The Case: DKA or not DKA? That Is the Question

Presentation

Fluffy, an 8-year-old spayed toy poodle, was presented for vomiting and anorexia. The owner had been out of town for a week, returning 2 days prior to presentation. The pet sitter reported to the owners that the dog had not been eating for the last 3 days and was hiding under the bed. Fluffy had been vomiting since the owner returned home and would not eat her regular food (a home-prepared raw diet).  She would eat offered “human food” but then would vomit the food back up. The owner also reported Fluffy had a decreased appetite over the last month or two. Patient has a history of marked periodontal disease, with multiple extractions about a year ago, but no other chronic illnesses. Fluffy shares the house with 2 other dogs.  All are indoor dogs but occasionally go to dog parks. 

Physical Examination: The dog is quiet, alert, and responsive but weak and stumbles when walking. She has mild bilateral seromucoid ocular discharge and severe dental calculus and gingivitis.

• Weight/body condition score: 1.43 kg/3 of 9 

• Temperature: 100.5⁰F (38.1⁰C)

• Pulse: 140 bpm; fair, synchronous 

• Respiratory rate: 60 bpm

• Mucous membranes: pink, tacky

• Capillary refill time:  <2 sec

• Hydration:  ~8% dehydrated

• Tense on cranial abdominal palpation; very small urinary bladder

Management

DAY 1

The patient was hospitalized for observation. 

6 pm

• Blood glucose (BG): 375 mg/dL (range, 70-138) (20.8 mmol/L [range, 3.9-7.7])

• Potassium: 3.5 mEq/L (range, 3.6-5.5) (3.5 mmol/L [range, 3.6-5.5])

• Lactate: 3.3 mmol/L (range, 0.6-2.9)

• Packed cell volume: 48% (range, 34%-55%)

• Total protein: 7.8 g/dL (78 g/L) (range, 5.0-7.4)

• Plasmalyte* IV fluid (30 mL bolus). After the bolus, administered at a rate of 15 mL/hr for 6 hours, then 8 mL/hr with the following added: potassium chloride (20 mEq),  potassium phosphate (20 mEq), and dextrose 5% (50%, 100 mL/L)

• Maropitant: 1 mg/kg IV q24h

• Famotidine: 0.7 mg/kg IV q12h

• Buprenorphine: 0.02 mg/kg (20 μg/kg) IV q12h

• Fed 1-2 tbsp boiled chicken every 3 hours. Appetite was excellent each time food was offered.

8 pm

• Serum ketones (Ketostix): moderate amount present

• Blood glucose: 299 mg/dL (range, 70-138) (16.6 mmol/L [range, 3.9-7.7])

• Insulin: Administered ½ U regular insulin IM after 8 pm BG reading. 

Tentative diagnosis: diabetic ketoacidosis 

11 pm

• Blood glucose: 113 mg/dL (range, 70-138) (6.3 mmol/L [range, 3.9-7.7])

• Complete blood count: within normal limits

• Serum chemistry:  

• Amylase: 294 IU/L (range, 29-1125)

• Calcium:  7.2 mg/dL (range, 8.9-11.4) (1.8 mmol/L [range, 2.23-2.85])

• Creatinine: 0.4 mg/dL (range, 0.5-1.6) (35.4 μmol/L [range, 44.2-141.4])

• Glucose:  216 mg/dL (range, 70-135) (12.0 mmol/L [range 3.9-7.5])

• Phosphorus (PO₄):  2.3 mg/dL (range, 2.5-6.0) (0.74 mmol/L [range, 0.81-1.94])

• Total bilirubin: 1.0 mg/dL (range, 0.1-0.3) (17.1 μmol/L [range, 1.7-5.1])

• Gamma glutamyl tranferase: 12 IU/L (range, 1-12)

DAY 2

Blood glucose (range, 70-138 mg/dL [3.9-7.7 mmol/L])

12 am: 36 mg/dL (2.0 mmol/L)

1 am: 656 mg/dL (36.4 mmol/L)

Regular insulin ½ U IM was administered

4 am: 396 mg/dL (22.0 mmol/L)

Urine ketones: negative

7 am: 106 mg/dL (5.9 mmol/L)

8 am: 67 mg/dL (3.7 mmol/L)

10 am: 151 mg/dL (8.4 mmol/L)

