HHS is "defined" by severe hyperglycemia with serum glucose usually >600 milligrams/dL (>33.3 mmol/L), an elevated calculated plasma osmolality of >315 mOsm/kg (>315 mmol/kg), serum bicarbonate >15 mEq/L (>15 mmol/L), an arterial pH >7.3, and serum ketones that are negative to mildly positive in a 1:2 dilution (by nitroprusside method). These values, however, are fairly arbitrary. Metabolic acidosis or ketonemia associated with HHS is likely to be due to tissue hypoperfusion (lactic acidosis), starvation ketosis, and azotemia in various combinations, although there is growing evidence for ketosis-prone type 2 diabetic subgroups. It is important to recognize the potential for a variety of mixed acid-base patterns in patients with HHS.
A comparison of the laboratory features of diabetic ketoacidosis and HHS is shown in Table 227-3.
TABLE 227-3Diagnostic Criteria for Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) ||Download (.pdf) TABLE 227-3 Diagnostic Criteria for Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)
| ||DKA ||HHS |
|Plasma glucose ||>250 milligrams/dL (>13.8 mmol/L) ||>600 milligrams/dL (>33.3 mmol/L) |
|Serum bicarbonate ||≤18 mEq/L (<18 mmol/L) ||>15 mEq/L (>15 mmol/L) |
|Urine acetoacetate* ||+ ||– or small |
|Serum ketones† ||+ ||– or small |
|Serum osmolality‡ ||Variable ||>320 mOsm/kg (>320 mmol/kg) |
|Anion gap# ||>12 mEq/L (>12 mmol/L) ||<12 mEq/L (<12 mmol/L) |
|Arterial/venous pH ||<7.30 ||>7.30 |
LABORATORY TESTING AND IMAGING
Tailor laboratory tests to the patient and the clinical findings. A comprehensive metabolic profile, calculated and measured serum osmolality, urine osmolality, lactic acid, serum ketones, magnesium, CBC with differential, and blood and urine cultures should all be considered. In addition, cardiac markers, total creatine phosphokinase, arterial or venous blood gas, thyroid function studies, procalcitonin, and coagulation profiles might be needed. Chest radiographs and electrocardiograms are generally recommended. Diagnostic studies, such as CT, lumbar puncture, and toxicologic studies, should be patient specific.
In general, electrolyte abnormalities vary. Initially, contraction alkalosis due to a profound water deficit may occur. An anion gap metabolic acidosis is often attribuTable to sepsis, poor tissue perfusion, starvation ketosis, or renal impairment.
Serum sodium level varies and is not a reliable indicator of the degree of volume contraction. Hyperglycemia has a dilutional effect on measured serum sodium: Serum Na+ decreases by approximately 1.6 mEq/L (1.6 mmol/L) for every 100 milligrams/dL (5.6 mmol/L) increase in serum glucose >100 milligrams/dL (5.6 mmol/L) (Formula 222-1).
Formula for correction of sodium in presence of severe hyperglycemia.
For glucose levels >400 milligrams/dL (22.2 mmol/L), a correction factor of 2.4 may be more accurate.
Osmolality Serum osmolality correlates positively with severity of disease as well as mental status changes and coma. A calculated effective serum osmolality excludes osmotically inactive urea, which is usually included in laboratory measures of osmolality (Formula 227-2).
Formula for calculation of serum osmolality in presence of severe hyperglycemia.
The normal serum osmolality range is approximately 275 to 295 mOsm/kg. Values >300 mOsm/kg are usually indicative of significant hyperosmolality, and those >320 mOsm are commonly associated with alterations in cognitive function.
On average, potassium losses range from 4 to 6 mEq/kg, although deficits can be as high as 10 mEq/kg body weight. Despite these total body deficits, initial serum laboratory measurements may be normal or even high in the presence of acidemia. Initial values may be reported as normal with volume contraction and with metabolic acidosis when intravascular [H+] ions are exchanged for intracellular [K+] ions. As intravascular volume is replaced and acidemia is reversed, [K+] deficiency becomes more apparent.
Hypomagnesemia is common, and serum magnesium levels should be monitored and replaced as appropriate.10 Consequences of hypophosphatemia, such as CNS abnormalities, cardiac dysfunction, and rhabdomyolysis, are uncommon and usually associated with serum phosphate levels below 1.0 milligram/dL. Routine replacement of phosphate, unless severe, is usually unnecessary, and replacement may lower ionized calcium levels.11 Prerenal azotemia is common, with plasma blood urea nitrogen:creatinine ratios often exceeding 30:1. Leukocytosis is variable but is usually due to infection or hemoconcentration.