Metabolic acidosis in poisoning Taken from Metabolic acidosis

Metabolic acidosis in poisoning • Taken from Metabolic acidosis: differentiating the causes in the poisoned patient B Judge Med Clinic N Am 2005, 89: 1107

Metabolic acidosis • Definition: process that lowers serum HCO 3 • Occurs when H+ ion production exceeds body’s ability to compensate adequately via buffering or ventilation Mechanisms of metabolic acidosis in poisoning • Increased acid production • Impaired acid elimination

Calculations • Note the low p. H (or high H+) • Then calculate Anion Gap (AG) AG = [Na+] – ([Cl-] + [HCO 3 -]) Usual range = 12 +/- 4 m/Eq/L (more recently 7 +/- 4) • If toxic alcohols suspected, calculate osmolality: 2 x [Na+] + [glucose] + [urea] and request a measured osmolality on a blood sample Osmol Gap = measured osmolality – calculated osmolality

AG & metabolic acidosis • High AG Occurs when an acid is paired with an unmeasured anion (eg lactate, formate) • Normal AG Occurs with gain of both H+ and Cl- ions, or a loss of HCO 3 - and retention of Cl-, preserving electroneutrality • However, AG can be affected by errors of calculation or assay, and by numerous disease states. So the lack of a high AG does not exclude any particular cause

Classical causes of high AG metabolic acidosis • Methanol • Uremia • Diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis • Paraldehyde • Iron, isoniazid • Lactic acidosis • Ethylene glycol • Salicylates

Common toxicological causes of high AG metabolic acidosis • • • Paracetamol Amphetamines Carbon monoxide Cocaine Toluene, benzene Valproate Salicylates [NSAIDs, metformin, glycols] [ARVs: Zidovudine, didanosine, stavudine]

Use of the osmol gap in patients with a high AG metabolic acidosis • Osmol gap may provide extra information if a toxic alcohol is suspected. • However, be aware that other medical conditions such as ketoacidosis and renal failure also cause a raised OG • Normal osmol gap = less than 10 +/- 6 m. Osm/L • However, normal range has problems due to wide variability between people and assays

Toxins associated with a high osmol gap • Mannitol • Alcohols: ethanol, etylene glycol, isopropanol, methanol, propylene glycol • Diatrizoate (amidothizoate) • Glycerol • Acetone • Sorbitol

Metabolism of toxic alcohols • Ethylene glycol • Methanol • Glyceraldehyde • Formaldehyde • Glycolate • Formate • Glyoxylaye • Oxalate

The mountain Mycyk & Aks, 2003

Common causes of normal AG metabolic acidosis • • Acetazolamide Acids (NH 4 Cl, HCl) Cholestyramine Mg Cl Mafenide acetate Topiramate Ureteroenterostomy • • • Diarrhoea Hyper-alimentation Pancreatic fistula Post-hypocapnia Rapid IV fluid administration Renal tubular acidosis

Mechanisms of increased acid production • Toxins are acids (eg HCl vs. sulphuric acid) • Toxins have acid metabolites (eg metabolism of alcohols to acids) • Toxins affect ATP consumption/production in mitochondria (eg pcm, valproate, ARVs, metformin, CO, cyanide, formate, +++ adrenergic stimulation) [uncoupling oxidative phosphorylation or inhibiting cytochromes of the electron transport chain] • Toxins create ketoacids (eg ethanol, isoniazid)

Mechanisms of impaired acid elimination • Toxin metabolites damage kidneys (ethylene glycol) • Toxin causes distal RTA (eg toluene)

Treatment • Give supportive care and stop offending drug • HCO 3 - administration generally not recommended Appropriate for increasing poison elimination (eg salicylates) and countering Na channel block (eg TCA) • Consider antidotes where available (eg ethanol or fomepizole for toxic alcohol ingestion) • Thiamine, pyridoxine and folate for toxic alcohols