Hyperglycemia syndromesDiabetic KetoacidosisKetoacidosis-Hypersomolar ComaUTHSCSA Pediatric Resident Curriculum for the PICU
Spectrum of DKA and Hyperosmolar ComaPure KetoacidosisKetoacidosis-HyperosmolarComaPureHyperosmolarComaRapid OnsetMarked InsulinLackIntermediateSlow OnsetMild InsulinLack
Diabetic KetoacidosisHyperglycemia Ketonemia Metabolic Acidosis
PathophysiologyInsulin Deficiency is the primary defect in patients with DKAMuscleHepatocyteAdiposeGlucoseAminoAcidsGlucose-PGlycogenPyruvate, CO2GlucoseFreefattyacidsKetoacidsNormal Insulin Activity
Insulin DeficiencyBreakdown of storage forms of energy to meet energy needs. (Catabolism)GlycogenolysisLipolysisGluconeogenesis (from amino acids, lipids)Glucagon unopposed by Insulin stimulates this catabolic reaction
PathophysiologySkeletal and cardiac tissues are able to use free fatty acids and ketone bodies as an energy source.Glucose can not be used by these tissues in the absence of insulin.The brain is an insulin-independent tissue and continues to use available glucose.
Persistent CatabolismHyperglycemia is worsened by further intake of glucose.Excess Ketone bodies from LipolysisAcetone-hydroxybutyrate (BHB)Acetoacetate (AA)Ratio of BHB/AA normally 3:1 is driven to 15:1 in severe DKAKetone test measures only acetoacetate
Hyperosmolar StateHyperglycemia acts as an osmotic diuretic with obligatory loss of water and electrolytes.Osmolality = 2(Na) + Glucose/18 + BUN/2.8 (normal 293 )Ketosis/hyperglycemia stimulate vomiting with aggravation of dehydration
Hyperosmolar StateHypovolemia secondary to dehydration can promote decreased tissue perfusion with anaerobic metabolism and elevated lactate production Total fluid deficit in severe DKA usually averages around 10% of the total body weight
Electrolyte LossGlucoseKetoacidsKetoacids draw out intravascular cationsof Sodium and PotassiumIntracellular exchangeof potassium with hydrogen ionsH+K+Phosphorous is also depleted in the osmotic diuresisKIDNEY
Fluid Balance in DiabeticHyperosmolarityECF = 14 LICF = 28 LH2OECFICFH2OOsmotic DiuresisOsmotic DiuresisECF hyperosmolar from ICF autotransfusionECF and ICF both hyperosmolar
Clinical Findings in DKAPolyuria, Polydipsia, PolyphagiaDehydration + orthostasisVomiting (50-80%) Kssmaul respiration if pH < 7.2Temperature usually normal or low, if elevated think infection!Abdominal pain present in at least 30%.
Clinical Findings of HyperosmolarityLethargy, deliriumHyperosmolar coma is the first sign of diabetes in 50-60 % of adult patients.Hyperglycemia usually > 700-800mg/dlOsmolarity above 340 mOsm/L is required for coma to be present.
Precipitating Factors for HyperosmolarityToo little insulinInfection, even minor.Severe stress.Hypokalemia (Required by insulin).Inadequate fluid intakeInfancy (can not ask for fluids)Incapacitation (can not get to fluids/ask)
Laboratory Findings in DKA-HyperosmolarityGlucose > 700mg/dlTotal body sodium low, level high, normal or low.Potassium high, normal or low.Large urine ketonesBicarbonate < 15 mEq/L, pH < 7.2Leukocytosis 15,000-40,000 even without infection. High temp = infection.
Calculation of OsmolarityEffective Osmolarity(mOsm/L)2(Na = K) + Glucose (mg/dl)/20 = 280 - 295 mOsm/LA calculated osmolarity less than 340 mOsm/L is unlikely to cause coma. Other processes must beconsidered (stroke, infection, toxin).DKA does not cause coma in the absence of hyperosmolarity.
Effective OsmolarityThe effective osmolarity calculation uses only those biologically effective molecules which are able to draw water out of the cell.Urea and other molecules measured in the lab (alcohol) move freely between the intra and extravascular spaces and dont draw water out of the cell.
