5. MANAGEMENT OF DIABETIC KETOACIDOSIS (2).pptx

DKA

1. HYPERGLYCEMIC EMERGENCIES

2. DIABETIC KETOACIDOSIS DKA IS THE LIFE THREATENING BUT REVERSIBLE COMPLICATION OF DIABETES MELLITUS MOST COMMONLY OCCUR WITH T1 DM . IT CAN ALSO OCCURS WITH TYPE 2 DM UNDER CONDITIONS OF EXTREME STRESS LIKE INFECTION, TRAUMA, MI ETC. DKA MORE COMMON IN ADULT THAN CHILDREN

3. TRIAD DKA HYPERGLYCEMIA (BLOOD GLUCOSE > 250 MG /DL OR 13.9 MMOL/L) ACIDOSIS (HCO3 <15 MEQ/L, PH<7.3) KETONEMIA AND KETONURIA

4. DIABETIC KETOACIDOSIS

5. SPECTRUM OF PRESENTATION PATIENT MAY PRESENT WITH HIGH BLOOD SUGAR AND KETONURIA STILL AMBULANT (AMBULANT KETOSIS) HAVING ACIDOSIS BUT CONSCIOUS (DIABETIC KETOSIS) STUPUROUS STATE (DIABETIC KETOACIDOSIS) UNCONSCIOUS STATE (DIABETIC KETOACIDOTIC COMA)

6. PRECIPITATING FACTORS INFECTION (PNEUMONIA/ UTI/ AGE/ SEPSIS ) - MOST IMPORTANT CAUSE INADEQUATE INSULIN OR SKIPPING THE DOSE – 2 ND COMMON CAUSE NEW ONSET DIABETES (20-25%) TRAUMA SURGERY DRUGS ( CLOZAPINE, OLANZAPINE, THIAZIDES, TERBUTALINE, STEROIDS,DOBUTAMINE,COCAINE,TACROLIMUS,PENTAMIDINE, INDINAVIR,LAMIVUDINE, STAVUDINE ETC.) ACUTE ILLNESS LIKE MI, CVA RARELY ACROMEGALY AND CUSHING’S DISEASE PRIMARY PRESENTATION IN 20% CASES CAUSE CANNOT BE ASCERTAINED

7. PATHOPHYSIOLOGY The basic underlying mechanisms are: -Absolute/relative deficiency of circulating insulin . - Secretion of insulin counterregulatory hormones; glucagon, adrenaline, cortisol and growth hormone. Decreased peripheral utilisation of glucose, glycogenolysis , gluconeogenesis, lipolysis and increased protein breakdown Increased blood level of glucose, FFA, amino acid, glycerol, Pyruvate and lactate

8. KETOGENESIS BETA HYDROXY BUTYRATE FORMED 3 TIMES GREATER THAN ACETOACETATE BUT IT CANNOT BE DETECTED BY URINE NITROPRUSSIDE TEST.THE RATIO MAY REACH UPTO 7:1 IN SEVERE SHOCK AND HYPOXIA CAPTOPRIL AND PENICILLAMINE MAY GIVE FALSE POSITIVE REACTION

9. FLUID LOSS HYPERGLYCEMIA HYPEROSMOLARITY OF BLOOD INTRACELLULAR DEHYDRATION AND ECF VOLUME EXPANSION RENAL GLYCOSURIA AND OSMOTIC DIURESIS DEHYDRATION AND VOLUME DEPLETION DIMINISHED URINE FLOW AND INCREASED RETENTION OF GLUCOSE IN BLOOD VOMITING DUE TO DKA ALSO CAUSE HYPOVOLEMIA .

