Pediatric Diabetes 2007: 8: 28–43 # 2007 The Authors

All rights reserved Journal compilation # 2007 Blackwell Munksgaard

Pediatric Diabetes

ISPAD Clinical Practice Consensus Guidelines 2006–2007

Diabetic ketoacidosis
d
Wolfsdorf J, Craig ME, Daneman D, Dunger D, Edge J, Lee Department of Paediatrics, University of Cambridge,
WRW, Rosenbloom A, Sperling MA, Hanas R. Diabetic Addenbrooke’s Hospital, Cambridge, UK
e
ketoacidosis. Department of Paediatrics, John Radcliffe Hospital, Oxford,
Pediatric Diabetes 2007: 8: 28–42. UK
f
Endocrinology Service Department of Paediatric Medicine,
KK Children’s Hospital, Singapore
Joseph Wolfsdorf a g
Division of Endocrinology, Department of Pediatrics,
Maria E Craig b University of Florida College of Medicine, Gainesville, FL,
Denis Daneman c USA
h
Department of Pediatric Endocrinology, Children’s Hospital,
David Dunger d University of Pittsburgh, PA, USA
Julie Edge e i
Department of Pediatrics, Uddevalla Hospital, Uddevalla,
WR Warren Lee f Sweden
Arlan Rosenbloom g
Mark A Sperling h and Corresponding author:
Ragnar Hanas i Ragnar Hanas, MD, PhD,
Department of Pediatrics, Uddevalla Hospital,
S-451 80 Uddevalla, Sweden.
a
Division of Endocrinology, Children’s Hospital Boston, MA, Tel: 146-522-92000;
USA e-mail: ragnar.hanas@vgregion.se
b
School of Women’s and Children’s Health, University of New
South Wales, Sydney, Australia Editors of the ISPAD Clinical Practice Consensus Guidelines
c
University of Toronto, The Hospital for Sick Children, Toronto, 2006–2007; Ragnar Hanas, Kim Donaghue, Georgeanna
Canada Klingensmith, Peter Swift

Diabetic ketoacidosis (DKA) results from absolute utilization resulting in hyperglycemia and hyperosmo-
or relative deficiency of circulating insulin and the lality, and increased lipolysis and ketogenesis, causing
combined effects of increased levels of the counter- ketonemia and metabolic acidosis. Hyperglycemia that
regulatory hormones: catecholamines, glucagon, exceeds the renal threshold [approximately 10 mmol/L
cortisol, and growth hormone (1, 2). Absolute insulin (180 mg/dL), although the range in normal and diabetic
deficiency occurs in previously undiagnosed type 1 individuals is very wide)] and hyperketonemia causes
diabetes mellitus (T1DM) and when patients on osmotic diuresis, dehydration, and obligatory loss of elec-
treatment deliberately or inadvertently do not take trolytes, which often is aggravated by vomiting. These
insulin, especially the long-acting component of a changes stimulate further stress hormone production,
basal-bolus regimen. Patients who use an insulin which induces more severe insulin resistance and
pump can rapidly develop DKA when insulin delivery worsening hyperglycemia and hyperketonemia. If this
fails for any reason. Relative insulin deficiency occurs cycle is not interrupted with exogenous insulin and fluid
when the concentrations of counter-regulatory hor- and electrolyte therapy, fatal dehydration and metabolic
mones increase in response to stress in conditions such acidosis will ensue. Ketoacidosis may be aggravated by
as sepsis, trauma, or gastrointestinal illness with lactic acidosis from poor tissue perfusion or sepsis.
diarrhea and vomiting. The pathophysiology of DKA is characterized by severe depletion of water
DKA in children is summarized in Fig. 1. and electrolytes from both the intra- and extracellular
The combination of low serum insulin and high fluid (ECF) compartments; the range of losses is
counter-regulatory hormone concentrations results in shown in Table 1. Despite their dehydration, patients
an accelerated catabolic state with increased glucose continue to maintain normal blood pressure and have
production by the liver and kidney (via glycogenolysis considerable urine output until extreme volume
and gluconeogenesis), impaired peripheral glucose depletion leads to a critical decrease in renal blood
28

the ¤ Increased leukocyte count with left shift magnitude of specific deficits in an individual patient ¤ Non-specific elevation of serum amylase varies depending upon the duration and severity of ¤ Fever only when infection is present illness. vomiting. Reprinted with permission from The American Diabetes Association. ¤ Hyperglycemia (blood glucose . From Diabetes Care. 80–82). and abdominal pain mimicking consumed little or no carbohydrates may have. actual losses may be less or greater than the ranges shown in the Table (E). Losses of fluids and electrolytes in diabetic ketoacidosis (DKA) and maintenance requirements in normal children Average (range) losses per kg 24-h maintenance requirements Water 70 mL (30–100) *10 kg 100 mL/kg/24 h 11–20 kg 1000 mL 1 50 mL/kg/24 h for each kg from 11–20 . Consumption of fluids with a high. 145). †Maintenance electrolyte requirements in children are per 100 mL of maintenance IV fluid (144.20 Sodium 6 mmol (5–13) 2–4 mmol† Potassium 5 mmol (3–6) 2–3 mmol Chloride 4 mmol (3–9) 2–3 mmol Phosphate (0. 1. on an acute abdomen rare occasion. 6). a simplified Holliday–Segar formula† (see below). .20 kg 1500 mL 1 20 mL/kg/24 h for each kg . Copyright # 2006 American Diabetes Association. Pathophysiology of diabetic ketoacidosis.10 kg 4 mL/kg/h. 11 mmol/L [200 Clinical manifestations of DKA mg/dL]) ¤ Venous pH .3 or bicarbonate . Table 1. and the content of food and fluids consumed before coming to Definition of DKA medical attention.5) mmol 1–2 mmol Data are from measurements in only a few children and adolescents (41.20 kg 60 1 1 mL/kg/h for each kg . infection or insufficient insulin intake Counter-regulatory hormones Glucagon Cortisol Catecholamines Growth Hormone Lipolysis Glucose utilization Proteolysis Glycogenolysis Protein synthesis Gluconeogenic substrates ++ FFA to liver Gluconeogenesis Ketogenesis Hyperglycemia Alkali reserve Glucosuria (osmotic diuresis) Acidosis Loss of water and electrolytes Decreased fluid intake Lactate Dehydration Hyperosmolarity Impaired renal function Fig. Three methods for determining maintenance water requirements in children are commonly used: *the Holliday–Segar formula (143) (shown in this Table). In any individual patient. 29. 42. The biochemical criteria for the diagnosis of DKA carbohydrate content (juices or sugar containing soft are (4): drinks) exacerbates the hyperglycemia (3). deep.20. Pediatric Diabetes 2007: 8: 28–43 29 . 11–20 kg 40 1 2 mL/kg/h for each kg between 11 and 20. Consensus Guidelines Pathophysiology of Diabetic Ketoacidosis (DKA) Absolute insulin deficiency or Stress. At presentation. 2006. only modestly increased blood glucose ¤ Progressive obtundation and loss of consciousness concentrations (Ôeuglycemic ketoacidosis’) (5. 7. flow and glomerular filtration. the extent to which the patient was able to maintain intake of fluid and electrolytes. †Simplified method based on Holliday–Segar: . 15 mmol/L ¤ Dehydration ¤ Ketonemia and ketonuria ¤ Rapid. Vol.5–2. sighing (Kussmaul respiration) Partially treated children and children who have ¤ Nausea. 1150–1159. and a formula based on body surface area for children more than 10 kg (1500 mL/m2/24 h) (144).

