DKA is more common in young (<65 years old) diabetic patients and in women compared to men with the ratio of 1:3. Cytokines (e.g. which promote gluconeogenesis and glycogenolysis. DKA) I. Introduction Diabetic Ketoacidosis (DKA) is an acute complication of Type I DM that is characterized by uncontrolled lypolysis.a. hyperkalemia and other electrolyte imbalances and metabolic acidosis.k. ketogenesis. The prognosis of DKA is substantially worse at the extremes of age and in the presence of coma and hypotension. interleukin-1) are increased . It stimulates the release of counterregulatory hormones. Infection is the most common precipitating factor in the development of DKA. Mortality in DKA is primarily due to the underlying precipitating illness and only rarely to the metabolic complications of hyperglycemia or ketoacidosis. DKA can be precipitated by many conditions that result in insufficient circulating levels of insulin or lead to the development of insulin resistance. Some of these conditions may promote transient hyperglycemia in patients without established diabetes.DIABETIC KETOACIDOSIS (a.

This causes your blood sugar level to drop. muscles and nerves. A low potassium level can impair the activities of your heart.The fluids and insulin used to treat diabetic ketoacidosis may cause your potassium level to drop too low. potassium and chloride — and insulin. you may develop low blood sugar. it narrows and thickens and can .Adjusting your blood sugar level too quickly can produce swelling in your brain. Diabetic ketoacidosis is treated with fluids. the most common complications of diabetic ketoacidosis are related to this lifesaving treatment: 1) Low blood sugar (hypoglycemia) . 4) Renal Failure Due to the hyperfiltration and hyperfunction of kidneys to excrete the excessive substances to maintain homeostasis.Insulin allows sugar to enter your cells. 5) Stroke .Lipolysis can cause fats to store in the walls of blood vessels and as a result. especially those who have newly diagnosed diabetes. Insulin omission in patient with Type1 and Type 2 DM and Untreated or Undiagnosed DM can also be risk factors. Perhaps surprisingly. If your blood sugar level drops too quickly. 2) Low potassium (hypokalemia) . 3) Swelling in the brain (cerebral edema) . electrolytes — such as sodium.and may also be implicated. This complication appears to be more common in children.

Diabetic ketoacidosis can lead to loss of consciousness. Left untreated. the risks are much greater. Pathophysiology .cause atherosclerosis. diabetic ketoacidosis can be fatal. Atherosclerosis will lead to insufficient supply of oxygen in the brain therefore leading to stroke. Eventually. II.

Acetone . which is stimulated by the excess of glucagon that accompanies insulin deficiency. Stress hormones accelerate and exaggerate the rate and magnitude of metabolic decompensation. The major ketoacids produced. acetoacetic acid and β-hydroxybutyric acid. but ketogenesis proceeds in the absence of insulin. as does alanine from muscle catabolism. counterregulatory/ stress hormones are released. Primarily. due to the β cell destruction. are strong organic acids that create metabolic acidosis. To address the decreased glucose utilization and cellular starvation because of insulin deficiency. Insulin normally blocks ketogenesis by inhibiting the transport of FFA derivatives into the mitochondrial matrix. Glucagon also stimulates mitochondrial conversion of FFAs into ketones. Serum levels of glycerol and free fatty acids (FFAs) rise because of unrestrained lipolysis. Glycerol and alanine provide substrate for hepatic gluconeogenesis. the pancreas cannot secrete insulin that can lead to absent of insulin or insulin deficiency. Insulin deficiency causes the body to metabolize triglycerides and muscle instead of glucose for energy.DKA is usually an acute complication of DM Type 1.

Urinary excretion of ketones obligates additional losses of Sodium and Potassium. initial serum Potassium is typically normal or elevated because of the extracellular migration of Potassium in response to acidosis. nausea and vomiting and acetone breath.derived from the metabolism of acetoacetic acid accumulates in serum can lead to metabolic acidosis and is slowly disposed as manifested by kussmaul’s respiration. Despite a significant total body deficit of Potassium. Compensatory Attempts Excessive ketone production causes metabolic acidosis. DKA occurs when the increased production of ketoacids overwhelms attempts at compensation. The body uses three defense mechanisms in an attempt to . sometimes > 300 mEq/24 hours. Hyperglycemia caused by insulin deficiency produces an osmotic diuresis that leads to marked urinary losses of water and electrolytes. Potassium levels generally fall further during treatment as insulin therapy drives potassium into cells. If serum potassium is not monitored and replaced as needed. Serum sodium may fall from natriuresis or rise due to excretion of large volumes of free water. The rapid overproduction of ketoacids depletes the buffering effect bicarbonate and results in acidosis. lifethreatening hypokalemia may develop. Potassium is also lost in large quantities.

