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Diabetic Ketoacidosis

- All but mild cases require inpatient management. - Severe DKA requires an ICU setting. - Goals - Fluid resuscitation - Insulin therapy to normalize serum glucose - Resolution of anion gap acidosis - Correction of electrolytes

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  • Diagnostic criteria (1)[C]: Hyperglycemia (glucose usually 250 to 800 mg/dL) Low HCO3 (usually ≤18 mEq/L) Metabolic acidosis on arterial blood gases (pH <7.3) Anion gap = serum sodium - (serum chloride + bicarbonate), > 10 mmol
  • Other important labs: Serum ketosis: Check β-hydroxybutyrate (β-HB) instead of ketones to evaluate ketosis (2)[B]. β-HB is the predominant ketone produced and is preferred over serum ketones. β-HB >3 mg/dL is abnormal and should be decreased to <1.5 mg/dL within 12 to 24 hours (3)[B]. Urine ketosis (urinalysis [UA]) may only identify acetoacetate and not β-HB. Glycosuria Hyperamylasemia, hyperlipasemia Hypertriglyceridemia/hypercholesterolemia Increased creatinine and BUN: Markedly increased serum ketones may cross-react and cause a falsely high serum creatinine. Pseudohyponatremia: Hyperglycemia or hypertriglyceridemia may cause an artificially low sodium concentration. The measured sodium is suppressed by 1.6 mg/dL for every 100 mg/dL of glucose over 100 mg/dL. Decreased calculated total body K+: Severe acidosis gives an artificially high K+ level. Increased serum osmolality (mOsm/kg) = [2 пїЅ serum Na (mEq/L) + glucose (mg/dL)/18 + BUN (mg/dL)/2.8]; if calculated osmolality <320 mOsm/kg, consider etiologies other than diabetic ketoacidosis (DKA) Elevated base deficit A1C helps determine history of diabetic control.
  • CBC, electrolytes, BUN, creatinine
  • Serum β-HB or ketones
  • Arterial blood gases (ABGs); venous blood gases (VBGs) may also be used (VBG pH correlates with 0.03 lower than ABG pH).
  • Chest x-ray to rule out pulmonary infection
  • Head CT scan if suspected CVA or cerebral edema
  • If necessary, cardiac enzymes and blood cultures

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Diagnostic Procedures/Other

Only if surgical problem is the underlying precipitant (e.g., appendicitis, cholecystitis) пїЅ

TREATMENT

  • Oxygen and airway management, as needed
  • Establish IV access.
  • Cardiac monitoring
  • Start isotonic crystalloid solution (0.9% saline).
  • Fingerstick glucose testing

GENERAL MEASURES

  • All but mild cases require inpatient management.
  • Severe DKA requires an ICU setting.
  • GoalsFluid resuscitationInsulin therapy to normalize serum glucoseResolution of anion gap acidosisCorrection of electrolytes
  • Identify and treat the precipitating cause (e.g., infection, MI)
  • Laboratory testing during management:Serum glucose q1-2h until stableElectrolytes, phosphorus, and venous pH q2-6h as needed