and generally shows only fair to to quench thirst and replace urinary losses prior to moderate agreement among examiners. 33. approximately 5% of patients stances (e. population (7). except for those because of ¤ Effective serum osmolality . including those Japanese children and adolescents are detected in with eating disorders asymptomatic individuals by routine urine screening ¤ Children with difficult or unstable family circum- (14. rates inversely correlate with s abnormal respiratory pattern (hyperpnea) (31) the regional incidence of T1DM. absent to mild ketonemia (serum pump failure management guidelines accounts for b-hydroxybutyrate 1  0.1. dehydration in young children and predicting at least 5% dehydration and acidosis are: Frequency of DKA s prolonged capillary refill time (normal capillary At disease onset refill is 1. overall. In recurrent DKA. especially when there is very used for calculations and not the weight from severe dehydration. 7. with more severe dehydration (31). 15 mmol/L of insulin delivery for any reason rapidly leads to ¤ Moderate: pH . 19). depend.3 mmol/L (600 ¤ Perform a clinical evaluation to confirm the mg/dL) diagnosis and determine its cause. and cool extremities. Therapy must be appropriately modi. 24. ¤ Clinical assessment of dehydration is imprecise.g. and least in Canadian First Nation teenagers ¤ Peripubertal and adolescent girls (8–13). sunken eyes.Wolfsdorf et al. common in younger children (. have mild or moderate acidosis. associated with In children with established diabetes increased rates and severity of obesity.30 for evidence of infection. less so in episodes of DKA Hispanic. however.2. some children with T1DM may have ¤ Assess clinical severity of dehydration.. carbohydrate-containing beverages have been used inaccurate.5–2 s) There is wide geographic variation in the frequency of s abnormal skin turgor (Ôtenting’ or inelastic skin) DKA at onset of diabetes. parental abuse) with T2DM have DKA at the time of diagnosis (16).2 (SEM) mmol/L (2)) almost all episodes. ¤ Serum bicarbonate . to determine surface area. be based on a combination of physical signs. It should diagnosis (3). The fied to address the pathophysiology and unique three most useful individual signs for assessing biochemical disturbances of each individual patient. 15 mmol/L insulin omission or failure to follow sick day or ¤ Small ketonuria.5 yr of age). 5 mmol/L Hyperglycemic hyperosmolar state (HHS) also may occur in young patients with T2DM (18. 15). Carefully look ¤ Arterial pH . C) (26–29). Conversely. measure height or length characteristic features of HHS and DKA may occur. Acute decompensation with DKA has Risk is increased in (28): been recognized to occur at the time of diagnosis in as many as 25% of children with T2DM (7). 10 mmol/L insulin deficiency) (29) (C) ¤ Severe: pH . features of HHS (severe hyperglycemia) if high. 7. a previous office visit or hospital record. and in absent tears. DKA at diagnosis is more tion include dry mucus membranes. The majority of new cases of diabetes in ¤ Children with psychiatric disorders. weak pulses. This is more ¤ Children with poor metabolic control or previous likely in those of African-American descent. interruption ¤ Mild: venous pH . (If body surface area is used for It is important to recognize that overlap between the fluid therapy calculations. Frequencies range from approximately 15% to 70% in Europe and ¤ Other useful signs in assessing degree of dehydra- North America (A) (20–24). children whose families do not have ready access to More signs of dehydration tend to be associated medical care for social or economic reasons (A) (6.3 or bicarbonate . ¤ Stupor or coma ¤ Weigh the patient. 25). bicarbonate . Type 2 diabetes mellitus (T2DM). 320 mOsm/kg acute severe febrile or gastrointestinal illness. 7. The risk of DKA in established T1DM is 1–10% per ing on the socioeconomic and ethnic composition of the patient per year (A. The Management of DKA criteria for HHS include (2): Emergency assessment ¤ Plasma glucose concentration . ¤ Children who omit insulin (30) (C) The severity of DKA is categorized by the degree of ¤ Children with limited access to medical services acidosis (17): ¤ Insulin pump therapy (as only rapid-acting or short-acting insulin is used in pumps. 30 Pediatric Diabetes 2007: 8: 28–43 . in some centers (recurrent DKA) now accounts for as much as one half of newly diagnosed diabetes in children aged 10–21 yr. bicarbonate .) This weight should be Some patients with HHS. 7.

moaning 3. only 2. concentrations (if possible). impairment or shock. and magnesium for evidence of hyper. HbA1c. it may be and management useful to obtain a blood sample for determination of ¤ Written guidelines for DKA management in serum free insulin concentration (even when children children have been treated exclusively with biosynthetic ¤ Access to laboratories for frequent and timely human insulin. which cannot be assessed in non-verbal young children. Eyes open to incomprehensible restless. No words. Table 2.. necessary. The GCS consists of three parameters and is scored between 3 and 15 (32). Inconsolable. 2. No verbal response 1.g. Words. No motor response 2. ¤ Secure the airway and empty the stomach by ¤ Obtain a blood sample for laboratory measurement continuous nasogastric suction to prevent pulmo- of serum or plasma glucose. throat). 36). blood urea obtunded patient. ¤ In the child with established diabetes (recurrent ¤ Experienced nursing staff trained in monitoring DKA) and suspected insulin omission. 36). ¤ Give oxygen to patients with severe circulatory ¤ Perform a urinalysis for ketones. hemoglobin and placed for convenient and painless repetitive blood hematocrit or complete blood count (an increased sampling. Orientated. tension. phosphorus. irritable. Pediatric Diabetes 2007: 8: 28–43 31 . appropriate cultures of body fluids. nitrogen. anti-insulin antibodies may be present evaluation of biochemical variables in the serum and interfere with insulin immunoassays. and oliguria. cries (decerebrate posture) verbal command sounds. no sustained conversational exchange. Smiles. perform an electrocardiogram (ECG) for should receive care in a unit that has: baseline evaluation of potassium status (35. but if the child is unconscious or unable ¤ Obtain appropriate specimens for culture (blood. Extension to pain 3. The white cell count need not be ¤ A cardiac monitor should be used for continuous measured unless there is evidence of concurrent electrocardiographic monitoring to assess T waves infection). Eyes open to pain 2. Obeys commands 5. disoriented 4. No response 1. ¤ If laboratory measurement of serum potassium is Where should the child be managed? The child delayed. No eye opening 1. creatinine. Thus anti-insulin antibodies must be eliminated A specialist/consultant pediatrician with training before the concentration of free (active) insulin is and expertise in the management of DKA should determined (27)) before insulin is administered direct inpatient management. An arterial catheter may be necessary in white blood cell count in response to stress is some critically ill patients managed in an intensive characteristic of DKA and is not indicative of care unit. calcium. Best eye response Best verbal response Best verbal response Best motor response (non-verbal children) 1. dosis and may be used to monitor the response to ¤ Catheterization of the bladder is usually not treatment (33. ¤ Give antibiotics to febrile patients after obtaining tration. Glasgow coma scale or score. but shows some disorientation. Supportive measures ¤ Assess level of consciousness [Glasgow coma scale (GCS) – see Table 2] (32). but incoherent* sounds 4. Withdrawal from pain 4. normal inappropriately conversation 5. 34). if available. oriented to sound. hypo. Consolable when 5. Flexion to pain 4. osmolality. pCO2. ¤ Measurement of blood b-hydroxybutyrate concen. †Attention can be held. Eyes open and groaning and moans. if there is evidence of infection. to void on demand (e. infection (22). follows objects and interacts *Inappropriate words. Inconsistently consolable 3.or hypokalemia (35. makes vocal (decorticate posture) spontaneously 3. may not be available or accurate (37). is useful to confirm ketoaci. Consensus Guidelines s 10% dehydration is suggested by the presence because the history of recent insulin administration of weak or impalpable peripheral pulses. One of the components of the GCS is the best verbal response. venous (or arterial ¤ A peripheral intravenous (IV) catheter should be in critically ill patient) pH. Localizes pain conversation† crying and interacts 6. responds in a conversational manner. Confused. children) the bladder should be catheterized. infants and very ill young urine. A modification of the GCS was created for children too young to talk. 3 being the worst and 15 the best. electrolytes (including nary aspiration in the unconscious or severely bicarbonate or total carbon dioxide).

subcutaneous Fig. slowing heart rate.9% 10-20 ml/kg over 1-2 h.5-1 g/kg Transition to SC Insulin Restrict IV fluids by one-third Start SC insulin then stop IV insulin after an Call senior staff appropriate interval Move to ICU Consider cranial imaging only after patient stabilised Adapted from Dunger et al. ECG for abnormal T-waves & repeat until circulation is Add KCL 40 mmol per litre fluid restored) but do not exceed 30 ml/kg No improvement Continuous insulin infusion 0.Wolfsdorf et al. 32 Pediatric Diabetes 2007: 8: 28–43 .1999. NG. Karger Pub. Immediate assessment Clinical Signs Biochemical Features & Investigations Assess dehydration Deep sighing respiration (Kussmaul) Ketones in urine Clinical History Elevated blood glucose Smell of ketones Polyuria Lethargy/drowsiness ± vomiting Acidemia Polydipsia Blood gases.ev aluate Change to 0. decreased conscious level.45% saline + 5% glucose signs Adjust sodium infusion to promote an IV fluid calculations increase in measured serum sodium Insulin delivery system & dose Exclude hypoglycaemia Need for additional resuscitation Is it cerebral edema? Consider sepsis Improvement Clinicallywell. tolerating oral fluids Management Give mannitol 0.9% saline Saline 0. Algorithm for the immediate assessment and management of diabetic ketoacidosis (DKA). 2. IV Therapy specific neurological Re. electrolytes Weight loss (Weigh) Other investigations as Abdominal pain indicated Tiredness Diagnosis Confirmed Vomiting Confusion Diabetic Ketoacidosis (DKA) Contact Senior Staff Shock (reduced peripheral pulses) Dehydration >5% Minimal dehydration Reduced conscious level/coma Not in shock Tolerating oral fluid Acidotic (hyperventilation) Vomiting Resuscitation IV Therapy Therapy Airway ± NG tube Calculate fluid requirements Start with SC insulin Breathing (100% oxygen) Correct over 48 hours Continue oral hydration Circulation (0.1 unit/kg/hour Critical Observations Hourly blood glucose Hourly fluid input & output Neurological status at least hourly Electrolytes 2 hourly after start of IV therapy Monitor ECG for T-wave changes Acidosis not improving Blood glucose 17 mmol/l Neurological deterioration or WARNING SIGNS: blood glucose falls >5 mmol/l/hour headache. SC. irritability. urea. nasogastric. incontinence.

