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Home , Diabetic ketoacidosis, Ketonuria, Urine specific gravity

Diabetic

Diabetic Ketoacidosis

Dr. Christiane Stengel Dipl. ECVIM-CA (IM) FTÄ für Kleintiere

High blood with the presence of ketones in the and bloodstream, often caused by having/giving too little or during illness.

Dr. Christiane Stengel Diabetic ketoacidosis

v mellitus not diagnosed so far (common) v Or „derailed“ Diabetes (possible) & a “triggering condition” lead to increased „counter- regulatory“ hormones: o ↑ o Cortisol ↑ o Adrenalin ↑ o GH ↑ v Low insulin and high glucagon ‰ increased glucagon:insulin-ratio

medpets.de

v Bacterial v o Urinary tract o Hypercortisolism o o Hypothyroidism o Pyometra /prostatitis o o Pyoderma o Acromegaly v Inflammatory v Physiological condition endocrine change o Pancreatitis o Dioestrus v Iatrogenic v Miscellaneous o Steroid administration o Chronic disease o Neoplasia

Dr. Christiane Stengel Diabetic ketoacidosis

v , lethargy, , weakness, (PU/PD), triggering effect signs v Severe (hypovolaemic ) o Glukosuria ‰ osmotic o ‰ osmotic diuresis o Fluid loss from vomiting o Decreased fluid intake from anorexia and lethargy A. Kussmaul v , change in pulse quality, colour and capillary refill time v Increased breathing effort (often with normal frequency) due to metabolic () , ketone smell

v Haematology v Biochemistry profile ± ketones in plasma v Urinalysis and urine culture v Blood gas analysis v ± abdominal ultrasound v ± thoracic radiographs v ± tests for triggering effect (cPL/fPL)

Dr. Christiane Stengel Diabetic ketoacidosis

v commonly > 1.020 (even >1.045) v Urinalysis: o Glukosuria o Ketonuria v Plasma: o Ketonaemia

v DKA is confirmed when high ketone concentration is found v Ketones in urine are diagnosed on dip-stick v Urinary dipstick can also be used on serum (where ketones appear earlier)

v Dipstick uses nitroprusside reaction ‰ measures only and acetoacetate ‰ does not measure β-hydroxybuturate (β-HB)

In shock: more β-HB and less acetone/acetoacetate ‰ Dipstick can be falsely negative

(MediSense Optium®, Abbott)

(PrecisionXtra®, Abbott)

(PrecisionXceed®, Abbott)

Dr. Christiane Stengel Diabetic ketoacidosis

Precision Xceed Abbott

Can be used in full blood, heparinised plasma and serum Ear pick capillary blood can be used Measures β-HB and acetoacetate Confindence Value (CV) in all samples: <5% Can measure glucose and ketones in dogs and cats

Veterinary Clinical Pathology Volume 41, Issue 1, pages 114-118, 17 JAN 2012 DOI: 10.1111/j.1939-165X.2011.00389.x http://onlinelibrary.wiley.com/doi/10.1111/j.1939-165X.2011.00389.x/full#vcp389-fig-0001

Venous reference DKA value pH 7,4 ↓ pCO2 (mmHg) 40 ↓ (resp. compensation) PO2 (mmHg) 55 - HCO 3 (mmol/l) 22 ↓ BE (mmol/l) -2

+ + - - v (Na + K ) – (Cl + HCO 3 ) o 12-24 mmol/l (Hund) o 13-27 mmol/l (Katze)

Dr. Christiane Stengel Diabetic ketoacidosis

v Normochloraemic v Hyperchloraemic = high AG = normal AG o DKA o Diarrhoea o o o Uraemic acidosis o Drugs (carbonic o Toxins (ethylene anhydrase inhibitors) glycol, salicylates) o Dilutional acidosis o Hypoadrenocorticism *

v Glucosuria & hyperglycaemia v Ketonuria / ketonaemia v High v Azotaemia (prerenal, high urine specific gravity) v Increased enzymes v Electrolyte changes possible (Na, K, P, Mg)

1. Increase circulatory volume and improve tissue perfusion => Infusion 2. Correct electrolyte disturbance => Fluid type 3. Address hyperglycaemia and abnormal osmolality => Insulin 4. Address acidosis and abnormal ketones 5. Treat potential triggering effects

