Associated with adverse drug interactions - acid–base and electrolyte disorders

Red flags

High anion gap metabolic acidosis in a patient on metformin with AKI/hypoxia - lactic acidosis
Salicylate toxicity with mixed respiratory alkalosis + metabolic acidosis
Severe hyperkalaemia with ECG changes on ACE-I/ARB/potassium-sparing diuretic/spironolactone
Refractory hypokalaemia despite replacement - consider hypomagnesaemia (diuretics, PPIs) or amphotericin B

Metabolic acidosis (raised anion gap)

Metformin-associated lactic acidosis - risk rises sharply with AKI, hypoxia, sepsis, contrast
Salicylate toxicity - early respiratory alkalosis (direct medullary stimulation) then mixed/metabolic acidosis as toxicity progresses
Propylene glycol (IV lorazepam/phenytoin infusions), methanol/ethylene glycol (osmolar gap)
Isoniazid, iron - both cause lactic acidosis via different mechanisms

Metabolic alkalosis

Hyperkalaemia

ACE-I/ARB, potassium-sparing diuretics (spironolactone, amiloride), NSAIDs, trimethoprim, beta-blockers
Combination of these agents multiplies risk, esp. with renal impairment

Hypokalaemia

Loop/thiazide diuretics, beta-agonists (salbutamol), insulin, theophylline, amphotericin B, laxatives

Hyponatraemia

Hypomagnesaemia

Diuretic, ACE-I/ARB, metformin use and recent dose changes
Intercurrent illness causing dehydration/AKI (precipitates metformin lactic acidosis, digoxin toxicity)
PPI duration (years, associated with hypomagnesaemia)
Salicylate ingestion history and timing

Volume status, Kussmaul breathing (metabolic acidosis), tachypnoea (salicylate)
Cardiac rhythm - hyperkalaemia (peaked T, widened QRS), hypokalaemia (U waves, arrhythmia)
Neuromuscular - weakness (severe hypo/hyperkalaemia), tetany (hypomagnesaemia)

Stop the causative agent and treat the electrolyte/acid-base derangement per standard protocols
Metformin lactic acidosis: stop metformin, supportive care, haemodialysis clears both metformin and lactate in severe cases
Salicylate toxicity: urinary alkalinisation (IV sodium bicarbonate) to enhance elimination and limit CNS penetration; haemodialysis for severe toxicity
Drug-induced hyperkalaemia: standard stabilisation (calcium, insulin/dextrose, salbutamol) + withhold the causative drug(s)
Replace magnesium before/alongside potassium in refractory hypokalaemia
Review and simplify polypharmacy contributing to the derangement

Refractory hypokalaemia is often actually hypomagnesaemia - replace Mg2+ first
Metformin lactic acidosis risk is dramatically higher with any acute kidney injury - "sick day rules" apply
Salicylate toxicity respiratory alkalosis can mask the severity of the underlying metabolic acidosis - watch the anion gap trend, not just pH
Combining ACE-I/ARB + spironolactone + NSAID is a common preventable cause of severe hyperkalaemia

1. Anion gap tells the story

"A raised anion gap with metformin and any hint of AKI or hypoxia means lactic acidosis until excluded."

2. Magnesium before potassium

"Refractory hypokalaemia on a diuretic or PPI - I check and replace magnesium first."

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