Diabetic KetoacidosisDiabetic Ketoacidosis
Ketoacidosis-Hypersomolar ComaKetoacidosis-Hypersomolar Coma
UTHSCSA Pediatric Resident Curriculum for the PICUUTHSCSA Pediatric Resident Curriculum for the PICU
Spectrum of DKA and Hyperosmolar Coma
Rapid OnsetMarked InsulinLack
Intermediate Slow OnsetMild InsulinLack
Insulin Deficiency is the primary defect in patients with DKA
Muscle Hepatocyte Adipose
Normal Insulin Activity
Breakdown of storage forms of energy to meet energy needs. (Catabolism)– Glycogenolysis– Lipolysis– Gluconeogenesis (from amino acids,
lipids) Glucagon unopposed by Insulin
stimulates this catabolic reaction
Skeletal and cardiac tissues are able to use free fatty acids and ketone bodies as an energy source.
Glucose can not be used by these tissues in the absence of insulin.
The brain is an insulin-independent tissue and continues to use available glucose.
Persistent Catabolism Hyperglycemia is worsened by further
intake of glucose. Excess Ketone bodies from Lipolysis
– Acetone -hydroxybutyrate (BHB)– Acetoacetate (AA)
Ratio of BHB/AA normally 3:1 is driven to 15:1 in severe DKA– Ketone test measures only acetoacetate
• Hyperglycemia acts as an osmotic diuretic with obligatory loss of water and electrolytes.
• Osmolality = 2(Na) + Glucose/18 + BUN/2.8 (normal 293 )
• Ketosis/hyperglycemia stimulate vomiting with aggravation of dehydration
Hypovolemia secondary to dehydration can promote decreased tissue perfusion with anaerobic metabolism and elevated lactate production
Total fluid deficit in severe DKA usually averages around 10% of the total body weight
Ketoacids draw out intravascular cationsof Sodium and Potassium
Intracellular exchangeof potassium with hydrogen ions
Phosphorous is also depleted in the osmotic diuresis
Fluid Balance in DiabeticHyperosmolarity
ECF = 14 L ICF = 28 L
Osmotic Diuresis ECF hyperosmolar from ICF autotransfusion
ECF and ICF both hyperosmolar
Clinical Findings in DKA
Polyuria, Polydipsia, Polyphagia Dehydration + orthostasis Vomiting (50-80%) Küssmaul respiration if pH < 7.2 Temperature usually normal or low, if
elevated think infection! Abdominal pain present in at least
Clinical Findings of Hyperosmolarity Lethargy, delirium Hyperosmolar coma is the first sign of
diabetes in 50-60 % of adult patients. Hyperglycemia usually > 700-800mg/dl Osmolarity above 340 mOsm/L is
required for coma to be present.
Precipitating Factors for Hyperosmolarity Too little insulin Infection, even minor. Severe stress. Hypokalemia (Required by insulin). Inadequate fluid intake
– Infancy (can not ask for fluids)– Incapacitation (can not get to fluids/ask)
Laboratory Findings in DKA-Hyperosmolarity Glucose > 700mg/dl Total body sodium low, level high,
normal or low. Potassium high, normal or low. Large urine ketones Bicarbonate < 15 mEq/L, pH < 7.2 Leukocytosis 15,000-40,000 even
without infection. High temp = infection.
Calculation of Osmolarity
2(Na = K) + Glucose (mg/dl)/20 = 280 - 295 mOsm/L
A calculated osmolarity less than 340 mOsm/L is unlikely to cause coma. Other processes must beconsidered (stroke, infection, toxin).
DKA does not cause coma in the absence of hyperosmolarity.
The effective osmolarity calculation uses only those biologically effective molecules which are able to draw water out of the cell.
Urea and other molecules measured in the lab (alcohol) move freely between the intra and extravascular spaces and don’t draw water out of the cell.
Approach to Therapy
Correcting the hyperosmolar state and dehydration is the initial aim of therapy.
Insulin therapy should be undertaken only after the patient is stable hemodynamically.
Glucose and H2O
H2O lost in urine Loss of ECF, vascular collapse and death
Consider most patients with DKA to be approximately 10% dehydrated.
The difference between the patient’s weight at baseline and presentation is an accurate measure of volume loss.
