Dka by dr.irappa madabhavi

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Dka by dr.irappa madabhavi

  1. 1. DIABETIC KETOACIDOSIS Andrew J. Bauer Pediatric Endocrinology WRAMC
  2. 2. GOALS• REVIEW TYPE 1 DIABETES AND METABOLISM AS THEY RELATES TO DKA• CLINICAL DIAGNOSIS and MISLEADING LABS• TREATMENT and CONTROVERSIES• TREATMENT GUIDELINES
  3. 3. Type 1 DM• Autoimmune destruction of the pancreatic islet cell• Hallmark = lymphocytic infiltration of islets• Progresses over years• Leads to insulin deficiency• Later may be associated with glucagon deficiency as well
  4. 4. Progression to Type 1 DM Autoimmune destruction Honeymoon 100% Islet loss “Diabetes threshold”
  5. 5. Typical Presentation• Polyuria, polydypsia, weight loss• Vomiting• Rapid-deep respiration• CNS depression – coma• Precipitating event
  6. 6. “Typical” Setting…..• 9 yo boy presents to clinic with CC “ 6 day history of stomach pain and diarrhea.” “Vomiting started 2 days ago and has persisted.” – (+) weight loss – PE: HR 140, RR 28, T97.8 Weight: 27 Kg • Tachy mucous membranes • Abd - soft, (+)BS, mild left CVA tenderness – DX: viral gastroenteritis with mild dehydration• Returned to ER 24 hours later – PE: cachectic, quiet, tired, cooperative, (+) ketotic breath
  7. 7. Background• 15-30% of new diabetics present in DKA – < 4 yrs of age = 40% with DKA @ diagnosis• Most common cause of death in diabetics less than 20 years of age – 70% of related deaths in diabetics less than 10 yrs of age• Mortality: 5-15% (1-2% at MEDCEN)• Preventable
  8. 8. Diagnostic Criteria• Blood glucose > 250 mg/dl• pH < 7.35• HCO3 < 20 mEq/L• Anion Gap > 12• ketonemia
  9. 9. Etiology• Results from inadequate insulin – Accidental or intentional omission – Inappropriate intervention when stressed
  10. 10. Etiology² DKA violates rules of common sense • Increased insulin requirement despite decreased food intake • Marked urine output in setting of dehydration • Catabolic state in setting of hyperglycemia and hyperlipidemia
  11. 11. Pathophysiology Counter-Regulatory Hormones • Insulin Deficiency is the Primary defect • Stress hormones accelerate and exaggerate the rate and magnitude of metabolic decompensationPathophysiology Hormone• Impaired insulin secretion Epi• Anti-insulin action Epi, cortisol, GH• Promoting catabolism All• Dec glucose utilization Epi, cortisol, GH
  12. 12. Islets of β-cell destruction Insulin Deficiency Langerhans l Ep i,Cortiso Decreased Glucose Utilization & Stress GH Increased Production MuscleAdipo- Amino Glucagon Increased Livercytes Acids Protein Catabolism Increased Ketogenesis FattyAcids Gluconeogenesis, IncreasedLipolysis Glycogenolysis Polyuria Threshold 180 mg/dl Hyperglycemia Volume Depletion Ketoacidosis Ketonuria HyperTG
  13. 13. Pathophysiology Glucagon Epinephrine Cortisol Insulin Growth Hormone
  14. 14. Pathophysiology Glucagon Epinephrine Insulin Cortisol Growth Hormone Dec Glucose Utilization Lipolysis
  15. 15. Decreased Utilization DKA - Early ² post-prandial• Relative Insulin Deficiency and Stress-Induced² Glycogenolysis & hyperglycemiagluconeogenesis restrained Peripheral glucose uptake Elevates blood glucose
  16. 16. Pathophysiology Glucagon Insulin Epinephrine Cortisol Growth Hormone Gluconeogenesis Glycogenolysis Lipolysis Ketogenesis
  17. 17. DKA - Late Increased Production & Decreased Utilization• Insulin Deficiency ² Fasting Glycogenolysis hyperglycemia Gluconeogenesis Hepatic glucose output Peripheral glucose uptake Elevates blood glucose Lipolysis Release FFA -> liver VLDL & ketones Ketonemia and hyperTG ² Acidosis & Diuresis
  18. 18. DKAInitial Evaluation• Hx and PE - – Duration of onset – Level of dehydration Osmolality = 2 x (Na + K) – Evidence of infection + Glucose/18• Labs - STAT + BUN/3 – Electrolytes – Venous blood gas – Serum Osmolality – U/a
  19. 19. 9 yo lab Evaluation• 148| 109| 32 16.8 518 700 24.4 5.6 | <5 | 1.4 47.5• Blood Gas - pH 7.0 5/1.020 Glu >1000, (+) Ketones
  20. 20. 9 yo lab Evaluation• 148| 109| 32 16.8 518 700 24.4 5.6 | <5 | 1.4 47.5• Blood Gas - pH 7.0 5/1.020 Glu >1000, (+) Ketones
