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 Trauma
Pneumonia Acute Pancreatitis
Gastroenteritis Myocardial Infarction
UTI Stroke
Sepsis Endocrine
Meningitis Acromegaly
Influenza Thyrotoxicosis
Mucormycosis Cushings S.
Omission of Antidiabetic Mxs
Emotional Problems 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
Precipitating Factors
Absolute Relative
Insulin Glucagon Insulin
Deficiency Catecholamines Deficiency
Cortisol
Growth Hormone

Lipolysis Proteolysis Minimal Lipolysis

FFAs Gluconeogenic
Substrates

Ketogenesis Gluconeogenesis Glycogenolysis

Ketoacidosis Hyperglycemia Hyperosmolality

Glucosuria
Triglycerides (Osmotic Diuresis) Decreased GFR

Hyperlipidemia Loss of Water

& Electrolytes Dehydration
 DKA/HHS
Enhanced Glucose Production

cAMP
+ Glycogen
PKA +
- G-6-P Glucose
PFK-2
F-6-P
PFK-1 F1,6BP
F-2,6P2
F-1,6-P2
Glycerol
Alanine PYR
CO2 Fat
 DKA/HHS
Ketone Body Formation in Liver

Glucose Fatty Acids Insulin

Fatty Acyl-CoA Triglycerides

Fatty Acyl-CoA

Acetyl-CoA

Acetoacetyl-CoA

b-Hydroxy-b-methylglutaryl CoA

Acetoacetate b -Hydroxybutyrate
NADH
Acetone NAD
 DKA/HHS
Glucagon-induced
Glucose Catabolic Cascade in Liver Glucose

Glycogenolysis Gluconeogenesis
Glycogen Formation Glycolysis

Fatty
Fatty acyl CoA
Acids Malonyl-CoA
ACC

Fatty Acid Acetyl-CoA

Oxidation Ketones
 DKA/HHS
Ketone Body Utilization in Muscle

EXTACELLULAR MITOCHONDRION

b -Hydroxybutyrate b -Hydroxybutyrate
NAD
NADH + H+
Acetoacetate Acetoacetate
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)

DKA HHS
Plasma Glucose (mg/dl) 616 930
Serum Na+ (mEq/l) 134 149
Serum K+ (mEq/l) 4.5 3.9
Serum HCO3- (mEq/l) 9.4 18
Arterial pH 7.12 7.30
pCO2 20 35
Anion Gap 17 11
Effective Serum Osmolality (mOsm/kg) 310 360
BUN (mg/dl) 30 65
Creatinine (mg/dl) 1.1 1.4
Urine Ketones Pos Pos
Plasma Ketones (positive) 1:16 1:1
From: Gerich et al. (1971) Diabetes 20:228
 DKA/HHS
Typical Water and Electrolyte
Deficits
DKA HHS
Total Water 6 9
Water (ml/kg) 50-100 100-200
Na+ (mEq/kg) 7-10 5-13
Cl- (mEq/kg) 4-7 5-15
K+ (mEq/kg) 3-12 4-6
PO4 (mmol/kg) 1 3-7
Mg++ (mEq/kg) 1 1-2
Ca++ (mEq/kg) 1 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 1h
Vital Sgs 1h
Body Weight 6-12 h
ECG As indicated
 DKA/HHS
Monitoring Lab Values

Laboratory Monitoring Interval

Glucose 1h
Potassium, pH 1-2 h
Sodium, Chloride, Bicarb 2-4 h
BUN, Creatinine 4-6 h
Phosphate, Magnesium 4-6 h
Urine Ketones 2-4 h
Calcium As indicated
Hematocrit As indicated
 DKA/HHS
Monitoring Therapy

Therapy Monitoring Interval

Fluid Intake & Output 1-4 h
Insulin (U/h) 1-4 h
Potassium (mEq/h) 1-4 h
Glucose (g/h) 1-4 h
Bicarb & Phos (mEq/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

PYR
CO2 Fat
 DKA/HHS
-induced
Glucose Anabolic Cascade in Liver Glucose

Glycogenolysis Gluconeogenesis
Glycogen Formation Glycolysis
Fatty
Acids Fatty acyl CoA
CPT1 - Malonyl-CoA

TG Fatty Acid
Oxidation Acetyl-CoA
Ketones
 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