FRCA Notes

Diabetic Ketoacidosis

Resources

  • DKA is a medical emergency, characterised by the triad of:
    1. Blood glucose level >11mmol/L (or >13.9mmol/L) or known diagnosis of diabetes mellitus
    2. Ketonaemia >3mmol/L or ketonuria ≥2+
    3. Venous pH <7.30 or serum bicarbonate <15mmol/L

  • It remains a frequent and life-threatening complication of both T1DM and T2DM

Epidemiology

  • Of those admitted to hospital with a primary diagnosis of DKA, 13% require ICU admission
  • This represents 2% of all ICU admissions

  • 0.5% of inpatients with diabetes develop DKA

Aetiology

  • Typically one of:
    • A first presentation of diabetes
    • Due to underlying infection or inflammatory response, including acute coronary syndromes or surgical intervention
    • Due to missed or inadequate insulin therapy, particularly in hospital-acquired DKA

  • May also be triggered by drugs affecting glucose metabolism such as steroids, catecholamines, phenytoin, diuretics or TPN

  • There is:
    • A relative or absolute insulin deficiency
    • A concomitant increase in counter-regulatory hormones such as glucagon, catecholamines, cortisol or growth hormone
  • The combination of increased gluconeogenesis and glycogenolysis, with impaired peripheral glucose utilisation, leads to hyperglycaemia

  • This also causes release of free fatty acids, which undergo β-oxidation in the liver to ketones:
    • 3-β-hydroxybutyrate (predominantly)
    • Acetone
    • Acetoacetate
  • There is thus ketosis

  • Ketone bodies dissociate, releasing hydrogen ions and causing metabolic acidosis

  • Hyperglycaemia has further sequelae, including:
    • Osmotic shift of fluid from intracellular to extracellular compartments
    • Glycosuria due to exceeded tubular glucose threshold in the proximal convoluted tubule
    • Osmotic diuresis from increased renal glucose excretion, causing dehydration and loss of sodium, potassium and phosphate

  • There is a broad spectrum of clinical presentations
  • Onset is generally more rapid than that of HHS, and acidosis is the major feature (vs. hyperglycaemia in HHS)
Respiratory Cardiovascular Neurological Electrolyte & acid-base Gastrointestinal Renal
Breathlessness Tachycardia Reduced consciousness Severe ketosis Acute abdominal pain AKI
Tachypnoea/Kussmaul's breathing Hypotension Confusion or agitation HAGMA Vomiting Polyuria
Hypocapnoea Anxiety Pseudohyponatraemia Ileus Severe ketosis

Establish DKA

  1. Measure capillary blood glucose

  2. Measure capillary or urinary ketones

  3. Blood gas to measure venous pH/bicarbonate
    • Although minimal difference in venous/arterial values, venous blood gases are recommended as it avoids unnecessary arterial puncture
  • The use of SGLT2 inhibitors has increased the incidence of euglycaemic DKA i.e. ketoacidosis with normoglycaemia
  • This is generally treated in the same way as hyperglycaemic DKA
  • It should prompt permanent cessation of SGLT2 inhibitor therapy

Identify underlying cause

  • Search for infection e.g. FBC | CRP | PCT | Cultures | System-specific investigations e.g. CXR, urine dip
  • Exclude other causes for abdominal pain e.g. pregnancy test, amylase, LFTs
  • ECG ± troponin if concerns re: acute coronary syndrome

Monitoring

  • U&E to check for electrolyte disarray and AKI

  • Blood glucose is a poor marker of both severity and success of treatment, especially as euglycaemic DKA can occur

  • Ketones, pH and potassium should initially be monitored at least 2hrly

  • An initial ABCDE approach may be warranted, focusing on adequate oxygenation (Sats 94 - 98%), venous access (likely to need at least two cannulas) and treatment of underlying causes
  • Patients should be referred to inpatient diabetic specialist or Endocrine teams

Fluid resuscitation

  • The most important initial therapeutic intervention in DKA is fluid replacement, as patients have a water deficit of approximately 100ml/kg
  • Crystalloids with a [Na+] 130 - 154mmol/L should be used i.e. 0.9% NaCl or Hartmann's
    • Although they are largely similar with respect to outcomes, balanced crystalloids are associated with:
      • Faster resolution of metabolic acidosis by about 2hrs (but not shorter ICU stay)
      • Less hyperchloraemic metabolic acidosis
      • Longer time to resolution of hyperglycaemia
    • Outside of higher care areas, 0.9% NaCl with added potassium is typically used as balanced crystalloids do not contain adequate potassium to be used alone

  • Although protocols exist, regimens will need to be tailored to the individual patient; their underlying pathology, comorbidities, response to treatment and markers of volume status e.g. urine output

Fixed-rate insulin infusion (FRII)

  • Alongside fluid, administration of IV insulin is the next most important intervention
  • FRII have superseded previous VRII regimes, in order to avoid down-titration of infusions based on falling glucose when the patient is still ketotic
  • It is made by adding 50 units of Actrapid (or Humilin S) to 0.9% NaCl to give a 1unit/ml infusion
  • This is administered at a rate of 0.1units/kg/hr [using current weight in pregnancy or estimated weight if unknown]

  • The goals of FRII are:
    1. Reduction in blood glucose by 3mmol/L/hr
    2. Reduction of blood ketones by at least 0.5mmol/L/hr
    3. Increase in venous bicarbonate by 3mmol/L/hr

  • A failure to acheive the above goals should prompt:
    • Checking proper administration of insulin e.g. check cannula not tissued, pump still running
    • Increase FRII by increments of 1unit/hr with a maximum rate of 15units/hr
    • Senior clinical review

