Diabetic Ketoacidosis: Maintaining Glucose Control

Pharmacy TimesOctober 2011 Diabetes
Volume 77
Issue 10

The metabolic chain reaction that precedes diabetic ketoacidosis can occur rapidly and this potentially life-threatening condition requires swift recognition and treatment.

The metabolic chain reaction that precedes diabetic ketoacidosis can occur rapidly, and this potentially life-threatening condition requires swift recognition and treatment.

Two critical words in a diabetic’s vocabulary are “management” and “control.” When a patient with diabetes fails to manage food intake and loses control of blood sugar levels, hyperglycemia follows. In most cases, blood sugar levels elevate slightly, which prompts the individual with diabetes to take action to lower those levels. Under some conditions, blood sugar rises precipitously, which is usually caused by 1 or more of the following1-3 :

• Developing or fulminant infection (especially Klebsiella pneumonia) or illness

• Serious disruption of insulin treatment

• New onset of diabetes

• Physical or emotional stress

• Adverse drug reaction (especially to corticosteroids, pentamidine, thiazides, sympathomimetics, or secondgeneration antipsychotics4 )

Acute, life-threatening diabetic ketoacidosis (DKA) can develop rapidly. Table 11,2 describes criteria usually used to define DKA. We typically associate this metabolic abnormality with type 1 diabetes, but it also occurs in some patients with type 2 diabetes, with infection or an adverse drug reaction as the primary causes. As blood sugar rises in DKA, the patient becomes dehydrated and metabolic changes produce acidosis.1,2,4,5


DKA usually occurs when absolute or relative insulin deficiency leads to increased counter-regulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine). These hormones enhance hepatic glucose production (gluconeogenesis), glycogenolysis, and lipolysis, all of which increase free fatty acids (FFAs) in circulation. With insulin unavailable, the liver turns to FFAs as an alternative energy source; FFA metabolism releases ketones in large quantities. Metabolic acidosis follows.

During metabolic acidosis, the kidneys—concentrating glucose and ketones in the urine in an attempt to remove them—require more water than normal; osmotic diuresis causes dehydration. Hydrogen ions accumulate extracellularly and shift potassium from the intracellular to the extracellular space, and it, too, is lost in the urine. Thus, both hyper- and hypokalemia frequently occur.

Patients may begin to breathe shallowly (deep sighing respirations) as the respiratory system tries to compensate for acidosis. Ketones also cause nausea and vomiting—and more dehydration—and acetone produces DKA’s characteristic fruity breath odor. Loss of potassium, sodium, and chloride creates a downward spiral of serum hyperosmolarity, dehydration, and acidosis. This increases brain cell osmolarity, altering level of consciousness. Most patients experiencing DKA lose 6 L or nearly 100 mL/kg of body weight, initially from intracellular fluid and later from extracellular fluid.1,2

DKA is more common in young children and adolescents than in adults, but in all age groups, hospitalizations pursuant to DKA are increasing. Approximately half of all diabetes-related hospital admissions in diabetics younger than 44 years result from DKA. It is a presenting symptom leading to the diagnosis of type 1 diabetes in about 3% of patients overall, but up to 25% of newly diagnosed children.6 Prognosis is good if patients are treated promptly.

Prognosis worsens in older patients with diabetes who have severe intercurrent illnesses (eg, myocardial infarction, sepsis, or pneumonia), deep coma, hypothermia, or oliguria. Prognosis also worsens if treatment is provided outside an intensive care unit (ICU). The overall mortality rate for DKA is less than 2%. With aggressive, state-of-the-art fluid management, few patients develop residual effects.1,2

Sign, Symptoms, and Red Flags

Most pharmacists are keenly aware of DKA’s acute signs: insidious increased thirst (polydipsia), increased urination (polyuria), malaise, weakness, and fatigue. Patients usually develop nausea and vomiting. Diffuse abdominal pain, decreased appetite, and anorexia are possible. Sometimes, patients report decreased perspiration, and they may be disoriented or confused. Coma is an uncommon, late red flag. Cerebral edema from rapid intracellular fluid shifts can occur, and is the most frequent cause of death. If DKA is caused by an underlying condition or infection, additional symptoms will be present.1,2,7

Best care requires constant vigilance. Consensus is that patients who present with DKA should be treated in the intensive care unit for the first 24 to 48 hours. Staff there will focus on 5 steps, described in Table 2.1,2,4,8,9 Note that the need for hour-by-hour clinical observation and close coordination between the clinical team and the laboratory is usually detailed in the treating organization’s DKA protocol.

