Critical Care of the Acute Renal Failure Patient
Melissa S. Wallace, DVM, Diplomate ACVIM
Acute renal failure is a sudden loss of the homeostatic and excretory functions of the kidneys, due to intrinsic damage to the renal parenchyma. Common etiologies are toxins, drugs, ischemic insults, and infectious/inflammatory diseases. It is important to differentiate ARF from CRF. ARF is more difficult to manage and the animal is more likely to die within a short period of time. The patient requires extensive and expensive therapy to increase the chance of recovery. Failure to intensively manage these critical patients may result in the death of some pets that could have recovered, so referral to a 24-hour care facility may be advised. Although the short-term prognosis is guarded, some patients with ARF will go on to heal and recover from the disease.
Characteristics of Acute Renal Failure
Clinical Signs & Physical Examination
Rapid onset of lethargy, anorexia, vomiting, +/- halitosis.
Good body condition, +/- flank pain, +/- fever, +/- halitosis/ulcers
Elevations in BUN, creatinine, phosphorus, +/- isosthenuria, usually no anemia
Radiographs and ultrasound
Normal to slightly enlarged kidneys with normal architecture, +/- hyperechoic cortices (R/O ethylene glycol), +/- pyelectasia or hydronephrosis
Diagnostic Evaluation of Acute Renal Failure:
Monitoring ARF Patients
Central venous pressures (BID - QID)
Serial body weights (TID - QID)
Urine output (q 2 - 6 hours)
Blood pressure (SID - BID)
BUN, Creatinine, Phosphorus (SID)
PCV, TP, Lytes, Blood Gases (BID - QID)
THERAPY OF ACUTE RENAL FAILURE
1. Establish Renal Perfusion
Correct fluid deficits rapidly; IV over six hours.
mL of fluid = % dehydration x body weight (kg) x 1000
Give maintenance fluid IV at a rate of 50 - 60 ml/kg/day.
Give a slight increase for volume expansion (i.e. the 'push'). This is usually 3 - 5% of the body weight as fluid over 24 hours.
Add fluid for contemporary losses (e.g. vomiting, diarrhea) if severe.
Monitor body weight, hydration, CVP, BP, and urine output carefully to adjust fluid rate. The body weight should rise by the percentage dehydration you calculated, and then stay relatively constant (except for a loss of 0.5 - 1% per day from anorexia). The blood pressure should be at the high end of normal or slightly above normal, and the CVP should be above normal but not so high as to induce pulmonary edema (goal = 6 - 10 mm H2O).
Fluid choice; start with 0.9% saline for rehydration, then switch to a balanced electrolyte solution (e.g. lactated Ringer's). The fluid choice depends on the animal's sodium, potassium, and acid-base balance. 0.45% saline with 2.5% dextrose is used in animals with hypernatremia after rehydration.
2. Correct Electrolyte Disturbances
Acute renal failure patients are very often hyperkalemic, because excretion of potassium depends on GFR and urine output.
If the animal is hyperkalemic (> 4.5 mEq/L) be sure that fluids do not contain potassium.
If the serum potassium concentration is > 7.0 mEq/L and/or there are electrocardiographic changes, provide emergency therapy. ECG changes typical of hyperkalemia are: tall, tented T waves, prolonged P waves, prolonged PR interval, absent P waves, bradyarrhythmia, or a sinoventricular rhythm.
Therapeutic options for hyperkalemia:
Insulin and Dextrose: this shifts potassium into cells as glucose moves into cells. Give 0.5 units/kg of regular insulin IV followed immediately by 1 gram of dextrose per unit of insulin IV (dilute the dextrose to 20% in sterile water). Then add dextrose to the IV fluids at a rate of 1 gram per unit of insulin for the next six hours, or 5% dextrose, whichever is greater. Monitor blood glucose over the next 6 hours.
Sodium bicarbonate: this shifts potassium into cells in exchange for hydrogen ions. Give 1 - 2 mEq/kg slowly IV over 15 - 20 minutes.
Calcium gluconate: this counteracts the effect of hyperkalemia on the cardiac conduction system. This is the most rapid therapy. Giving calcium to hyperphosphatemic patients is relatively contraindicated, so this is only used in severe cases. Give 0.5 - 1 ml/kg IV over 10 - 15 minutes.
Intractable or recurrent hyperkalemia is an indication for peritoneal dialysis or hemodialysis.
Hypernatremia may develop in some ARF patients due to inability to excrete a sodium load. For animals with hypernatremia, use ½ strength fluids (saline or LRS) with 2.5% dextrose.
ARF patients are usually hypermagnesemic, but this is rarely severe enough to warrant therapy. Rational therapy would be calcium gluconate, as for hyperkalemia. If hypomagnesemia develops, the IV fluids can be supplemented with magnesium sulfate.