Urine ketones: negative

12 pm: 148 mg/dL (8.2 mmol/L)

3 pm: 130 mg/dL (7.2 mmol/L)

8 pm: 126 mg/dL (7.0 mmol/L)

Urine ketones: negative

10 pm: 125 mg/dL (6.9 mmol/L)

8:45 pm

• Sodium: 151 mEq/L (range, 139-154) (151 mmol/L [range 139-154])

• Potassium:  4.0 mEq/L (range, 3.6-5.5) (4.0 mmol/L [range, 3.6-5.5])

• Phosphorus (PO₄): 3.5 mg/dL (range, 2.5-6.0) (1.13 mmol/L [range, 0.81-1.94])

• Urine ketones: negative

Discontinued dextrose in IV fluids at 10 pm.

DAY 3

Blood glucose (range, 70-138 mg/dL [3.9-7.7 mmol/L])

12 am: 126 mg/dL (7.0 mmol/L)3 am: 107 mg/dL (5.9 mmol/L)6 am: 126 mg/dL (7.0 mmol/L)9 am: 114 mg/dL (6.3 mmol/L)

Outcome: Fluffy was discharged at 10 am. She received only 2 doses of insulin during hospitalization because blood sugar levels normalized after the second insulin injection and remained stable. The veterinarian recommended abdominal ultrasonography to investigate the cause of vomiting, but further diagnostic testing was declined by the owner due to financial concerns. It was suspected that the ketonuria was due to a combination of anorexia, vomiting, and stress.  Owner decided to take Fluffy home. Patient was discharged with maropitant 4 mg (¼ of 16-mg tablet) PO q24h and famotidine 2.5 mg (¼ of 10-mg tablet) PO q12h.

*A multiple electrolyte solution

The Generalist’s Opinion

Barak Benaryeh, DVM, DABVP

The looming question here is whether this dog had diabetic ketoacidosis. Ketones were found in the serum and the dog was symptomatic, so instituting treatment was appropriate and clearly effective. This case is interesting from a diagnostic as well as a treatment perspective.

Diagnosing Diabetic Ketoacidosis (DKA)

Most patients presenting with DKA have a history leading up to the event of weight loss, polyuria, and polydipsia. The diagnosis of DKA includes a high blood glucose, glucosuria, and ketones in urine or serum. Other diagnostic criteria may be present and strengthen the index of suspicion. These include electrolyte abnormalities, non-regenerative anemia, azotemia, and elevated hepatic enzymes. While the patient had clinical signs of gastroenteritis, elevated blood glucose, and was positive for serum ketones, there was no history of weight loss or changes in water consumption. Urine was not analyzed until day 2, when it is mentioned that urine ketones were negative. Ideally urine would have been obtained as soon as possible, checked for presence of glucose and ketones, complete urinalysis performed, and submitted for a culture. Without these diagnostic aids, we are missing information.

Treatment of DKA

The clinicians did a good job of managing this patient, choosing an intramuscular (IM) as opposed to an intravenous insulin protocol by constant rate infusion (CRI). Some studies have compared IM to CRI infusion of insulin.¹ Both methods are considered appropriate. Clinician preference and comfort levels vary as to which should be used. This patient clearly improved and had an excellent outcome.

What Happened and Why?

The patient was consuming a raw diet as well as table food. If the dog was ingesting an excessive amount of protein, there may not have been enough carbohydrates to trigger insulin secretion. Insulin blocks lipolysis; in the absence of insulin the body breaks down fats into ketone bodies for energy. To my knowledge, there is no description in the veterinary literature of ketosis in a dog secondary to a high protein diet. The problem has been documented in humans and is a concern for people on the Atkins diet. There are numerous reports of people hospitalized due to ketosis from excessive protein consumption.^2,3 Dogs’ metabolism differs significantly, however, as evidenced by the fact that they can go without food for long periods and not produce ketone bodies, which is a reason that veterinarians do not encounter ketosis from high protein diets. In the absence of an early urinalysis, we cannot know if glucose or ketones were present in the urine, information that would have helped determine whether ketosis was the primary problem causing the gastroenteritis or if this dog had a separate reason for GI disease and was secondarily ketotic.

