Diabetic Ketoacidosis (DKA) Title of Guideline (must include the word Guideline (not protocol, policy, procedure etc) Contact Name and Job Title (author) Directorate & Speciality Date of submission February Date when guideline reviewed February 2020 Guideline Number 1935 Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis) Abstract Key Words Guideline for the management of Diabetic Ketoacidosis in Children and Young People Dr Tabitha Randell, Consultant in Paediatric Endocrinology and Diabetes Anis Mohd Fozi, ST3 in Paediatrics Directorate: Family Health Children Speciality: Endocrinology Children and young people with diabetes aged 18 and under admitted with diabetic ketoacidosis This guideline describes the assessment and management of children and young people with diabetes who are admitted with diabetic ketoacidosis Paediatrics. Children. (Plus any others you want) diabetes, diabetes ketoacidosis, DKA, Statement of the evidence base of the guideline has the guideline been peer reviewed by colleagues? meta analysis of randomised controlled Put a cross (X) in the highest level of evidence. 1a trials 2a at least one well-designed controlled study without randomisation 2b at least one other type of well-designed quasi-experimental study 3 well designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practise based on the clinical experience of the guideline developer Consultation Process Updated in line with NICE Guidance 2015 and BSPED National Guideline 2015 Reviewed initially by paediatric diabetes team then by Nottingham emergency department, children s Staff at Nottingham Children s Hospital via the Guidelines E-mail process. Staff at the Nottingham Children s Hospital Target audience This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.
Document Control Document Amendment Record Version Issue Date Author V1 May 2010 Dr T Randell V2 Aug 2013 Dr T Randell V3 Sept 2015 Dr T Randell V4 Feb Dr T Randell General Notes: Summary of changes for new version: Updated in line with NICE Guidance 2015 and BSPED National Guideline 2015: 1. Change in the degree of dehydration to be used to calculate fluids; 5% for mild to moderate DKA and 10% for severe DKA, based on ph 2. De-emphasise sodium chloride bolus at the start of treatment apart from the sickest children 3. No more than one 10ml/kg fluid bolus to be given without discussion with a senior doctor 4. Further reduction in maintenance fluid rates, and simpler calculation of fluid rates 5. No longer to subtract any boluses given up to 20 ml/kg from the fluid calculation (as the rate is already reduced significantly from previous guidelines) 6. Continuation of 0.9% sodium chloride (instead of changing to 0.45% sodium chloride) for the full duration of rehydration 7. Option for using an intravenous insulin infusion rate of 0.05 Units//kg/hour OR 0.1 Units/kg/hour Statement of Compliance with Child Health Guidelines SOP This guideline has had only minor changes made and therefore this version has not been circulated to all for review. A previous version had been approved by circulation to senior team members. Martin Hewitt Clinical Guideline Lead 09 February
Diabetic Ketoacidosis (DKA) Definition It is severe uncontrolled diabetes with ketosis, requiring emergency treatment with intravenous fluids and insulin. The following must be present: ph < 7.3 or Bicarbonate <15 + Glucose >11 mmol/l + Evidence of ketones ( ketones >3 or large urine ketones) If ph is greater than 7.3, please refer to alternative protocols for well, newly diagnosed diabetics or sick day rules as appropriate. Incidence Young children and infants are more likely to have delayed recognition and greater metabolic decompensation. Diabetic ketoacidosis is becoming less frequent among children with established diabetes as community care and liaison services improve. Mortality Fortunately this is low among children and adolescents (less than 1%). Recognised causes include cerebral oedema; hypokalaemia induced cardiac dysrhythmias and aspiration pneumonia. Mechanisms of Ketoacidosis 1) Relative insulin deficiency 2) Excess stress hormones 3) Fasting 4) Dehydration Both hyperglycaemia (causing osmotic diuresis) and ketosis (causing vomiting) provoke fluid and electrolyte depletion and reduced circulating volume. The resultant fall in renal perfusion leads to accumulation of glucose and hydrogen ions. IF A CHILD OR YOUNG PERSON UNDER 18 PRESENTS TO THE EMERGENCYDEPARTMENT WITH SUSPECTED DIABETIC KETOACIDOSIS YOU MUST CONTACT THE PAEDIATRIC REGISTRAR ON CALL IMMEDIATELY AND MANAGE THE CHILD IN THE EMERGENCY DEPARTMENT The initial management of children and young people in DKA is very different from adults because of the risk of cerebral oedema. Patients with any of the following features will need immediate discussion with the paediatric consultant on call. ph < 7.1 any child ph<7.25 and under 2 years of age Blood glucose > 40mmol/l Potassium <2.5mmol/l Sodium >150mmol/l Shock requiring >20ml/kg fluid Deteriorating clinical state Worsening hyponatraemia Suspicion of cerebral oedema Remember that there is always a shop floor consultant in the Emergency Department available for consultation and a consultant on-call for paediatric endocrinology 24 hours a day contactable through switchboard, as well.