Improvements in laboratory technology have helped clinicians’ ability to monitor these patients. Point-of-care testing provides almost immediate results for bedside blood glucose and ketone levels. Clinicians will also monitor blood gas and blood electrolytes routinely and frequently, including bicarbonate and venous pH. Clinicians must monitor vigilantly and juggle interventions cautiously to avoid potentially life-threatening hypokalemia and hyperkalemia, as well as rebound ketosis and hypoglycemia.10-12

Although patients may be able to leave the ICU when they stabilize, they must remain hospitalized until their pH exceeds 7.3, their bicarbonate level exceeds 18 mEq/L, and they successfully switch back to daily insulin. Once the patient is stable, clinicians will allow him or her to eat a meal, administering subcutaneous regular insulin before the meal. The dose will depend on whether the patient is a longstanding diabetic or newly diagnosed and the type of insulin the patient used before the DKA. Long-acting insulins can be reinitiated at the patient’s previous dose. Neutral protamine Hagedorn insulin should be introduced with more care at approximately half the previous dose, increasing the dose as the patient tolerates it. If ketosis doesn’t occur, the insulin infusion can be discontinued 30 minutes later. Otherwise, the clinical team continues to monitor, using an intravenous insulin infusion and glucose to manage hyper- and hypoglycemia.2,13,14


Teaching patients to monitor blood glucose frequently during the day is important if they are to maintain control. Emphasizing that they need to explore possible reasons for unexpectedly high blood glucose values decreases the likelihood of DKA.

Pharmacists need to be particularly attentive to patients at high risk for DKA: patients who control their diabetes poorly; patients with lower socioeconomic status or inadequate access to outpatient care; adolescents who have or may have eating disorders; and patients with recurrent ketoacidosis. Patients treated with insulin pumps also have higher risk for DKA, because undetected insulin delivery interruption can precipitate DKA in as little as 4 hours.15-17 Advise these patients to monitor more often, and teach them the signs of poor control: thirst, frequent urination, and fatigue. PT

Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The views expressed are those of the author and not those of any government agency.


1. Joint British Diabetes Societies Inpatient Care Group. The management of diabetic ketoacidosis in adults. London: NHS Diabetes; 2010. www.diabetes.nhs.uk/document.php?o=1336.

2. Wolfsdorf J, Glaser N, Sperling MA. American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:1150-1159.

3. Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diab Care. 2004;27:553-591.

4. Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. In: DeFronzo RA, Ferrannini E, Keen H, Zimmet P, eds. International Textbook of Diabetes Mellitus. 3rd ed. Chichester, UK: John Wiley & Sons; 2004:1101-1119.

5. Bowden SA, Duck MM, Hoffman RP. Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor. Pediatr Diabetes. 2008;9(3, pt 1):197-201.

6. Rewers A, Klingensmith G, Davis C, et al. The SEARCH for Diabetes in Youth Study Group: Diabetic ketoacidosis at onset of diabetes: the SEARCH for Diabetes in Youth Study (Abstract). Diabetes. 2005;54(suppl 1):A63.

7. Glaser NS, Marcin JP, Wootton-Gorges SL, et al. Correlation of clinical and biochemical findings with diabetic ketoacidosis-related cerebral edema in children using magnetic resonance diffusion-weighted imaging. J Pediatr. 2008;153:541-546.

8. Waldhausl W, Kleinberger G, Korn A, Dudczak R, Bratusch-Marrain P, Nowotny P. Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentration. Diabetes. 1979;28:570-584.

9. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diab Care. 2009;32:1335.

10. Bektas F, Eray O, Sari R, Akbas H. Point of care testing of diabetic patients in the emergency department. Endocr Res. 2004;30:395-402.

11. Khan ASA, Talbot JA, Tiezen KL, et al. Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance. Diab Med. 2004;21:782-785.

12. Wallace TM, Matthews DR. Recent advances in the monitoring and management of diabetic ketoacidosis. QJM. 2004;97:773-780.

13. Cavan DA, Hamilton P, Everett J, Kerr D. Reducing hospital inpatient length of stay for patients with diabetes. Diab Med. 2001;18:162-164.

14. Joint British Diabetes Societies Inpatient Care Group. The management of diabetic ketoacidosis in adults. www.diabetes.nhs.uk/document.php?o=1336. Published March 2010. Accessed July 27, 2011.

15. Rewers A. Current controversies in treatment and prevention of diabetic ketoacidosis. Adv Pediatr. 2010;57:247-267.

16. Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002;287:2511-2518.

17. Levine BS, Anderson BJ, Butler DA, Antisdel JE, Brackett J, Laffel LM. Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes. J Pediatr. 2001;139:197-203.

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