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Treatment and complications of diabetic ketoacidosis in children and adolescents

Author:
    Morey W Haymond, MD
Section Editors:
    Joseph I Wolfsdorf, MB, BCh
    Adrienne G Randolph, MD, MSc
Deputy Editor:
    Alison G Hoppin, MD

Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jan 24, 2017.

INTRODUCTION — Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (T1DM), with a case fatality rate ranging from 0.15 percent to 0.31 percent [1-3]. DKA also can occur in children with type 2 DM (T2DM); this presentation is most common among youth of African-American descent [4-8]. (See “Classification of diabetes mellitus and genetic diabetic syndromes”.)

The management of DKA in children will be reviewed here (table 1). There is limited experience in the management and outcomes of DKA in children with T2DM, although the same principles should apply. The clinical manifestations and diagnosis of DKA in children and the pathogenesis of DKA are discussed elsewhere. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents” and “Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis”.)

DEFINITION

●Diabetic ketoacidosis – A consensus statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2014 defined the following biochemical criteria for the diagnosis of diabetic ketoacidosis (DKA) [9]:

•Hyperglycemia – Blood glucose of >200 mg/dL (11 mmol/L) AND

•Metabolic acidosis – Venous pH <7.3 or a plasma bicarbonate <15 mEq/L (15 mmol/L) AND

•Ketosis – Determined by the presence of ketones in the blood or urine.

Ketosis is ideally determined by measuring serum beta-hydroxybutyrate (BOHB) in the laboratory or by a point-of-care device. BOHB concentrations ≥3 mmol/L (31 mg/dL) are consistent with DKA [9,10] and provide a more accurate index of ketosis than the use of older methods using nitroprusside, which measure only acetoacetate (the ketone body present at a lower concentration) resulting in an underestimate of the severity of ketonemia. If it can be established by any means that the patient has severe ketosis (in the absence of hyperlactatemia) and measurement of blood BOHB is not available, sequential calculation of the anion gap is a useful means to track the progressive improvement in ketonemia. (See ‘Assessment of severity’ below.)

Disturbances in fluid and electrolyte balance result in volume depletion and mild to moderate serum hyperosmolality. The clinical manifestations of DKA are related to the degree of hyperosmolality, volume depletion, and severity of acidosis [11]. Some children present with severe hyperglycemia (blood glucose >600 to 2500 mg/dL) and severe ketoacidosis. These children are frequently the youngest and sickest of patients. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”.)

●Hyperglycemic hyperosmolar state – Hyperosmolar hyperglycemic state (HHS) is a hyperglycemia emergency, distinguished from classic DKA by marked hyperglycemia (plasma glucose >600 mg/dL [>33.3 mmol/L]) and sometimes very severe hyperglycemia (2500 mg/dL), without significant acidosis or ketosis. These individuals frequently have altered consciousness and moderate lactic acidosis. HHS requires prompt recognition and management that is distinct from that of DKA. HHS is more common among adolescents at the onset of type 2 diabetes, compared with type 1 diabetes mellitus (T1DM) [12,13]. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”, section on ‘Definition’ and “Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment”.)

INITIAL RAPID ASSESSMENT — All patients with suspected DKA should be rapidly evaluated as follows.

Clinical assessment

●Measure vital signs and assess for signs of shock caused by volume depletion (eg, decreased blood pressure, reduced peripheral pulses, tachycardia, and significant postural changes in blood pressure).

●Measure weight (and length if possible) – For use in calculating fluid replacement and insulin infusion rates. If recent measurements of weight are available, these can be compared with the current weight to estimate the fluid deficit.

●Estimate the degree of dehydration – Note that clinical symptoms and signs of dehydration, such as skin turgor and dryness of mucus membranes, tend to underestimate the degree of dehydration in a child with DKA, and urine specific gravity is not valid as a result of both glycosuria and ketonuria. Therefore, targets for fluid repletion generally rely on assumptions of a 5 to 10 percent fluid deficit, rather than on clinical estimates of dehydration. (See ‘Dehydration’ below.)

●Neurologic assessment – All patients should have a rapid assessment of level of consciousness at presentation using the Glasgow coma scale (table 2). This should be followed by a more detailed assessment for the more subtle signs of cerebral edema, which include headache (especially sudden onset), altered or sluggish pupillary responses, age-inappropriate incontinence, as well as vomiting, restlessness, irritability, or drowsiness. Decreased heart rate, increasing blood pressure, and opisthotonic posturing are late signs in the evolution of cerebral edema (table 3). The neurological assessment should be repeated hourly throughout treatment or until the patient is clinically recovered from ketoacidosis and their mental status examination is normal. (See ‘Cerebral edema’ below.)

Severe neurologic compromise at presentation is associated with poor prognosis, primarily because such patients may have cerebral edema or be at increased risk for developing cerebral edema during therapy. This was illustrated in a retrospective multicenter study of 61 children with DKA and cerebral edema; all patients who either died or survived in a persistent vegetative state had a Glasgow coma score on admission ≤7 (score of 6 to 7 includes an abnormal or absent purposeful response to pain) [14]. As a result, these children must be very carefully rehydrated and closely monitored during the initial 24 hours of therapy. If cerebral edema is suspected, the clinician should not hesitate to use mannitol or 3 percent saline. (See “Cerebral edema in children with diabetic ketoacidosis”, section on ‘Treatment’.)

Laboratory testing

●Immediate testing – Measure using a point-of-care meter, if available, to confirm the diagnosis of DKA:

•Blood glucose – Blood glucose >200 mg/dL (11 mmol/L) confirms hyperglycemia.

•Blood beta-hydroxybutyrate – Plasma beta-hydroxybutyrate (BOHB) concentrations are the most direct and reliable measure of the degree of ketoacidemia. BOHB concentrations ≥3 mmol/L (31 mg/dL) document the severity of ketonemia, and together with the blood glucose confirm the presence of DKA [9]. Once the initial degree of ketonemia has been established, either BOHB or the anion gap may be used to monitor the response to treatment, as described below. (See ‘Monitoring’ below.)

