1. DKA & HHS Ahmad F. Mady MD 11/26/2015 10:30:08 PM 1

2. Diabetes 1552 BC, Diabetes 1st Described In Writing on 3 rd Dynasty Eqyptian papyrus by physician Hesy-Ra: mentions polyuria as a symptom. 250 BC, Apollonius of Memphis coined the name "diabetes” meaning "to go through" or siphon. He understood that the disease drained more fluid than a person could consume. 11/26/2015 10:30:08 PM 2

3. Diabetes Mellitus Gradually the Latin word for honey, "mellitus," was added to diabetes because it made the urine sweet. Up to 11 th century diabetes was commonly diagnosed by “water tasters” who drank the urine of those suspected of having diabetes, as it was sweet-tasting. 11/26/2015 10:30:08 PM 3

4. Early Diabetes Discoveries In the 1869, Paul Langerhans, a German medical student announced in a thesis, that the pancreas contains two systems of cells. In the1889 Oskar Minkowski and Joseph von Mering in France, removed the pancreas from a dog to determine the effect of an absent pancreas on digestion 11/26/2015 10:30:08 PM 4

5. Fredrick Banting & Charles Best 11/26/2015 10:30:08 PM 5

6. Leonard Thompson 11/26/2015 10:30:08 PM 6

7. Three months later 11/26/2015 10:30:08 PM 7

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10. Ppt Factors of DKA&HHS Approximate frequencyFactor 35%Infection 30%Omission of insulin or inadequate insulin 20%Initial presentation of diabetes mellitus 10%Medical illness 5%Unknown 11/26/2015 10:30:08 PM 10

11. Clinical Presentation of DKA History of polyuria, polydipsia, polyphagia, weight loss Nausea, vomiting, abdominal pain Acidemia leading to hyperventilation,Kussmaul breathing,Ketotic odour. Clouding of sensorium, weakness, and coma Dehydration and shock 11/26/2015 10:30:08 PM 11

12. Clinical Presentation of HHS Similar to DKA but coma is more frequent Severe dehydration is the rule Focal neurologic deficits may be found at presentation Usually more elderly patients Acidemia not pronounced 11/26/2015 10:30:08 PM 12

13. Laboratory Findings Serum osmolality290+_10<320>320 11/26/2015 10:30:08 PM 13

14. Treatment involves 5 key components: Monitoring Fluid resuscitation Insulin and dextrose infusion Electrolyte repletion Treating underlying cause Therapeutic goals 11/26/2015 10:30:08 PM 14

15. Dehydration WHY……? 11/26/2015 10:30:08 PM 15

16. Mild dehydration = 10% deficit – orthostatic change in pulse only – about 2L loss Moderate dehydration = 15% -20% deficit – Orthostatic change in blood pressure – about 4L loss Severe dehydration = >20% deficit – Supine hypotension – about 8L loss Estimation of TBW deficit in DKA 11/26/2015 10:30:08 PM 16

17. Fluids, fluids, fluids! Restores circulatory volume Diminish concentration of catecholamines, glucagon 11/26/2015 10:30:08 PM 17

18. Caution! Excessive therapy may result in ARDS Cerebral edema Hyperchloremic acidosis 11/26/2015 10:30:08 PM 18

19. Fluid replacement in DKA Initial fluid = normal saline – 15ml to 20ml/kg, about 1-2L in 1 hour – 500 ml/h for next 2 hours or 1L /h if in shock – 500-250 ml/h according to hydration status (RBS 250mg/dl) Subsequent change in fluids – half normal saline START when urine output improves and BP stable – D5 1/2 NS START when blood glucose <250 mg/dl Endpoint - resolution of ketonemia and acidosis - Se bicarbonate >18 11/26/2015 10:30:08 PM 19

20. If SBP<90 mmHg  Initially give 1 litre of Normal Saline per hour. If SBP>90 mmHg  0.45% N/S if serum sodium is high or normal  0.9% N/S if serum sodium is low. Rate and volume as for DKA. Rate should be adjusted for cardiac function Fluid replacement in HHS 11/26/2015 10:30:08 PM 20

21. Insulin administration in DKA&HHS Withhold insulin therapy until the serum potassium concentration has been determined. Initial regular insulin – Goal = reduce hourly glucose by 50-70 mg/dl – Bolus = 0.15u/kg or 10u bolus – IV infusion = 0.1u/kg/hr till RBS 250mg/dl then follow iv infusion protocol 11/26/2015 10:30:08 PM 21

22. Insulin administration in DKA&HHS Endpoint for continuous/hourly regular insulin – Se bicarbonate >18, anion gap <14 – Absence of serum ketones Switch over to maintenance Plasma glucose is less than 250 mg/dl DKA has resolved Patient is tolerating PO It is important to give the first s.c. injection of insulin approximately 2 hours before stopping the i.v. route 11/26/2015 10:30:08 PM 22

