Diabetic Ketoacidosis:Medication

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Diabetic Ketoacidosis:Medication
February 12, 2008
Donald W Rucker, MD, MBA, MS
eMedicine

Treatment of ketoacidosis should aim at correcting dehydration, reversing the acidosis and ketosis, reducing plasma glucose concentration to normal, replenishing electrolyte and volume losses, and identifying the underlying cause.

See Diabetes Mellitus, Type 1 - A Review and Diabetes Mellitus, Type 2 - A Review for dosing regimens.

Drug Category: Antihyperglycemic agent

These agents lower plasma glucose and ketone levels.
Drug Name Insulin (Humulin R, Novolin R)
Description In addition to lowering glucose levels and preventing further ketone production, insulin stimulates cellular uptake of potassium within 20-30 min. Glucose should be administered along with insulin to prevent hypoglycemia once glucose levels are lowered to 200 mg/dL. Monitor blood glucose levels frequently.
Regular insulin is used to reduce blood glucose levels in DKA.
Adult Dose Check potassium levels and start intravenous fluid replacement before initiating insulin, typically an hour earlier
Loading dose: 0.1-0.15 U/kg IV bolus (note that some consider this optional)
Maintenance ED doses: 0.1 U/kg/h IV infusion, typically 5-7 U/h
Goal is to reduce glucose by 50-70 mg/dL/h
Pediatric Dose Administer as in adults without loading dose (may increase risk of cerebral edema)
Contraindications Documented hypersensitivity; hypoglycemia; profound hypokalemia
Interactions Not a clinical concern in the treatment of DKA in the ED
Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions Monitor glucose and potassium and institute D5 isotonic saline with 3-7 U/h insulin IV/IM/SC once serum glucose reaches 200 mg/dL to prevent iatrogenic hypoglycemia

Drug Name Insulin aspart recombinant (NovoRapid)
Description Mechanisms and insulin-specific issues are the same in the ultra–short-acting insulins (NovoRapid - insulin aspart; Humalog - insulin lispro). They start to work about 15 min after being injected, peak after an hour, and last for 3-5 h. Umpierrez et al found that ultra–short-acting insulin aspart had the same effect in treating DKA as regular insulin given IV.3 They had both hourly and every 2 h aspart injection protocols and both worked.
Dosages listed below are from the Umpierrez et al protocol.3
Adult Dose Load with 0.3 U/kg SC followed by 0.1 U/kg/h
or alternatively, load with 0.3 U/kg SC followed by 0.2 U/kg 1 h after load and q2h thereafter
Pediatric Dose Not established
Contraindications Documented hypersensitivity; hypoglycemia
Interactions Not a clinical concern in the treatment of DKA in the ED
Pregnancy A - Fetal risk not revealed in controlled studies in humans
Precautions Per Umpierrez protocol cited above, when plasma glucose level drops below 250 mg/dL, change IV fluids to D5% 0.45% saline and reduce aspart to 0.1 U/kg given q2h to keep glucose level at roughly 200 mg/dL until resolution of DKA

Drug Category: Mineral solutions

These solutions replenish mineral deficiencies.
Drug Name Potassium chloride (Klor-Con, K-Dur, Kaon Cl)
Description Potassium deficits are high in DKA, even with paradoxically high K+ due to acidotic state, which shifts H+ into cells and K+ out of cells into blood. Monitor potassium level q1-2h initially. Repletion with potassium phosphate often thought unnecessary, although some recommend giving potassium phosphate to replete both of these electrolytes.
Adult Dose 20-40 mEq/L of KCl to each liter of fluid once K+ is <5.5 mEq/L; give two thirds as KCl and one third as KPO4+
Pediatric Dose Administer as in adults
Contraindications Hyperkalemia; renal failure; conditions associated with potassium retention; oliguria or azotemia; crush syndrome; severe hemolytic reactions; anuria; adrenocortical insufficiency
Interactions Concurrent ACE inhibitors may elevate serum potassium concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin toxicity; caution if discontinuing potassium administration in patients maintained on digoxin
Pregnancy A - Fetal risk not revealed in controlled studies in humans
Precautions In patients with elevated potassium initially, hold until K+ <5.5 mEq/L—should happen rapidly with saline/insulin treatment; can check ECG to assess effects of elevated potassium if in doubt, but mildly elevated potassium levels may not produce ECG changes