10. METABOLIC ACIDOSIS KETOACIDS ( ACETOACETATE AND BETA HYDROXY BUTYRATE ) ARE STRONG ACIDS. ACETOACETATE COMBINES WITH SODIUM BICARBONATE TO FORM SODIUM ACETATE AND CARBONIC ACID. SODIUM ACETATE EXCRETED IN URINE . BICARBONATE LOSS LEADS TO METABOLIC ACIDOSIS DUE TO LARGE AMOUNT OF KETONES, ANION GAP IS HIGH SEVERE DEHYDRATION  RENAL HYPO PERFUSION  IMPAIRED RENAL FUNCTION MAY ALSO CONTRIBUTE TO ACIDOSIS

11. ELECTROLYTE DISTURBANCES POTASSIUM IN DKA HYPERKALEMIA CAN OCCUR DUE TO METABOLIC ACIDOSIS AND INSULIN DEFICIENCY. OSMOTIC DIURESIS LEADS TO CONTINUOUS LOSS OF k+ IN URINE. LOSS MAY OCCUR DUE TO VOMITING AND INCREASE CORTISOL LEVEL THESE LEADS TO DEFICIT IN TOTAL BODY POTTASIUM SO IN DKA, SERUM K+ MAY BE HIGH,NORMAL OR LOW BUT THERE WILL BE DEFICIT OF TOTAL BODY POTTASIUM

12. SODIUM THREE MAJOR MECHANISM FOR SODIUM LOSS OSMOTIC DIURESIS EXCRETION AFTER COMBINIG WITH ACETOACETIC ACID FROM GASTRIC JUICE DURING VOMITING TRANSLOCATIONAL EACH 100 MG INCREASE IN S. GLUCOSE ABOVE 100 MG/DL CAUSE 1.6 MEQ DECREASE IN SODIUM PHOSPHATE AND MAGNESIUM LOSS ALSO OCCURS DUE TO DIURESIS.

13. PHYSICAL SIGNS OF DKA: A-GENERAL SIGNS : ILL APPEARANCE AND DISTURBED CONSCIOUSNESS. B-SIGNS OF DEHYDRATION: -SKIN: DRY, HOT, FLUSHED, AND LOSS OF SKIN TURGOR. -TONGUE: DRY (SOMETIMES WOODY TONGUE). -EYES: SUNKEN EYES AND DARK CIRCLES UNDER THE EYES. - DEHYDRATION ASSOCIATED WITH POLYURIA C-VITAL SIGNS: -TACHYCARDIA, HYPOTENSION AND TACHYPNEA.

14. CONTD…… D-SPECIFIC SIGNS: -KETOTIC BREATH: A STRONG, FRUITY BREATH ODOUR (SIMILAR TO NAIL POLISH REMOVER OR ACETONE) -ACIDOTIC BREATH (KUSSMAUL'S RESPIRATION): DEEP AND RAPID -ABDOMINAL TENDERNESS ( RESEMBLES ACUTE ABDOMEN)

15. ASSESSMENT OF DEHYDRTAION Decreased skin turgor - 5% Orthostatic change in pulse - 10% Orthostatic change in pulse and bp (> 15/min and .> 10 mm hg change) - 15-20% Supine hypotension (severe dehydration) - >20%

16. MANAGEMENT SPECIFIC TREATMENT GENERAL MEASURES TREAT THE PRECIPITATING CAUSE

17. SPECIFIC TREATMENT FLUIDS INSULIN POTASSIUM BICARBONATE PHOPHORUS

18. AVERAGE DEFICITS OF WATER AND ELECTROLYTE PER KG BODY WEIGHT IN DKA WATER 100 ML Na 7-10 mEq /L Cl 3-5 mEq /L K 3-5 mEq /L Mg 1-2 mEq /L PO4 1-2 mEq /L

19. FLUIDS TO RESTORE CIRCULATORY VOLUME TO REPLENISH TOTAL BODY WATER DEFICITS MAINTANENCE OF FLUID REPLACEMENT

20. FLUIDS HYPER vs HYPO vs ISOTONIC FLUID CRYSTALLOID vs COLLOID 0.9%NS, 0.45%NS, RL, 5%D PACE OF FLUID REPLACEMENT RATE OF FLUID ADMINISTRATION

21. FLUID TITRATION HOURS VOLUME 1/2 to 1 hour 1 L 2 nd hour 1L 3 rd hour 500- 1 L 4 th hour 500- 1 L 5 th hour 500- 1L 1 st 5 hours 3.5-5 L 6 th -12 th hour 250- 500 ml/ hr

22. INSULIN MODE OF ADMINISTRATION LOW DOSE vs. HIGH DOSE LONG ACTING vs. SHORT ACTING CONTINUOUS vs. INTERMITTENT

23. INSULIN WHY BOLUS INSULIN?? HOW IS IT CALCULATED?? HIGH DOSE vs. LOW DOSE BOLUS IS BOLUS NECESSARY?? PRECAUTION BEFORE BOLUS?? SECOND BOLUS??

