Diabetic ketoacidosis

Background

Epidemiology

• Mortality rate approximately 2-5%

Pathophysiology

• Defining features include hyperglycemia (glucose > 250mg/dl), acidosis (pH < 7.3), and ketonemia/ketonuria

Hyperglycemia

• Leads to osmotic diuresis and depletion of electrolytes including sodium, magnesium, calcium and phosphorous.
• Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure

Acidosis

• Due to lipolysis / accumulation of of ketoacids (represented by increased anion gap)
• Compensatory respiratory alkalosis (i.e. tachypnea and hyperpnea - Kussmaul breathing)
• Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate

Dehydration

• Causes activation of RAAS in addition to the osmotic diuresis
• Cation loss (in exchange for chloride) worsens metabolic acidosis

Clinical Features

History

• May be the initial presenting of an unrecognized T1DM patient
• Presenting signs/symptoms include altered mental status, tachypnea, abdominal pain, hypotension, decreased urine output.
• Perform a thorough neurologic exam (cerebral edema increases mortality significantly, especially in children)
• Assess for possible inciting cause (especially for ongoing infection; see Differential Diagnosis section)

Physical

• Ill appearance.
• Acetone breath.
• Drowsiness with decreased reflexes
• Tachypnea (Kussmaul's breathing)
• Signs of dehydration with dry mouth and dry mucosa.
• Perform a thorough neurologic exam as cerebral edema increases mortality significantly, especially in children
• There may be signs from underlying cause (eg pneumonia)

Differential Diagnosis

Causes of DKA

• Insulin or oral hypoglycemic medication non-compliance
• Infection
• Cardiac Ischemia
• Intra-abdominal infections
• Steroid use
• ETOH Abuse
• Drug abuse
• Pregnancy
• Hyperthyroidism
• GI Hemorrhage
• CVA
• PE
• Pancreatitis
• Renal Failure
• GI Bleed
• Alcoholic Ketoacidosis

Hyperglycemia

• Diabetic foot infection
• Diabetic ketoacidosis (DKA)
• Diabetic ketoacidosis (peds)
  • Cerebral edema in DKA
• Hemochromatosis
• Hyperosmolar hyperglycemic state (HONC)
• Iron toxicity
• New onset diabetes mellitus
  • Diabetic peripheral neuropathy
• Nonketotic hyperglycemia
• Sepsis

Evaluation

• Diagnosis is made based on the presence of acidosis and ketonemia in the setting of diabetes.
• Strongly consider capnography for respiratory distress

Workup

• CBC
• Blood glucose
• BMP
• Mag
• Phos
• Urinalysis
• VBG/ABG
• Beta-hydroxybutyrate

Blood Glucose

• Capillary blood sugar >250mg/dL
• Blood sugar may not be very elevated if there is impaired gluconeogenesis (eg liver failure, severe alcoholism) or patient is taking a SGLT-2 Inhibitor

Blood Gas

• No need to perform Arterial blood gas. Venous blood gas is sufficient
• Difference in pH from VBG vs ABG will be ±0.02pH units

Elevated Anion Gap

• Bicarb may be normal due to compensatory and contraction alcoholosis so the elevated anion gap or ketonuria may be the only clues to the DKA
• VBG (equivalent to ABG for assessment of acid-base status)

Serum ketones

• Beta hydroxybutyrate will be elevated

Urinary analysis (ketonuria)

• Note that urine dipstick may give a false negative for ketones since it does not detect beta-hydroxybutyrate
• As acetoacetate is converted to beta-hydroxybutyrate the urinary ketones may turn negative
• Urinalysis will be positive very early in DKA

ECG

• Assessing for any cardiac dysfunction

Infectious evaluation

• This should be done as appropriate if the suspected underlying cause for DKA is an infection. (eg chest X-ray , blood cultures)

End Tidal CO2

• ETCO2 can be used for bedside assessment of DKA
  • An ETCO2 of ≥35 is 100% sensitive to rule out DKA
  • An ETCO2 of ≤21 is 100% specific to diagnosis DKA

Management

Algorithm for the management of diabetic ketoacidosis

Volume Repletion

• Administer 20-30cc/kg normal saline bolus during the first hour
  • Most important step in treatment since osmotic diuresis is the major driving force
  • Most adult patients are 3-6L depleted
• Consider LRs to avoid worsening acidosis with contributory hyperchloremic metabolic acidosis
• When blood sugar(BS) < 250 switch to Dextrose 5% 50-200ml/hr (+/- KCl)