•Urine ketones – Measurement of urine ketones should not be used to judge the severity of ketonemia or acidosis, as this test only measures acetoacetate. Moreover, a “large” reading in urinary acetoacetate can be reached when BOHB is only 2 to 3 mmol/L.

●Send to laboratory for urgent testing, for more accurate measurements, and to further characterize the patient’s acid-base status and dehydration:

Blood specimens:

•Blood glucose.

•BOHB – Even if point-of-care testing is also available.

•Blood lactate – If available, to exclude coexistence of both lactic and ketoacidosis.

•Electrolytes – Including bicarbonate.

•Blood urea nitrogen (BUN), creatinine.

•Venous pH and pCO2.

•Complete blood count.

•Calcium, phosphorus, magnesium – These are performed by some clinicians to screen for abnormalities in these values, which are unusual. If abnormalities are present, they usually resolve during treatment for DKA.

Other specimens:

•Urinalysis (for ketones), if serum beta-hydroxybutyrate measurement is not available.

•Cultures of blood, urine, and/or throat if fever or localizing signs of infection are present.

•Electrocardiogram (ECG), to look for evidence of hyperkalemia (peaked T wave) if laboratory measurement of potassium status is delayed.

Assessment of severity — Categorizing the severity of DKA at presentation helps to determine the appropriate level of care (eg, need for intensive care unit [ICU] admission). The severity of DKA at presentation is typically categorized by acid-base status, as indicated by venous pH and serum bicarbonate concentrations (table 4):

•Mild – pH 7.2 to 7.3; bicarbonate 10 to 15 mEq/L

•Moderate – pH 7.1 to 7.2; bicarbonate 5 to 10 mEq/L

•Severe – pH <7.1; bicarbonate <5 mEq/L

The anion gap can be used as an index of the severity of the metabolic acidosis and is calculated from the following equation:

Anion gap = Sodium – (chloride + bicarbonate); a normal anion gap is 12±2

However, the presence of a large anion gap in the absence of significant ketosis (BOHB ❤ mmol) strongly suggests significant lactic acidosis and the possibility of hyperosmolar hyperglycemic state (HHS) or sepsis [9] (see ‘Definition’ above). During treatment, the anion gap tends to normalize before resolution of the acidosis, frequently resulting in a mild “non-gap” acidosis as treatment progresses. This is usually associated with hyperchloremic metabolic acidosis result from the large amount of chloride administered during rehydration. Therefore, the anion gap is a better measure of effective treatment than the serum bicarbonate concentration. (See ‘Metabolic acidosis’ below.)

The respiratory rate also may be a helpful clue to the acid-base status because the minute volume generally increases in proportion to the severity of the acidosis. Other factors that predict more severe ketoacidosis include longer duration of symptoms, depressed level of consciousness, or compromised circulation [15-17].

Disposition — All patients with DKA should be managed in a unit with personnel and facilities capable of frequent monitoring of clinical symptoms, fluid status, and laboratory results. The experienced clinician is in the best position to determine the safest place for therapy within their individual institutions. In most tertiary care institutions, patients should be triaged as follows [9]:

●Pediatric intensive care unit (PICU) or specialized inpatient diabetes care unit – For patients with signs of or risk factors for cerebral edema (altered consciousness, younger than five years of age, severe acidosis [venous pH <7.1 or low pCO2], high BUN, hyper- or hypokalemia, or long duration of clinical symptoms of DKA). In some institutions, this includes patients receiving intravenous (IV) insulin and those who need frequent monitoring.

●Regular inpatient care area (if capable of providing close monitoring) – Most other patients with DKA, except for those with mild DKA who do not meet the standards below.

●Emergency Department care with outpatient follow-up – Patients with established diabetes and mild DKA should be evaluated initially in an emergency room. A full clinical and laboratory evaluation in an emergency room setting is particularly important for patients with documented BOHB concentrations >3 mmol/L or concerns about neurologic signs. In cases of mild DKA, initial fluid and insulin therapy in the Emergency Department can significantly improve the clinical picture and allow the medical team to discharge patients home, provided that the patient has access to point-of-care testing of both blood glucose and BOHB, and the caretakers are proficient in diabetes sick-day management. However, close monitoring and follow-up by an experienced diabetes team is required. (See ‘Mild DKA’ below.)

Hospitalization with close monitoring is appropriate for young children (eg, <five years of age) because of their sensitivity to insulin as compared with older children and because of their increased risk for cerebral edema. Children of any age should be treated in a hospital if the home environment does not provide close supervision and monitoring.

TREATMENT — The approach and principles of management are the same for all children with DKA, regardless of the severity of DKA. The clinician must individualize the treatment plan based on the child’s physical and laboratory findings, and treatment will need to be adjusted over time for each child. Protocols for management of fluids and insulin dosing are helpful but should be used in conjunction with clinical reassessments and judgement. We recommend use of a flow chart to track hourly vital signs and neurologic symptoms, fluid status (goals, input, and output), and insulin dosing, as well as laboratory results (table 5). During initial therapy, the patient should be carefully monitored for signs of cerebral edema. (See ‘Monitoring’ below and ‘Cerebral edema’ below.)

Moderate and severe DKA — The main principles of management are to administer insulin and to correct the fluid and electrolyte abnormalities of hypovolemia and whole body sodium and potassium depletion. Studies have estimated water losses of approximately 70 mL/kg (range, 30 to 100 mL/kg), sodium 5 to 13 mEq/kg, and potassium 6 to 7 mEq/kg [18-20]. Approaches are based primarily on case series and clinical experience, generally focusing on the outcome of avoiding cerebral edema.

Dehydration — DKA is a state of hyperosmolar dehydration. The volume depletion is caused by urinary losses from osmotic diuresis (due to osmotic action of glucose and ketones in the urine), as well as gastrointestinal losses from vomiting and/or diarrhea, if present. The overall volume deficit in children with DKA is typically between 5 and 10 percent. Fluid administration is required but should proceed cautiously to minimize the risk for cerebral edema. The goals of initial volume expansion are to restore the effective circulating volume by acutely replacing some of the sodium and water loss, and to restore glomerular filtration rate to enhance clearance of ketones and glucose from the blood [15,16].

