Christina Kanaka-Gantenbein, MD, PhD
The goals of first-line management of DKA are:4
- Correct dehydration
- Correct acidosis and reverse ketosis
- Restore blood glucose to near normal values
- Avoid complications, such as cerebral edema
- Identify and treat any precipitating event…..
Correction of dehydration
Pediatric patients with DKA have a deficit of extracellular fluid volume of around 5 – 10%. Since clinical assessment of the volume deficit is inaccurate and subjective, it is usual to calculate 5 – 7% deficit in moderate DKA and about 7 – 10% fluid deficit in severe DKA.12,13
Increased serum urea nitrogen and hematocrit can be useful markers of the severity of extracellular fluid contraction. On the other hand, serum sodium levels are factitious, mainly because of a water shift from the intracellular compartment to the intravascular one due to the osmotic action of high glucose concentrations.14,15 Therefore, one has to calculate the corrected sodium concentration using the following formula4:
Corrected sodium concentration = measured Na + 2([plasma glucose in mmol/L − 5.6]/5.6)
where 1 mmol/L of glucose corresponds to 18 mg/dl.
Upon fluid and insulin administration, plasma glucose levels will decrease and the measured sodium concentration is expected to increase. A failure of serum sodium levels to increase or a further decline in levels is a potentially ominous sign of impending cerebral edema.4,16,17
The principles of fluid administration are as follows:
- Water and salt deficits must be replaced, but it is important to replace fluid deficits slowly over 48 hours.
- Intravenous or oral fluids that may have been given in another facility before assessment should be factored into calculations of deficit and repair.
- For patients who are not severely dehydrated, volume expansion should start with 0.9% saline.
- For patients who are severely volume depleted, but not in shock, volume expansion should begin immediately with 0.9% saline to restore the peripheral circulation.
- In the rare patient with DKA who presents in shock, rapidly restore circulatory volume with isotonic saline in 20 ml/kg boluses infused as quickly as possible with reassessment after each bolus.
- The volume and rate of administration depends on circulatory status and, where it is clinically indicated, the volume administered is 10 ml/kg per hour, repeated if necessary.
- Use crystalloid, not colloid! There are no data to support the use of colloid in preference to crystalloid in the treatment of DKA.
- Subsequent fluid management should be with 0.9% saline (or Ringer’s) for at least 4 – 6 hours.
- Thereafter, deficit replacement should be with a solution that has a tonicity equal to or greater than 0.45% saline with added potassium chloride, potassium phosphate, or potassium acetate.
- The rate of fluid (IV and oral) should be calculated to rehydrate evenly over 48 hours. It might be dangerous to cover the fluid deficit in a few hours.
- Remember to provide potassium in the fluids administered as soon as urine output has been documented or even earlier in the hypokalemic patient, as is discussed in detail below.
- In addition to clinical assessment of dehydration, calculation of effective osmolality may be valuable to guide fluid and electrolyte therapy, according to the following formula:4
Effective osmolality (in mOsm/kg) = 2 × Na + K) + glucose (in mmol/L)
- Urinary losses should not routinely be added to the replacement fluid calculation, but this may be necessary in rare circumstances.
- The sodium content of the fluids may rarely need to be increased if measured serum sodium is low and does not rise appropriately as the plasma concentration falls. However, the use of large amounts of 0.9% saline has been associated with the development of hyperchloremic metabolic acidosis.18
- In practice, the fluids administered are calculated as the sum of fluid losses (usually a fluid deficit of 5 – 10% exists) plus the maintenance fluid requirement for 48 hours, evenly distributed over 48 hours, as illustrated in Tables 2.2 a and b.
Table 2.2a Calculation of fluids and electrolytes to be administered during the management of DKA. The total amount of losses in addition with the 2-days’ 24-hour maintenance requirements should be evenly given over 48 hours.
Data are from measurements in only a few children and adolescents. In any individual patient, actual losses may be less or greater than the ranges shown. † Maintenance electrolyte requirements in children are per 100 ml of maintenance IV fl uid following the Holliday-Segar formula of fl uid requirements calculation according to body weight. Reproduced from reference 4 with permission.