calcium. s change in neurological status (restlessness. it is important to ¤ Capillary blood glucose should be measured hourly calculate the corrected sodium (using the above (but must be cross-checked against laboratory venous formula) and monitor its changes throughout the glucose. Shock with hemodynamic compromise is rare (heart rate.g. largely restricted to the extracel- palsies. such as a child. Consensus Guidelines Children with severe DKA (long duration of hematocrit. and ketosis without vomiting or severe dehydration can ¤ Calculations: be managed at home or in an outpatient health care facility (e. deficit are subjective and inaccurate (43. Increased s inappropriate slowing of heart rate serum urea nitrogen and hematocrit may be useful s recurrence of vomiting markers of the severity of ECF contraction (40.. The effective osmolality (formula above) is fre- s headache quently in the range of 300–350 mmol/kg. Clinical estimates of the volume ¤ Hourly (or more frequently as indicated) neurolog. glucose. neurological status and laboratory results can be monitored frequently s Corrected sodium ¼ measured Na 1 2 3 ([plasma glucose 2 5. increase. . respiratory rate. abnormal pupillary responses) lular space. incontinence) or measure of the degree of ECF contraction for two specific neurologic signs (e.. 45).E) (17. Children and adolescents with DKA should be an anion gap .g. every 2 be considered for immediate treatment in an intensive h (34) care unit (pediatric. hyperglycemia adjunct to laboratory-based determinations. if available. as capillary methods may be inaccurate in the course of therapy. ¤ Hourly (or more frequently as indicated) accurate The latter is not a concern with most modern methods fluid input (including all oral fluid) and output for measuring sodium. provided an experienced s Anion gap ¼ Na 2 (Cl 1 HCO3): normal is 12  diabetes team supervises the care (C. serum electrolytes and blood ketones on In a child with established diabetes. ¤ Restore blood glucose to near normal ¤ Avoid complications of therapy There should be documentation on a flow chart of ¤ Identify and treat any precipitating event hour-by-hour clinical observations. if available) or in a unit that has ¤ If the laboratory cannot provide timely results. high blood urea nitrogen) should tyrate (BOHB) concentrations. ¤ Laboratory tests: serum electrolytes. emergency ward). 38). Monitor- Fluids and salt. Therefore. there- ical observations (Glasgow coma score) for warning fore. blood the measured serum sodium concentration should urea nitrogen.35 mmol/L suggests concomi- managed in centers experienced in its treatment tant lactic acidosis (E) and where vital signs. 44). compromised circulation. but it is important to appreciate that this Pediatric Diabetes 2007: 8: 28–43 33 . and laboratory results. whose parents have fingerstick blood samples at the bedside is a useful been trained in sick day management. causes osmotic movement of water into s rising blood pressure the extracellular space thereby inducing dilutional s decreased oxygen saturation hyponatremia (46. Patients with DKA have a deficit in ing should include the following: ECF volume that usually is in the range 5–10% (C) ¤ Hourly (or more frequently as indicated) vital signs (41. or depressed 2–4 hourly. irri- The serum sodium concentration is an unreliable tability.g.5 yr of age. fluids. or more frequently. phosphorus.. 2 mmol/L j In DKA the anion gap is typically 20–30 mmol/L. portable biochemical analyzer that measures plasma ren’s ward specializing in diabetes care (C. and (2) the low sodium content ¤ Amount of administered insulin of the elevated lipid fraction of the serum in DKA. in more severe cases risk for cerebral edema (e. cranial nerve reasons: (1) glucose. 39. 42). in moderate DKA use 5–7% and in severe DKA signs and symptoms of cerebral edema (see below) 7–10% dehydration. severe ¤ Urine ketones until cleared or blood b-hydroxybu- acidosis. low pCO2. As the plasma glucose concentra- presence of poor peripheral circulation and acidosis) tion decreases after administering fluid and insulin.E) (4. magnesium. blood pressure) in pediatric DKA. IV and oral medications. a equivalent resources and supervision. 40).6]/5. as clinically indi- level of consciousness) or those who are at increased cated.6) mmol/L s Effective osmolality ¼ 2 3 (Na 1 K) 1 plasma Clinical and biochemical monitoring glucose mOsm/kg Successful management of DKA and HHS demands meticulous monitoring of the patient’s clinical and Goals of therapy biochemical response to treatment so that timely ¤ Correct dehydration adjustments in treatment can be made when indicated ¤ Correct acidosis and reverse ketosis by the patient’s clinical or laboratory data (E). increased drowsiness. glucose. 47). and blood gases should be repeated symptoms.

1 U/kg/h. cortisol). i. by a panel of expert physicians representing the Lawson ¤ The use of large amounts of 0. ¤ IV or oral fluids that may have been given in another facility before assessment should be DKA is caused by either relative or absolute insulin factored into calculation of deficit and repair (E). 62). catecholamines.5–2 times the usual daily clearance of glucose and ketones from the blood maintenance requirement based on age. does not indicate a worsening of the hypertonic state. 1 unit ¼ 1 mL) (64. strategy can be definitively recommended as being ¤ The sodium content of the fluid may need to be superior to another based on evidence. but may be development of cerebral edema (51). 49.C) (65). ¤ Correction of insulin deficiency ¤ Subsequent fluid management (deficit replacement) s Dose: 0. growth hor- rehydrate evenly over 48 h at a rate rarely in excess of mone. Despite much effort to find the cause of cerebral edema calculation of effective osmolality may be valuable it remains a mystery. 57). 52). deficit replacement should be with A failure of measured serum sodium levels to rise or a solution that has a tonicity equal to or greater a further decline in serum sodium levels with therapy than 0.45% saline with added potassium chlo- is thought to be a potentially ominous sign of ride. Subsequent insulin associated with increases in counter-regulatory fluid administration (including oral fluids) should hormones (glucagon. and may be repeated. ¤ Restoration of circulating volume s As the severity of dehydration may be difficult to ¤ Replacement of sodium and the ECF and intracel. an association between the rate of fluid or sodium ¤ Urinary losses should not routinely be added to the administration used in the treatment of DKA and the calculation of replacement fluid.E) (45. See Table 3 for examples of calculations.5–2 times the usual daily maintenance. volume Begin with 0.9% saline has been Wilkins Pediatric Endocrine Society (LWPES). one method is should be with 0. determine and frequently is under. 53–55).or over- lular fluid deficit of water estimated (C) (44). crystalloid in the treatment of DKA. ¤ Start insulin infusion 1–2 h after starting fluid s Use crystalloid not colloid (E). Principles of water and salt replacement ¤ In addition to clinical assessment of dehydration. 49. s The volume and rate of administration depends Extensive evidence indicates that Ôlow dose’ IV on circulatory status and.E) The objectives of fluid and electrolyte replacement (45. or potassium acetate impending cerebral edema (48–50). There are no data replacement therapy. (see below under potassium replacement) (C. Insulin therapy Begin with fluid replacement before insulin therapy. 10–20 mL/kg over 1–2 h. some decrease in blood glucose concentration (61. deficiency. the associated with the development of hyperchloremic European Society for Paediatric Endocrinology metabolic acidosis (59. There is no convincing evidence of to guide fluid and electrolyte therapy (E). the volume administered typically is (A) (64).Wolfsdorf et al. 1–2 h AFTER starting fluid expansion (resuscitation) should begin immediately replacement therapy. and suppress lipolysis and ketogenesis (A) (63).. The principles increased if measured serum sodium is low and described below were developed after a comprehensive does not rise appropriately as the plasma glucose review of the literature and were accepted and endorsed concentration falls (C) (48. mL normal saline. No treatment necessary in rare circumstances (E). s Thereafter. potassium phosphate. ¤ If needed to restore peripheral circulation. if necessary (E).e. weight. with 0. (ESPE). Volume expansion (resuscitation) is required only if DKA is caused by a decrease in effective circulating needed to restore peripheral circulation.9% saline or Ringer’s acetate for to dilute 50 units regular [soluble] insulin in 50 at least 4–6 h (C. insulin therapy is essential to normalize blood glucose ¤ Water and salt deficits must be replaced (A). 66) 34 Pediatric Diabetes 2007: 8: 28–43 .1 unit/kg/h (for example. Although rehydration alone causes 1. therapy are: s The rate of fluid (IV and oral) should be calculated to rehydrate evenly over 48 h (C. after the patient has to support the use of colloid in preference to received initial volume expansion (E. E) (4. where it is clinically insulin administration should be the standard of care indicated. 45). 60). infuse fluid each day at a rate ¤ Improved glomerular filtration with enhanced rarely in excess of 1. 53.9% saline (E). and the International Society for Pediatric and Adolescent Diabetes (ISPAD) (4. 58). 56. ¤ Reduction of risk of cerebral edema or body surface area (E) (4).