Section A General Management o o Airway, Breathing, Circulation Confirm diagnosis o characteristic history polydipsia, polyuria o biochemistry ketones, glucose, ph o clinical assessment full examination o severity of dehydration o evidence of acidosis hyperventilation o assessment of conscious level o Admit to a paediatric ward: CAU/E37/D33 or HDU (or paediatric intensive care unit if child very unwell). o Consider high flow oxygen esp. if conscious level impaired or in shock. o WEIGH! (Compare to recent clinic weights). Repeat weight 12 hourly until stable if practical. o Identify provoking factors, e.g. sepsis. Leucocytosis is common in DKA and does not necessarily indicate sepsis. However fever is not part of DKA. o Initial Investigations: All Cases Glucose HbA1c U+E s Venous gas, Blood ketones FBC LFT Newly diagnosed GAD, IA2, ZnT8 antibodies XTFT Coeliac screen o Commence IV infusion via a good size cannula with sodium chloride 0.9% and document fluids meticulously. (see Section B- Principles for Fluid Management. Page 6) Continue basal subcutaneous insulin if pre-existing diabetes o Avoid oral fluids for first 8-12 hours (until ph >7.3) and consider nasogastric tube and gastric suction if vomiting or semiconscious. o Connect ECG: monitor lead II for potassium related T wave changes. o Accurate data collection on DKA prescription charts (ensure continuity from ED to ward): Clinical status (including Glasgow Coma Scale). GCS should be recorded whether or not the child is drowsy on admission and should be rechecked hourly until ph more than 7.3. Strict fluid balance including the fluid given in emergency department. Hourly pressure and basic observations including ECG monitoring for T wave changes related to deranged potassium level Biochemical status monitor:
Time from start of treatment 0hr +0.5hr +1hr +1.5hr +2hr +6hr UE, Venous gas Capillary glucose and ketones Capillary glucose Capillary glucose and ketones Capillary glucose * UE, gas, capillary glucose and ketones **UE, gas IF BLOOD KETONES ARE IMPROVING BUT ph IS NOT, CONSIDER OTHER CAUSES FOR ACIDOSIS AND DISCUSS WITH PAEDIATRIC ENDOCRINOLOGIST ON CALL. REPORT IMMEDIATELY TO THE MEDICAL STAFF ANY SYMPTOMS OF HEADACHE, BRADYCARDIA, CHANGE IN BEHAVIOUR OR CONSCIOUS LEVEL
Section B Principles of Fluid Management DO NOT USE PLASMALYTE FOR FLUIDS IN DIABETIC KETOACIDOSIS Bolus rules: 1. Do not routinely give intravenous fluid bolus to children with DKA. 2. Do not give more than 10ml/kg 0.9% sodium chloride without discussion with PICU Consultant or Paediatric Endocrine Consultant on call. Step 1: Estimating volume fluid deficit: Severity of DKA Indicator Fluid deficit Mild to moderate ph 7.1 or above 5% Severe ph below 7.1 10% Step 2: Calculate the maintenance fluid requirement using the following 'reduced volume' rules: Weight <10kg 10-40kg >40kg Fluid rate 2ml/kg/hour 1ml/kg/hr 40ml/hr (fixed rate, not per kg) Calculate total volume requirement and plan to replace deficit over 48 hours. Continuing losses-replaced only if urine output or vomiting is excessive (discuss with paediatric endocrine consultant on call) Step 3: Subtract: If more than 20 ml/kg of fluid has been given, subtract any additional bolus volumes from the total fluid calculation for the 48-hour period.
