What is the role of sodium bicarbonate (NaHCO3) in the treatment of severe metabolic acidosis in Intensive Care Unit (ICU) settings, as investigated by the Bicarb ICU 1 trial?

Sodium Bicarbonate in ICU Metabolic Acidosis: The BICAR-ICU Trial Findings

Primary Recommendation

The BICAR-ICU trial demonstrated that sodium bicarbonate infusion does not improve the composite outcome of 28-day mortality and organ failure in critically ill patients with severe metabolic acidosis (pH ≤7.20), except in the prespecified subgroup of patients with acute kidney injury (AKIN score 2-3), where it significantly reduced 28-day mortality. 1

Key Trial Results

Overall Population

• No benefit on primary composite outcome: The primary endpoint (death by day 28 or organ failure at day 7) occurred in 71% of control patients versus 66% of bicarbonate-treated patients (p=0.24), showing no significant difference 1
• No significant mortality benefit overall: 28-day survival was 46% in controls versus 55% in the bicarbonate group (p=0.09), which did not reach statistical significance 1

Critical Subgroup Finding: Acute Kidney Injury

• Significant mortality reduction in AKI patients: Among patients with AKIN score 2-3, bicarbonate therapy significantly improved 28-day survival from 37% to 54% (p=0.0283) 1
• This represents the most important actionable finding from the trial, identifying a specific population that benefits from intervention 1

Clinical Algorithm for Bicarbonate Use in ICU

When to Consider Bicarbonate (Based on Guidelines and BICAR-ICU)

Step 1: Assess pH threshold

• Do NOT use bicarbonate if pH ≥7.15 in sepsis-related lactic acidosis, as recommended by the Surviving Sepsis Campaign 2, 3
• Consider bicarbonate only when pH <7.15 with documented metabolic acidosis 3

Step 2: Identify specific indications where benefit is established

• Acute kidney injury (AKIN 2-3) with severe acidosis: This is the strongest indication based on BICAR-ICU subgroup analysis 1
• Hyperkalemia: Bicarbonate shifts potassium intracellularly 3
• Tricyclic antidepressant overdose: Strongly recommended (Class 1) for life-threatening cardiotoxicity with QRS >120ms 3, 4
• Sodium channel blocker toxicity: Reasonable to use (Class 2a) 3

Step 3: Exclude contraindications and assess risks

• Avoid in hypoperfusion-induced lactic acidemia with pH ≥7.15 2, 3
• Do NOT use routinely in cardiac arrest 3
• Recognize potential harms: sodium/fluid overload, increased lactate production, increased PCO2, decreased ionized calcium 3, 1

Dosing Protocol from BICAR-ICU

For severe metabolic acidosis (pH ≤7.20):

• Use 4.2% sodium bicarbonate solution (isotonic formulation) 1
• Infuse 125-250 mL over 30 minutes 1
• Maximum 1000 mL within 24 hours after inclusion 1
• Target pH >7.30 (not higher to avoid alkalemia) 1
• For adults with pH <7.1, alternative dosing is 1-2 mEq/kg IV given slowly 3

Safety Profile from BICAR-ICU

Adverse effects observed more frequently with bicarbonate:

• Metabolic alkalosis 1
• Hypernatremia 1
• Hypocalcemia 1
• No life-threatening complications reported in the trial 1

Reconciling Conflicting Evidence

Why Guidelines Recommend Against Routine Use

• The 2012 Surviving Sepsis Campaign explicitly recommends against bicarbonate for pH ≥7.15 in hypoperfusion-induced lactic acidemia (Grade 2B) 2
• Two prior blinded RCTs showed no difference in hemodynamic variables or vasopressor requirements 3

Why BICAR-ICU Changes Practice for AKI Patients

• The AKI subgroup represents a distinct pathophysiology: These patients cannot renally compensate for acidosis, unlike those with intact kidney function 1
• The 17% absolute mortality reduction (37% vs 54% survival) in AKI patients is clinically meaningful and statistically significant 1
• A 2025 target trial emulation from Australian ICUs corroborated a small mortality benefit (1.9% absolute reduction, RR 0.86) across all patients with metabolic acidosis, with sustained effects at 30 days 5

Critical Pitfalls to Avoid

Do not give bicarbonate for:

• Diabetic ketoacidosis unless pH <6.9 (no benefit shown, potential harm in pediatrics) 3, 6
• Routine cardiac arrest (no outcome benefit) 3
• Lactic acidosis with pH ≥7.15 (no benefit, potential harm) 2, 3
• Rhabdomyolysis for urinary alkalinization (does not improve patient-centered outcomes) 6

Essential monitoring requirements:

• Ensure adequate ventilation before and during therapy to eliminate excess CO2 produced 3
• Monitor serum sodium (keep <150-155 mEq/L) 3
• Monitor pH (keep <7.50-7.55 to avoid alkalemia) 3
• Monitor and treat hypokalemia during alkalemia 3
• Never mix with calcium-containing solutions or vasoactive amines 3

Bottom Line for Clinical Practice

Use sodium bicarbonate in ICU patients with severe metabolic acidosis (pH ≤7.20) primarily when acute kidney injury (AKIN 2-3) is present, as this is the only population with proven mortality benefit from the BICAR-ICU trial. 1 For other indications, restrict use to specific toxicologic emergencies (tricyclic overdose, sodium channel blockers) and hyperkalemia, while avoiding routine administration in septic lactic acidosis with pH ≥7.15. 2, 3, 4