diabetic ketoacidosis dr. osama y kentab, m.d,faap,facep assistant professor of emergency medicine -...

Diabetic Ketoacidosis

Dr. Osama Y Kentab, M.D,FAAP,FACEP

Assistant Professor of Emergency Medicine - KSAU

Clinical Assistant Professor Pediatrics – KSU

Consultant Pediatric Emergency Medicine

KAMC – KFH - Riyadh

Definition

Diabetic Ketoacidosis is a stat of metabolic acidosis, hyperglycemia and ketonemia where:

Acidosis: arterial ( or capillary) pH < 7.3 and/ or serum HCO3- OF < 15 mmol/L

Hyperglycemia: Blood glucose of > 15 mmol/L Ketonemia: positive ketones in serum or urine

Pathophysiology

Diabetic ketoacidosis is the result of complex metabolic derangements caused by insulinopenia and increased levels of counter regulatory hormones mainly glucagon.

Metabolic consequences of DKA includes the following:

Hyperglycemia

Ketoacidosis

Hypovolemia

Electrolyte Disturbances

Hyperglycemia

Two hormonal abnormalities appear to be necessary for expression of these abnormalities:

insulin deficiency (and/or resistance)

glucagon excess (which may be induced both by removal of the normal suppressive effect of insulin and by a concurrent defect in the pancreatic A cell).

With hyperglycemia, for example, insulin deficiency impairs peripheral glucose utilization in skeletal muscle and increases both fat and muscle breakdown, leading to enhanced delivery of gluconeogenetic precursors (glycerol and alanine) to the liver .

Both insulin deficiency and, more importantly, glucagon excess then promote hepatic gluconeogenesis

The genesis of ketoacidosis

Insulin deficiency leads to enhanced lipolysis → ↑ free fatty acid delivery to the liver. Normal subjects, however, will convert these fatty acids primarily

into triglycerides.

The development of ketoacidosis requires a specific alteration in hepatic metabolism so that free fatty acyl CoA can enter the mitochondria, where conversion to ketones occurs . Mitochondrial entry is regulated by the enzyme carnitine palmitoyl

transferase, the activity of which is low in the fed state but is markedly increased by glucagon excess.

Hypovolemia

Osmotic diuresis due to hyperglycemia leads to renal free water loss.

Hypovolemia will increase catecholamines level. 

Electrolyte Disturbances:

Potassium Total body potassium is depleted due to renal loss. However , the intial serum

potassium is either normal or increase due to acidosis. Once acidosis is corrected the serum level of potassium will decrease.

Sodium Serum level is decreased due to dilution effect of hyperglycemia and partially

due to renal loss. Sodium will decrease by 1.6 meq/L for every 100 mg/dL increment in blood

glucose above 100mg/dL Phosphate, magnesium and calcium :

Are always depleted due to renal loss. However, they usually do not present a problem unless they are very low. Phosphate therapy is not recommended because it precipitates with calcium, causing hypocalcemia.

Differential diagnosis

DKA must be differentiated from other causes of coma and metabolic acidosis, these include:

hypoglycemia

uremia

gastroenteritis with metabolic acidosis

lactic acidosis

salicylate intoxication

encephalitis and other intracranial lesions

Nonketotic hyperosmolar coma

DIAGNOSIS

The diagnosis of DKA is usually suspected from the history and the presence of hyperglycemia with a high anion gap metabolic acidosis.

  History:

Polydipsia, polyuria and may have abdomial pain and/ or vomiting

Clinical: Acidotic respiration, dehydration.

Confirmation of the diagnosis requires the demonstration of hyperglucosemia plus ketonemia or ketonuria .

Investigations

blood glucose

urea and electrolytes

venous blood gas except if patient is in coma or hemodynamically unstable

urinalysis for glucose, ketones, protein

ECG for hypo or hyperkalemia

Others if indicated: CBC, Blood C/S, Urine for micro, culture and sensitivity , CXR.