Normal Saline is the replacement fluid of choice to restore hemodynamics.
Bolus fluids until correction of circulatory failure.
Correct deficit over 36 to 48 hours. – Provide maintenance fluids
(1600cc/m2/d) at the same time.– Subtract resuscitation fluids from
deficit. Avoid fluid administration > 4L/m2/d
Sodium content varies between 75 to 154 mEq/L. Reduce as sodium levels approach normal.
Total body potassium is reduced. When K levels reach “normal” add 20-40 mEq/L as both KCL and Kphos.
Maximum K infusion rate 0.5 mEq/kg/hr.
Insulin is essential for lowering glucose to normal and correcting acidosis.
Following initial fluid replacement, then administer 0.1U/kg IV and initiate an infusion at 0.1U/kg/hr. (Regular Insulin).
Check serum glucose hourly and avoid dropping glucose > 100mg/dl/h.
When serum glucose falls below 300 mg/dl, add 5% Dextrose to maintain stable glucose levels.
Falling glucose should be managed with increased glucose concentration. Do not decrease insulin infusion until the metabolic acidosis is corrected.
Should only be used to treat symptomatic hyperkalemia.
May be used for pH less than 7.0 to provide some relief of Küssmaul respiration (1mEg/kg over 1-2 hours).
Inappropriate use may result in hypokalemia and paradoxical CNS acidosis.
Intubation Most patients requiring intubation have
hypovolemia. – Avoid drugs which lower blood pressure.– Consider a small volume load first.
For patients with cerebral edema, avoid medication which raise ICP (Ketamine, Succinylcholine). – Consider Thiopental and Lidocaine.– Have Mannitol available for sudden ICP.
May be sub-clinical at start of therapy. CSF pressure is usually normal
initially. Usually occurs unpredictably within
the first 24 hours of therapy. Classically, patient’s labs are
improving. No way to determine who will get this
Brain conserves water by producing osmoprotective molecules (taurine).
Osmolarity becomes disproportionately higher in the brain than other tissues.
Sudden fall in serum osmolarity moves fluid across the blood-brain barrier.
Brain becomes relatively hypervolemic.
Cerebral Edema-Clinical Signs
Initial complaint of headache. Progresses to decreasing level of
consciousness, hypertension, papilledema and bradycardia.
Coma and death soon follow. Cerebral edema is a complication of
therapy, not a progression of DKA.
Cerebral Edema - Therapy
The best therapy is to prevent it with careful rehydration.
Diagnosis available with CT scan. Therapy for acute episode:
– Intubation and hyperventilation– IV Mannitol 0.5 - 1.0 Gram/Kg as
bolus.– IV sedation.– Slow the rate of osmolar correction.
Evaluation of Therapy
Controlled reduction in serum glucose. Correction of acidosis “closing the gap”. Clearing of serum ketones. Clinical improvement
– fall in respiratory rate– improved perfusion– improving mental status.
Infection esp. urinary tract infection. Pancreatitis Disseminated intravascular coagulation. Arterial and venous thrombosis. Hypoglycemia with seizure. Hypokalemia with dysrhythmias.
Thromboembolism in Diabetes In several studies, thromboembolism
accounted for 20 to 50% of mortality. Virchow’s triad: stasis, endothelial
damage and hypercoagulopathy. Hypercoagulopathy:
– Hyperreactivity of platelets– Hyperfibrinogenemia (Especially Type
2)– Elevated plasminogen activator (Type
Endothelial Damage– Elevated levels of von Willebrand
factor associated with endothelial damage• Seen in decompensated diabetes
esp. those with microvascular disease
– Catheter placement • Promotes venous stasis• Potential endothelial damage
DKA in Type 2 Diabetics
Recent study: Arch of Internal Medicine– 39% of patients had Type 2 diabetes.– Majority of patients with Type 2
diabetes were Hispanic.– 51% of patients were obese
Type 2 diabetics more likely to have slow onset of ketoacidosis and progression to hyperosmolar coma.
DKA in Type 2 Diabetes
Hyperosmolarity, obesity, lethargy, and a relative hypercoagulopathy increase the propensity for EMBOLISM and THROMBOSIS in Type 2 diabetics.