Example 1: A 20 kg 6 year old boy who is 5% dehydrated and has not received any fluid bolus: Component for Calculation Total (ml) 48 hrs Deficit 5%deficit) x 20(Kg) x 10 = 1000 ml 1000 Maintenance 480ml for each 24hrs 960 Continued Losses If necessary Subtract additional fluid bolus after 20ml/kg No bolus given - replacement TOTAL for 48 Hrs 1960 Infuse at 40.8ml/hr Example 2: A 20 kg 6 year old boy who is 10% dehydrated and has already received 30 ml/kg of 0.9% sodium chloride will require: Component for Calculation Total (ml) 48 hrs Deficit 10(%deficit) x 20(Kg) x 10 = 2000 ml 2000 Maintenance 480ml for each 24hrs 960 Continued Losses If necessary Subtract additional fluid bolus after 20ml/kg 10 x 20 = 200-200 replacement TOTAL for 48 Hrs 2760 Infuse at 57.5ml/hr NB-Fluid calculations must be written in the notes and checked by 2 doctors to avoid mistakes. Online DKA Fluid Calculator can be found through Google search DKA Calculator BSPED Strategy for Fluid Replacement 1. Re-expand circulating volume urgently (0-1 hour) only if shocked 10ml / kg of sodium chloride 0.9% 0.9% saline is usually appropriate although the majority of it transfers to the interstitial space. 10ml/kg can be repeated up to three times if clinical status dictates. (Consider central venous pressure measurement in those children who fail to respond). 2. Early rehydration (See management plan on Page 6) Continue sodium chloride 0.9% and KCL If glucose is <14 mmol/l then the child may well still be sodium depleted. Add glucose to 0.9% saline to increase the amount of glucose infused, initially to 5% glucose equivalent. If glucose is less than 6mmol/l make up to a 10% equivalent solution and if <4, treat with IV 10% glucose bolus 2ml/kg. If there is uncertainty about the appropriate fluid to use, please contact a senior colleague or the on-call endocrine consultant
2. Intermediate / late rehydration Continue 0.9% saline, 5% or 10% glucose (according to glucose levels) and KCL until patient metabolically stable and able to recommence full oral fluid intake. Initial oral intake is given as sips of water or ice to suck, once ph >7.3. Only change to subcutaneous insulin once ketone levels are below 1.0 mmol/l.
Plasma Sodium The observed plasma sodium is usually low at presentation. In addition to actual deficit due to vomiting and polyuria, there is depression caused by: a) Lipaemia b) Hyperglycaemia (an arbitrary calculation allows for a 1 mmol fall in sodium for each 3.5 mmol glucose excess over 5 mmol/l) c) Transfer of free water from intracellular space. A normal or elevated sodium level at presentation is indicative of osmotic decompensation. There is still a total body water and sodium deficit, but there has been a relatively greater loss of water than sodium. An initially low plasma sodium should rise during management to partially compensate for the fall in osmolality accompanying correction of hyperglycaemia (and uraemia). d) If the child is severely dehydrated and in a hypernatraemic / hyperosmolar state, plasma sodium should be reduced very slowly and admit to PICU. Plasma Potassium Once the child has been resuscitated, KCl should be added to infusion immediately unless anuria is suspected. Potassium is an intracellular ion. There is always depletion of total body potassium in DKA, although initial plasma levels may be normal or high. Insulin will push potassium back into the cells with the risk of hypokalaemia once the infusion has started. Use bags with 20 mmol KCl added to every 500 ml of fluid (i.e. 40mmol/L). Check U&Es 2 hours after resuscitation has begun and then at least 4 hourly and adjust potassium replacement accordingly. Plasma Potassium (mmol/l) Potassium Chloride Concentration Under 3 May need > 20mmol in 500ml bag (consider HDU admission for higher KCl Infusion) 3 6 20mmol in 500ml bag Over 6.0 10mmol in 500ml bag and repeat plasma levels in 2hrs. DISCUSS WITH PAEDIATRIC ENDOCRINOLOGIST ON-CALL Observe the ECG monitor for changes (such as low voltage T waves, U waves and a prolonged QT interval) in addition to regularly checking plasma potassium. Bicarbonate This is rarely if ever necessary. Continuing acidosis usually means insufficient resuscitation or insufficient insulin. It can also be iatrogenic due to hyperchloraemic acidosis caused by excess 0.9% saline. This should only be considered in children who are profoundly acidotic (ph<6.9) and shocked with circulatory failure. Its only purpose is to improve cardiac contractility in severe shock. Do not start any bicarbonate until discussed with paediatric endocrinologist on call. Bicarbonate infusion can be harmful because it: a) Provokes decrease in intracellular ph b) Provokes decrease in CSF ph c) Provokes increase in CSF lactate d) Decreases tissue oxygenation (modifies oxygen off-loading by haemoglobin) e) Accentuates problems of hypokalaemia
