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Diabetic Ketoacidosis A Practical Approach to Management
Kristin Welch, DVM, DACVECC
© DVM STAT 24/7 2019

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History
- DM is often a NEW diagnosis
- 50-60% of cats and 65% of dogs
- PU/PD, PP
- Weight loss
- Lethargy
- Inappetence, anorexia
- Vomiting

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Clinical Signs
- Dehydration
- Lethargy
- Depression
- Dull mentation
- Cataracts
- Cranial abdominal organomegaly
- Abdominal pain
- Tachypnea

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Don't Forget About Comorbidities!
- 70% of dogs and 90% of cats have concurrent disease(s)
Cats
Pancreatitis UTI UTI IBD Exogenous steroids CKD Exogenous steroids Acromegaly
Dogs
Pancreatitis

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An Important Clinical Distinction...
Healthy DKA
- Chronic DM signs
- Small to trace ketones
- No V
- Anorexia
Sick DKA
- Altered mentation
- Severe dehydration
- Vomiting

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On Presentation
- IVC placement
- Collect minimum of BG, lytes, PCV/TS, Chemistry
- Ideally CBC, venous blood gas as well
- Urine if able for UA and culture (+ ketones)
- Start IVF resuscitation
- Active warming to 99 F
- Baseline ECG
- Baseline BP

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Minimum Data Base Expected Diagnostic
Findings Chemistry Hyperglycemia
increased LES Hypercholesterolemia, Hyperlipidemia increased Amylase, lipase Azotemia Hypophosphatemia (or normal Phos)
Serum or Urine Ketones Urine ketones may be negative
early
Electrolytes Hyponatremia
Normal to increased potassium

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Minimum Data Base Expected Diagnostic
Findings
CBC Stress leukogram,
Hemoconcentration
UAUrine culture
Glucosuria (threshold 180- 225 mg/dL) Ketonuria Most UTIs are SILENT
Venous blood gas Metabolic acidosis
BE < -4
decreased HCO3

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Important Biochemical Abnormalities
- Hyperglycemia
- Ketonemia/uria
- Metabolic acidosis
- High anion gap
- AG = (Na+ + K+) - (Cl- + HCO3-)
- Hyponatremia
- Hypokalemia
- Hyperosmolarity
- Osm = [2 x Na+]+[BUN/2.8]+[glucose/18]

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Important Calculations
- Corrected Na+
- Corrected sodium = Measured sodium + [1.6 (glucose - 100) / 100]
- Anion gap
- AG = (Na+ + K+) - (Cl- + HCO3-)
- Osmolarity
- Osm = [2 x Na+]+[BUN/2.8]+[glucose/18]

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Acid-Base Status
- Severe metabolic acidosis is common
- Ketones
- Lactic acidosis from hypovolemia
- **Importance of the venous blood gas
- Treatment
- Fluids, fluids, fluids
- Dilution and correction of lactic acidosis
- Sodium bicarbonate uncommonly
- Only if pH < 7.1
- Insulin therapy ONLY once rehydrated

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Potassium on Presentation
- Severe total body [K+] depletion
- Osmotic diuresis
- GI loss with vomiting, diarrhea
- Decreased intake
- Serum [K+] on presentation is NOT representative
- Acidosis triggers K+ shifts from intracellular to intravascular
- H+ moves intracellular and K+ moves extracellular

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Effect of Treatment on potassium
- Hypokalemia worsens once insulin is started
- Insulin
- Potassium is co-transported with glucose intracellularly
- Resolution of metabolic acidosis
- H+ moves from intracellular to extracellular and K+ moves intracellularly

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Phosphorus is Often Forgotten
- Hypophosphatemia is very common in DKA
- Osmotic diuresis
- Decreased intake
- Decreased renal tubular absorption from metabolic acidosis
- Extracellular shifts in acidosis may ""mask"" true hypophosphatemia early in DKA
- 40% of cats on presentation, increased # develop during treatment

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Sodium is Always Important
- Severe hypo and hypernatremia can cause significant neurologic complications
- Cerebral edema
- Osmotic demyelination
- Hyponatremia is most common with severe hyperglycemia Corrected sodium = measured sodium + [1.6 (glucose - 100) / 100]
- Hypernatremia occurs secondary to free water loss from osmotic diuresis

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Magnesium - The Forgotten One
- Hypomagnesemia
- Osmotic diuresis
- Decreased intake
- Mg is essential for ATPase activity
- Muscle weakness
- Arrhythmias
- CNS depression
- Seizures

