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Diabetic Ketoacidosis (DKA) DKA, primarily a type I diabetes complication, occurs mainly in younger adults and people in their

teenage years. DKA can develop in a new-onset type I diabetic or a diabetic who misses insulin doses. Often it occurs with poor insulin compliance and lack of knowledge about managing insulin administration in acute illness. The patient who is feeling unwell may believe that he/she does not need insulin while not eating. Precipitating factors include medications and drugs that affect carbohydrate metabolism such as corticosteroids, thiazides, loop diuretics, sympathomimetics, anti-hypertensives, anti-histamines, tricyclic antidepressants, alcohol, cocaine and ecstasy1. Often DKA develops because of an acute illness or infection such as pneumonia or urinary tract infection. Pregnancy, gastroenteritis, trauma, burns, surgery, sepsis, pancreatitis, stroke and silent myocardial infarction can also provoke DKA1. The patient fails to meet the increased insulin demand when these physical stressors occur. The stressors provoke an excessive release of counter-regulatory hormones such as glucagon, catecholamines, cortisol and growth hormone and the elevation of pro-inflammatory cytokines. In this fight-or-flight stress response energy stores from fat, protein and glycogen are mobilized and new glucose is produced. The Four (4) Main Characteristics of DKA 1. Hyperglycaemia Insulin deficiency leads to accumulation of glucose in the blood as glucose cannot enter the cells. Normally insulin suppresses glucose production and lipolysis in the liver. Therefore insulin deficiency leads to hepatic glucose overproduction. Counter-regulatory hormones, glucagon, cortisol and catecholamines increase the glucose level through gluconeogenesis (formation of new glucose) and glycogenolysis (breakdown of complex glycogen into simple glucose). The process of gluconeogenesis is driven by the high availability of all the precursors: amino acids (from protein breakdown), lactate (from muscle glycogenolysis), and glycerol (from increased lipolysis). It is thought that when serum osmolality is high, even less insulin is produced and insulin resistance increases. These processes make it even more difficult for tissues to take up glucose. As a result hyperglycaemia worsens. 2. Ketosis and acidosis Insulin deficiency and elevated counter-regulatory hormones promote lipolysis in adipose tissue and inhibit lipogenesis, leading to increased release of fatty acids and glycerol. The liver is stimulated by glucagon to oxidize free fatty acids to ketone bodies such as beta-hydroxybutyrate and acetoacetate. The

production of ketone bodies exceeds the ability of tissues to utilize them, resulting in ketonaemia. Ketone bodies fully dissociate into ketone anions and hydrogen ions. The body attempts to maintain extracellular pH by binding the hydrogen ions with bicarbonate ions thus depleting its alkali reserves. Acidosis develops. The respiratory system compensates for acidosis by increasing the depth and rate of breathing to exhale more carbon dioxide. This is called Kussmaul respiration. The breath has a fruity, acetone-like odour (nail polish remover), because the acetone ketones are exhaled. The kidneys excrete ketone bodies (ketonuria), and large amounts of glucose spill over into the urine leading to osmotic diuresis, dehydration and haemoconcentration. This in turn causes tissue ischaemia and increased lactic acid production that worsens the acidosis1. Increased acidosis causes enzymes to become ineffective and metabolism decelerates. Even fewer ketone bodies are metabolised and acidosis worsens. Acidosis can cause hypotension due to its vasodilating effect and negative effect on heart contractility.

Dehydration Hyperglycaemia raises extracellular fluid osmolality. Water is drawn from the cell into the extracellular compartment and intracellular dehydration follows. Hyperosmolality is the main contributor to altered mental status, which can lead to coma1. Cellular dehydration and acid overload can also affect mental status. The development of total body dehydration and sodium depletion is the result of increased urinary output and electrolyte losses. With marked hyperglycaemia the serum glucose threshold for glucose reabsorption in the kidneys of 10mmol/L is exceeded, and glucose is excreted in urine (glucosuria6). Glucosuria causes obligatory losses of water and electrolytes such as sodium, potassium, magnesium, calcium and phosphate (osmotic diuresis). Excretion of ketone anions also contributes to osmotic diuresis6, and causes additional obligatory losses of urinary cations (sodium, potassium and ammonium salts). Insulin deficiency per se might also contribute to renal losses of water and electrolytes, because insulin stimulates salt and water reabsorption by the nephron and phosphate reabsorption in the proximal tubule. Acidosis can cause nausea and vomiting and this leads to further fluid loss. There is increased insensible fluid loss through Kussmaul respiration. Severe dehydration reduces renal blood flow and decreases glomerular filtration, and may progress to hypovolaemic shock. Electrolyte imbalance