Section C Insulin Infusion Low dosage insulin infusion regimens have several advantages: a) Relative simplicity b) More physiological serum insulin levels c) Gradual correction of hyperglycaemia and osmolar adjustment d) Avoid hypoglycaemia e) Avoid hypokalaemia There is now some evidence that early commencement of insulin therapy increases the risk of cerebral oedema and so deferred therapy is recommended. Management Plan 1. Start IV fluid replacement with 0.9% saline and 20 mmol KCl/ 500ml bag Intravenous fluids alone will cause the glucose level to drop. Commence syringe pump infusion of insulin solution (50 units human soluble insulin (Actrapid or Humulin S) per 50 mls 0.9% saline) an hour after starting IV fluids. Connect to main infusion line and infuse at rate of 0.1units/kg/hour. 2. An initial bolus should NOT be given the constant infusion is effective and avoids hazards associated with sudden influx of supraphysiological insulin concentration. Insulin should be started at a rate of 0.1units/kg/hour. The dose is written on the front of the DKA prescription chart. It should be signed by one doctor, checked and countersigned by another doctor. If glucose is < 4mmol/l, give bolus of 2ml/kg 10% glucose IV and increase glucose in IV fluids. If already on 10% dextrose containing fluids, then decrease insulin rate to 0.05 units/kg/hour. DO NOT STOP INSULIN INFUSION. If any concerns about rate of fall of glucose, discuss with the paediatric endocrinologist on-call (contactable via switch) 4. Compare glucose (BG) meter readings with lab glucose values at 0, 2 and 6hrs (when checking electrolytes) and more regularly if BG meter readings are not matching clinical condition or if unexpectedly high or low (ketoacidosis can affect reliability of BG results). 5. If glucose falls below 14 mmo/l before 12 hours the child may still be sodium depleted. Continue with 0.9% saline but with added glucose (see below). 6. For BM < 4 give a bolus of 2ml/kg of 10% glucose IV and add extra glucose to the IV fluids, rather than stopping the insulin. Please see the DKA prescription chart for details of how to do this 7. If ph >7.3 and/or ketones <3 with stable glucose readings between 4-15 and receiving glucose-containing IV fluids, insulin infusion can be reduced to 0.05u/kg/hr. DO NOT REDUCE INSULIN BELOW THIS LEVEL. IF BLOOD glucose < 4mmol/l ON 0.05U/KG/hr IV INSULIN, INCREASE THE AMOUNT OF GLUCOSE BEING GIVEN IV INSTEAD OR ALLOW TO EAT. A switch to subcutaneous insulin can be considered at this point.
8. If the BG meter reading rises above 15 mmol/l after decreasing insulin to 0.05u/kg/hr, first check that the insulin infusion is still running and going at correct rate, then double the insulin rate (to a maximum of 0.1 units/kg/hour). 9. Continue the insulin infusion until the child is drinking well and able to tolerate food. Then convert to usual subcutaneous insulin regimen (see separate protocol - insulin strategies in newly diagnosed diabetes). DO NOT STOP THE INSULIN INFUSION UNTIL 10 MINS AFTER SUB-CUTANEOUS INSULIN HAS BEEN GIVEN IF ANALOGUE INSULIN, 1 HOUR AFTER IF SC MIXED INSULIN GIVEN. LONG ACTING INSULIN MAY NEED TO BE GIVEN EARLY IF INFUSION STOPS BEFORE USUAL TIME OF LONG ACTING INSULIN DOSE. IN PATIENTS KNOWN TO HAVE DIABETES, LONG ACTING INSULIN SHOULD CONTINUE TO BE GIVEN AT NORMAL TIME, IN ADDITION TO IV INSULIN INFUSION. 11. Please page the paediatric diabetes specialist nurse using the emergency pager 07659132445 and bleep Paediatric Diabetes doctors if admission between 8.00-18.00, Mon-Fri, 8-12.00 weekends and bank holidays. If out of hours e-mail the paediatric diabetes team (under Paediatric Diabetes Team on global e-mail list) to inform them of the child s admission. 12. For children on continuous subcutaneous insulin infusion (CSII) pump therapy, stop the pump when starting DKA treatment. DO NOT RESTART PUMP THERAPY BEFORE DISCUSSING WITH PAEDIATRIC DIABETES TEAM OR PAEDIATRIC ENDOCRINOLOGIST ON CALL. Anticoagulant Prophylaxis 1. There is significant risk of femoral vein thrombosis in young and very sick children with DKA who have femoral line inserted. Therefore children with DKA and a femoral line inserted should have enoxaparin prescribed (dose as per cbnf).this should also be considered in those children who are significantly hyperosmolar.