23. Intravenous Insulin Infusion Protocol Capillary blood glucose in mg/dl (mmol/L) Units of Insulin per Hour <99 (5.5)0.5 100-149 (5.6-8.2)1 150-199 (8.3-11.0)2 200-249 (11.1-13.8)3 250-299 (13.9-16.6)4 300-349 (16.7-19.4)5 350-399 (19.5- 22.2)6 400-450 (22.3-24.9)8 >450 (24.9)10 11/26/2015 10:30:08 PM 23

24. Who saved me: the insulin or the nurse ? 11/26/2015 10:30:08 PM 24

25. Potassium Therapy may be normal or elevated at the time of diagnosis Goal is to maintain Se K between 4 and 5 K+ 3.3 mEq/L K+ > 5.5 mEq/L initially, hold K+ supply and recheck q2h 3.3 < K+ < 5.5, give K+ 20-30 mEq/L Check potassium level every 1 to 2 hours initially 11/26/2015 10:30:08 PM 25

26. Potassium Therapy may be normal or elevated at the time of diagnosis Goal is to maintain Se K between 4 and 5 If serum K>5 do not give K but recheck in one hour If serum K is 4-5 give KCl 20 mEq in each litre of fluid If serum K is 3-4 give KCl 30 mEq in each litre of fluid If serum K is <3 hold insuline,give KCl 40 mEq over 1hr then recheck K 11/26/2015 10:30:08 PM 26

27. Bicarbonate Therapy Controversial – Most literature shows no benefit to using bicarbonate with patients who have DKAor HHS No differences in reduction of glucose or ketoanion May increase hypokalemia, cerebral acidosis and cardiac dysfunction – For patients with pH < 7.0, they may benefit from bicarbonate therapy pH 6.9-7.0 may give 50 mEq of bicarb pH <6.9, may give 100 mEq of bicarb 11/26/2015 10:30:08 PM 27

28. Phosphate Therapy Phosphate deficiency – Osmotic diuresis → urinary phosphate losses – Insulin therapy → serum phosphate reenters intracellular compartment Adverse complications may occur if P < 1.0 mg/dl – Respiratory depression – Skeletal muscle weakness – Hemolytic anema – Cardiac dysfunction May be useful to replace 1/3 potassium as K3PO4, reduce chloride load, prevent hyperchloremic acidosis. 11/26/2015 10:30:08 PM 28

29. Investigations to be done Serum glucose initially then hourly Serum K initially then hourly if 5 otherwise 2 hourly till stable Na, urea, creatinine initially then 4 hourly till stable ABG initially then as often as necessary Serum osmolality & Na hourly initially in HHS CBC with differential white count ECG, CXR Urine analysis Urine culture if pus cells or bacteria in U/A or patient is septic Blood culture if patient is febrile or WBC>12,000 Serum Mg and Ca Cardiac enzymes if ECG abnormal initially and after 8 hours Throat swab culture if signs of pharyngitis present Sputum culture if purulent looking or infiltrate on CXR Serum amylase (often raised-up to 10 times-even in the absence of pancreatitis) 11/26/2015 10:30:08 PM 29

30. Avoid overhydration Note: Nitroprusside can be used to detect ketones but is not accurate ….why? Prophylaxis small doses of LMW heparin Antibiotics: NOT routine Do consider anti-peptic ulcer prophylaxis Considerations in management 11/26/2015 10:30:08 PM 30

31. Complications Lactic acidosis – Due to prolonged dehydration, shock, infection and tissue hypoxia – Should be suspected in pt with refractory metabolic acidosis and persistent anion gap Arterial thrombosis – Stroke, MI, or an ischemic limb Cerebral edema – Over hydration of free water, excessively rapid correction of hyperglycemia are risk factors ARDS – Excessive crystalloid infusion – Pulmonary rales, increased AaO2 gradient 11/26/2015 10:30:08 PM 31

32. Mortality from DKA is due to? 1) Hyperglycemia 2) Acidosis 3) Sepsis 4) Hypokalemia 5) Cerebral edema 11/26/2015 10:30:08 PM 32

33. ProtocolDKA ProtocolDKA 11/26/2015 10:30:08 PM 33

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35. Three Take Home Messages 1. DKA &HHS may be life threatening 2. Fluids and Insulin along with frequent monitoring is essential 3. Watch for hypokalemia and cerebral edema 11/26/2015 10:30:08 PM 35

36. Thank you for your attention Thank you for saving me from DKA&HHS 11/26/2015 10:30:08 PM 36

37. Thank you AHMAD F. MADY MD

38. Mental Status and Osmolality 11/26/2015 10:30:08 PM 38

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