Diabetic Ketoacidocis, increasing your success rate by knowing the right tricks

Transcription

1 Diabetic Ketoacidocis, increasing your success rate by knowing the right tricks Stijn Niessen DVM PhD DECVIM PGCVetEd FHEA MRCVS Veterinary Specialist Internal Medicine Senior Lecturer Internal Medicine NVF Oslo 2016

2 Case Badger

3 Badger 12 yr MN DSH Longterm DM 3 iu BID caninsulin Purina DM (tin) Variable appetite longterm Now: 2 days anorexia, lethargy, vomiting PE: quiet, T:38.8, HR180, RR: 40, no other findings

4 Emergency bloods Result Range Total protein g/l Albumin g/l Globulin g/l Urea mmol/l Creatinine umol/l Total bilirubin 5.2 <3.0 umol/l Sodium mmol/l Potassium mmol/l Chloride mmol/l ALP U/l ALT U/l CK u/l Glucose mmol/l ph pco po Urine + plasma Ketones: +++

5 DKA Deadly before insulin discovered 1920: DKA fatal Mortality humans remains 5-10%! Glucose deficiency: oxidation NEFA by liver as alternative energy source

6 DKA Oxidation FFA-> acetoacetate ->(NADH)-> o B-hydroxybutyrate ->(spont decarbox) o ->acetone Conditions ketogenesis # Mobilisation FFA from TG in fat Liver: fat synthesis->fat oxidation Insulin inhibitor lipolysis and FFA oxidation

7 Approach to DKA First questions: WHY DID THIS HAPPEN??? What was the factor that pushed animal into DKA? (ignored DM, pancreatitis,insulin,steroids?) What can we do about this inducing factor?

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9 Key question... Is the animal ill and ketotic? Yes: intensive treatment - DKA ( aggressive insulin, fluid/electrolytes) No: as per normal diabetic - DK

10 ICU is best... Ill DKA patient METABOLIC EMERGENCY needs intensive care! Basic work-up: urinalysis, hematocrit, TP, BG, venous CO2 or arterial acid-base, BUN/Creat, Na, K, Calcium, PO4 Guides formulation of plan Fluids, correction lytes, acid/base, renal function Additional data depends on history, PE, concurrent disorders Radiographs, abdo US, fpli, cpli

11 Approach to DKA 1. Fluid therapy 2. Bicarbonate therapy 3. Insulin therapy 4. Ancillary therapy 5. Monitoring

12 What is the most important step in this approach? 1. Fluid therapy 2. Bicarbonate therapy 3. Insulin therapy 4. Ancillary therapy 5. Monitoring

13 Approach to DKA 1. Fluid therapy 2. Bicarbonate therapy 3. Insulin therapy 4. Ancillary therapy 5. Monitoring

14 1. Fluid therapy At least as important as insulin! Rehydrate Inhibit ongoing peripheral lipolysis Diuresis ketone bodies Type: 0.9% saline initially or 0.45% Rate: ml/kg/24hrs Hydration status Urine output Continued fluid loss (V,D)

15 1. Fluid therapy K supplementation: based on initial + continued measurement; if unknown add 40 meq KCl/L Phosphate supplementation: add if PO 4 less than 0.5 mmol/l or if signs of haemolytic anemia IV infusion mmol/kg/hr in calcium free fluids (0.9% saline) Compromise: 20 mmol/l KCl + 20 mmol/l KPO 4 Dextrose: not until BG<15 mmol/l, then 5% dextrose infusion

16 1. Fluid therapy In times of acidosis H + H + H + K + K + K + H + H +

17 1. Fluid therapy Potassium Potassium Potassium H + WILL H + drop!!! H + H + H + Potassium Two main reasons for Potassium to drop: n1. Acidosis improves n2. Insulin Potassium K +

18 Fluid therapy Initial fluid 0.9% NaCl First 24 hrs: %dehydrationxbwx ml/kg/day+20-40ml/kg/day Monitor (SBP, UO, Resp, CVP,Lytes, bg 1-2hrs) BG<15->add dextrose 2.5-5% Na<140mEq/l: normal NaCl >155: 0.45% Saline or 5% dextrose in H2O

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20 2. Bicarbonate Therapy Correct treatment can make unnecessary Both fluid and insulin therapy will help acidosis 1 meq of HCO 3 generated from each meq of ketoacid Not without danger! Adverse effects HCO 3- : worsen hypokalemia, cause paradoxical cerebral acidosis, delay decrease in blood lactate and KB levels If plasma HCO 3 - <12 meq/l or venous CO 2 <12mmol/l

21 What is paradoxical cerebral acidosis in the context of DKA? A. Comatose state when ph in brain becomes to low in untreated patients B. Neuronal destruction when there are too many protons through excess lipolysis C. Proton migration through blood brain barrier D. Bicarbonate induced CO2 production which enters the brain

22 HCO 3- + H + H 2 CO 3 H 2 O + CO 2 ph (ph normal) HCO3 - + H + H2CO3 H2O+ CO2

23 2. Bicarbonate Therapy If unknown: do NOT give unless animal severely ill and then give only one dose and focus on other tx If known: HCO 3- (meq): BW(kg)x0.4x(12-patient HCO 3 - )x0.5 If unkwown: HCO 3- (meq): BW(kg)x2 Add to IVFT over 6 hours, NOT bolus Repeat only if HCO 3- <12 meq/l after 6hrs

