2.  Lack of insulin production prevents glucose uptake by muscle and allows unrestrained hepatic glucose production.  Lack of suppression of lipolysis leads to excess circulating FFAs which are converted into ketoacids (B-OH-butyrate and acetoacetate) by the liver.

3.  This leads to acidemia which may impair vascular tone and cardiac function.  Marked hyperglycemia and ketonemia cause osmotic diuresis with loss of water and electrolytes.

4.  Nausea, emesis  Abdominal pain (2/2 delayed gastric emptying/ileus 2/2 acidosis and lyte abnormalities and may correlate with degree of acidosis)  Polyuria/Polydipsia  Lethargy  Headache  Anorexia  Usually develop over 24h or less in DKA; over multiple days more insidiously in HHS.

5.  Possible precipitating events (“Is”) › Infection (UTI? PNA?) › Insulin (incorrect dosing/noncompliance) › Ischemia (myocardial….mesenteric) › Initial presentation of DM.

6. › More uncommon causes › Med effect – meds that affect carb metabolism › Steroids › High-dose thiazides › Atypical antipsychotics › CVA › Pancreatitis › Cocaine use

7.  In hospitalized pts without DKA who present with CVA, MI, or infection and glucose >250… › Maintain high suspicion for DKA – check RFP for AG and serum/urine ketones.

8.  ABCs  Mental status  Evidence of intercurrent illness (infection, MI, CVA, pancreatitis)  Abdominal exam – TTP, hypoactive BS  Volume status › Skin turgor › Mucosa › Flat neck veins › Orthostatic hypotension

9.  RFP – for lytes, glc, CALCULATE AG  CBC  UA/ketones  Plasma osmolality  Serum ketones if urine ketones are present (B-OH-Butyrate, Acetone, Acetaoacetate)  ABG if serum HCO3 reduced  ECG  Consider infectious w/u(blood, urine, sputum, CXR)  HbA1C may be useful

10. DKAHHS MildModSevere Plasma Glc>250 >600 Arterial pH7.25-7.307.0-7.24<7.0>7.30 HCO315-1810-<15<10>18 Urine ketones +++Small Serum osmVariable >320 Anion Gap>10>12 Variable

12. DKALactic Acidosis UremiaETOH Keto- acidosis ASA Intox MeOH/ Ethy Glycol Intox pHLow Mild Low ??Low Plasma GlcHighNormal Low/NlNl/LowNl GlycosuriaHighNegativeNeg Plasma KetonesHighNormal Sm-ModNormal Anion GapHigh Sl HighHigh OsmolalityHighNormalHighNormal High Uric AcidHighNormal HighNormal

13.  B-OH-Butyrate  Acetone & Acetoacetate  Direct measurement of B-OH-Butyrate is preferable for monitoring degree of ketonemia and is available at UHCMC (not VA)  Standard ketones may become increasingly positive as conversion from B- OH-Butyrate to acetone/acetoacetate occurs

14.  5 Step Approach to ABGs without memorizing formulas….

15. 1. Identify alkalosis/acidosis by pH change from 7.4. (>7.4 = alkalosis. <7.4 = acidosis). 2. Determine if primary disorder is respiratory or metabolic based on direction of change of PCO2. If pH and PCO2 change in same direction - metabolic If pH and PCO2 change in opposite direction - respiratory

16. 3. Check compensation to identify other primary disorders. Metabolic Acidosis - Check Resp Compensation. PCO2 = (1.5 × [HCO3-]) + 8 ± 2 Simplified: For every 1 mEq decrease in HCO3, PCO2 should decrease by 1.2 mmHg. Example: If HCO3 is 9...24-9 = 15. PCO2 reduction should be 15x1.2 = 18. 40-18 = 22mmHg. Metabolic Alkalosis – Check Resp Compensation. PCO2 rises 0.7mmHg for each 1.0 mEq rise in HCO3. Example: If HCO3 is 34...34-24 = 10. 10 x 0.7 = 7. 40+7 = 47mmHg.

17. Acute Respiratory Acidosis: Every 10 mmHg rise in PCO2 = 1 meq rise in HCO3 Chronic Respiratory Acidosis: For every 10 mmHg rise in PCO2 = 3.5 mEq rise in HCO3

18. Acute Respiratory Alkalosis: Every 10 mmHg drop in PCO2 = 2 meq drop in HCO3 Chronic Respiratory Alkalosis: For every 10 mmHg drop in PCO2 = 5 mEq drop in HCO3

19. 4. If metabolic acidosis - calculate anion gap. Na - (Cl+HCO3) Normal gap 12 or less. For each gram of albumin drop less than 4 add 2.5 to calculated gap to get actual gap. Example: Calculated gap 9. Albumin 2. Add 5 to gap = 14.