Elevations in the blood urea nitrogen (BUN) and hematocrit (Hct) are useful to confirm hypovolemia in DKA and to follow its correction with rehydration. Many of the clinical findings used to assess volume status are unreliable, such as the condition of the patient’s oral mucus membrane, which is almost always dry because of hyperventilation and mouth breathing. Changes in skin turgor tend to underestimate the degree of dehydration because the fluid losses are from both the extracellular and intracellular spaces. In addition, the degree of extracellular fluid loss is in part masked because hyperglycemia results in a shift of water from the intracellular to the extracellular fluid compartment [21]. Elevated urine specific gravity cannot be used as a measure of hypovolemia in patients with DKA because glucose and, to a lesser degree, ketones raise the specific gravity. Hypovolemic shock is a rare occurrence in DKA but, if present, should be promptly treated. The patient in shock should be evaluated for other causes of shock, such as sepsis. A well-planned approach to management will yield consistent progress toward recovery. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”, section on ‘Signs and symptoms’.)

Most experts recommend accomplishing the volume expansion gradually and with isotonic fluids because these approaches might reduce the risk for cerebral edema [16,17,22]. The evidence underlying this possible association is weak and conflicting. In one clinical study in children, high volume of fluid administration during the first four hours of treatment was one of several risk factors that predicted cerebral edema [23]. However, several other clinical studies failed to show such an association [24-26]. Nonetheless, gradual correction of the deficit and the initial use of isotonic fluids seems prudent. In patients who are not markedly hypovolemic, this approach may even result in earlier reversal of the acidosis [27,28].

Initial volume expansion — For patients with moderate to severe DKA, we suggest initiating fluid repletion with an infusion of 10 mL/kg (up to a maximum volume of 1000 mL) over one hour, using isotonic saline or Ringer’s lactate [15,16,29]. If the effective circulating volume is still compromised, an additional infusion of 10 mL/kg can be given over the next hour. We generally do not give more than 20 mL/kg in total boluses unless the patient’s cardiovascular status is compromised. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”, section on ‘Signs and symptoms’.)

Patients with mild DKA also may benefit from an intravenous (IV) fluid bolus and/or fluid infusion during management in the Emergency Department, to hasten recovery. (See ‘Mild DKA’ below.)

Subsequent fluid administration — Once the child is hemodynamically stable, subsequent volume expansion should be given more slowly, with a goal of replacing the remaining fluid deficit over 24 to 72 hours, depending on the rate of clinical recovery. We use a rate of about 2500 mL/m2 per 24 hours, or 1.5 times the usual maintenance rate of fluid requirement. The rate of fluid administration should not exceed 3000 mL/m2 per 24 hours, or 2 times the maintenance rate, unless there is objective evidence of shock. Excessive fluids may increase the risk for cerebral edema, at least over the initial 24 to 36 hours. If the child takes oral fluids, this intake should be included in the calculation of overall fluid administration during the first 48 hours of treatment [9]. After the first 48 hours of treatment, hourly rates of fluid administration can be liberalized to as much as 3500 mL/m2 per 24 hours (including oral fluids), to achieve full hydration over 48 to 72 hours [15,16]. Fluids may be liberalized somewhat earlier for patients with mild DKA. (See “Maintenance fluid therapy in children” and ‘Cerebral edema’ below.)

The solution used for this ongoing volume repletion should initially consist of isotonic saline (normal saline [0.9 percent saline]) or Ringer’s lactate for at least the first four to six hours. For most patients, 40 mEq/L of potassium salts should be added to the solution to correct the total body potassium deficit. However, the appropriate solution depends on the serum potassium concentrations, and the clinician should be alert to the possibility that acute renal failure may develop due to renal vein thrombosis or acute tubular necrosis (see ‘Serum potassium’ below). In our practice, we use Ringer’s lactate solution, to which 35 mEq/L of potassium is added (20 mEq/L as potassium phosphate and 15 mEq/L as potassium chloride) throughout the period of rehydration.

After the first four to six hours of treatment, some clinicians reduce the sodium concentration to not less than one-half isotonic (ie, ≥0.45 percent saline), provided that the serum sodium concentration is rising appropriately as the serum glucose concentration falls, and that the patient’s circulatory and mental status are stable. The choice between one-half isotonic, Ringer’s lactate solution or isotonic saline depends on the patient’s circulatory status and the rise in serum sodium as the hyperglycemia is corrected. The concentration of potassium salts included in the replacement fluid should be based on serum potassium concentrations.

Hyperglycemia — Subsequently, an insulin infusion is begun at a rate of 0.1 unit/kg per hour [15,16]. To avoid unnecessary delay, we suggest initiating the order for the insulin infusion as soon as DKA is recognized, and preparing the insulin infusion while the fluid bolus is being administered. A lower dose of 0.05 unit/kg per hour may be used initially in younger children who may be more sensitive to insulin [9,30]. The efficacy of a lower initial dose of insulin is supported by a randomized trial in a study of 50 children with DKA, which reported that a low-dose insulin infusion (0.05 unit/kg per hour) was as effective as standard dose insulin (0.1 unit/kg per hour) in rate of blood glucose decrease and time to achieve the blood glucose target of 250 mg/dL [31]. Further trials are needed to determine whether there are any advantages or complications arising from the use of the low-dose infusion. There is no specific evidence that the established initial dose of insulin (0.1 units/kg per hour) is the etiology of any of the complications associated with our standard management of DKA in children and adolescents.

Guidelines suggest delaying the start of the insulin infusion for at least one hour after starting fluid replacement and avoiding an initial insulin bolus because of concerns that more vigorous insulin replacement might increase the risk for cerebral edema [9,17]. However, it should be recognized that these approaches are based on limited data from a single clinical study [23] that may be underpowered to have confidence in this conclusion.

●Technique – The insulin can be mixed in one-half isotonic saline and administered in a syringe infusion pump to control the rate of insulin administration. The solution should be concentrated as much as possible and should be flushed through the tubing, to minimize binding of insulin to the tubing and syringe. As an example, 50 units of short-acting (“regular”) insulin are added to 50 mL of one-half isotonic saline, providing 1 unit per mL of infusate. The syringe is then “piggybacked” into the patient’s indwelling IV catheter as close as possible to the venous site.

