F l u i d an d E l e c t ro l y t e

T h e r a p y in D i a b e t i c
Ketoacidosis
Elizabeth Thomovsky, DVM, MS

KEYWORDS
 Diabetic ketoacidosis  Insulin  Crystalloid fluid  Hyperglycemia  Acidosis
 Sodium  Potassium  Phosphorus

KEY POINTS
 Treatment of diabetic ketoacidosis is relatively straightforward in its approach.
 The difficulty comes in fine-tuning the basic treatment protocol to each animal.
 Using crystalloid fluids in addition to insulin therapy with frequent rechecks of
blood glucose, electrolytes, and blood pH, resolution of the hyperglycemia and
other abnormalities is almost always successful.

INTRODUCTION

Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus commonly encoun-

tered in dogs and cats. This article presents an approach to fluid and electrolyte ther-
apy for DKA. Although an extensive discussion of the pathophysiology and clinical
presentation is beyond the confines of this article, this article will briefly touch on
the important points related to this disease before discussing details of fluid and elec-
trolyte management.

PATHOPHYSIOLOGY OF DIABETIC KETOACIDOSIS

Diabetes mellitus refers to a deficiency of insulin in the body that can be relative or ab-
solute.1,2 Regardless of the exact reason for the deficiency of insulin, the result is that
the diabetic dog or cat is unable to move glucose from the bloodstream into the cells
to fuel cellular metabolic processes. In response, the cells of the body begin to mobi-
lize alternative energy sources such as fats and proteins to provide fuel for meta-
bolism. See Fig. 1A, B for more details.3,4

The author has nothing to disclose.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University,
625 Harrison Street, West Lafayette, IN 47906, USA
E-mail address: ethomovs@purdue.edu

Vet Clin Small Anim - (2016) --

http://dx.doi.org/10.1016/j.cvsm.2016.09.012 vetsmall.theclinics.com
0195-5616/16/ 2016 Elsevier Inc. All rights reserved.
2 Thomovsky

In this climate of cellular demand for energy, the body is initially able to supply
enough energy to the cells, largely through metabolism of fats. However, in the pro-
cess of breaking down fats to make energy, ketoacids are also formed in excess.2
Although some of the ketoacids are used by the myocardium, skeletal muscle, kidney
cells, and brain, those remaining need to be excreted by the kidneys.2
In most cases, ketoacids are formed in excess when cellular energy demand in-
creases above normal.5 In diabetic patients, this often occurs when hormones such
as epinephrine, glucagon, cortisol, and growth hormone are produced. These hor-
mones may be produced when there is a concurrent disease process but can simply
be produced when the body perceives that it requires more energy in the cells.5 Con-
current diseases range from the relatively benign (urinary tract infection) to more severe
disorders such as pancreatitis or neoplasia. These ketogenic hormones increase fatty
acid breakdown (glucagon), further decrease insulins efficacy (growth hormone,
epinephrine, and cortisol), and increase protein breakdown (cortisol and epinephrine).5
Oxidation of fats to form ketone bodies liberates carboxylic acids that release
hydrogen ions.2 Therefore, overproduction of ketone bodies also leads to an overpro-
duction of hydrogen ions, thus decreasing the blood pH and leading to acidosis. A dia-
betic patient can be ketotic without acidosis if the bicarbonate buffering system in the
body can bind to and buffer the hydrogen ions. When the amount of hydrogen ions
created exceeds the bicarbonate buffering systems ability to bind hydrogen, acidosis
results.2
Contributing to the development of acidosis (and hence DKA) is the mechanism of
ketoacid excretion in the kidneys. To be excreted from the kidneys, the ketoacids
combine with sodium found in the extracellular fluid (blood and interstitial fluid).6
Hydrogen ions are then used by the body to replace the sodium ions in the extracel-
lular fluid, further decreasing the pH of the bloodstream and interstitial tissues.1,6

NONPHARMACOLOGIC TREATMENT OPTIONS FOR DIABETIC KETOACIDOSIS

Once a patient has been diagnosed with DKA by a combination of documented hyper-
glycemia, glucosuria, ketonuria, and acidemia, the first order of business is to initiate
treatment. The mainstays of treatment of ketoacidosis are fluids and insulin therapy.
Obviously, if there is another concurrent disorder in the dog or cat that has led to
the development of DKA, such as a urinary tract infection, pancreatitis, or any other
disease, specific treatment of that condition should be instigated as well. This article
focuses on the fluid therapy aspects and briefly touches on insulin therapy; veterinar-
ians are urged to consult other resources for information about treating disorders con-
current with DKA.

