Topics

■ Diabetic Ketoacidosis
◻ Epidemiology
◻ Pathophysiology
◻ Diagnosis
◻ Treatment

■ Hyperosmolar Hyperglycemic State

◻ AKA Nonketotic Hyperglycemia, Hyperosmolar Nonketotic Coma
 DKA Statistics
■ Type 1 Diabetes
■ Type 1b Ketosis prone Diabetics
■ Occasionally in Type 2
◻ Infection, Trauma, Cardiac
◻ Newly diagnosed Type 2 DM

■ Cost
◻ Annual hospital cost $1 billion
◻ ¼ of health care dollars spent on Type 1
 DKA Mortality

n Mortality primarily due to precipitating illness

n Prognosis worse with old age, coma and hypotension
 HHS Statistics
■ <1% of all diabetes-related admissions
■ More common in elderly diabetics
■ frail
■ poor access to water
■ Decreased GFR
■ Mortality
◻ Variable 10-50%
◻ Most often due to the precipitating illness
Role of Insulin
 Ketoacidosis
■ Lipolysis→Increased FFA→Converted to Ketones in
Liver
■ Three ketones
◻ Acetoacetic Acid; Beta-Hydroxybutyric Acid; Acetone
■ Accumulation leads to acidosis (↓pH) & formation of
anion gap
■ Differential Diagnosis
◻ Alcoholic Ketoacidosis
◻ Starvation Ketosis
 Diagnostic criteria
DKA HHS
• blood glucose >250 mg/dl, •
blood glucose >600 mg/dl
•

• arterial pH <7.3, •
arterial pH >7.3,
•

• bicarbonate <15 mEq/l, and •

bicarbonate >15 mEq/l,
•

• moderate ketonuria or •
mild ketonuria or ketonemia, and
ketonemia •

•
effective serum osmolality >320
mOsm/kg H2O.
•
longer time for development of
the disease
 Causes of DKA/HHS
■ New diagnosis of Diabetes
■ Infection: Pneumonia, Gastroenteritis, UTI
■ Pancreatitis
■ Acute MI/ACS
■ Stroke
■ Trauma
■ Alcohol/Drugs/Medications
■ Missed Insulin/Compliance
 In between type 1 

and type 2

•Unprovoked ketosis

•Absent islet cell antibodies

•Frequent evolution to Insulin independence over time

 Symptoms of DKA
■ Develops rapidly
■ Earliest symptoms are due hyperglycemia
◻ Polyuria, Polydipsia, Weight loss
■ Neurologic symptoms
■ Abdominal pain, nausea, vomiting
◻ Up to 50% of DKA
◻ Associated with degree of acidosis
◻ ?Delayed gastric emptying/ileus
 Physical Exam in DKA
■ Signs of dehydration
◻ Tachycardia, hypotension
■ Neurologic exam
■ “Acetone breath”
■ Kussmaul Respirations
■ Fever is rare, even with infection
 Evaluation
■ Laboratory • Other
◻ Glucose o Electrocardiogram
◻ Electrolytes o Chest X-Ray
◻ CBC o Blood Culture
◻ Serum Ketones o Urine Culture
◻ Plasma Osmolality o Sputum Culture
◻ ABG (venous pH 0.03
lower)
◻ Urinalysis
◻ ?Amylase/Lipase
Labs in DKA: ABG and
ketones
 Labs in DKA: Glucose
■ Usually between 300-500 mg/dl
■ “Euglycemic DKA”
◻ Nutritional deficiency
◻ Pregnancy
◻ Prior use of insulin en route to the E.R.
 Labs in DKA: Sodium
■ Variable sodium levels
■ Direct effect of hyperglycemia leads to
hyponatremia (↓1meq/L for every 62 mg/dl rise in BS)
due to fluid shift from intracellular to extracellular
space
■ Need to compute for corrected sodium
■ Corrected Na = serum sodium +1.6 for ever 100 mg/dl above 100

■ Secondary effect of osmotic diuresis which causes

loss of free water→hypernatremia
■ Most are mildly hyponatremic
 Labs in DKA: Potassium
■ Overall potassium deficit
◻ Renal loss with osmotic diuresis & ketone excretion
◻ GI loss

■ However, on initial evaluation, K level is usually

normal or elevated
◻ Hyperosmolarity
◻ Insulin deficiency
◻ ?Acidemia

■ Take great care in monitoring/repleting K for fear of

arrythmias
 Labs in DKA: Other
■ Phosphate
◻ Usually body depleted, but initial levels may be normal or high
■ Amylase/Lipase
◻ May be elevated, even without pancreatitis
■ Elevated WBC
■ Hyperlipidemia
◻ Elevated TC & Trigs
 Formulas
•Corrected Na = serum sodium +1.6 for ever 100 mg/dl
above 100

•Fluid deficit = (Corrected Na- Goal of 140/ 140) x 0.6 x

kg BW

•Anion Gap = Na – (Cl+HC03)

