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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• early symptoms: polyuria, polydipsia, malaise,
nocturia, weight loss
• late signs and symptoms
• anorexia, N/V, dyspnea (often due to acidosis),
fatigue
• abdominal pain
• drowsiness, stupor, coma
• Kussmaul’s respiration
• fruity acetone breath
• investigations
• CBC, glucose, electrolytes, BUN/Cr, Ca2+,
Mg2+, PO4
• , urine glucose and ketones
• ABG
• 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) Hyperglycemic Hyperosmolar State (HHS)
Absolute (or near-absolute) insulin Severe relative insulin deficiency, resulting
deficiency, resulting in in
• Severe hyperglycemia • Profound hyperglycemia and
• Ketone body production hyperosmolality (from urinary free
• Systemic acidosis water losses)
• No significant ketone production or
acidosis
Develops over hours to 1-2 days Develops over days to weeks
Most common in type 1 diabetes, but Typically presents in type 2 or previously
increasingly seen in type 2 diabetes 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.
rehydration
• bolus of NS, then high rate NS infusion (beware of
overhydration and cerebral edema, especially in
pediatric patients)
• potassium
• essential to avoid hypokalemia: replace KCl (20 mEq/L
if adequate renal function and
• initial K+ <5.5 mEg/L)
• use cardiac monitoring if potassium levels normal or
low
• insulin
• critical, as this is the only way to turn off
gluconeogenesis/ketosis
• initial short-acting/regular insulin (or 0.2 U/kg) IV in adults
• (controversial – may just start with infusion)
• followed by continuous (or 0.1 U/kg) per h
• add D5W to IV fluids when blood glucose <270 mg/dL to
prevent hypoglycemia
• 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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