Hyperosmolar Hyperglycemic State

Dr Sudeepta Rao, PG 2nd yr – Gen Med

DCMS

Introduction

• Hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA) represent two distinct metabolic derangements manifested by insulin deficiency and severe hyperglycemia

• DKA is defined as the presence of all three of the following: (i) hyperglycemia (glucose >250 mg/dL), (ii) ketosis, and (iii) acidemia (pH <7.3) .

• HHS is characterized by severe hyperglycemia and hyperosmolarity.

• HHS and DKA are not mutually exclusive but rather two conditions that both result from some degree of insulin deficiency. They can and often do occur simultaneously

Incidence of DKA 1980-2003

Mortality rate of DKA 1980-2001

Introduction

• Age adjusted mortality rates in the U.S. have dropped by 22% between 1980 and 2001

• Contrary to DKA mortality, the mortality rate of HHS has remained high, ~ 15%, compared to less than 5% in patients with DKA

• Severe dehydration, older age, and the presence of comorbid conditions in patients with HHS, account for the higher mortality in these patients .

Definitions

• DKA consists of the biochemical triad of hyperglycemia, ketonemia and metabolic high anion gap acidosis

• The term “hyperglycemic hyperosmolar nonketotic coma” has been replaced with the term “hyperglycemic hyperosmolar state” (HHS)

• 1)the hyperglycemic hyperosmolar state may consist of moderate to variable degrees of clinical ketosis detected by nitroprusside method and

• 2) alterations in consciousness may often be present without coma .

Pathophysiology

• The underlying defects in DKA and HHS are 1) reduced net effective action of circulating insulin as a result

of decreased insulin secretion (DKA) or ineffective action of insulin in HHS

2) elevated levels of counterregulatory hormones: glucagon, catecholamines , cortisol, and growth hormone, resulting in increased hepatic glucose production and impaired glucose utilization in peripheral tissues

3) dehydration and electrolytes abnormalities mainly due to osmotic diuresis caused by glycosuria

4) If insulin deficiency is severe enough, ketosis and ultimately acidosis develop .

Pathophysiology

• In HHS:1) there is enough insulin to prevent lipolysis and

ketogenesis but not adequate to cause glucose utilization (as it takes 1/10 as much insulin to suppress lipolysis as it does to stimulate glucose utilization)

2) possible smaller increases in counterregulatory hormones

Hyperglycemia

Dehydration & Hyperosmolarity:

Hyperglycemia

Osmotic Diuresis

Dehydration

Hyper Osmolarity

Glycosuria

Increased GFR

Hypovolemia

Decreased GFR & Renal Glucose Loss

Hyperglycemia

Ketogenesis and Acidosis:

Precipitating Causes:

History and Physical Examination:• DKA usually evolves over a shorter period (usually less than 24 hours)

than HHS, which tends to evolve over a few days.

• The common clinical pictures in DKA and HHS due to hyperglycemia include polyuria, polyphagia, polydipsia, weight loss, weakness and physical signs of dehydration such as dry buccal mucosa, sunken eye balls, poor skin turgor, tachycardia, hypotension and shock in severe cases.

• Kussmaul respiration, acetone breath, nausea, vomiting and abdominal pain may also occur primarily in DKA.

• Mental status in DKA may vary from full alertness to profound lethargy or coma but less frequent than HHS.

Initial Evaluation of the Patient:

Assessment of the degree of dehydration

• Decreased tissue turgor suggests 5% dehydration. • An orthostatic change in pulse alone suggests that there has been loss of

approximately 10% of extracellular fluid volume (~2 L), • orthostatic change in pulse and blood pressure (>15/10 mm Hg) suggests

a 15% to 20% fluid deficit (3 to 4 L). • Supine hypotension, when present, suggests either severe dehydration

and a decrease in extracellular fluid volume of more than 20% or underlying sepsis.

• Assessment of degree of dehydration may be difficult in the elderly and those with underlying autonomic neuropathy, who may have orthostatic hypotension at baseline.

Relationship between serum osmolality and level of consciousness:

Admission Clinical And Biochemical Profile And Response To Therapy Of Comatose Vs. Non

comatose Patients:

Laboratory Evaluation:

* Blood urea nitrogen Serum chloride Carbon dioxide, also known as CO2 Creatinine Blood glucose Serum potassium Serum sodium

*

Admission biochemical data in patients with HHS and DKA

Serum Sodium

• The serum sodium level may be low or normal. It may even be elevated in patients who are severely dehydrated even though total body sodium is depleted.