. (2) intracellular buffering.19. and (3) renal correction. This results in tachypnea or Kussmaul’s respiration. In addition. buffering occurs when excess hydrogen ions move intracellularly in exchange for potassium ions to maintain a neutral intracellular charge. Acidosis will continue to worsen if not corrected by the administration of insulin. The kidneys attempt to correct ketoacidosis by increasing the excretion of ketoacids.32 Excess carbon dioxide is exhaled to correct the metabolic acidosis.counter impending acidosis: (1) respiratory compensation.

cortisol and growth hormone Stimulation of hunger mechanism via hypothalamus Hung er Polyphagi Polyphagi a a ↑ Glucogenolysi s ↑Glucose ↑ Lypolysis ↑ Release of Fatty Acids to liver Ketogenes is ↑ Ketones ↑ Ketones formation formation Accumulation of β – Hydroxybuterate and Acetone Acetic acid in the blood Metabolic Metabolic Acidosis Acidosis Abdominal Abdominal Pain Pain ↑ Fat content in the blood Hyperlipide mia Formation of fats on the walls of BV Atherosclero Atherosclero sis sis ↑ Proteolysis Amino acid production Gluconeogen esis Hyperglyce Hyperglyce mia mia Osmotic Diuresis Polyuri Polyuri a a Glycosuri Glycosuri a a Dehydratio Dehydratio n n Hypovolem ia ↑ Thirst Hyperosmolal ity Polydyps Polydyps ia ia Ketonuria Ketonuria N/V Poor Poor appetite appetite Weight Weight loss loss Weaknes Weaknes s s ↓Cellular K+ Arrhythmi Arrhythmi as as Body attempts to prevent further ↓ in pH Kussmaul’ Kussmaul’ s s respiration respiration Acetone Acetone breath breath Depressed Depressed CNS CNS Headac Headac he he Com Com a a ↓ BP Shoc k . glucagon.Insufficient/Absence of Insulin Infection Undiagnosed/Untreated type 1 DM Cellular Cellular Starvation Starvation Secretion of counterregulatory hormones such as: catecholamines.

Initially arterial pH. Urine ketone test based on the nitoprusside reaction measures acetoacetate and acetone but not beta-hydroxybutyrate (B-OHB). but following pH can be venous as venous pH correlates well with arterial pH3 (venous pH is usually 0. acidaemia. Initial blood glucose levels can be as high as 30-45mmol/L. Serum bicarbonate <18mmol/L.5-6. . When pH drops below 7.03 units lower than arterial pH). Directly measured B-OHB is the preferred test for ketonaemia as B-OHB is the strongest and most prevalent acid in DKA. but not current state. indicators of renal function.  Arterial blood gas (ABG) to measure degree of acidosis and degree of compensatory hypocarbia (PaCo2). in severe DKA <15 mmol/L  Urinalysis (U/a) dipstick: testing for positive urine ketones (ketonuria) and glucose (glucosuria).III. Normal value for creatinine: 60120μmol/l. Reduced renal blood flow results in decreased glomerular filtration rate and elevated urea and creatinine levels. Urine reflects changes over previous several hours.  Urea and creatinine.4mmol/l. Normal value for urea: 2. U/a is unreliable as a marker for resolving of acidosis because ketone bodies can still be detected in urine long after ketoacidosis is resolved. Diagnostic Procedures  Initial diagnosis of DKA: serum glucose level >11mmol/L.2 hyperventilation and hypocarbia are more pronounced. Capillary blood ketone testing would be a more reliable marker for ketoacidosis as it reflects real time. and presence of ketones in urine6  Blood sugar level (BSL) hourly measures.

The accumulation of keto-acid-anions is not measured directly in laboratory. moderate 12mmol/L.50mmol/L) can be low due to loss in urine.07-1. such as keto-acids anions. It can be low due to increased amount of extracellular water in hyperosmolar state.5-5. low serum potassium reflects the total body potassium depletion. Hyperosmolality is the main factor for decreased consciousness . • Magnesium and phosphate: Magnesium (normal value: 0. Elevated anion gap is an indicator for metabolic acidosis. Normal value <12mmol/L.0mmol/L.80-1. Normal values: Serum potassium elevated due to 3.  Serum osmolality (normally 280-295 mosm/L) is elevated in DKA.10mmol/L) and phosphate (normal value: 0. severe 16mmol/L). • Sodium (normal value: 136-145mmol/L) can be high due to osmotic diuresis and excessive water loss. Elevated anion gap results from accumulation of keto-acid anions (mild anion gap >10mmol/L. This is called anion gap. The excess of cations over anions provides a clue about the amount of unmeasured anions.  Elevated anion gap [calculated as (sodium + potassium) minus (chloride + bicarbonate)]. extracellular shift of potassium caused by insulin deficiency and acidosis. Blood urea also elevated through protein catabolism  Serum electrolytes: • Potassium (particularly important!). Later. The amount of total cations (sodium and potassium) and most anions (chloride and bicarbonate) are measured.