depending on the timing and 9 710 1160 48 amount of glucose administration (C) (69–75). s An IV bolus is unnecessary (67). 76–79). and consider other possible causes of 50 2100 4200 175 55 2210 4420 184 impaired response to insulin. 17 1120 1970 82 18 1150 2050 85 19 1190 2140 89 s It may be necessary to use 10% or even 12.7. shown in the Table. 10 780 1280 53 ¤ To prevent an unduly rapid decrease in plasma 11 840 1390 58 glucose concentration and hypoglycemia. The Table is based on maintenance volumes SC insulin lispro or aspart at 0.5% 20 1230 2230 93 dextrose to prevent hypoglycemia while continuing 22 1300 2400 100 to infuse insulin to correct the metabolic acidosis.3 unit/kg. and should not be mmol/L (250 mg/dL). s If blood glucose falls to . the dose may be decreased to 0. Fluids given orally (when patient has improved) should be subtracted from the amount in the s Initial dose SC: 0. 5% glu- 12 890 1490 62 13 940 1590 66 cose should be added to the IV fluid (e. 38 1790 3580 149 ¤ If biochemical parameters of DKA (pH.32 kg.05 unit/kg/h to keep blood glucose 11 mmol/L (200 mg/dL) until resolution of DKA.1 unit/kg/h at least until resolution of DKA (pH . the volumes have been adjusted so as not to exceed hour. anion gap) 40 1850 3700 154 do not improve. infection.30). reduce SC insulin lispro or used at the start of therapy (C) aspart to 0. DKA: give maintenance 1 5% patients with HHS. 7. reassess the patient. Do normalization of blood glucose concentrations not decrease the insulin infusion. may increase s When DKA has resolved and blood glucose is . or less.. and some older children with of body weight/24 h established diabetes). but should Table gives volumes for maintenance and rehydration per 24 h and per hour. hourly.14 mmol/L (250 mg/dL) before DKA has resolved (pH still . not be used in subjects whose peripheral circulation the volume should not be subtracted from the amount is impaired (E).g. 5% glucose 14 990 1690 70 in 0. 15 mmol/L and/or closure of If the blood glucose concentration decreases too quickly or too low before DKA has resolved.. twice the maintenance rate of fluid administration.5 mmol/L/h) 30 1560 3060 128 after initial fluid expansion consider adding glucose 32 1620 3220 134 even before plasma glucose has decreased to 17 34 1680 3360 140 36 1730 3460 144 mmol/L (E). or 2-hourly subcutane- 75 2590 5180 216 ous (SC) or intramuscular (IM) administration of 80 2690 5380 224 a short. followed 1 h later by table. some young children with DKA.. 24 1360 2560 107 26 1430 2730 114 28 1490 2890 120 ¤ If blood glucose falls very rapidly (. or 16 1070 1870 78 sooner if the rate of fall is precipitous (B). bicarbonate . ¤ The dose of insulin should usually remain at 0. and assuming 10% dehydration. add 5% s Route of administration IV (A) glucose and continue with insulin as above. Consensus Guidelines Table 3. 65 2410 4820 201 ¤ In circumstances where continuous IV administra- 70 2500 5000 208 tion is not possible. errors 60 2320 4640 193 in insulin preparation (E). Pediatric Diabetes 2007: 8: 28–43 35 . weight kg mL/24 h mL/24 h mL/h ¤ During initial volume expansion the plasma glucose 4 325 530 22 concentration falls steeply (61) (C). review insulin 45 1980 3960 165 therapy.20 units/kg every 2 h.or rapid-acting insulin analog (insulin lispro After initial resuscitation. and 5 405 650 27 after commencing insulin therapy. Shows an alternative example of fluid volumes ¤ If the patient demonstrates marked sensitivity to for the subsequent phase of rehydration insulin (e.g. or insulin aspart) is safe and may be as effective as IV the total amount of fluid should be given over 48 h. e.1 unit/kg every according to Darrow (146). or 0. The regular insulin infusion (C) (70.14 the risk of cerebral edema (65). For body weights .05 unit/kg/h. Thereafter.45% saline) when the plasma glucose falls to 15 1030 1780 74 approximately 14–17 mmol/L (250–300 mg/dL). provided that metabolic Body Maintenance acidosis continues to resolve. which invariably takes longer than increase the amount of glucose administered. the anion gap). If fluid has been given for resuscitation. the plasma 6 485 790 33 7 570 920 38 glucose concentration typically decreases at a rate 8 640 1040 43 of 2–5 mmol/L/h.15–0. (B) (68).30.g.

80–82). contributes to hyper. there is always a total body deficit unexplained weakness should be treated (E) (99). ate therapy may cause paradoxical CNS acidosis (106. Administration of insulin and the disturbances (90–92). which unavailable. pre- disposing the patient to cardiac arrhythmias. out IV fluid therapy (E). The serum prolonged beyond 24 h (41. and the appearance of U waves indicate hypokalemia. 42. depletion has been associated with a variety of metabolic kalemia (83). Never- s If potassium is given with the initial rapid theless.9) in whom decreased cardiac contractility and peripheral vasodila- ¤ Potassium phosphate may be used together with tation can further impair tissue perfusion. Volume depletion causes secondary hyperaldosteronism. which promotes uri. potassium concentration may decrease abruptly. Begin with 40 mmol potassium/L in the infusate or 20 mmol potassium/L in the hypokalemic ¤ Administration of phosphate may induce hypocal- patient receiving fluid at a rate . 107). 6. decreasing serum levels (84). The major ¤ Potassium replacement should continue through- loss of potassium is from the intracellular pool.or hypokalemia (C) (35. or decreased (83). defer potassium replace. ¤ Prospective studies have not shown clinical benefit from phosphate replacement (A) (93–98). but at presentation serum potassium 80). improves tissue perfusion and renal function increas- Flattening of the T wave. and this is exacerbated by insulin. ¤ The maximum recommended rate of IV potassium cellular shifts of this ion caused by hypertonicity replacement is usually 0. If the patient is hyperkalemic. ¤ Potassium phosphate salts may be safely used as an ¤ Replacement therapy is required regardless of the alternative to or combined with potassium chloride serum potassium concentration (A) (85.E). insulin stops further ketoacid production ¤ If immediate serum potassium measurements are and allows ketoacids to be metabolized. by enhancing hyperglycemia and of phosphate into cells (87–89). or acetate. replacement.. Controlled trials have shown no clinical benefit from Tall. Treatment of hypovolemia the child has hyper. ing the excretion of organic acids. (increased plasma osmolality causes solvent drag in ¤ If hypokalemia persists despite maximum rate of which water and potassium are drawn out of cells) and potassium replacement. Depletion of intracellular phosphate occurs in DKA and nary potassium excretion. increased. which promotes entry Renal dysfunction. start potassium serum calcium is performed to avoid hypocalcemia replacement at the time of initial volume expansion (C) (100. an ECG may help to determine whether generates bicarbonate (A). Severe acidosis is reversible by fluid and insulin ment therapy until urine output is documented (E). Bicarbon- the QT interval are signs of hyperkalemia. potassium occurs. ¤ The starting potassium concentration in the in. Subsequent potassium causes hypokalemia (106.C) (102–105).5 mmol/kg/h (E). then the rate of insulin glycogenolysis and proteolysis secondary to insulin infusion can be reduced. total body depletion of phosphate is lost as a result of osmotic diuresis (41. e. 36 Pediatric Diabetes 2007: 8: 28–43 .10 mL/kg/h. with severe acidemia (arterial pH . appropriately reducing the NaCl concentration of the fluids can result in increasing osmolality (106). Total body phosphate reducing potassium excretion. of the order of 3–6 mmol/kg (41. provided that careful monitoring of ¤ If the patient is hypokalemic. start replacing potassium after initial volume expansion Acidosis and concurrent with starting insulin therapy. deficiency cause potassium efflux from cells. 86).g. 42. Intracellular potassium is depleted because of trans.Wolfsdorf et al. T waves and shortening of bicarbonate administration (B. rapid correction of acidosis with bicarbonate fusate should be 40 mmol/L. and before starting insulin therapy. 80). and patients potassium chloride or acetate. 36). These include: patients L should be used. Potassium replacement potassium chloride and 20 mmol/L potassium phosphate or 20 mmol/L potassium phosphate Children with DKA suffer total body potassium deficits and 20 mmol/L potassium acetate (C. 101). 109). there may be selected patients who may benefit volume expansion. peaked. cemia (C) (100. 101). symmetrical. 42. Clinically significant hypophos- correction of acidosis will drive potassium back into phatemia may occur if IV therapy without food intake is the cells. and failure to replacement therapy should be based on serum account for the sodium being administered and potassium measurements (E). Phosphate quence of osmotic diuresis. Even with normal or high levels of serum potassium ¤ Severe hypophosphatemia in conjunction with at presentation. Potassium is lost from the body from vomiting and as a conse. 108. 20 mmol/L with life-threatening hyperkalemia (E) (110). Plasma phosphate levels fall after starting treatment levels may be normal. Otherwise. a concentration of 20 mmol/ from cautious alkali therapy. widening of the QT interval. Thus. of potassium.

an increased risk of cerebral edema include: ¤ When ketoacidosis has resolved. and the change to SC insulin is planned. basilar artery thrombosis) give 1–2 mmol/kg over 60 min (E). ¤ Peripheral venous thrombosis ¤ Sepsis ¤ Rhinocerebral or pulmonary mucormycosis Complications of therapy ¤ Aspiration pneumonia ¤ Inadequate rehydration ¤ Pulmonary edema ¤ Hypoglycemia ¤ Adult respiratory distress syndrome (ARDS) ¤ Hypokalemia ¤ Pneumothorax. frequent blood concentrations during therapy (C) (48–50) glucose monitoring is required to avoid marked ¤ Greater volumes of fluid given in the first 4 h (65) hyperglycemia and hypoglycemia (E).or long-acting insulin. ¤ When oral fluid is tolerated. seminated intravascular coagulation. injection should be given 15–30 min (with rapid- In addition. the first dose of basal insulin may (C) (50) be administered in the evening and the insulin ¤ More severe acidosis at presentation (C) (65. 118) lowered.B) (50. These risk associations may reflect the greater ¤ To prevent rebound hyperglycemia the first SC likelihood of severe DKA.g. 113. 119) infusion is stopped the next morning (E). Cerebral edema accounts for 60–90% of all DKA increased drowsiness. incontinence) deaths (C. irritability.5–0. cautiously thrombosis. 113). the overlap ¤ Greater hypocapnia at presentation after adjusting should be longer and the IV insulin gradually for degree of acidosis (C) (50. Pediatric Diabetes 2007: 8: 28–43 37 . 120) according to local preferences and circumstances. ¤ New onset diabetes (B) (112) (C) (116) the most convenient time to change to SC insulin is ¤ Longer duration of symptoms (C) (117) just before a mealtime (E). Consensus Guidelines Other rare causes of morbidity and mortality include: There is no evidence that bicarbonate is either necessary or safe in DKA. oral intake is ¤ Younger age (C) (116) tolerated. From 10% to 25% of survivors Specific neurological signs (e. epidemiological studies have identified acting insulin) or 1–2 h (with regular insulin) before several potential risk factors at diagnosis or during stopping the insulin infusion to allow sufficient treatment of DKA. IV fluid should be Demographic factors that have been associated with reduced (E).. cranial nerve palsies) of cerebral edema have significant residual morbidity Rising blood pressure Decreased O2 saturation (C.30% (C. These include: time for the insulin to be absorbed (E). Change in neurological status (restlessness. ¤ An attenuated rise in measured serum sodium ¤ After transitioning to SC insulin. 21–24% (50.9% and the mortality rate is (mild acidosis/ketosis may still be present) (E). ¤ Bicarbonate treatment for correction of acidosis ¤ The dose and type of SC insulin should be (C) (50. the mortality rate from Headache & slowing of heart rate DKA in children is 0.B) (50. 112).15–0. 114). 114). For example.B) (111. for patients on a basal-bolus ¤ Increased serum urea nitrogen at presentation insulin regimen. ¤ Administration of insulin in the first hour of fluid treatment (65) Morbidity and mortality Warning signs and symptoms of cerebral edema include: In national population studies. 113. ¤ Hypokalemia ¤ Hyperkalemia ¤ Bicarbonate administration is not recommended ¤ Severe hypophosphatemia unless the acidosis is profound and likely to affect ¤ Hypoglycemia adversely the action of adrenaline/epinephrine ¤ Other central nervous system complications (dis- during resuscitation (A). pneumomediastinum and SC ¤ Hyperchloremic acidosis ¤ Cerebral edema emphysema ¤ Rhabdomyolysis ¤ Acute renal failure ¤ Acute pancreatitis (115) Introduction of oral fluids and transition to SC insulin injections Cerebral edema ¤ Oral fluids should be introduced only when The incidence of cerebral edema in national popula- substantial clinical improvement has occurred tion studies is 0. With intermediate. dural sinus ¤ If bicarbonate is considered necessary.