24. INSULIN ACTION IN DKA INSULIN-MEDIATED GLUCOSE UPTAKE REDUCES HEPATIC GLUCONEOGENESIS REDUCES LIPOLYSIS INCREASES PERIPHERAL KETONE BODY USE PROMOTES BICARBONATE REGENERATION.

25. DOSE DEPENDENT INSULIN ACTION

26. TO CONTINUE INFUSION TILL… ACIDOSIS RESOLVES METABOLICALLY STABLE BLOOD GLUCOSE < 80MG/DL

27. TO INCREASE INFUSION…. INCREASE INFUSION – 1U/HR < 10% REDUCTION OF GLUCOSE NO IMPROVEMENT IN ABG AIM – REDUCE 50 -75 MG/HR

28. TO DECREASE INFUSION…. TO DECREASE THE INFUSION – 1-2U/HR GLUCOSE <250MG/DL >75MG/HR REDUCTION IMPROVED CLINICAL STATUS

29. AS PATIENT IMPROVES…. OVERLAP- INFUSION & SHORT-ACTING S.C KNOWN DIABETIC- RETURN TO PRIOR DOSE NEW DIABETIC- 0.6U/KG/DAY

30. TO START S.C.INSULIN WHEN ORAL INTAKE RESUMES ACIDOSIS RESOLVES SEPSIS SETTLED 8 HOURS AFTER FLUID CORRECTION BOTH PREMEAL AND BASAL

31. ORDER OF RECOVERY

32. POTASSIUM MAY BE HIGH / NORMAL / LOW MAINTAIN Sr. K+ AROUND 4-5meq/l INFUSION STARTED ONLY IF URINE OUTPUT IS GOOD – 50ml/ hr INCREASE THE DOSE IF CONCOMITANT HCO3 INFUSION

33. POTASSIUM CORRECTION SERUM POTASSIUM POTASSIUM REPLACEMENT <3.3 mEq /L 20-30 mEq /L/HR 3.3-<5.2 mEq /L 10 meq /l PER LITRE OF IV FLUID >5.2 mEq /L NO INFUSION. REPEAT EVERY 2 HOURS

34. POTASSIUM LOSS DURING TREATMENT INSULIN ASSOCIATED ACIDOSIS RENAL LOSS (K SALTS OF ACID)

35. BICARBONATE INDICATIONS Serum PH < 7 Shock or coma Serum HCO3 < 5 MEQ/L Acidosis induced cardiac dysfunction Severe hyperkalemia GIVE POTASSIUM SUPPLEMENTATION DILUTION 1:4

36. ADVERSE EFFECTS OF HCO3 overshoot alkalosis paradoxical cerebrospinal fluid acidosis hypokalemia volume overload alteration in tissue oxygenation overproduction of ketoacids INCREASED RISK OF CEREBRAL EDEMA IN CHILDREN

37. PHOSPHATES LOSS – MUSCLE WEAKNESS AND LETHARGY WORSENS WITH FLUID REPLACEMENT CORRECTION ONLY IF <1meq/l 1-2 WITH CARDIAC DYSFUCTION OR RESPIRATORY DEPRESSION HEMOLYSIS ORAL DIET - MILK

38. FLOWCHART TIME MENTATION BP PULSE RBS Na+ K+ Cl- HCO3 Ca++ PO4 AG KETONE ABG

39. LABORATORY PITFALLS KETONURIA LEUKOCYTOSIS HYPO OR HYPERNATREMIA HYPERTRIGLYCERIDEMIA HYPERKALEMIA HYPERAMYLASEMIA LIPASE ELEVATION DECREASED LEPTIN TROPONIN I