000 suggests infection.  Serum amylase.  Blood. .000 attributed to dehydration and stress.  Cardiac enzymes to detect myocardial infarction. Severe leucocytosis >30. urine and sputum cultures to detect source of infection.000-20. Full blood count (FBC): Mild leucocytosis of 10. an indicator for quality of diabetes control.  Haemoglobin A1C. or new-onset diabetes. serum lipase and liver enzymes to detect pancreatitis.

or profound acidosis. as this may be caused by cerebral edema.Imaging Studies  Chest radiography: Use this to rule out pulmonary infection. severe dehydration. An significant hypokalemia or hyperkalemia.  Telemetry: Consider telemetry in those with comorbidities (especially cardiac). known significant electrolyte abnormalities. Many of the changes may be seen late on head imaging and should not delay administration of hypertonic saline or mannitol in those pediatric cases where cerebral edema is suspected. also a and rapid the way physiological cause to cardiac assess diabetic ECG ketoacidosis may complications.  CT scanning: The threshold should be low for obtaining a head CT scan in children with diabetic ketoacidosis (DKA) who have altered mental status. Other Tests  Electrocardiography (ECG): Diabetic ketoacidosis may be precipitated disturbances by of a cardiac is event. .

admission to ICU is necessary. Management Oxygenation/ventilation Airway and breathing remain the first priority. Fluid replacement should be initiated immediately. breathing and level of consciousness have to be monitored throughout the treatment of DKA. Two large-bore intravenous cannulas or a central venous catheter (such as PICC) should be inserted. DKA patients are severely dehydrated and can be in hypovolaemic shock. Airway. and counterregulatory hormones. Fluid replacement Circulation is the second priority. Insert nasogastric tube and leave on free drainage if the patient is drowsy and vomiting or if patient has recurrent vomiting. If the patient presents with reduced consciousness/coma (GCS<8) consider intubation and ventilation. IV. Fluid resuscitation reduces hyperglycaemia. Insulin therapy is therefore most effective when it is preceded by initial fluid and electrolyte replacement. particularly in the first few hours. the patient can be managed on the ward. If the patient has moderate or severe form of DKA. In obtunded patients airway can be temporarily maintained by insertion of Guedel’s airway. thus reducing the resistance to insulin. The total body water deficit can be 10% of the body weight and more than 6 litres of fluid may have to be replaced. Immediate fluid resuscitation aims to restore intravascular volume and improve renal perfusion with crystalloid solutions. Apply oxygen via Hudson mask or non-rebreather mask if indicated. although colloids can be used if the patient . hyperosmolality.If the patient presents with a mild form of DKA.

Fluid resuscitation also should be less aggressive in patients with heart failure. but the patient is more likely to have total body potassium depletion. Electrolyte replacement Dehydration and osmotic diuresis cause enormous electrolyte shifts in cells and serum. As a guide. and urinary volumes decrease. N/saline (0. which is equivalent to 1-1. Hyperkalaemia may result from reduced renal function. mental status and meticulous fluid balance are necessary to avoid fluid overload. Intracellular potassium depletion results from a lack of . and then 4-10ml/kg/hour for the following hours1. Aggressive reduction of blood glucose and high rates of fluid resuscitation are associated with cerebral edema in 1% of children and adolescents. the initial bolus of fluid is 15-20ml/kg over an hour. If the patient is not cardiac-compromised. Ideally 50% of the total body water deficit should be replaced within the first eight hours and the other 50% within the following 24 hours. serum osmolality should decrease by less than 3mOsm/L/hour. Hartman’s solution or Plasmalyte are also suitable (they have the advantage of providing a bicarbonate precursor). renal function. One recommendation limits fluid resuscitation in the first 4 hours of therapy to <50ml/kg isotonic in hypovolaemic shock2. Careful monitoring of haemodynamic status (in unstable patients every 15 minutes).5L in the first hour.9%NaCl) is most appropriate initially.  Potassium: Potassium is the major intracellular positive ion. Intravenous fluids should be reduced as soon as the osmotic dieresis resolves. Exclusive use of normal saline often contributes to a hyperchloraemic acidosis some days later. responsible for maintenance of the electropotential gradient of the cell membrane.