OVERVIEW OF FLUID THERAPY IN DIABETIC KETOACIDOSIS

Fluids are given to patients with DKA for several reasons:

 Dehydration (see Box 1 for the mechanism of this change in DKA)
 Hypovolemia (see Box 1)
 Improve glomerular filtration in the kidneys (see Box 1)
 Increase excretion of glucose through the kidneys
 Increase excretion of ketoacids and hydrogen ions through the kidneys
 Decreases acidosis
 Resolve hypernatremia (see Box 2 for mechanism of electrolyte changes)
 Supply potassium (see Box 2)
 Supply phosphorus if indicated (see Box 2).
 DKA FluidsElectrolytes 3

Box 1
Effects of diabetes mellitus on fluid and electrolytes in the body

 Increased concentrations of glucose in the blood will remain either in the intravascular space
or diffuse into the interstitial space. The cell membrane is relatively impermeable to glucose
and, therefore, the glucose does not enter the cells. Instead, the glucose will draw fluid from
the intracellular space into the vascular and interstitial spaces. This dehydrates the
intracellular space.
 Glucose contained the blood is filtered at the glomeruli and excreted through the renal
tubules.
 Glucose contained in the renal tubules holds water in the tubules and decreases tubular
water reabsorption.
 Water is lost in large quantities through the kidneys causing polyuria (osmotic diuresis).
 Lack of water reabsorption in the kidney / decreased vascular volume / fluid shifts from
the interstitium into the vascular space (interstitial dehydration) / fluid shifts from the
intracellular space into the vasculature (intracellular dehydration) / when no more fluid
can leave either the intracellular or interstitial space, the vascular volume decreases
(hypovolemia).
 Diabetes can cause both intracellular and interstitial dehydration.
 Diabetes can also lead to hypovolemia in untreated cases, especially when an animal is
unable to take in water (polydipsia) to compensate for the loss of water from the
interstitial and intracellular spaces.
 Ketoacids filtered at the glomeruli and excreted through the renal tubules / cotransported
with sodium / sodium holds water in the tubules and decreases tubular reabsorption of
fluid / excrete sodium, water, and ketoacids.

Adapted from Hall JE. Insulin, glucose and diabetes mellitus. In: Guyton and Hall textbook of
medical physiology 12th edition. Philadelphia: Saunders Elsevier; 2011.

Fluid Type
The first order of business is determining which fluid type is best for an animal with
DKA. Because animals with DKA are dehydrated in the interstitial and intracellular
spaces on presentation, giving a crystalloid fluid is indicated because up to 75% of
these fluids naturally shift from the intravascular space into the interstitial and intracel-
lular spaces within 20 to 30 minutes of administration. Therefore, fluid is returned
quickly to the dehydrated spaces. In addition, because hypovolemia in DKA results
from dehydration of the interstitial and intracellular spaces (thus causing loss of fluid
that would normally be used to replenish the intravascular space), hypovolemia will
also be improved by refilling those deficient compartments, allowing for return of fluid
to the vascular space.10
Human (and older veterinary) resources have recommended 0.9% sodium chloride
(NaCl) as the fluid of choice. The reasons for this were largely because this fluid has the
highest sodium concentration and, therefore, can treat the hyponatremia often
observed in DKA patients (see Box 2). However, due to the increased chloride in these
fluids and the lack of a buffer, they have been shown to cause hyperchloremic meta-
bolic acidosis in DKA patients, all of whom already have a high anion gap metabolic
acidosis from the ketone body production.11
Therefore, using a balanced crystalloid with a buffer (such as lactated Ringer solu-
tion or plasmalyte-148) is recommended in veterinary medicine. Plasmalyte-148 was
shown to improve resolution of acidosis within the first 12 hours of infusion versus
0.9% NaCl in adult human patients with DKA.11 Additionally, humans receiving
4 Thomovsky

