Diabetic Ketoacidosis (DKA) &
Hyperglycemic Hyperosmolar State
(HHS)
Ulrich K. Schubart, MD
JMC/AECOM
DKA/HHS
Presenting Symptoms

Nausea and Vomiting
 Polyuria and Polydipsia
 Weakness and/or Anorexia
 Abdominal Pain
 Visual Disturbances
 Somnolence
DKA/HHS
Presenting Signs

Tachycardia
 Hypotension
 Dehydration
 Hypothermia
 Warm dry Skin
 Kussmaul Respiration
 Lethargy or Coma
 Fruity Odor
Compensatory Hyperventilation in
DKA
From UpToDate
Kety et al. JCI 1948
DKA/HHS
Precipitating Factors
Any major Stress/Acute Illness
•Infection
Pneumonia
Gastroenteritis
UTI
Sepsis
Meningitis
Influenza
Mucormycosis
•Emotional Problems
•Trauma
•Acute Pancreatitis
•Myocardial Infarction
•Stroke
•Endocrine
Acromegaly
Thyrotoxicosis
Cushing’s S.
•Omission of Antidiabetic Mx’s
•Drugs
DKA/HHS
Drugs that can Precipitate
•Psychotropic Drugs
Chlorpromazine
Clozapine
Risperidone
Loxapine
•Steroids
•Immunosuppressants
•Beta Blockers
•Calcium Channel Blockers
•Diuretics
•Anticonvulsants
•Diazoxide
DKA/HHS
Pathogenesis
Absolute
Insulin
Deficiency
Precipitating Factors
Glucagon
Catecholamines
Cortisol
Growth Hormone
Lipolysis
Proteolysis
FFAs
Gluconeogenic
Substrates
Ketogenesis
Ketoacidosis
Triglycerides
Hyperlipidemia
Gluconeogenesis
Hyperglycemia
Relative
Insulin
Deficiency
Minimal Lipolysis
Glycogenolysis
Hyperosmolality
Glucosuria
(Osmotic Diuresis)
Decreased GFR
Loss of Water
& Electrolytes
Dehydration
DKA/HHS
Enhanced Glucose Production
cAMP
Glycogen
+
G-6-P
+
PKA
-
Glucose
PFK-2
F-6-P
F-2,6P2
PFK-1
F1,6BP
F-1,6-P2
Glycerol
Alanine
PYR
CO2
Fat
DKA/HHS
Ketone Body Formation in Liver
Glucose
Fatty Acids
Fatty Acyl-CoA
Insulin
Triglycerides
Fatty Acyl-CoA
Acetyl-CoA
Acetoacetyl-CoA
b-Hydroxy-b-methylglutaryl CoA
Acetoacetate
NADH
Acetone
b -Hydroxybutyrate
NAD
Glucose
DKA/HHS
Glucagon-induced
Catabolic Cascade in Liver
Glycogenolysis
Gluconeogenesis
Glycogen Formation
Fatty
Acids
Glycolysis
Fatty acyl CoA
Malonyl-CoA
ACC
Fatty Acid
Oxidation
Acetyl-CoA
Ketones
Glucose
DKA/HHS
Ketone Body Utilization in Muscle
EXTACELLULAR
b -Hydroxybutyrate
MITOCHONDRION
b -Hydroxybutyrate
NAD
NADH
Acetoacetate
Acetoacetate
+ H+
Succinyl-CoA
Succinate
Acetoacetyl-CoA
CoA
Fatty Acids
Acetyl-CoA
Citric Acid Cycle
DKA/HHS
Glucotoxicty & Lipotoxicity
1.
Relatively Short Term:
Reversible Inhibition of:
a) Glucose Uptake and Utilization in
Insulin-Responsive Target Tissues
b) Insulin Secretion
2.
Long-term:
a) & b) + Apoptosis of Beta-Cells
DKA/HHS
Essential 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
appendicitis
cholecystitis
pancreatitis
diverticulitis
PID
 Obtain CXR
 Check urine sediment
DKA/HHS
Hyperosmolality
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 Osmolality
OsmEff (>320 =HHS)
= 2 x measured Na+ (mEq/l) + glucose (mg/dl) /18
DKA/HHS
Sodium Correction
Corrected Sodium =
Measured Sodium +
1.6 x plasma glucose (mg/dl) – 100
100
DKA/HHS
Metabolic Acidosis
Plasma Anion Gap =
Na+ - [Cl- + HCO3-] (mEq/l)
DKA/HHS
Diagnosis (Average Values)
Plasma 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)
DKA
HHS
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/HHS
Typical Water and Electrolyte
Deficits
Total Water
Water (ml/kg)
Na+ (mEq/kg)
Cl- (mEq/kg)
K+ (mEq/kg)
PO4 (mmol/kg)
Mg++ (mEq/kg)
Ca++ (mEq/kg)
DKA
HHS
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/HHS
Poor Prognostic Indicators

