Paediatric Diabetic Ketoacidosis

Author: Richard Freeman, April Donne / Editor: John Scanlon, Richard Freeman / Reviewer: Jon Bailey / Codes: C3AP4, EnC2, EnP2, SLO5Published: 10/06/2021

Context

Fig 1: All unwell children should have their blood sugar checked as part of the initial assessment

Young people with type 1 diabetes mellitus (T1DM) can present with life threatening complications to the emergency department (ED).

Diabetic ketoacidosis (DKA) occurs following an absolute or relative deficit in insulin and has a risk of 1-10% per patient per year [1-7]. Mortality is estimated at 0.15-0.3% [8-10] with 60-90% of deaths related to cerebral oedema 11,12].

DKA can also occur as the initial presentation of diabetes in 15-70% of cases13-21.

During this session we will explore the management of this condition with reference to published evidence and national guidelines

Definition

Diagnosis of DKA is based upon the presence of both biochemical & clinical features[22]:

A) Biochemical criteria[22-25]

  • Hyperglycaemia (blood glucose >11 mmol/L)
  • Acidosis (pH < 7.3 OR bicarbonate <15 mmol/L)
  • Ketosis (blood ketones >3mmol/L or, if blood ketone monitoring is not available, moderate to large ketonuria)

B) Clinical criteria[22]

  • Young person who is more than 3% dehydrated
  • & or vomiting
  • & or drowsy
  • & or clinically acidotic

C) Severity of DKA[22,25-26]

  • Mild
    • pH <7.3 or serum bicarbonate <15mmol/L
    • Assume to be 5% dehydrated
  • Moderate
    • pH <7.2 or serum bicarbonate <10mmol/L
    • Assume to be 7% dehydrated
  • Severe
    • pH <7.1 or serum bicarbonate <5mmol/L
    • Assume to be 10% dehydrated

NB: it is not possible to accurately assess the degree of dehydration (& thus fluid deficit) based upon clinical parameters.

Pathophysiology of DKA

Fig 2: Pathophysiology of DKA [25]

 

Insulin

Consequence of a deliberate or inadvertent failure to take exogenous insulin (known patient) or as part of the initial presentation of T1DM.

Counter-regulatory hormones

Low levels of insulin stimulate the release of glucagon, ACTH, growth hormone, prolactin and catecholamines.

Gluconeogenesis

Amino acids, lactate and glycerol are converted to glucose within the liver and released into the circulation.

Glycogenolysis

Breakdown of glycogen stores within the striated muscle and liver release glucose into the circulation.

Reduced glucose uptake

Despite the presence of high blood glucose, low levels of insulin inhibit uptake by the peripheral tissues, further exacerbating hyperglycaemia.

Lipolysis

Triglycerides within adipose tissue are broken down due to release of free fatty acids. These are subsequently oxidised to form ketone bodies (acetoacetate and β-hydroxybutyrate).

Osmotic diuresis

Plasma glucose concentration increases until it exceeds the reabsorptive capacity of the nephron. At this point, glucose is excreted into the urine along with water and solutes (osmotic diuresis). This leads to significant dehydration and electrolyte imbalance.

Ketoacidosis

As ketone bodies accumulate, the bicarbonate buffering system is overcome resulting in a progressive metabolic acidosis.

Clinical Manifestations

Fig 3: Young people presenting to the ED with DKA will appear unwell

The clinical manifestations of DKA include [25]:

  • Dehydration
  • Kussmaul respiration (deep, rapid, sighing)
  • Nausea and vomiting
  • Abdominal pain (can mimic an acute abdomen)
  • Progressive clouding of consciousness and coma
  • Increased leukocyte count with left shift (does not necessarily indicate sepsis)
  • Non-specific elevation of serum amylase
  • Ketotic breath
  • Increased heart rate

Fever is not a feature of DKA.  Think about sepsis in a child or young person with DKA who has any of the following:

  • fever or hypothermia
  • hypotension
  • refractory acidosis
  • lactic acidosis

