Diabetic Ketoacidosis (DKA)

  • DKA is a dangerous complication of T1 diabetes occurring due to an absence of insulin causing significant ketogenesis

Definition

    • DKA is sefined as a triad of:
      1. Hyperglycaemia (>11mmol
      2. Metabolic acidosis (pH < 7.3, HCO3 <15mmol)
      3. Ketosis – capillary ketones (>3mmol/L)
  • All 3 must be present for it to be DKA
    • NB May present with euglycaemic DKA
      • This is often DKA which has been partially self-treated by the patient who has recognised it coming on
      • Also rarely found in patients on SGLT2 inhibitors as the glucose is peed away (uncommon as SGLT2 inhibitors are rarely used in T1DM)
Epidemiology
  • DKA is the most common endocrine emergency
  • Mortality rate of 10%
  • Usually affects T1DM
    • Can also occur in longstanding T2DM where virtually no insulin is being made
Pathogenesis

(see metabolic changes in T1DM to contextualise this)

  • Absence of insulin independently causes two things:
    1. Hyperglycaemia due to a lack of glucose uptake and gluconeogenesis
    2. Gluconeogenesis which is normally inhibited by insulin
      • Lipolysis/proteolysis occurs instead of glycogenolysis when there is no insulin
      • The ketogenic products are metabolised in the liver to form acidic ketones
        • There are many ketones – the main relevant one is 3-hydroxybutrate which is detected
        • Results in ketoacidosis
Aetiology

DKA can present in several scenarios

  1. DKA is often the first presentation of T1DM
  2. Often follows the interruption of insulin therapy in T1 patients  when not eating
    • Hence, ‘sick day rules’ are crucial in prevention
  3. Other causes
    • Acute illnesses (infections and Infarcts)
    • Stress
    • These often combine with insulin interruption)
  4. The trigger is idiopathic in around 40% of cases

Clinical PresentatioN
  • Ketogenesis (Ketones Waste the Gut, Brain, and Heart) – note that these features aren’t found in HHS
    • Lipolysis/proteolysis causes weight loss and muscle wasting
    • GIT:
      • N&V
      • Abdominal pain
    • CNS:
      • Generally weakness, fatigue
      • Drowsiness, Confusion
      • Blurred vision
      • Coma
    • CVS:
      • Hypotension
    • Ketotic breath (pear drops)
  • Acidosis
    • Kussmaul respiration to compensate for metabolic acidosis may be seen
      • A type of deep ‘sighing’ hyperventilation
  • HyperglycaemiaSx of this will not always occur
    • Profound dehydration and electrolyte loss due to massive osmotic diuresis (as DKA coincides with severe hyperglycaemia)
      • Features of dehydration – see separate
    • CNS features (similar to those above)
Complications of DKA
  • The symptoms above result in a variety of potentially fatal complications
    • These occur either iatrogenically or due to micro and macro vascular obstruction leading to ischaemia
  • Remember (TAHOPS) – 2 of these are iatrogenic
    • Thromboembolism due to increased viscosity of blood can be either arterial or venous
    • ARDS
    • Hyper/hypokalaemia
      • Hypokalemia if too much insulin is given and hyperkalemia if not enough
    • Cerebral Oedema can occur if osmolality is brought down too quickly (e.g. by giving too much fluid too quickly)
      • Main cause of death in these patients
      • Therefore lower glucose slowly (3mM/hour)
    • Aspiration Pneumonia with depressed consciousness + vomiting
    • Shock with depressed consciousness + vomiting

Assessment

History and examination

  • History:
    • Any precipitating factor?
    • Previous management if a known diabetic?
  • Physical examination:
    • Look for causes and symptoms of DKA
    1. Respiratory exam – pneumonia?
    2. Cardiac exam – esp consider dehydration and MI
    3. Abdominal exam – acute abdomen
    4. Neurological exam + GCS

Investigations:

The following must be both investigated at diagnosis and monitored regularly after this

  • Bedside
    • Obs – Signs of dehydration
    • ECG
      • Insulin deficiency causes hyperkalemiatall tented T waves, PR interval, P wave, etc
      • Also excludes MI
  • Urine dipstick
    • Urine Ketones (at least ++) – NB this is delayed compared to capillary ketones
    • Urine Glucose
    • Urine output is also required for dehydration
  • Blood
    • Capillary tests are done first
      1. Blood capillary glucose
      2. Blood capillary ketones
    • Serum tests
      • Serum BGL – more reliable than capillary/blood gas readings
      • Serum Ketones (>3.0)
        • NB these clear faster than urinary ketones 
      • U&Es:
        • K+
          • Hyperkalemia due to loss of insulin and acidosis both allowing K+ to move out of cells.
          • Total K+ may be low as excretion also increases with hyperglycaemia but will typically be high due to metabolic shift
          • Monitor during treatment – see below
        • Urea and creatinine raised dehydration
          • Na+ can be high or low
          • Calculate anion gap if possible
      • Clotting – informs thromboprophylaxis 
      • Septic screen – if suspecting infection (DKA does also cause a SIRS response
        • FBC
        • CRP/ESR
        • ± blood cultures
      • ?troponin – if suspecting MI
      • ABG/VBG is crucial to show acidosis as well as electrolytes and glucose
  • Imaging
    • CXR if suspecting infection