Within 60 minutes, steady state serum insulin levels are achieved (100 to 200 microU/mL), which offset insulin resistance, suppress glucose and fatty acid mobilization (and indirectly inhibits ketogenesis), and stimulate peripheral glucose uptake and metabolism [32,33]. In addition, volume expansion will lower the serum glucose by dilution. (See “Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis”.)

●Two-bag system – Some institutions, including our own, use a “two bag system” to maintain the patient’s plasma glucose in an acceptable range [27,34]. In this technique, two bags of the selected saline solution are prepared, one of which contains 10 percent dextrose and the other does not contain dextrose. By adjusting the relative rates of fluid administration from each bag, the rate of fluid administration can be maintained constant, while the variable rate of dextrose infusion can be achieved to respond to changes in the patient’s serum glucose concentrations.

●Dose adjustment – In most patients, the hyperglycemia corrects before the ketoacidosis. When the serum glucose concentration decreases to 250 to 300 mg/dL (13.9 to 16.7 mmol/L), the IV fluid infusion should be changed to 5 percent dextrose in normal saline, one-half normal saline, or Ringer’s lactate solution. This allows continued administration of insulin, which is often necessary to correct the residual ketoacidosis [17]. If the serum glucose falls below 150 mg/dL (8.0 mmol/L) before complete resolution of the ketoacidosis, the concentration of dextrose in the IV solution should be increased (eg, to 10 or 12.5 percent) to permit continued or increased rates of insulin infusion. To avoid hypoglycemia or hyperglycemia, it is advisable to keep serum glucose concentrations around 100 to 150 mg/dL in older children (5.5 to 8.3 mmol/L), or 150 to 180 mg/dL (8.3 to 11.1 mmol/L) for younger children, throughout the insulin infusion.

For most patients, the insulin infusion rate should be reduced only after the ketoacidosis is corrected or nearly corrected. However, if the patient shows marked sensitivity to insulin, as in some younger or malnourished children, it may be necessary to decrease the insulin infusion rate to avoid hypoglycemia (eg, to 0.05 units/kg/hour), provided that the ketoacidosis continues to improve [9].

If the ketoacidosis does not improve during the first two to four hours of the insulin infusion, the patient should be reassessed. Possible explanations are severe insulin resistance (due to infection, dehydration, acidosis, etc), incorrect preparation of the insulin infusion, and decreased insulin delivery due to binding of insulin to the IV tubing or pump failure. We recommend preparing a new insulin syringe and a new pump to rule out these possibilities. In many such patients, the insulin dose just needs to be increased.

In unusual circumstances, and especially if facilities to administer IV insulin are not readily available, subcutaneous or intramuscular insulin can be used as initial therapy [9,35,36]. However, when insulin is administered subcutaneously, absorption may be inconsistent, particularly in the setting of volume depletion and secondary sympathetic activation, which can decrease local perfusion [37].

Electrolyte and acid-base disturbances

Serum sodium — Serum sodium concentration at the time of diagnosis with DKA can vary widely, but many patients have mild hyponatremia due to osmotic effects of hyperglycemia combined with intake of free water. Measurements of serum sodium are also artifactually decreased by lipemia (severe hyperlipidemia causes pseudohyponatremia). (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”.)

Despite the variability in serum sodium concentration at the time of presentation, DKA is a form of hypertonic dehydration, and care must be taken in rehydrating the patient to minimize risks from rapid fluid shifts, which may precipitate or be involved in the development of cerebral edema. Reversing the hyperglycemia with fluid expansion and insulin administration will lower the plasma osmolality, cause water to move from the extracellular fluid into the cells, and raise the serum sodium concentration. During rehydration, the clinician must serially assess the serum sodium concentration and ensure that it is rising gradually and appropriately as plasma glucose concentration decreases. Failure of the serum sodium to rise appropriately could be an early sign that the patient is at risk for cerebral edema, as suggested by a few studies [38-42]. However, a causal association between the rate or concentration of sodium administered during treatment for DKA and the development of cerebral edema has not been conclusively established [22].

In our practice, we measure serum sodium hourly for the first three to four hours and then every two hours, to assess the anticipated changes of serum sodium described above. When clinically appropriate, the frequency of measurement can be reduced to every four to six hours.

With appropriate replacement of fluids and electrolytes in a child who is otherwise improving, the serum sodium concentration should gradually increase. The expected rise in serum sodium (Na) attributable to the decrease in serum glucose can be calculated according to the following formula [43]:

Corrected serum Na = Measured serum Na + [ΔSG ÷ 42]

ΔSG is the increment above normal in the serum glucose concentration (in mg/dL; the ΔSG should be divided by 2.3 if measured in mmol/L). Thus, serum sodium should rise by approximately 2.4 mEq/L for every 100 mg/dL decrease in plasma glucose concentration, or 0.5 mmol/L for each 1 mmol/L decrease in plasma glucose [9]. Some clinicians plot the sodium concentration on a nomogram (figure 1) to facilitate tracking of changes in serum sodium during insulin treatment and to help identify patients in whom the serum sodium does not rise appropriately.

If the serum sodium fails to rise appropriately, consideration should be given to increasing the sodium concentration in the infused fluids and decreasing their rate of administration. The patient should be carefully monitored for early signs of cerebral edema. (See ‘Cerebral edema’ below and “Cerebral edema in children with diabetic ketoacidosis”.)

Serum potassium — Patients with DKA always have a total body deficit of potassium because of both renal and gastrointestinal losses. However, serum potassium at the time of presentation can be normal, increased, or decreased. This is because the combination of insulin deficiency, which impairs potassium entry into the cells, and hyperosmolality, which pulls water and potassium out of the cells, tend to raise the serum potassium, and often result in normal or elevated serum levels of potassium despite the total body deficit.

Regardless of the initial serum potassium level, insulin therapy drives potassium into cells, resulting in a fall in the serum potassium concentration. Thus, potassium replacement will almost always be required within one to two hours of the initiation of fluid and insulin therapy in children with DKA, except in those with renal failure. In our experience, most patients present with potassium levels in the normal or high range, due to dehydration and prerenal azotemia. After initial IV expansion, the potassium concentration generally falls into the normokalemic or mildly hypokalemic range. It is uncommon for patients to have hypokalemia before fluid expansion. However, should this be the case, more aggressive potassium replacement is indicated.

