Professor and Associate Chair, University of Florida, College of Veterinary Medicine
Gainesville, FL, USA
Fluid and Electrolytes
Disturbances in hydration and electrolyte balance are of great importance in diabetic ketoacidosis (DKA) and require expedient correction when present. The calculated fluid requirements include the patient's dehydration deficits, the 24 hour maintenance needs, and extra losses that result from vomiting or diarrhea. The dehydration status is approximated on a scale ranging from a mild (5%) to extreme (12%). The needed isotonic replacement volume is calculated by either of the following two methods:
1. Dehydration volume deficit (ml) =
= % dehydration x kg body wt x 1000
2. Dehydration volume deficit (ml) =
= % dehydration x lb body weight x 500
The 24 hour maintenance volume is roughly estimated (assuming adequate urine output) at 60 ml/kg (30 ml/lb). Therefore, the initial first 24 hour total fluid volume is the sum of the dehydration and the maintenance volumes plus any on-going losses.
If the animal is 8-12% dehydrated, 2 of the estimated dehydration deficit should be administered intravenously over the first 2-4 hour period of hospitalization with the remaining replacement and maintenance volumes given over the following 20-22 hour period. When hypovolemic shock is present, the initial first hour's fluid dose is 70-90 ml/kg for a dog or 35-40 ml/kg for a cat. Close patient monitoring is essential during rapid intravenous infusions.
It is important to remember that hydration alone can decrease the levels of the blood glucose and certain counterregulatory hormones. Most investigators believe that the mechanism of lowering the blood glucose by hydration is caused by increased osmotic diuresis and glucosuria. It is suggested that prior hydration will make the response to insulin more predictable. I prefer to correct hypovolemia with isotonic solutions such as lactated Ringer's or 0.9% saline. Acetated solutions, on the other hand, are not recommended since they may theoretically result in increased ketone body production. Recommended maintenance solutions include 0.4 5% saline or 2-strength lactated Ringer's solution. These half-strength solutions are also used for the hyperosmolar patient. Dextrose solutions (22-5%) are reserved for use when the patient's blood glucose declines to 250 mg/dl (13.7 mm/L) or less in the setting of continued insulin administration.
Hyponatremia is corrected with intravenous 0.9% saline solution in order to avoid any plasma hypoosmolality that might occur when the hyperglycemia is reduced with insulin treatment. Plasma hypoosmolality can cause a reversal of osmotic gradients and an overexpansion of the intracellular compartment, particularly in the central nervous system where cerebral edema can occur.
Hypokalemia is the most common and probably most important serum electrolyte disorder in DKA. The reasons for potassium loss include cell catabolism, osmotic diuresis and vomiting. This loss is furthered by additional losses from: (1) serum dilution from rehydration; (2) continued urinary losses brought about by sodium ion delivery to the distal renal tubule; (3) correction of acidosis and the accompanying cellular influx of potassium ions; and (4) increased cellular uptake of potassium due to insulin. One way of avoiding hypokalemia initially is to allow for the infusion of potassium supplemented fluids for the first 2-4 hours before any insulin is administered.
Potassium supplementation is best provided with potassium chloride (KCl) solution, which is added to the parenteral fluids. If concurrent hypophosphatemia is present, potassium phosphate solution can be added and cautiously administered as well. Potassium supplementation is best begun after the first 2 hour period of fluid replacement when hydration, blood pressure, and urine output are improved. If the patient is initially hypokalemic, KCl can be added to the hydrating solution, but the infusion is slowed down to where one-half of the dehydration replacement volume is delivered over an additional 1-to 3-hr period. The recommended amount of potassium supplementation to be administered over a 24-hour period is as follows:
1. Mild hypokalemia (serum K+ = 3.0-3.5 mmol/L): give 2-3 mEq KCl/kg
2. Moderate hypokalemia (serum K+ = 2.5-3.0 mmol/L): give 3-5 mEq KCl/kg
3. Severe hypokalemia (serum K+ = < 2.5 mmol/L): give 5-10 mEq KCl/kg
The daily potassium dose for the average diabetic is 3-5 mEq/kg. Potassium chloride can also be added to the parenteral fluids in amounts ranging from 20-60 mEq/L depending on the severity of the hypokalemia.
Daily serum electrolyte determinations and the necessary treatment adjustments are made until normal values are obtained. The intravenous fluids are discontinued when serum biochemistries are normal, euhydration is present, and the patient is able to eat.