Management of DKA 
  • There are 3 steps to the management of DKA:
    1. Resuscitate
      • I.e. treat and prevent complications (ABCDE)
    2. Reverse the DKA
      1. Treat hyperglycaemia (aim for <14mM at a rate of <3mmol/hr)
      2. Treat ketosis (aim for ketones <0.3mM
      3. Teeat acidosis (aim for VBG pH>7.3)
      4. Treat hyperkalaemia/hypokalaemia (aim for 3.5-5.5mmol)
    3. Secondary Prevention (Long-term treatment):
      • Find and treat the precipitant and underlying conditions
  • Monitoring is key to consider at all stages
  • ITU referral is generally indicated by
    1. Severe derangement of DKA parameters (e.g. ketones, pH, potassium – but not glucose)
    2. Poor general health (BP, HR, GCS, SaO2)

Resuscitation

  • Patients may present with life-threatening complications
    • Would take an ABC approach
    • As part of this, some of the DKA management would be initiated
  • Mainly aim to prevent the complications – thrombosis, hypokalemia/hyperkalemia, ARDS, aspiration pneumonia
  • An ABCDE approach may show the following:
    • A
      • Patient may be unconscious
    • B
      • Patient may be at risk of ARDS or aspiration pneumonia
        • NGT  can drain  if vomiting or disturbed GCS to prevent aspiration pneumonia
    • C
      • Fluid therapy (see DKA)
        • Start with a STAT dose if shocked
      • Prevent cerebral oedema
        • (see above) bring down osmolality (glucose, sodium) slowly
      • Hypokalaemia  – need continuous ECG monitoring
    • D
      • Glucose obviously is checked
      • Consciousness may be disturbed and must be formally assessed (GCS)
    • E
      • Thromboprophylaxis may be done  using heparin

Reversing DKA

    • 3 main interventions (RIP) are done at the same time followed by monitoring and complication prevention (MC)
  • End-points for DKA reversal:
    1. BMs <11
      • Aim to drop by ≤3mmol/hour – prevents cerebral oedema
      • Once bgl <14mmol, add glucose (NB this ≠ a sliding scale as the insulin remains given at a constant rate)
    2. Ketones <0.5
      • Aim to drop by >0.5mmol/l/hr
    3. PH neutral
      • Aim to increase HCO3 by 3mmol/l/hr
  • Usually should be out of DKA by 12 hours – ketone free and E&D
  • Rehydrate:
    • Replace lost fluid to treat dehydration and lower glucose/Ketones/K+
      • Usually lose about 6L has been lost
    • 0.9% Saline is typically used
      • Titrate to BP but usually give 6L – 1L every 1/2/2/4/6/8 hours
      • If shocked, a STAT bolus of  500ml may be given before the 6L
    • Add 10% glucose when [blood glucose] <14mmol/l to prevent hypoglycaemia (whilst still correcting the dehydration)
      • Usually given at a rate of 125ml/h (i.e. a bag over 8 hours)
      • Not always necessary
    • HCO3 is only used if severely acidotic –  pH <7.0
    • Beware cerebral oedema which occurs when bringing down serum osmolality too fast  (i.e. urea, K+, Na+, and glucose)
      • Especially consider sodium which accounts for most of the serum osmolality
  • Insulin (Fixed Rate Infusion) – This treats the DKA, hyperglycaemia, and suppresses lipolysis very well
    • Dosage
      • Actrapid 0.1units/kg/hr is used
        • Given in 50u/49.5ml saline (i.e. 1u/ml)
        • Nowadays some areas may give rapid-acting analogues instead
      • Increase by 1 unit/hr if ketones + glucose are not improving
      • Transfer to SC insulin once DKA is resolved and patient is eating  and drinking and aims have been met (see below)
        • If patient is not ketotic but also not E&D, move to a sliding scale
      • NB: previously prescribed basal insulin is continued
        • However, discontinue the mealtime bolus insulin
        • Continue the basal because it takes a while to reinstate it after it is stopped
  • Potassium replacement
    • Patient will (usually) be initially hyperkalemic in the blood but actually have low total potassium in the body.
      • Redistribution with fluid replacement and insulin moves K+ out of the blood and can therefore rapidly cause iatrogenic hypokalemia
    • Give potassium fluids with each bag of NaCl after the first bag
      • Usually come as premixed bags
    • Titrate according to blood [K+] measured by 2-hourly VBG
      • Aim between 3.5-5.5 – hospital will give rates adjusted to the VBG
      • 20mM per L of saline is usually given if normokalemic and no K+ is given if >5.5mmol
    • Can give a max of 20mM/hour
    • Ensure patient is on ECG monitoring
  • Regular Monitoring is necessary throughout the DKA treatment:
    • Hourly BGLs aim for a max drop of 3/hr
    • Hourly Capillary ketones
    • 2-Hourly VBGmeasures K+ (titrate), Na+/glucose (cerebral oedema), pH
    • Catheterisationaccurately indicates hydration level
    • ECG for hyperkalemia

Further treatment (once DKA has resolved stable patient)

  • The patient is regularly reassessed and weaned off insulin when appropriate
    • Usually done by Diabetic Specialist Nurses
  • Usually switch over to SC insulin once the patient is eating
    • If basal-bolus regimen:
      • Start on basal insulin (if not previously on it anyway) while still on the infusion
      • Start mealtime insulins (short-acting) with the next meal – stop the IV insulin after the meal
    • If on a premixed regimen, it is a bit more complicated
      • May or may not be stopped during the DKA protocol
      • Usually start with the next meal
      • NB premixed is rare