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Urine vs. Serum Ketones
- Ketone strips detect acetone and acetoacetate
- Serum ketones are earlier than urine ketones
- Heparinized plasma or urine can be used (JVECC 2013)
- If serum ketones is negative (false-neg??)
- Add 2-3 drop H2O2 to urine or serum and assess a new ketone strip
- H2O2 converts beta-hydroxybutyrate to acetoacetate and acetone

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DKA Treatment Goals
- Reduce BG
- Correct fluid deficits
- Correct electrolyte abnormalities
- Determine the precipitating cause of DKA and treat it!
- Don't forget about the whole patient assessment
- CXR, AUS, urine culture

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Fluid Therapy in DKA
- Maintenance 60-66 ml/kg/d
- Dehydration deficit - % dehydration x kg = ml
- Replace deficit over 6-12 hours
- If hyperosmolar, replace over 12-24 hours
- Calculate for ongoing losses
- ** Don't forget K+ supplementation
- IV fluid therapy for a minimum of 2-8 hours prior to starting insulin
- I wait 6 hours unless hyperosmolar (12 hours)

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Potassium Supplementation is Critical
- Early KCl supplementation
- Remember Kmax = 0.5 mEq/kg/hr
- Calculate rate of K+ mEq/ml/hr for each patient to ensure you are less than Kmax
- If KCl is Kmax or greater, monitor with ECG and recheck lytes every 2 hours

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Potassium Supplementation
Initial Serum [K+] mEq KCl to add to 1 L
fluids <2.5 CRI @ 0.3 mEq/kg/hr for 4
hours and recheck K+ < 3.0 60-80 mEq/L 3.1-4.0 40-60 mEq/L 4.1-5.5 20-40 mEq/L > 5.5 Wait 2 hrs and recheck K+

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Don't Forget to Supplement Phosphorus
- Severe hypophosphatemia leads to hemolysis
- < 1.5 mg/dl or 0.48 mmol/L
- Potassium Phosphate (KPhos)
- Per ml = 4.4 mEq K+ and 3 mMol Phos
Initial Serum (Phos] mg/dL mMol/kg/hr < 3.0 - 0.03 mMol/kg/hr
- Add 50% of the K supplementation using KPhos (Per ml = 4.4 mEq K+and 3 mMol Phos)
< 2.0 0.1 mMol/kg/hr

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Magnesium Supplementation
- Treat if < 1.5 mg/dL (0.62 mmol/L)
- Magnesium Sulfate
Initial Serum (Mg] mg/dL MgSO4 mEq/kg/day CRI < 1.5 0.5-1.0

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Insulun is Not a Priority in DKA Treatment
- Patient must be cardiovascularly stable, normokalemic and nearly rehydrated
- Humulin R
- IM protocol:
- 0.2 U/kg SQ then 0.1 U/kg every hour until BG is = 300 mg/dL
- 0.1-0.2 U/kg IM q 4-6 hours (or SQ q6-8 hours)
- Insulin CRI

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Insulun CRI
- In 250 ml saline
- 1.1 U/kg in cats or 2.2 U/kg in dogs
- If severe cardiac disease, can increase concentration of insulin and decrease Insulin CRI rates by 50%
- Goal is to reduce glucose by < 50-100 mg/dL/hr
BG (mg/dL) % Dextrose in IV fluid Insulin CRI rate (ml/hr) >250 None 10 200-250 None 7 150-199 2.5% 5 100-149 5% 5 (or 3) <100 5% 0
- Allow 1st 50 ml to be discarded through the IV set

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Insulun CRI
BG (mg/dL) % Dextrose in
CRI IV fluid
rate (ml/hr) >250 None 10 200-250 None 7 150-199 2.5% 5 100-149 5% 5 (or 3) <100 5% 0

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Insulun CRI - LOW VOLUME
- In 250 ml saline
- 2.2 U/kg in cats or 4.4 U/kg in dogs
BG (mg/dL) % Dextrose in IV fluid Insulin CRI rate (ml/hr)
>250 None 5
200-250 None 3
150-199 2.5% 3
100-149 - Allow 1st 50 ml 5% to be discarded through 2
the IV set <100 5% 0

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Frequent Monitoring is Needed
- Electrolytes
- Every 2-4 hours in ALL DKA patients until stabilized and fluid resuscitated
- Every 4-6 hours after insulin is started
- Phosphorus
- Every 4 hours until stabilized then q12-24 depending on supplementation
- BG
- Every 2-4 hours throughout hospitalization
- Ketones once a day