Insulin Overview

• Check Potassium prior to insulin treatment!
  • If potassium <3.5mEq/L, do not administer insulin until potassium supplementation is underway (to avoid worsening of hypokalemia)
  • If potassium >3.5mEq/L and <5.5 mEq/L, start potassium repletion along with your insulin
• A bolus dose is unnecessary and may contribute to increased hypoglycemic episodes
• Expect BS to fall by 50-100mg/dL per hr if you administer 0.1units/kg/hr of insulin
• Refractory hyperglycemia may be due to an associated infectious process contributing to the DKA

IV Insulin Regimen

• Initial infusion 0.1units/kg/hr of insulin
• When BS <250mg/dL, halve the rate of infusion to 0.05units/kg/hr IV OR give subQ 0.1 U/kg q2hr and switch IV fluids to Dextrose 5% at 150cc/hr
• Maintain BS between 150 and 200mg/dL until resolution of acidosis
  • May require IV fluids to be switched to Dextrose 10% when BS <150mg/dL
• Continue IV infusion for 2 hrs after subcutaneous insulin is begun
• SubQ route (appropriate only for mild DKA)

Do not stop insulin infusion until AG normalized AND bicarb normalized, despite resolution of blood sugar. Aim of insulin regime is to correct the acidosis, not merely the hyperglycemia.

SubQ(SC) Insulin Regimen

A subcuntenous regemin must use short acting insulin and follow either a 1hr or 2hr dosing protocol. Regular insulin is not effective

1hr Protocol

• Initial dose SC Aspart: 0.3 units/kg body wt, followed by
  • SC aspart insulin at 0.1 units/kg every hour
  • When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5<sub 0.45%NS and reduce SC aspart insulin to 0.05 units/kg/hr
  • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

2hr Protocol

• Initial dose SC Aspart: 0.3 units/kg body wt, followed by
  • SC aspart insulin at 0.2 units/kg 1 hr later followed by Q2hr dosing
  • When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC aspart insulin to 0.1 units/kg/ 2hr
  • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

Electrolyte Repletion

• Potassium repletion is most important. Patients in DKA are almost always K+ depleted despite initially fairly normal K+. This is due to extracellular shift of K+ due to acidosis as well as insulin infusion, which increases uptake of K+ intracellularly.
• Sodium
  • Hyponatremia may be due to translational hyponatraemia
  • Na+ decreases by 1.6mEq/L for every 100mg/dL increase in glucose (ie pseudohyponatremia)
  • Correction of glucose will result in normalization of Na+
  • If truly hyponatraemic, start NS 250-500ml/hr
  • If Hypernatremic then consider starting half-strength NS 250-500ml/hr after initial fluid bolus
• Hypophosphatemia: If < 1.0 mEq/L, start repletion.
  • IV K2PO4 at 1mL/hour (contains 4.4meqK+ & 93mg phos)
  • Severe hypophosphatemia can cause cardiac and respiratory dysfunction
• Hypomagnesemia – All patients who are hypokalemic are hypomagnesemic. Replete together as long as kidney function intact and if Mg<2.0mg/DL or symptoms suggest hypomagnesemia
  • 2g MgSO4 IV over 1h

Bicarbonate

• No evidence supports the use of sodium bicarb in DKA, with a pH >6.9
• However, no studies have been performed for patients with pH <6.9 and the most recent ADA guidelines recommend it for patients with pH <7.1
• Pitfalls of sodium bicarbonate therapy in DKA (outside of last ditch efforts in severe acidemia)
  • Paradoxical CSF acidosis
  • Hypokalemia from H+ and K+ shifts
  • Large sodium bolus
  • Cerebral edema
  • Shifts oxygen-hemoglobin dissociation curve to left, decreasing O2 delivery to tissues

Subsequent Management

Labs/Monitoring

• Glucose check Q1hr
• Chem 10 Q4hr (initially Q2hr)
• Check pH prn based on clinical status (eval respiratory compensation)
• Check appropriateness of insulin dose Q1hr (see below)
• Corrected Electrolytes

Sliding Scale

• Insulin Sliding Scale to be started once patient's DKA has resolved and eating a full diet.

Intubation

• Avoid intubation unless patient cannot generate respiratory alkalosis compensation due to extreme fatigue
• Risks associated with intubation in DKA:
  • During sedation/paralysis, a rise in PaCO2 can decrease pH considerably
  • Severe gastroparesis in DKA creates a significant risk for aspiration
  • Strong DKA patients generally can achieve greater hyperventilation than mechanical ventilated patients
• See Intubation for more information

Disposition

• Admit

Complications

• Cerebral Edema in DKA

See Also

• Diabetes mellitus (main)
• Evidence Review Sodium Bicarbonate in DKA
• Diabetic ketoacidosis (peds)
• Ketonemia

External Links

• British Society for Paediatric Endocrinology and Diabetes - Paediatric Diabetic Ketoacidosis
• DDxOf: Management of DIabetic Ketoacidosis

References

Authors

Ross Donaldson