MEDICATION

First Line

  • Insulin (1)[C]Bolus 0.1 U/kg IV then continuous infusion at 0.1 U/kg/hr (do not use initial insulin bolus in children)If without bolus, 0.14 U/kg/hr continuous infusion (4)Aim for rate of serum glucose decline of 100mg/dL/hrWhen glucose 200 mg/dL, reduce infusion to 0.02 to 0.05 U/kg/hr IV or give rapid-acting insulin at 0.1 U/kg SC q2h; goal glucose is 150 to 200 mg/dL.Overlap and continue IV insulin infusion for 1 to 2 hours after SC insulin is initiated.
  • IV fluids to correct dehydration: Start with 0.9% NaCl bolus, calculate corrected sodium; if serum Na+ is high, consider 0.45% NaCl to replace free fluid loss or when adding potassium replacement.When glucose is 200 mg/dL, change to 5% dextrose with 0.45% NaCl at 150 to 250 mL/hr.
  • Potassium: falsely elevated due to acidosis; when K+ ≤5.2 mg/dL and if urine output is adequate, start replacement with 20 to 30 mEq/L of K+ in 1 L IV fluids (1).Hold insulin if K+ ≤3.3 mg/dL; give IV potassium 20 to 30 mEq/hr with fluids until >3.3 mg/dL to prevent cardiac arrhythmia (class III).For each 0.1 unit of pH, serum K+ will change by ~0.6 mEq in opposite direction.
  • Phosphorus: Routine replacement may lead to hypocalcemia; if very low (<1.0), give 20 to 30 mEq/L of K-Phos in fluids.
  • Sodium bicarbonate: no demonstrable benefit with a pH >7.0 (2,5)[B]; rehydration usually leads to resolution of acidosis. Guidelines recommend its use with pH <6.9 or in patients with life-threatening hyperkalemia; however, there is evidence that it may increase cerebral edema, especially in children (6)[A].
  • Magnesium: If Mg ≤1.8 mg/dL and the patient is symptomatic, consider replacement.
  • PrecautionsIf the patient is on an insulin pump, it should be stopped.If glucose does not fall by 10% in 1st hour, give regular insulin 0.14 U/kg IV bolus, then continuous infusion at previous rate.If using bicarbonate, add 100 mmol or 2 ampules of sodium bicarbonate to 400 mL isotonic solution with 20 mEq KCL over 200 mL/hr for 2 hours until venous pH is >7.0, then stop infusion (1).

Second Line

Insulin, SC or IM: Load with 0.3 U/kg SC, followed by 0.1 U/kg/hr; space dosing to q2h once glucose <250 mg/dL; in uncomplicated DKA, may be safe and cost effective (7)[B] пїЅ

Pediatric Considerations

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Geriatric Considerations

Must be careful with impaired renal function or congestive heart failure when correcting fluid and electrolyte abnormalities

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Pregnancy Considerations

  • Pregnancy itself is diabetogenic and also results in a compensated respiratory alkalosis (HCO3 19 to 20 mEq/L) with theoretically reduced buffering capacity
  • Pregnant women are more susceptible to DKA.
  • Euglycemic DKA
  • Increased risk of preeclampsia and fetal death
  • β-Tocolytics and corticosteroids can trigger DKA.
  • Perinatal death: 9-35%

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INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

ADA admission guidelines: blood glucose >250 mg/dL; pH <7.3; HCO3 ≤15 mEq/L; ketones in urine; ICU setting for severe DKA (10) �

IV Fluids

  • 1 to 1.5 L over the 1st hour, then, if serum corrected Na is high or normal, give 0.45% NaCl at 250 to 500 mL/hr depending on hydration state.
  • Switch to 5% dextrose in 0.45% saline at maintenance rate when serum glucose <200 mg/dL; maintain blood glucose between 150 and 250 mg/dL.
  • Overly rapid correction of fluid balance may precipitate cerebral edema (2)[C]; if the blood glucose level is falling too rapidly, consider using a 10% dextrose solution instead.

Pediatric Considerations

Bolus 10 to 20 mL/kg initially; 4-hour fluid total should be <50 mL/kg to reduce chance of cerebral edema.

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Discharge Criteria

  • Discharge when DKA has resolved: anion gap <12, glucose <200 mg/dL; pH >7.3; bicarbonate >18 mEq/L; additionally, patients must be tolerating PO intake and able to resume home medication regimen
  • Underlying precipitant (e.g., infection) must be identified and treated.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Monitor mental status, vital signs, and urine output q30-60min until improved, then q2-4h
  • Monitor blood sugar q1h until <200 mg/dL, then q2-6h.
  • Monitor electrolytes, BUN, venous pH, and creatinine q2-4h.

DIET

  • NPO initially
  • Advance to preketotic diet when nausea and vomiting are controlled.
  • Avoid foods with high glycemic index (e.g., soft drinks, fruit juice, white bread, etc.).

PROGNOSIS

  • 16% of all diabetes-related fatalities
  • Overall DKA mortality of 0.5-2%.
  • In children <10 years of age, DKA causes 70% of diabetes-related fatalities.