Approach to TherapyCorrecting the hyperosmolar state and dehydration is the initial aim of therapy.Insulin therapy should be undertaken only after the patient is stable hemodynamically.Glucose and H2OH2O lost in urineLoss of ECF, vascular collapse and death
RehydrationConsider most patients with DKA to be approximately 10% dehydrated.The difference between the patients weight at baseline and presentation is an accurate measure of volume loss.Normal Saline is the replacement fluid of choice to restore hemodynamics.
RehydrationBolus fluids until correction of circulatory failure.Correct deficit over 36 to 48 hours. Provide maintenance fluids (1600cc/m2/d) at the same time.Subtract resuscitation fluids from deficit.Avoid fluid administration > 4L/m2/d
ElectrolytesSodium content varies between 75 to 154 mEq/L. Reduce as sodium levels approach normal.Total body potassium is reduced. When K levels reach normal add 20-40 mEq/L as both KCL and Kphos.Maximum K infusion rate 0.5 mEq/kg/hr.
Insulin ReplacementInsulin is essential for lowering glucose to normal and correcting acidosis.Following initial fluid replacement, then administer 0.1U/kg IV and initiate an infusion at 0.1U/kg/hr. (Regular Insulin).Check serum glucose hourly and avoid dropping glucose > 100mg/dl/h.
Insulin ReplacementWhen serum glucose falls below 300 mg/dl, add 5% Dextrose to maintain stable glucose levels.Falling glucose should be managed with increased glucose concentration. Do not decrease insulin infusion until the metabolic acidosis is corrected.
BicarbonateShould only be used to treat symptomatic hyperkalemia.May be used for pH less than 7.0 to provide some relief of Kssmaul respiration (1mEg/kg over 1-2 hours).Inappropriate use may result in hypokalemia and paradoxical CNS acidosis.
IntubationMost patients requiring intubation have hypovolemia. Avoid drugs which lower blood pressure.Consider a small volume load first.For patients with cerebral edema, avoid medication which raise ICP (Ketamine, Succinylcholine). Consider Thiopental and Lidocaine.Have Mannitol available for sudden ICP.
Cerebral EdemaMay be sub-clinical at start of therapy. CSF pressure is usually normal initially.Usually occurs unpredictably within the first 24 hours of therapy.Classically, patients labs are improving.No way to determine who will get this complication.
PathophysiologyBrain conserves water by producing osmoprotective molecules (taurine).Osmolarity becomes disproportionately higher in the brain than other tissues.Sudden fall in serum osmolarity moves fluid across the blood-brain barrier.Brain becomes relatively hypervolemic.
Cerebral Edema-Clinical SignsInitial complaint of headache.Progresses to decreasing level of consciousness, hypertension, papilledema and bradycardia.Coma and death soon follow.Cerebral edema is a complication of therapy, not a progression of DKA.
Cerebral Edema - TherapyThe best therapy is to prevent it with careful rehydration.Diagnosis available with CT scan.Therapy for acute episode:Intubation and hyperventilationIV Mannitol 0.5 - 1.0 Gram/Kg as bolus.IV sedation.Slow the rate of osmolar correction.
Evaluation of TherapyControlled reduction in serum glucose.Correction of acidosis closing the gap.Clearing of serum ketones.Clinical improvementfall in respiratory rateimproved perfusionimproving mental status.
ComplicationsInfection esp. urinary tract infection.PancreatitisDisseminated intravascular coagulation. Arterial and venous thrombosis.Hypoglycemia with seizure.Hypokalemia with dysrhythmias.
Thromboembolism in DiabetesIn several studies, thromboembolism accounted for 20 to 50% of mortality.Virchows triad: stasis, endothelial damage and hypercoagulopathy.Hypercoagulopathy:Hyperreactivity of plateletsHyperfibrinogenemia (Especially Type 2)Elevated plasminogen activator (Type 2).
ThromboembolismEndothelial DamageElevated levels of von Willebrand factor associated with endothelial damageSeen in decompensated diabetes esp. those with microvascular diseaseCatheter placement Promotes venous stasisPotential endothelial damage
DKA in Type 2 DiabeticsRecent study: Arch of Internal Medicine39% of patients had Type 2 diabetes.Majority of patients with Type 2 diabetes were Hispanic.51% of patients were obeseType 2 diabetics more likely to have slow onset of ketoacidosis and progression to hyperosmolar coma.
DKA in Type 2 DiabetesHyperosmolarity, obesity, lethargy, and a relative hypercoagulopathy increase the propensity for EMBOLISM and THROMBOSIS in Type 2 diabetics.