Box 2
Mechanisms of electrolyte disorders in diabetic ketoacidosis

 Hyponatremia7
 Increased concentration of ketoacids in blood / sodium (Na1) excreted with ketoacids in
kidneys via a cotransporter.
 Hyperglycemia / increased osmolality in blood / fluid shifts from interstitium and
intracellular space into blood / decreases the sodium concentration by dilution of
existing sodium.
- For every 100 mg/dL increase in glucose in blood, there is at least a 1.6 mEq/L decrease in
Na1 concentration.
 Increased renal filtration of glucose / retain Na1 and water in renal tubules (osmotic
diuresis) / Na1 loss in urine.
 Hypokalemia8
 Loss in kidneys
1 1
- Lack of insulin / potassium (K ) remains in blood / K filtered through glomeruli /
K1 lost through renal tubules with excessive water and glucose (osmotic diuresis).
1 1
- Acidosis / hydrogen (H ) ions shift into cells and K moves into bloodstream from cells
/ potassium filtered at kidney / K1 lost through renal tubules with excessive water
and glucose (osmotic diuresis).
 Insulin therapy / movement glucose and potassium into cells / hypokalemia.
 Epinephrine release / shifts glucose and potassium into cells / hypokalemia.
 Hypophosphatemia6,9
 Phosphate (PO4) deficit
- Loss of muscle mass during amino acid breakdown (see Fig. 1B) / less stored PO4 in the
body.
- Loss of phosphorus in the urine
 Decreased insulin concentration / decreased movement PO4 into cells / more PO4
filtered at glomeruli and into renal tubules / loss of PO4 in urine.
 Decreased insulin concentration / decreased reabsorption PO4 in the kidney / loss
of PO4 in urine.
 Fluid therapy / increased renal PO4 excretion (with sodium phosphorus
cotransporter).
 Movement phosphorus into cells
- Insulin therapy during treatment shifts PO4 into cells with glucose /
hypophosphatemia.

plasmalyte-148 do not have increases in their chloride concentrations contributing to

metabolic acidosis.11
Insulin Therapy
The goal of giving insulin to a diabetic patient is to resolve hyperglycemia by storing
circulating serum glucose in the liver as glycogen (increase glycogen synthesis) and
as triacylglycerols in the adipose tissue (increase fatty acid synthesis).1,2 Additionally,
the insulin transports glucose into the cells to be used in glycolysis and the tricarbox-
ylic acid (TCA) cycle (ie, re-establish normal metabolism, Fig. 1A) so that further fat
and protein breakdown for energy and, therefore, ketone body production is not
necessary.2 Because insulin allows for improvement of blood glucose concentration,
and decreased ketonemia and concurrent acidemia, one of the goals of treatment is to
continuously and consistently administer insulin as long as possible to a patient.
There has been much published on various techniques of insulin administration. His-
torically, in both human and veterinary medicine, regular insulin (a short-acting insulin)
is indicated in the acute period.1215 There are multiple ways to administer regular in-
sulin with routes ranging from intravenous to intramuscular, with frequencies reported
 DKA FluidsElectrolytes 5

from continuous to every 1 to 4 hours.12 Veterinarians are urged to use whatever reg-
ular insulin protocol they are most comfortable with.
The goal of any insulin regimen is to maintain serum glucose concentration between
100 to 250 g/dL. Table 1 is a sample treatment chart. The frequency of blood glucose
monitoring depends on the exact insulin protocol initiated. Typically, continuous infu-
sions of insulin have blood glucose monitoring every 1 to 2 hours, whereas intramus-
cular injection protocols call for monitoring of blood glucose every 4 hours. Regardless
of the frequency of glucose monitoring, note that when the animals blood glucose de-
creases, dextrose is added to the crystalloid fluids so as to continue to allow admin-
istration of insulin without causing hypoglycemia.
In recent years, 2 publications have reported using different short-acting human in-
sulin products in dogs with DKA.16,17 One product is called lispro and it was adminis-
tered at a dosage of 2.2 U/kg/d mixed in 0.9% saline and given as a continuous
infusion (see Table 1). In a study of 12 dogs, 6 dogs received lispro insulin and their
ketonemia, hyperglycemia, and acidemia were normalized in a median of 26 hours
(range 2650 hours), whereas 6 dogs received regular insulin and had resolution of
signs in a median of 51 hours (range 5082 hours).16 The second product is called in-
sulin aspart. It was used in 6 dogs and given intravenously continuously at a dosage of
2.2 U/kg/d mixed in 0.9% saline (see Table 1).17 The dogs given insulin aspart had a
median time to resolution of ketonemia, hyperglycemia, and acidemia of 28 hours
(range 20116 hours).17 Therefore, the use of any short-acting insulin product (regular,
lispro, or aspart) continuously intravenously is effective in decreasing the blood sugar
in dogs. Neither lispro nor aspart insulin has been tested in cats.

