Basics
Description
Insulin deficiency and excess of counterregulatory hormones (catecholamines, glucagon, growth hormone, and cortisol) resulting in:
- Dehydration (osmotic, hyperglycemic, diuresis, and decreased oral intake)
- Acidosis (anion gap metabolic acidosis)
- Ketone formation (unrestrained lipolysis and ketogenesis)
- Hyperglycemia (unrestrained glycogenolysis and gluconeogenesis)
- Electrolyte disturbances (hypokalemia, hypo/hypernatremia, hypophosphatemia)
Etiology
- Medication noncompliance (>50%)
- New-onset diabetes (type I or II)
- Underlying medical illness (increased counterregulatory hormones and insulin resistance):
- Infectious process
- MI
- GI bleed
- CNS event
- Pregnancy (relative insulin deficiency and counterregulatory hormone excess)
- Medications (protease inhibitors and atypical antipsychotics: Olanzapine, clozapine)
- Alcohol abuse
Diagnosis
Signs and Symptoms
History
- Medication noncompliance
- Polyuria, polydipsia
- Weakness
- Abdominal pain, nausea, vomiting
- Altered mental status
- Chest pain
- Febrile illness
Physical Exam
- Tachycardia
- Hypotension (dehydration, sepsis)
- Tachypnea (hyperpnea)
- Kussmaul respirations
- Hyperthermia/hypothermia (coexisting infection)
- Dehydration:
- Poor skin turgor
- Dry mucous membranes
- Odor of ketones on breath
- Diffuse abdominal tenderness
Essential Workup
- Diagnostic criteria:
- pH <7.3 with ketonemia
- Bicarbonate <15 mEq/L
- Glucose >250 mg/dL
- Bedside glucose measurement
- Venous blood gas
- Urine dip for ketones
- Serum electrolytes, glucose, BUN/creatinine
- Search for precipitating cause
Diagnosis Tests & Interpretation
Lab
- Serum glucose measurement:
- Electrolyte measurement:
- Increased anion gap metabolic acidosis: [Na - (Cl + HCO3)] >12
- Sodium:
- Pseudohyponatremia (from hyperglycemia) correction factor; add 1.6 mEq/L to the measured sodium for every 100 mg/dL of blood glucose >100 mg/dL.
- Potassium:
- Initial serum level may be normal to high owing to extracellular shift as compensation for acidosis.
- Total body deficit usually 3-5 mEq/kg
- As acidosis improves, for every 0.1 increase in the pH, serum potassium decreases 0.5 mEq/L.
- Can drop precipitously with insulin and fluids
- Bicarbonate:
- Usually <15 mEq/L
- May be higher owing to coexisting volume contraction alkalosis
- BUN/creatinine:
- Usually shows prerenal azotemia owing to dehydration
- Serum ketones:
- Must be present to make diagnosis of DKA.
- β-Hydroxybutyrate is the predominant ketoacid, but acetoacetate and acetone are also present:
- β-Hydroxybutyrate is not measured by most hospital serum and urine ketone tests (nitroprusside reaction measures only acetoacetate and acetone), thus there is a theoretical risk of missing the presence of ketones using these tests.
- Urine ketone dip test (UKDT) is 97% sensitive for presence of serum ketones and a negative UKDT has a negative predictive value of 100% in ruling out the presence of DKA.
- Point-of-care capillary testing for β-hydroxybutyrate is 98% sensitive for serum ketones:
- May be used with capillary glucose testing in triage to detect DKA early in the ED course.
- Urinalysis:
- Ketonuria, glucosuria
- Pregnancy (UhCG)
- Venous blood gas:
- Essential to assess patients pH
- pH correlates well with arterial pH
- Avoids need for repeated arterial sticks
- ABG should be performed if oxygenation/ventilation needs assessment.
- Serum osmolarity:
- May be measured in the lab and calculated
- Calculated: 2(Na) + glucose/18 + BUN/2.8 (normal 285-300 mOsm/L)
- Significant hyperosmolarity >320
- CBC:
- Leukocytosis may be present without infection.
- If left shift in differential, suspect infection.
- Other lab tests:
- Amylase: Elevation is nonspecific in DKA
- Lipase: Elevation specific for pancreatitis
- Calcium, Mg, Phosphate: All usually decreased as is K+
Imaging
- CT head to rule out other causes of altered mental status.
- CXR if pneumonia suspected as precipitant or hypoxia present
- EKG to rule out ischemia as a precipitant and look for signs of hyper/hypo K+
Differential Diagnosis
- Other causes of anion gap acidosis
- Use ACAT MUD PILES mnemonic:
- Alcoholic ketoacidosis
- Carbon monoxide/cyanide
- Aspirin
- Toluene
- Methanol
- Uremia
- Diabetic ketoacidosis
- Paraldehyde
- Iron/isoniazid
- Lactic acidosis
- Ethylene glycol
- Starvation/sepsis
- Hyperglycemic hyperosmolar nonketotic syndrome
Treatment
Pre-Hospital
- Fluid bolus often initiated in field
- Quantify amount given by paramedics to guide further ED fluids.
Initial Stabilization/Therapy
- ABCs for patients with altered mental status
- Coma cocktail for AMS: Naloxone, thiamine, blood sugar
- 0.9% NS bolus for hypotension/tachycardia
Ed Treatment/Procedures
- Cardiac monitor and pulse oximetry for patients with abnormal vitals
- Fluids:
- Average adult water deficit is 100 mL/kg (5-10 L).
- Initial 1-2 L bolus of 0.9% NS to restore intravascular volume over 1st hr.
- If corrected serum sodium is low, continue with 0.9% NS, giving 1-2 more liters over the next 2-4 hr.