Risk Factors

Fig 4: Young people who use insulin pumps to control their diabetes are at greater risk of DKA

The risk factos for DKA include [4,5]:

  • New diagnosis in children of young age
  • Delayed diagnosis
  • Poor diabetic control/previous DKA
  • Peri-pubertal or adolescent girls
  • Patients with psychiatric morbidity (including eating disorders)
  • Patients with unstable family circumstances
  • Patients who omit insulin (deliberate or unintentional)
  • Patients with limited access to medical services
  • Patients who use an insulin pump[1,27]:
    • Such devices only utilise rapid acting insulin (i.e. Novorapid®)
    • Hence, any interruption in supply can lead to rapid ketosis

In this section we will look at the assessment process of young people with DKA.

Fig 5: Components of the clinical assessment and risk stratification process

 

Initial Emergency Assessment

Fig 6: Patients with DKA can be critically ill at presentation and should be managed systematically

Airway, breathing and circulation form part of the initial emergency management of paediatric DKA [22,25]:

Airway

  • Ensure patent
  • Consider adjuncts or definitive airway if indicated
  • Seek anaesthetic support if there are concerns
  • Due to the high risk of aspiration pneumonia an NG tube should be seriously considered in the following situations:
    • a child with reduced level of consciousness
    • and/or recurrent vomiting
    • & or recent consumption of a large volume of fruit juice or high sugar drinks[28-29]

Breathing

  • Give 100% oxygen by non re-breathe mask

Circulation

  • Obtain IV access
    • Ideally 2 points of access
    • Avoid central access due to increased risk of thrombus
  • Attach patient to a cardiac monitor[30,31]
    • Perform a 12 lead ECG, and evaluate for T wave changes, and assess for signs of shock
  • All patients should be given fluid replacement and this should occur before insulin/immediately. The amount of fluid is dependant on if they are shocked:
    • Shocked patients (heart rate, capillary refill time):
      • 20ml/kg of 0.9% (normal) saline over 15 minutes
      • If required, further 10ml/kg boluses up to a maximum of 40ml/kg at which point inotropes should be considered
      • Boluses for shocked patients should not be subtracted from the fluid deficit
    • Non-shocked patients
      • 10ml/kg bolus of 0.9% (normal) saline over 60 minutes
      • Do not give more than 10ml/kg without decision with the responsible consultant
      • Boluses for non-shocked patients should be subtracted from the fluid deficit
Fig 7: Resuscitation fluid

Confirm the diagnosis

Table1: Symptoms, signs & biochemical features of DKA

Initial investigations

  • Blood glucose
  • Laboratory U&Es, Osmolality, FBC, CRP, Albumin, Calcium, Phosphate and Magnesium
  • Venous blood gas
    • pH and PC02 are comparable to arterial samples
    • Blood gas electrolytes are useful in guiding early fluid management before laboratory results are available
  • Blood ketones
    • Near patient test similar to bedside glucose meters
    • Superior to urinary ketones as:
      • Rapid result
      • Quantitative rather than qualitative (mmol/L)
  • ECG

NB: Other investigations should only be performed if indicated (i.e. septic screen in patients who are febrile, CXR etc.)

Fig.8

 

 

 

 

 

 

 

Full clinical assessment

1) Assessment of conscious level

  • Assessed using the Glasgow Coma Score[32]
  • If the child is comatose or has a reduced conscious level:
    • Consider transfer to PICU/HDU if available
    • Consider treatment for raised intracranial pressure (if clinical suspicion)
    • Seek anaesthetic and senior paediatric support

Table2: Components of the Glasgow Coma Score (older children and adults)

2) Full physical examination

  • The presence of the following should be excluded:
    • Cerebral oedema
    • Infection
    • Ileus

3) Weigh the child

  • If not possible due to the child’s clinical condition:
    • Most recent clinic weight
    • Estimated weight from centile charts