COMPLICATIONS

  • Cerebral edema (most common cause of death in children with DKA)
  • Pulmonary edema
  • Vascular thrombosis
  • Hypokalemia
  • Hypophosphatemia
  • Cardiac dysrhythmia (secondary to hypokalemia or acidosis)
  • MI, myocardial injury
  • Acute gastric dilatation
  • Late hypoglycemia (secondary to treatment)
  • Erosive gastritis
  • Infection, mucormycosis
  • Respiratory distress

REFERENCES

11 Kitabchi пїЅAE, Umpierrez пїЅGE, Miles пїЅJM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343.22 Agus пїЅMS, Wolfsdorf пїЅJI. Diabetic ketoacidosis in children. Pediatr Clin North Am. 2005;52(4):1147-1163.33 Trachtenbarg пїЅDE. Diabetic ketoacidosis. Am Fam Physician. 2005;71(9):1705-1714.44 Kitabchi пїЅAE, Murphy пїЅMB, Spencer пїЅJ, et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care. 2008;31(11):2081-2085.55 Kitabchi пїЅAE, Umpierrez пїЅGE, Murphy пїЅMB, et al. Hyperglycemic crises in diabetes. Diabetes Care. 2004;27(Suppl 1):S94-S102.66 Chua пїЅHR, Schneider пїЅA, Bellomo пїЅR. Bicarbonate in diabetic ketoacidosis-a systematic review. Ann Intensive Care. 2011;1(1):23.77 Umpierrez пїЅGE, Latif пїЅK, Stoever пїЅJ, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117(5):291-296.88 Watts пїЅW, Edge пїЅJA. How can cerebral edema during treatment of diabetic ketoacidosis be avoided? Pediatr Diabetes. 2014;15(4):271-276.99 Brown пїЅTB. Cerebral oedema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J. 2004;21(2):141-144.1010 American Diabetes Association. Hospital admission guidelines for diabetes. Diabetes Care. 2004;27(Suppl 1):S103.

ADDITIONAL READING

  • American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care. 2013;36(Suppl 1):S11-S66.
  • Sheikh-Ali пїЅM, Karon пїЅBS, Basu пїЅA, et al. Can serum beta-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care. 2008;31(4):643-647.

SEE ALSO

Diabetes Mellitus, Type 1 пїЅ

CODES

ICD10

  • E10.10 Type 1 diabetes mellitus with ketoacidosis without coma
  • E13.10 Oth diabetes mellitus with ketoacidosis without coma
  • E10.11 Type 1 diabetes mellitus with ketoacidosis with coma
  • E13.11 Oth diabetes mellitus with ketoacidosis with coma
  • E08.11 Diabetes due to underlying condition w ketoacidosis w coma
  • E08.10 Diabetes due to underlying condition w ketoacidosis w/o coma

ICD9

  • 250.11 Diabetes with ketoacidosis, type I [juvenile type], not stated as uncontrolled
  • 250.10 Diabetes with ketoacidosis, type II or unspecified type, not stated as uncontrolled
  • 250.12 Diabetes with ketoacidosis, type II or unspecified type, uncontrolled
  • 250.13 Diabetes with ketoacidosis, type I [juvenile type], uncontrolled

SNOMED

  • 420422005 ketoacidosis in diabetes mellitus (disorder)
  • 420270002 Ketoacidosis in type I diabetes mellitus (disorder)
  • 421750000 Ketoacidosis in type II diabetes mellitus (disorder)
  • 26298008 Diabetic coma with ketoacidosis (disorder)
  • 421075007 ketoacidotic coma in type I diabetes mellitus (disorder)
  • 421847006 Ketoacidotic coma in type II diabetes mellitus (disorder)

CLINICAL PEARLS

  • Admit if blood glucose >250 mg/dL, pH <7.3, HCO3 ≤15 mEq/L, and ketones in urine.
  • Potassium is falsely elevated due to acidosis; start replacement when K+ ≤5.2 mg/dL and urine output is adequate.