  • The FRII should be continued until resolution of the ketosis, i.e. capillary ketones <0.6mmol/L, a pH >7.30 and a venous bicarbonate of >15mmol/L
  • Before stopping the FRII, ensure other insulin is given:
    • If the patient is eating & drinking → their normal regimen
    • If not eating & drinking → VRII with concurrent 0.45% NaCl + 0.15% KCl + 5% dextrose

Electrolyte replacement

  • There is generally a 3-5mmol/kg deficit in potassium
  • Hypokalaemia occurs as potassium shifts to the extracellular space in exchange for hydrogen ions, and is then lost as part of the osmotic diuresis of DKA
  • Unless K+ >5.5mmol/L or oliguric, fluid (except the first infusion) should contain potassium

  • Sodium (7-10mmol/kg deficit), chloride (3-5mmol/kg deficit), phosphate (1mmol/kg deficit) and bicarbonate levels typically resolve alongside the DKA

Blood glucose and other insulins

  • The FRII may cause hypoglycaemia before the ketosis has resolved
  • Therefore, once capillary glucose is <14mmol/L, an infusion of 10% dextrose should be added e.g. 125ml/hr (or titrated to fluid balance)
  • In euglycaemic DKA, start 10% glucose infusion 125ml/hr straight away (as glucose <14mmol/L)
    • If glucose falling despite this, reduce FRII to 0.05units/kg/hr

  • To aid transition from IV to SC insulin, long-acting insulin analogues (Levemir, Lantus, Tresiba) should be continued
    • Helps avoid rebound hypoglycaemia
    • May reduce length of stay
  • Continuous, subcutaneous insulin infusion pumps (CSII) should be stopped and disconnected during an episode of DKA, but restarted following diabetic specialist team input

Supportive management

  • Ketosis causes delayed gastric emptying; NG tube placement may reduce aspiration risk in the patient with low GCS or undergoing surgery

  • A catheter should be inserted to help measure urine output and monitor fluid balance, especially if altered mental state or requiring critical care

  • Appropriate antibiotics should be prescribed if it is felt infection is contributing to DKA

  • VTE prophylaxis is imperative given high risk of thromboembolism due to dehydration

Critical care referral (NB referral, not necessarily admission)

Criteria Value
SpO2 <92%
HR
SBP		 <60bpm or >100bpm
<90mmHg
GCS <12
Potassium <3.5mmol/L
Acidaemia Ketones >6mmol/L
pH <7.0
Bicarbonate <5mmol/L
Anion gap >16



Complications of DKA
Hypokalaemia
Hypoglycaemia
Renal impairment
Pulmonary oedema
Cerebral oedema
Death

Cerebral oedema

  • Cerebral oedema is the most common cause of death from DKA in children
  • It is felt to primarily arise due to cerebral hypoperfusion followed by reperfusion injury and vasogenic oedema
  • The osmotic fluctuations during DKA do not play a primary causal role

  • Risk factors:
Patient factors Fluid resuscitation factors Other factors
Young age >40ml/kg in first 4hrs Boluses of insulin
Newly diagnosed DM Administration of hypotonic fluid Raised serum urea
Bicarbonate therapy Initial pH <7.10
Hypocapnoea

  • It is a clinical diagnosis with various symptoms and signs, including altered mental status, headache, cranial nerve palsies or sometimes Cushing's triad
  • Suspicion of cerebral oedema should instigate an urgent CT brain
  • Management includes immediate administration of hypertonic saline (3 - 5ml/kg of 3%) or mannitol (0.5g/kg i.e. 2.5ml/kg of 20% solution)

Mortality

  • Overall mortality from DKA has fallen to <1%
  • In elderly or comorbid patients, however, mortality remains >5%
  • Co-morbid states such as sepsis, pneumonia, acute lung injury or MI are associated with increased mortality

Perioperative management of patient with DKA requiring surgery

  • Some patients will have a surgical trigger for their DKA and require intervention
  • It is important to ensure the 'acute abdomen' is not merely a symptom of DKA
  • Timing of surgery will be based on the balance between need for rapid surgery vs. the complications of anaesthetising and operating on a physiologically deranged individual

  • Focus on optimising medically as much as possible
  • Certainly requires a senior anaesthetist

  • A CVC will almost certainly be necessary to help facilitate administration of multiple drugs and fluids, as will need administration of:
    • DKA resuscitation fluid via a pump e.g. 0.9% NaCl + 40mmol KCL
    • FRII or VRII via a pump
    • Glucose 10 - 20% once blood glucose <14mmol/L
    • Intra-operative resuscitation fluid e.g. Hartmann's
    • ± central KCl if hypokalaemic
    • Anaesthetic drugs
    • Regular sampling of glucose, potassium and pH at least hourly under anaesthesia

Monitoring

  • AAGBI
  • Arterial line to facilitate continuous monitoring and sampling
  • CVC as above

Anaesthetic technique

  • High risk of aspiration due to delayed gastric emptying from ketosis so:
    • NG tube inserted and aspirated prior to induction
    • RSI technique

  • Cardiovascularly stable induction drug combination as hypovolaemia and acidosis will exaggerate effects of induction
  • Mandatory ventilation to ensure no iatrogenic respiratory acidosis

Glucose, ketone and pH management

  • Hourly checks on glucose - may need to start glucose infusion once <14mmol/L and on FRII
  • Hourly potassium level ± replacement as necessary

  • Almost certainly going to need a higher care area e.g. HDU, ICU
  • Ongoing management of DKA as above