Diabetic Ketoacidosis (DKA) &Diabetic Ketoacidosis (DKA) &Hyperglycemic Hyperosmolar State Hyperglycemic Hyperosmolar State
(HHS)(HHS)
Ulrich K. Schubart, MD
JMC/AECOM
DKA/HHSDKA/HHSPresenting SymptomsPresenting Symptoms
Nausea and VomitingPolyuria and PolydipsiaWeakness and/or AnorexiaAbdominal PainVisual DisturbancesSomnolence
DKA/HHSDKA/HHSPresenting SignsPresenting SignsTachycardiaHypotensionDehydrationHypothermiaWarm dry SkinKussmaul RespirationLethargy or ComaFruity Odor
Compensatory Hyperventilation inDKA
From UpToDate
Kety et al. JCI 1948
DKA/HHSDKA/HHS Precipitating FactorsPrecipitating Factors
•InfectionPneumoniaGastroenteritisUTISepsisMeningitisInfluenzaMucormycosis
•Emotional Problems
•Trauma•Acute Pancreatitis•Myocardial Infarction•Stroke•Endocrine
AcromegalyThyrotoxicosisCushing’s S.
•Omission of Antidiabetic Mx’s•Drugs
Any major Stress/Acute Illness
DKA/HHSDKA/HHS Drugs that can PrecipitateDrugs that can Precipitate
•Psychotropic DrugsChlorpromazineClozapineRisperidoneLoxapine
•Steroids•Immunosuppressants•Beta Blockers•Calcium Channel Blockers•Diuretics•Anticonvulsants•Diazoxide
DKA/HHSDKA/HHSPathogenesisPathogenesis
Precipitating Factors
GlucagonCatecholaminesCortisolGrowth Hormone
AbsoluteInsulin
Deficiency
RelativeInsulin
Deficiency
Lipolysis
FFAs
Proteolysis
GluconeogenesisKetogenesis Glycogenolysis
Minimal Lipolysis
GluconeogenicSubstrates
Ketoacidosis Hyperglycemia HyperosmolalityGlucosuria
(Osmotic Diuresis)
Loss of Water& Electrolytes
Triglycerides
HyperlipidemiaDehydration
Decreased GFR
DKA/HHSDKA/HHSEnhanced Glucose ProductionEnhanced Glucose Production
G-6-P
cAMPGlycogen
F-6-P
F-1,6-P2
PYR
PFK-2
FatCO2
PKAGlucose
Alanine
F-2,6P2
PFK-1 F1,6BP
+
Glycerol
-
+
DKA/HHSDKA/HHS Ketone Body Formation in LiverKetone Body Formation in Liver
Fatty Acids
Fatty Acyl-CoA Triglycerides
Glucose
Fatty Acyl-CoA
Acetyl-CoA
Acetoacetyl-CoA
-Hydroxy--methylglutaryl CoA
Acetoacetate -Hydroxybutyrate
AcetoneNADH NAD
Insulin
DKA/HHSDKA/HHS Glucagon-inducedGlucagon-induced
Catabolic Cascade in LiverCatabolic Cascade in Liver
GlycogenolysisGlycogen Formation
GluconeogenesisGlycolysis
Fatty acyl CoA
Fatty AcidOxidation Ketones
FattyAcids Malonyl-CoA
Acetyl-CoA
Glucose Glucose
ACC
DKA/HHSDKA/HHS Ketone Body Utilization in MuscleKetone Body Utilization in Muscle
-Hydroxybutyrate
Acetoacetate
Acetoacetyl-CoA
Acetyl-CoA
Citric Acid Cycle
Succinyl-CoA
Succinate
CoA
NAD
NADH + H+
EXTACELLULAR MITOCHONDRION
-Hydroxybutyrate
Acetoacetate
Fatty Acids
DKA/HHSDKA/HHSGlucotoxicty & LipotoxicityGlucotoxicty & Lipotoxicity
1. Relatively Short Term:Reversible Inhibition of:
a) Glucose Uptake and Utilization inInsulin-Responsive Target Tissues
b) Insulin Secretion
2. Long-term:a) & b) + Apoptosis of Beta-Cells
DKA/HHSDKA/HHSEssential to R/o InfectionEssential to R/o Infection
Look for meningeal signs - Head CT/MR followed by LP may be indicated
Look for necrotic lesions in nasal turbinates to r/o mucormycosis
For abdominal pain consider appendicitischolecystitispancreatitisdiverticulitisPID
Obtain CXR Check urine sediment
DKA/HHSDKA/HHS HyperosmolalityHyperosmolality
Measure 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/HHSDKA/HHS Sodium CorrectionSodium Correction
Corrected Sodium =
Measured Sodium +
1.6 x plasma glucose (mg/dl) – 100
100
DKA/HHSDKA/HHS Metabolic AcidosisMetabolic Acidosis
Plasma Anion Gap =
Na+ - [Cl- + HCO3-] (mEq/l)
DKA/HHSDKA/HHSDiagnosis (Average Values)Diagnosis (Average Values)
DKA HHSPlasma Glucose (mg/dl)
Serum Na+ (mEq/l)
Serum K+ (mEq/l)
Serum HCO3- (mEq/l)
Arterial pH
pCO2
Anion Gap
Effective Serum Osmolality (mOsm/kg)
BUN (mg/dl)
Creatinine (mg/dl)
Urine Ketones
Plasma Ketones (positive)
616
134
4.5
9.4
7.12
20
17
310
30
1.1
Pos
1:16
930
149
3.9
18
7.30