  21. 21. Misleading Labs• Sodium• Potassium• Ketones• WBC
  22. 22. Misleading Labs Sodium• Na+ depressed 1.6 mEq/L per 100 mg% glucose• Corrected Na+ = measured Na + 1.6 meq/L x (glucose-100)/100))• Example: – Na+ = 123 meq/L and Glucose = 1,250 mg/dl – 1,250 – 100 = 1,150 / 100 = 11.5 x 1.6 = 18 meq/L – Corrected Na+ = 123 + 18 = 141 meq/L
  23. 23. Misleading Labs Sodium• Triglycerides also artificially lower Na Lipid Lipid Na Na Na Na Na Na Serum Na Na Na Na Na Gluc Na Na Gluc
  24. 24. Misleading LabsPotassium• Acidosis leads to flux of K+ out of cells as H+ enters cells to buffer• Dehydration and volume depletion – Aldosterone ² Na reabsorption and K+ wasting² Serum K+ usually normal or high, but total body K+ is low
  25. 25. DKA- Risks of TherapyHypokalemia/Hyperkalemia• With insulin therapy – K+ moves into cells (1 meq/L / 0.1 unit pH )• Even with K+ you must – Give large doses (40 meq/L) K+ – Monitor K+ levels and EKG • High K - tall peaked T, long PR, wide QRS • Low K - depressed ST, diphasic T, Prom U-wave – Cardiac dysrythmia
  26. 26. Misleading Labs Ketones• In the absence of insulin, FFA go to the liver, and Nitroprusside reaction into mitochondria via carnitine• ß-oxidation excess acetylCoA• Acetyl-CoA condenses to acetoacetate• Insulin prevents utilization of acetoacetate• so levels and shunt to ß-hydroxybutyrate and acetone
  27. 27. Misleading LabsScreening for Ketonemia• Urine Dip stick vs. anion gap/serum bicarb Sensitivity SpecificityDKA 99 % 69 %² Diabetic with minor signs and symptoms and negative urine ketone dip stick is unlikely to have acidosis = high negative predictive value for excluding DKA Am J Emer Med 34: 1999
  28. 28. Misleading LabsWBC count• N = 247 DKA admissions over 6 years – Mean WBC = 17,519/mm3 (+/- 9,582) – 69% without infection – 17.8% presumed viral infection – 12.9% bacterial infection - more common in children < 3 years of age ² All need to be evaluated and re-evaluated if persistent acidosis Am J Emer Med 19: 270-3, 2001
  29. 29. Let’s start treatment…..
  30. 30. Controversies and Risks of Therapy • Fluids - composition, bolus amount and total fluids/day Cerebral • Use of Bicarbonate Edema • Phosphate replacement
  31. 31. DKA – ControversyCerebral Edema - Truths ? Acute • Idiogenic osmoles in CNS accumulate fluid • Cerebral edema – present in 100% of patients prior to therapy • Treatment exacerbates cerebral edema – Vigorous fluid administration Late Sequelae – Hypotonic fluids – Bicarbonate
  32. 32. DKA – Cerebral EdemaActualities•Etiology is not known•Occurs exclusively in pediatric patients•Mortality Rate = 21%•Morbidity Rate = 27% (permanent neurologic sequelae)² Difficulty is relatively rare occurrence (1-3 %) with subsequent small numbers of patients in retrospective or prospective studies
  33. 33. DKA – Cerebral EdemaActualities• NEJM - Jan 2001 – N = 6977 DKA patients from 10 centers over 15 years – 61 developed cerebral edema (0.9%)• Pediatrics - Sep 2001 – N = 520 DKA patients over 5 1/2 years – 2 developed cerebral edema
  34. 34. DKA – Cerebral EdemaTotal Fluids• > 4 L/m2/day, or > 50 ml/kg in first 4 hrs α JCEM 85:509-513, 2000 J Peds 113:10-14, 1988 hyponatremia α herniation – May occur in patients that receive less – Of 52 patients with neurologic complications 21 had either a rise of serum Na or fall less than 4 mmol/L² Attention to fluid rate and tonicity is essential, but may not be sufficient to predict subset that will develop neurologic complications
  35. 35. DKA – Cerebral EdemaTotal Fluids• > 4 L/m2/day, or > 50 ml/kg in first 4 hrs α JCEM 85:509-513, 2000 J Peds 113:10-14, 1988 hyponatremia α herniation – May occur in patients that receive less – Of 52 patients with neurologic complications 21 had either a rise of serum Na or fall less than 4 mmol/L² Attention to fluid rate and tonicity is essential, but may not be sufficient to predict subset that will develop neurologic complications