•Osmolarity = 2Na +glucose in mg/dl/18

 Anion Gap
■ AG= Na – (Cl + HCO3)
■ Normal <12; DKA >20
■ Accumulation of BHB & AA
■ Test in serum & urine
■ Nitroprusside reaction converts AA to acetone and
(does not detect BHB)
◻ Test may be negative test if most of the anions are BHB
◻ Adding Hydrogen Peroxide to urine the urine converts BHB to AA & allows
NP reaction
 Anion Gap
High Anion Gap Normal Anion Gap
•Methanol •ureteroenterostomies
•Uremia and RF •Sulfamylon
•Diabetes and other •Enteric fistulas
ketotic states •Diarrhea
•Paraldehyde •Cholestyramine
•INH •Aldactone, acidifying
•Ethylene glycol agents,actazolamide
•Salicylate •RTA
add lactic acidosis add HAL
 Treatment of DKA
■ Initial Evaluation: ABCs; Exam; Labs; Causes
■ Close Monitoring
■ Fluid Replacement
■ Insulin Therapy
■ Electrolyte Replacement
■ Resolution & Conversion to home therapies
 Monitoring

■ICU Status
■Blood sugar monitoring q1 hr
■Electrolytes ,venous pH q2-4 hrs
■Ketones q 6H
■Close evaluation of vitals & neuro status
■Consider use of flowsheet
 Fluid Replacement
■ Mainstay of initial therapy
■ Expand the intravascular volume & improve renal
blood flow
■ Ave fluid loss for DKA: 3-6 Liters (8-10 in HHS)
■ Isotonic saline
◻ Rapidly infuse volume without acute lowering of plasma
osmolarity
◻ Switch to ½ NS in subacute phase if Na normal or high
■ 15-20 ml/kg initially then decrease to 5-10ml/kg/hr
■ Fluids alone my initially decrease BG by 35-70
 ER doc’s recommendation: Hardern and Quinn Emerg

Med J 2003; 20:210-13

• 500 ml x 4 hours then 250 x 4 hours

• Make sure lines are in

• Insert NGT and Urine catheter

 Insulin Therapy
■ Role of Insulin
◻ Lower serum glucose (mainly by decreasing liver
production)
◻ Reduce ketogenesis in liver by reducing lipolysis and
glucagon secretion
◻ Increase ketone utilization
■ Insulin IV bolus and continuous drip is standard of
care
◻ Some studies have looked at frequent, rapid-acting insulin,
but not enough data to support use except in mild DKA
cases
 Insulin Therapy
■ Check Potassium first!
◻ If K <3.3, delay insulin until begin K repletion
◻ May drive insulin into the cells and lead to life-threatening hypokalemia

■ IV bolus of regular insulin: 0.1 U/Kg

■ Continuous infusion, start at 0.1 U/Kg/hr
■ Goal is to decrease glucose by 50-70 mg/dl per
hour; will require further titration of drip
■ Higher rates in the young compared to the old
■ Higher rates in those with Type 2 diabetes
 Insulin Therapy
■ Once BS < 200 (<300 in HHS) start dextrose (usually
D5 ½ NS) and decrease insulin drip rate to 1/5 of
previous
■ Addition of dextrose to IVF
◻ Avoid hypoglycemia
◻ Continue insulin drip while awaiting resolution of ketoacidosis
◻ Continue nutrition while patient NPO

■ Need to overlap IV drip with SQ insulin to avoid

going back into ketosis
 Potassium Replacement
■ If initial K high, should not need more therapy than
insulin, which will drive K into the cells
■ To prevent hypokalemia, add KCl to IVF if K<5.3
◻ If K normal, 20-30 meq/liter of IVF is adequate
◻ If K low, may need more aggressive rx
◻ If using 40 meq KCl in saline, may use ½ NS as this will create isotonic
solution
■ NS = 154 cation equiv
■ ½ NS = 77; ½ NS + 40 meq KCl = 117 (~3/4 NS)
 Effects of acidosis in
experimental studies
• Initially acidosis from ketones, lactic acidosis and
renal dysfunction
• Subsequently, Hyperchloremic acidosis due to
preferential excretion of ketones over chloride and
from saline administration

• Impairs myocardial contractility

• Reduces cardiac output
• Affect oxyhemoglobin dissociation and tissue
oxygen delivery
• Inhibit intracellular enzymes
• Alter cellular metabolism
 Bicarbonate Therapy
■Concerns with use:
◻ Rapid rise in pH will shift the O2 dissociaiton curve to the left. This
results in decrease tissue oxygenation. The rise in pCO2 results in
an increase in lactate and acidosis
◻ The rise in lactate may lead to fall in cerebral pH contributing to
edema

■Consider use with:

◻ pH <7.0, especially if decreased cardiac function
◻ Life-threatening hyperkalemia
■Dose:50-100 meq NaHCO3 (1-2 amps) over 2 hours
■Does not apply to HHS
 Phosphate Therapy
■ Most patients phosphate depleted
■ Usually level will fall with initial therapy
◻ Driven into the cells with resolving acidosis
◻ Improved renal perfusion→excretion
■ Most patients do not have symptoms related to
hypophosphatemia
■ Routine use not necessary
■ If evidence of cardiac dysfunction, hemolytic anemia,
or respiratory depression in pts with phos <1.0 mg/dl
◻ 20-30 meq/L of Potassium Phosphate, added to IVF
 Resolution
DKA
•Blood glucose <200 mg/dl
•PLUS 2 0f the following:
o Bicarbonate ≥15 mEq/ml
o Venous ph 7.3
o Anion gap ≤12 mEq/l

HHS
•Normal osmolality
•Normal mental status