• True sodium concentration (millimolar )can be obtained by multiplying excess glucose above 100 mg/dl by 1.6 /100 *. If the corrected sodium level is extremely low , hypertriglyceridemia (secondary to uncontrolled diabetes ) should be suspected.

*

Serum Potassium

• Serum potassium levels at presentation may be high, normal, or low even though total body potassium may be depleted.

• Unless the initial serum potassium is elevated above 5.5 mEq/L or the patient is in acute renal failure or oliguric, potassium replacement is required when treatment is initiated

Laboratory Evaluation(contd)

• level of consciousness correlates more closely with serum osmolality than with pH.

• Coma in an individual whose serum osmolality is less than 320 mOsm/kg warrants further evaluation for other causes of the coma.

• Leukocytosis is a common finding in patients with DKA or HHS, but leukocytosis greater than 25,000 /μL suggests ongoing infection.

Pitfalls of Laboratory Tests

• elevation of serum creatinine, either as a result of dehydration or interference from ketone bodies if a colorimetric method is used.

• Most of the laboratory tests for ketone bodies use the nitroprusside method, which detects acetoacetate, but not β hydroxybutyrate (BOHB ) .

• Serum ketones may be negative in some situations, such as alcoholic ketoacidosis or DKA associated with hypoxia.

• Under “normal” conditions, the ratio of β-hydroxybutyrate to acetoacetate is 3:1. This increases to 8:1 in alcoholic ketoacidosis or DKA associated with severe hypoxia

• drugs that have sulfhydryl groups can interact with the reagent in the nitroprusside reaction, giving a false positive result. Particularly important in this regard is captopril, an angiotensin converting enzyme inhibitor prescribed for the treatment of hypertension and diabetic nephropathy.

Treatment

• The goals of therapy in patients with DKA and HHS include

1) Improvement of circulatory volume and tissue perfusion,

2) Gradual reduction of serum glucose and plasma osmolarity,

3) Correction of electrolyte imbalance, and in DKA steady resolution of ketosis,

4) Identification and prompt treatment of co-morbid precipitating causes

Fluid Therapy

• DKA and HHS are volume-depleted states with water deficit of approximately 6 L in DKA and 9 L in HHS

• The initial fluid of choice is isotonic saline, which we recommend

to be infused at the rate of 15–20 ml /kg body weight per hour or 1–1.5 L during the first hour.

• The choice of fluid for continued repletion depends on the

hydration status, serum electrolyte levels, and urinary output. • In patients who are hypernatremic or eunatremic, 0.45% NaCl

infused at 4–14 ml/kg/hour is appropriate and in patients with hyponatremia 0.9% NaCl at a similar rate is preferred.

Fluid Therapy(Contd)

• The goal is to replace half of the estimated water deficit over a period of 12- 24 hours.

• In patients with hypotension, aggressive fluid therapy with isotonic saline should continue until blood pressure is stabilized. The administration of insulin without fluid replacement in such patients may further aggravate hypotension.

• Patients with DKA and HHS require calories for proper metabolism of ketone bodies.

Fluid Therapy(Contd)

• Therefore in DKA, as soon as blood glucose falls below 200 mg/dl, the sodium chloride solution should be replaced with 5% glucose containing saline solution with a reduced rate of insulin administration until acidosis and ketosis are controlled while avoiding too rapid correction of hyperglycemia (which may be associated with cerebral edema especially in children) and also inhibiting hypoglycemia.

• In HHS, the use of D5 ½ NS should start when blood glucose reaches 300 mg/dl, because overzealous replacement with hypotonic fluids has been associated with the development of cerebral edema

Insulin Therapy

• starting with an intravenous loading dose of 0.15 U/kg body weight (usually 10 U in adults)

• followed by a continuous infusion of insulin at a rate of 0.1 U/kg per hour (usually 5 to 7 U per hour in adults)

• If the patient is in shock or the initial serum potassium level is less than 3.3 mEq/L, resuscitation with intravenous fluids or potassium replacement or both is instituted before commencing the insulin infusion

• An insulin infusion of 5 to 7 U per hour should lower serum glucose concentrations by 50 to 75 mg/dL per hour

Insulin Therapy

• The insulin infusion rate should be continually reassessed and increased if the rate of decrease in glucose is less than 50 mg/dL per hour, providing that other causes for the lack of response to therapy have been excluded.

• The rate of insulin should be adjusted to maintain blood glucose between 150-200 mg/dl in DKA and 250-300 mg/dl for HHS until DKA is resolved or mental obtundation and hyperosmolar state are corrected in HHS

Potassium Therapy

Ongoing Monitoring

Thankyou