Observations & monitoring

  • Hourly
    • Neurological & basic observations
      • NB: Half-hourly neurological observations should be employed in children under 2 years &/or those with severe DKA (increased risk of cerebral oedema)
    • Strict fluid balance
    • Capillary blood glucose & ketones
      • Urine ketones can be used if blood testing not available
  • Medical review, venous blood gases, U&Es & glucose
    • Check 2 hours after management commenced
    • Then at least 4 hourly
  • Medical staff should be informed immediately if:
    • Headache, change in CGS or behaviour
    • Slowing of pulse, changes in the ECG trace (especially T wave changes)
 
Fig 9: Young people with DKA should be monitored regularly during their treatment  

Introduction

Fig 10: The trinity of managing paediatric DKA: intravenous fluids, potassium and insulin

The management of DKA is largely dependant upon three factors:

1. Intravenous fluid therapy:

  • Volume of fluid required
  • Type of fluid required

2. Potassium

3. Insulin:

  • Intravenous
  • Subcutaneous

 

Volume of fluid required

The volume of fluid needed depends upon the following factors[22,25]:

1) Resuscitation fluid

  • Shocked patients (↑heart rate, ↑capillary refill time):
    • 20ml/kg of 0.9% (normal) saline over 15 minutes
    • If required, further 10ml/kg boluses up to a maximum of 40ml/kg at which point inotropes should be considered
    • Boluses for shocked patients should not be subtracted from the fluid deficit
  • Non-shocked patients
    • 10ml/kg bolus of 0.9% (normal) saline over 60 minutes
    • Do not give more than 10ml/kg without decision with the responsible consultant
    • Boluses for non-shocked patients should be subtracted from the fluid deficit

2) Fluid deficit

  • Deficit (ml) = % dehydration X weight (kg) X 10
    • Assume 5% dehydration in mild DKA (pH<7.3 or serum bicarbonate <15mmol/L)
    • Assume 7% dehydration in moderate DKA (pH<7.2 or serum bicarbonate <10mmol/L)
    • Assume 10% dehydration in severe DKA (pH<7.1 or serum bicarbonate <5mmol/L)

3) Maintenance fluid

    • Calculations are based upon body weight using the Holliday-Segar formula:
1st 10kg = 100ml/kg/day
Plus 50ml/kg/day for next 10kg
Plus 20ml/kg/day for each additional kg above 20kg
(up to a maximum of 80kg total body weight)
  • For DKA fluid calculations this volume needs be doubled as correction occurs over 48 hours[23,33-34]
  • APLS maintenance fluid calculations over-estimate requirement (particularly at younger ages) & should NOT be used

4) Fluid calculation

Hourly rate = (Deficit/48 hours) + maintenance per hour
  • Correction should occur over 48 hours[23,33-34]
  • Care should be taken when calculating fluid requirement & this should be documented in the patient’s notes
  • Do not give additional fluid to replace urinary losses
  • Greater volumes of fluid given within the first 4 hours have been shown to increase the risk of cerebral oedema[35]
  • BSPED have an online DKA fluid calculator[36]
Fig.11: Fluid requirement

Example

What is the fluid requirement for a 20kg boy who has a pH of 7.15 who is not clinically shocked?

Answer

Fluid bolus= 10ml x 20kg = 200ml
Deficit percentage= 7%
Deficit volume= 7% x 20kg x 10 = 1400ml
Deficit volume minus bolus volume = 1400ml – 200ml = 1200ml
Deficit replacement rate = 1200ml ÷48 hours = 25ml/hour
Daily maintenance volume (using Holliday-Segar formula) = 1500ml
Maintenance rate = 1500ml ÷ 24 = 62.5ml/hour
Starting fluid rate = deficit replacement rate + maintenance rate = 87.5ml/hour
Insulin infusion rate = 0.05 units/kg/hour x 20kg = 1.0 units/hour

 

Fig.12: Intravenous fluid volumes should be calculated carefully & documented in the patient’s notes

 