Dr. Christiane Stengel Diabetic ketoacidosis

v Diagnosis often quite easy v Discuss with owner before „spending too much money“ o Emergency therapy needed o Prolonged hospitalisation o Cost involved o Emotional impact o Afterwards commonly diabetic patient in need of insulin

v Discharge from hospital: 70% of dogs and cats

v Number one treatment v Must be administered intravenously! v Amount: maintenance + dehydration + ongoing loss v Type: supplementation & electrolyte substitution

v Corresponds to normal „loss“ o Urine / faeces o Breathing o Skin v Dog: 60 - 80 (-100) ml/kg/day ≈ 2.5ml/kg/h v Cat: 40 - 60 ml/kg/day

v Substitute with ½ Lact.-Ringer + ½ Glucose 5% + 20 mmol/l

Dr. Christiane Stengel Diabetic ketoacidosis

Parameter 5-7% 8-10% 11-14% dehydration dehydration dehydration Heart rate* 130-150 150-170 170-220 Mucous Normal to pinker Pale pink Grey, white or membrane colour than normal muddy CRF Rapid (<1sec) Normal (1-2 sec) Prolonged (>2sec) or absent Pulse amplitude Increased Mild to mod. Severely decreased decreased Pulse duration Mildly reduced Mod. Reduced Severely reduced Metatarsal pulse Easily palpable Just palpable Absent Suggested initial 10-20ml/kg over 20-40 ml/kg over 40-60 ml/kg over bolus ½ - 1 hour ½ to 1 hour ¼ to 1 hour *for adult dogs

v Vomiting v Diarrhoea v kirasoftware.de

Dog, 20 kg, 10% dehydrated, polyuric, vomiting since 3 days, Na 142mmol/l, K 2.4mmol/l deficit : 10% x 20 kg = 2kg = 2000ml (2000ml lactated ringer solution + 60 mmol K+) maintenance: 60ml/kg/d x 20 kg = 1200 ml (600 ml crystalloid + 600 ml glucose 5% + 20mmol/l K+) loss: estimated at 600 ml (vomiting and polyuria) (600 ml crystalloid) Total = 3800 ml Give: 1000 ml within first 4 hours = 250 ml/h Afterwards: 140 ml/h

Dr. Christiane Stengel Diabetic ketoacidosis

v Initially start with resuscitation fluid with Na-concentration close to animals sodium concentration

v Patient sodium concentration o < 140 mmol/l: give 0.9 % NaCl o normal: ringerorlact.-Ringer o > 150 mmol/l: 0.45% NaCl or lact. Ringer

v Patient glucose concentration o > 15 mmol/l [250 mg/dl]: give 0.9% NaCl or lact. Ringer o < 15 mmol/l [250 mg/dl]: 2.5 – 5% glucose infusion

v Metab. acidosis: K + moves from ICF to ECF v Animal is often K + depleted even if Serum-[K +] WNL

v Decreased K+ due to: Rehydration correction of acidosis Insulin (K + and Glucose → ICF) Loss (via urine and faeces)

v K+-supplementation: depending on Serum-[K +]

KCl+KPO 4 1:1 check and modify K in infusion q6h

Dr. Christiane Stengel Diabetic ketoacidosis

Serum potassium mmol/l KCl to add to 1 Maxiumum recommended mmol/l liter of fluid infusion rate for supplemented fluids (ml/kg/h)

3.6 – 5.0 20 25

3.1 – 3.5 30 17

2.6 – 3.0 40 12

2.1 – 2.5 60 8

< 2.0 80 6

(max. 0,5 mmol/kg/h )

2- v Metab. acidosis: PO 4 -ICF → ECF v Animal is often P + depleted even if Serum-[P] WNL v Commonly seen after 1-2 days insulin therapy

v P-deficiency: haemolytic anaemia (cats!) weakness, ataxia, seizures

v Substitution: if [P] < 0.35 mmol/l or with symptoms

give as KCl + K 3PO 4 1:1 0.01-0.03mmol/kg/h for 6 hours monitor q4-12h

v Mg 2+ deficiency: common in human DKA v Mg 2+ deficiency : ↓ orale Aufnahme ↓ Absorption ↑ Diurese v Effect of low Mg 2+ : refractory v Dose: 0.5 – 1 mmol/kg/d (in iv. fluid)

Dr. Christiane Stengel Diabetic ketoacidosis

v Controversial if Na- is needed - v If HCO 3 < 12 mmol/l ? v If pH < 7.1 with no marked change after therapy ? v Substitute only if acid-base measurement possible v Amount of NaHCO : - o kg x 0.4 x (12-patient HCO 3 ) x 0.5 o BE x 0.3 x body weight v Give one-third to one-half of this dose SLOWLY iv over 15-30 minutes v Remainder can be added to infusion and given over 12- 24 hours

v Danger: o Hypokalaemia o Hypophosphataemia o Hypoglycaemia

v In case of hypokalaemia o Give first 2-4 hours infusion with K + o Lower insulin dose by 25-50%