3. Correct Severe Acid-Base Disturbances
Renal failure patients usually have a high anion gap metabolic acidosis. The anion gap will be especially high in cases of ethylene glycol. If the animal's brainstem and respiratory system are functioning adequately, respiratory compensation will be present to some degree.
Severely acidemic patients may benefit from therapy with sodium bicarbonate (NaHCO3). A rule of thumb is that if the blood bicarbonate is < 10 mEq/L and/or the pH is < 7.1, consider therapy. Avoid therapy in animals with hypernatremia or other causes of hyperosmolarity, because NaHCO3 has a very high sodium content and is hyperosmolar.
The dose calculation is: 0.3 x body weight (kg) x base deficit. If the blood gas machine does not calculate a base deficit, estimate it as (21 - patient's HCO3-). Total CO2 can be used instead of HCO3-. Give ¼ of this calculated dose as a slow IV bolus and another ¼ in the IV fluids over the next six hours, and then reassess the blood gases if possible.
4. Induce Polyuria in Oliguric/Anuric Animals
Anuria is a lack of urine production. Oliguria is defined as urine production of < 0.27 ml/kg/hr. However, in ARF patients in which diuresis is being attempted, urine output < 1 - 2 ml/kg/hr is considered inadequate, especially if it persists.
Anuria or oliguria can not be assessed accurately until the animal is adequately rehydrated, with a normal or slightly elevated blood pressure and a CVP > 5 cm H2O. If in doubt, the response to a small fluid bolus may be evaluated. If oliguria persists, pharmacological intervention to attempt to convert the patient to polyuria is warranted.
Mannitol is an osmotic diuretic agent. It is a mild free radical scavenger and a weak renal vasodilator. The principal action of mannitol is to increase tubular flow to help prevent or reduce tubular obstruction from cellular debris and/or tubular collapse. Give 0.5 g/kg as a slow IV bolus over 15 - 20 minutes. Assess urine output over the next hour. If no response is seen, a second dose may be given. If an effect is seen, it can be followed by a constant rate infusion of 1 mg/kg/min not to exceed 2 g/kg/day. If oliguria or anuria persists and overhydration is suspected, do not continue mannitol, because pulmonary edema can occur.
Furosemide acts as a renal vasodilator and as a diuretic. Some nephrologists use furosemide before trying mannitol. Using them in combination if a single agent has failed may also help. Give 2 - 20 mg/kg IV boluses, starting at the low end of the dose and increasing (double the dose) if no response is seen. Furosemide is usually given as QID IV boluses, but some criticalists use a constant rate infusion. Inadequate response to initial furosemide is a good indication to give it with mannitol or with low dose dopamine.
Dopamine at low doses acts on dopaminergic receptors as a renal vasodilator. At moderate doses it stimulates the beta1-adrenergic receptors exerting a positive inotropic effect, and at high doses it has alpha-adrenergic effects and is a systemic vasopressor. In most cases of ARF, the low dose is given, often in conjunction with furosemide. Give 0.5 - 3 ug/kg/min as a constant rate IV infusion with a syringe pump in D-5-W, normal saline, or LRS. Cats do not have renal dopamine receptors.
5. Avoid Overhydration and Pulmonary Edema
If the animal is volume expanded and remains oliguric or anuric, the initial fluid calculation will cause rapid overhydration and pulmonary edema if continued. This is why assessing urine output, CVP and serial body weight is so critical in ARF patients. At this point, the fluid management must be changed to a system called 'Ins and Outs'.
Ins and Outs: Measure the urine output with an indwelling urinary collection system or by completely 'catching' all of the urine. Give the patient, as IV fluids (Ins), the same volume that he produces as urine (Outs), plus insensible loss. Insensible loss is metabolic and respiratory water loss, and is ~ 20 ml/kg/day. If the patient is losing a lot of fluid in vomiting or diarrhea, that should be estimated and added into the calculation as contemporary loss.
The more often you measure the urine output and recalculate the IV fluid rate, the more accurately you will match the patient's needs. In a human CCU, this is usually done hourly. In veterinary medicine, it is usually done every 4 or 6 hours.
Example: To do 'ins and outs' every four hours, calculate the daily insensible loss and divide by 6 to figure out the insensible loss per 4 hours. Then, using a flow chart, the technician or doctor measures the urine output every four hours. This volume plus the 4-hour insensible loss figure are added together, and this is the amount of fluid that should be given over the next four hours. Divide that by four to get the ml/hr and reset the fluid pump. Any time spent off of the IV fluid pump will need to be accounted for and added back in to avoid volume depletion.