Raw and High-Protein Diets

There is significant controversy over raw diets. Studies have shown them to present potential for zoonotic disease as well as occasionally being deficient in nutrients.^4,5 Nevertheless, they are gaining in popularity. This case is a good cautionary tale to discuss with any clients feeding homemade or raw diets. The patient recovered too quickly to have been truly diabetic. We cannot know the root cause of this dog’s disease but the presence of ketone bodies was likely exacerbated, if not caused, by the diet. A recommendation for a more traditional diet would have been a good idea.

The Specialist’s Opinion

Katharine F. Lunn, BVMS, MS, PhD, MRCVS, DACVIM

There are really 3 questions to be answered in this case. Is this dog diabetic? Was this dog ketotic? Was this dog ketoacidotic?

Is This Dog Diabetic?

The answer is “probably.” Fluffy was markedly hyperglycemic on presentation. Stress hyperglycemia to this extent is unusual in dogs. Transient diabetes mellitus (DM) is uncommon in dogs, although it can be seen in association with certain medications, such as glucocorticoids or progestogens, and it can also occur in intact females in diestrus. This patient is spayed and no drug history was provided. This author has also seen pancreatitis associated with transient DM in dogs. Pancreatitis would explain the vomiting, the tense cranial abdomen, the increased bilirubin, and the hypocalcemia. The normal amylase is not sufficient to rule out pancreatitis.

Other evidence in support of DM in this case is the low body condition score. However, the progression of any weight loss is unknown and no past weight data were provided. There was also no information provided regarding any history of polyuria/polydipsia, as would be expected in DM. Serum fructosamine taken at the time of initial presentation would have been useful and could have helped determine whether or not hyperglycemia had been present over the previous 2 to 3 weeks.

Was This Dog Ketotic?

The answer is “yes.” Using a urine dipstick to detect ketones in the serum is a valid test,¹ particularly if a urine sample cannot be obtained in a dehydrated patient. Moderate ketones were present and therefore the patient was ketotic. DM and starvation are the most common causes. Ketosis would not be expected after a short period of anorexia and is not typically associated with vomiting or stress. DM (even if transient) is the most likely cause in this case.

Was This Dog Ketoacidotic?

The answer is “we don’t know.” A blood gas analysis (venous would be sufficient) is necessary to answer this question. It is quite possible to be ketotic and not acidotic, but the diagnosis of acidemia requires measurement of blood pH.

Patient Management

The patient was appropriately managed for the metabolic derangements that were detected. Fluid therapy was provided with a fluid that has mild alkalinizing effects. The hyperglycemia was corrected by administration of conservative doses of intramuscular (IM) regular insulin, and blood glucose (BG) was monitored frequently. Intermittent IM insulin is an accepted method for management of suspected or proven DKA. Supplementation of fluids with potassium is appropriate in the face of mild hypokalemia, and particularly when insulin is being administered to correct suspected DKA. It is also common to give the potassium as 50% potassium chloride and 50% potassium phosphate, as hypophosphatemia can result from initiation of insulin therapy. The addition of dextrose to the fluids is sometimes delayed until BG has fallen further, but, in this case, it appeared to prevent the BG from falling too rapidly. The combination of insulin therapy and dextrose administration likely allowed the ketosis to resolve. However, it should be remembered that dipsticks cannot detect beta-hydroxybutyrate. Therefore the negative ketones on the dipstick could potentially be a false negative.

Additional diagnostic tests that could have been considered include a full urinalysis and urine culture, as dogs with DM are predisposed to urinary tract infections. Further investigation of the hypocalcemia through measurement of ionized calcium would also be useful. The recommendation of abdominal ultrasound examination was appropriate, but was declined due to financial concerns. This is not unreasonable as the client may need to conserve finances for possible future management of pancreatitis and/or diabetes.

Patient Discharge

As noted above, transient diabetes is rare in dogs. A good plan for this patient would have been to send the owner home with dipsticks for detection of glucose +/- ketones in the urine. Detection of glucosuria would indicate that this patient needs to return to the veterinarian to further confirm the diagnosis of DM. In addition, dietary advice should be provided, specifically recommending against feeding raw food. A prescription diet formulated for management of pancreatitis would be a reasonable initial choice in this case.

Conclusion

Patient therapy and monitoring during hospitalization were effective in resolving the metabolic abnormalities in this dog. The question of whether or not the dog has DM is unresolved, and simple at-home monitoring could shed further light on this.