tachypnea. 30). which may be and the dose to be given calculated beforehand. 5–10 mL/kg over 30 min. s There may be dissociation between urine ketone Have mannitol or hypertonic saline at the bedside and serum BOHB concentrations. Minor criteria. Clinically significant cerebral edema usually devel. but can occur ¤ Intubation may be necessary for the patient with before treatment has begun (50. when compared with urine ketone testing. espe- ¤ Abnormal motor or verbal response to pain cially thrombosis (133–136) or hemorrhage.5–1 g/kg IV over 20 min and s a means of escaping an intolerable or abusive repeat if there is no initial response in 30 min to 2 h home situation. Prevention of recurrent DKA apneusis) Management of an episode of DKA is not complete Major criteria. or small ketonuria (138). 2. either leads to ketosis (E). (C. Cheyne-Stokes respiration. ¤ Elevate the head of the bed. 131). and gender. ops 4–12 h after treatment has started.. Symptoms and Hg]) has been associated with poor outcome and is signs are variable. ¤ Cranial nerve palsy (especially III. A method of clinical diagnosis not recommended (C) (132). impending respiratory failure. and VI) ¤ Abnormal neurogenic respiratory pattern (e. ¤ There usually is an important psychosocial reason Treatment of cerebral edema for insulin omission.g. neurologic deterioration (10% of cases).B) (50. a pump because interrupted insulin delivery rapidly weight. which vary depending on height. ¤ Give mannitol 0. mannitol a urine ketone test is negative or shows only trace should be given immediately. either inadvertently or deliber- ately. 114. ¤ Lethargy or not easily arousable ¤ Home measurement of blood BOHB concentra- ¤ Diastolic blood pressure .5 yr decreases diabetes-related hospital visits (both One diagnostic criterion. is the cause in most cases (C. 116. based on bedside evaluation of neurological state is ¤ After treatment for cerebral edema has been shown below (C) (126): started. 121–124) or. ¤ Sustained heart rate deceleration (decrease more than 20 beats per minute) not attributable to All cases of recurrent DKA are preventable improved intravascular volume or sleep state ¤ Age-inappropriate incontinence ¤ Insulin omission. Blood BOHB measurements may be espe- A chart with the reference ranges for blood pressure cially valuable to prevent DKA in patients who use and heart rate. 90 mm Hg tions. a cranial CT scan should be obtained to rule out other possible intracerebral causes of Diagnostic criteria. (137). should be readily available.E) (127–129). in the patient’s chart or at the bedside. ¤ Age . In increased to levels consistent with DKA when case of profound neurological symptoms.Wolfsdorf et al. especially if there ¤ An infection that is not associated with vomiting is no initial response to mannitol (C) (130. ¤ Hypertonic saline (3%). A) (28. IV. which ¤ Decorticate or decerebrate posture may benefit from specific therapy. family is properly educated in diabetes manage- able at the bedside. or one emergency department visits and hospitalizations) major and two minor criteria have a sensitivity of 92% by the early identification and treatment of ketosis and a false positive rate of only 4%. and diarrhea is seldom the cause when the patient/ s Mannitol or hypertonic saline should be avail. 125). until its cause has been identified and an attempt ¤ Altered mentation/fluctuating level of consciousness made to treat it. grunting. ¤ The most common cause of DKA in insulin pump users is failure to take extra insulin with a pen or ¤ Vomiting syringe when hyperglycemia and hyperketonemia ¤ Headache or ketonuria occur (E). but aggressive uncommonly. may develop as late as 24–48 h after the hyperventilation (to a pCO2 . with an eating disorder. may be an alternative to mannitol. ¤ Initiate treatment as soon as the condition is s an attempt to lose weight in an adolescent girl suspected. s clinical depression or other reason for inability of ¤ Reduce the rate of fluid administration by one-third.9 kPa [22 mm start of treatment (C. two major criteria. ment and is receiving appropriate follow-up care by 38 Pediatric Diabetes 2007: 8: 28–43 . the patient to manage the diabetes unassisted.

Diabetes Care 2001: 24: 131–153. Arch Dis Child 1996: 75: hydrate drinks worsening initial presentation? Pediatr 410–415. DOLAN LM. CHASE HP. J Pediatr 2004: 144: 270–273. 279–284. HARDY KJ. Diabetes Care 1998: 21: insulin administration (B) (142). CHEN YD. in Finland Study Group. helpline for emergency advice and treatment (B) Diabetes Metab Res Rev 2002: 18: 135–142. PINHAS-HAMIEL O. Euro- in children and adolescents. KEENAN H. Diabetic ketoa- is a mechanism for the development of euglycemic cidosis and cerebral edema in Sweden – a 2-year ketoacidosis during periods of insulin deficiency. Diabetic ketoaci- Guidelines is the same as that used by the American dosis in children and the role of outpatient manage- Diabetes Association. KUBOTA S. and treat impending DKA with additional rapid. PINKEY JH. KOMULAINEN J. Childhood Diabetes hyperosmolarity and hypernatremia: are high-carbo. HARADA K. children at the time of diagnosis. SELLERS EA. KNIP M. Childhood diabetes presenting with hyper- References osmolar dehydration but without ketoacidosis: a report of three cases. Type 2 diabetes in children with type 1 diabetes. KITAGAWA T. Diabetes Care 2000: 23: 1202–1204. study. ISPAD Clinical Practice Consensus Guidelines in 18. 14: 65–75. LOUNAMAA R. CRADOCK MM. Diabetes Care 1997: 20: 484–486. J Clin population study. Diabet Med 1992: 9: 2. Short-term fasting 23. provide education. 22. Consensus Guidelines a diabetes team with a 24-h telephone helpline (B) 8. Consensus Guidelines 2006–2007 of the International OWADA M. WERTHER GA. 24. GARG SK. JELLEY DH. See the Introduction of the ment. (insulin dependent) diabetes mellitus is related to CAMERON FJ. NEWTON T. 10. will later be published as a compendium. REWERS A. SAVOLA K et al. SAWTELL PA. MCDONNELL CM. DAVIS C et al. Pediatr Diabetes 2004: 5: 212–218. LINDBLAD B. HAMILTON J. Arch Dis Child 2004: 89: pean and Diabetes. 80–86. BINGLEY PJ. Diabet Med 2004: 21: 1144–1148. should be consulted to identify the psychosocial Characteristics of youth-onset noninsulin-dependent reason(s) contributing to development of DKA (E). NEUFELD ND. DEAN HJ. Diabetologia 2001: 44(Suppl. Annual incidence and clinical characteristics of type 2 diabetes in children as detected Society for Pediatric and Adolescent Diabetes (ISPAD. MATSUURA N. NITADORI Y. Diabetic ketoacidosis. 1. KOHNO H et al. Geo- 4. ESPE/ graphical variation of presentation at diagnosis of type LWPES consensus statement on diabetic ketoacidosis I diabetes in children: the EURODIAB study. LINDGREN F. Early presentation of type 2 diabetes treatment combined with adult supervision of in Mexican-American youth. 20. ONYEMERE KU. 19. BARRETT TG. KLINGENSMITH G. Pediatr Rev 1990: 11: 297–304. The metabolic derange. AKERBLOM HK. Jpn Clin Pediatr Endocrinol 2005: directed to the Corresponding Author. poor residual beta cell function. ment of hyperglycemic crises in patients with diabetes. 12. The evidence grading system used in the ISPAD 17. PEDREIRA CC. Diabetes 2005: 6: 90–94. Survey of comments. SCOTT CR. LANDON C. KIRK J. ¤ A psychiatric social worker or clinical psychologist 9. diabetes by urine glucose testing at school in Japan. KIKUCHI N. ROSENBLOOM AL. Death caused by hyperglycemic hyperosmolar state at the onset of type Pediatric Diabetes 2006: 7: 341–342. YOKOTA Y. Manage. ments and treatment of diabetic ketoacidosis. PAPOZ L. SMITH JM. Clinical. there may be as much as a tenfold reduction in 14. PIHOKER C. SCHADE DS. Diabet Med 2005: 22: 645–647. MURPHY M et al. Diabetes 2005: 54(Suppl. SASAKI N. clarifications or corrections should be current medical treatments for childhood-onset type 2 diabetes mellitus. HANAS R. Diabetes Care 1999: 22: betes Care 2000: 23: 381–389. Diabetic ketoacidosis: a com- s Parents and patients should learn how to recognize plication of type 2 diabetes in Canadian aboriginal youth. Diabetes 2004: 53(Suppl. Diabetologia 25. by urine glucose screening in the Tokyo metropolitan www.ispad. (Consensus statement). FOSTER DW. SUGIHARA S. Diabetes Care 2005: 28: 1876–1881. BERRY K. KOMULAINEN J. Endocrinol Metab 1993: 76: 1192–1198. MORALES AE. KAPRIO EA. and genetic characteristics of very young 7. Presentation and progress of childhood diabetes in youth study. LEVY-MARCHAL C. 2 diabetes. PATTERSON CC. 1985–1994. The Bart’s-Oxford Study Group. 2): A421. KULMALA P. GREEN A. BURGE MR.org). KITABCHI A. Pediatrics 1997: 100: 84–91. Childhood Diabetes in children and adolescents. Presentation (139) and course of Type 2 diabetes in youth in a large multi- s When a responsible adult administers insulin ethnic city. B75–B80. 13. Additional 16. DE BEAUFORT C et al. or short-acting insulin and oral fluids (E) Incidence and onset features of diabetes in African- s Patients should have access to a 24-h telephone American and Latino children in Chicago. DANEMAN D. MCGARRY JD. 1950–1955. 1994: 37: 70–74. VADAMALAYAN B. Diabetic 6. Screening for frequency of recurrent DKA (B) (142). autoimmune. ZDRAVKOVIC V. LIPTON R. Ketoacidosis at the diagnosis of type 1 3. AMERICAN DIABETES ASSOCIATION. FREELS S. Pediatric Diabetes 2007: 8: 28–43 39 . ZEITLER PS. RAFFEL LJ. Dia. SPERLING MA. KERSHAW MJ. This article is a Chapter in the ISPAD Clinical Practice 15. The complete set of these Guidelines area. ACERINI CL et al. 21. 3): 188–194. DUNGER DB. UMPIERREZ G. psychosocial evaluation and VADHEIM CM. Diabetic (139–141). ketoacidosis at onset of diabetes: the SEARCH for GALE EA. ketoacidosis among obese African-American adolescents with NIDDM. diabetes mellitus and insulin-dependent diabetes melli- ¤ Insulin omission can be prevented by schemes that tus at diagnosis. 11. DUNGER DB. Finland (DiMe) Study Group. URAKAMI T. 1): diabetes mellitus: a prospective population-based A63. LEVY-MARCHAL C. N Engl J Clinical and laboratory features of type 1 diabetic Med 1983: 309: 159–169. 5.