or infused separately if the IV resuscitation fluid rate is > 150ml/h (eg piggybacked from a syringe driver). the sodium level will return to normal.0mmol/l. . Vomiting can further cause potassium depletion. Potassium shifts into the cells with the passage of glucose. correction of acidosis and fluid resuscitation will decrease serum potassium levels.insulin. Potassium should not be replaced if the level is >5.0mmol/L6. intracellular dehydration. During DKA management insulin therapy. acidosis and hydrogen ion shift. The potassium can be added to a burette. If potassium is <3. Serum potassium of 3mmol/L in an average adult suggests a deficit of 200mmol. As excess water moves out of the extracellular space with the correction of hyperglycaemia. serum potassium of 2. Serum potassium is monitored every 2 to 4 hours. During potassium replacement the patient has to be placed on a cardiac monitor for detection of arrhythmias and the ivcannula site has to be inspected regularly to avoid tissue damage. The serum potassium level can indicate the severity of the potassium deficit. The potassium is replaced at 10mmol/hr until serum potassium is >4.3mmol/L it has to be replaced before commencing insulin infusion11. Urinary output has to be confirmed prior to potassium replacement. Therefore the potassium level has to be checked before starting insulin therapy.5mmol/L suggests a deficit of 300mmol and serum potassium of 2mmol/L suggests a deficit of 400mmol15.  Sodium: Early “hyponatraemia” in DKA does not usually require specific treatment. it is an artefact arising from dilution by the hyperglycaemiainduced water shifts.

Insulin therapy Insulin therapy is crucial to DKA management.1 units/kg/hour for children. correction of cell metabolism and acidosis.05-0. Phosphate will move into cells with glucose and potassium once insulin therapy has started. or 0. The infusion rate is 5 units/hour. and is most likely to occur in children with newly diagnosed diabetes.3-DPG and a right-shift of the oxygenhaemoglobin-dissociation curve13. Insulin infusion should slowly reduce blood glucose level. The patient. and phosphate replacement is likely to be required if the serum levels are in the low end of the normal range. The rate at which serum glucose falls should not exceed 4mmol/L per hour. The usual dose in 24 hours is 30-60mmol for an adult. while . or just low. Phosphate: Total body phosphate can be low due to loss from osmotic diuresis. cardiac muscle weakness. Hypophosphataemia of < 0. Initially blood glucose can be as high as 30-45mmol/L. This is because the intracellular change in osmolality lags behind the extracellular changes in osmolality.3mmol/l can cause respiratory muscle weakness.1units/kg or a bolus of 5 or 10 units. Cerebral oedema is rare in adults with DKA. decreased 2. The blood glucose level must be checked hourly until urinary ketones are gone. It facilitates glucose uptake into the cell. Insulin is initially given as an intravenous bolus of 0. Phosphate can be given in the form of KH2PO4 at a rate of 10mmol/hr. and than can be checked less frequently (2nd hrly and later 4th hrly). Then a continuous insulin infusion of 50 units of Actrapid in 50ml N/Saline is commenced. A slow normalisation of osmolality is desired. This is important because if it falls too rapidly cerebral oedema may result through the influx of water into the brain cells1.

but it is one of the major aspects in DKA management and cannot be emphasized enough. Insulin therapy suppresses fat catabolism and counteracts further ketone production. ketoacidosis would return and the patient’s condition would deteriorate. The dextrose infusion is titrated to the BSL (not vice versa!) and can be increased up to 250ml/hour if BSL is low. Once BSL has fallen <15mmol/L. It facilitates metabolism of ketone acids. thus the correction of acidosis. The most important thing to remember is that the insulin infusion rate stays constant and insulin infusion should never be discontinued even if BSL becomes normal or low. and urinary ketones have disappeared. Alternatively 10% dextrose can be used instead of 5% dextrose if BSL falls too rapidly. The principle of titrating glucose infusion to the BSL and not titrating insulin to BSL.acidotic. In summary the patient has three concurrent infusions: rehydration fluid. Sodium Bicarbonate . as we would usually do it. a 5%-dextrose infusion is started at 80ml/hour to slow the correction of the hyperglycaemia and prevent hypoglycaemia. If insulin were reduced or ceased prematurely. is kept nil by mouth to maximize the speed at which ketoacidosis can resolve (food might slow resolution). The BSL can be kept at 12-15mmol/l for several hours while the hyperosmolality and mental state improve. Decreasing the insulin infusion rate should only be considered once ketoacidosis has resolved. insulin infusion and dextrose infusion. Aim ultimately for a BSL of 6-10mmol/L. may be a difficult concept to grasp. This is discussed later.

In acidosis myocardial contractility and catecholamine function are impaired. Bicarbonate is not routinely recommended if the initial pH is 6. Surgical Procedure . however.9 or more. V. Multiple studies. have shown that the treatment of metabolic acidosis with sodium bicarbonate is not helpful1. because the is acidosis will correct as the with insulin therapy. However. Sodium bicarbonate infusion can cause paradoxical central nervous system acidosis. one clear indication for bicarbonate therapy is life-threatening hyperkalaemia. hypokalaemia and tissue hypoxia through decreased tissue oxygen uptake and a left-shift of the oxy-haemoglobin-dissociation curve. are Bicarbonate regenerated ketone anions metabolised.

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