Table 2.2b Calculation of fluids to be administered during the management of DKA
Main principles of insulin administration
- Start insulin infusion 1-2 hours after starting fluid replacement therapy
- Insulin therapy is necessary not only to lower blood glucose levels but more importantly to suppress lipolysis and ketogenesis and therefore to eliminate metabolic acidosis
- An IV insulin bolus administration in children is unnecessary, since it may increase the risk of cerebral edema, and should not be used at the initiation of treatment
- An IV insulin bolus administration should be avoided. 4,21,22
- The dose of insulin should invariably remain at the initial rate at least until resolution of DKA (pH > 7.30, bicarbonate > 15 mmol/L and/or normalization of the anion gap), which invariably takes longer than normalization of the blood glucose concentrations.
- If the patient demonstrates marked sensitivity to insulin (for example very young patients, as reported above) the dose may be decreased to 0.05 IU/kg per hour, or less, provided that metabolic acidosis continues to resolve.
Modification of insulin/fluid administration in specific cases
- During initial volume expansion the plasma glucose concentration falls steeply. Thereafter, and after initiation of insulin administration, the plasma glucose concentration typically decreases at a rate of 36 – 90 mg/dl (2 – 5 mmol/L), depending on the timing and amount of glucose administration. To prevent an unduly rapid decrease of plasma glucose concentration and the risk of hypoglycemia, 5% glucose should be added to the IV fluid (e.g., 5% glucose in 0.45% saline) when the plasma glucose falls to approximately 250 – 300 mg/dl (14 – 17 mmol/L), or sooner if the rate of blood glucose fall is steeper. It may even rarely be necessary to infuse 10 – 12.5% dextrose in order to prevent hypoglycemia while continuing to infuse insulin to correct the metabolic acidosis. 4
- If blood glucose falls very rapidly (> 5 mmol/L) after initial fluid expansion, consider adding glucose even before plasma glucose has decreased to 300 mg/dl (17 mmol/L).
- If biochemical parameters of DKA (pH, anion gap) do not improve, reassess the patient, review insulin therapy, and consider other possible causes for poor response such as inadequate fluid or insulin infusion at the infusion site, etc.
- If IV insulin administration is not possible, consider subcutaneous (or even IM) administration of rapid-acting analogs, such as lispro or aspart at 1-to 2-hour intervals. The insulin dose should be initially 0.3 IU/kg, followed 1 hour later by 0.1 IU/kg of insulin lispro or aspart SC hourly or at a dose of 0.15 – 0.2 IU/kg every 2 hours.
- If blood glucose falls to < 250 mg/dl (14 mmol/L) before DKA has resolved (pH still < 7.30), add 5% glucose solution IV and continue insulin as above.
- It is prudent to keep blood glucose at a level of about 200 mg/dl (11 mmol/L) until resolution of DKA.
Children with DKA suffer total body potassium deficits in the range of 3 – 6 mmol/L, mainly due to intracellular compartment depletion.4 However, at initial presentation serum potassium levels may be normal, decreased, or even elevated.23 Administration of insulin and correction of acidosis will drive potassium back into the cells, decreasing serum levels.4 Therefore:
- Potassium replacement therapy is necessary regardless of the initial serum potassium concentration.
- If the patient is already hypokalemic at presentation, potassium administration should be initiated immediately at the time of initial volume expansion before starting insulin administration.
- If the patient is hyperkalemic, defer potassium replacement therapy until urine output has been documented.
- The starting potassium concentration in the infusate should be 40 mmol/L and subsequently adjusted according to biochemical serum potassium measurements. Potassium phosphate may be used together with potassium chloride or potassium acetate, especially when critically low serum phosphate levels have been documented. However, in clinical practice, phosphate supplementation is rarely needed and serum phosphate levels return to normal upon resolution of acidosis. 24 – 27
- Potassium replacement should be continued throughout IV fluid therapy.
- If hypokalemia persists despite maximum rate of potassium replacement, then a reduction in insulin infusion rate should be considered and eventually extra potassium administration should be initiated.
ECG findings in potassium disorders are as follows.
- ECG findings in hypokalemia:
- Flattening of the T wave
- Widening of the QT interval
- Appearance of U waves
- ECG findings in hyperkalemia:
- Tall, peaked, symmetrical T waves
- Shortening of the QT interval.
