An 85-year-old male is admitted to the ICU with urosepsis. His blood sugar is 720 mg/dL.
Which of the following is TRUE about hyperglycemic hyperosmolar state (HHS)?
Correct Answer: C
Though HHS is usually associated with type 2 diabetes mellitus and older age, the pathophysiology is similar to that of DKA. However, unlike DKA, patients with HHS usually have enough insulin to prevent ketosis. It should be noted that there is a subpopulation of patients with type 2 diabetes that can present with ketosis.
Given its slower onset (over several days to several weeks), patients with HHS usually have greater free water and electrolyte deficits than patients with DKA due to more prolonged glycosuria and lack of hydration due to concomitant illness. This results in a hyperosmolar state with a serum osmolarity of >320 mmol/kg.
ADA guidelines for diagnosis of HHS include a glucose level of >600 mg/dL, pH >7.3, and bicarbonate level >20 mEq/L. Although HHS is usually not associated with a metabolic acidosis, acidosis may occur due to dehydration and lactate acidosis, concomitant illness (sepsis), or renal failure.
Mortality in HHS ranges from 5% to 16%, which is 10 times higher than mortality in DKA. The higher mortality may reflect the precipitating factor and not hyperglycemia and concomitant metabolic disarray.
Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patient with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(12):2739-2748.
Milanesi A, Weinreb J. Hyperglycemic hyperosmolar state. In: DeGroot LJ, Chrousous G, Dungan K, et al. eds. Endotext. South Darmouth, MA: MDText.com, Inc. www.endotext.org. Accessed December 20, 2018.
You calculate the Δ anion gap/Δ bicarbonate ratio in your patient with DKA and find that it is greater than 1. Explanations include all of the following EXCEPT:
Correct Answer: B
The “delta ratio” or the (change in anion gap)/(change in bicarbonate) is used to determine whether a mixed acid base disorder is present in the setting of a high anion gap metabolic acidosis. A delta ratio of 1 is indicative of an uncomplicated high anion gap metabolic acidosis.
Conditions that increase the serum bicarbonate concentration (metabolic alkalosis or chronic respiratory acidosis) cause a smaller change in bicarbonate and an increased delta ratio (typically >2). Young patients with diabetes have relatively normal renal function and can excrete large quantities of ketoacids in the urine and thus, have a delta ratio of 1 or less. However, if renal function is abnormal (eg due to diabetic nephropathy or volume depletion), less ketoacid anions are excreted resulting in an increased change in anion gap as compared to the change in bicarbonate.
A nonanion gap metabolic acidosis results from an increased chloride and decreased bicarbonate. A delta ratio of <1 is indicative of a combined anion gap metabolic acidosis and nonanion gap metabolic acidosis.
Calculation of the delta ratio is to diagnose mixed acid base disorders in patients with anion gap metabolic acidosis is controversial. Sources of error include the assumption that all buffering of acid occur in the extracellular space, acid anions are buffered solely by bicarbonate, and the distribution and clearance of acid anions and H+ are the same. Furthermore, the calculation of anion gap is derived from the measurement of three or four electrolytes (sodium, potassium, chloride, and bicarbonate) each with its own measurement error. As well, there is the assumption that the normal anion gap is 12 and the normal serum bicarbonate is 24. Thus, the delta ratio should not be used as the sole method to diagnose mixed acid base disturbances in the patient with anion gap metabolic acidosis.
A 68-year-old female with a history of type 2 diabetes mellitus is admitted to the ICU with pancreatitis. Her ICU course is notable for vasodilatory shock requiring vasopressors, respiratory failure requiring mechanical ventilation, renal failure requiring renal replacement therapy, and multiple episodes of hypoglycemia (blood glucose <80 mg/dL). TRUE statements include:
The NICE-SUGAR trial showed that patients receiving intensive glucose control (target blood glucose 81-108 mg/dL) had more episodes of severe hypoglycemia (blood glucose ≤40 mg/dL) than patients in the conventional glucose control (blood glucose <180 mg/dL) group. A subsequent study using data from the NICE-SUGAR database examined the relationship between hypoglycemia and mortality. This study found an increased mortality in patients with hypoglycemia. Furthermore, patients with severe hypoglycemia (blood glucose <40 mg/dL) had a higher risk of death when compared to normoglycemic patients than patients with moderate hypoglycemia (blood glucose between 40 and 79). Patients with more than 1 day of hypoglycemia were also more likely to die than those with 1 day of hypoglycemia. Although hypoglycemia occurred more frequently in patients in the intensive glucose control group, the association between hypoglycemia and death was similar in the two groups.
Patients who had an ICU stay of 7 days or longer were more likely to have moderate/severe hypoglycemia than those whose ICU length of stay was shorter. Patients with moderate and severe hypoglycemia also had an increased risk of death from vasodilatory shock when compared with patients who did not have hypoglycemia.
This study did not show a difference between risk of death with moderate and severe hypoglycemia in patients with and without diabetes. However, another study showed that poorly controlled diabetic patients (as reflected by Hgb A1c level within a 3-month period preceding ICU admission) were more likely to have moderate/severe hypoglycemia and higher risk of death.
Although these studies show an association between hypoglycemia and death, they do not prove causality. The current consensus for blood sugar management in critically ill patients is to target a blood sugar between 140 to 180 mg/dL. Patients with poorly controlled diabetes may benefit from closer blood sugar monitoring as they are more likely to become hypoglycemic and have poorer outcomes.
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