1. DKA - Some objective and evidence based aspects that may change our standard management. Sources: 1 ADA Clinical Practice Recommendations 2013 2 Joint British Diabetes Societies Impatient Care Group. Management of DKA in Adults 2010 3 CMDT 2012 4 Uptodate.com and Epocrates 5 Kitabchi Et al on DKA management (Diabetes Care) A presentation by Dr SOURABH PATHAK – Emergency Medicine Resident, Peerless Hospital

2. Diabetes Ketoacidosis (DKA)Definition All the major definitions by various authorities are rather subjective but emphasize on the following points :  1 Acute life threatening metabolic complication of diabetes  2 Characterized by absolute insulin deficiency and hyperglycemia Note: DKA was a “life threatening” condition (90% mortality ) before the advent of Insulin –but today with Insulin treatment the mortality of this condition is very low.

3. Essentials of Diagnosis (CMDT 2012)  RBS > 250 mg/dl……. so be careful!  Serum ketone positive (Not urine ketones !)  Acidosis with Ph less than 7.3  Serum bicarbonate less than 15 mEq/L

4. Clinical Classification of DKA (Kitabchi et al – Diabetes care ) -0f limited clinical utility Mild DKAModerate DKASevere DKA Plasma glucose More than 250 mg /dl in all grades ph7.25 to 7.3 7 to 7.24Less than 7 Bicarbonate15 -1810 to 15Less than 10 Anion Gap> 10>12 Mental StatusAertAltert & or drowsyStuper & or coma

5. Management (AS per ADA guidelines 2012) Essential therapy (in all patients of DKA )  IV fluids  Supportive Care +/- ICU admission  K treatment  IV Insulin once K is more than / equal to 3.3 mEq/l Adjuvant Treatment (in select cases )  Vesopressors  Bicarbonate  Phosphate

6. IV fluids (Initial fluid & maintenance fluid)  Initial Fluid (first one Hour ) Isotonic saline (0.9 NaCl ) is the initial fluid of choice in all cases irrespective of volume status and sodium status Goal : Restoration of Tissue Perfusion Dose 15 to 20 ml / Kg in 1 hour This translates to 1 - 1.5 l in first one hour in normal adults. As per ADA guidelines 2013

7. IV fluid- Maintenance fluid(after first 1 hour)  If Severely volume Depleted : Signs Orthostatic/ Supine hypotension Dry mucus membrane Poor skin turgor Recommendation is to continue fluid resuscitation with frequent monitoring and rate adjustments as required until the patient becomes stable Fluid of choice : 0.9 % NS As per ADA guidelines 2013

8. Maintenance fluid(after 1 hour)- if not severely volume depleted.  For Moderate to mildly hypovolumic patients :After first 1 hour fluid resuscitation with NS measure Corrected Serum sodium  Recommended Rate of infusion : 250 to 500 ml /hr  Goal :To replenish half of fluid deficit gradually in 12 to 24 hrs to prevent complications like cerebral edema.  Once RBS is 200 mg /dl (earlier 250) shift to DNS @150 -250 ml/hr As per ADA guidelines 2013 Corrected Na = Measured Na + 0.016 x (glucose -100) If HyponatremicIf Normo/Hyperntremic 0.9 % NS0.45 NaCl

9. ICU admission /Maintenance  ICU admission criteria: Hemodynamic instability Respiratory Insufficiency Altered mental status Severe Acidosis Maintenance (all Evidence based)  Regular NG suction (Frequent Illeus and aspiration)  Hourly K  2 to 4 hourly : BUN, Cr, Glucose, Venous PH Till all criteria of resolution is met : RBS 7.3, HCO 3 >18, Anion Gap <10 As per ADA guidelines 2013

10. Potassium Therapy  Surum K may be high, low or normal at various stages of DKA but DKA is always a state of Total K depletion irrespective serum K levels (due to osmotic Diuresis)  K should be checked Hourly  Start K therapy @ 20-30 mEq /hr infused in IV FLUID as soon as initial K levels are available (hold if K >5.3) to maintain K between 3.3 and 5.3  Insulin should be stopped if K falls below 3.3  K should be given as 2/3 KCL and 1/3 potassium phosphate (to avoid Chloride overload) As per ADA guidelines 2013

11. Insulin Therapy As per ADA guidelines 2013  Start Insulin if K >3.3 stop Insulin at any point where K falls below 3.3  Dose IV Regular Insulin @ 0.1 unit /kg/hr >>if RBS doesn’t fall by 10% in first hour double the dose. Once RBS falls below 200 half the current dose and continue IV insulin till all the criteria of resolution are met : RBS 7.3, HCO3 >18, Anion Gap <10 Once these criteria are met and patient is able to tolerate oral intake switch to S/C insulin Give S/C Insulin 2 hrs prior to stoppage of IV insulin Dose : earlier dose or Total insulin = 0.5 -0.8 U/kg /day, 30% to 50% of this as basal night time insulin Rest as fast acting insulin in divided doses before meals.