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25 3. Insulin therapy Type: regular/neutral/soluble IM techniques: various Initial dose 0.2 iu/kg IM Then 0.1 iu/kg IM q 1h Until BG mmol/l, then IM iu/kg q 6-8hrs Or, if hydration status okay: SC Start dextrose iv 1-2 times maintenance If BG>15 mmol/l, adjust insulin/dextrose If BG<10 mmol/l, adjust insulin/dextrose If eating and happy: switch traditional insulin regimens and types

26 Why start dextrose if blood glucose is finally down? A. Because insulin is too good at lowering BG B. Because the body needs extra energy in ketoacidosis C. Because the ketolysis is promoted by dextrose

27 3. Insulin therapy IV insulin protocol using volumetric pump Advantage: more control over serum insulin levels more predictable bioavailability corrections made quickly if BG drops too quickly less labour-intensive Less stressful?

28 3. Insulin therapy Initial rate iu/kg/hr Prepare solution: 25 iu in 500ml NaCl bag=50/1000=0.05 iu/ml ->1ml/kg/hr=0.05 iu/kg/hr Separate line attached to Y-piece + run through 30 secs Aim 2 mmol/l BG drop/ hour, not more! When BG mmol/l: half insulin rate + swap fluids for combination 0.45% NaCl + 2.5% dextrose at 2x maintenance dextrose to maintain BG stable

29 3. Insulin therapy Ketogenesis reversed patient will feel better Eating SC regular insulin iu/kg q 6-8hours traditional insulin possible

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31 Badger

32 What is going on here??? A. We got the diagnosis wrong B. We need to give more insulin C. This can be sign of success! D. We have to give dextrose

33 Diagnosis DKA Diagnosis DM Concurrent ketonuria/aemia Nitroprusside urine keto-sticks measure acetoacetate+acetone Do not measure B-OH-Butyrate! Clinical implication: Missing diagnosis possible in case of circulatory collapse lactic acid # redox potential Δ BOH-But # + Acetoacetate $ Discouraging initial results: B-OH-But Acetoacetate

34 Physiology of DKA Triglyceride Free Fatty Acids Fatty Acyl Co A Acetyl Co A HMA Co A Acetoacetate Insulin Acetone 3β hydroxybutyrate

35 4. Ancillary Therapy Concurrent disease: pancreatitis! IVFT, plasma administration, pain relief 0.01 mg/kg Buprenorphine SC/IV dietary precautions anti-emetics UTIs and other infections: broad spectrum Abs

36 Concurrent disorders in dogs with diabetes mellitus: 221 cases ( ) Hess et al. JAVMA % UTI 16% dermatitis or otitis 23% HAC 13% acute pancreatitis 5% neoplasia 4% hypothyroid

37 PANCREATITIS

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41 Badger Deteriorates weaker mentation worsens. 2am 6am Normal ph pco Hct Na K Cl BG Urea Creat Plasma Ketonen ve

42 What is going on? A. We did not normalise the ph aggressively enough B. We did not remove ketones quickly enough C. He has another primary disease, probably brain disease D. He has renal failure E. Something else

43 Badger Complications Rapid lowering BG causes cerebral oedema 2am 6am Noraal ph pco Hct Na K Cl BG Urea Creat Plasma Ketonen ve

44 nduring hyperglycaemia brain makes sorbitol H2O H2O H2O

45 nbrain makes sorbitol during hyperglycamia H2O H2O H2O

46 H2O H2O H2O nwith start therapy hypertonicity is reduced nwater moves to sorbitolrich environment of the brain cells (hyperosmotic) H2O

47 H2O H2O H2O H2O H2O H2O H2O H2O

48 H2O H2O H2O H2O H2O Clinical: Reduced function CNS H2O H2O H2O

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50 Prevention: Don t lower BG by more than > 2-3/mmol/l/hr Don t lower osmolality more than osmol/hr (2x(Na+K)+BUN+BG)

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53 5. Patient monitoring BG q 1-2 hrs initially Adjust insulin+begin glucose/dextrose when <12-15 mmol/l Hydration, respiration, pulse q2-4 hrs Electrolytes (K+PO4!) + CO 2 /acid/base q 4-12 hours Urine output, glycosuria, ketonuria q 2-4 hours BW (fluid overload!), PCV (haemolysis), temperature (sepsis, shock, infection), SBP 1-2/day Additional monitoring according to concurrent dx present Monitoring is the basis of success in DKA!!!

54 The mortality rate of dogs and cats with DKA is 30-40% High mortality rates are usually associated with underlying disease or inadequate monitoring Check for underlying disease!!!

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56 The future? New analogs of human insulin that have a rapid onset...represent potential alternatives to the use of regular insulin in the treatment of DKA. In several trials...a safe, cost-effective and technically simpler treatment that precludes intensive care unit admission without significant differences in outcome in the management of patients with mild to moderate, uncomplicated DKA.

57 Approach to DKA 1. Fluid therapy 2. Bicarbonate therapy 3. Insulin therapy 4. Ancillary therapy 5. Monitoring DKA? Panic!? No: an opportunity for vet and nurse to excel as a team

58 Want to know more about feline diabetes? Only want evidence-based information? Like and follow :