Optimal therapy varies with the initial serum potassium concentration. Regardless of the regimen, the serum potassium should be carefully monitored during therapy. In addition, electrocardiographic monitoring is recommended in patients with either hyperkalemia or hypokalemia.

●If the patient is hyperkalemic, potassium replacement should not be given initially, but should be initiated when the serum potassium falls to normal and after verifying urine production. Verifying urine production is important before beginning potassium replacement because acute renal failure may develop during DKA, due to acute tubular necrosis from volume depletion, or renal vein thrombosis.

●If the patient is normokalemic and voiding, potassium replacement should be given with the start of insulin therapy. The usual starting concentration is 40 mEq/L (40 mmol/L) of potassium added to the saline solution (but not in the initial fluid bolus). Potassium replacement is needed because insulin will reduce the serum potassium by increasing its transport to the intracellular space. In addition, with the correction of the metabolic acidosis, potassium will be exchanged for intracellularly-buffered hydrogen ions.

●If the patient is hypokalemic, potassium replacement should be started immediately, and the insulin infusion should be delayed until serum potassium has been restored to a near normal concentration. The maximum recommended rate of IV potassium replacement is usually 0.5 mEq/kg/hour (0.5 mmol/kg/hour) [17]. The serum potassium concentrations should be monitored hourly and the replacement adjusted as needed. Hypokalemia preceding volume expansion is uncommon, and potassium replacement should be based on laboratory measurements and not started empirically.

Potassium replacement is usually given as potassium chloride. In our practice, we have chosen to use potassium phosphate and potassium acetate as they decrease the chloride load and decrease the severity or likelihood of the development of hyperchloremic metabolic acidosis. Potassium replacement therapy should continue throughout IV insulin and fluid therapy, and the serum potassium should be carefully monitored. Oral potassium supplements may be used if the patient is receiving maximum allowable IV supplementation. Continuous electrocardiogram (ECG) monitoring is prudent, especially for patients with hypokalemia or severe DKA at baseline. ECG features of hypokalemia include T-wave flattening or inversion, appearance of a U-wave, and prolonged PR interval [9].

Metabolic acidosis — Once the diagnosis of ketoacidosis has been established (as opposed to lactic acidosis), either the calculated anion gap or measured beta-hydroxybutyrate (BOHB) concentrations can be used to monitor the progress of treatment. The blood bicarbonate concentration is not a good parameter to monitor the progress of treatment, or resolution of the ketoacidosis, as explained below.

During treatment, insulin and fluid repletion leads to partial correction of the acidosis. Insulin promotes the metabolism of ketoacid anions (BOHB and acetoacetic acid), resulting in the generation of bicarbonate. Insulin also halts the production of new ketoacids, which are generated in the liver from free fatty acids mobilized from fat in the absence of insulin. Meanwhile, the rehydration improves renal perfusion and promotes renal excretion of the glucose and ketone bodies. Improved tissue perfusion corrects any mild lactic acidosis that might be present.

During this process, the anion gap is a better indicator of effective clearance of ketosis than the serum bicarbonate, because the ketoacids could be cleared before the acidosis totally resolves. Although oxidation of the ketoacids helps to reduce the acidosis (some to refer to these ketoacids as “potential bicarbonate”), some ketoacids are lost in the urine before they can be converted into bicarbonate. Moreover, regeneration of bicarbonate in the kidney is delayed by the high chloride content in IV fluids; a patient with hyperchloremic metabolic acidosis may have normal anion gap and BOHB, but a low bicarbonate concentration.

Measurements of serum beta-hydroxybutyrate permit direct measurement of the degree of ketoacidosis. One study concluded that two successive beta-hydroxybutyrate values ≤1 mmol/L (10.4 mg/dL) with venous pH ≥7.3 provides an accurate endpoint for recovery from DKA [10,44].

Bicarbonate therapy generally should not be used in children with DKA. However, a few highly selected patients may benefit from cautious alkali therapy, such as those with severe acidosis (arterial pH <6.90), particularly those with impairment of cardiac contractility or life-threatening hyperkalemia [9]. Controlled trials both in adults and children with admission pH values >6.9 have been unable to demonstrate any clinical benefit from the routine administration of sodium bicarbonate [45,46].

In addition to lack of benefit, there are potential risks from bicarbonate therapy:

●Excessive bicarbonate therapy to a near-normal pH can lead to a rapid rise in PCO2 (thus decreasing the acidemic stimulus for hyperventilation), resulting in a paradoxical fall in cerebral pH as the lipid-soluble CO2 rapidly crosses the blood-brain barrier [15,16].

●The administration of alkali may slow the rate of recovery of ketosis. One report evaluating seven patients found that the three who received bicarbonate had a rise in plasma ketoacid levels during bicarbonate infusion and also had a six-hour delay in improvement of ketosis [47].

●The administration of bicarbonate can lead to a post-treatment metabolic alkalosis, after insulin-induced metabolism of ketoacid anions results in the regeneration of bicarbonate and spontaneous correction of most of the metabolic acidosis.

●Bicarbonate therapy has been associated with the development of cerebral edema [26]. (See ‘Cerebral edema’ below.)

●The rapid correction of acidosis with bicarbonate therapy may result in significant hypokalemia [15,16].

●The additional sodium load can further increase the degree of hyperosmolality before decreasing glucose concentration with fluid and insulin therapy.

Phosphate — Cellular phosphate depletion is a common problem in uncontrolled diabetes mellitus. The serum 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. Plasma phosphate levels frequently fall as low as 1 mg/dL during treatment of DKA and rarely have evident adverse consequences.

Phosphate replacement is not necessary or recommended for patients with mild asymptomatic hypophosphatemia (serum phosphate ≥1 mg/dL). IV phosphate administration may induce hypocalcemia and hypomagnesemia, and is generally not necessary or sufficient to replace the total body phosphate deficit [48]. The phosphate deficit will be repleted after the DKA resolves and the patient resumes eating.