Potassium is the electrolyte that is most affected in DKA. Acidosis causes hydrogen ions to move from the extracellular fluid into the intracellular space. Hydrogen movement into the cell promotes movement of potassium out of the cell into the extracellular compartment (including the intravascular space). Severe intracellular potassium depletion follows. As the liver is stimulated by the counterregulatory hormones to break down protein, nitrogen accumulates, causing a rise in blood urea nitrogen. Proteolysis leads to further loss of intracellular potassium and increases intravascular potassium. The body excretes this mobilized potassium in urine by osmotic diuresis, and loses additional potassium through vomiting. Serum potassium readings can be normal or high, but this is misleading, because there is an intracellular and total body potassium deficit. Sodium, phosphate, chloride and bicarbonate are also lost in urine and vomitus. Sodium levels are lowered (diluted) by the movement of water from the intracellular to the extracellular space in response to hyperglycaemia. A formula that corrects the sodium level is: Corrected Na = measured Na + 0.3(glucose 5.5). Clinical Manifestations Feeling unwell for a short period, often less than 24 hours6 Polydipsia and increased thirst Polyuria/ nocturia Polyphagia Weight loss Nausea and vomiting, vomitus can have coffee-ground colour due to haemorrhagic gastritis. Abdominal pain, due to dehydration and acidosis1 Weakness Neurologic signs: restlessness, agitation, lethargy and drowsiness, coma. Increased osmolality is the main factor that contributes to altered mental status. Visual disturbances due to hyperglycaemia Deep and rapid breathing, known as Kussmaul breathing, may have acetone odor on breath. Signs of dehydration due to fluid loss through polyuria, vomiting and breathing: reduced skin turgor, dry mucous membranes Signs of hypovolaemia: tachycardia, hypotension, postural hypotension due to fluid loss over 3 litres. Mild hypothermia due to acidosis-induced peripheral vasodilation, warm dry skin. Fevers are rare despite infection. Severe hypothermia is a poor prognostic sign.

The nurse should have a high suspicion of DKA when a patient presents with unresponsiveness and hyperventilation. It could be first known onset of diabetes mellitus. Diagnostic Procedures Hyperglycemia and hyperosmolality are the two primary laboratory findings in patients with DKA or HHS; patients with DKA also have a high anion gap metabolic acidosis. Most patients also have acute elevations in the blood urea nitrogen (BUN) and serum creatinine concentration, which reflect the reduction in glomerular filtration rate induced by hypovolemia. A variety of additional laboratory tests may be affected. The impact of hyperglycemia, insulin deficiency, osmotic diuresis, and fluid intake in individual patients leads to variability in laboratory findings, depending upon the relative importance of these factors. The initial laboratory evaluation of a patient with suspected DKA or HHS should include determination of:

Serum glucose Serum electrolytes (with calculation of the anion gap), BUN, and serum creatinine Complete blood count with differential Urinalysis, and urine ketones by dipstick Plasma osmolality Serum ketones (if urine ketones are present) Arterial blood gas (if urine ketones or anion gap are present) Electrocardiogram Additional testing, such as cultures of urine, sputum, and blood, serum lipase and amylase, and

chest x-ray, should be performed on a case-by-case basis. Measurement of A1C may be useful in determining whether the acute episode is the culmination of an evolutionary process in previously undiagnosed or poorly controlled diabetes or a truly acute episode in an otherwise well-controlled patient. Serum glucose The serum glucose concentration frequently exceeds 1000 mg/dL (56 mmol/L) in HHS, but is generally below 800 mg/dL (44 mmol/L) in DKA. Euglycemic DKA, in which the serum glucose is normal or near normal but the patient requires insulin therapy for the clearance of ketoacidosis, has been described, particularly in the presence of poor oral intake or pregnancy. At least two factors contribute to the lesser degree of hyperglycemia in DKA compared with HHS:

Patients with DKA often present early with symptoms of ketoacidosis (such as shortness of breath and abdominal pain), rather than late with those of hyperosmolality.

