1. Hyperosmolar Hyperglycemic
State
Dr Sudeepta Rao,
PG 2nd yr – Gen Med
DCMS

2. 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

3. Incidence of DKA 1980-2003

4. Mortality rate of DKA 1980-2001

5. 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 .

6. 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 .

8. 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 .

9. 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

12. Hyperglycemia

13. Dehydration & Hyperosmolarity:
Hyperglycemia Glycosuria
Osmotic Diuresis Increased GFR
Dehydration Hypovolemia
Hyper Osmolarity Decreased GFR & Renal
Glucose Loss
Hyperglycemia

14. Ketogenesis and Acidosis:

15. Precipitating Causes:

16. 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.

17. Initial Evaluation of the Patient:

18. 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.

19. Relationship between serum
osmolality and level of consciousness:

20. Admission Clinical And Biochemical Profile And
Response To Therapy Of Comatose Vs. Non
comatose Patients:

21. Laboratory Evaluation:
*
* Blood urea nitrogen Serum chloride Carbon dioxide, also known as CO2 Creatinine
Blood glucose Serum potassium Serum sodium

23. Admission biochemical data in patients
with HHS and DKA

24. 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.
*

25. 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

26. 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.

27. 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.

28. 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

30. 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.

31. 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.

32. 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

33. 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

34. 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

36. Potassium Therapy

37. Ongoing Monitoring

38. Thankyou