  36. 36. DKA – Cerebral Edema Variable Time of Onset# of Children with Neurologic Deterioration 7 Prior to therapy; longer duration 6 symptoms before diagnosis 5 4 3 2 NEJM 344:264-69, 2001 1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 25 Hours after Initiation of Therapy
  37. 37. DKA – Cerebral Edema Other • Hypoxemia – Children’s brains have higher oxygen requirement, 5.1 mL/100g vs. 3.3 mL/100g – Hypophosphatemia with resultant decreased 2,3-DPG decreases O2 delivery to brain cells – Mannitol - earliest effects are related to decreased viscosity, not to shift of fluid from extravascular spaceNeurosurg 21: 147-156, 1987
  38. 38. DKA – Cerebral EdemaSigns and Symptoms1. Sudden and persistent drop in heart rate - not bradychardia - not assoc with HTN - not related to hydration status2. Change in sensorium 7. Fall in serum3. Headache Na, or failure4. Emesis to rise5. Incontinence6. Unexplained tachypnea JCEM 85:509-513, 2000
  39. 39. DKA – Cerebral EdemaEvaluation• CT may be non-diagnostic at time of symptoms – 9 of 30 - no edema, 6 read as normal – 5 of 9 - 2.5 to 8 hours after onset of coma, read as normal ² Cerebral Edema is a clinical diagnosis. Need to treat BEFORE imaging. JCEM 85:509-513, 2000
  40. 40. DKA – Risks of TherapyBicarbonate Administration• Administration to acidotic patient generates rapid rise in CO2• CO2 enters CNS rapidly• HCO3- is delayed by blood-brain barrier• Increased CNS CO2 exacerbates cerebral acidosis CO2 + H2O H2CO3 H+ + HCO3-• May also reduce partial pressure of O2 in CSF
  41. 41. DKA – Risks of Therapy Bicarbonate Administration• Multi-center study from 10 pediatric centers, USA and Melbourne, Australia over 15 yr period – 6977 DKA hospitalizations: 61 cases cerebral edema (0.9%)• Presentation: PaCO2 BUN Glucose Bicarb Cerebral Edema 11.3 27 758 23/61 (32%) Controls 15.1 21 700 43/174 (23%)∀ ≠ fluid, insulin, or sodium administration, nor rate of fall in glucose was associated NEJM 344:264-269, 2001
  42. 42. **** **** ****DKA – Risks of Therapy **** **** **** ********Bicarbonate Administration• Variations in treatment exacerbate an on-going pathologic process• Brain ischemia is major underline etiology – Hyperglycemia increases extent of neurologic damage – Extreme dehydration, hypocapnia – Concept of idiogenic osmotically active substances not supported (no relationship to change in glucose, rate of fluid or Na administration) ² Risk related to duration and severity of DKA NEJM 344:264-269, 2001
  43. 43. DKA- Controversy PhosphateTheoretical • Essential phosphate deficit • W/treatment serum phosphate and 2,3-DPG fall • Shift oxyhemoglobin curve reducing O2 deliverPractical • No evidence of direct benefit, but less Cl- • Give ½ K+ replacement as K-phos x 8 hours • Limit to 2 mEq/kg/day to avoid hypocalcemia Endo Met Clin 29:Dec 2000
  44. 44. Elements of Therapy
  45. 45. Elements of Therapy• Fluids – treat shock, then sufficient to reverse dehydration and replace ongoing losses (will correct hyperglycemia)• Insulin – sufficient to suppress ketosis, reverse acidosis, promote glucose uptake and utilization (will stop ketosis)• Electrolytes – replace profound Na+ and K+ losses
  46. 46. Typical Therapy - Fluids• 10% dehydration is standard estimate (use vweight if known) – Bolus: treat shock, usual 20-30cc/kg given 10cc/kg at a time – Replace deficit over 48-72 hours – ie. 10 % in 20 Kg pt = 2000ml over 48hrs = maintenance + 42cc/hr x 48 hours
  47. 47. Typical Therapy - Fluids• Use ½ NS to NS• Average = 2 x maintenance – 4:2:1 cc/kg/hr or 100:50:20 cc/kg/day – ie. 25 kg patient • (4 x 10) + (2 x 10) + (1 x 5) = 65 cc/hr • (100 x 10) + (50 x 10) + (20 x 5)/24 hours = 66.7 cc/hr
  48. 48. DKA – Risks of Therapy Insulin 100% Biological 0.1 units/kg/hr effectCurrent therapy usescontinuous insulin drip 100 uU/ml² Drop glucose Insulin Level50-100 mg/dl/hr
  49. 49. Typical Therapy - Insulin• 0.1 unit/kg/hr continuous drip (regular) – Flush tubing with 50 ml – 250 units regular in 250 cc NS (1.0 units/ ml) = 0.1 u/kg/hr = 0.1 ml/kg/hr