Fluid Rates and Administration

Guidelines for humans assume that all DKA patients presenting at the hospital have a
5% to 10% dehydration (corresponding to a deficit of 69 L of fluid).13 Recommenda-
tions for humans specify that 50% of this deficit is replaced within 8 to 12 hours, with
the total dehydration deficit given over 24 to 36 hours.13 Veterinary medicine lacks
such specific guidelines and allows for more individualized treatment. The author pre-
sents a potential way to approach fluid therapy.

Step 1. Initial treatment (06 hours postpresentation)

 Examine the patient and estimate dehydration paying attention to whether there
is concern that the animal is hypovolemic (Table 2 shows guidelines on esti-
mating dehydration and calculating the dehydration deficit).

Table 1
A sample protocol for continuous intravenous administration of short-acting insulin (regular
insulin, lispro insulin, or insulin aspart in dogs; or regular insulin in cats)

Measured Blood Glucose (mg/dL) Dextrose in Crystalloid Fluids Insulin Rate (mL/h)a
250 None 10
200250 2.5% dextrose 7
150200 2.5% dextrose 5
100150 5% dextrose 5
<100 5% dextrose No insulin
a
All insulin administered is created in the following way: 250 mL bag of 0.9% saline 1 2.2 U/kg of
short-acting insulin (dogs) or 1.1 U/kg regular insulin only (cats).
Data from Refs.12,16,17
6 Thomovsky

Table 2
Guidelines for estimation of dehydration based on physical examination findings in dogs and
cats

Percent Dehydration Compartment Involved Clinical Signsa

<5% ISF History of anorexia
Decreased or absent drinking
Vomiting, diarrhea
5% ISF Tacky mucous membranes
1/ skin tent
7%8% ISF / IC Skin tent
Dull corneas
10% IC Sunken eyes
Depressed mentation
10%12% IC / IV Tachycardia
Decreased blood pressure
Severe depression
12%15% IV Worsening signs of hypovolemia (die at 15%)

Calculating dehydration deficit: (wt in kg)  (% dehydration) 5 L of fluid.

Abbreviations: IC, intracellular compartment; ISF, interstitial fluid compartment; IV, intravascular
space.
a
Only new findings that occur at that level of dehydration are listed; it is assumed that all pre-
vious findings are still present.

 Administer a portion of this dehydration deficit in the first 2 to 6 hours of treatment

with the timing and amount based on clinical judgment of this particular patients
condition. Use a balanced crystalloid solution such as lactated Ringer solution or
plasmalyte-148.
 An example is to give one-half of the dehydration deficit over 4 hours.
 Factors to take into account include the degree of dehydration (hypovolemic or
severely dehydrated patients need more fluid faster) and comorbidities (ani-
mals with heart disease often require slower more deliberate fluid
administration).
 No insulin is administered during this rehydration period because the goal is to
restore hemodynamic stability (ie, treat hypovolemia if present) and improve
filtration in the kidneys.
 Fluid therapy itself will decrease the initial presenting glucose concentration;
therefore, withholding insulin therapy until the fluid-induced decrease in
glucose concentration in the blood occurs is wise.
 Fluid therapy will potentially cause alterations in the presenting concentrations
of potassium, phosphorus, and sodium. Therefore, specific treatment of the
electrolyte abnormalities noted on initial bloodwork should not be imple-
mented until after this initial fluid therapy period.
Step 2. Correction of remaining dehydration, acidosis, and electrolyte abnormalities
(the first 24 hours of hospitalization)
 After the initial fluid administration (roughly 26 hours after presentation), take a
blood sample to determine the animals electrolytes, blood pH, and blood
glucose concentration.
 Depending on the animals blood glucose concentration, initiate regular insulin
therapy using the veterinarians preferred technique and dosing (see Table 1
of regular and other short-acting insulins).
 DKA FluidsElectrolytes 7

 Determine the remaining amount of fluid required to replace the animals dehy-
dration (ie, subtract what has been given thus far from the initial estimated
amount). Give what remains over the next 12 to 24 hours, depending on the an-
imals comorbidities (ie, animals with heart disease or heart murmurs might
receive fluids at a slower rate than those without).
 Provide maintenance fluids to the animal in addition to the dehydration fluids.
 Consider supplementing dextrose or electrolytes to the animal (see subsequent
sections).

