Insulin deficiency Metabolism of TAG and AA Gycerol + FFA ++, alanine= +hepatic gluconeogenesis +Glucagon (not inhibited by insulin) Xblock of ketogenesis +Acetoacetic acid + bHB->metabolic acidosis Hyperglycemia->osmotic diuresis, +Na and K losses Serum K may rise in response to acidosis, but total depletion
Infection Initial presentation Infarction Intoxication Insulin missed
early symptoms: polyuria, polydipsia, malaise, nocturia, weight loss late signs and symptoms anorexia, nausea, vomiting, dyspnea (often due to acidosis), fatigue abdominal pain drowsiness, stupor, coma Kussmaul’s respiration fruity acetone breath Evidence of cause: infection, MI, intoxication
Level of consciousness Hydration status->tachyC, hypoT, poor perfusion, -ve skin turgor, dry mucus membranes May have fever Kussmauls breathing, acetone breath Evidence of infection
Investigations and findings
Plasma glucose ++ ABG->respiratory acidosis, low bicarbonate Urinalysis->+glucose, ketones, may have infection UEC: Urea->elevated Creatinine->elevated Sodium low Potassium elevated Chloride, Mg, Ca low Phosphate high Elevated anion gap Lactate ++ LFTs normal Amylase elevated Lipase normal Serum osmolarity variable FBC elevated WCC Consider: ECG, troponins CXR Blood, urine, sputum cultures if considering infection
Pediatric patients presenting with >11.1mml, next step
Serum ketones measured at bedside If +ve, assess for acidosis Urinalysis if ketones serum not available
Assessment of adolescents and children
1. Level of dehydration 2. Level of consciousness (GCS) 3. Investigations -FBE -Blood glucose, UEC, CMP -Blood ketones at bedside -VBG -Urine -Ix for precipitant cause- if clinical signs of infection: septic workup
Level of deH % and findings
1. Degree Of Dehydration (often over-estimated)
None/Mild (< 4%): no clinical signs
Moderate (4-7%): easily detectable dehydration eg. reduced skin turgor, poor capillary return
Severe(>7%): poor perfusion, rapid pulse, reduced blood pressure i.e. shock
Special care requirements re staff for children with DKA
Children and adolescents with DKA should be managed in a unit that has: Experienced nursing staff trained in the monitoring and management of DKA A paediatric endocrinologist, paediatrician or paediatric critical care specialist with training and expertise in the management of DKA. Where such expertise is not available on-site, telephone advice should be sought from the appropriate specialists Access to laboratories for frequent and timely evaluation of biochemical variables
Acute management DKA
1. ABC 2. Supportive measures to considerif appropriate -Secure the airway and consider ng tube placement (to avoid aspiration) in the unconscious / severely obtunded patient -Insert a second peripheral IV catheter for convenient and painless repetitive blood sampling -Give oxygen to patients with severe circulatory impairment or shock. -Use a cardiac monitor for continuous electrocardiographic monitoring to assess for signs of hyperkalemia (peaked T-waves, widened QRS) or hypokalemia (flattened or inverted T waves, ST depression, wide PR interval). -Consider antibiotics for febrile patients after obtaining appropriate cultures -Catheterise the bladder if the patient is unconscious or unable to void on demand to allow for strict fluid balance (e.g. in infants and very ill young children). 3. Fluid -Bolus, Keep NBM until alert and stable, NGT if comatose, recurrent vomiting -Fluid replacement->NS and potassium for at least 6 hours. If glucose falls rapid or 12-15, change to NS + 5% dextrose + potassium 4. Glucose monitoring 5. Potassium replacement 6. Insulin 7. Ongoing monitoring -Strict fluid balance -Hourly observations-> pulse, BP, respiratory rate, level of consciousness (GCS), and neurological status (pupillary responses, assess for change eg restlessness, irritability, headache) -Hourly glucose and ketones -Re-check potassium -VBG + lab glucose 2/24 for 6/24, then 2-4/24 after -Monitor UEC 2-4/24 -Temperature 2-4/24 -Should be nursed heads up->avoid cerebral edema
Fluid bolus requirements
If hypoperfusion is present, give 0.9% saline at 10 ml/kg and reassess. If centralcapillary refill remains > 2 seconds, a further bolus of 10ml/kg 0.9% saline may be given In adults: BP NS 500ml IV over 10-15 minutes BP >90->NS 1L IV over 60 minutes
What happens to sodium as blood glucose levels fall
Remains stable of falls (corrected sodium)
Fluids beyond 6 hours- possible choice
Beyond the initial 6 hours, 0.45% NaCl with 5% dextrose and potassium may be used once the BGL is <12
What level to aim for blood glucose
Aim for 5-12mmol/L
What to do if BGL <5mmol/L
increase the dextrose concentration in the fluid to 10%. The insulin infusion rate should only be turned down if BGL continues to fall despite use of 10% dextrose
How long to take for completion of rehydration
in the first 24-36 hours
Regimen for K+ replacement
Defer initial potassium replacement if the serum level is > 5.5 mmol/l or if the patient is anuric (until K+ is 30 kg 2. Subsequent replacement is based on serum potassium levels 3. Potassium replacement should continue throughout i.v. fluid and insulin therapy 4. Once insulin is commenced, a repeat K+ should be taken within one hour In adults: serum potassium under 3.5 mmol/L—give potassium 40 mmol/hour under specialist advice in a critical care environment serum potassium 3.5 to 4.5 mmol/L—give potassium 20 mmol/hour serum potassium 4.5 to 5.5 mmol/L—give potassium 10 mmol/hour serum potassium above 5.5 mmol/L—stop potassium infusion.