Type of fluid required

  • Resusitation fluid
    • 0.9% saline
    • There is no evidence to support the use of colloids or volume expanders in preference to crystalloids
    • There is evidence that rapid reduction in plasma osmolality increase risk of cerebral oedema[33] & hence, 0.45% saline should NOT be used in initial therapy
  • Initial intravenous therapy
    • 0.9% saline with 20mmol potassium in 500ml now continues throughout treatment
    • When blood sugar is less than 14mmol/L OR if it drops more than 5mmol/L/hour glucose is added

NB: the insulin infusion is also adjusted (see next section)

  • When blood sugar <14 MMOL/L
    • 0.9% saline & 5% glucose with 20mmol KCl in 500ml
  • If blood sugar <6MMOL/L
    • 0.9% saline & 10% glucose with 20mmol KCl in 500ml
      • Do not stop the insulin infusion
  • If blood sugar <4MMOL/L
    • Give a 2ml/kg bolus of 10% glucose
    • Temporarily pause the insulin infusion for 1 hour.

NB: greater ketosis indicates a need for more insulin hence, higher concentrations of glucose are required to prevent hypoglycaemia

Fig.13: Insulin and glucose requirements

 

Potassium

The average child in DKA is depleted in total body potassium irrespective of plasma level[37]

  • Average losses are 3-6mmol/kg[38-42]
  • i.e. our 20ml/kg boy in the previous example will be deficient by around 100mmol!

In addition, once insulin is started potassium will be driven into the intracellular compartment & plasma levels with decline rapidly[39]

ECG changes & cardiac arrhythmias can occur with hypokalaemia

  • Therefore (unless the child is anuric):
    • Always ensure every 500ml bag contains 20mmol potassium (40mmol/L)
    • Check electrolytes 2 hours after the start of fluid management & then at least 4 hourly
    • Use a cardiac monitor to detect T wave changes
    • If K<3mmol/L discuss with critical care as central access will be required for higher concentration replacement

Learning bite:

Potassium should be added to fluid regardless of serum level unless the patient is anuric.

 

Insulin

Insulin is required to normalise blood glucose & suppress ketogenesis

A continuous low dose IV infusion should be used

  • 50 units of Actrapid® in 50ml of 0.9% saline (1unit/ml solution)
  • Commence at EITHER 0.05 or 0.1 units/kg/hour
  • There is no evidence that one dose is superior to the other. 0.05 units/kg/hour should be sufficient in most cases. 0.1 units/kg/hour may be required in severe cases.

Do NOT add insulin directly to the fluid bags and do NOT give an insulin bolus

There is evidence that insulin given within the first hour of treatment increases the risk of cerebral oedema[35, 43-44]

Therefore, do NOT start insulin until intravenous fluids have been running for at least an hour[35]

  • Long acting insulin (i.e. Lantus®)
    • For patients with previously known diagnosis of diabetes, long acting insulin may be given subcutaneously at the normal dose & time during DKA treatment
    • For patients with first presentation of diabetes consider starting long acting insulin alongside DKA treatment
    • Check local policy for further information
  • Patients who use an insulin pump
    • The device should be turned off when starting DKA treatmentFig.14: A continuous Insulin infusion should be maintained during acute treatment

 

Other Considerations

Bicarbonate[45-52]

  • There is evidence that when used in DKA the risk of cerebral oedema is increased
  • Do not given IV sodium bicarbonate to young people with DKA

Phosphate

  • Intracellular ion that is depleted during DKA (~0.5-2.5mmol/kg) [38-40,53]
  • There is no evidence that correction improves outcome & in fact may result in hypocalcaemia[54-59]

Risk of venous thrombosis[22,25]

  • Be aware there is significant risk of DVT in patients who have a femoral venous line in situ

 

When to Convert to SC Insulin

Fig 15: Continue intravenous therapy until the child is well and eating and drinking without ketoacidosis
  • Continue IV therapy until:
    • pH normal or blood ketones <1.0mmol/L
    • Urinary ketones may still be positive60-61
    • Clinically well
    • Eating & drinking
  • First give SC insulin (usual regimen of basal and bolus)
    • At least 30 minutes before stopping the infusion
    • 60 minutes if on an insulin pumps
  • Then stop insulin infusion
    • The aim is to avoid rebound hyperglycaemia

On-going home management & follow-up should be discussed with the young person’s Consultant or Diabetic Specialist Nurse.

