Diabetic Ketoacidosis

DKA is a syndrome of hyperglycemia (blood glucose >13.8 mmol/L), metabolic acidosis (pH <7.30, serum bicarbonate <18 mmol/L, anion gap >10), ketosis, and severe volume depletion. DKA occurs mainly in insulin-dependent diabetics, and severe insulin deficiency is the hallmark of this syndrome. Raised serum levels of stress hormones (glucagon, catecholamines, cortisol, and growth hormone) are also a feature. The hyperglycemia results in a glucose load in the glomerular filtrate that overwhelms the reabsorptive capacity of the renal tubules, resulting in an osmotic diuresis with fluid and electrolyte depletion. Ketone bodies contribute to this osmotic diuretic effect. The lack of insulin causes unfettered lipolysis and formation of ketoacids.

DKA has an incidence of approximately 8.6% in diabetics² and occurs in a younger age group (mean age, 33 years) compared with DKA-HNHS (44 years) or HNHS (69 years).¹ Precipitating factors associated with the development of DKA include^3–5:

Although there are many “stressors” in the intensive care unit (ICU) environment that could potentially cause or predispose to DKA (e.g., sepsis, altered caloric intake, use of total parenteral nutrition, catecholamine use), new development of DKA in the ICU is not common, presumably because of the high level of vigilance in this environment. Presenting clinical features of DKA reflect the underlying metabolic derangements of dehydration, ketosis, and metabolic acidosis and include:

Laboratory tests supporting the diagnosis of DKA commonly reveal the following:

Hyperosmolar Nonketotic Hyperglycemia Syndrome

The defining features of HNHS include hyperglycemia (blood glucose level >33.3 mmol/L), acidemia (pH <7.3, bicarbonate >15), dehydration, and hyperosmolality (serum osmolality >320) without ketoacidosis. The main differentiation from DKA appears to be the presence of at least some insulin (i.e., relative rather than absolute lack of insulin), more variable levels of stress hormones or counter-regulatory hormones, and the fact that renal dysfunction is commonly present. Renal dysfunction and impaired tubular function result in less capacity to deal with high solute and osmotic loads. This, together with impaired water intake, may result in severe dehydration.

As mentioned earlier, HNHS is less common than DKA, occurs in an older age group, and has a higher mortality rate. Mortality may be associated with missed diagnosis (especially if the patient’s mental state is impaired), comorbidity, or delayed or inappropriate therapy.

For HNHS, particularly in elderly patients, the precipitating factors (in addition to those listed for DKA above) commonly feature:

Laboratory test results are similar to those listed for DKA but differ somewhat in degree, in that:

Metabolic Derangements in Hyperglycemic Syndromes

The main metabolic derangements that result in morbidity and must be urgently addressed in the management of both DKA and HNHS are severe dehydration, insulin deficit, electrolyte depletion, and metabolic acidosis. These are discussed in detail in Chapters 12 and 18.

Severe dehydration is estimated to be a water deficit in the range of 100 to 200 mL/kg.⁴ Although there is no consensus on the ideal approach to fluid management in these patients, prompt restoration of the circulation with isotonic fluid (e.g., normal saline or preferably compound sodium lactate solution), followed by more moderate replacement of the water deficit using hypotonic fluid, are the underlying principles.

The insulin deficit should be treated initially with intravenous soluble insulin to produce normal blood glucose levels within 12 to 24 hours. More rapid correction may predispose to cerebral edema.

Electrolyte depletion is treated by appropriate replacement of sodium, potassium, magnesium, calcium, and chloride, as indicated by frequent laboratory testing during the early phase after presentation.

Metabolic acidosis rarely requires specific therapy and corrects with volume expansion and insulin therapy. Bicarbonate therapy is controversial but currently is not advocated, regardless of the presenting pH, because of the possibilities of exacerbation of hypokalemia, intracellular acidosis, reduced myocardial contractility, and reduced tissue oxygenation.

Figure 163-1 shows serial measurements taken from a typical patient with DKA on presentation and during his treatment in the ICU.

Figure 163-1 Trends in metabolic parameters monitored during treatment of diabetic ketoacidosis. ABG, arterial blood gases.

Therapy may be complicated if there is severe comorbidity such as acute or acute-on-chronic renal failure or severe congestive heart failure, and in the patient who requires complex postsurgical care. In all cases, treatment of hyperglycemic syndromes should occur in an appropriate ICU environment with adequate monitoring and meticulous attention to detail to avoid the neurologic sequelae associated with these syndromes.

Altered Mental State