Fluid treatment for renal failure (Proceedings)

Kidney disease is classically compartmentalized into acute and chronic disease, which is a convenient way to view what are very frequently markedly different manifestations of kidney disease. There is some overlap, however, in that a decompensated patient with chronic kidney disease (CKD) has a superimposed acute kidney injury (AKI) that may require hospitalization for fluid therapy. Although significant renal disease can be present without azotemia, fluid therapy is generally not necessary in those situations. In fact, fluid therapy may not be necessary in compensated chronic renal failure with mild to moderate azotemia.

Normal fluid losses consist of insensible and sensible losses. Insensible losses are those that are not consciously perceived, such as water lost via respiration, normal stool or sweating. Sweating is a negligible volume in dogs and cats. There is variation in respiratory losses in dogs, which may lose considerable amounts of fluid by excessive panting, but 22 ml/kg/day is the average. The main sensible fluid loss in the normal patient is urine output. Additional sensible losses include the volume lost from vomiting, diarrhea, body cavity drainage, burns, etc. In healthy animals, these losses are replaced by drinking and the fluid contained in food. In sick animals, who may not be voluntarily consuming food or water, or who may be restricted from consumption due to vomiting, fluid therapy is necessary to replace these losses. With renal disease, urine volume is frequently abnormally high or low, or inappropriate for the situation, and fluid therapy is tailored for the individual patient to maintain fluid balance.

Fluid therapy for hospitalized patients

Many drugs have been evaluated for their benefit in treating AKI, and some are helpful in certain settings. However the most effective therapy of AKI is careful management of fluid balance, which involves thoughtful assessment of hydration, a fluid treatment plan personalized for the specific patient, repeated and frequent reassessment of fluid and electrolyte balance, with appropriate changes in the treatment plan in response to the rapidly changing clinical situation of the renal failure patient.

Assessing hydration

The key feature to an appropriate fluid plan is accurate determination of hydration status. A deficit of the extravascular fluid compartment (interstitial and intracellular) causes dehydration. A severe deficit may decrease the intravascular compartment, leading to poor perfusion. Dehydration of less than approximately 5% is difficult to detect clinically. A 5 to 6% deficit leads to sticky mucous membranes. Six to eight percent dehydration causes dry mucous membranes and decreased skin elasticity. By 8-10% dehydration, the eyes may be sunken, and over 12% dehydration, corneas are dry, mentation is dull, and perfusion is impaired. Overhydration may manifest as wet mucous membranes, increased skin elasticity (heavy or gelatinous), shivering, nausea, vomiting, restlessness, serous nasal discharge, chemosis, tachypnea, cough, dyspnea, pulmonary crackles and edema, pleural effusion, ascites, diarrhea, or subcutaneous edema (especially hock joints and intermandibular space). Uremic patients frequently have xerostomia, causing dry mucous membranes independent of hydration status. Hypoalbuminemia or vasculitis may cause interstitial fluid accumulation despite an intravascular volume deficit. Emaciation or advanced age decrease elasticity of the skin.

An accurate body weight recorded prior to illness is an invaluable aid to assessing hydration. Body weight should be measured several times a day on the same scale. A sick animal may lose up to 0.5-1% body weight per day due to anorexia; changes in excess of this amount are due to changes in fluid status. An increase in blood pressure may indicate a gain of fluid; conversely, a decrease in blood pressure may indicate a net loss of fluid. Because of the high percentage of patients with hypertension (80% of dogs with severe acute uremia and 20-30% of dogs and cats with CKD), the trend rather than the absolute value is of more utility in assessing changes in hydration status. Similarly, changes in trends for PCV and total solids may reflect changes in volume, in the absence of bleeding or blood transfusion. Central venous pressure (CVP) measurement through a centrally placed intravenous catheter may provide information about intravascular filling. A volume depleted animal will have a CVP less than 0 cm H20. A CVP over 10 cm H20 is consistent with volume overload or right sided congestive heart failure. However, pleural effusion falsely elevates the CVP. Because each parameter is impacted by aspects beyond hydration status, these factors must be viewed in aggregate.