TREATMENT

Therapy in DKA include the administration of insulin and correction of each the fluid and electrolyte abnormalities that is present: hyperglycemia Hyperosmolality Hypovolemia metabolic acidosis potassium and phosphate depletion

TREATMENT

Insulin Insulin acts to lower the plasma glucose concentration

(primarily by decreasing hepatic glucose production rather than enhancing peripheral utilization) , to diminish ketone production (by reducing both lipolysis and glucagon secretion), and perhaps to augment ketone utilization .

The net effect is a 65 to 125 mg/dL (3.6 to 7 mmol/L) per hour reduction in the plasma glucose concentration induced by insulin alone , with fluid repletion adding another 35 to 70 mg/dL (2 to 4 mmol/L) per hour

TREATMENT

Insulin therapy may be withheld for 30 to 60 minutes in patients who are markedly hypovolemic to allow the initial administration of 1 to 2 liters of isotonic saline.

Insulin alone drives glucose and, due to the ensuing fall in plasma osmolality, water into the cells, an effect that can exacerbate the extracellular volume depletion.

TREATMENT

Hypovolemia The aim of therapy is to replete the

extracellular fluid volume without inducing cerebral edema due to too rapid reduction in the plasma osmolality.

TREATMENT

Potassium depletion Both renal and gastrointestinal losses can contribute to an

often marked degree of potassium depletion.

The plasma potassium concentration is usually normal or, in about one-third of cases, elevated at presentation due primarily to hyperosmolality and insulin deficiency .

Careful monitoring is required, with potassium repletion being instituted once insulin and fluids have lowered to plasma potassium concentration to 4.5 meq/L.

TREATMENT

Metabolic acidosis Insulin largely corrects the acidemia in DKA, as

bicarbonate is generated from the metabolism of ketoacid anions.

The major indications for bicarbonate supplementation are severe acidemia (arterial pH below 7.0 ), a relatively normal anion gap due to the urinary loss of the ketoacid anions, or severe hyperkalemia (since bicarbonate will drive some of the excess potassium into the cells).

TREATMENT

Phosphate depletion Cellular phosphate depletion is another common problem in

uncontrolled diabetes mellitus, although the plasma phosphate concentration may initially be normal or elevated due to movement of phosphate out of the cells .

As with hyperkalemia, the phosphate depletion is rapidly unmasked following the institution of insulin therapy, frequently leading to hypophosphatemia.

Most patients remain asymptomatic and prophylactic phosphate administration is more likely to be harmful than beneficial.

Management

Full clinical assessment and observations:

Assess and record in the notes, so that comparisons can be made by others later.

Degree of Dehydration:

Conscious Level:

If alert or drowsy institute hourly neurological observations. If in coma on admission, or there is any subsequent deterioration, record Glasgow Coma Score transfer to ICU consider instituting cerebral oedema management

Full Examination

looking particularly for evidence of –

cerebral oedema irritability, slow pulse, high blood pressure, papilloedema.

N.B. Examine fundi but this a late sign.

Management

Does the child need to be in ICU? YES if comatose, or >10% dehydrated with shock, or staffing levels on

the wards are insufficient to allow adequate monitoring.

Observations to be carried out: Ensure full instructions are given to the senior nursing staff

emphasizing the need for:

strict fluid balance and urine testing of every sample

daily weight

hourly or more frequent neuro observations initially

reporting immediately to the medical staff, even at night, symptoms of headache or any change in either conscious level or behavior

reporting any changes in the ECG trace, especially T wave changes.

Steps in Management of Diabetic Ketoacidosis

ABCsProtect the airwayTreat shockDetermine underlying cause

Steps in Management of Diabetic Ketoacidosis

 Fluid Initial

10 mL/kg normal saline in 1 hr. (20 mL/kg rapidly if in shock) This may be repeated as necessary. Subsequently

Assume 10% dehydration ,Fluid replacement should be gradual (24 hr)

Maximum fluid administration 4 L/m2/day (including initial boluses)

Normal saline used from 1 to 6 hr. then 50% normal saline

D5 ½ N.S. if blood sugar < 18mmol/dl

Continue intravenous fluids until oral fluids are well tolerated and the metabolic defects are corrected.