40. GENERAL MEASURES GASTRIC ASPIRATION CATHETERISATION ANTIBIOTICS O2 DELIVERY CVP

41. TREAT THE CAUSE SEARCH FOR THE SOURCE OF INFECTION IV ANTIBIOTICS

42. PROGNOSIS TIME LAPSE COMA & NEUROLOGICAL SYMPTOMS SEVERE SHOCK pH<6.8

43. COMPLICATIONS OF DKA CEREBRAL EDEMA LACTIC ACIDOSIS ARTERIAL THROMBOSIS REBOUND KETOACIDOSIS

44. ARTERIAL THROMBUS CORTICAL VEIN THROMBOSIS ISCHEMIC STROKE MYOCARDIAL INFARCTION MESENTRIC ISCHEMIA

45. REBOUND KETOACIDOSIS PREMATURE CESSATION OF IV INSULIN INFUSION INADEQUATE DOSES OF INSULIN AFTER CESSATION OF INFUSION HYPOGLYCEMIA REQUIRE BOTH BASAL AND PREMEAL INSULIN

46. DIFFERENTIAL DIAGNOSIS K - KETO ACIDOSIS U - UREMIA S - SALICYLATE POISONING S - STARVATION M - METHANOL POISONING A - ALCOHOL(ETHANOL) POISONING U - L - LACTIC ACIDOSIS

47. CLINICAL MANIFESTATIONS THAT MIMIC DKA ALTERED MENTAL STATUS HYPERVENTILATION GI SYMPTOMS CVA BRAIN STEM HEMORRHAGE GASTROENTERITIS HYPOGLYCEMIA UREMIA HHS SALICYLATE POISONING METHANOL POISONING ETHYLENE GLYCOL POISONING

48. SICK DAY RULES Frequently measure the capillary blood glucose Measure urinary ketones when the serum glucose 300 mg/ dL Drink fluids to maintain hydration Continue or increase insulin seek medical attention if SYMPTOMATIC.

49. DKA IN CKD MINIMAL DEHYDRATION POOR GFR- NO OSMOTIC DIURESIS FLUID AND POTASSIUM PULMONARY EDEMA INSULIN AND HEMODIALYSIS

50. DKA IN PREGNANCY RAPID ESTABLISHMENT OF DKA PRECIPITATING FACTORS KETOACIDS CROSS PLACENTA CONTINUOUS FETAL MONITORING INSULIN AND FLUIDS MgSO4

51. HYPEROSMOLAR HYPERGLYCEMIC STATE

52. INTRODUCTION CHARECTERISTICS FEATURES OF HHS INCLUDE MARKED HYPEROSMOLARITY 330-380MOSM/ML MARKED HYPERGLYCEMIA 600-1200MG% SEVERE DEHYDRATION : FLUID LOSS ALMOST 100-220ML/KG

53. HHS AND DKA ARE NOT MUTUALLY EXCLUSIVE AND THEY CAN AND OFTEN DO OCCUR SIMULTANEOUSLY . HHS IS PRIMARILY SEEN IN TYPE2 DM WHILE DKA PRESENT WITHIN HOURS OF ONSET, HHS DEVELOPES OVER MANY DAYS... AND DEHYDRATION AND METABOLIC DISTURBANCES ARE MORE EXTREME

54. WHY NO KETOSIS???

55. RELATIVE INSULIN DEFICIENCY PREVENTS BREAKDOWN OF FREE FATTY ACIDS HYPEROSMOLARITY ITSELF MAY DECREASE LIPOLYSIS LOWER LEVELS OF COUNTER REGULATORY HORMONES THAN DKA PORTAL VEIN INSULIN SUFFICIENT TO PREVENT KETOGENESIS IN LIVER

56. PRECIPITATING FACTORS

57. PRECIPITATING FACTORS

58. ON EXAMINATION EARLIER CALLED HYPEROSMOLAR NON KETOTIC COMA LEVEL OF CONSIOUSNESS: MAY VARY ALERT ..... DROWSY.....COMA LEVEL OF CONSIOUSNESS CORELATE WITH SERUM OSMOLARITY UNLIKE DKA PATIENT MAY PRESENT WITH SEIZURES

59. ASSESS VOLUME STATUS AND DEGREE OF DEHYDRATION PROFOUND DEHYDRATION: LONGER DURATION OF ILLNESS ABSENCE OF KUSSMAUL RESPIRATION

60. LABORATORY EVALUATION

61. S. CHLORIDE, PHOSPHATE: NORMAL PRERENAL AZOTEMIA OSMOLARITY = 2*( S.Na +S.K) + glucose(mg %)/18+ BUN/2.8 330-380 mosm /ml