Advanced Age
 Low pH
 Hypotension
 Marked Hyperosmolality
 High BUN
 Associated Diseases
DKA/HHS
Treatment 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/HHS
Other Considerations in Tx

Type & Cross-match as indicated
 Blood (and other) Cultures as indicated
 Aspirate Gastric Contents if Comatose
 Catherize if needed for Output
Measurement
 Give Oxygen if indicated
 Keep patient NPO
DKA/HHS
Essential Components in Tx
 IV Fluids
 Insulin
 Potassium
DKA/HHS
Essential Components in Tx
IV Fluids

2-3 L 0.9% saline during first 3 h
 Subsequently, 0.45% saline at 150-300 ml/h
 Add 5% dextrose when plasma glucose
reaches 250 mg/dl
DKA/HHS
Essential Components in Tx
Insulin

10 U/h iv infusion of short-acting insulin
 Increase rate 2-10 fold if no response by 4 h
 Decrease to 1-2 U/h when acidosis is
corrected
 Administer sc insulin before stopping iv
infusion
DKA/HHS
Essential Components in Tx
Potassium

10-20 mEq/h when plasma K<6.0, ECG
normal, urine flow documented
 40-80 mEq/h when plasma K <3.5 or if
bicarb is given
DKA/HHS
Clinical Monitoring
Clinical Parameters
Monitoring Interval
Mental Status
Vital Sg’s
Body Weight
ECG
1h
1h
6-12 h
As indicated
DKA/HHS
Monitoring Lab Values
Laboratory
Glucose
Potassium, pH
Sodium, Chloride, Bicarb
BUN, Creatinine
Phosphate, Magnesium
Urine Ketones
Calcium
Hematocrit
Monitoring Interval
1h
1-2 h
2-4 h
4-6 h
4-6 h
2-4 h
As indicated
As indicated
DKA/HHS
Monitoring 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/HHS
Stimulation of Glucose Utilization
and Glycogen Formation by
Glycogen
+
G-6-P
Glucose
PFK-2
F-6-P
F-2,6P2
+
PFK-1
F1,6BP
F-1,6-P2
CO2
PYR
Fat
DKA/HHS
-induced
Anabolic Cascade in Liver
Glucose
Glycogenolysis
Gluconeogenesis
Glycogen Formation
Fatty
Acids
Glycolysis
Fatty acyl CoA
-
Malonyl-CoA
Fatty Acid
Oxidation
Acetyl-CoA
CPT1
TG
Ketones
Glucose
DKA/HHS
Adverse Effects of Severe Acidosis
 Impaired
Cardiac Contractility
 Decreased
Response to Vasoconstrictors
 Inhibition
of Respiration
DKA/HHS
Potential Adverse Effect of
Bicarbonate Administration

Significantly Increased
Risk of Hypokalemia

Decreased Tissue Oxygen Delivery
DKA/HHS
Indications for Considering
Bicarbonate Administration
 pH < 7.0 or HCO3- < 5.0
 K+ > 6.5
 Hypotension refractory to fluid replacement
 Severely impaired LV function
 Respiratory depression
 Marked late hyperchloremic acidosis
 Significant lactic acidosis
Compensatory Hyperventilation in
DKA
From UpToDate
Kety et al. JCI 1948
DKA/HHS
Complications of Therapy

Hypoglycemia
 Hypokalemia or Hyperkalemia
 Fluid Overload
 Hyperchloremic Acidosis
 Cerebral Edema
 ARDS
 Thromboembolic Episodes
DKA/HHS
Prevention

Education
of Patient and Health Care Providers