HIPOROSMOLAR NON

KETOTIK

Lita Septina

Internal Medicine Dept

Islamic University of Sumatera Utara

Acute Complication of Diabetes

Mellitus
HyperOsmolar Non Ketotic Coma (HONK)
Diabetic ketoacidosis (DKA)
Hypoglycemia

Hyperosmolar Non Ketotic Coma

In 1957 Summent and Schwarts described a syndrome of

marked diabetic stupor with hyperglycemia and

hyperosmolarity in the absence of ketosis.
The syndrome has been given a number of names :
nonketotic hyperosmolar coma, diabetic hyperosmolar
state, hyperosmolar nonacidotic diabetes and
hyperglycemia hyperosmolar state (HHS) (ADA)
17,5 cases per 100.000 person-years and 1 in 1000
admissions to the hospital, in US
The mortality rate as high as 12% to 46%. The mortality
rate increases with higher levels of serum osmolarity.

HONK: Differences from DKA

Patients usually older- typically 60 or more
Major pathophysiologic differences
longer uncompensated osmotic diuresis
greater volume depletion
Acidemia (pH > 7.3) and ketosis are mild
Higher mortality often 30-50%
primarily due to underlying vascular or infectious
event
Occurs in Type 2 diabetics, often mild or unrecognized

Basic physiology
Blood glucose homeostasis involves neural, metabolic, and
hormonal reactions
Insulin + glucagon + epinephrine work together to
maintain blood sugar levels initially by glycogenolysis,
then through gluconeogenesis
Glucose metabolism in the fed state : Gambar 1
Glucose metabolism in the fasting state : Gambar 2
Prolonged fasting leads to the non-insulin mediated fuel
source :
1. lipolysis produces glyserol which, when combined with
lactat from recycled glucose, can provided
gluconeogenesis
2. proteolysis, mediated by cortisol and glucagon,
mobilizes amino acids from muscle tissue

Regulatory hormone

Insulin acts at the liver by :

1. Supressing endogenous glucose production (gluconeogenesis)
2. Increasing glucose storage as glycogen (glycogenesis)
3. Inhibiting glycogen breakdown (glycogenolysis)
NET EFFECT : store glucose as glycogen

Insulin acts at the liver and adipose cells by :

1. Produces triglycerides from glycerol and free fatty acids
2. Inhibit breakdown of triglycerids
NET EFFECT : increase lipogenesis in liver

Insulin acts at muscle cells by :

1.
2.

Stimulating uptake of amino acids

Preventing release of amino acids from muscle cells and
hepatic protein source
NET EFFECT : increase muscle protein

Counter-regulatory hormones
Glucagon : promotes hepatic production of glucose and

ketones
Catecholamines : promotes hepatic glucose output
(glycogenolysis), inhibits mucle glucose uptake,
enhances fatty acid mobilization (lipolysis)
Cortisol and Growth Hormone : promotes hepatic
glucose production and antagonizes the peripheral
effects of insulin on glucose disposal, primarily in the
mucle

Patofisiologi HONK/DKA

Clinical Presentation of HONK

History

Physical
examination

Laboratory results

Insufficient fluid
intake, polyuria
Decreasing polydipsia
Depressed mentation
Mild or undiagnosed
diabetes
Evolution over days
to weeks

Stupor in majority
Profound
dehydration
Shallow breathing
No acetone odor
Multiple
neurological
disorders
Rare cerebral
edema

Normal serum pH
Serum glucose >600
mg/dl, glycosuria
Serum osmo >350
Normal anion gap
Normal serum
ketones
Normal uric acid

Clinical Findings of Hyperosmolarity

HHS should be suspect : elderly patient with or without

the preexisting diagnosis of diabetes who exhibits acute

or subacute deterioration of CNS function and severely
dehydrated
Tachycardia
Low grade fever
Low or normal blood pressure
Dehydration dry mucous membrane, absent axillary
sweat, poor skin turgor.
Nausea, vomiting, distension, and pain-gastroparesis is
due to hypertonicity
Lethargy, hallucinations, and psychosis

Laboratory Findings in
Hyperosmolarity

Blood Glucose: usually > 600mg/dl

AGDA ; pH 7.3
BUN/creatinin : increased
Osmolality >330mOsm/kg
Total body sodium low, level high, normal or low.
Potassium high, normal or low.
Leukocytosis 15,000-40,000 even without infection
( response to catecholamine-related stress and
dehydration)
Hb,Ht increased due to dehydration

Hyperosmolar State
Hyperglycemia acts as an osmotic diuretic

with obligatory loss of water and

electrolytes.
Osmolality = 2(Na) + Glucose/18 + BUN/2.8
(normal 293 )
Ketosis/hyperglycemia stimulate vomiting
with aggravation of dehydration

Fluid Balance in Diabetic

Hyperosmolarity
ECF = 14 L

ICF = 28 L

ECF

ICF

H2O

ECF hyperosmolar from ICF autotransfusion

Osmotic Diuresis
H2O

Osmotic Diuresis

ECF and ICF both hyperosmolar

Precipitating Factors for

hyperosmolarity

Medical management of type 2 diabetes, fourth

edition. ADA, Clinical Education Series

Priority in the Treatment of

HONK
Replacing volume deficits normal saline according
to BP, urine output and CVP value for old age, total
deficits around 6-9 liters.

Correcting hyperosmolarity to 300 milliosmoles/L

Managing any underlying illnesses
Insulin for for acidotic, hyperkalameic or renal failure

patients RI 0.15u/kg bolus then0.1/kg/hr infusion until

blood sugar about 250mg/dl or osmo about 315

Approach to Therapy
Correcting the hyperosmolar state and

dehydration is the initial aim of therapy.

Insulin therapy should be undertaken
only after the patient is stable
hemodynamically.
Glucose and H2O

H2O lost in urine

Loss of ECF, vascular collapse and death

Rehydration
Bolus fluids until correction of circulatory
failure.
Correct deficit over 36 to 48 hours.

Provide maintenance fluids (1600cc/m2/d) at

the same time.
Subtract resuscitation fluids from deficit.

Avoid fluid administration > 4L/m2/d

Fluid and Electrolytes

Volume
1 l/h 2-3, thereafter adjusted according
to need; usually 4-6 l in first 24 h

Fluids

Isotonic saline
Hypotonic saline if plasma Na> 150 mmol/l
(no more than 1-2 lconsider D5W with
insulin if marked hypernatremia)
5% dextrose 1l 4-6 hourly when blood
glucose has fallen to 250 mg/dl.

Electrolytes
Sodium content varies between 75 to

154 mEq/L. Reduce as sodium levels

approach normal.
Total body potassium is reduced. When
K levels reach < 3,3 add 20-40 mEq/L
as both KCL and Kphos.
Maximum K infusion rate 0.5 mEq/kg/hr.

Insulin
10-15 U of RI IV bolus
Continuous intravenous infusion:
5-10 U/h (0.1 U/kg/h) initially until blood
glucose has fallen to < 300 mg/dl.
Thereafter, adjust rate (1-4U/h) during
dextrose infusion to maintain blood glucose
150-250 mg/dl.
When oral intake is resumed, SC insulin is
given, before stop IV insulin.

Complications of HONK
Hypoglycemia
Hypokalemia
Cerebral edema

Glucose metabolism : post-absortive state

Glucose metabolism : Fasting state