Hypophosphatemia is known to occur in some patients with DKA. Although plasma phosphate may fall to levels that are experimentally shown to be associated with altered consciousness, rhabdomyolysis, muscle weakness, impaired cardiac function, hemolysis, and respiratory failure; phosphate depletion in DKA is usually clinically silent and shows up only in clinical measurements. Nevertheless, if the clinician is concerned about severe hypophosphatemia that is present before treatment (usually < 1 mg/dl or 0.32 mmol/L), phosphate supplementation can be provided in the form of potassium phosphate solution at the recommended dose of 0.01 to 0.03 mmol of phosphate/kg/hr followed by repeat serum phosphorus determinations every 6 hours. Caution should be exercised to avoid any consequences resulting from hyperphosphatemia which can include soft tissue mineralization and hypocalcemia.
Sodium bicarbonate treatment is another matter of controversy in treating DKA. The advocates of treatment express their concern that severe acidosis can adversely effect cardiac function, as seen experimentally, while opponents of bicarbonate therapy base their concerns on its cause and effect relationship with paradoxical central nervous system acidosis. The use of sodium bicarbonate is often restricted to those patients with a blood pH < 7.1. During most treatment courses, the metabolic acidosis will reverse due to: (1) the cessation of ketogenesis; (2) metabolic conversion of ketones to bicarbonate following commencement of insulin treatments; (3) improved renal function, and (4) conversion of the lactate in lactated Ringer's solution to bicarbonate. In severe metabolic acidosis, where the anion gap > 30 mEq/L and the arterial pH < 7.1, sodium bicarbonate can be given at the following dose schedule:
Amount NaHCO3 = base deficit x 0.3 x body weight kg
The base deficit equals the difference between the desired serum bicarbonate level and the measured level. Subsequent alkali treatment will depend on the results of repeated plasma pH measurements; it should be discontinued when the blood pH is restored to a level of 7.2 or greater.
Regular crystalline insulin is used when the DKA patient has signs of depression, dehydration, anorexia, and vomiting. The advantages of regular insulin include: (1) various routes of administration (IV, IM and SQ); (2) rapid onset of action; and (3) short duration of action. These properties allow adequate insulin titration throughout the day according to the animal's needs. The clinician must acknowledge that blood glucose levels decline much earlier than ketone levels and therefore anticipate the persistence of some ketonemia and ketonuria for the first 48-72 hr. In other words: "Don't chase ketones."
Bolus intravenous doses of insulin offer the advantage of an immediate onset of action for the critically hypotensive patient. The recommended amount for a medium-sized to large dog is 1-2 units/kg. In the small dog and cat, the dose is reduced to 0.5 units/kg. Subsequent doses are given at the same or varying amounts every 2-3 hr until the blood glucose levels decrease to less than 250 mg/dl, at which time subcutaneous insulin injections can be given approximately every 6 hr. The disadvantages of this technique include the need for intensive care monitoring with frequent (every 1-2 hr) blood glucose determinations, the likelihood of hypoglycemia and hypokalemia, and the possibility of cerebral edema resulting from a too-rapid fall in blood glucose levels. Mannitol is the preferred treatment should this complication occur. The maximum route of blood glucose decline should not exceed 75-100 mg/dl/hr or 4.1-5.5 mmol/L/hr.
When laboratory facilities are unavailable, blood glucose reagent strips can be used to determine approximate blood glucose levels. Several reflectance colorimeters are now commercially available to enhance the accuracy of these reagent strips.
To help avoid the occurrence of the aforementioned side effects associated with intravenous bolusing, a continuous low-dose insulin infusion can be used. One successfully applied technique in the dog involves adding 5 units of regular insulin to a 500 ml bottle of lactated Ringer's solution after the first 2 hr of rehydration and adjusting the pediatric infusion set or pump whereby 0.5-1.0 unit/hr is delivered to the patient. Care must be taken to avoid intravascular fluid overload in the small animal which might result from the technique. This can be accomplished by infusing the insulin containing solution through a separate intravenous catheter. Blood glucose determinations should be made every 1-2 hr.
Low-doses of regular insulin can also be given intramuscularly. Initially 2 units are given into the thigh muscles of cats and dogs weighing less than 10 kg. For dogs weighing more than 10 kg, the initial dose is 0.25 unit/kg. Subsequent hourly injections of 1 unit for cats and small dogs and 0.1 unit/kg for larger dogs are given until the blood glucose level is less than 250 mg/dl, at which time the subcutaneous route can be used on an every 6 hr or as needed basis. The low doses used in this technique can be accurately measured with low-dose insulin syringes.
Subcutaneous regular insulin treatment is a suitable alternative to the intravenous and intramuscular methods when intensive care monitoring is unavailable. The initial dose is 0.5 unit/kg followed by subsequent doses every 6-10 hr depending on need.
The patient is regarded as stable and able to receive intermediate action (NPH) bid or ultra long-acting (PZI or Glargine) insulin when normal hydration is restored, blood glucose levels range between 150-250 mg/dl (75-12.5 mmol/L), serum or urine ketones are minimal to absent, and oral feedings are accepted.