FRCA Notes

Glucose and Ketone Meters

This topic comes under the curriculum item: "Principles of measurement of parameters such as... blood glucose using near-patient testing devices".

It may seem an esoteric inclusion but has come up in the Primary viva in the past.

Resources

  • Point-of-care glucose and ketone meters allow rapid bedside measurement from a capillary, venous or arterial blood sample
  • Most use an enzymatic, electrochemical (amperometric) method, in which an enzyme reaction generates an electrical current proportional to analyte concentration
  • Peri-operatively, capillary blood glucose (CBG) is checked at least hourly in patients with diabetes, and ketones when glucose is raised or patients take SGLT2 inhibitors

Principle

  • A disposable test strip contains an electrode coated with an enzyme, either:
    • Glucose oxidase (GOx), or
    • Glucose dehydrogenase (GDH)

  • Glucose in the blood sample is oxidised by the enzyme, which is itself reduced
  • A mediator (e.g. ferricyanide) re-oxidises the enzyme, and is then re-oxidised at the electrode
  • This transfer of electrons generates a small electric current
  • The current is proportional to the glucose concentration in the sample

  • With glucose oxidase, the reaction is:
    • Glucose + O2 → gluconolactone + H2O2
    • Oxygen can therefore compete with the mediator, which is why GOx strips are affected by sample PO2

Other methods

  • Older strips used a colorimetric (reflectance photometry) method, in which a colour change is read by a light source and photodetector
  • Blood gas analysers use a similar enzymatic electrode separated from the sample by a membrane, and measure plasma glucose with greater accuracy
  • Laboratory analysers use enzymatic methods such as hexokinase, which remain the reference standard

Plasma vs. whole blood

  • Glucose concentration is ~11% higher in plasma than whole blood, as red cells contain less water
  • Most meters are calibrated to report a plasma-equivalent value

  • Works on the same electrochemical principle as the glucometer, using a separate strip
  • The enzyme is β-hydroxybutyrate dehydrogenase, which oxidises β-hydroxybutyrate and reduces NAD+ to NADH
  • NADH is re-oxidised via a mediator at the electrode, generating a current proportional to β-hydroxybutyrate concentration

  • The three ketone bodies are β-hydroxybutyrate, acetoacetate and acetone
  • β-hydroxybutyrate is the predominant ketone in DKA (up to 10:1 relative to acetoacetate), so blood ketone meters measure the most relevant one

Urine ketones

  • Urine dipsticks use the nitroprusside reaction, which detects acetoacetate (and acetone) but not β-hydroxybutyrate
  • They therefore underestimate ketosis, lag behind blood levels and may appear to worsen during treatment as β-hydroxybutyrate is converted to acetoacetate
  • Blood ketone measurement is preferred

Capillary ketones (mmol/L) Interpretation
<0.6 Normal
0.6-1.5 Raised: recheck and consider extra insulin if hyperglycaemic
1.5-3.0 High risk of DKA
>3.0 Consistent with DKA (with acidosis); seek urgent help


  • Accuracy is set by ISO 15197: 95% of results must lie within ±0.83mmol/L of the reference when glucose is <5.55mmol/L, or within ±15% above this
  • Meters are least accurate at the extremes of the range, particularly in hypoglycaemia

Source of error Effect
High haematocrit Falsely low glucose (less plasma in the sample)
Low haematocrit (anaemia) Falsely high glucose
High PO2 (e.g. arterial sample on high FiO2) Falsely low glucose with GOx strips
Low PO2 Falsely high glucose with GOx strips
Peripheral hypoperfusion (shock, vasopressors, hypothermia) Capillary samples may not reflect arterial glucose; use arterial or venous blood
Maltose, xylose, icodextrin (peritoneal dialysis) Falsely high glucose with some GDH strips
Paracetamol, ascorbic acid, uric acid Interference with electrode reactions
Contamination e.g. sugar on fingers, sampling near a dextrose infusion Falsely high glucose
Temperature, altitude, expired or poorly stored strips Variable error

  • In the critically ill, arterial samples analysed on a blood gas analyser or in the laboratory are preferred to capillary meters
  • Unexpected results should be confirmed with a laboratory sample

  • A small subcutaneous sensor measures interstitial fluid glucose every few minutes using a glucose oxidase electrode
  • Interstitial glucose lags behind blood glucose by ~5-15mins, more so when glucose is changing rapidly
  • Increasingly used by patients, often linked to insulin pumps in hybrid closed-loop systems

  • Not validated under anaesthesia: accuracy may be affected by hypoperfusion, hypothermia, pressure on the sensor and diathermy
  • Peri-operative readings should therefore be confirmed with capillary or arterial measurement
  • Sensors should be sited away from the surgical field and removed for MRI