The advantage of this system is that if the animal becomes polyuric, you will automatically increase the IV fluids going in to match the output, avoiding dehydration and hypovolemia. You can initiate or continue pharmacologic attempts at inducing polyuria while performing 'Ins and Outs'.
6. Control Signs of Uremia
Signs of uremia include: lethargy, vomiting, gastrointestinal ulceration, diarrhea, stomatitis and oral ulceration, weight loss, anemia, uremic pneumonitis, uremic encephalopathy, myopathy, neuropathy, immune failure, etc.
One of the most important signs to treat is nausea and vomiting. This is often accomplished by the use of antiemetics, such as metoclopramide, which can be given as a subcutaneous injection (0.2 - 0.4 mg/kg TID SQ) or as a constant rate infusion (1 - 2 mg/kg/day IV). Metoclopramide works both in the G.I. tract and on dopaminergic receptors in the brain. If given as an IV infusion, the bag and tubing should be protected from the light. Since metoclopramide is renally excreted, conservative dosing to effect is advised. Prochlorperazine at low doses may be effective in severe cases. Deleterious side effects in ARF patients are hypotension and sedation.
Animals with renal failure tend to have gastric hyperacidity, in addition to irritation of the G.I. mucosal from uremic toxins (e.g. ammonia), and they are very prone to gastrointestinal ulceration. Using H2 receptor-blocking agents is helpful. Ranitidine (1 - 2 mg/kg BID IV or SQ) and famotidine (0.5 - 1 mg/kg SID IV or SQ) are currently the most commonly used agents. Sucralfate, an orally administered gastrointestinal protectant that binds to ulcer sites, may also be helpful.
Uremic stomatitis and ulceration can be severe, and contributes to patient discomfort and anorexia. Cleansing the mouth with a gentle chlorhexidine oral solution 2 - 3 times daily may be helpful. Viscous lidocaine gel applied to ulcers in dogs ~ 15 minutes before feeding may also be useful.
Hyperphosphatemia contributes to the uremic syndrome; administration of phosphate binding agents may be helpful. They work better in animals that are receiving oral or enteral nutrition, but may have some effect even in anorectic patients.
Some animals with acute renal failure have significant pain due to their primary disease process (e.g. pancreatitis) or due to renal pain (e.g. pyelonephritis, Leptospirosis, ureteral obstruction). Using low doses of narcotic analgesics, such as butorphenol as a constant rate infusion, may make the patient more comfortable and aid in the healing process.
7. Provide Nutritional Support
Unless the animal is likely to recover sufficiently to regain an appetite in less than 4 days, nutritional support should be instituted. Nutrition is vital to buying the animal enough time for recovery, and to maximize the healing process. If uremic vomiting is not too severe, use the intestinal tract. Tube feeding with a nasoesophageal tube, esophagostomy tube, or percutaneous gastrostomy tube are all good choices. The veterinarian's experience and comfort with the rapid placement of whatever tube is used is the critical factor. A feeding tube often helps to manage the animal at home earlier, because fluid and medications can be administered through the tube when the patient is considered stable. Avoid prolonged anesthetic procedures in the face of acute renal failure if possible, as any hypotension will cause further damage to the kidneys, which have lost autoregulation of intrarenal blood flow.
If vomiting is persistent, then partial parenteral nutrition or total parenteral nutrition can be instituted. If the animal is oliguric, the volume of PPN/TPN calculated may be more than the patient can tolerate. Still, some nutrition is always better than no nutrition. Because PPN and TPN require careful handling and mixing, and must be administered continuously once started, cases that need this level of critical care are often referred to a secondary or tertiary care facility. However, a local human hospital pharmacy can often prepare the solutions if the veterinarian formulates the patient's prescription.
Formulations should be moderately protein (or amino acid) restricted, so that less BUN is formed. This will reduce uremia and acidosis, and may improve the prognosis. In addition, lower protein diets are also lower in phosphorus, which will improve the mineral balance of the patient, reduce soft tissue mineralization, and reduce signs of uremia.
For animals that do not respond to aggressive medical management, dialysis is an option. The two techniques are peritoneal dialysis and hemodialysis. The following is a list of indications for dialysis:
1. Intractable uremic syndrome (vomiting, depression, anorexia, seizures, neuromuscular signs).
2. Persistent hyperkalemia (> 7.0 mEq/L)
3. Persistent oliguria/anuria
4. Overhydration (especially with oliguria)
5. Severe metabolic acidosis
6. Persistently elevated BUN/Creatinine (BUN >150 mg/dL, creatinine > 10 mg/dl)
Currently, hemodialysis is available at the University of California, Davis, The Animal Medical Center in New York City, and VCA in Gaithersburg, MD.