Steps in Management of Diabetic Ketoacidosis

Insulin Initial

IV: 0.1 unit/kg/hr by continuous infusion after 1st hour of fliud therapy

Subsequent Double if no improvement in glucose or pH by 3 hr.

Maximum glucose decline: 3 to 5 mmol/L/hr.

At 15 mmol/L glucose, add dextrose to intravenous solutions (up to 12.5%) as needed to maintain plasma glucose at 12- 15 mmol/L

Continue insulin regimen until the academia is corrected (pH >7.3 and/or HCO3 >18)

Start subcutaneous insulin with a 1-hr overlap in the intravenous.

Steps in Management of Diabetic Ketoacidosis

Potassium Monitor ECG If the K+ is <3.5 mEq/L, add 40 to 60 mEq/L; if

3.5 to 5, and 30 mEq/L; if >5.0, then hold K+ replacement

After 3-5 hr. half of K+ replacement as K+ phosphate

Steps in Management of Diabetic Ketoacidosis

Bicarbonate Only use bicarbonate (HCO3

-) for pH <7.0

Increase pH to 7.1 or final bicarbonate to 12 mEq/L

[mEq HCO3- = 12- measured HCO3

- x 0.6 x body weight (in kg]

Add HCO3- slowly maximum 50 mEq/500 mL IV

solution (over 2-3 hr) Maximum HCO3- should be

50 mEq/500 mL IV solution

COMPLICATIONS OF DKA

Hypoglycemia

Hypophosphasemic muscle weakness during recovery from DKA

Acute tubular necrosis from severe dehydration

Hemolysis due to acidosis

Myoglobinuria due to acidosis

Pulmonary edema and adult respiratory distress syndrome secondary to fluid overload

Cardiovascular complications ( seen more in adults than children)

CNS complications:

Thrombovascular phenomena (22 to dehydration and hypercoagulability of DKA)

cerebral edema.

Cerebral edema

may cause brain herniation and consequent severe brain damage or death.

Occur after or during recovery from diabetic ketoacidosis

Etiology: unknown seen mainly in children with DKA.

Cerebral edema

hypothesis:hyponatermia leading to inappropriate

regulation of vassopressin secreation.idiogenic osmoles

Cerebral edema

Idiogenic osmolesDuring DKA:

Osmotic disequilibrium between brain and periphery is connected to intracerebrally by the generation of hypothetical osmotically active particles termed idiogenic osmoles that serve to maintain brain tissue isosmolar with the blood.

Recovery from DKA:If rapid: dissipation of idiogenic osmoles may be

inappropriately slow and influx of water into cerebral cells causes brain edema.

Cerebral edema-signs and symptoms

headache that is often sudden and severe confusion irritability reduced conscious level fits (seizures) small pupils increasing BP, slowing pulse papilloedema (not always present acutely) possibly respiratory impairment

Cerebral edema-Management

Exclude hypoglycemia

The following measures should be taken:

give Mannitol 0.5 g/kg stat (=2.5 ml/kg Mannitol 20% over 15 minutes). This needs to be given within 10 minutes.

restrict IV fluids to 2/3 maintenance and replace deficit over 72 rather than 24 hours

the child will need to be moved to ICU (if not there already)

arrange for the child to be intubated and, hyperventilated to reduced blood pCO2

inform neurosurgeons

exclude other diagnoses by CT scan – other intracerebral events may occur (thrombosis, hemorrhage or infarction) and present in the same way

intracerebral pressure monitoring may be required

repeated doses of Mannitol (above dose every 6 hours) should be used to control intracranial pressure.

Cerebral edema-Prognosis

50% die 50% survive but majority with severe brain

damage