Acute severe metabolic acidosis: approach, anion gap, and lactate

Lactate and mortality: admission lactate >4 — mortality ~30%; lactate not clearing by 10% in 2-6h — worse outcomes (Jansen 2010, Arnold 2009). Lactate clearance as goal of resuscitation (Jansen TRIUMPH — no benefit of targeted clearance, but clearance correlates with survival).[6] } BICAR-ICU (Jaber 2018, Lancet): pH ≤7.20 — no overall benefit of bicarbonate; subgroup AKI grade 3-4 benefited (less death/RRT). Controversial.[3] } Sodium bicarbonate meta-analyses: no consistent mortality benefit in lactic acidosis (except BICAR-ICU AKI subgroup).[8] } Toxic alcohol: fomepizole + dialysis — survival good if treated early (AACT/EAPCCT guidelines).[14] } Salicylate: urinary alkalinisation + dialysis — good outcomes if recognised.[1] } Metformin-associated lactic acidosis: mortality 20-50% (often sepsis co-existing); RRT effective.[2] }

DESIGN: Multicentre (26 French ICUs), open-label, randomised controlled phase 3 trial. Jaber et al., Lancet 2018.[3] } POPULATION: 389 adults with severe metabolic acidaemia (pH ≤7.20, HCO3 ≤20, PaCO2 ≤32) — EXCLUDED DKA and purely toxic causes (where bicarbonate has specific role). Randomised to 4.2% sodium bicarbonate vs no bicarbonate (controls could receive if pH <7.0 or per strict criteria). PRIMARY OUTCOME (composite: death +/or need for RRT by day 28): NO significant difference overall (66% vs 64%, p=0.24). PRESPECIFIED SUBGROUPS: (1) AKI KDIGO stage 2-3: bicarbonate REDUCED primary outcome (55% vs 67%) AND less need for RRT. (2) No benefit in AKI stage 1 / no AKI. SECONDARY: bicarbonate group had less severe hyperchloraemia-driven acidosis and a trend to fewer arrhythmias; more hypernatraemia. INTERPRETATION: Bicarbonate is NOT routine for severe acidosis. MAY be considered in severe acidosis (pH ≤7.20) WITH severe AKI (KDIGO 3-4) — the only subgroup showing benefit. Editorial (Kraut & Madias): confirms equipoise; bicarbonate remains a 'last-resort' for pH <7.1 with instability.[7] } CLINICAL BOTTOM LINE: Treat the cause; reserve bicarbonate for pH <7.1-7.2 + instability, severe AKI, TCA overdose, hyperkalaemia, salicylate (urinary alkalinisation).[8] }

Surviving Sepsis Campaign 2021 (Evans et al.): measure lactate within 3h of sepsis recognition; resuscitate to normalise lactate (weak recommendation) OR guide by lactate clearance (weak).[16] } Casserly et al. 2015 (Surviving Sepsis Campaign database): admission lactate and lactate trajectory strongly predict mortality; lactate >4 mmol/L = severe sepsis criterion.[6] } Jansen TRIUMPH (2010): early lactate-guided therapy did NOT reduce mortality overall, but subgroup with elevated admission lactate showed trend to benefit. Lactate clearance correlates with survival but is NOT proven as a causal treatment target. ProCESS / ARISE / ProMISe (EGDT trials): lactate-based / ScvO2-based early goal-directed therapy not superior to usual care — but lactate REMAINS a key prognostic marker and trigger for reassessment of perfusion. PRACTICE POINT: Use lactate as a perfusion marker (with ΔPCO2 + MAP + urine output), not as the sole resuscitation target. Rising or static lactate → reassess source, perfusion, mesenteric ischaemia, occult bleed.

Methanol (AACT/EAPCCT guidelines, Barceloux 1999): fomepizole blocks alcohol dehydrogenase → halts formate production. Indications: methanol level >20 mg/dL, or HAGMA + osmolar gap + history, or visual symptoms. Add folate/leucovorin (speeds formate → CO2 + H2O). Dialysis if level >50 mg/dL, severe acidosis, visual symptoms, end-organ damage. Survival >90% with early fomepizole + dialysis; visual sequelae depend on cumulative formate exposure.[15] } Ethylene glycol (AACT/EAPCCT guidelines, Barceloux 2002): fomepizole + thiamine + pyridoxine (divert glyoxylate away from oxalate) + dialysis. Dialysis if level >50 mg/dL, severe acidosis, AKI. Outcomes good if treated before AKI established; renal recovery variable.[14] } Key point: empirical fomepizole on suspicion (do NOT wait for confirmatory levels) — safe, well-tolerated, dramatically changes outcome. Antidote threshold is low.

THAM (tris-hydroxymethyl aminomethane): small trials (Hoste 2005) show comparable pH correction to sodium bicarbonate in mild ICU metabolic acidosis, with less CO2 generation (useful in hypercapnic / ventilated patients).[17] } Limitations: no large multicentre RCT equivalent to BICAR-ICU; not universally available; risk of hyperkalaemia, hypoglycaemia, extravasation necrosis, contraindicated in severe renal/hepatic failure (drug accumulation). Role: adjunct when bicarbonate contraindicated (hypernatraemia, hypercapnia) or investigational; not first-line. Carbicarb (equimolar Na2CO3/NaHCO3): theoretical advantage (less CO2 generation) — limited availability, sparse human data.