Patients with DKA tend to be young and to have a glomerular filtration rate that, at least in the first five years, may be as much as 50 percent above normal. As a result, they have a much greater capacity to excrete glucose than the usually older patients with HHS, thereby limiting the degree of hyperglycemia.

Patients with end-stage renal disease can develop severe hyperglycemia, but develop few if any neurologic symptoms, because there is no osmotic diuresis that is largely responsible for the marked rise in plasma osmolality.

Serum ketones Three ketone bodies are produced in DKA: acetoacetic acid, which is the only true ketoacid; beta-hydroxybutyric acid, a hydroxyacid formed from the reduction of acetoacetic acid; and acetone, which is derived from the decarboxylation of acetic acid. Acetone is a true ketone but is chemically neutral and therefore not an acid. Urine ketone bodies are detected by a dipstick. Testing for serum ketones is performed if urine testing is positive, using nitroprusside (Acetest) tablets or reagent sticks. A 4+ reaction with serum diluted 1:1 is strongly suggestive of ketoacidosis. False negative tests Nitroprusside reacts with acetoacetate and acetone, but not with betahydroxybutyrate. This is important because beta-hydroxybutyrate is the predominant ketone, particularly in severe DKA. It is therefore possible, although unusual, to have a negative serum nitroprusside reaction in the presence of severe ketosis. An indirect method to circumvent the masking of ketoacidosis is to add a few drops of hydrogen peroxide to a urine specimen. This will nonenzymatically convert beta-hydroxybutyrate to acetoacetate, which will then be detectable by nitroprusside. An alternative is to directly measure beta-hydroxybutyrate in the blood; monitors are available to measure beta-hydroxybutyrate at the bedside, but this assay may not be available in many hospitals. False positive tests Sulfhydryl drugs, such as captopril, penicillamine, and mesna, interact with the nitroprusside reagent and can lead to a false positive ketone test. Thus, a positive nitroprusside test cannot be reliably interpreted in patients treated with these drugs and direct measurement of betahydroxybutyrate is recommended. If it is not available, the diagnosis of DKA in this setting should be made on the basis of clinical presentation and an otherwise unexplained high anion gap metabolic acidosis in association with hyperglycemia.

Anion gap metabolic acidosis The serum bicarbonate concentration in DKA is reduced to a variable degree, ranging from mild to severe. In contrast, the serum bicarbonate concentration is normal or only mildly reduced in HHS. The sine qua non of DKA is an elevated anion gap metabolic acidosis, due to the production and accumulation of beta-hydroxybutyrate and acetoacetate. Compensatory hyperventilation results in a fall in the partial pressure of CO2 that minimizes the fall in arterial pH. The arterial pH in DKA is less than 7.30 and can be lower than 6.90. The severity of the metabolic acidosis is dependent upon a number of factors:

The rate of ketoacid production. The duration of increased ketoacid production. The acidosis will be less severe in patients who present early due, as an example, to abdominal pain or an underlying infection that precipitated the ketoacidosis.

The rate of acid excretion in the urine. Patients with relatively normal renal function can markedly increase acid excretion, thereby minimizing the severity of the acidosis. The magnitude of this effect was illustrated in a study of patients with DKA: ketone production averaged 51 meq/hour, while net acid excretion with the ketoacid anions averaged 15 meq/hour or 30 percent of the ketoacid load. The conversion of acetoacetic acid to acetone can neutralize another 15 to 25 percent of the acid load. The serum anion gap provides an estimate of the quantity of unmeasured anions in the serum,