Route of fluid administration

In most hospitalized patients, the intravenous route is the most appropriate route of administration. In some situations, such as extremely small patients, including neonatal puppies or kittens, IV catheterization may be difficult. Intraosseous fluid administration can be used in that setting. In dehydrated patients, fluids administered into the peritoneal cavity will be readily absorbed, but this method is not reliable for promoting diuresis or in oliguric patients. Fluid administered subcutaneously may not be absorbed rapidly or completely, and it is not possible to administer a large volume by this route, making subcutaneous fluid inappropriate for the hospital setting.

Type of fluid

A balanced polyionic solution (i.e., lactated ringer's solution [LRS], Plasmalyte-148, Normosol-R) is an appropriate choice for the initial volume resuscitation fluid and replacement of the dehydration deficits. Physiologic (0.9%) NaCl contains no potassium and is a suitable choice for the hyperkalemic patient.

After rehydration, maintenance fluids with a lower sodium concentration are more appropriate (i.e., 0.45% NaCl with 2.5% dextrose, ½ strength LRS with 2.5% dextrose). Dextrose 5% in water (D5W) is rarely appropriate as sole fluid choice, but may be combined with LRS or 0.9% saline to make ½ or 3/4 strength sodium solutions (25 ml LRS + 25 ml D5W = 50 ml ½ strength LRS + 2.5% dextrose).

Colloidal solutions (i.e., hydroxyethyl starch, 6% dextran) may be appropriate if hypoalbuminemia is present. The recommended dose is 20 ml/kg/day, and may be used to replace the insensible portion when using the "ins-and-outs" method (see below). Higher doses may be associated with coagulopathy. An alternative to synthetic colloids is human albumin, but this product carries a risk of anaphylaxis.

Treatment of the patient with an acute uremic crisis from a protein-losing nephropathy with severe hypoalbuminemia involves additional considerations. An increase in the intravascular volume and hydrostatic pressure from crystalloid infusion is not opposed by colloid oncotic pressure in the plasma, enhancing interstitial edema in the periphery. Even with use of a colloidal solution, aggressive diuresis with a crystalloid may not be possible without creating peripheral edema.

Red blood cell transfusion may be indicated if symptomatic anemia is present. Red cell survival is shorter in the uremic environment, blood sampling may create substantial losses, and erythropoietin production is generally suppressed. Gastrointestinal bleeding can acutely cause anemia, and if bleeding is brisk, hypotension and hypovolemia may occur and require rapid infusion of crystalloid or colloid solutions. Intensive diuresis may exacerbate high output heart failure in cats with anemia. Conversely, rapid blood transfusion may cause congestive heart failure. In patients with compromised cardiovascular function or incipient volume overload, transfusions may need to be given more slowly than usual.

A sometimes overlooked fluid choice is water given enterally. Because vomiting is a common problem with uremia, enteral food or water is frequently contraindicated, and many uremic patients will not voluntarily consume water. However, water administered through a feeding tube should be included in water calculations.

Ultimately, the fluid choice must be guided by monitoring the patient's fluid and electrolyte balance. A major determining factor in the appropriate fluid choice is the sodium concentration, because the degree of free water loss relative to sodium loss varies greatly in patients with AKI. The guiding principal in treating a sodium disorder is to reverse it at the same rate at which it developed as rapid increases or decreases in sodium concentration may cause CNS dysfunction.

Volume and Rate

Some patients may present in hypovolemic shock, which is manifest as dull mentation, hypotension (systolic blood pressure < 80 mmHg), poor perfusion of the periphery (cold extremities, pale/grey mucous membranes with slow capillary refill time), hypothermia, or tachycardia. Immediate correction of shock is necessary to prevent further and irreversible organ damage. The standard dose of crystalloid is 60-90 ml/kg for dogs and 45-60 ml/kg for cats, of which ¼ is given over 5 to 15 minutes. If hemodynamic parameters do not improve sufficiently with the first ¼ dose, a second dose should be given. Resuscitation efforts are continued until the patient is hemodynamically sound. If the patient remains hypotensive and there are concerns about volume overload, central venous pressure monitoring may be helpful. A 10-15 ml/kg bolus of crystalloid or 3-5 ml/kg of colloid will not change the CVP in hypovolemic patients, but will transiently increase the CVP by 2-4 cm H2O in the euvolemic patient, and cause a rise of over 4 cm H2O in the hypervolemic patient.