Pitfalls

Non-resolution of acidosis and ketosis

Table 3: Causes of persistent acidosis and ketosis in young people with DKA
Acidosis not improving Ketosis not improving
Insufficient insulin or drug error? Check infusion lines
Inadequate resuscitation? Insufficient insulin prescribed?
Underlying sepsis? Incorrect preparation of insulin infusion?
Hyperchloraemic acidosis? (related to excessive use of chloride containing fluids) Inadequate fluid input?
Recreational or prescription drugs? Underlying sepsis?

Cerebral oedema

Fig 16: Cerebral oedema is a potentially life-threatening complication of DKA in young people

Cerebral oedema has high mortality and morbidity[11-12,58] Late signs are associated with extremely poor prognosis. Senior staff must be informed immediately if suspected. Discuss with PICU consultant & arrange urgent transfer. Immediate management of cerebral oedema involves the following[22]:

  • Exclude hypoglycaemia
  • Give hypertonic (2.7%) saline or mannitol urgently
  • Adjust IV fluids Reduce to 1/2 maintenance
  • Do not intubate and ventilate until an experienced doctor is available
  • Once stable a CT scan should be conducted to exclude other intra-cerebral events (thrombosis, haemorrhage or infarction) that have a similar presentation
Table 4
Warning signs[22,25] Risk factors[25]
Headache Younger age[63]
Change in neurological status (reduction in GCS, change in restlessness, irritability or incontinence) Initial presentation of T1DM[9,63]
Focal neurological signs (i.e. cranial nerve palsies) Longer duration of symptoms[64]
Relative bradycardia & hypertension (Cushing’s reflex) Greater volumes of fluid within the first 4 hours of treatment[33,65-66]
Reduced oxygen saturations Insulin infusion started within the first hour of treatment[33]
Abnormal posturing Use of bicarbonate during treatment[11,67]
Oculomotor palsies, pupillary inequality or dilatation Greater hypocapnia at presentation[11,65,68]
Late signs: convulsions, coma, papilloedema, respiratory arrest Increased serum nitrogen at presentation[11,68]
  More severe acidosis at presentation[33,66,69]

Accurate documentation

Fig 17: Accurate documentation is required in the management of all critically ill patientsAs with all critically ill patients ensure notes are:

As with all critically ill patients ensure notes are:

  • Timed (24 hour clock) & dated
  • Legible, accurate, sufficiently detailed & contemporaneous as possible
  • Completed with the clinician’s name, designation & signature
  • Complete with regards to discussions with senior colleagues & that the advice given is clearly documented

