Diabetic ketoacidosis( DKA) and

hyperosmolar hyperglycemic state(HHS)

BY: Dr.sabah
• A diagnosis of diabetic ketoacidosis requires
the patient’s
– glucose concentration to be above 250 mg per dL
(although it usually is much higher),
– the pH level to be less than 7.30, and
– the bicarbonate level to be 18 mEq per L or less.
 Definition of Diabetic Ketoacidosis*
Acidosis

*
Ketosis
Hyperglycemia
Adapted from Kitabchi AE, Fisher JN. Diabetes Mellitus. In: Glew RA, Peters SP, ed. Clinical
Studies in Medical Biochemistry. New York, NY: Oxford University Press; 1987:105.
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• severe insulin deficiency resulting in
hyperglycemia (200-1,000 mg/dL),
dehydration, and electrolyte abnormalities
• • history and physical exam – often young,
type 1 DM, may be first presentation of
undiagnosed DM (may occur in small
percentage of type 2 DM patients)
Pathophysiology
• Secondary to insulin deficiency, and the action of
counter-regulatory hormones, blood glucose
increases leading to hyperglycemia and glucosuria.
Glucosuria causes an osmotic diuresis, leading to
water & Na loss.
• In the absence of insulin activity the body
fails to utilize glucose as fuel and uses fats
instead. This leads to ketosis.
 Clinical Presentation of
Diabetic Ketoacidosis
History Physical Exam
• Thirst • Kussmaul respirations
• Polyuria • Fruity breath
• Abdominal pain • Relative hypothermia
• Nausea and/or vomiting • Tachycardia
• Profound weakness • Supine hypotension,
orthostatic drop of blood
Patients with any form of diabetes pressure
who present with abdominal pain,
nausea, fatigue, and/or dyspnea • Dry mucous membranes
should be evaluated for DKA. • Poor skin turgor

Handelsman Y, et al. Endocr Pract. 2016;22:753-762.

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• ƒ early symptoms: polyuria, polydipsia, malaise,
nocturia, weight loss
• ƒ late signs and symptoms
• Š anorexia, N/V, dyspnea (often due to acidosis),
fatigue
• Š abdominal pain
• Š drowsiness, stupor, coma
• Š Kussmaul’s respiration
• Š fruity acetone breath
• investigations
• ƒ CBC, glucose, electrolytes, BUN/Cr, Ca2+,
Mg2+, PO4
• , urine glucose and ketones
• ƒ ABG
• ƒ ECG (MI possible precipitant; electrolyte
disturbances may predispose to dysrhythmia)
 Potassium Balance in DKA
• Potassium is dominantly intracellular
• Urinary losses occur during evolution of DKA (due to glycosuria)
• Total body potassium stores are greatly reduced in any patient
with DKA
• Potassium moves from inside the cell to the extracellular space
(plasma)
– During insulin deficiency
– In presence of high blood glucose
– As cells buffer hydrogen ions
• Blood levels of potassium prior to treatment are usually high
but may drop precipitously during therapy

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Causes of Morbidity and Mortality in DKA

• Shock • Acute renal failure

• Hypokalemia during • Adult respiratory
treatment distress syndrome
• Hypoglycemia during • Vascular thrombosis
treatment • Precipitating illness,
• Cerebral edema during including MI, stroke,
treatment sepsis, pancreatitis,
• Hypophosphatemia pneumonia

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 DKA and HHS Are Life-Threatening
Emergencies

Diabetic Ketoacidosis (DKA) Hyperglycemic Hyperosmolar State (HHS)

Plasma glucose >250 mg/dL Plasma glucose >600 mg/dL

Arterial pH <7.3 Arterial pH >7.3

Bicarbonate <15 mEq/L Bicarbonate >15 mEq/L

Moderate ketonuria or ketonemia Minimal ketonuria and ketonemia

Anion gap >12 mEq/L Serum osmolality >320 mosm/L

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 Characteristics of DKA and HHS
Diabetic Ketoacidosis (DKA)
Absolute (or near-absolute) insulin
deficiency, resulting in
• Severe hyperglycemia
• Ketone body production
• Systemic acidosis
Develops over hours to 1-2 days
Most common in type 1 diabetes, but
increasingly seen in type 2 diabetes
Hyperglycemic Hyperosmolar State (HHS)
Severe relative insulin deficiency, resulting
in
• Profound hyperglycemia and
hyperosmolality (from urinary free
water losses)
• No significant ketone production or
acidosis
Develops over days to weeks
Typically presents in type 2 or previously
unrecognized diabetes
Higher mortality rate
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 Clinical Presentation of
Hyperglycemic Hyperosmolar State
• Compared to DKA, in HHS there is greater
severity of:
– Dehydration
– Hyperglycemia
– Hypernatremia
– Hyperosmolality
• Because some insulin typically persists in HHS,
ketogenesis is absent to minimal and is
insufficient to produce significant acidosis
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 Clinical Presentation of
Hyperglycemic Hyperosmolar State
Patient Profile Disease Characteristics
• Older • More insidious
• More comorbidities development than DKA
• History of type 2 diabetes, (weeks vs hours/days)
which may have been • Greater osmolality and
unrecognized mental status changes than
DKA
• Dehydration presenting
with a shock-like state