35
11
360
65
1.4
Pos
1:1
From: Gerich et al. (1971) Diabetes 20:228
DKA/HHSDKA/HHSTypical Water and Electrolyte Typical Water and Electrolyte
DeficitsDeficitsDKA HHS
Total Water
Water (ml/kg)
Na+ (mEq/kg)
Cl- (mEq/kg)
K+ (mEq/kg)
PO4 (mmol/kg)
Mg++ (mEq/kg)
Ca++ (mEq/kg)
6
50-100
7-10
4-7
3-12
1
1
1
9
100-200
5-13
5-15
4-6
3-7
1-2
1-2
DKA/HHSDKA/HHSPoor Prognostic IndicatorsPoor Prognostic Indicators
Advanced AgeLow pHHypotensionMarked HyperosmolalityHigh BUNAssociated Diseases
DKA/HHSDKA/HHSTreatment ConsiderationsTreatment Considerations
Precipitating Cause evident in 80% ECG indicated in all adult patients Isotonic NaCl preferred for initial rehydration IV Insulin preferred mode of administration Potassium depletion in all patients Prevention is long-term goal of management Bicarbonate administration rarely indicated
DKA/HHSDKA/HHSOther Considerations in TxOther Considerations in Tx
Type & Cross-match as indicatedBlood (and other) Cultures as indicatedAspirate Gastric Contents if ComatoseCatherize if needed for Output
MeasurementGive Oxygen if indicatedKeep patient NPO
DKA/HHSDKA/HHSEssential Components in TxEssential Components in Tx
IV Fluids
Insulin
Potassium
DKA/HHSDKA/HHSEssential Components in TxEssential Components in Tx
IV 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/HHSDKA/HHSEssential Components in TxEssential Components in Tx
Insulin 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/HHSDKA/HHSEssential Components in TxEssential Components in Tx
Potassium10-20 mEq/h when plasma K<6.0, ECG
normal, urine flow documented40-80 mEq/h when plasma K <3.5 or if
bicarb is given
DKA/HHSDKA/HHS ClinicalClinical MonitoringMonitoring
Clinical Parameters Monitoring Interval
Mental Status
Vital Sg’s
Body Weight
ECG
1 h
1 h
6-12 h
As indicated
DKA/HHSDKA/HHSMonitoring Lab ValuesMonitoring Lab Values
Laboratory Monitoring IntervalGlucose
Potassium, pH
Sodium, Chloride, Bicarb
BUN, Creatinine
Phosphate, Magnesium
Urine Ketones
Calcium
Hematocrit
1 h
1-2 h
2-4 h
4-6 h
4-6 h
2-4 h
As indicated
As indicated
DKA/HHSDKA/HHSMonitoring TherapyMonitoring Therapy
Therapy Monitoring Interval
Fluid Intake & Output
Insulin (U/h)
Potassium (mEq/h)
Glucose (g/h)
Bicarb & Phos (mEq/h)
1-4 h
1-4 h
1-4 h
1-4 h
1-4 h
DKA/HHSDKA/HHSStimulation of Glucose Utilization Stimulation of Glucose Utilization
and Glycogen Formation byand Glycogen Formation by
G-6-P
Glycogen
F-6-P
F-1,6-P2
PYR
PFK-2
FatCO2
Glucose
F-2,6P2PFK-1 F1,6BP+
+
DKA/HHSDKA/HHS -induced-induced
Anabolic Cascade in LiverAnabolic Cascade in Liver
Glycogenolysis
Glycogen FormationGluconeogenesis
Glycolysis
Fatty acyl CoA
Fatty AcidOxidation
Ketones
FattyAcids
Malonyl-CoA
Acetyl-CoA
Glucose Glucose
CPT1 --
TG
DKA/HHSDKA/HHS Adverse Effects of Adverse Effects of Severe AcidosisSevere Acidosis
Impaired Cardiac Contractility
Decreased Response to Vasoconstrictors
Inhibition of Respiration
DKA/HHSDKA/HHS Potential Adverse Effect of Potential Adverse Effect of Bicarbonate AdministrationBicarbonate Administration
Significantly Increased
Risk of Hypokalemia
Decreased Tissue Oxygen Delivery
DKA/HHSDKA/HHSIndications for ConsideringIndications for ConsideringBicarbonate AdministrationBicarbonate Administration
pH < 7.0 or HCO3- < 5.0
K+ > 6.5Hypotension refractory to fluid replacementSeverely impaired LV functionRespiratory depressionMarked late hyperchloremic acidosisSignificant lactic acidosis
Compensatory Hyperventilation inDKA
From UpToDate
Kety et al. JCI 1948
DKA/HHSDKA/HHSComplications of TherapyComplications of Therapy
HypoglycemiaHypokalemia or HyperkalemiaFluid OverloadHyperchloremic AcidosisCerebral EdemaARDSThromboembolic Episodes
DKA/HHSDKA/HHSPreventionPrevention
Education of Patient and Health Care Providers
Recommended