There have been concerns that low plasma phosphate concentrations could result in metabolic disturbances. In theory, a decrease erythrocyte 2,3-diphosphoglycerate concentration could shift the oxyhemoglobin dissociation curve and have adverse effects on tissue oxygenation [49]. However, hypophosphatemia has not been shown to affect tissue oxygenation in adult patients with DKA [50], and randomized trials of phosphate replacement in adults have failed to show clinical benefit [51,52].

The main indication for phosphate therapy is a serum phosphate concentration less than 1.0 mg/dL (0.32 mmol/L), although many experts believe that it has no meaningful benefit. When phosphate is given, careful monitoring of the serum calcium and magnesium is required [15,16]. In this case, phosphate can be given by using potassium phosphate salts instead of potassium chloride to provide potassium replacement. It is also reasonable to use potassium phosphate salts for part of the potassium replacement for patients with lesser degrees of hypophosphatemia. Symptoms of hypophosphatemia include encephalopathy, impaired myocardial contractility, respiratory and generalized muscle weakness, dysphagia, and ileus [9]. (See “Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment”, section on ‘Phosphate depletion’.)

Monitoring — The initial evaluation of the child with DKA is discussed separately. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”.)

Treatment of DKA requires close monitoring of the patient’s clinical condition including changes in vital signs, neurologic status, fluid status, and metabolic state (eg, serum electrolytes, glucose, urea nitrogen, Hct, and venous pH) (table 5) [15,16]. These parameters should be documented in a way that is easy to follow and permits detection of clinical changes that would require medical intervention. Most institutions use a flowchart or electronic spreadsheet for calculation and tracking.

The key parameters are outlined below:

●Monitor blood glucose hourly during the initial four to six hours of fluid and insulin therapy. Subsequently, the frequency of blood glucose measurements should be dictated by the rapidity of correction of the metabolic acidosis and hyperglycemia. If capillary samples are obtained for the measurement of blood glucose, they should initially be compared with a venous measurement. These measurements should be used to adjust the rate of dextrose infusion by adjusting the dextrose concentration in the fluids (but not the rate of fluid or insulin infusion), until the metabolic acidosis due to ketosis is predominantly cleared. It is important to remember that insulin and fluids will not correct a metabolic acidosis due to hyperchloremia. As the ketonemia is nearly resolved, consideration can be given to decreasing the insulin infusion rate, which will result in a decreased IV fluid infusion rate, and permitting oral hydration. (See ‘Hyperglycemia’ above.)

●Electrolytes and venous pH should be evaluated hourly for the first three to four hours and then every two hours. When clinically appropriate, the frequency of measurement can be reduced to every four to six hours. These measurements are used to assess the anticipated changes of sodium, potassium, bicarbonate, and anion gap. Measurement of serum beta-hydroxybutyrate, if available, should be used because this test permits direct monitoring of ketoacidosis during recovery. (See ‘Serum sodium’ above.)

●Clinical parameters including heart rate, respiratory rate, blood pressure, oxygen saturation, and neurologic status should be monitored continuously. In patients with severe DKA or altered mental status, frequent neurologic examinations are recommended. Monitor for warning signs and symptoms of cerebral edema including headache, inappropriate decrease in heart rate, recurrence of vomiting, changes in neurologic status, rising blood pressure, and decreased oxygen saturation. (See ‘Cerebral edema’ below.)

●Initiate electrocardiographic monitoring in patients with severe DKA or abnormal serum potassium concentrations. Evaluate the tracing for changes characteristic of hyperkalemia or hypokalemia. (See “ECG tutorial: Miscellaneous diagnoses”, section on ‘Electrolyte abnormalities’.)

●Measure and record fluid input and output accurately. If the patient is neurologically impaired or it is difficult to ascertain urine output, a urine catheter should be placed.

●If vomiting persists, a nasogastric tube should be placed to decrease the risk of aspiration of vomitus.

Discontinuing the insulin infusion — The insulin infusion should continue at 0.05 to 0.1 units/kg per hour until all of the following conditions are met [15-17]:

●Serum anion gap reduced to normal (12 ± 2 mEq/L), or serum beta-hydroxybutyrate ≤1 mmol/L (10.4 mg/dL) on two successive occasions

●Venous pH is >7.30 or serum HCO3 is >15 mEq/L

●Plasma glucose <200 mg/dL (11.1 mmol/L)

●Tolerating oral intake

Note that patients may continue to have mild acidosis and ketonuria for several hours after the above conditions are met. Several explanations might be suggested: first, during the course of rehydration, the patients have received an excess of chloride and have developed a hyperchloremic metabolic acidosis. In addition, correction of the ketoacidosis may not necessarily result in complete correction of the metabolic acidosis. The residual acidosis is associated with a normal anion gap that is due to urinary loss of ketoacid anions, which represents the loss of “potential bicarbonate,” as noted above. In either case, insulin therapy will have no further effect on the acidosis. Thus, a persistent acidosis with normal anion gap is not a contraindication for switching the patient to subcutaneous insulin, since there are no circulating ketoacids remaining. (See ‘Metabolic acidosis’ above.)

When the above conditions are met, the patient can be transitioned from the insulin infusion to subcutaneous insulin injections. The first subcutaneous injection should be given at an appropriate interval to allow for absorption before stopping insulin infusion. The onset of rapid-acting insulin (rapid acting recombinant modified human insulin) is approximately 15 minutes, whereas that of short-acting (regular) insulin is 30 to 60 minutes. The most convenient time to transition to subcutaneous injections is just before a mealtime.

Mild DKA — Older children and adolescents with established diabetes and mild DKA (table 4) should be managed initially in an emergency department. After assessment and stabilization, such patients frequently can be managed at home, provided they have access to point-of-care testing of both blood glucose and beta-hydroxybutyrate, and the caretakers are proficient in diabetes sick-day management. (See ‘Disposition’ above.)

Patients with mild DKA generally do not require a fluid bolus. However, placement of an IV may be helpful in some cases, especially for those with nausea from DKA or an underlying gastroenteritis. If an IV is placed, a 10 cc/kg bolus of volume-expanding fluids will frequently result in subjective improvement. With or without a volume expanding bolus of fluids, several hours of IV infusion is sufficient to rehydrate the patient and correct a mild dehydration and ketosis.

