Diabetic Ketoacidosis ManagementHeidi Chamberlain Shea, MDEndocrine Associates of Dallas
Goals of DiscussionPathophysiology of DKABiochemical criteria for DKATreatment of DKA Prevention of DKAHyperosmolar Nonketoic Syndrome
EpidemiologyAnnual incidence in U.S. 5-8 per 1000 diabetic subjects2.8% of all diabetic admissions are due to DKAOverall mortality rate ranges from 2-10%Higher is older patients
DKAPrecipitating FactorsFailure to take insulinFailure to increase insulinIllness/InfectionPneumoniaMIStrokeAcute stressTraumaEmotional
Medical StressCounterregulatory hormonesOppose insulinStimulate glucagon releaseHypovolmemiaIncreases glucagon and catecholaminesDecreased renal blood flowDecreases glucagon degradation by the kidney
Diabetic KetoacidosisDue to:Severe insulin deficiencyExcess counterregulatory hormonesGlucagonEpinephrineCortisolGrowth hormone
Role of InsulinRequired for transport of glucose intoMuscleAdiposeLiverInhibits lipolysisAbsence of insulinGlucose accumulates in the bloodLiver Uses amino acids for gluconeogenesisConverts fatty acids into ketone bodiesAcetone, Acetoacetate, -hydroxybutyrateIncreased counterregulatory hormones
Counterregulatory Hormones - DKA
Increases insulin resistanceActivates glycogenolysis and gluconeogenesisActivates lipolysisInhibits insulin secretionEpinephrineXXXXGlucagonXCortisolXXGrowth HormoneXXX
Insulin DeficiencyGlucose uptakeProteolysisLipolysisAmino AcidsGlycerolFree Fatty AcidsGluconeogenesisGlycogenolysisHyperglycemiaKetogenesisAcidosisOsmotic diuresisDehydration
Signs and Symptoms of DKAPolyuria, polydipsiaEnuresisDehydrationTachycardiaOrthostasisAbdominal painNauseaVomiting
Fruity breathAcetoneKussmaul breathingMental status changesCombativeDrunkComa
- Lab FindingsHyperglycemiaAnion gap acidosis(Na + K) (Cl + Bicarb) >12Bicarbonate
Differential Diagnosis Anion Gap AcidosisAlcoholic ketoacidosisLactic acidosisRenal failureEthylene glycol or methyl alcohol poisoningStarvation in late pregnancy or lactation (rare)
- Atypical PresentationsDKA can be present with BS
Treatment of DKAInitial hospital managementReplace fluid and electrolytesIV Insulin therapyGlucose administrationWatch for complicationsDisconnect insulin pumpOnce resolvedConvert to home insulin regimenPrevent recurrence
Treatment of DKAFluids and ElectrolytesFluid replacementRestores perfusion of the tissuesLowers counterregulatory hormonesAverage fluid deficit 3-5 litersInitial resuscitation1-2 liters of normal saline over the first 2 hoursSlower rates of 500cc/hr x 4 hrs or 250 cc/hr x 4 hours When fluid overload is a concernIf hypernatremia develops NS can be used
- Treatment of DKAFluids and ElectrolytesHyperkalemia initially presentResolves quickly with insulin dripOnce urine output is present and K 3.0 prior to start of insulinRemember to check magnesiumPhosphate deficitMay want to use KphosBicarbonate not given unless pH
Treatment of DKAInsulin TherapyIV bolus of 0.1-0.2 units/kg (~ 10 units) regular insulinFollow with hourly regular insulin infusionGlucose levels Decrease 75-100 mg/dl hourMinimize rapid fluid shiftsContinue IV insulin until urine is free of ketones
- Treatment of DKAGlucose AdministrationSupplemental glucoseHypoglycemia occursInsulin has restored glucose uptake Suppressed glucagonPrevents rapid decline in plasma osmolalityRapid decrease in insulin could lead to cerebral edemaGlucose decreases before ketone levels decreaseStart glucose when plasma glucose
Insulin-Glucose Infusion for DKA
Blood glucoseInsulin InfusionD5W Infusion50020.00
Complications of DKAInfectionPrecipitates DKAFeverLeukocytosis can be secondary to acidosisShockIf not improving with fluids r/o MIVascular thrombosisSevere dehydrationCerebral vesselsOccurs hours to days after DKAPulmonary EdemaResult of aggressive fluid resuscitation
Cerebral EdemaFirst 24 hoursMental status changesTx: MannitolMay require intubation with hyperventilation
Once DKA ResolvedTreatmentMost patients require 0.5-0.6 units/kg/dayPubertal or highly insulin resistant patients0.8-1.0 units/kg/dayLong acting insulin1/2-2/3 daily requirementNPH, Levemir or LantusShort acting insulin1/3-1/2 given at mealsRegular, Humalog, Novolog or Apidra