such as albumin and, in DKA, ketoacids. It is calculated by subtracting the major measured anions (chloride and bicarbonate) from the major measured cation (sodium): Serum anion gap = Serum sodium - (serum chloride + bicarbonate) Patients with DKA usually present with a serum anion gap greater than 20 meq/L. However, the increase in anion gap is variable, being determined by two factors: the rate and duration of ketoacid production, and the rate of loss of ketoacid anions in the urine. With respect to ketonuria, excretion of the sodium and potassium salts of beta-hydroxybutyrate and acetoacetate lowers the serum anion gap without affecting the serum bicarbonate concentration and therefore the degree of acidosis. The amount of ketoacid anions excreted depends upon the degree to which glomerular filtration is maintained. Patients with relatively normal renal function can lose large quantities of ketoacids (as much as 30 percent of the ketoacid load), which minimizes the elevation in anion gap. Rarely, patients excrete so much ketoacids that they present with only a small elevation in serum anion gap. In addition, all patients, except those with end-stage renal disease, will develop a normal anion gap during the treatment

phase of DKA because of the urinary ketoacid anion losses. These principles are discussed in detail elsewhere. Serum sodium The measured serum sodium concentration in uncontrolled diabetes mellitus is variable, as factors are present that can both lower and raise the measured value. The final serum sodium concentration will reflect the balance between dilution of sodium due to osmotic water movement out of the cells, and concentration of sodium due to glucosuria-induced osmotic diuresis resulting in water loss in excess of sodium. Physiologic calculations suggest that the serum sodium concentration should fall by 1 meq/L for every 62 mg/dL (3.5 mmol/L) rise in the serum concentration of glucose. However, this standard correction factor was not verified experimentally. In an experimental model, hyperglycemia was induced in six healthy subjects by the administration of somatostatin (to block endogenous insulin secretion) and a hypertonic dextrose solution. A nonlinear relationship was observed between the changes in the glucose and sodium concentrations:













400 mg/dL (22.2 mmol/L).

At higher glucose concentrations, there was a greater reduction in the serum sodium concentration (1:25 ratio, a 4 meq/L reduction in serum sodium per 100 mg/dLfurther increase in serum glucose).

An overall ratio of 1:42 (a 2.4 meq/L reduction in the serum sodium concentration for every 100 mg/dL [5.5 mmol/L] elevation in the serum glucose) provided a better estimate of this association than the usual 1:62 ratio. The direct effect of hyperglycemia on the serum sodium concentration is counteracted to a

variable degree by the glucosuria-induced osmotic diuresis. The diuresis results in water loss in excess of sodium and potassium, which will tend to raise the serum sodium concentration and plasma osmolality unless there is a comparable increase in water intake. Some patients with uncontrolled diabetes have such a marked osmotic diuresis that, at presentation, the serum sodium concentration is increased and the serum osmolality is markedly elevated. Inadequate water intake prevents partial correction of the hyperosmolality and is a particular problem in hot weather and in elderly patients who may have an impaired thirst mechanism. The above calculations are best used to estimate how much the serum sodium concentration will rise as the hyperglycemia is corrected. The administration of insulin drives glucose and water into the cells, reversing the initial direction of water movement and raising the serum sodium concentration.

Most patients with DKA and HHS are mildly hyponatremic. However, patients with HHS who have a marked osmotic diuresis may have a normal or even elevated serum sodium concentration despite a serum glucose concentration that can exceed 1000 mg/dL (56 mmol/L). These patients are extremely hyperosmolar and often have neurologic symptoms that can include seizures and coma. In contrast, the osmotic diuresis is attenuated in patients with advanced underlying renal disease (usually due to diabetic nephropathy) and does not occur in patients already on maintenance dialysis. In this setting, there is hyperglycemia-induced hyponatremia (with the serum sodium concentration falling below 125 meq/L in many cases), only a modest elevation in the plasma osmolality (due to the counterbalancing effects of hyperglycemia and hyponatremia), and usually no neurologic symptoms despite marked hyperglycemia. Pseudohyponatremia Some patients with uncontrolled diabetes have marked hyperlipidemia and lactescent serum. In this setting, each liter of serum contains less water and therefore less sodium. As a result, the measured serum sodium concentration will fall, even though the physiologically important serum water sodium concentration and plasma osmolality are not affected. Ion-selective electrodes will reveal a normal serum sodium concentration if an instrument employing direct potentiometry is used. The effect of therapy on the serum sodium concentration in DKA is discussed separately. Serum potassium Patients with DKA or HHS, at presentation, have a potassium deficit that averages 300 to 600 mEq. A number of factors contribute to this deficit, particularly increased urinary losses due both to the glucose osmotic diuresis and to the need to maintain electroneutrality as ketoacid anions are excreted. Gastrointestinal losses and the loss of potassium from the cells due to glycogenolysis and proteolysis also may play a contributory role. Despite these potassium losses, the serum potassium concentration is usually normal or, in one-third of patients, elevated on admission. It is thought that hyperosmolality and insulin deficiency are primarily responsible for the relative rise in the serum potassium concentration in this setting. The rise in plasma osmolality leads to osmotic water movement out of the cells. This can promote the parallel movement of potassium into the extracellular fluid by two mechanisms: the rise in cell potassium concentration induced by water loss favors passive potassium exit through potassium channels in the cell membrane, and the frictional forces between solvent (water) and solute can result in potassium being carried out through the water pores in the cell membrane (a process that is called solvent drag) [47].