For patients presenting with dehydration, the dehydration deficit is calculated as body weight (in kgs) x estimated % dehydration = fluid deficit in L. Because dehydration of less than 5% cannot be detected clinically, a 5% dehydration deficit is presumed in patients that appear normally hydrated. If a fluid bolus was used for resuscitation, that volume is subtracted from the dehydration deficit.

The rate of replacing the dehydration deficit depends on the clinical situation. In patients with AKI, who have presumptively become dehydrated over a short period of time, rapid replacement is prudent. This restores renal perfusion to normal levels and may help prevent further damage to the kidneys. In situations where urine output may be diminished, rapid replacement of dehydration deficits allows the clinician to quickly determine if oliguria is an appropriate response to volume depletion or is a pathologic change from renal failure. In that setting, replacing the deficit in 2-4 hours is recommended. If there is potential compromise of diastolic function of the heart, a rapid fluid bolus may precipitate congestive heart failure, and a more gradual rehydration rate (i.e., over 12-24 hours) may be prudent. In patients with chronic dehydration, a more gradual replacement of the fluid deficit is acceptable to minimize the risk of cardiac problems or rapid electrolyte changes, and 24 hours is a commonly selected time frame. In severely dehydrated, chronic debilitated patients, it may take up to 48 hours to rehydrate.

The concept of maintenance fluid rate is based on average fluid losses from insensible (respiration) and sensible (urine output) sources. The most commonly quoted value is 66 ml/kg/day. Ignoring normal individual variation, the presumption with this value is that urine output is normal and there are no other sources of fluid loss, which is rarely the case in patients with renal failure. However, it makes a reasonable starting point for calculating fluid administration volumes. If accurate measurement of urine output and on-going losses is available, fluid therapy can be adjusted precisely (see "ins-and-outs" method below). If these parameters are not accurately measured, an estimate of the loss should be included in the fluid administration rate. In practical terms, after an initial fluid resuscitation if needed for shock, the volume of fluid to administer is calculated by adding average maintenance fluids (66 ml/kg/day) plus replacement of dehydration (over selected time frame) plus ongoing losses (estimated volume of polyuria, vomiting).

Because uremic toxins are retained in renal failure, administration of a volume of fluid exceeding "maintenance" can improve excretion of some uremic toxins in animals with the ability to increase urine output in response to a fluid challenge. The volume is varied based on clinical situation and clinician preferences, but generally ranges from 2.5-6% of body weight per day, in addition to maintenance fluid administration rate. In practical terms, twice the maintenance fluid rate is equivalent to a maintenance rate plus a 6% "push" for diuresis (60 ml/kg/day = 6% of body weight).

If the urine output varies substantially from normal, either oliguria (< 0.5 ml/kg/hr) or polyuria (> 2 ml/kg/hr), a fluid plan based on these assumptions may be inadequate. Animals with renal failure may have urine output in a "normal" range (0.5-2.0 ml/kg/hr), but if their kidneys are unable to alter the urine volume to excrete a fluid load, the patient has "relative oliguria." The ins-and-outs method of fluid administration is appropriate in these situations. It should only be used after rehydration is complete and is not appropriate if a patient is still dehydrated.

There are three components of volume calculations in the "Ins-and-Outs" method, consisting of 1) insensible loss (fluid lost via respiration and normal stool) = 22 ml/kg/day, 2) urine volume replacement calculated by actual measurement (see below for measuring techniques), and 3) on-going losses (i.e., vomiting, diarrhea, body cavity drainage) which are generally estimated.

To write treatment orders for "ins and outs" using two IV catheters, divide the daily insensible loss by 4 to determine the QID dose of IV fluid for one catheter. You can use this fluid dose to deliver any drugs that need to be given by constant rate infusion (CRI) (metoclopramide, furosemide, mannitol, etc.). For the starting fluid dose, select a volume based on your estimate of the patient's needs. The fluid rate is then recalculated every 6 hours. Use the previous 6 hour urine output volume plus an estimate of losses during that time period (vomiting and diarrhea) as the volume to deliver over the next QID treatment in the second catheter. If only one IV catheter is available, calculate the amount of medication to be administered by CRI to give over 6 hours. Add this amount to the fluid volume required over the next 6 hours (6 hours of insensible losses + previous 6 hour urine output). Divide the total volume by 6 to get the hourly rate for the CRI. If a fluid pump is available, calculate daily insensible fluid needs and divide by 24 to get hourly rate. Add to this the hourly volume of urine output over the previous monitoring interval, plus an estimate of on-going losses.