Key Learning Points

  • The risk of DKA in established T1DM is 1-10% per patient per year (A, C)
  • Risk factors include children who omit insulin and those on insulin pump therapy (C)
  • Children with severe DKA or those at increased risk of cerebral oedema should be considered for treatment in an intensive care setting (C)
  • All children with DKA should receive a fluid bolus, the volume of which should be based on whether they are clinically shocked (E)
  • Water and salt deficits should be replaced (A) over 48 hours (C) with crystalloid rather than colloid (E)
  • Insulin is required to normalise blood glucose & suppress ketogenesis (A). An IV infusion (A) should be started at least 1 hour after starting fluid replacement therapy (C, E)
  • Potassium replacement therapy should be commenced regardless of serum concentration (A) at a concentration of 40mmol/L (i.e. 20mmol in 500ml)(E)
  • There is no clinical benefit in routine bicarbonate (B, C) or phosphate (A) replacement
  • Risk factors for cerebral oedema include young age, new onset T1DM, longer duration of symptoms, severe acidosis & bicarbonate correction (C)
  • Suspected cerebral oedema should be treated with hypertonic saline (C) or mannitol (C, E)
  1. Hanas R, Lindgren F, Lindblad B. A 2-yr national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use. Pediatr Diabetes. 2009;10(1):33-37.
  2. Rosilio M, Cotton JB, Wieliczko MC, et al.Factors associated with glycemic control. A cross-sectional nationwide study in 2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group. Diabetes Care. 1998;21(7):1146-1153.
  3. Smith CP, Firth D, Bennett S, et al.Ketoacidosis occurring in newly diagnosed and established diabetic children. ActaPaediatr. 1998;87(5):537-541.
  4. Morris AD, Boyle DI, McMahon AD, et al., Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland Medicines Monitoring Unit. Lancet. 1997;350(9090):1505-1510.
  5. Rewers A, Chase HP, Mackenzie T, et al., Predictors of acute complications in children with type 1 diabetes. JAMA. 2002;287(19):2511-2518.
  6. Cengiz E, Xing D, Wong JC, et al.Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D exchange clinic registry. Pediatr Diabetes. 2013;14(6):447-454.
  7. Maahs DM, Hermann JM, Holman N, et al.Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. Diabetes Care. 2015;38(10):1876-1882.
  8. Curtis JR, To T, Muirhead S, et al., Recent trends in hospitalization for diabetic ketoacidosis in Ontario children. Diabetes Care. 2002;25(9):1591-1596.
  9. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child. 1999;81(4):318-323.
  10. Decourcey DD, Steil GM, Wypij D, et al.Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality. Pediatr Crit Care Med. 2013;14(7):694-700.
  11. Glaser N, Barnett P, McCaslin I, et al., Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001;344(4):264-269
  12. Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child. 2001;85(1):16-22.
  13. Dabelea D, Rewers A, Stafford JM, et al.Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014;133(4):e938-e945.
  14. Levy-Marchal C, Papoz L, de Beaufort C, et al., Clinical and laboratory features of type 1 diabetic children at the time of diagnosis. Diabet Med. 1992;9(3):279-284.
  15. Komulainen J, Lounamaa R, Knip M, et al. Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group. Arch Dis Child. 1996;75(5):410-415.
  16. Levy-Marchal C, Patterson CC, Green A. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Dibetes. Diabetologia. 2001;44((suppl 3)): B75-B80.
  17. Hanas R, Lindgren F, Lindblad B. Diabetic ketoacidosis and cerebral oedema in Sweden – a 2-year paediatric population study. Diabet Med. 2007;24(10):1080-1085.
  18. Rodacki M, Pereira JR, Nabuco de Oliveira AM, et al., Ethnicity and young age influence the frequency of diabetic ketoacidosis at the onset of type 1 diabetes. Diabetes Res Clin Pract. 2007;78(2): 259-262.
  19. Usher-Smith JA, Thompson M, Ercole A, et al., Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia. 2012;55(11):2878-2894.