Add 50 units of clear/rapid-acting insulin (Actrapid HM or Humulin R) to 49.5 ml 0.9% NaCl (1 unit/ml solution). Start rates: 1. 0.1 units/kg/hr in newly diagnosed children, and those with established diabetes who have glucose levels > 15 mmol/l. 2. 0.05 units/kg/hour for children with established diabetes who have had their usual insulin and whose blood glucose level is This rate should also be considered in young children and may be appropriate during inter-hospital transfer when biochemical monitoring is more limited (NB a doctor should accompany any patient in DKA requiring insulin infusion during transfer).
When to cease insulin infusion, best time to change to SC insulin
when the child is alert and metabolically stable (pH > 7.30 and HCO3 > 15). The best time to change to s.c. insulin is just before meal time. The insulin infusion should only be stopped 30 minutes after the first s.c. injection of rapid-acting insulin.
How to "correct serum sodium"
Corrected (i.e. actual) Na = measured Na + 0.3 (glucose - 5.5) mmol/l i.e 3 mmol/l of sodium to be added for every 10 mmol/l of glucose above 5.5 mmol/l.
Management of hypoglycemia: when still acidotic, when not responding to 10% dextrose and when ph >7.3
1. If blood glucose falls below 4.0 mol/l and patient is still acidotic, give i.v. 10% dextrose 2-5 ml/kg as a bolus and use a 10% dextrose concentration for ongoing iv fluids (with 0.45% NaCl and K+ supplements). Do not discontinue the insulin infusion. 2. If hypoglycaemia occurred despite use of 10% dextrose in the preceding 2 or more hours, the rate of the insulin infusion may be decreased to 0.05U/kg/hr as long as ketosis and acidosis are clearing. Continue with a 10% dextrose concentration in i.v. fluids until BGL stable. 3. If blood glucose falls below 4.0mmol/l and most recent pH is >7.30, oral treatment for hypoglycaemia (jelly beans + 1 serve of complex carbohydrate) can be used instead of an i.v. bolus of dextrose 10%
Optimally, what is the rate of fall in blood glucose and serum osmolarity mmol/hr
should not exceed 5 mmol/l/hr,
Cerebral edmea: prevention, warning signs and treatment
Prevention: -Slow correction
Warning: -First presentation, long hx poor control, no rise in sodium with glucose on correction falling, hyponatremia during therapy. HA, irritability, lethargy, depressed consciousness, incontinence,thermal instability, very late vitals
Treatment: Mannitol, reduce fluid input 1/3, nurse head up, transfer to ICU
Investigations: new diabetes, mildly ill
Blood ketones Glucose UEC GAD antibodies, insulin antibodies, coeliac screen, thyroid function tests If overweight->lipids, LFTs
Mx initial diabetes mildly ill
0.25 units/kg of quick-acting insulin s.c. stat. If within 2 hr prior to a meal defer and give meal-time dose only. Halve dose if ≤4 yr old. Dose may be lower if not ketotic.
Ongoing treatment in mildly ill new diabetes
1. Twice daily injections of a mixture of short and intermediate-acting insulins: ->Usually commence with total daily dose (TDD) of 1 unit/kg/day ->This is given as 2/3 of TDD in morning, 1/3 of TDD at night. 2/3 of each dose as intermediate-acting insulin, 1/3 as short-acting insulin. 2. Multiple daily injections (MDI) of insulin using a long-acting insulin analogue at night and pre-meal injections of rapid-acting insulin analogue ->Also start with TDD of ~1.0 U/kg/day. ->Give 0.4U/kg as basal insulin (long-acting insulin analogue eg insulin glargine) at ~20,00- 21,00 hrs. Give the remainder as rapid-acting insulin in 3 equal doses before meals (i.e. ~0.2 U/kg before each main meal).
Hyperglycemic, hyperketotic, established diabetes
(i) Patients on intermittent daily injections of insulin (bd or MDI) ->Give 10% of the patient's total daily insulin dose as a sub-cut injection of rapid-acting insulin (this is in addition to usual insulin regimen). ->Monitor BGL and ketones 1-2 hourly. This dose of rapid-acting insulin can be repeated after 2-4 hours if blood ketones are not Need to assume line failure / blockage has interrupted insulin delivery. ->Give 20% of the patient's total daily insulin dose as a s.c. injection of rapid-acting insulin (higher dose relative to above patient group is because there is no longer acting insulin 'on board' in pump patients). ->Once s.c. insulin has been given, ask the patient or family to resite the pump cannula and commence delivery at usual settings. ->Monitor BGL and ketones 1-2 hourly. For patients on pump therapy, ketones should clear to
What is the biochemical diagnosis
1. venous pH is <7.3 or bicarb <15 mmoll
2. Serum or urinary ketones