- Dunger DB, Sperling MA, Acerini CL, et al. European Society for Paediatric Endocrinology; Lawson Wilkins Pediatric Endocrine Society. European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics 2004; 113: e133 – 40.
- Dunger DB, Sperling MA, Acerini CL, et al. ESPE; LWPES. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004; 89: 188 – 94.
- Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29: 1150 – 9.
- Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis in children and adolescents with diabetes. ISPAD Clinical Practice Consensus Guidelines 2009 Compendium. Pediatr Diabetes 2009; 10 (Suppl 12): 118 – 33.
- Hanas R, Lindgren F, Lindblad B. A 2-year national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use. Pediatr Diabetes 2009; 10: 33 – 7.
- Neu A, Hofer SE, Karges B, et al. DPV Initiative and the German BMBF Competency Network for Diabetes Mellitus. Ketoacidosis at diabetes onset is still frequent in children and adolescents: a multicenter analysis of 14,664 patients from 106 institutions. Diabetes Care 2009; 32: 1647 – 8.
- Schober E, Rami B, Waldhoer T; Austrian Diabetes Incidence Study Group. Diabetic ketoacidosis at diagnosis in Austrian children in 1989 – 2008: a population-based analysis. Diabetologia 2010; 53: 1057 – 61.
- Sapru A, Gitelman SE, Bhatia S, et al. Prevalence and characteristics of Type 2 diabetes mellitus in 9 – 18 year-old children with diabetic ketoacidosis. J Pediatr Endocrinol Metab 2005; 18: 865 – 72.
- Zdravkovic V, Daneman D, Hamilton J. Presentation and course of type 2 diabetes in youth in a large multi-ethnic city. Diabet Med 2004; 21: 1144 – 8.
- Rewers A, Klingensmith G, Davis C, et al. Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study. Pediatrics 2008; 121: e1258 – 66.
- Hekkala A, Reunanen A, Koski M, et al. Finnish Pediatric Diabetes Register. Age-related differences in the frequency of ketoacidosis at diagnosis of Type 1 diabetes in children and adolescents. Diabetes Care 2010; 33: 1500 – 2.
- Fagan MJ, Avner J, Khine H. Initial fl uid resuscitation for patients with diabetic ketoacidosis: how dry are they? Clin Pediatr (Phila) 2008; 47: 851 – 5.
- Koves IH, Neutze J, Donath S, et al. The accuracy of clinical assessment of dehydration during diabetic ketoacidosis in childhood. Diabetes Care 2004; 27: 2485 – 7.
- Katz MA. Hyperglycemia-induced hyponatremia – calculation of expected serum sodium depression. N Engl J Med 1973; 289: 843 – 4.
- Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: Evaluating the correction factor for hyperglycemia. Am J Med 1999: 106: 399 – 403.
- Glaser N, Barnett P, McCaslin I, et al for the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Risk factors for cerebral edema in children with diabetic ketoacidosis.. N Engl J Med 2001; 344: 264 – 9.
- Dunger DB, Edge JA. Predicting cerebral edema during diabetic ketoacidosis. N Engl J Med 2001; 344: 302 – 3.
- Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloraemic and hyperchloraemic acidosis in diabetic ketoacidosis. Nephron 1990; 54: 1 – 6.
- Puttha R, Cooke D, Subbarayan A, et al. North West England Paediatric Diabetes Network. Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with Type 1 diabetes — an observational study. Pediatr Diabetes 2010; 11: 12 – 7.
- Al Hanshi S, Shann F. Insulin infused at 0.05 versus 0.1 u/kg/hr in children admitted to intensive care with diabetic ketoacidosis. Pediatr Crit Care Med. 2011 Mar; 12(2): 137 – 40.
Professor of Internal Medicine
Athens University Medical School
Evgenideion Hospital and Research Laboratory ‘Christeas Hall’
Associate Professor of Pediatric Endocrinology and Diabetology
First Department of Pediatrics, University of Athens
Agia Sofia Children’s Hospital
Consultant in Internal Medicine and Diabetology
Laiko General Hospital
Assistant Professor of Internal Medicine and Diabetology
Athens University Medical School
Laiko General Hospital
Assistant Professor of Internal Medicine and Diabetology
University of Athens
Laiko General Hospital