Step 3. Reassess fluid rate, insulin administration, and electrolyte supplementation

(every 612 hours during hospitalization)
 When the calculated dehydration deficit has been completely administered, re-
assess the patient to ensure that the animal no longer seems to be dehydrated
(see Table 2).
 If the animal is still clinically dehydrated, recalculate the dehydration deficit and
administer it over the next 4 to 12 hours.
 If the animal is no longer clinically dehydrated, decrease the crystalloid fluid
rate to maintenance (ie, 60 mL/kg/d) or to an amount that matches the urine
production in severely polyuric animals.
 If the animal has ongoing losses, such as vomiting or diarrhea, estimate that
amount. Administer fluids to replace the ongoing losses in addition to the main-
tenance fluids.
 Recheck blood glucose concentration regularly as dictated by the insulin regime
(usually every 14 hours). Administer insulin as dictated by the blood glucose
concentration (see Table 1).
 At least every 12 hours (often every 46 hours depending on how sick the animal
is), recheck the electrolytes and blood pH. Adjust supplementation as indicated
(see subsequent sections).

Other Considerations When Administering Fluids

It is important to remember that frequent reassessment of patients is important to
ensure that enough but not too much fluid is being given. The author typically does
a physical examination at least every 12 hours on these animals, paying particular
attention to whether or not the physical findings consistent with dehydration have
improved. In the authors experience, it is not uncommon to underestimate the ani-
mals dehydration, especially because many of the clinical findings can be affected
by age or breed, as well as behaviors such as panting or hypersalivating from nausea.
Also, these animals are losing large amounts of fluid in their urine due to osmotic
diuresis, which can lead to continued dehydration despite fluid therapy. Interestingly,
studies of humans using standard levels of dehydration at which every patient re-
ceives the same amount of fluid (without a physical examination or personalized
recommendation) lead to overzealous volumes of fluid administration in up to 2 out
of 3 of patients.18
Using serial body weights is very helpful when determining if the animal is properly
rehydrated. Remember that correction of a 10% dehydration deficit should corre-
spond to an approximately 10% body weight gain (ie, a 10 kg animal becomes an
11 kg animal after fluid therapy). Additionally, properly rehydrated animals should
be urinating frequently. Animals with DKA and osmotic diuresis obviously have poly-
uria and if you do not see frequent urination, the animal is still dehydrated. Urine spe-
cific gravities with glucosuria and osmotic diuresis should not be higher than 1.015.
Higher specific gravities are likely consistent with persistent dehydration.
8 Thomovsky

Human pediatric patients with DKA are at a high risk of developing cerebral edema.
This has led to recommendations in children in which fluid therapy is limited in the
initial 3 to 4 hours and fluid rates in general are more restricted and aimed at giving
fluid with lower amounts of sodium (0.45% saline vs 0.9% saline) over longer periods
of time (48 hours rather than 24 hours) in children.14 However, newer information sug-
gests that cerebral edema is due to reperfusion of ischemic brain tissue and increased
vascular permeability rather than shifting of water into brain cells, making fluid therapy
rarely, if ever, a contributing factor.14 There is nothing in the veterinary literature that
indicates veterinary patients are at a significant risk of developing cerebral edema
when treated for DKA.

Supplementation of Electrolytes and Dextrose

 Sodium7
 There are no concerns about improving sodium concentrations through
administration of sodium.
- Any crystalloid fluid will have enough sodium.

- Older recommendations of 0.9% saline are not absolute requirements.

 As ketone body production decreases, concurrent loss of sodium with ketones

through the kidney will decrease.
 Volume resuscitation alone will decrease hyperglycemia.
- Decreases osmolarity in the blood vessel / decreases movement of water

into the vascular space from the extravascular space / decreases dilution
of sodium.
- Decreases osmolarity in the renal tubule / decreases movement of sodium

and water out of the kidneys / more sodium retained by the kidneys.
 Potassium8
 All DKA patients require potassium supplementation regardless of measured
serum potassium concentration.
- Potassium has been lost through kidneys.

