Hyperglycemic Hyperosmolar Syndrome

Chapter 68 Hyperglycemic Hyperosmolar Syndrome



Amie Koenig, DVM, DACVIM, DACVECC



KEY POINTS



• Hyperglycemic hyperosmolar syndrome (HHS) is a form of diabetic crisis marked by severe hyperglycemia (>600 mg/dl) and hyperosmolality with no or minimal urine ketones.

• Absence or resistance to insulin and increases in diabetogenic hormone levels stimulate glycogenolysis, and gluconeogenesis, hyperglycemia, osmotic diuresis, and dehydration result.

• Reduction of glomerular filtration rate (GFR) is essential to attain the severe, progressive hyperglycemia associated with HHS.

• Renal failure and congestive heart failure are common concurrent diseases. These likely contribute to HHS via effects on reduction of GFR.

• The most important goals of therapy are to replace fluid deficits and then slowly decrease the glucose concentration, thereby avoiding rapid intracranial shifts in osmolality and preventing cerebral edema. Fluid therapy will start to reduce blood glucose levels via dilution and by increasing GFR and subsequent urinary glucose excretion.

• Prognosis for HHS patients is poor, primarily as a result of concurrent disease.


INTRODUCTION


Nonketotic HHS is an uncommon form of diabetic crisis marked by severe hyperglycemia (>600 mg/dl), minimal or absent urine ketones, and serum osmolality more than 350 mOsm/kg.1 Other names for this syndrome include hyperosmolar hyperglycemic nonketotic state and hyperosmolar nonketotic coma. These terms have been replaced by hyperglycemic hyperosmolar syndrome in human medicine to better reflect the variable degrees of ketosis and inconsistent incidence of coma that occur with this syndrome.2,3 Coma appears to be an uncommon form of this syndrome in animals.


Hyperglycemic Hyperosmolar Syndrome (HHS) is an infrequent, albeit well documented, complication of diabetes mellitus.4-7 The incidence in human diabetics has been estimated to represent less than 1% of all human diabetic hospital admissions.3,8,9 In comparison, HHS accounted for 6.4% of total emergency room visits by diabetic cats in one retrospective study.4 The incidence in dogs is unknown.


This chapter will review the pathogenesis, clinical findings, diagnostic evaluation, and treatment of HHS.



PATHOGENESIS


Pathogenesis of HHS involves hormonal alterations, reduction of glomerular filtration rate (GFR), and contributions from concurrent disease.



Hormonal Alterations


HHS begins with a relative or absolute lack of insulin coupled with increases in circulating levels of counterregulatory hormones including glucagon, epinephrine, cortisol, and growth hormone. These counterregulatory hormones are elevated in response to an additional stressor, such as concurrent disease. Epinephrine and glucagon inhibit insulin-mediated glucose uptake in muscle and stimulate hepatic glycogenolysis and gluconeogenesis, increasing circulating glucose concentration. Cortisol and growth hormone inhibit insulin activity and potentiate the effects of glucagon and epinephrine on hepatic glycogenolysis and gluconeogenesis. In conjunction with insulin deficiency, increases in the diabetogenic hormones increase protein catabolism, which in turn impairs insulin activity in muscle and provides amino acids for hepatic gluconeogenesis.10 Pathogenesis of HHS is very similar to that of diabetic ketoacidosis, except that in HHS it is believed that small amounts of insulin and hepatic glucagon resistance inhibit lipolysis, thereby preventing ketosis3,11,12 and instead promoting HHS. Lower levels of growth hormone have also been documented in patients with HHS.12,13


Hyperglycemia is the primary result of these hormonal alterations. It promotes osmotic diuresis, and osmotic diuresis increases the magnitude of the hyperglycemia, thus leading to a vicious circle of progressive dehydration and hyperosmolality. Neurologic signs are thought to develop secondary to cerebral dehydration induced by the severe hyperosmolality. In humans, elevated blood urea nitrogen (BUN) levels, acidemia, elevated sodium concentration and osmolality, but not glucose concentration, are correlated with the severity of neurologic signs.14



Reduction of Glomerular Filtration Rate


Osmotic diuresis, additional losses such as via vomiting, and decreased water intake contribute to progressive dehydration, hypovolemia, and ultimately a reduction in the GFR as the syndrome progresses. Severe hyperglycemia can occur only in the presence of reduced GFR, because there is no maximum rate of glucose loss via the kidney.15,16 That is, all glucose that enters the kidney in excess of the renal threshold will be excreted in the urine. An inverse correlation exists between GFR and serum glucose in diabetic humans.15 Reductions in GFR increase the magnitude of hyperglycemia, which exacerbates glucosuria and osmotic diuresis. Human HHS survivors have also shown a reduced thirst response to rising vasopressin levels, which may also contribute to dehydration17 and decreased GFR.



Influence of Concurrent Disease


Concurrent disease is important for initiating the hormonal changes associated with HHS and can also be important for exacerbating hyperglycemia. Diseases that are thought to predispose previously stable diabetics to a diabetic crisis include renal failure, congestive heart failure (CHF), infection, neoplasia, and other endocrinopathies,1,18 although any disease can occur. Pancreatitis and hepatic disease seemed to be uncommon concurrent diseases in cats with HHS.4


Renal failure and CHF also exacerbate the hyperglycemia associated with HHS because of their effects on GFR. Decreased GFR is inherent to renal failure. Inability to concentrate urine provides another source for obligatory diuresis. Myocardial failure, diuretic use, and third spacing of fluids associated with CHF may decrease GFR. Cardiac medications such as β-blockers and diuretics are also known to alter carbohydrate metabolism, thus predisposing to diabetic crisis.3



HISTORY AND CLINICAL SIGNS


Animals diagnosed with HHS may be previously diagnosed diabetics receiving insulin or may be newly diagnosed at the time HHS is recognized. The most common client complaints are fairly nonspecific and include decreased appetite, lethargy, vomiting, and weakness. Owners may report polyuria, polydipsia, and polyphagia consistent with diabetes, although these clinical signs may have gone unrecognized. History may also reveal recent onset of neurologic signs including circling, pacing, mentation changes, or seizure. Weight loss is an inconsistent finding.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Hyperglycemic Hyperosmolar Syndrome

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