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Nutritional Support
- Start enteral nutrition ASAP
- Offer tempting choices
- Syringe feeding
- Appetite stimulants
- Mirtazapine (PO or transdermal)
- Cyproheptadine
- Entyce (capromorelin)
- Feeding tubes
- Cats especially (hepatic lipidosis)
- Parenteral nutrition rarely
- PPN such as Procalamine
- Avoid TPN due to glucose load

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Ancillary Medical Therapy - 4A's
- Antiemetics
- Antacids
- Analgesics
- Reserved for patients with pancreatitis, pyelonephritis
- Antibiotics
- Only if documented UTI or other infection
- Ideally, submit culture first
- UTI requires 4 week culture directed course due to diabetes ('complicated UTI')

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Long Acting Insulun
- Once stabilized and eating meals BID
- Discontinue insulin CRI ~ 1 hr before insulin administration
- Consider dose reducing insulin if patient eats less than 75% of the offered meal
- 50-75% of intended dose
- Monitor BGs q2-4 for at least 12 hours prior to intended discharge
- At minimum until 1 value past the nadir

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Insulun Options for Cats
- Vetsulin (U-40)
- Starting dose 0.25-0.5 U/kg SQ BID
- Glargine (U-100)
- Starting dose 0.25 U/kg SQ BID
- ProZinc (U-40)
- Starting dose 0.1-0.3 U/kg SQ BID
- Humulin N (U-100)
- Starting dose 0.25-0.5 U/kg SQ BID
- Novalin N

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Insulun Options for Dogs
- Vetsulin (U-40)
- Starting dose 0.25-0.5 U/kg SQ BID
- Humulin N (U-100)
- Starting dose 0.5 U/kg SQ BID
- Novalin N --> not interchangeable
- Levemir (U-100)
- Starting dose 0.1-0.2 U/kg SQ BID

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Glucose Goals Prior to Discharge
- Adequate glucose control to minimize chance of hypoglycemia (<100 mg/dL) and significant hyperglycemia (>300 mg/dL)
- Initial glycemic control will not be ideal
- Adjustments can be made in 5-7 days after discharge after a 12-hour glucose curve to obtain more ideal glucose control

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When to Discharge
- Eating 2 meals per day
- No longer vomiting
- Normalized electrolytes
- Started on long acting insulin for at least 12 hours in hospital to ensure 'safe' starting dose
- Serum/urine ketones 1+ or less
- Duration of hospitalization
- I always tell owners 4-6 days

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Prognosis
- ~70% survive to discharge
- Ketone resolution 23-55 hours after starting insulin
- Median hospitalization 5-6 days
- Quality of life after discharge is excellent
- Owner has to be ready to give BID insulin FOR LIFE
- Much less common for remission in feline DM unless history of exogenous steroids, severe pancreatic disease etc.

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Long Term Monitoring
- Glucose curves
- 5-7 days after discharge
- 5-7 days after every dose change
- Every 3 months long term
- Urine cultures
- Recommended every 6 months for 'silent UTI' screening
- UA not an acceptable substitute
- CBC/Chemistry annually

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At Home vs. In Hospital Glucose Curves
- Clinician dependent recommendations
- I am a fan of at home glucose curves
- Less patient stress
- Increased owner compliance with frequency of curves
- Worth the initial financial investment
- Owner compliance is essential
- No dose adjustments without DVM recommendation
- Avoid dose adjustments based on spot check BG
- If history of poor compliance then likely not a good candidate for at home monitoring

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Continuous Glucose Monitoring
- 'Flash' Interstitial continuous glucose monitoring
- Evaluated in diabetic dogs on insulin (JVIM 2016)
- Glucose varied from 2.3-46.8 mg/dL from reference measurement
- 93% accurate at low BG, 99% accurate at normal and high BG measurements
- When compared to glucometer, BGs were 2-45 mg/dL less on the ICGM than glucometer - good for trends
- Low interstitial BG - I always check an glucometer or Catalyst BG for confirmation
- Can be difficult to adhere to patient skin

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Take Home
- Diabetic ketotic patients require close monitoring
- Remember comorbid conditions
- Don't believe a 'normal' K or P on the presentation bloodwork; all patients have a whole body deficit and require supplementation
- Owner education is imperative

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© DVM STAT 24/7 2019