- Potassium has shifted from storage inside cells into the bloodstream sec-

ondary to acidosis and insulin therapy.

 Falsely increases serum potassium concentration.
 Total body potassium concentrations are decreased as intracellular
stored potassium shifts out of cells.
 If serum potassium concentrations are in the normal range (generally 3.55.5
mEq/L)
- Add 20 mEq/L of potassium chloride (KCl) to crystalloid fluids or infuse

approximately 0.1 mEq/kg/h to patient.

 If serum potassium concentrations are low, use Sliding Scale of Scott (Table 3)
or administer 0.1 to 0.5 mEq/kg/h KCl (with rate depending on sequentially
measured serum potassium concentrations).
- Be careful exceeding 0.5 mEq/kg/h of potassium supplementation.

- Hyperkalemia can cause cardiac arrhythmias, including atrial standstill and

asystole.
- Be sure to thoroughly mix all supplemental potassium in crystalloid fluid bags

to prevent excessively high concentrations (potentially life-threatening) of po-

tassium in the initial milliliters of fluids administered from un-mixed bags.19
 Phosphorus9
 Typically, even normal serum phosphorus concentrations are expected to
decrease when insulin therapy initiated.
- Insulin moves phosphate (PO4) into the cells.
 DKA FluidsElectrolytes 9

Table 3
Sliding Scale of Scott for potassium supplementation

Measured Serum mEq KCl Added to Maximum Daily Fluid

Potassium Concentration (mEq/L) 1 L Crystalloid Fluid Rate (mL/Kg/d)a
<2.0 80 144
2.12.5 60 192
2.63.0 40 288
3.13.5 28 432
3.65.0 20 600
a
If crystalloid fluid rate exceeds the listed rate, decrease the mEq KCl added to the 1 L bag so as to
not exceed 0.5 mEq/kg/h of potassium administration.
Data from DiBartola SP, De Morais HA. Disorders of potassium: hyperkalemia and hypokalemia.
In: DiBartola SP, editor. Fluid, electrolyte and acid base disorders in small animal practice, 4th edi-
tion. St Louis (MO): Elsevier Saunders; 2012. p. 92119.

-It is important to serially evaluate serum PO4 concentration during the

course of treatment.
- The author suggests obtaining baseline serum phosphorus concentrations

and then checking serum phosphorus between 6 to 12 hours after initiating in-
sulin therapy, even if the serum phosphorus concentration was initially normal.
 Hypophosphatemia requiring treatment is usually considered to be lower than
1.5 mg/dL.
- Supplement phosphorus (potassium phosphate [KPO4] solution)
intravenously.
- Administer 0.01 to 0.06 mmol/kg/h diluted in 0.9% saline.

- Be aware that KPO4 will also supply potassium to the animal. Decrease KCl

administered so as to limit the amount of potassium given to the animal.

 Determine potassium supplementation using the Sliding Scale of Scott
(see Table 3).
 Give one-half of the potassium requirement as KCl and one-half as
KPO4.
 Typically, this will be an adequate amount of PO4 for the animal while
giving appropriate amounts of potassium.
 Alternatively, determine potassium supplementation by calculation
(0.10.5 mEq/kg/h).
 Give one-half of the potassium requirement as KCl and one-half as
KPO4.
 Typically, this will be an adequate amount of PO4 for the animal while
giving appropriate amounts of potassium.
 Dextrose
 Most DKA patients require dextrose supplementation at some point in their
treatment.
- Most dogs and cats do not eat food during the initial stages of treatment due

to nausea resulting from acidosis or other underlying diseases such as

pancreatitis.
- Administration of insulin will decrease serum glucose concentration, espe-

cially in anorexic patients.

 Insulin helps to move ketones as well as glucose into the cells.
- Glucose is converted into glycogen that can then be broken down via glycol-

ysis to yield acetyl coenzyme A (A-CoA) (see Fig. 1A).

