A 67 year old man presented
with a one day history of diarrhoea, vomiting and lethargy. He was
confused. He was on glibenclamide and phenformin for non-insulin
dependent diabetes. (The phenformin had been obtained in China). There
was no history of renal or hepatic disease or of alcohol use. His
respiratory rate was 22 breaths per minute. Examination was otherwise
unremarkable. Plasma glucose was 0.5 mmol/l. He became
alert after receiving 100 mls of 50% dextrose IV.
Initial pathology: Na+
144, K+ 3.9, Cl-
112, creatinine 0.14, lactate 24.6 mmol/l.
[Case reported by Lu et
al Diabetes Care 1996 Dec;19(12):1449-50
Firstly, initial clinical assessment (on the first gas results):
1. pH: The severe acidaemia indicates a severe acidosis.
2. Pattern: The very low bicarbonate and decreased pCO2 is
due to severe metabolic acidosis with respiratory compensation.
3. Clues: The lactate level is markedly elevated. The anion
gap is high (26) as in the chloride level.
4. Compensation: The expected pCO2
is 17mmHg. The actual pCO2
is higher than this which may indicate a small component of respiratory
acidosis. Central depression due to the hypoglycaemia may have caused
some central respiratory depression.
5. Formulation: There is no evidence of ketoacidosis or
toxic ingestions. Renal failure is not severe enough to cause acidosis
due to retention of acid anions but renal failure does predispose
towards the development of lactic acidosis with phenformin. There is a
severe metabolic acidosis (lactic acidosis type B2) due to use of
phenformin. The Delta ratio is (26-12)/(24-6) =
0.78. When the Delta ratio has a value of 0.4 to 0.8 this usually
indicates a combined high anion gap and hyperchloraemic acidosis. The
plasma chloride in this case is elevated so there is a component of
hyperchloraemic acidosis present.
6. Confirmation: No specific tests are required here.
This patient has a phenformin associated
severe lactic acidosis. There is also:
The diagnosis here is type
B lactic acidosis due to use of phenformin. This condition has a
reported 50% mortality rate. Phenformin has been removed from the market
in Australia because of the problem of lactic acidosis. Metformin is
still used and may cause lactic acidosis.
The lactate level exceeds
its typical renal threshold and urinary lactate loss may have been
associated with chloride retention. Hyperchloraemia may also result if
urinary fluid and lactate losses are replaced by IV Normal saline
solution. The exchange of lactate for chloride across the cell membrane
via an antiport may also be responsible for a hyperchloraemic component
in lactic acidosis. Diarrhoea can cause a hyperchloraemic acidosis.
All material © Copyright - Kerry Brandis, 2001