Transcript DKA.HHS.ppt
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