10 Thomovsky

Fig. 1. Normal cellular energy usage versus cellular energy production in diabetes mellitus/
DKA.24 (A) In the normal setting glucose enters cells under the influence of insulin and is
converted to A-CoA via glycolysis. The A-CoA is then incorporated into the citric acid (TCA)
 DKA FluidsElectrolytes 11

Box 3
Mechanism of bicarbonate to resolve metabolic acidosis while potentially leading to other
complications
HCO3- 1 H1 4 H2CO3 4 H2O 1 CO2
HCO3- 5 bicarbonate. H1 5 hydrogen ion. H2CO3 5 carbonic acid. H2O 5 water. CO2 5 carbon
dioxide.
 The administration of HCO3- will bind to H1 and reduce acidemia.
 However, giving extra bicarbonate will lead to increased production of CO2 (the equation
shifts to the right).
 If the patient is unable to increase respiratory rate and effort to remove the excess CO2,
carbon dioxide will accumulate in the blood.
 Examples of patients who cannot compensate to remove CO2 via the respiratory system
include those with severe hypokalemia with concurrent respiratory muscle weakness,
recumbent animals, or those with concurrent respiratory diseases.
 Excess CO2 diffuses into the central nervous system (CNS) more readily than HCO3- / CNS
acidosis (paradoxic CNS acidosis)
 Excess CO2 can cause the equation to shift back to the left, increasing serum
H1 concentration and further decreasing blood pH (respiratory acidosis).
 Excess HCO3- created when the equation shifts back to the left must be removed by the
kidneys (a problem when there is concurrent renal disease) / can lead to metabolic
alkalosis.

Adapted from DiBartola SP. Metabolic acid-base disorders. In: DiBartola SP, editor. Fluid, elec-
trolyte and acid base disorders in small animal practice, 4th edition. St Louis (MO): Elsevier Sa-
unders; 2012.

- Ketones are removed from the blood and shifted into cells / more rapidly
resolves the acidosis.
 A goal of treatment is to be able to administer as much insulin to a DKA patient
as possible during the animals hospitalization.
 Many animals will receive concurrent insulin and dextrose supplementation as
indicated in Table 1 to avoid hypoglycemia while receiving insulin therapy.
 Bicarbonate
 This is given to improve blood pH. Box 3 lists its effects.

=
cycle. The resulting electrons liberated in the TCA cycle are transported to the electron
transport chain in the mitochondrion where they fuel oxidative phosphorylation and
make adenosine triphosphate (ATP). (B) In the diabetic patient, the lack of insulin limits
the amount of glucose that is transported into the cell from the bloodstream, causing the
body to make use of primarily fatty acids and secondarily amino acids from protein break-
down to provide the A-CoA needed for the TCA cycle and eventual production of ATP. This
beta-oxidation of fatty acids primarily takes place in the liver using coenzyme A. As the dia-
betic continues to break down fat to make A-CoA, the rate of this conversion is limited by
the amount of coenzyme A in the liver, eventually leading to a maximal rate of fatty acid
breakdown. In addition, the TCA cycle becomes saturated with A-CoA and cannot operate
faster despite being faced with increased amounts of A-CoA. One of the intermediates in
the TCA cycle (oxaloacetate) is also converted back to glucose in an attempt to provide
cellular energy, further limiting the ability of the TCA cycle to take up and convert
A-CoA. Thus, there is an excess of A-CoA. It is this excess of A-CoA that the body uses to
form ketone bodies. Conversion to ketone bodies liberates coenzyme A to continue fatty
acid breakdown in the liver. Ketone bodies can be used in the heart, skeletal muscle, kidney,
and brain to provide energy or can be excreted through the kidney.
12 Thomovsky

 Bicarbonate is not recommended in humans for blood pH greater than 7.013,20

and veterinarians have followed this recommendation.12,15
- There is no evidence that even human patients with severe acidosis (blood

pH <6.9) had improved time to resolution of acidosis or time to hospital

discharge or time to hospital discharge when given bicarbonate.20
- There is a concern for reflex respiratory acidosis in patients treated with bi-

carbonate (see Box 3).

 Decrease in ketones via renal excretion (administration of intravenous fluids)
and insulin therapy will improve acidosis, negating the need for bicarbonate
therapy in most patients.
 In the authors experience, unless the kidneys are unable to reabsorb bicar-
bonate on their own to resolve the acidosis and waste the ketoacids, therapy
with exogenous bicarbonate is not needed.

SUMMARY

Treatment of DKA is relatively straightforward in its approach. The difficulty comes in

fine-tuning the basic treatment protocol to each animal. However, if veterinarians
remember to use crystalloid fluids in addition to insulin therapy, with frequent rechecks
of blood glucose, electrolytes, and blood pH, resolution of the hyperglycemia and
other abnormalities is almost always successful.