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 Initial Laboratory Evaluation of
Hyperglycemic Emergencies
• Comprehensive metabolic profile
• Serum osmolality
• Serum and urine ketones
• Arterial blood gases
• CBC
• Urinalysis
• ECG
• Blood cultures (?)
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 Management of DKA and HHS
• Replacement of fluids losses
• Correction of hyperglycemia/metabolic
acidosis
• Replacement of electrolytes losses
• Detection and treatment of precipitating
causes
• Conversion to a maintenance diabetes
regimen (prevention of recurrence)
Kitabchi AE, et al. Diabetes Care. 2009;32:1335-1343.
ƒ rehydration
• Š bolus of NS, then high rate NS infusion (beware of
overhydration and cerebral edema, especially in
pediatric patients)
• ƒ potassium
• Š essential to avoid hypokalemia: replace KCl (20 mEq/L
if adequate renal function and
• initial K+ <5.5 mEg/L)
• Š use cardiac monitoring if potassium levels normal or
low
• insulin
• Š critical, as this is the only way to turn off
gluconeogenesis/ketosis
• Š initial short-acting/regular insulin (or 0.2 U/kg) IV in adults
• (controversial – may just start with infusion)
• Š followed by continuous (or 0.1 U/kg) per h
• Š add D5W to IV fluids when blood glucose <270 mg/dL to
prevent hypoglycemia
• ƒ bicarbonate is not given unless patient is at risk of death or
shock (typically pH <7.0)
 Fluid Therapy in DKA

Normal saline, 1-2 L over 1-2 h

Calculate corrected serum sodium

High or normal Low serum sodium

serum sodium

½ NS at 250-500 NS at
mL/h 250-500 mL/h

Glucose < 250 mg/dl

Change to D5% NS or 1/2NS

ADA. Diabetes Care. 2003;26:S109-S117.

 Intravenous Insulin Therapy in DKA

IV bolus: 0.1 U/kg body weight

IV drip: 0.1 U/kg/h body weight

Glucose < 250 mg/dl

IV drip: 0.05 – 0.1 U/kg/h

until resolution of ketoacidosis

ADA. Diabetes Care. 2003;26:S109-S117.

 Bicarbonate Administration
• pH > 7.0: no bicarbonate

• pH < 7.0 and bicarbonate < 5 mEq/L:

44.6 mEq in 500 mL 0.45% saline over 1 h until
pH > 7.0

ADA. Diabetes Care. 2003;26:S109-S117.

 Subcutaneous Insulin Protocols
Rapid Acting Insulin Rapid Acting Insulin Every
Every 1 Hour 2 Hours
• Initial dose • Initial dose
– 0.2 U/kg of body weight, – 0.3 U/kg of body weight,
followed by 0.1 U/kg/h followed by 0.2 U/kg 1 h later,
then
• When BG <250 mg/dL – Rapid acting insulin at 0.2 U/kg
– Change IVF to D5%-0.45% every 2 h
saline • When BG <250 mg/dL
– Reduce rapid acting insulin to – Change IVF to D5%-0.45% saline
0.05 unit/kg/h – Reduce rapid acting insulin to
– Keep glucose ≈ 200 mg/dL 0.1 U/kg every 2 h
until resolution of DKA – Keep glucose ≈ 200 mg/dL until
resolution of DKA
Haw SJ, et al. In: Managing Diabetes and Hyperglycemia in the Hospital
Setting: A Clinician’s Guide. Draznin B, ed. Alexandria, VA: American
Diabetes Association; 2016;284-297.
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 Potassium Replacement
• K+ = > 5.5 mEq/L: no supplemental is required

• K+ = 4 - 5 mEq/L: 20 mEq/L of replacement

fluid

• K+ = 3 - 4 mEq/L: 40
If admission K+ = <3 mEmEq/L of replacement fluidq/L
give 10-20 mEq/h until
K+ >3 mEq/L, then add 40 mEq/L to replacement fluid
ADA. Diabetes Care. 2003;26:S109-S117.
Correction of Acidosis
• Insulin therapy stops lipolysis and
promotes the metabolism of ketone bodies.
This together with correction of dehydration
normalize the blood PH.
 Bicarbonate therapy should not be used unless
severe acidosis (pH<7.0) results in hemodynamic
instability. If it must be given, it must infused slowly
over several hours.
 As acidosis is corrected, urine KB appear to rise.
Urine KB are not of prognostic value in DKA.
Fluid and Electrolyte Management in HHS

• Treatment of HHS requires more free water and

greater volume replacement than needed for
patients with DKA
• To avoid heart failure, caution is required in the
elderly with preexisting heart disease
• Potassium
– Usually not significantly elevated on admission
(unless in renal failure)
– Replacement required during treatment
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