  50. 50. Typical TherapyGlucose - 2 Bag Method• Goal - decrease blood glucose by 50-100 mg/dl/hr• Must continue insulin therapy to correct acidosis• Order D10 NS to bedside – when serum glucose < 300: add D5NS ( = 1/2 D10NS + maintenance bag) – when serum glucose < 200: Change to D10NS
  51. 51. Typical Therapy• K+ 40 meq/L (split between KCl and Kphos)• Reverse insulin resistance – Treat infection – Treat underlying illness - stress• Bicarb - only if severe circulatory failure and high risk of cardiac decompensation from profound acidosis
  52. 52. Monitor• ICU - pH < 7.3 and/or HCO3 < 15• Available staff• Strict I/O (NPO) – Fluid calculations must account for ongoing losses – vomiting, diarrhea, excessive urine – ? If > 4 L/m2/day• CNS activity - headache, change in sensorium
  53. 53. Monitor• Vitals - sudden drop in HR, tachypnea• Neurologic checks - q30-60 minutes• Weight - bid• Labs – dstick q1 hour – Urine dip q void - resolution of ketonuria may lag behind clinical improvement
  54. 54. Monitor• Labs – Lytes, VBG q 2-4 hours ² Drop in Na - increase risk of cerebral edema, ? SIADH vs. cerebral salt wasting ² HCO3- / pH in first 2-3 hours may drop further due to re-perfusion of tissue, lactic acidosis
  55. 55. DKAGuidelines• Common ground to start from• Does not eliminate need to individualize therapy• Large deviations should be an opportunity to critically review clinical and therapeutic course
  56. 56. DKAFlowsheet• CIS is not a flow sheet, but rather a database• Inability to review all data at one time decreases ability to make sound decisions• Maintenance of flowsheet is the first step in critical analysis of response to therapy
  57. 57. 9 yo lab Evaluation• 27 Kg - assume 10% dehydrated• 148| 109| 32 16.8 518 700 24.4 5.6 | <5 | 1.4 47.5• Anion Gap = • Fluid Def =• Osm = • Maintenance =• Corrected Na = • IV rate (24hrs) =
  58. 58. Transport of Patient with DKA• 2 large bore PIV• Must have documentation of previous treatments – PE with vitals and notes on mental status – Fluids - bolus and current – ? SQ Insulin given - time and amount – Contact phone number for labs/cultures• Must have glucagon, mannitol and IV glucose with patient at ALL times
  59. 59. DKAPrevention• 50% DKA admissions are in known diabetics• Failure of Physician-Patient relationship – non-compliance – Inappropriate intervention – Sick day rules need to be understood and followed – Availability is essential
  60. 60. Typical Therapy - FluidsImproved Management ?• All patients given 20 cc/kg NS bolus over 30-45 minutes• Started on 0.1 units/kg/hour Insulin without bolus• Fluids - 2.5 x maintenance of 3/4 NS regardless of degree of dehydration• Glucose used to maintain insulin rate Pediatrics 108: 735-740; 2001
  61. 61. Typical Therapy - FluidsImproved Management ?• Outcome – 23 % fewer fluid changes = decreased error risk – Mean total fluids in first 24 hours lower (5 vs 4 l/m2/day) – Dec time to resolve acidosis shorter (16 vs 12 hours) ?? – Reduced fluid cost ($1060 to $776) Pediatrics 108: 735-740; 2001
  62. 62. “Typical” Setting…..• 7 yo boy with 24 hour history of n/v/d. Diagnosed with IDDM 2 yrs ago. Woke up with moderate ketones and dstick of 350 mg/dl. – Is this DKA ? – What is your responsibility ?• 12 yo patient on CSII. Last 4 hours dsticks increasing from 120 to 450 mg/dl. Now complaining of headache and nausea. Large ketones on dip-stick.
  63. 63. DKA• Acidosis – Primary buffer is intracellular protein – K+ moves out of cells and H+ moves in – In association with aldosterone (induced from hypovolemia) • Potentiates K+ wasting ²² Hypokalemia
  64. 64. EKG Changes During DKA NormalHi K Lo K
  65. 65. DKA – Cerebral EdemaOther• Insulin associated activation of Na+/H+ pump – Not commonly found during initial treatment – As acidosis resolves, H+ diffuses out of brain cells and Na+ enters (along with H20) – Rabbit model - drop in glucose secondary to insulin administration vs. peritoneal dialysis results in cerebral edema
  66. 66. 140012001000 800 Glucose 600 400 200 0 12 1 2 3 4 5 6 7 8 7 6.5 6 5.5 5 K 4.5 4 3.5 3 12 1 2 3 4 5 6 7 8 8 7.5 7 pH 6.5 6 12 1 2 3 4 5 6 7 8

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