Since insulin normally promotes potassium uptake by the cells, insulin deficiency also contributes to elevated serum potassium levels.

Acidemia probably does not play a major role in the elevated serum potassium associated with DKA. Although a transcellular exchange of potassium with hydrogen ions resulting in a rise in serum potassium occurs in most forms of metabolic acidosis, it does not appear to play a major role in ketoacidosis (or lactic acidosis). The greater importance of hyperosmolality and insulin deficiency is illustrated by the observation that hyperkalemia also occurs in HHS despite the absence of acidosis. Insulin therapy lowers the potassium concentration and may cause severe hypokalemia, particularly in patients with a normal or low serum potassium concentration at presentation. Thus, careful monitoring and timely administration of potassium supplementation are essential. Serum phosphate Patients with uncontrolled hyperglycemia are typically in negative phosphate balance because of decreased phosphate intake and phosphaturia caused by osmotic diuresis. Despite phosphate depletion, the serum phosphate concentration at presentation is usually normal or even high because both insulin deficiency and metabolic acidosis cause a shift of phosphate out of the cells. This transcellular shift is reversed and the true state of phosphate balance is unmasked after treatment with insulin. In a review of 69 episodes of DKA, the mean serum phosphate concentration fell from 9.2 mg/dL (3 mmol/L) at presentation to 2.8 mg/dL (0.9 mmol/L) at 12 hours, and some patients had values as low as 1.0 mg/dL (0.32mmol/L). Serum amylase and lipase Serum amylase and lipase are the standard tests to diagnose acute pancreatitis, which may precipitate DKA, but both are often elevated in patients with DKA who do not have pancreatitis. As a result, the diagnosis of pancreatitis in patients with DKA should be based upon clinical findings and imaging. The mechanisms for hyperamylasemia and hyperlipasemia in DKA are not well defined, but the following observations have been made:

In 100 consecutive cases of DKA, 11 had acute pancreatitis as confirmed by CT scan; the most common causes were hypertriglyceridemia and alcohol intake. Two of the 10 evaluable patients (one was comatose) did not have abdominal pain.

In a review of 134 consecutive episodes of DKA in patients with no CT evidence of acute pancreatitis, elevations of serum amylase and lipase (threefold or higher in some patients) were seen in 17 and 24 percent, respectively. Abdominal pain was present in 19 percent of the patients in this series.

The source of these nonspecific amylase elevations is most often salivary, though may also be pancreatic. The source of nonspecific lipase elevations is not known.

The rise in amylase correlates with pH and plasma osmolality, while the rise in lipase correlates only with plasma osmolality. Peak values are seen within 24 hours of presentation.

Leukocytosis The majority of patients with hyperglycemic emergencies present with leukocytosis, which is proportional to the degree of ketonemia. Leukocytosis unrelated to infection may occur as a result of hypercortisolemia and increased catecholamine secretion. However, a white blood cell count greater than 25,000/microLor a band count greater than 10 percent may designate infection and indicates a need for further work up. Lipids Patients with DKA or HHS may present with marked hyperlipidemia and lactescent serum. In a study of 13 patients with DKA, the mean plasma triglyceride and cholesterol levels on admission were 574 mg/dL (6.5 mmol/L) and 212 mg/dL (5.5 mmol/L), respectively. Triglycerides fell below

