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Diabetic Ketoacidosis (DKA) & Hyperglycemic Hyperosmolar State (HHS) Ulrich K. Schubart, MD JMC/AECOM

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  • Diabetic Ketoacidosis (DKA) &Hyperglycemic Hyperosmolar State (HHS)

    Ulrich K. Schubart, MDJMC/AECOM

  • DKA/HHSPresenting SymptomsNausea and VomitingPolyuria and PolydipsiaWeakness and/or AnorexiaAbdominal PainVisual DisturbancesSomnolence

  • DKA/HHSPresenting SignsTachycardiaHypotensionDehydrationHypothermiaWarm dry SkinKussmaul RespirationLethargy or ComaFruity Odor

  • Compensatory Hyperventilation inDKAFrom UpToDateKety et al. JCI 1948

  • DKA/HHS Precipitating FactorsInfectionPneumoniaGastroenteritisUTISepsisMeningitisInfluenzaMucormycosis

    Emotional ProblemsTraumaAcute PancreatitisMyocardial InfarctionStrokeEndocrineAcromegalyThyrotoxicosisCushings S.Omission of Antidiabetic MxsDrugs

    Any major Stress/Acute Illness

  • DKA/HHS Drugs that can Precipitate

    Psychotropic DrugsChlorpromazineClozapineRisperidoneLoxapineSteroidsImmunosuppressantsBeta BlockersCalcium Channel BlockersDiureticsAnticonvulsantsDiazoxide

  • DKA/HHSPathogenesisPrecipitating FactorsGlucagonCatecholaminesCortisolGrowth HormoneAbsoluteInsulinDeficiencyRelativeInsulinDeficiencyLipolysisFFAsProteolysisGluconeogenesisKetogenesisGlycogenolysisMinimal LipolysisGluconeogenicSubstratesKetoacidosisHyperglycemiaHyperosmolalityGlucosuria(Osmotic Diuresis)Loss of Water& ElectrolytesTriglyceridesHyperlipidemiaDehydrationDecreased GFR

  • DKA/HHSEnhanced Glucose ProductionG-6-PcAMPGlycogenF-6-PF-1,6-P2PYRPFK-2FatCO2GlucoseAlanineF-2,6P2Glycerol

  • DKA/HHS Ketone Body Formation in LiverFatty AcidsFatty Acyl-CoATriglyceridesGlucoseFatty Acyl-CoAAcetyl-CoAAcetoacetyl-CoAb-Hydroxy-b-methylglutaryl CoAAcetoacetateb -HydroxybutyrateAcetoneNADHNAD

  • DKA/HHS Glucagon-inducedCatabolic Cascade in LiverGlycogenolysisGlycogen FormationGluconeogenesisGlycolysisFatty acyl CoAKetonesFattyAcidsMalonyl-CoAAcetyl-CoAGlucoseGlucoseACC

  • DKA/HHS Ketone Body Utilization in Muscleb -HydroxybutyrateAcetoacetateAcetoacetyl-CoAAcetyl-CoACitric Acid CycleSuccinyl-CoASuccinateCoAEXTACELLULAR MITOCHONDRIONb -HydroxybutyrateAcetoacetateFatty Acids

  • DKA/HHSGlucotoxicty & Lipotoxicity

    Relatively Short Term:Reversible Inhibition of:a)Glucose Uptake and Utilization inInsulin-Responsive Target Tissuesb)Insulin Secretion

    Long-term:a) & b) + Apoptosis of Beta-Cells

  • DKA/HHSEssential to R/o InfectionLook for meningeal signs - Head CT/MR followed by LP may be indicatedLook for necrotic lesions in nasal turbinates to r/o mucormycosisFor abdominal pain considerappendicitischolecystitispancreatitisdiverticulitisPIDObtain CXRCheck urine sediment

  • DKA/HHS HyperosmolalityMeasure and Calculate Serum Osmolality= 2 x measured Na+ (mEq/l) + glucose (mg/dl) /18 + BUN (mg/dl)/2.8

    Osmolar Gap = Measured Calculated Serum Osmolality

    Effective Serum OsmolalityOsmEff (>320 =HHS)= 2 x measured Na+ (mEq/l) + glucose (mg/dl) /18

  • DKA/HHS Sodium CorrectionCorrected Sodium =Measured Sodium +1.6 x plasma glucose (mg/dl) 100100

  • DKA/HHS Metabolic Acidosis

    Plasma Anion Gap =Na+ - [Cl- + HCO3-] (mEq/l)

  • DKA/HHSDiagnosis (Average Values)

  • DKA/HHSTypical Water and Electrolyte Deficits

  • DKA/HHSPoor Prognostic IndicatorsAdvanced AgeLow pHHypotensionMarked HyperosmolalityHigh BUNAssociated Diseases

  • DKA/HHSTreatment ConsiderationsPrecipitating Cause evident in 80%ECG indicated in all adult patientsIsotonic NaCl preferred for initial rehydrationIV Insulin preferred mode of administrationPotassium depletion in all patientsPrevention is long-term goal of managementBicarbonate administration rarely indicated

  • DKA/HHSOther Considerations in TxType & Cross-match as indicatedBlood (and other) Cultures as indicatedAspirate Gastric Contents if ComatoseCatherize if needed for Output MeasurementGive Oxygen if indicatedKeep patient NPO

  • DKA/HHSEssential Components in TxIV Fluids



  • DKA/HHSEssential Components in TxIV Fluids2-3 L 0.9% saline during first 3 hSubsequently, 0.45% saline at 150-300 ml/hAdd 5% dextrose when plasma glucose reaches 250 mg/dl

  • DKA/HHSEssential Components in TxInsulin 10 U/h iv infusion of short-acting insulinIncrease rate 2-10 fold if no response by 4 hDecrease to 1-2 U/h when acidosis is correctedAdminister sc insulin before stopping iv infusion

  • DKA/HHSEssential Components in TxPotassium10-20 mEq/h when plasma K
  • DKA/HHS Clinical Monitoring

  • DKA/HHSMonitoring Lab Values

  • DKA/HHSMonitoring Therapy

  • DKA/HHSStimulation of Glucose Utilization and Glycogen Formation byG-6-PGlycogenF-6-PF-1,6-P2PYRPFK-2FatCO2GlucoseF-2,6P2

  • DKA/HHS -inducedAnabolic Cascade in LiverGlycogenolysisGlycogen FormationGluconeogenesisGlycolysisFatty acyl CoAKetonesFattyAcidsMalonyl-CoAAcetyl-CoAGlucoseGlucoseCPT1TG

  • DKA/HHS Adverse Effects of Severe Acidosis

    Impaired Cardiac Contractility

    Decreased Response to Vasoconstrictors

    Inhibition of Respiration

  • DKA/HHS Potential Adverse Effect of Bicarbonate AdministrationSignificantly Increased Risk of Hypokalemia

    Decreased Tissue Oxygen Delivery

  • DKA/HHSIndications for ConsideringBicarbonate AdministrationpH < 7.0 or HCO3- < 5.0K+ > 6.5Hypotension refractory to fluid replacementSeverely impaired LV functionRespiratory depressionMarked late hyperchloremic acidosisSignificant lactic acidosis

  • Compensatory Hyperventilation inDKAFrom UpToDateKety et al. JCI 1948

  • DKA/HHSComplications of TherapyHypoglycemiaHypokalemia or HyperkalemiaFluid OverloadHyperchloremic AcidosisCerebral EdemaARDSThromboembolic Episodes

  • DKA/HHSPreventionEducation of Patient and Health Care Providers