12. Subcutaneous Insulin is Recommended over IV Insulin in DKA by some authorities if :  No severe Volume depletion  Not Associated with MI, End stage Renal/ Hepatic D/s  Not Pregnant  RBS >250  Venus Ph 7.0 to 7.3  Bicarbonate 10 to 18 However its USE IS CONTROVERSIAL in DKA and needs more studies – Presently it’s a LeVEL C (Expert Opinion) ADA recommendation (2013). Dose (As per ADA guidelines 2013) LISPRO/ASPART S/C 0.3 U/Kg stat >>1hr >>0.2U /Kg every 2 hrs till RBS < 250 Then 0.1U /kg every 2 hrs till resolution of DKA. NOTE : Use Only Ultra short acting Insulin (lispro and aspart ) NOT Regular insulin if S/c insulin is used in DKA

13. Adjuvant therapy (0nly in Special cases) As per ADA guidelines 2013 Therapy Indication and Dose Bicarbonate (bicarbonate decreases K) ph < 7or Bicarbonate < 5 Dose ph 6.9 to 7 : 50 mmol NaHO 3 ( (1 amp) in 200 ml sterile water with 10mEq KCL Hourly till ph is more than 7 Ph<6.9 : 100mmol NaHO 3 (2 amp) in 400 ml sterile water with 20 mEq KCL @ 200ml/hr till ph is more than 7 Phosphate (decreases with Insulin therapy) ONLY if Serum phosphate < 1mg/dl Dose Potassium Phosphate 20 -30 mEq /L in IV fluid Vesopressors In hemodynamic instability (hypotension) First stat Dopamine 5-10 mcg/kg/min adjust with BP If not effective in moderate does then start Noradrenalin Start with 0.5 mcg/kg/min titrate to maintain MAP 60

14. Pathophysiology Stress Missed Insulin/Less Insulin in circulation Infection /MI Counter regulatory Hormones Hyperglycemia >>Osmotic Diuresis Ketosis Effects Dehydration Metabolic Acidosis

15. Risk Factors of DKA (with strong associations)

16. Risk Factors (with weak associations)  Pancreatitis  CVA  Acromegaly/Hyperthyroidism/Cushing’s Syndrome  Drugs (Steroids, Thiazides,Cocaine,Sympathomimmetics,Second Generation Anti Psychotics )  Hispanic/ Blacks

17. Conditions and associated Symptoms HYPERGLYCEMIA : Polyuria, polydipsia, weight loss, Weakness Acidosis:Nausia, Vomiting, Abdominal Pain,Altered Mental status, Kussmaul Respiration (rapid &deep) Volume Depletion Dry Mucus, poor skin turgor, shrunken eyes, tachycardia, hypotension Ketosis Acetone Breadth ( AIIMS 2006 MCQ!!!!) HYPOTHERMIA (due to peripheral vasodilatation..Rare but poor prognosis indicator) note: though there is infection fever is generally absent

18. Notable lab Findings  BUN, Cr increased due to volume depletion  Na generally decreased due to osmotic reflux of intercellular water to extracellular space.  K Initially may be elevated due to extracellular shift due to insulin deficiency then levels rapidly fall with Insulin treatment. But there is ALWAYS a Total K deficit of 3 to 5 mEq/Kg  Cl, Mg, Ca usually low  Phosphate normal/elevated (though there is total deficit and serum phosphate decrease with Isulin therapy)  High Amylase with Normal Lipase  Leukocytosis ( correlates with serum ketone levels however if more than 25000 think of infection )

19. Complications

20. Diabetic Hyper Osmolar Coma (DHOC) -How is it different from DKA? Insidious onset evolve over days to week (DKA is more acute ) Older patients (type 2 ) nursing home residents with poor fluid intake are at risk of DHOC though they can also present as DKA Mental obtundation / coma / Seizures / Neurological signs are more common in DHOC than DKA. RBS is almost always more than 600 mg/dl in DHOC (vs >250 in DKA) Osmolarity >320 mOsm/kg in DHOC (vs variable in DKA) Serum ketone will be negative in DHOC (always positive in DKA) - Hence No acidosis due to Ketosis in DHOC and ph is generally more than 7.3 (however DHOC may present with Lactic Acidosis due to poor tissue perfusion )