150 mg/dL (1.7 mmol/L) in 24 hours with insulin therapy. Insulin is the most anti-lipolytic hormone. Insulin deficiency, combined with elevated levels of lipolytic hormones (catecholamines, growth hormone, ACTH, and glucagon) in DKA and HHS result in accumulation of free fatty acids. The increase in serum fatty acids leads to inhibition of glycolysis, production of triacylglycerol, and increased ketones by fatty acid entry into mitochondria where they serve as a substrate for ketogenesis. Differential Diagnosis Alcoholic and fasting ketoacidosis Alcoholic ketoacidosis (AKA) and starvation ketosis are other causes of ketoacidosis. The acidosis can be relatively severe in alcoholic ketoacidosis. In comparison, ketoacid levels in fasting ketoacidosis do not exceed 10 meq/L with prolonged fasting alone, which means that the serum bicarbonate concentration is typically above 14 meq/L. The presence of ketoacidosis without hyperglycemia in an alcoholic patient is virtually diagnostic of AKA. However, modest elevations in serum glucose have been reported in alcoholic ketoacidosis. This may reflect underlying unrecognized diabetes or a catecholamine-mediated stress response. Measurement of A1C may be helpful to detect chronic hyperglycemia. In addition to fasting, a case report suggested a relationship between low carbohydrate diet and ketoacidosis. Anion gap acidosis DKA must also be distinguished from other causes of high anion gap metabolic acidosis including lactic acidosis (which can be induced by metformin, particularly in patients with impaired renal function); ingestion of drugs such as aspirin, methanol, and ethylene glycol; and advanced chronic kidney disease. None of these disorders causes ketoacidosis.

Other Investigations 12-lead ECG to detect ischaemia and changes due to hyperkalaemia or hypokalaemia3 Chest x-ray to detect pneumonia CT scan to detect neurological changes (eg if stroke is suspected). If the patient presents with a mild form of DKA, the patient can be managed on the ward. If the patient has moderate or severe form of DKA, admission to ICU is necessary. Management of DKA Oxygenation/Ventilation Airway and breathing remain the first priority. If the patient presents with reduced consciousness/coma (GCS<8) consider intubation and ventilation. In obtunded patients airway can be temporarily maintained by insertion of Guedels airway. Apply oxygen via Hudson mask or non rebreather mask if indicated. Insert nasogastric tube and leave on free drainage if the patient is drowsy and vomiting or if patient has recurrent vomiting. Airway, breathing and level of consciousness have to be monitored throughout the treatment of DKA. Fluid replacement Circulation is the second priority. DKA patients are severely dehydrated and can be in hypovolaemic shock. Fluid replacement should be initiated immediately. Fluid resuscitation reduces hyperglycaemia, hyperosmolality, and counter-regulatory hormones, particularly in the first few hours, thus reducing the resistance to insulin. Insulin therapy is therefore most effective when it is preceded by initial fluid and electrolyte replacement.

Two large-bore intravenous cannulas or a central venous catheter (such as PICC) should be inserted. 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, although colloids can be used if the patient is in hypovolaemic shock2. N/saline (0.9%NaCl) is most appropriate initially. Hartmans solution or Plasmalyte are also suitable (they have the advantage of providing a bicarbonate precursor). Exclusive use of normal saline often contributes to a hyperchloraemic acidosis some days later. If the patient is not cardiaccompromised, the initial bolus of fluid is 15-20ml/kg over an hour, which is equivalent to 1-1.5L in the first hour, and then 4-10ml/kg/hour for the following hours1. 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. As a guide, serum osmolality should decrease by less than 3mOsm/L/hour. Careful monitoring of haemodynamic status (in unstable patients every 15 minutes), renal function, mental status and meticulous fluid balance are necessary to avoid fluid overload. Intravenous fluids should be reduced as soon as the osmotic dieresis resolves, and urinary volumes decrease. Aggressive reduction of blood glucose and high rates of fluid resuscitation are associated with cerebral edema in 1% of children and adolescents. One recommendation limits fluid resuscitation in the first 4 hours of therapy to <50ml/kg isotonic solution. Fluid resuscitation also should be less aggressive in patients with heart failure. Electrolyte replacement Dehydration and osmotic diuresis cause enormous electrolyte shifts in cells and serum. Potassium: Potassium is the major intracellular positive ion, responsible for maintenance of the electro-potential gradient of the cell membrane. Hyperkalaemia may result from reduced renal function, but the patient is more likely to have total body potassium depletion. Intracellular potassium depletion results from a lack of insulin, intracellular dehydration, acidosis and hydrogen ion shift. Vomiting can further cause potassium depletion. During DKA management insulin therapy, correction of acidosis and fluid resuscitation will decrease serum potassium levels. Potassium shifts into the cells with the passage of glucose. Therefore the potassium level has to be checked before starting insulin therapy6. The serum potassium level can indicate the severity of the potassium deficit. Serum potassium of 3mmol/L in an average adult suggests a deficit of 200mmol, serum potassium of 2.5mmol/L suggests a deficit of 300mmol and serum potassium of 2mmol/L suggests a deficit of 400mmol15. If potassium is <3.3mmol/L it has to be replaced before commencing insulin infusion11. Urinary output has to be confirmed prior to potassium replacement. The potassium is replaced at 10mmol/hr until serum potassium is > 4.0mmol/l. The potassium can be added to a burette, or infused