62. S. BICARBONATE :NORMAL/ SLIGHT DECREASE PH > 7.3 ANION GAP : NORMAL TO SLIGHT INCREASE MODERATE KETONURIA IF PRESENT DUE TO STARVATION

63. TREATMENT GOALS To treat the underlying cause To gradually and safely : NORMALISE THE OSMOLALITY REPLACE FLUID AND ELECTROLYTES NORMALISE BLOOD GLUCOSE

64. THE OTHER GOALS INCLUDE PREVENTION OF: ARTERIAL AND VENOUS THROMBOSIS OTHER POTENTIAL COMPLICATIONS; cerebral edema / central pontine myelinolysis FOOT ULCERATION

65. FLUID MANAGEMENT THE GOAL OF INITIAL THERAPY IS TO EXPAND INTRAVASCULAR AND EXTRAVASCULAR VOLUME AND TO RESTORE THE PERIPHERAL PERFUSION AS THE MAJORITY OF ELECTROLYTE LOSSES ARE SODIUM , CHLORIDE AND POTASSIUM; THE BASE FLUID THAT SHOULD BE USED IS 0.9% NS WITH POTASSIUM ADDED AS REQUIRED RECENT STUDIES FAILED TO SHOW BENEFIT FROM USING RL COMPARED TO NS

66. TOO RAPID REVERSAL MAY WORSEN NEUROLOGICAL FUNCTION

67. INSULIN THERAPY All patients with HHS require insulin therapy , but immediate treatment with insulin is contraindicated in the initial management of HHS THE OSMOTIC PRESSURE THAT GLUCOSE EXERTS WITHIN VASCULAR SPACE MAINTAINS THE CIRCULATING VOLUME IN SEVERELY DEHYDRATED PATIENTS; IV INSULIN DRIVES GLU, POT, WATER INTO CELLS; RESULTING IN CIRCULATORY COLLAPSE IF FLUID HAS NOT BEEN REPLACED FIRST

68. INSULIN REGIMEN as in DKA.. IV BOLUS OF 0.1 UNITS/KG FOLLOWED BY INSULIN INFUSION AT CONSTANT RATE OF 0.1 UNITS /KG . DO NOT DISCONTINUE INSULIN DRIP , ADJUST THE DOSES.

69. SET THE TARGET BLOOD GLUCOSE AT 250-300MG% FOR ATLEAST ONE DAY. THIS TARGET LEVEL IS ADJUSTED DOWN WARD AFTER THE PATIENT IS STABILISED, CONSIOUS LEVEL IMPROVES. AFTER MAINTAINING ADEQUATE GLYCEMIC CONTROL WITH INSULIN FOR SEVERAL DAYS CONSIDER SWITCHING PATIENTS TO AN ORAL REGIMEN

70. NEUROLOGICAL MONITORING IS INDICATED IN ALL PATIENTS WITH HHS WHO PRESENTS WITH ALTERED SENSORIUM. HYPEROSMOLARITY TRIGGERS VARIOUS NEUROLOGICAL SYNDROMES IF PATIENT HAS SEIZURES, BZD ARE THE DRUG OF CHOICE IN HHS

71. ANTI PYRETICS, ANTIEMETICS, AND ANTIBIOTICS ARE ADDED TO CONTROL FEVER AND VOMITING AND TO TREAT UNDERLYING INFECTION IF ONE IS SUSPECTED

72. ALL PATIENTS SHOULD RECEIVE PROPHYLACTIC LOW MOLECULAR WEIGHT HEPARIN FOR FULL DURATION OF ADMISSION UNLESS CONTRAINDICATED FULL DOSE ANTICOAGULATION IS INDICATED ONLY IN PATIENTS SUSPECTED TO HAVE THROMBOSIS OR ACS

73. FOOT PROTECTION AND PREVENTION OF BEDSORES ELDERLY MALNOURISHED PATIENTS WHEN STARTED ON ORAL DIET MAY DEVELOPE REFEEDING SYNDROME . IF HYPOPHOSPHATEMIA PERSIST BEYOND ACUTE TREATMENT OF HHS REPLACEMENT SHOULD BE CONSIDERED