J 40. Factors associated with brain Dis Child 1988: 142: 448–450. GUTZEIT MF. DEWALT DA. of electrolyte balances following the withdrawal and 60. NEUTZE J. treatment. ROSILIO M. BENNETT MA. The value of electrocardio. Pediatr Emerg Care 1996: 12: 347–351. BRODSKY SJ. HILLIER TA. HARRIS GD. FINBERG L. Diabetes Care 1997: 20: 1347–1352. COTTON JB. CHISHOLM Engl J Med 1973: 289: 843–844. conditions and insulin pump use in a 2-year population 49. BYERLEY JS. Diabetes Care 1999: 22: 674– Electrocardiogram as a guide to potassium replacement 677. SCHUNK JE. URIBARRI J. Effect of rehydration 37. Assessment of coma and 21: 141–144. Diabetes Care 2004: 27: effects of partial rehydration during diabetic ketoaci- 2485–2487. KORN A. RICHARDS D Jr. homeostasis re-evaluated. JENNETT B. BENEDICT E. impaired consciousness. ABBOTT RD. The French Pediatric Diabetes 1994: 148: 1046–1052. HARPER R et al. Diabetic therapy. EKNOYAN G. A 5-year prospective pediatric nationwide study in 2. Plasma free insulin concen. and new onset type I diabetes. Factors predicting cerebral 2005: 54(Suppl. Predisposing tive and prospective study. LINARES MY. MALONE JI. BARNETT P. A practical scale. gram monitoring in diabetic ketoacidosis. BONADIO WA. WERTHER GA. N Engl J Med 2001: 344: 264–269. FITZGERALD MG. BENNETT S. NOWOTNY P. SOLER NG. MALONE JI. Nephron 1990: 54: 1–6. Pediatrics 2001: 108: 39. BARRETT EJ. Am J Manag Care 1997: 3: 253–258. Pediatrics. LINDSAY R. WAGNER A. SMITH DS. ketoacidosis: is treatment a factor? Emerg Med J 2004: 32. LICHT JH. NABARRO J. Diabetes 1974: 23: 610–615. OKADA P. 1): A455. emergency management. GREENE SA. of modest fluid replacement in the treatment of adults 34. Renal function and ketoacidosis in childhood. J Med 1999: 106: 399–403. Diabetes Audit and Research dosis. On diabetic ketoacidosis: a detailed study 598. dose insulin application. ROTHER KI. The DARTS/ for cerebral edema in children with diabetic ketoaci- MEMO Collaboration. Pediatr Diabetes 54. Diabetes Care 1998: 21: 1146–1153 (See 46. Outpatient management of diabetic ketoacidosis. WALDHAUSL W. SHANN F. The Pediatric Emergency Medicine Collabora- in Tayside Scotland. SMITH CP. European Society for Paediatric Endocrinology/Law- 33. KLEINBERGER G. MALINS JM. Acta Paediatr 1997: 86: MACDONALD TM. with diabetic ketoacidosis. Am J 58. Therapy of severe Care 1980: 3: 543–547. Metabolic studies 61. LIPMAN TH. DUNGER DB. Cerebral oedema in childhood diabetic dehydrated? JAMA 2004: 291: 2746–2754. J Clin Invest 1933: normochloremic and hyperchloremic acidosis in dia- 12: 297–326. Treatment son Wilkins Pediatric Endocrine Society consensus of diabetic ketoacidosis using normalization of blood statement on diabetic ketoacidosis in children and 3-hydroxybutyrate concentration as the endpoint of adolescents. 2: 81–84. J Pediatr 1981: 99: 862–867. Lancet 1989: 2: 605–607. WHITE PC. WIELICZKO MC et al. BROWN TB. MCCASLIN I et al. STOWERS J. WIGGAM MI. OH MS. Ketoacidosis occurring in newly diagnosed and 47. Mechanism of reestablishment of insulin therapy. O’KANE MJ. LOEB R. JAMA 1989: 262: 2108–2113. glycaemic control. ments and blood glucose concentration. The accuracy of 28: 577–584. BRATUSCH-MARRAIN P. CARROLL HJ. FIORDALISI I. HOWARD C. NEWTON RW. Bedside ketone with diabetic ketoacidosis. during treatment of diabetic ketoacidemia: a retrospec- 29. KING W. LINDBLAD B. Factors 45. in severe diabetic ketosis.579 French children with experience in 231 episodes. SPENCER A. Acta Paediatr 1998: 87: evaluating the correction factor for hyperglycemia. Incidence and outcome of 2004: 5: 39–43. MACKENZIE A. MEL JM. HAM MR. Am 537–541. and ketosis in the acute care setting. HARRIS WL. KATZ MA. OWEN OE. 31. 735–740. ROOT AW. Lancet 1974: 52. predictors? J Paediatr Child Health 1995: 31: 17–20. Risk factors insulin-dependent diabetes mellitus. Kidney Int 1984: 25: 591– DRISCOLL M. Pediatrics 2004: 113: e133–e140. Arch Pediatr Adolesc Med type 1 diabetes. J Pediatr 1990: 117: 22–31. Zero-mortality under very-low- 36. ketoacidosis: role of the kidney in the acid-base 41. diabetic ketoacidosis in children. clinical assessment of dehydration during diabetic 62. LINDGREN F. BARNES G. Physiologic management of associated with glycemic control. in diabetic ketoacidosis. SPERLING MA. Predictors of 48. Diabetes 1979: 44. Adherence to insulin 626–631. STEINER MJ. Is this child 51. HARRIS GD. BOYLE DI. Q J Med 1952: 82: 225–248. SUKI WK. herniation in the treatment of diabetic ketoacidosis. 42. FIRTH D. ACERINI CL et al. Severe hypergly- 43. BRILL HL et al. edema in young children with diabetic ketoacidosis 30. DUDCZAK R. Use of PRISM 1149–1153. MOSOVICH LL. Minimizing the risk of brain herniation JAMA 15 2002: 287: 2511–2518. BRAUNSTEIN AW. fluid with 75 mmol/L of sodium on serum sodium trations: keystone to effective management of diabetes concentration and serum osmolality in young patients mellitus in children. diabetic cerebral oedema in childhood: are there 35. study of pediatric ketoacidosis in Sweden. P. scores in triage of pediatric patients with diabetic 57. A cross-sectional diabetic ketoacidemia. Medicines Monitoring Unit. ADROGUE HJ. Group. LOSEK JD. ATCHISON JA. 28. SAPIR DG. BARRERO J. and ketoacidosis in 50. ADROGUE HJ. dosis. MACKENZIE T et al. Use in patients without determination in diabetic children with hyperglycemia extreme volume deficit. DUCK SC. CHASE HP. MONROE KW. Clinical signs of cemia: effects of rehydration on endocrine derange- dehydration in children. HALE PM. diabetic ketoacidosis. MCMAHON AD. A randomized controlled 53. FIORDALISI I. TEASDALE G. RISSE A. betic ketoacidosis.Wolfsdorf et al. ATCHLEY D. Improving management of ketoacidosis. KOVES IH. N 27. 26. Hyponatremia: established diabetic children. GARIBALDI L. EKNOYAN G. DONATH S et al. REZVANI I. MORRIS AD. Hyperglycemia-induced hyponatremia – comments) calculation of expected serum sodium depression. Mayo Clin Proc 1994: 69: 38. 40 Pediatric Diabetes 2007: 8: 28–43 . FELNER EI. presentation in diabetic ketoacidosis and duration of 59. WYATT DT. REWERS A. SCHWENK WFN. tive Research Committee of the American Academy of Lancet 1997: 350: 1505–1510. WHITE PC. Diabetes 1981: 30: 510–518. HANAS R. 56. Diabetes MARTINEZ N. Diabetes 55. Salutary effects study. Laboratory Pediatr 1988: 113: 10–14. acute complications in children with type 1 diabetes. GLASER N.