separately if the IV resuscitation fluid rate is > 150ml/h (eg piggybacked from a syringe driver). Potassium should not be replaced if the level is >5.0mmol/L6. 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 iv-cannula site has to be inspected regularly to avoid tissue damage. Sodium: Early hyponatraemia in DKA does not usually require specific treatment, it is an artefact arising from dilution by the hyperglycaemiainduced water shifts. As excess water moves out of the extracellular space with the correction of hyperglycaemia, the sodium level will return to normal. Phosphate: Total body phosphate can be low due to loss from osmotic diuresis. Phosphate will move into cells with glucose and potassium once insulin therapy has started, and phosphate replacement is likely to be required if the serum levels are in the low end of the normal range, or just low. Hypophosphataemia of < 0.3mmol/l can cause respiratory muscle weakness, cardiac muscle weakness, decreased 2,3-DPG and a right-shift of the oxygen-haemoglobin-dissociation curve13. Phosphate can be given in the form of KH2PO4 at a rate of 10mmol/hr. The usual dose in 24 hours is 30-60mmol for an adult.

Insulin therapy Insulin therapy is crucial to DKA management. It facilitates glucose uptake into the cell, correction of cell metabolism and acidosis. Insulin is initially given as an intravenous bolus of 0.1units/kg or a bolus of 5 or 10 units. Then a continuous insulin infusion of 50 units of Actrapid in 50ml N/Saline is commenced. The infusion rate is 5 units/hour, or 0.05-0.1 units/kg/hour for children16. The blood glucose level must be checked hourly until urinary ketones are gone, and than can be checked less frequently (2nd hrly and later 4th hrly). Initially blood glucose can be as high as 30-45mmol/L. Insulin infusion should slowly reduce blood glucose level. The rate at which serum glucose falls should not exceed 4mmol/L per hour. This is important because if it falls too rapidly cerebral oedema may result through the influx of water into the brain cells. This is because the intracellular change in osmolality lags behind the extracellular changes in osmolality. Cerebral oedema is rare in adults with DKA, and is most likely to occur in children with newly diagnosed diabetes. A slow normalisation of osmolality is desired. The patient, while acidotic, is kept nil by mouth to maximize the speed at which ketoacidosis can resolve (food might slow resolution). Once BSL has fallen <15mmol/L, a 5%-dextrose infusion is started at 80 ml/hour to slow the correction of the hyperglycaemia and prevent hypoglycaemia16. The BSL can be kept at 12-15mmol/l for

