2. Metformin overdose Dr. TS Au PYNEH 16 Feb 2005

3. Toxicology case presentation M/56 unemployed and divorced Hx of DM, HT, depression FU in GP Attempted suicide by taking >100 tablets of diabetmin 500 mg (metformin) before 3 pm Suicidal notes written Developed repeated vomiting and diarrhoea since then Sent to AED at 18:33

4. Triage and Ix BP 198/54 P 102 /min SpO2 100% (RA) RR 22/min Temp 36.4 ℃ Hemostix = 13.0 ECG: sinus rhythm 95/min, normal QRS P/E: dehydrated

5. Progress in AED Given activated charcoal 50 g orally IV NS 500 ml Q8H BP/P GCS all along stable Last BP 160/84, P 78 /min Medical contacted, suggested admitted to general ward

6. Arterial blood gases 1st 2nd pH 7.248 7.223 pCO2 4.70 4.44 pO2 14.15 16.11 HCO3 15.0 13.4 BE -11.2 -13.1 Metabolic acidosis with respiratory compensation

7. Blood tests ABG: pH 7.248 pCO2 4.70 HCO3 15.0 BE -11.2 RFT: Na 144 K 4.6 Cl 108 Cr 160 Glucose 12.4 Anion gap: 144 – 108 – 15 = 21 Anion gap metabolic acidosis Lactate = 9.07 mmol/L (N : 0.3 – 1.3)

8. Progress Transferred to ICU after first blood tests Developed ARF RFT D1 D3 D9 D15 D17 Cr 160 360 904 152 119 Put on continuous venovenous haemofiltration (CVVH) Improving trend for acidosis and RFT

9. Outcome Transfer out to general ward on D3 Continue renal support by HD in medical ward Cr back to normal on D17 Psychiatric assessment Refused psychiatric ward admission Home on D20

10. Metformin overdose Metformin – common biguanide used as an OHA Mechanism of action: ↓hepatic gluconeogenesis MAJOR + ↑peripheral glucose utilization did not lower blood glucose unless other OHA coingested (sulfonylurea)

11. Anion gap metabolic acidosis MUDPILES M – methanol U – uraemia D – DKA / AKA / SKA P – paraldehyde / phenformin/ metformin I – isoniazid / iron L – lactate E – ethylene glycol S – salicylate

12. Toxicity of metformin Lactic acidosis esp in patients with renal impairment GI effects: anorexia, vomiting and diarrhoea, abdominal pain Rarely hypoglycemia Fulminant GI distress leading to ARF, which↑ lactic acidosis

13. Management GI decontamination: activated charcoal for early presentation Antidote for metabolic acidosis: sodium bicarbonate Supportive care for refractory acidosis and ARF: Hemodialysis

14. Learning points Activated charcoal may not be justified as there may be persistent vomiting Patient should be admitted to ICU right away ? Aggressive use of NaHCO3 ? initiated in AED after blood taken