Once DKA ResolvedTreatmentGive SQ insulin at least 2 hours prior to stopping insulin infusion.Lantus or LevemirSteady state at 2-4 hrsShort acting analogs for meal timesIf transitioning to the pumpRestart the pump and after 30 minutes stop insulin infusionMay still be more insulin resistant so will need more than usual doseCheck blood sugars in 2 hrs Offer supplemental
I
Insulin Types and Action
INSULIN TYPE
ONSET OF ACTION
PEAK EFFECT
DURATION OF ACTION
Humalog
Novolog
Apidra
15 MIN
1 HOURS
3 HOURS
REGULAR
30 MIN
2-3 HOURS
4-6 HOURS
NPH
2-3 HOURS
6-8 HOURS
12-16 HOURS
LENTE
3-4 HOURS
8-12 HOURS
12-18 HOURS
Glargine
Detemir
1-2 hrs
24 hrs
Prevention of DKASick Day RulesNever omit insulinCut long acting in halfPrevent dehydration and hypoglycemiaMonitor blood sugars frequentlyMonitor for ketosisProvide supplemental fast acting insulinTreat underlying triggersMaintain contact with medical team
Preventing DKAEducationSick days or NPODo not stop insulin but adjustContinue basal insulinNPH insulin- decrease by 30-50%Use short actingQ2-3 hrs with Novolog, Humalog and ApidraQ4 hrs with regular insulinHyperglycemiaIf > 300 mg/dl, then check urine ketonesIf ketones positiveIncrease fluidsTake supplemental insulin Q2 hrsInsulin temperature sensitive< 77 degreesTeenagers, homeless, pen and pump usersDo not store insulin in the carTraveling and summer outdoor activitiesMay need to replace more frequently
Pump patientsIf blood sugars are increasing (>200 mg/dl)BolusCheck 2 hrs later, if climbingGive SQ correctionChange siteMake sure pump is workingChange insulinPump patients need long acting back up at home and when traveling
Pump patientsIf in DKADisconnect the pumpTransitioning back to pumpStart pump with basal x 2 hrs, then stop insulin dripCheck blood sugars every 2 hrs to make sure they are in range
Clinical TrialsImmune modulating studieswww.jdrf.orgwww.ClinicalTrials.govAnti CD3- monoclonal ABPhase 3 trialsNewly diagnosed Type 1 DiabetesCall Research Institute of Dallas 214-363-5535Immune modulating vaccinesStem cell and pancreas transplants
Goals of DiscussionPathophysiology of DKABiochemical criteria for DKATreatment of DKA Prevention of DKAHyperosmolar Nonketoic Syndrome
Hyperosmolar Nonketotic SyndromeExtreme hyperglycemia and dehydrationUnable to excrete glucose as quickly as it enters the extracellular spaceMaximum hepatic glucose output results in a plateau of plasma glucose no higher than 300-500 mg/dlWhen sum of glucose excretion plus metabolism is less than the rate which glucose enters extracellular space.
Hyperosmolar Nonketotic SyndromeExtreme hyperglycemia and hyperosmolarityHigh mortality (12-46%)At riskOlder patients with intercurrent illnessImpaired ability to ingest fluidsUrine volume fallsDecreased glucose excretionElevated glucose causes CNS dysfunction and fluid intake impairedNo ketonesSome insulin may be presentExtreme hyperglycemia inhibits lipolysis
Hyperosmolar Nonketotic Syndrome PresentationExtreme dehydrationSupine or orthostatic hypotensionConfusion comaNeurological findingsSeizuresTransient hemiparesisHyperreflexiaGeneralized areflexia
Hyperosmolar Nonketotic Syndrome PresentationGlucose >600 mg/dlSodiumNormal, elevated or lowPotassiumNormal or elevatedBicarbonate >15 mEq/LOsmolality >320 mOsm/L
Hyperosmolar Nonketotic Syndrome TreatmentFluid repletionNS 2-3 liters rapidlyTotal deficit = 10 litersReplete in first 6 hoursInsulinMake sure perfusion is adequate Insulin drip 0.1U/kg/hrTreat underlying precipitating illness
Clinical ErrorsFluid shift and shock Giving insulin without sufficient fluidsUsing hypertonic glucose solutionsHyperkalemiaPremature potassium administration before insulin has begun to act HypokalemiaFailure to administer potassium once levels fallingRecurrent ketoacidosis Premature discontinuation of insulin and fluids when ketones still presentHypoglycemiaInsufficient glucose administration
ConclusionSuccessful management requiresJudicious use of fluidsEstablish good perfusionInsulin dripSteady declineComplete resolution of ketosisElectrolyte replacementFrequent neurological evaluations High suspicion for complicationsDetermine etiology to avoid recurrent episodes
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