  20. Fritsch M, Schober E, Rami-Merhar B, et al., Diabetic ketoacidosis at diagnosis in Austrian children: a population-based analysis, 1989-2011. J Pediatr. 2013;163: 1484-8.e1.
  21. Zucchini S, Scaramuzza AE, Bonfanti R, et al.A multicenter retrospective survey regarding diabetic ketoacidosis management in Italian children with type 1 diabetes. J Diabetes Res. 2016;2016:5719470.
  22. BSPED Interim Guideline for the Management of Children and Young People under the age of 18 years with Diabetic Ketoacidosis. British Society of Paediatric Endocrinology and Diabetes. [Accessed 7th April 2021].
  23. Dunger DB, Sperling MA, Acerini CL, et al., ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child. 2004;89(2):188-194.
  24. Sheikh-Ali M, Karon BS, Basu A, et al., Can serum beta-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care. 2008;31(4):643-647.
  25. Wolfsdorf JI, Glaser N, Agus M, et al.ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatric Diabetes. 2018;19:155-177.
  26. Chase HP, Garg SK, Jelley DH. Diabetic ketoacidosis in children and the role of outpatient management. Pediatr Rev. 1990;11(10): 297-304.
  27. Cope JU, Morrison AE, Samuels-Reid J. Adolescent use of insulin and patient-controlled analgesia pump technology: a 10-year Food and Drug Administration retrospective study of adverse events. Pediatrics. 2008;121(5):e1133-e1138.
  28. Carlotti AP, St George-Hyslop C, Guerguerian AM, et al., Occult risk factor for the development of cerebral edema in children with diabetic ketoacidosis: possible role for stomach emptying. Pediatr Diabetes. 2009;10(8):522-533.
  29. Davids MR, Edoute Y, Stock S, et al.Severe degree of hyperglycaemia: insights from integrative physiology. QJM. 2002;95(2): 113-124.
  30. Malone JI, Brodsky SJ. The value of electrocardiogram monitoring in diabetic ketoacidosis. Diabetes Care. 1980;3(4):543-547.
  31. Soler NG, Bennett MA, Fitzgerald MG, et al., Electrocardiogram as a guide to potassium replacement in diabetic ketoacidosis. Diabetes. 1974;23(7):610-615.
  32. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet1974;2(7872):81-4.
  33. Harris GD, Fiordalisi I. Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in 231 episodes. Arch Pediatr Adolesc Med. 1994;148(10):1046-1052.
  34. Fiordalisi I, Novotny WE, Holbert D, et al., An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment. Pediatr Diabetes. 2007;8(3):142-149.
  35. Edge JA, Jakes RW, Roy Y, et al., The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia. 2006;49(9):2002-2009.
  36. Leach, D. and Barton, J. 2021. Paediatric DKA Protocol Generator. [Accessed 7 April 2021].
  37. Tattersall RB. A paper which changed clinical practice (slowly). Jacob Holler on potassium deficiency in diabetic acidosis (1946). Diabet Med 1999;16(12):978–84.
  38. Atchley D, Loeb R, Richards D Jr, Benedict E, et al., On diabetic ketoacidosis: a detailed study of electrolyte balances following the withdrawal and reestablishment of insulin therapy. J Clin Invest. 1933;12:297-326.
  39. Nabarro J, Spencer A, Stowers J. Metabolic studies in severe diabetic ketosis. Q J Med. 1952;82:225-248.
  40. Butler A, Talbot N, Burnett C, et al. Metabolic studies in diabetic coma. Trans Assoc Am Phys. 1947;60:102-109.
  41. Danowski T, Peters J, Rathbun J, et al., Studies in diabetic acidosis and coma, with particular emphasis on the retention of administered potassium. J Clin Invest. 1949;28:1-9.
  42. Darrow D, Pratt E. Retention of water and electrolyte during recovery in a patient with diabetic acidosis. J Pediatr. 1952;41:688-696.
  43. Hoorn EJ, Carlotti AP, Costa LA, et al.Preventing a drop in effective plasma osmolality to minimize the likelihood of cerebral edema during treatment of children with diabetic ketoacidosis. J Pediatr. 2007; 150(5):467-473.
  44. Van der Meulen JA, Klip A, Grinstein S. Possible mechanism for cerebral oedema in diabetic ketoacidosis. Lancet. 1987;2(8554):306-308.
  45. Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis. Br Med J (Clin Res Ed). 1984; 289(6451):1035-1038.
  46. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med. 1986;105(6):836-840.