An anuric patient should receive fluid administration to replace insensible loss only. If the patient is overhydrated, withhold the insensible loss. Overhydration in an anuric patient or inability to induce diuresis in an oliguric or anuric patient is an indication for dialysis.

Converting oliguria to non-oliguria

An appropriate renal response to inadequate renal perfusion from hypovolemia or hypotension includes fluid retention with a concomitant decrease in urine volume. Before determining whether oliguria is pathologic or physiologic, renal perfusion should be optimized by ensuring adequate hydration and blood pressure. Healthy kidneys can autoregulate renal blood flow at perfusion pressures between 80-180 mmHg, but renal perfusion may be more linear in damaged kidneys. The mean arterial pressure should be maintained above 60-80 mmHg, or the systolic pressure above 80-100 mmHg when measured by Doppler technology. Apparent anuria due to obstruction of the urinary tract or leakage into the peritoneal, retroperitoneal, or subcutaneous tissues should be excluded before determining that a lack of urine is due to intrinsic renal damage. Various diuretics, including mannitol and furosemide, may increase urine volume, but in general, diuretics do not improve glomerular filtration rate. Although oliguria or anuria are the classic manifestation of acute kidney injury, AKI may present with polyuria which frequently portends a less severe renal injury.

Monitoring fluid therapy

Monitoring fluid status is an ongoing process that must be repeated throughout the day. Physical examination and body weight should be assessed at least twice daily, and the fluid plan adjusted accordingly. Blood pressure should also be monitored. Urine output and other fluid loss should be monitored and correlated to other findings of volume status.

Determining urine volume can be performed by a variety of methods. An indwelling catheter is usually the most precise method, although technical issues such as urine leakage around the catheter or inadvertent disconnection may cause an artifactually low measurement. The risk of an iatrogenic urinary tract infection from the catheter can be decreased by careful attention to catheter and patient hygiene, including cleaning the external portions of the catheter with antiseptic multiple times daily and changing the collection bag and tubing daily. Complete collection of voided urine may be difficult in many patients, because of lack of patient cooperation, or urinary incontinence in obtunded or recumbent patients. An accurate scale is necessary to measure small volumes of urine in cats and small dogs, but weighing cage bedding or litter pans before and after use may provide an adequate assessment of urine volume in some patients (1ml of urine = 1 gm). Fluid losses from vomiting and diarrhea are usually estimated, and other losses such as body cavity drainage or nasogastric tube suctioning can be measured.

Discontinuing fluid therapy

With AKI, once a diuresis has been established, polyuria can be quite profound. Weaning these patients off of IV fluids is a crucial step. When the azotemia has resolved or has reached a plateau, the fluid dose can be decreased by 25% per day. If the urine output diminishes by a corresponding degree and the azotemia does not return, continue tapering over 2 to 3 days. If the urine output does not diminish, the kidneys are unable to regulate fluid balance and further reduction in the fluid administered will lead to dehydration. Attempts to taper the fluid rate can be made again after several days, but generally at an even slower rate (10-20% per day). It can take weeks for the kidneys to regain the ability to control fluid volume in rare cases.

With CKD, once the prerenal component of the azotemia has resolved, the serum creatinine concentration will usually decrease by at least 1 mg/dl per day. When the creatinine concentration reaches a baseline value, fluids should be tapered in preparation for patient discharge. Aggressive diuresis should be tapered gradually over about 2 to 3 days.

Outpatient Fluid Therapy

Chronic dehydration or persistent signs of uremia are rational indications for chronic subcutaneous fluid administration. Dose is empirical, based on subjective assessment of the patient's well-being and hydration status. A typical starting dose for cats is 100-150 ml daily to every other day. Lactated ringers solution or 0.9% saline are appropriate fluids choices. Dextrose containing fluids increase the risk of abscess formation, and Plasmalyte is reported to sting. Many owners can be taught to administer the fluid dose at home. An administration tube can be implanted in the subcutaneous space, but this method increases the risk of infection at the skin exit site, and subcutaneous fibrosis with subsequent pain during administration and decreased capacity has been observed.