Outpatient management of mild DKA includes:

●Subcutaneous insulin – A short-acting insulin (eg, recombinant modified human insulin, also known as “regular” insulin) can be given subcutaneously and repeated at three- to six-hour intervals as needed. The dose is adjusted depending upon the response.

●Rehydration – Commercially available fluids for oral hydration such as Rehydralyte (75 meq/L sodium and 20 meq/L potassium) can be used alone or in combination with initial parenteral fluid repletion. These fluids contain dextrose 2.5 g/dL (2.5 percent).

●Monitoring – Close monitoring of serum electrolytes, glucose, and fluid balance is required, including recording of fluid intake and frequent self-monitoring of blood glucose. The patient should be transferred to an appropriate inpatient setting if there is an inadequate response or the clinical condition deteriorates.

COMPLICATIONS AND MORTALITY — Reported mortality rates for DKA are consistent in developed countries, ranging from 0.15 to 0.51 percent in national population studies in Canada, the United Kingdom, and the United States [1-3,53]. Cerebral edema accounts for the majority of deaths (60 to 90 percent) [26,54]. Other causes include aspiration pneumonia, multiple organ failure, gastric perforation, and traumatic hydrothorax [2].

Cerebral edema — Cerebral edema occurs in 0.3 to 1 percent of children with DKA and has a high mortality rate of 21 to 24 percent [9,15-17,53]. Children who are younger, newly diagnosed with diabetes, or who have severe acidosis or dehydration are at the greatest risk. When cerebral edema does occur, it generally develops during the first 12 hours of treatment rather than before treatment, and protocols were strongly influenced by efforts to reduce risks. Nonetheless, cerebral edema can occur in optimally managed cases, and its immediate causes have not been established. Up to 20 percent of cases of cerebral edema occur before the initiation of therapy [26].

All children should be carefully monitored for early signs of cerebral edema throughout the course of treatment for DKA (table 3) [22]. The Glasgow coma scale can be used to evaluate for neurologic dysfunction, but may not be adequately sensitive to identify children early enough for effective intervention. More subtle neurological symptoms such as new onset or intensifying headache, altered consciousness, recurrent vomiting, age-inappropriate incontinence, irritability, or lethargy may be valuable as earlier indicators of cerebral edema [17,55]. Changes detectable by head computed tomography (CT) occur late in the development of cerebral edema. Therefore, the decision to treat should be based on clinical evaluation. Imaging may be useful to exclude other causes of neurological deterioration, but should not delay treatment. If cerebral edema is suspected, treatment should be initiated promptly, using mannitol (0.5 to 1 gm/kg) and/or hypertonic saline (3 percent saline, 5 to 10 mL/kg over 30 minutes).

The pathophysiology, risk factors, diagnosis, and treatment of cerebral edema in children with DKA are discussed in detail separately. (See “Cerebral edema in children with diabetic ketoacidosis”.)

Cognitive impairment — Preliminary evidence suggests that DKA may be associated with subsequent neurocognitive dysfunction, even in patients who did not have clinical evidence of cerebral edema [56,57]. There is insufficient information to determine if these effects are valid and, if so, are directly related to DKA or are a result of other complications of type 1 diabetes, such as recurrent hypoglycemia. (See “Hypoglycemia in children and adolescents with type 1 diabetes mellitus”, section on ‘Neurologic sequelae’.)

Venous thrombosis — Children with DKA appear to be at increased risk for deep venous thrombosis, particularly in association with femoral central venous catheter placement [58,59]. It has been suggested that this may in part be due to a prothrombotic state associated with DKA [60].

Aspiration — Children with DKA who have an altered state of consciousness and vomiting are at increased risk for aspiration. Placement of a nasogastric tube should be performed and stomach contents emptied if there is a concern that the child may aspirate. If necessary, intubation also should be performed to protect the airway.

Cardiac arrhythmia — Cardiac arrhythmias may be seen with either hypokalemia or hyperkalemia. In addition, asystole can be caused by inappropriate administration of IV potassium during treatment of hypokalemia. (See ‘Serum potassium’ above.)

Pancreatic enzyme elevations — Mild elevations in serum amylase and lipase are seen in about 40 percent of children with DKA and are also common in adults with DKA [61]. In most cases, this does not reflect acute pancreatitis. The diagnosis of acute pancreatitis should be based on clinical findings and confirmed by CT scan. (See “Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis”, section on ‘Serum amylase and lipase’.)

PREVENTION — Attempts should be made to prevent DKA both before and after the diagnosis of diabetes mellitus has been established. Methods that may promote earlier diagnosis of diabetes include increasing awareness among healthcare providers and the general public [62] and identifying high-risk individuals through family history, genetic, and immunologic screening [15,16]. (See “Prediction of type 1 diabetes mellitus” and “Prevention of type 1 diabetes mellitus”.)

Among children with known diabetes, a comprehensive diabetes care and education program may reduce the rates of DKA [63,64]. This is particularly important for patients with risk factors for recurrence. (See “Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents”.)

Worsening glycemic control often precedes the onset of DKA. Thus, the patient (and/or caregiver) should be taught to increase the frequency of testing blood glucose and measuring urine or blood ketones when the patient’s blood glucose is greater than 240 mg/dL (13.3 mmol/L). Failure to take insulin is the most common cause of recurrent DKA; this problem is typically addressed by increasing the intensity of parental involvement, reinforcing diabetes self-management education, and more frequent visits with the diabetes care team. Psychological counseling may be helpful. Recurrent DKA is likely to remain a problem in non-adherent patients until the adolescent (with help from the family) takes responsibility for their own diabetes management.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See “Society guideline links: Diabetes mellitus in children” and “Society guideline links: Hyperglycemic emergencies”.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see “Patient education: Diabetic ketoacidosis (The Basics)”)

SUMMARY AND RECOMMENDATIONS — The following is a summary of the above discussion regarding the treatment of diabetic ketoacidosis (DKA) and is consistent with consensus statements from the American Diabetes Association (ADA), European Society for Paediatric Endocrinology (ESPE), the Lawson Wilkins Pediatric Endocrine Society (LWPES), and the International Society for Pediatric and Adolescent Diabetes (ISPAD) (table 1) [15-17,22]:

●Obtain initial laboratory studies (blood glucose, electrolytes, blood urea nitrogen [BUN] and creatinine, venous pH, hematocrit (Hct), phosphorus, calcium, magnesium, and a urine analysis; and blood beta-hydroxybutyrate, if available) (table 5). Continue to monitor blood glucose hourly during the initial four to six hours of fluid and insulin therapy. Subsequently, the frequency of blood glucose measurements should be dictated by the rapidity of correction of the metabolic acidosis and hyperglycemia. Measure electrolytes and venous pH hourly for the first three to four hours, then every two hours thereafter until the metabolic acidosis is cleared. (See ‘Laboratory testing’ above and ‘Monitoring’ above.)