  47. Okuda Y, Adrogue HJ, Field JB, et al., Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab. 1996;81(1):314-320.
  48. Green SM, Rothrock SG, Ho JD, et al., Failure of adjunctive bicarbonate to improve outcome in severe pediatric diabetic ketoacidosis. Ann Emerg Med. 1998;31(1):41-48.
  49. Assal JP, Aoki TT, Manzano FM, et al., Metabolic effects of sodium bicarbonate in management of diabetic ketoacidosis. Diabetes. 1974;23(5):405-411.
  50. Ohman JL Jr, Marliss EB, Aoki TT, et al., The cerebrospinal fluid in diabetic ketoacidosis. N Engl J Med. 1971;284(6):283-290.
  51. Soler NG, Bennett MA, Dixon K, et al. Potassium balance during treatment of diabetic ketoacidosis with special reference to the use of bicarbonate. Lancet. 1972;2(7779):665-667.
  52. Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med. 1983;75(2):263-268.
  53. Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in patients with diabetes mellitus. N Engl J Med. 2015;373(6):548-559.
  54. Gibby OM, Veale KE, Hayes TM, et al., Oxygen availability from the blood and the effect of phosphate replacement on erythrocyte 2,3-diphosphoglycerate and haemoglobin-oxygen affinity in diabetic ketoacidosis. Diabetologia. 1978;15(5):381-385.
  55. Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion during treatment of diabetic ketoacidosis and hyperosmolar coma. Diabetes. 1980;29(2):87-95.
  56. Wilson HK, Keuer SP, Lea AS, et al., Phosphate therapy in diabetic ketoacidosis. Arch Intern Med. 1982;142(3): 517-520.
  57. Becker DJ, Brown DR, Steranka BH, et al. Phosphate replacement during treatment of diabetic ketosis. Effects on calcium and phosphorus homeostasis. Am J Dis Child. 1983;137(3):241-246.
  58. Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab. 1983; 57(1):177-180.
  59. Clerbaux T, Reynaert M, Willems E, et al., Effect of phosphate on oxygen-hemoglobin affinity, diphosphoglycerate and blood gases during recovery from diabetic ketoacidosis. Intensive Care Med. 1989;15(8):495-498.
  60. Vanelli M, Chiari G, Capuano C, et al., The direct measurement of 3-beta-hydroxy butyrate enhances the management of diabetic ketoacidosis in children and reduces time and costs of treatment. Diabetes Nutr Metab. 2003;16(5–6):312-316.
  61. Noyes KJ, Crofton P, Bath LE, et al.Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children. Pediatr Diabetes. 2007;8(3):150-156.
  62. Lawrence SE, Cummings EA, Gaboury I, et al., Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr. 2005;146(5): 688-692.
  63. Rosenbloom AL. Intracerebral crises during treatment of diabeticketoacidosis. Diabetes Care. 1990;13(1):22-33.
  64. Bello FA, Sotos JF. Cerebral oedema in diabetic ketoacidosis in children [letter]. Lancet. 1990;336(8706):64.
  65. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developingbrain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999;21(4):721-727.
  66. Durward A, Ferguson LP, Taylor D, et al., The temporal relationship between glucose-corrected serum sodium and neurological status in severe diabetic ketoacidosis. Arch Dis Child.2011;96:50-57.
  67. Bureau MA, Begin R, Berthiaume Y, et al., Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. J Pediatr. 1980;96(6):968-973.
  68. Glaser NS, Marcin JP, Wootton-Gorges SL, et al.Correlation of clinical and biochemical findings with diabetic ketoacidosis-related cerebral edema in children using magnetic resonance diffusion-weighted imaging. J Pediatr. 2008;153(4):541-546.
  69. Durr JA, Hoffman WH, Sklar AH, et al., Correlates of brain edema in uncontrolled IDDM. Diabetes. 1992;41(5):627-632.

Further reading:

6 Comments

  1. Dr Muhammad Yaseen says:

    Absolutely amazing, a difficult topic made easy. Thanks.

  2. Rashid says:

    Brilliant review of the new guidelines. Thank you.

  3. Obosa Iyamu says:

    Excellent way to revise

  4. Anil Medagam says:

    Useful information

  5. Dr. Yusuf Dala Gali says:

    Excellent up date.

  6. Dr Aravinth Kumar Kumarasamy says:

    Excellent module.

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