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Dka by dr.irappa madabhavi
The document discusses diabetic ketoacidosis (DKA), including its pathophysiology caused by a lack of insulin leading to gluconeogenesis, lipolysis, and ketone production. It outlines the clinical presentation of DKA with symptoms like vomiting, rapid breathing, and altered mental status. The treatment of DKA involves rehydration with intravenous fluids, administration of insulin to promote glucose uptake and utilization and reverse acidosis, and replacing electrolyte losses with sodium and potassium.
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Dka by dr.irappa madabhavi
- 1. DIABETIC KETOACIDOSIS Andrew J. Bauer Pediatric Endocrinology WRAMC
- 2. GOALS • REVIEW TYPE1 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 Type1 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….. • 9yo 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% ofnew 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 • Bloodglucose > 250 mg/dl • pH < 7.35 • HCO3 < 20 mEq/L • Anion Gap > 12 • ketonemia
- 9. Etiology • Results frominadequate insulin – Accidental or intentional omission – Inappropriate intervention when stressed
- 10. Etiology ² DKA violatesrules 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-RegulatoryHormones • Insulin Deficiency is the Primary defect • Stress hormones accelerate and exaggerate the rate and magnitude of metabolic decompensation Pathophysiology 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 Muscle Adipo- Amino Glucagon Increased Liver cytes 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-Induced ² Glycogenolysis & hyperglycemia gluconeogenesis 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. DKA Initial Evaluation • Hxand 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 labEvaluation • 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 labEvaluation • 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 Labs Potassium • Acidosisleads to flux of K+ out of cells as H+ enters cells to buffer • Dehydration and volume depletion – Aldosterone ² Na reabsorption and K+ wasting ² Serum K+ usually normal or high, but total body K+ is low
- 25. DKA- Risks ofTherapy Hypokalemia/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 Labs Screening forKetonemia • Urine Dip stick vs. anion gap/serum bicarb Sensitivity Specificity DKA 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 Labs WBC 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.
- 30. Controversies and Risksof Therapy • Fluids - composition, bolus amount and total fluids/day Cerebral • Use of Bicarbonate Edema • Phosphate replacement
- 31. DKA – Controversy CerebralEdema - 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 – CerebralEdema Actualities •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 – CerebralEdema Actualities • 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 – CerebralEdema Total 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/L ² Attention to fluid rate and tonicity is essential, but may not be sufficient to predict subset that will develop neurologic complications
- 35. DKA – CerebralEdema Total 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/L ² Attention to fluid rate and tonicity is essential, but may not be sufficient to predict subset that will develop neurologic complications
- 36. DKA – CerebralEdema 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 – CerebralEdema 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 space Neurosurg 21: 147-156, 1987
- 38. DKA – CerebralEdema Signs and Symptoms 1. Sudden and persistent drop in heart rate - not bradychardia - not assoc with HTN - not related to hydration status 2. Change in sensorium 7. Fall in serum 3. Headache Na, or failure 4. Emesis to rise 5. Incontinence 6. Unexplained tachypnea JCEM 85:509-513, 2000
- 39. DKA – CerebralEdema Evaluation • 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 – Risksof Therapy Bicarbonate 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 – Risksof 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 Phosphate Theoretical • Essential phosphate deficit • W/treatment serum phosphate and 2,3-DPG fall • Shift oxyhemoglobin curve reducing O2 deliver Practical • 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.
- 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 – Risksof Therapy Insulin 100% Biological 0.1 units/kg/hr effect Current therapy uses continuous insulin drip 100 uU/ml ² Drop glucose Insulin Level 50-100 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 Therapy Glucose -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. DKA Guidelines • Common groundto start from • Does not eliminate need to individualize therapy • Large deviations should be an opportunity to critically review clinical and therapeutic course
- 56. DKA Flowsheet • CIS isnot 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 labEvaluation • 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 Patientwith 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. DKA Prevention • 50% DKAadmissions 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 -Fluids Improved 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 -Fluids Improved 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….. • 7yo 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 DuringDKA Normal Hi K Lo K
- 65. DKA – CerebralEdema Other • 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. 1400 1200 1000 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