1. Section D Cerebral Oedema 0.4-1% of children with DKA develops cerebral oedema with a high mortality/morbidity. The signs and symptoms of cerebral oedema may include: headache confusion irritability or restlessness reduced conscious level fits small pupils increasing pressure, slowing pulse papilloedema (not always present acutely) possibly respiratory impairment and decreasing saturations abnormal posturing specific neurological signs (e.g. cranial nerve palsies) Recent research shows that the risk of cerebral oedema appears to be increased if insulin is started within an hour of starting IV fluids, hence the current recommendation to defer the insulin infusion for at least 1 hour after commencement of treatment. If cerebral oedema is suspected, inform the Paediatric consultant on-call and PICU immediately. If the child is still in ED, inform shop floor consultant as well. Emergency management The following measures should be taken: 1. Exclude hypoglycaemia and continue insulin infusion 2. Give hypertonic saline (2.7%) 5ml/kg over 5-10 minutes as soon as possible. A delay of even half an hour could cause significant damage. Hypertonic saline is only stocked in PICU. 3. Restrict IV fluids to 1/2 maintenance and plan to replace deficit over 72 hours rather than 48 hours. 4. If not already there, move the child to PICU. 5. Intubate the child and ventilate to low normal pco2, approx 4 kpa. 6. Exclude other diagnoses by cranial CT scan when stable. Thrombosis, infarction or haemorrhage may present in the same way. 7. Consider intracranial pressure monitoring. 8. Repeated doses of hypertonic saline (above dose 2hourly) may need to be given to control intracerebral pressure. 9. Close management of sodium is essential. If outside the range 135-150mmol/l, discuss with paediatric endocrinologist on-call.
References 1. DKA guidelines on British Society of Paediatric Endocrinology and Diabetes 2015. website. www.bsped.org.uk 2. NICE guidelines on type 1 diabetes in childhood 2015
Clinical history Clinical signs Biochemical signs -polyuria -assess dehydration -ketones in and/or -polydipsia -deep sighing respiration Urine -weight loss (Kussmaul) -elevated glucose -abdominal pain -smell of ketones (>11mmol/l) -weakness -lethargy, drowsiness -acidaemia (ph <7.3) -vomiting -confusion Confirm diagnosis Diabetic Ketoacidosis Call senior staff -take also for electrolytes, urea -perform other Shock -Reduced peripheral pulse volume -Reduced conscious level -Coma No signs of shock Clinically well Tolerating oral fluid Dehydration <5% Resuscitation -Airway + NG tube -Breathing (100% O2) -Circulation (10ml/kg of 0.9% Saline repeated until circulation restored; max 3 doses) Intravenous therapy -calculate fluid requirements (sec B) - correct over 48 hours -0.9% saline for at least 12 hours - add KCl 20 mmol to every 500ml - insulin (Actrapid or Humulin S) 0.1u/kg/hr by IV infusion first hour after fluid started (sec C) Therapy -start sc insulin -give oral fluids No improvement - ketones rising -looks unwell -starts vomiting No improvement Re-evaluate -fluid balance + IV therapy - if still acidotic, may need further fluid resuscitation - check correct insulin dose - consider sepsis Observations -hourly glucose-neurological status at least hourly -hourly fluid input: output -electrolytes 2 hours after start of IV therapy, then 4 hourly -1-2hourly ketones level Blood glucose <14mmol/L Neurological deterioration Warning signs Headache, Irritability Bradycardia, Reduced conscious level, Signs of raised ICP Exclude hypoglycaemia Is it cerebral oedema? Intravenous therapy -add 5% glucose to normal saline -continue monitoring as above -if glucose <4, give 2ml/kg 10% dextrose and add extra glucose to IV fluids or treat orally -consider reducing insulin 0.05u/kg/hr but only when ph>7.3 Management -give 5ml/kg of 2.7% saline -call senior staff -restrict IV fluids by 1/2 -move to PICU -CT when stable Insulin Start sc insulin then stop IV insulin as per protocol Resolution of DKA -Clinically well, tolerating drinks and food. -Blood ketones <1mmol/l or ph >7 3