→Start insulin 2-4 (-8) hours after fluid therapy with K +

v In early phase: use regular (neutral) insulin v Various protocols - either IM or (better) IV route (not SC) v Aim: o Blood glucose decreases by 3.0 – 4.0 mmol/h [50-75 mg/dl/h]) o Goal: Glucose 12 – 16 mmol/l [200-250 mg/dl]

v Risk: o Hypoglycaemia (often still ketotic when glucose close to reference value)

Dr. Christiane Stengel Diabetic ketoacidosis

v Advantage: o Glucose reduction in a reliable and constant way v Disadvantage: o Second IV catheter, better o Need to have infusion pump or syringe driver o Measure serum glucose every 1-2hours o Close monitoring of electrolytes o Frequent change of infusion type

v Make insulin solution by adding 25IU neutral insulin to 500 ml or 2.5IU to 50ml (syringe) of 0.9% NaCl v This results in a concentration of 0.05IU/ml v Infuse at 1 ml/kg/h until glucose <14-16mmol/l via a second infusion line (two catheters) v Glucose drops typically at 1-3mmol/h v Once glucose <15mmol/l reduce rate to 0.5ml/kg/h and add 2.5% or 5% glucose to IV fluid v If glucose < 8mmol/l ‰ stop insulin temporarily

o Need to flush infusion line with solution (50-100ml) as insulin sticks to plastic

v insulin solution: add (Actrapid) to NaCl in 50ml Syringe => amount see below v Flush syringe and extension line v Let incubate for 15min => discard whole fluid v Mix again in same syringe and extension line v Fluid rate: see below

Dr. Christiane Stengel Diabetic ketoacidosis

v Advantage: less laborious, less expensive

v Regular (neutral) soluble insulin v Inject initially 0.2 IU/kg i.m. v Measure blood glucose q1-2h v Inject 0.1 IU/kg as needed (q 1-2h) i.m. until glucose < 10-15mmol/l v If Glucose <10-15mmol/l but still ketotic ‰ add 2.5% or 5% glucose to infusion and continue with insulin i.m. at 0.1 IU/kg q1-4h v If glucose < 8mmol/l ‰ stop insulin temporarily

CRI: 2.2 IU/kg (dog) or 1.1 U/kg (cat) in 250 ml 0.9% NaCl

Intermittend i.m. q4-6h

v For first 24 hours: measure glucose q1h (-q2h)

➡ Glu ↓ 3-4 mmol/l/h [50 – 75 mg/dl]

➡ Glu: <15 mmol/l [< 260 mg/dl] → Insulin dosage ↓

➡ Glucose concentration: 12 - 16 mmol/l [200 – 275 mg/dl] until patient stable and eating well

➡ Titrate insulin up or down to maintain glucose concentration in desired range

Dr. Christiane Stengel Diabetic ketoacidosis

v v Glucose: initially q1h, (HR, CRT, MM colour, then q2-4h pulse): initially q1-2h, v PCV/TS: initially q2h, then q4-8h then q4-8h v Respiratory effort: q4-8h v Electrolytes und blood v Neurological status: gas: initially q2h, then q4- initially q1-2h, then q4-8h 8h v Temperature: q4-8h v Ketones: q12h v Body weight q8-12h v Urine output: initially q2- 4h

v Hypoglycaemia v Cerebral oedema (rapid change in Na) v Marked electrolyte alterations v Anaemia

v Thus: o Normalise abnormal parameters SLOWLY o Re-evaluate neurological status frequently o Control laboratory values regularly o Adjust infusion fluid and substitutions when needed o Assisted feeding or feeding tube

v Do not forget to treat and address triggering effects o Pyometra → surgery o → o Vomiting → antiemetics

Dr. Christiane Stengel Diabetic ketoacidosis

v Guarded v Depending on underlying triggering disease/-s and aggressiveness of management of DKA v Mortality in various studies: 20-30%

v 7/12 cats with DKA in remission

Remission of is also possible if initially presented as DKA

1. Place intravenos catheter(s) ➡Blood gas, CBC/biochemistry, plasma ketones, (?) ➡Urinalysis, urine ketones (+ urine culture)

2. Fluid and electrolyte replacement ➡Initial 0.9% NaCl ➡May need shock dose (and monitoring) ➡+/- potassium substitution ➡+/- phophate substitution

3. Insulin treatment AFTER 2-4 (-8) h ➡Depending on potassium concentration ➡Regular insulin via second i.v. catheter or i.m. ➡Goal: slow decrease of serum glucose

4. Bicarbonat??? ➡HCO3 < 12 mmol/l? pH < 7.1?

Dr. Christiane Stengel