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GENERAL GUSIDELINES AND REFERENCES FOR ADULT DIABETIC KETOACIDOSIS (DKA)

Level of Evidence = LOE

A = Randomized prospective controlled trials (control and intervention group are enrolled prior to measured

outcome)

B

= Nonrandomized prospective trials

C

= Retrospective analyses

E

= Expert opinion, guideline, consensus statement, textbook summary, articles that summarize

M = Meta-analyses

Q = Economic analyses

1. (LOE=E) American Diabetes Association Position Statement. Hyperglycemic crises in-patients with diabetes mellitus. Diabetes Care 2002; 25 (Suppl 1): S100-S108.

Diagnostic criteria for DKA

Plasma glucose > 250 mg/dL

Arterial pH < 7.30

Serum bicarbonate < 18 mEq/L

Presence of serum and/or urine ketones

Anion gap [ Na – (Cl + HCO3)] > 10

Diagnostic Studies in DKA (see #1 above too)

2.

(LOE=C) Hendey GW, Schwab T, Soliz T. Urine ketone dip test as a screen for ketonemia in diabetic ketoacidosis and ketosis in the emergency department. Ann Emerg Med 1997; 29: 735-738.

3.

(LOE=C) Paulson WD. Anion gap-bicarbonate relation in diabetic ketoacidosis. Am J Med 1986; 105(6):

995-1000.

4.

(LOE=A/B) Adrogue HJ, Wilson H, Boyd AE, Suki WN, Eknoyan G. Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med 1982; 307: 1603-1610.

5.

(LOE=B) Brandenburg MA, Dire, DJ. Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis. Ann Emerg Med 1998; 31(4): 459-

465.

Serial measurements of glucose, electrolytes, BUN, creatinine, osmolality and pH should be performed Q2-

4hrs until DKA has resolved Venous pH measurements accurately approximate arterial pH and are the recommended method for serial

pH measurements Serial ketone measurements are not recommended

Criteria for resolution of DKA = glucose < 200 mg/dL, serum bicarbonate > 18 mEq/L, venous pH > 7.3

Fluids and DKA (see #1 above too)

6.

Fein IA, Rackow EC, Sprung CL, Grodman R. Relation of colloid osmotic pressure to arterial hypoxemia and cerebral edema during crystalloid volume loading of patients with diabetic ketoacidosis. Ann Intern Med 1982; 96: 570-575. (LOE=B)

7.

Hillman K. Fluid resuscitation in diabetic emergencies – a reappraisal. Intensive Care Med 1987; 13: 4-8. (LOE=E)

Recommended rate of infusion = 15-20 mL/kg/hr for 1 hour, then 4-14 mL/kg/hr thereafter (adjusted for

hemodynamic status, cardiac and renal function) Choice of fluid depends upon corrected Na = [measured Na + {(glucose – 100)/100 x 1.6}]

0.9NS recommended if corrected Na low

0.45NS recommended if corrected Na normal or high

D5 should be added to fluids when blood glucose < 250 mg/dL and continued until DKA resolved and po intake resumed

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Potassium (20-40 mEq KCL per liter) should be added to fluids when serum K < 5.0 mEq/L and urine

output established Fluid rate should be adjusted so that the serum osmolality does not decrease at a rate > 3 mOsm/kg/hr

Insulin Therapy (see #1 above too)

8.

Butkiewicz EK, Leibson CL, O’Brien PC, Palumbo PJ, Rizza RA. Insulin therapy for diabetic ketoacidosis:

bolus injection versus continuous intravenous infusion. Diabetes Care 1995; 18(8): 1187-1190. (LOE=C)

9.

Kitabchi AE, Ayyagari V, Guerra SMO. The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis. Ann Intern Med 1976; 84: 633-638. (LOE=A)

10.

Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by different routes. N Engl J Med 1977; 297: 238-241. (LOE=A)

Regular insulin by continuous intravenous infusion is recommended until DKA is resolved; hourly SQ or

IM injections is acceptable if DKA is mild Recommended dosages of Regular insulin:

IV route: 0.15 units/kg bolus, then 0.1 units/kg/hr continuous drip

SQ/IM route: 0.4 units/kg bolus (50% of dose given IV, 50% given SQ or IM), then 0.1 units/kg/hr SQ or

IM Insulin should not be initiated if serum K < 3.3 mEq/L until potassium given and repeat K > 3.3 mEq/L

Blood glucose should be monitored by fingerstick Q1hr until DKA resolved and IV or hourly SQ/IM insulin

discontinued; thereafter, it can be monitored > Q4hrs with SQ regular insulin sliding scale coverage Insulin dose should be adjusted (and D5 added to IVF) after blood glucose < 250 mg/dL to keep glucose

150-200 mg/dL until DKA resolved If blood glucose does not decrease by > 50-70 mg/dL per hour, the insulin dose should be doubled

Long-acting insulin therapy may be initiated/resumed after DKA resolved and po intake resumes

Bicarbonate replacement and DKA (see #1 above too)

11.

Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, Bertrand JC. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med 1999; 27(12): 2690-2693. (LOE=C)

12.

Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 1996; 81: 314-320. (LOE=B)

13.

Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis. Br Med J (Clin Res Ed) 1984; 289:1035-1038. (LOE=A)

14.

Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986; 105(6): 836-840. (LOE=A)

Data does not show a beneficial effect of bicarbonate replacement on outcome of DKA when serum pH >

6.9; insufficient data for patients with pH < 6.9 Consider bicarbonate replacement if pH < 6.9 and/or in the presence of severe/symptomatic hyperkalemia or cardiovascular instability

Phosphate replacement and DKA (see #1 above too)

15 (LOE: A) Wilson HK, Keuer SP, Lea AS, Boyd AE, Eknoyan G. Phosphate therapy in diabetic ketoacidosis. Arch Intern Med 1982; 142: 517-520.

16 (LOE: A) Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 1983; 57: 177-180.

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Data does not show a beneficial effect of phosphate replacement on outcome of DKA regardless of serum

phosphate level Phosphate replacement may be considered if serum phosphate severely decreased ( < 1 mg/dL) or in the

presence of anemia, hypoxia, cardiac dysfunction, respiratory depression or other symptoms felt to be related to hypophosphatemia Risk of hypocalcemia is increased with phosphate therapy

If given, recommended dose is potassium phosphate 20-30 mEq (contains 13.6-20.4 mmol phosphate) per liter IVF