●Admission to a pediatric intensive care unit (PICU) for management of DKA is appropriate for children with increased risk for cerebral edema, including altered consciousness, younger than five years of age, severe acidosis (venous pH<7.1 or low pCO2), high BUN, or long duration of symptoms. (See ‘Disposition’ above.)

●We recommend careful evaluation and monitoring for signs and symptoms of cerebral edema in all children undergoing treatment for DKA (Grade 1C). Specific signs of increased intracranial pressure and changes detectable by head computed tomography (CT) often occur too late for effective intervention. Early symptoms that may indicate cerebral edema include new onset or intensifying headache, altered consciousness, and recurrent vomiting; ultimately progressing to increasing blood pressure, bradycardia, and opisthotonic posturing. (See ‘Cerebral edema’ above and “Cerebral edema in children with diabetic ketoacidosis”.)

●DKA is a state of hyperosmolar dehydration. Volume expansion is required, but should be achieved gradually and with isotonic fluids. This is because these approaches appear to reduce the risk for cerebral edema. (See ‘Dehydration’ above.)

•Fluid repletion should be initiated using an isotonic crystalloid solution at a rate of 10 mL/kg (up to a maximum volume of 1000 mL) in the first hour. Repeat this regimen if the effective circulatory volume remains compromised. (See ‘Initial volume expansion’ above.)

•Subsequently, an insulin infusion is begun at a rate of 0.1 unit/kg per hour. A lower dose of 0.05 unit/kg per hour may be used initially in younger children who may be more sensitive to insulin. An insulin bolus should NOT be given. Consider subcutaneous insulin when the venous pH is ≥7.30, the serum bicarbonate is ≥16 meq/L, or the anion gap is normal. (See ‘Hyperglycemia’ above.)

•Add 5 percent dextrose to the intravenous (IV) fluid when the serum glucose decreases to 250 to 300 mg/dL (13.9 to 16.7 mmol/L). If the serum glucose falls below 250 mg/dL (13.9 mmol/L) before resolution of the ketoacidosis, increase the concentration of dextrose in the IV fluid up to 10 or 12.5 percent. Use of a “two-bag system” can facilitate adjustments of dextrose infusion while maintaining a constant rate of fluid administration. (See ‘Hyperglycemia’ above.)

•After the initial fluid bolus, ongoing volume repletion should initially consist of isotonic saline (normal saline or lactated Ringers) at a rate that should not exceed 1.5 to 2 times maintenance and should not include urinary losses. The rate of IV fluid administration should be calculated to fully replete the patient’s estimated fluid deficit over 48 to 72 hours. (See ‘Subsequent fluid administration’ above.)

•After the first four to six hours of treatment, the IV fluid may be changed to one-half isotonic saline or continue with lactated Ringers, provided that the patient’s circulatory status is stable and the serum sodium concentration is rising appropriately as the serum glucose concentration falls. The choice between one-half isotonic and isotonic saline depends on the patient’s circulatory status and the rise in serum sodium as the hyperglycemia is corrected. The goal should be a slow decrease in serum osmolality to normal. In our practice, we generally use lactated Ringer’s solution for the entire course of rehydration and correction of the ketonemia. (See ‘Subsequent fluid administration’ above and ‘Serum sodium’ above.)

●Initial sodium concentrations will depend on the degree of net sodium and water losses prior to hospitalization, the degree of hyperglycemia, and the degree of lipemia (pseudohyponatremia). With the correction of hyperglycemia, serum sodium concentrations should rise (and should be permitted to rise). Children who do not exhibit the expected rise in serum sodium concentration during treatment appear to have increased risk of cerebral edema. During rehydration, the clinician should serially assess the serum sodium and employ anticipatory planning in fluid replacement. (See ‘Serum sodium’ above.)

●All patients with DKA require potassium repletion, but the timing varies with serum potassium concentration. Serum potassium should be carefully monitored during therapy. In addition, electrocardiographic monitoring is recommended in patients with either hyperkalemia or hypokalemia. (See ‘Serum potassium’ above.)

•If the patient is hyperkalemic, potassium replacement should be initiated when the serum potassium falls to normal and after documentation of urine production.

•If the patient is normokalemic, potassium replacement should be given with the start of insulin therapy; starting concentrations of 40 mEq/L KCl are reasonable, added to the saline solution (but not in the initial fluid bolus).

•If the patient is hypokalemic, potassium replacement should be started immediately, as insulin will further reduce the serum potassium. The insulin infusion should be delayed until the serum potassium level is in the normal range. The maximum recommended rate of IV potassium replacement is usually 0.5 mEq/kg/hour (0.5 mmol/kg/hour). Oral potassium replacement could be considered.

●Prior to treatment, the serum anion gap can be used as an index of the severity of the metabolic acidosis. During treatment, the anion gap tends to normalize prior to the acidosis, resulting in a mild “non-gap” acidosis as treatment progresses. Therefore, the anion gap is the appropriate measure of effective treatment, rather than serum bicarbonate. (See ‘Assessment of severity’ above and ‘Metabolic acidosis’ above.)

●We recommend NOT treating with bicarbonate (Grade 1B). However, a few highly selected patients may benefit from cautious alkali therapy, including those with severe acidosis (arterial pH <6.90), particularly those with impairment of cardiac contractility or life-threatening hyperkalemia. (See ‘Metabolic acidosis’ above.)