STEINMETZ L. Oxygen availability from the blood 74. BROWN DR. H AYES TM. Treatment of diabetic 98. Am acteristics of severe hypophosphatemia. Ann Intern Med 1979: 90: Phosphate replacement during treatment of diabetic 36–42. KITABCHI AE. BURGHEN GA. Med 1977: 137: 203–220. 71. FITZGERALD MG. Pediatrics 1977: 59: 733–738. DROP SL. subcutaneous insulin lispro versus continuous intrave. STOWERS JM. 2. Low-dose 90. SUKI WN. EKNOYAN G. KELLER U. FERRANNINI E. ketosis. A prospective affinity in diabetic ketoacidosis. sis. FERRANNINI E. K APPY MS. study of cerebral oedema complicating diabetic Determinants of plasma potassium levels in diabetic ketoacidosis in children. Diabetes Care 2005: 28: 1856– for hyperglycemia. KITABCHI AE. J Clin Endocrinol Metab 1977: 44: 1038– 1980: 238:E421–427. 70. with particular emphasis on the retention of adminis- sis. MALINS JM. ADROGUE HJ. KITABCHI AE. VEALE KE. BETHUNE JE. Arch Intern Med 1989: 149: 1423– 1861. KELCH RP. Am J Physiol regulation. KAPPY MS. 15: 381–385. P RATT E. ETTELDORF JN. Jacob Holler on potassium deficiency in low-dose insulin infusion for pediatric diabetic ketoa. Effect of phosphate on oxygen-hemoglobin affinity. Studies in diabetic acidosis and coma. SHAHSHAHANI MN. and the effect of phosphate replacement on erythrocyte Effectiveness of low-dose continuous intravenous 2. 93. DARLEY JH. The use of an insulin bolus in (slowly). MACLACHLAN E. SOLER NG. JAKES R. Treatment of 68. UMPIERREZ GE. SCHADE DS. 395. EDWARDS GA. SCHADE DS. 64. Diabet Med 1999: 16: 978–984. 81. WILSON HK. 80. WRIGHT AD. Large phosphate shifts with treatment diabetic ketoacidosis. FISHER JN. LIGHTNER ES. Metabolism 1979: 28: 191–194. LEA AS. DRASH AL. J Pediatr 1976: 89: 560–564. Am J Dis Child 1983: 137: 241–246. D ARROW D. Comparison of high-dose and low-dose insulin by mia by phosphate infusion during treatment of diabetic continuous intravenous infusion in the treatment of ketoacidosis and hyperosmolar coma. STOEVER J et al. ketoacidosis. LINDSAY R. BARRETT EJ. EATON RP. WARDROP CA. MARTIN MM. Low-dose intravenous 91. diabetic ketosis. DEFRONZO RA. DELLA MANNA T. SHAHSHAHANI M. sis. LATIF K. TALBOT N. KITABCHI AE. RATHBUN J. Consensus Guidelines 63. CUERVO R. SACKS HS. Effect of MCENERY PT. Efficacy of sis. 72. 73. ROY Y et al. J Clin Invest 1949: 28: 1–9. Diabetologia 2006: 49: 2002– ketoacidosis. Diabetes 1980: diabetic ketoacidosis in children. Continuous low-dose 88. GOBER AE. UMPIERREZ GE. BURNETT C. BOLTE RG. 95. KITABCHI 94. N Engl J Med 1977: 297: 238–241.3-Diphosphoglycerate and tissue oxygenation in ketoacidosis: biochemical effects in children. FISHER JN. WEHRING B. from diabetic ketoacidosis. Dose response to insulin in Effect of graded doses of insulin on splanchnic and man: differential effects on glucose and ketone body peripheral potassium metabolism in man. J Clin Endocrinol Metab 1983: 57: 177– 78. Lancet 17 1952: 1: 983–989. 85. KNOCHEL JP. REVSIN B. A randomized study of nous regular insulin for the treatment of patients with phosphate therapy in the treatment of diabetic diabetic ketoacidosis. O’CONNOR LR. KNOWLES HC. Prevention of hypophosphate- AQ. Medicine (Baltimore) 1986: 65: 163–172. REYNAERT M. J Pediatr 1977: 91: 701–705. HILL LL.3-diphosphoglycerate and haemoglobin-oxygen insulin infusion in diabetic ketoacidosis. 92. WHEELER WS. EDGE J. 1425. 2009. Diabetic 89. DUVAL-ARNOULD JM. The pathophysiology and clinical char- insulin in the treatment of diabetic ketoacidosis. LIGHTNER ES. 69. FELIG P. a controlled comparative study of diabetic ketoacido. FISHER JN. BUTLER A. Proc ketoacidosis in children. tes Care 2004: 27: 1873–1878. HAWKER CD. Diabetes Care 1980: 29: 87–95. FREIRE AX. 66. BECKER DJ. 86. GROOP LC. Am Diabetes Assoc 1947: 7: 95–115. J Pediatr 1952: 41: 688–696. FRANS A. nesemia. Effects on calcium and phosphorus homeosta- 77. Am J Dis Child 1942: 1221–1224. 100. 76. DEFRONZO RA. Hypocalcemia. WILLEMS E. Comparative study of different insulin regimens in 87. GIBBY OM. cidosis to low-dose insulin by intramuscular injection 96. PETERS J. LEDERER ED. BACON GE. 65. NABARRO JD. N Engl J Med 1977: 297: 901–903. Organic phosphates of the blood and mineral management of diabetic ketoacidosis. Diabetologia 1978: comparative study. LATIF K. EKNOYAN G. Pediatrics uncontrolled diabetes mellitus. Metabolic studies in diabetic coma. Arch Intern Med 1982: 142: 517–520. 64: 401–412. MARTIN AA. Metabolic effects of low-dose insulin GREENMAN L. GUEST G. 75. Arch Intern J Dis Child 1979: 133: 523–525. ZIPF WB. An alternative treatment for pediatric patients with 99. SPENCER AG. 3: 15–20. KEUER SP. EMERSON PM. J ONES JG. Am J Med 2004: 117: 291–296. ALBERTI KG. STERANKA BH. acidosis. Lancet 1975: 2: metabolism in diabetic acidosis. 180. diabetic acidosis (1946). routes. Low-dose insulin therapy in diabetic 82. RILEY MS. Phosphate therapy in diabetic ketoacido- YOUNG RT. KARABELL A. HOCKADAY intravenous insulin infusion in patients with diabetic TD. Diabetes 1988: 37: 1470–1477. BOYD AE 3rd. 1053. Low-dose intravenous hypophosphatemia on myocardial performance in insulin infusion versus subcutaneous insulin injection: man. STANBURY J. KOHAUT EC. A paper which changed clinical practice 67. and albumin-free infusion. The UK case-control 83. QUASHNOCK J. WAHREN J. HERSH JH. Diabe. and transient hypoparathyroidism during Pediatric Diabetes 2007: 8: 28–43 41 . diphosphoglycerate and blood gases during recovery 79. Effects of insulin ketoacidosis: low-dose insulin therapy by various infusion on plasma phosphate in diabetic patients. 97. therapy on glucose metabolism in diabetic ketoacido. TATTERSALL RB. Electrolytes of blood plasma infusion of insulin in the treatment of diabetic and cells in diabetic acidosis and during recovery. HOPWOOD NJ. DANOWSKI T. tered potassium. SPENCER ML. 84. cidosis. Pediatr Emerg Care 1989: 5: 77–79. Intensive Care Med 1989: Subcutaneous Use of a Fast-Acting Insulin Analog: 15: 495–498. Lancet 26 1972: 2: 391– 1977: 60: 681–688. Retention of water and ketoacidosis: fact or fiction? Diabetes Metab Rev 1989: electrolyte during recovery in a patient with diabetic 5: 337–363. CLERBAUX T. GUEST G. EATON RP. ketoacidosis with subcutaneous insulin aspart. RAPOPORT S. CAMPOS PR et al. KITABCHI AE. LUZI L. BOHANNON NJ. Similar responsiveness of diabetic ketoa. hypomag- Trans Assoc Am Phys 1947: 60: 102–109. FISHER JN. BERGER W.