- If corrected serum sodium is normal or elevated, use 0.45% NS giving 1-2 more liters over next 2-4 hr.
- Be careful to avoid fluid overload in patients with cardiac disease.
- Avoid precipitous falls in serum sodium/osmolality, as this may contribute to cerebral edema.
- Total fluid replacement should take 24-36 hr.
- Insulin:
- Reverses ketogenic state and down-regulates counterregulatory hormones
- Administered as continuous IV infusion of regular insulin at 0.1 U/kg/h:
- Adjust infusion in response to changes in glucose and anion gap
- Continue until pH >7.3 and resolution of anion gap
- Serum glucose will fall sooner than resolution of acidosis and should be kept >250 mg/dL with glucose-containing fluids such as D5 45% NS.
- Potassium:
- Administration is essential.
- Total body deficit of 3-5 mEq/kg
- Will drop precipitously with administration of fluid and insulin
- Administer KCl, 10 mEq/h IV once renal function is established and K+ is known to be <5.5 mEq/L.
- May need to give up to 20-40 mEq/h IV in cases where initial K+ is <3.5 mEq/L
- In hypokalemic patients, insulin therapy should be delayed until K+ is >3.5 mEq/L.
- Should measure q1-2h during 1st 4-6 hr of therapy
- Bicarbonate:
- No studies have shown clinical benefit in DKA, and its routine use is not advocated.
- Complications include hypokalemia, alkalosis, cerebral acidosis, and edema.
- Some advocate its use for pH <6.9 with cardiac instability.
- Phosphate:
- Not routinely replaced during initial ED therapy
- May supplement if <1 mg/dL and symptomatic muscle weakness.
- Administer as potassium phosphate.
- Magnesium:
- May supplement if <1.2 mg/dL
- Administer 2 g MgSO4 IV over 1 hr.
- Identify and treat precipitating cause.
- Fluids:
- Average fluid deficit is 100 mL/kg.
- Initial 10-20 mL/kg bolus of 0.9% NS to restore intravascular volume
- May repeat once in severely dehydrated children
- Should not exceed 40-50 mL/kg of fluid in 1st 4 hr of therapy
- Replace remainder of deficit at 1.5-2 times maintenance over 24-36 hr.
- Overzealous fluid administration is thought to contribute to cerebral edema.
- Cerebral edema:
- Occurs in 1-2% of children with DKA
- Causes 31% of deaths associated with DKA
- Exact causes unclear
- Suspect with coma, fluctuating mental status, bradycardia, HTN, severe headache, decreased urine output, or quickly falling corrected Na+ or osmolality to below normal levels
- Mannitol: 0.25-1 g/kg IV over 30 min should be given immediately and can be repeated hourly.
- Fluid rate should be decreased and other supportive measures instituted.
Medication
- D50: 1 amp (25 g) of 50% dextrose IVP (peds: 2-4 mL/kg D25)
- Insulin (100 U regular insulin in 100 mL NS) run at 0.1 U/kg/h
- MgSO4: 2 g of 20% solution
Follow-Up
Disposition
Admission Criteria
- ICU admission for pH <7, altered mental status, serious comorbid illness, and extremes of age (<2 yr or >60 yr)
- Monitored unit for moderate DKA (pH 7.01-7.24) with CHF or cardiac history
- General floor (nurses skilled with insulin infusions) for moderate DKA without comorbidities
- Observation unit (<23 hr admission) for mild DKA (pH 7.25-7.30) without precipitating illness
Discharge Criteria
- Resolution of anion gap acidosis
- Tolerating PO fluids
- No evidence of precipitating event
- Clear instructions on home insulin regimen
- Close primary care follow-up arranged
Pearls and Pitfalls
- Decreasing or discontinuing insulin drip when glucose normalizes is a pitfall. Insulin should only be stopped when pH improves and anion gap normalizes.
- Failure to replete potassium is a pitfall.
Additional Reading
- Goyal N, Miller JB, Sankey SS, et al. Utility of initial bolus insulin in the treatment of diabetic ketoacidosis. J Emerg Med. 2010;38(4):422-427.
- Kitabchi AE, Umpierrez GE, Murphy MB, et al.; American Diabetes Association. Hyperglycemic crises in diabetes. Diabetes Care. 2004;27(suppl 1):S94-S102.
- Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 2011;94(3):340-351.
See Also (Topic, Algorithm, Electronic Media Element)
Hyperosmolar Syndrome
Codes
ICD9
- 250.10 type II diabetes mellitus [non-insulin dependent type] [NIDDM type] [adult-onset type] or unspecified type, not stated as uncontrolled, with ketoacidosis
- 250.11 type I diabetes mellitus [insulin dependent type] [IDDM] [juvenile type], not stated as uncontrolled, with ketoacidosis
- 250.12 Diabetes with ketoacidosis, type II or unspecified type, uncontrolled
- 250.13 Diabetes with ketoacidosis, type I [juvenile type], uncontrolled
- 250.1 Diabetes with ketoacidosis
ICD10
- E10.10 Type 1 diabetes mellitus with ketoacidosis without coma
- E10.11 Type 1 diabetes mellitus with ketoacidosis with coma
- E13.10 Oth diabetes mellitus with ketoacidosis without coma
- E13.11 Oth diabetes mellitus with ketoacidosis with coma
- E10.1 Type 1 diabetes mellitus with ketoacidosis
- E13.1 Other specified diabetes mellitus with ketoacidosis
SNOMED
- 420422005 ketoacidosis in diabetes mellitus (disorder)
- 420270002 Ketoacidosis in type I diabetes mellitus (disorder)
- 421750000 Ketoacidosis in type II diabetes mellitus (disorder)
- 111556005 Diabetic ketoacidosis without coma