several hours while the hyperosmolality and mental state improve. The dextrose infusion is titrated to the BSL and can be increased up to 250ml/hour if BSL is low. Alternatively 10% dextrose can be used instead of 5% dextrose if BSL falls too rapidly. 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. The principle of titrating glucose infusion to the BSL and not titrating insulin to BSL, as we would usually do it, may be a difficult concept to grasp, 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. It facilitates metabolism of ketone acids, thus the correction of acidosis. If insulin were reduced or ceased prematurely, ketoacidosis would return and the patients condition would deteriorate. Decreasing the insulin infusion rate should only be considered once ketoacidosis has resolved, and urinary ketones have disappeared. This is discussed later. Aim ultimately for a BSL of 6-10mmol/L. In summary the patient has three concurrent infusions: rehydration fluid, insulin infusion and dextrose infusion. The Use of Bicarbonate In acidosis myocardial contractility and catecholamine function are impaired. Multiple studies, however, have shown that the treatment of metabolic acidosis with sodium bicarbonate is not helpful. Sodium bicarbonate infusion can cause paradoxical central nervous system acidosis, hypokalaemia and tissue hypoxia through decreased tissue oxygen uptake and a left-shift of the oxy-haemoglobindissociation curve. Bicarbonate is not routinely recommended if the initial pH is 6.9 or more, because the acidosis will correct with insulin therapy. Bicarbonate is regenerated as the ketone anions are metabolized. However, one clear indication for bicarbonate therapy is life-threatening hyperkalaemia. Nursing Management Vital signs: blood pressure, pulse, respirations, pulse oximetry, level of consciousness, temperature. Hourly BSL until ketones have disappeared, then 2 hourly. If BSL falls rapidly, 1/2 hourly checks may be necessary. Hourly ABG to monitor pH, bicarbonate and potassium until pH is above 7.10 then 2 hourly until pH is above 7.30 or bicarbonate above. Insertion of an arterial line advised due to frequent blood sampling. Insertion of a PICC line is useful for the number of infusions

Patient nil by mouth until acidosis is reversed. Acidosis can cause nausea and vomiting. Food intake could aggravate nausea and vomiting, increase BSL and make it difficult to titrate dextrose infusion to BSL. Assess fluid status: jugular venous pressure, peripheral perfusion, capillary refill, mucous membranes, pulse rate, urine output. Monitor other electrolytes, urea, creatinine hourly. Consider insertion of urinary catheter. Strict fluid balance. Urinalysis. Check urine for ketones 2-4 hourly if catheterized or every portion voided. Be aware that it takes longer for ketones to disappear than for hyperglycaemia and acidosis to resolve. Check for glucose. Insertion of a nasogastric tube if patient is vomiting. Provide oral hydration with ice chips and frequent oral hygiene. Provide comfort measures and manage pain. Give reassurance to relieve anxiety. Treatment of Co-morbid Precipitating Factors Resolving Acidosis, Dehydration and Hyperglycaemia Generally the endpoint of treatment is not normoglycaemia but the correction of acidosis. Acidosis is resolving when serum bicarbonate is >18mmol/L and blood pH >7.3. Resolution of ketosis takes longer than resolution of acidosis and hyperglycaemia. Correction of hyperglycaemia is achieved when blood glucose is <11mmol/L. When blood pH is above 7.3 and bicarbonate is >18mmol/L, the insulin infusion rate can be reduced to 0.05 units/kg/hour or to 3.5 units/h. Again it must be emphasized that the insulin infusion is not to be stopped. Ceasing the insulin infusion can lead to recurrence of ketoacidosis and deterioration of the patients condition. When acidosis has resolved, the patient may commence oral intake. However, if the patient cannot tolerate oral intake, dextrose infusion, N/saline infusion and intravenous insulin have to continue. If the patient is able to eat, insulin infusion continues and concurrent subcutaneous insulin is commenced. Insulin infusion should not cease until at least 2-4 hours after subcutaneous injection, because insulin has a short half-life and intravenous and subcutaneous insulin have to overlap6. Thus hyperglycaemia and recurrent ketoacidosis should be avoided. The patient is started on a multiple-dose split short-acting/ longacting insulin regimen9. If the patient is a known diabetic and the current illness is of short term, the patient may revert to the previous insulin routine. If the illness of a known diabetic is severe and prolonged, insulin may have to be increased in this time of prolonged stress. The patients endocrinologist

should be involved in the management at this stage, or the new diabetic should be referred to an endocrinologist. If the patient has not attended diabetic services for a long time, a newer and better insulin product may be introduced (Diabetic Services, Nepean Hospital, 8 January 2007, pers com). Re-hydration with Hartmanns solution continues until euvolaemia is achieved. Euvolaemia is attained when blood pressure and pulse rate are normal and urine output is adequate, neck veins are visible, mucous membranes are moist, and skin turgor is normal. The goals of DKA management are re-hydration of all fluid compartments, normal tissue perfusion and kidney function, and normal cell metabolism.