KHOURY K. MCSHANE MA. LEVER E. KOZAK GP. Ann 131. FIELD JB. TOVAR A. people with T1DM: a randomized clinical trial. ROSENBLOOM AL. GREEN SM. WINTER DL. Induction of hypocalcemia and outpatient therapy for diabetic ketoacidosis. J Clin Endocrinol Complications 2002: 16: 214–219. AOKI TT. KHANNA VV. identification. Risk factors ketone monitoring reduces hospital visits in young for developing brain herniation during diabetic ketoa. Lancet 1972: 2: 665–667. saline in the treatment of cerebral edema in diabetic 110. FORD-ADAMS ME. Lancet 1990: 336: 64 MOLTZ K. J Diabetes bicarbonate in diabetic ketoacidosis. EDGE JA. Pediatr Diabetes 2001: 2: 191–194. 136. Factors 25: 1591–1596. MORRIS LR. BERTHIAUME Y. BARNETT P et al. KITABCHI AE. status associated with diabetic ketoacidosis. 125. LAFFEL LM. in diabetic ketoacidosis. J Pediatr 2005: 146: 688–692. Diabet cidosis. LAFFEL L. The cerebrospinal Pediatrics 1982: 69: 87–90. NATTRASS M. ACKROYD S. edema and ophthalmoplegia reversed by mannitol in 107. 137. Cerebral oedema during treatment of 105. CURTIS JR. CRAWFORD TO. DIXON K. Diabetes Care therapy in severe diabetic ketoacidosis. Use of hypertonic 268. HARRIS GD. J Diabetes Com- factors for cerebral edema in pediatric diabetic plications 1996: 10: 100–108. Counterproductive effects of sodium swelling may lead to death before treatment. Development of fatal cerebral edema during Diabetic ketoacidosis. Use of Intern Med 1987: 106: 615–618. DUNGER DB. Early onset fatal 103. COUCH RM. J Pediatr cidosis. LIU J. diabetic ketoacidosis with special reference to the use 129. LOUGHLIN C. 96. SKLAR AH. MAHONEY CP. MUIRHEAD S. Arch Dis Child 2001: 85: 15: 175–176. Metab 1996: 81: 314–320. Cerebral venous thrombosis during diabetic enzyme elevations in children with diabetic ketoacido. Pediatr MAN D. QUISLING RG. CUMMINGS EA. ROSENBLOOM AL. O’NEILL P. GREEN OC. Service and education for the insulin-dependent child. AOKI TT. KEANE S. Pediatr Neurol 1999: 21: 721–727. OBERFIELD SE. radiographic findings. SLOVER RH. SOTOS JF. Diabetes Care 1990: 13: heterozygosity for factor V Leiden deficiency. Potassium balance during treatment of 570–573. WINTER RJ. COHEN JJ. ROE TF. ZIMMERMAN JJ. sis. Diabetes Care 1991: 14: bicarbonate in the treatment of diabetic ketoacidosis. FIORDALISI I. 101. ketoacidosis in Ontario children. DELAGUILA M. CORRALES R. Population-based study of incidence and risk children with diabetic ketoacidosis. DANEMAN KAUFMAN FR. trolled IDDM. LAWRENCE SE. Arterial thrombosis causing cerebral edema in associ- The risk and outcome of cerebral oedema developing ation with diabetic ketoacidosis. Arch Dis Child 1999: 81: 318–323. FRANKLIN B. GINSBERG-FELLNER F. Ann Intern 1991: 14: 78–79. HADDAD NG. Crit Care Med 1987: during diabetic ketoacidosis. MARLISS EB. OLIPHANT M. HOFFMAN WH. CS. J Pediatr 22–33. Recovery from symptomatic brain swelling 108. SOLER NG. KANTER RK. CRASE J. MUNICHOODAPPA a new case of insulin-dependent diabetes mellitus. 42 Pediatric Diabetes 2007: 8: 28–43 . ketoacidosis. 120. PHILLIPS LS. Am J Med Diab 1989: 6: 212–213. Sick-day management in type 1 diabetes. KHOURY C. STUART MJ. OHMAN JL Jr. Natural history. Cerebral Edema in Childhood Diabetic Ketoacidosis: 106. DUNGER DB. Cerebral oedema in dia. Med 2006: 23: 278–284. 119. DURR JA. 133. MANZANO FM. MARCIN JP. BEGIN R. Diabetic of bicarbonate. ROTHROCK SG. Jr. GALLAGHER A. Prehospital 104. VATS A. YANG MC. 115. CUMMINGS E. agement of diabetic ketoacidosis. bicarbonate infusion in diabetic acidosis. 16–22. WENTZELL K. Sodium bicarbonate therapy in Diabetes 2001: 2: 109–114. CHASE HP. Devastating cerebral edema in diabetic 102. BENNETT MA. ACOTT PD. NELSON MD. Diabetes Care 2002: 132. 1979: 67: 897–900. KOZAK GP. 135. severe diabetic ketoacidosis. Recent trends in hospitalization for diabetic Crit Care Med 2003: 4: 239–242. Sick day management using blood (Letter) 3-hydroxybutyrate (3-OHB) compared with urine 118. 113. FITZGERALD MG. JASPAN JB. BERNSTEIN SS. 121. HARRIS CJ. Diabetes 1974: 23: 127. ASSAL JP. cardiac arrest in diabetic ketoacidemia: why brain YAMASHITA K. 2004: 145: 561–562. MURPHY MB. DANEMAN D. ROSENBLOOM AL. Am J Med 1983: 75: 263– 130. Failure of diabetic ketoacidosis: are we any nearer finding adjunctive bicarbonate to improve outcome in severe a cause? Diabetes Metab Res Rev 2000: 16: 316–324. Ann Emerg Med 1998: 126. ketoacidosis. GROSS M. Diabetes 1992: 41: 627–632. Causes of diabetic ketoacidosis-related cerebral edema. CHECCHIA PA. Bicarbonate therapy for ketoacidosis (DKA). organic acidosis: the case for its continued use. Clin Pediatr (Phila) 1992: 31: MALINS JM. CURTIS JR. SHABBIR N. GLASGOW AM. Pract hypomagnesemia by phosphate therapy. 122. TO T. Metabolic effects of ketoacidosis before therapy. hypertonic saline for the treatment of altered mental 111. GLASER N. and early Metabolic effects of sodium bicarbonate in man. Endocrinol Metab Clin North Am 2000: 29: 707–723. 1980: 96: 968–973. BUREAU MA. associated with adverse outcomes in children with 112. ADROGUE HJ. CROFFIE JM. GABOURY I. betic ketoacidosis in children. fluid in diabetic ketoacidosis. Diabetes Care 2004: 27: 1541–1546. NARINS RG. therapy with potassium phosphate in diabetic ketoa. Med 1986: 105: 836–840. EUGSTER EA. DANE. HO JD et al. WONG GW. OKUDA Y. ROBERTS MD. NOHARA H. KAIRAM R. VLCEK BW. SHAPCOTT D. 117. 77–78 (Letter) BMJ (Clin Res Ed) 1984: 289: 1035–1038. 123. BRINK S. Cerebral 405–411. Diabetes Care 1979: 2: 265–268. EL GAMMAL T. 139. GAGNON N. N Engl J Med 1971: 128. 124. ketoacidosis in a child with previously unknown ment of diabetic ketoacidosis. Fatal cerebral infarctions in diabetic 116. STEINHART CM. 140. HOFFMAN WH. HUFF KR. DEEB L. GILLILAND MG.Wolfsdorf et al. COSTIN G. J Pediatr 2004: 145: 122–124. Brain infarction in D. ketoacidosis with intracerebral complications. 134. MUIR AB. LEVINE LS. EDGE JA. Correlates of brain edema in uncon. BELLO FA. Cerebral hypoxia from Diabetes Care 1978: 1: 285–288. HALE PJ. 31: 41–48. J Pediatr death in children with insulin dependent diabetes 1990– 2002: 141: 793–797. HAWKINS MM. pediatric diabetic ketoacidosis. Intracerebral crises during treat. BOHN D. KAMAT P. 284: 283–290. 114. Pancreatic EDGE JA. Pediatr 109. Bicarbonate cerebral edema in diabetic ketoacidosis. Arch Dis Child 2002: 86: 204–205. EDGE JA.

4th edn. WV. HERROLD AJ. HENDRICKS K. admission rates of children with diabetes mellitus. ORR DP. An approach to 146. review and a new approach. LI J. eds. Consensus Guidelines 140. GREY M. BOLAND EA. FRIEDMAN AL. The maintenance need for SPERLING MA. Assessment of the effect of a compre. DAVIDSON M.. Kidney Int 2005: 67: 380– 141. HOLLIDAY MA. Pediatric Diabetes 2007: 8: 28–43 43 . 2005 142. Pediatr Clin North pediatric population. The physiologic basis for estimating prevention of recurrent diabetic ketoacidosis in the requirements for parenteral fluids. TAMBORLANE 388. DARROW DC. GOLDEN MP. FRESON LS. Hamilton. SEGAR WE. Am 1959: 6: 29–41. 143. Manual of Pediatric mellitus has long-lasting effects on metabolic control Nutrition. DAWSON VA. 144. LONG DJ. and quality of life. Ontario: BC Decker. Pediatric hydration therapy: historical Diabetes Educ 1990: 16: 389–393. Pediatrics 1957: 19: hensive diabetes management program on hospital 823–832. Coping skills training for youth with diabetes 145. J Pediatr 1985: 107: 195–200. water in parenteral fluid therapy. DROZDA DJ. J Pediatr 2000: 137: 107–113. DUGGAN C.