20. 5. If AGMA - calculate delta gap. Change in gap divided by change in bicarbonate. (AG-12) / (24-HCO3) <1 – AGMA + NAGMA 1-2 - Pure AGMA >2 – AGMA + Metabolic Alkalosis

21.  In DKA, initially AGMA; as treatment proceeds many will develop a subsequent NAGMA. › Ketoacid anions are excreted in the urine with sodium which would have been used to reproduce HCO3 in the kidney  loss of “potential HCO3” which is equivalent to actual bicarb loss  subsequent NAGMA.

22.  Q1H POCT Glucose until stable  RFP/Serum osmolality q2-4h with close FU of HCO3.  Consider VBG rather than frequent ABGs for pt and intern comfort – venous pH is about 0.03 units lower than ABG.

25.  Severe Hypovolemia – NS 1000cc/h  Milder Dehydration – evaluate corrected Na (Corrected Na = Measured Na (Glc- 100/100) › Hyponatremia – 250-500cc/h NS › Normal-Hypernatremia – 250-500c/h 1/2NS When serum glc reaches 200 (or 300 in HHS)  Change to D51/2NS 150- 250cc/h

26.  Usually IV route except in mild DKA.  IV: Regular insulin 0.1U/kg bolus then 0.1U/kg/h continuous infusion OR no bolus with infusion rate alone at 0.14U/kg/h  SQ: Lispro 0.3U/kg x1 then 0.2U/kg in 1hr then 0.2U/kg SQ q2h.  If serum glc doesn’t fall by 50-70 mg/dL in 1 st hour double the IV or SQ dose.  K <3.3 is a CONTRAINDICATION to insulin.

27.  When glc to 200 (in DKA) or 250-300 (in HHS) reduce infusion to 0.02-0.05U/kg/h IV or change SQ dosing to 0.1U/kg q2h with goal glc 150-200.  Never discontinue insulin prior to closure of anion gap!

28.  If K <3.3 – hold insulin therapy and replete K with fluids – 40-60mEq/h to ½NS until K 3.3+ (assuming UOP 50cc/h+).  If K >5.3 – no K supplementation but check q2h.  3.3-5.3 – Give 20-30mEq per liter of 1/2NS goal K 4-5 (assuming UOP 50cc/h+).  Substantial losses in almost all 2/2 urine loss; shifts out of cells 2/2 insulin deficiency and hyperosmolality so K artifically elevated at presentation.

29.  Whole body PO4 depletion is common though PO4 will be normal or elevated initially due to migration out of cells.  With treatment hypophosphatemia will develop usually without adverse effects in a self-ltd fashion.  No benefit to repleting PO4 unless cardiac dysfx/hemolytic anemia/resp depression, concentration <1.

30.  pH <6.9  Consider HCO3 gtt (though small studies have shown minimal benefit…)  pH >7.0  No HCO3

31.  Ketoacidosis resolved – AG is normal (<12) › Ketonemia/Ketonuria may persist >36h without pt actually being in true ketoacidosis.  HHS pts are mentally alert and plasma osmolality is <315.  Pt is able to tolerate PO.

32.  Initiate SQ insulin AT MEALTIME with a 1- 2h taper of the gtt.  Insulin Naïve  0.5-0.8U/kg per day in sliding scale + long-acting regimen › 25% as long acting. › 25% as scheduled meal-time insulin › Sliding Scale  Known DM  start at previous insulin regimen.

33.  Cerebral edema › Very rare in adults but 40% mortality. › Sxs: ha, lethargy, decreased arousal  seizures, incontinence, brady, resp arrest, pupul changes. › Mortality 20-40%.  Prevented by following protocol, adding dextrose to fluids when appropriate.  Tx – unit, mannitol?, 3%NS?

34.  Non-cardiogenic pulmonary edema › Hypoxemia 2/2 decreased osmotic pressure  migration of fluid into lungs. › If initial A-a gradient is widened on ABG, higher risk of development of pulmonary edema.

35.  A 23-year-old woman with type 1 diabetes mellitus is admitted to the hospital with a diagnosis of community-acquired pneumonia and lethargy. Before admission, her insulin pump therapy was discontinued because of confused mentation. On physical examination, temperature is 37.5 °C (99.5 °F), blood pressure is 108/70 mm Hg, pulse rate is 100/min, and respiration rate is 24 min. There are decreased breath sounds in the posterior right lower lung. Neurologic examination reveals altered consciousness.

36.  Sodium 130 meq/L (130 mmol/L)  Potassium 5.0 meq/L (5.0 mmol/L)  Chloride 100 meq/L (100 mmol/L)  Bicarbonate 16 meq/L (16 mmol/L)  Blood urea nitrogen 38 mg/dL (13.6 mmol/L)  Creatinine 1.4 mg/dL (123.8 µmol/L  Glucose 262 mg/dL (14.5 mmol/L)  Urine ketones Positive

37.  Which of the following is the most appropriate next step in management? AAdd insulin glargine BAdd neutral protamine Hagedorn (NPH) insulin CImplement a sliding scale for regular insulin DStart an insulin drip

38.  Questions?