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

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

Insulin

Potassium

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/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