"Massive" metformin overdose

Chiew, Angela L., Wright, Daniel F. B., Dobos, Nicola M., McArdle, Kylie, Mostafa, Ahmed A., Newth, Annemarie, Roberts, Michael S. and Isbister, Geoffrey K. (2018) "Massive" metformin overdose. British Journal of Clinical Pharmacology, . doi:10.1111/bcp.13582

Author Chiew, Angela L.
Wright, Daniel F. B.
Dobos, Nicola M.
McArdle, Kylie
Mostafa, Ahmed A.
Newth, Annemarie
Roberts, Michael S.
Isbister, Geoffrey K.
Title "Massive" metformin overdose
Journal name British Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 1365-2125
Publication date 2018-03-13
Year available 2018
Sub-type Article (original research)
DOI 10.1111/bcp.13582
Open Access Status File (Author Post-print)
Place of publication Chichester, West Sussex United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old female presented 5h post multi-drug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH 7.0, lactate 17 mmol/L) and shock. Despite 3 hours of CVVHDF, her acidosis worsened (pH 6.83, lactate 24 mmol/L). Intermittent haemodialysis(IHD) improved acidosis (pH 7.13, lactate 26 mmol/l), but again worsened (pH 6.91, lactate 30 mmol/L) with CVVHDF recommencement. IHD (12 h), CVVHDF (26 h) and vasopressor support for 7 days resulted in survival. Measured metformin concentrations were extremely high with a peak of 292 μg/ml at 8 h post-ingestion. IHD, but not CVVHDF in this case was associated with improvement in metabolic acidosis and hyperlactatemia. Pharmacokinetic analysis of metformin concentrations found a reduced apparent oral clearance (CL/F) of 8.2 L/h and a half-life of approximately 30 h. During IHD, the CL/F increased to 22.2 L/h with an approximate half-life of 10 h. The impact of prolonged oral absorption from a pharmacobezoar and re-distribution of metformin from peripheral sites (including erythrocytes) on the pharmacokinetic profile cannot be determined from the data available.
Keyword Extracorporeal elimination
Metabolic acidosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
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Created: Wed, 21 Mar 2018, 10:07:32 EST