REFERENCES

1. Hall JE. Insulin, glucose and diabetes mellitus. In: Guyton and Hall textbook of med-
ical physiology 12th edition. Philadelphia: Saunders Elsevier; 2011. p. 93954.
2. Nelson DL, Cox MM. Hormonal regulation and integration of mammalian meta-
bolism. In: Lehninger principles of biochemistry 6th edition. New York: Freeman,
WH & Company; 2012. p. 92975.
3. Nelson DL, Cox MM. The citric acid cycle. In: Lehninger principles of biochem-
istry 6th edition. New York: Freeman, WH & Company; 2012. p. 63365.
4. Nelson DL, Cox MM. Fatty acid catabolism. In: Lehninger principles of biochem-
istry 6th edition. New York: Freeman, WH & Company; 2012. p. 66793.
5. Hall JE. Lipid metabolism. In: Guyton and Hall textbook of medical physiology
12th edition. Philadelphia: Saunders Elsevier; 2011. p. 81930.
6. Eaton DC, Pooler JP. Regulation of calcium, magnesium and phosphate. In: Van-
ders renal physiology 8th edition. New York: McGraw-Hill Education; 2013.
p. 17286.
7. DiBartola SP. Disorders of sodium and water: hypernatremia and hyponatremia.
In: DiBartola SP, editor. Fluid, electrolyte and acid base disorders in small animal
practice. 4th edition. St Louis (MO): Elsevier Saunders; 2012. p. 4579.
8. DiBartola SP, De Morais HA. Disorders of potassium: hyperkalemia and hypoka-
lemia. In: DiBartola SP, editor. Fluid, electrolyte and acid base disorders in small
animal practice. 4th edition. St Louis (MO): Elsevier Saunders; 2012. p. 92119.
9. DiBartola SP, Willard MD. Disorders of phosphorus: hyperphosphatemia and hy-
pophosphatemia. In: DiBartola SP, editor. Fluid, electrolyte and acid base disor-
ders in small animal practice. 4th edition. St Louis (MO): Elsevier Saunders; 2012.
p. 195211.
10. Wellman ML, DiBartola SP, Kohn CW. Applied physiology of body fluids. In:
DiBartola SP, editor. Fluid, electrolyte and acid base disorders in small animal
practice. 4th edition. St Louis (MO): Elsevier Saunders; 2012. p. 225.
 DKA FluidsElectrolytes 13

11. Chua H, Venkatesh B, Stachowski E, et al. Plasma-Lyte 148 vs 0.9% saline for
fluid resuscitation in diabetic ketoacidosis. J Crit Care 2012;27:13845.
12. Kerl ME. Diabetic ketoacidosis: treatment recommendations. Compend Contin
Educ Vet 2001;23:33040.
13. Gosmanov AR, Gosmanova EO, Dillard-Cannon E. Management of adult diabetic
ketoacidosis. Diabetes Metab Syndr Obes 2014;7:25564.
14. Watts W, Edge JA. How can cerebral edema during treatment of diabetic ketoa-
cidosis be avoided? Pediatr Diabetes 2014;15:2716.
15. Boysen SR. Fluid and electrolyte therapy in endocrine disorders: diabetes melli-
tus and hypoadrenocorticism. Vet Clin North Am Small Anim Pract 2008;38:
699717.
16. Sears KW, Drobatz KJ, Hess RS. Use of lispro insulin for treatment of diabetic ke-
toacidosis in dogs. J Vet Emerg Crit Care 2012;22:2118.
17. Walsh ES, Drobatz KJ, Hess RS. Use of intravenous insulin aspart for treatment of
naturally occurring diabetic ketoacidosis in dogs. J Vet Emerg Crit Care 2016;26:
1017.
18. Fagan MJ, Avner J, Khine H. Initial fluid resuscitation for patients with diabetic ke-
toacidosis: how dry are they? Clin Pediatr 2008;47:8515.
19. Hoehne SN, Hopper K, Epstein SE. Accuracy of potassium supplementation of
fluids administered intravenously. J Vet Intern Med 2015;24:8349.
20. Duhon B, Attridge RL, Franco-Martinez AC, et al. Intravenous sodium bicarbon-
ate therapy in severely acidotic diabetic ketoacidosis. Ann Pharmacother 2013;
47:9705.