication
In acute intoxication like that of ethylene glycol, the blood outflow rate during haemodialysis should be 10 to 20 ml/kg/min and duration 240 to 300 min. In non-azotemic animals at low risk of osmotic shift disequilibilum, the size of the dialyzer, blood flow rate, and duration of the session should be maximised to the limits of haemodynamic stability.
Dialysis for fluid removal
For fluid removal, as in case of pulmonary oedema, anasarca, the rate and volume of ultrafilteration is contingent upon the haemodynamic stability of the animal and the potential for osmotic shift disequilibrium.
Efficacy of haemodialysis
The efficacy of an individual dialysis treatment can be assessed by the following indices (11,12)
a) Kt/ V
where K = the dialyzer urea clearance (ml/min).
t = time on dialysis (min) and
V = the volume of urea distribution (litres) which is approximately equal to total body water. The higher
the Kt/V; the higher and more effective the dialysis. A Kt/V, value of 2.5 to 2.9 is considered as a highly effective dialysis dose.
b) The urea reduction ratio (URR)
Post-dialysis
URR= I -( ————————) BUN
Pre-dialysis
URR between 0.85 and 0.95 can be obtained in patients receiving standard dialysis prescription.
Kt/V and URR are useful indices to monitor the delivery of individual dialysis treatments, but just to assess the long term adequacy of dialysis because they ignore the frequency of dialysis and other factors (nutritional adequacy, dietary nitrogen and catabolic state) that modify urea metabolism. The long term effects of dialysis over multiple dialysis treatments can be evaluated by the time average urea concentration (TAC).
Complications of haemodialysis
a) Restlessness / tremors / vocalization / seizures: It occurs in cases of dialysis disequilibrium which causes an increase in brain water content. It can be treated with intravenous mannitol, diazepam and by slowing or discontinuing haemodialysis.
b) Hypotension: This occurs in cats and small dogs, because the volume of extracorporeal circuit relative to vascular volume is large. This can be minimized by priming the patient with colloidal solutions. Dialysis induced hypotension responds quickly to fluid supplementation.
c) Clotting in extracorporeal circuit: This may occur due to activation of the alternate complement pathway by contact of blood with the dialyzer membrane which causes leukocyte and platelet aggregation. This can be minimized by carefully managed heparinization. If the clots enter the pulmonary microvasculature and hypoxia results then prognosis for recovery is grave even with ventilatory support.
d) Blood loss: It occurs due to clotting in the dialyzer, repeated diagnostic blood sampling and bleeding from excess hepariniztion. There will be decrease in white blood and platelet cell counts also and this is routine during dialysis. Another persistent problem in dialysed animals is anaemia. In severe cases blood transfusion may be necessary.
e) Vomiting: It occurs secondary to hypotension and diversion of blood flow from the GIT, biocompatibility reaction to the membrane or contaminants in the dialysate. Dialysis disequilibrium can also cause vomiting. This can be minimized by using slow blood flow rate at the start of dialysis and then gradually increasing.
Other complications
Nausea is usually encountered at the start of the dialysis secondary to hypotension due to diversion of blood flow from gastrointestinal tract or contaminants in the dialysate. Hypoxemia of mild to severe degree is common within 30 to 60 minutes of the start of dialysis and resolves automatically within 2 hours after discontinuation of dialysis.
Washing and reuse of dialysers and tubings
Where owners can afford, fresh dialyser and tubings can be used for each dialysis. Because of the high cost it is customary practice that these are thoroughly washed, disinfected and stored properly with aseptic precautions and reused on the same patient. There are different procedures available for this. These materials can be reused three to four times and then discarded.
Conclusions
Haemodialysis is a safe, efficacious and indispensable therapy for both dogs and cats with life threatening renal failure. However, the complexity involved has limited its widespread usage. With growing awareness that there is no alternative except death in acute and chronic uremia, this area is expanding.
References
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