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Dka by dr.irappa madabhavi

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  • 1. DIABETIC KETOACIDOSIS Andrew J. Bauer Pediatric Endocrinology WRAMC
  • 2. GOALS• REVIEW TYPE 1 DIABETES AND METABOLISM AS THEY RELATES TO DKA• CLINICAL DIAGNOSIS and MISLEADING LABS• TREATMENT and CONTROVERSIES• TREATMENT GUIDELINES
  • 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. Progression to Type 1 DM Autoimmune destruction Honeymoon 100% Islet loss “Diabetes threshold”
  • 5. Typical Presentation• Polyuria, polydypsia, weight loss• Vomiting• Rapid-deep respiration• CNS depression – coma• Precipitating event
  • 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. 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. Diagnostic Criteria• Blood glucose > 250 mg/dl• pH < 7.35• HCO3 < 20 mEq/L• Anion Gap > 12• ketonemia
  • 9. Etiology• Results from inadequate insulin – Accidental or intentional omission – Inappropriate intervention when stressed
  • 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. 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. 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. Pathophysiology Glucagon Epinephrine Cortisol Insulin Growth Hormone
  • 14. Pathophysiology Glucagon Epinephrine Insulin Cortisol Growth Hormone Dec Glucose Utilization Lipolysis
  • 15. Decreased Utilization DKA - Early ² post-prandial• Relative Insulin Deficiency and Stress-Induced² Glycogenolysis & hyperglycemiagluconeogenesis restrained Peripheral glucose uptake Elevates blood glucose
  • 16. Pathophysiology Glucagon Insulin Epinephrine Cortisol Growth Hormone Gluconeogenesis Glycogenolysis Lipolysis Ketogenesis
  • 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. 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. 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. 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. Misleading Labs• Sodium• Potassium• Ketones• WBC
  • 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. 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. 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. 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. 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. 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. 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. Let’s start treatment…..
  • 30. Controversies and Risks of Therapy • Fluids - composition, bolus amount and total fluids/day Cerebral • Use of Bicarbonate Edema • Phosphate replacement
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. **** **** ****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. 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. Elements of Therapy
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. “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. 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. EKG Changes During DKA NormalHi K Lo K
  • 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. 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