Did the BICAR-ICU 2 trial show a difference in mortality for patients with Acute Kidney Injury (AKI) stage 2-3 compared to the BICAR-ICU 1 trial?

BICAR-ICU 2 vs BICAR-ICU 1 Mortality Comparison in AKI Stage 2-3

The BICAR-ICU 2 trial is specifically designed to evaluate mortality in patients with moderate-to-severe AKI (stage 2-3) and severe metabolic acidosis, representing a focused investigation of the subgroup that showed mortality benefit in BICAR-ICU 1. 1

Key Differences Between the Trials

BICAR-ICU 1 Findings

• The original BICAR-ICU 1 trial demonstrated that sodium bicarbonate infusion was associated with higher survival rates in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury 1
• This mortality benefit was observed as a secondary endpoint in the subgroup analysis, not the primary outcome of the overall trial 1
• Long-term follow-up showed 5-year overall survival of approximately 30% with no significant difference between bicarbonate and control groups in the general population 2

BICAR-ICU 2 Design Rationale

• BICAR-ICU 2 specifically targets patients with both severe metabolic acidemia (pH ≤7.20, PaCO2 ≤45 mmHg, bicarbonate ≤20 mmol/L) AND moderate-to-severe AKI 1
• This population has an expected day-28 mortality of approximately 55-60%, substantially higher than the general ICU population 1
• The primary outcome is day-90 mortality (not day-28), allowing assessment of longer-term survival impact 1

Clinical Context of AKI Stage 2-3 Mortality

Mortality Risk by AKI Stage

• AKI stage 2 and 3 patients have the highest mortality among all AKI stages 3
• Stage 2 AKI (creatinine increase 2.0-2.9 times baseline) is strongly correlated with increased mortality 3
• Stage 3 AKI (creatinine increase ≥3.0 times baseline or ≥4.0 mg/dL) carries the greatest mortality risk 3, 4

Attributable Mortality Data

• The attributable mortality of stage 2 AKI is 12.4% (95% CI 2.6-21.8%) 5
• The attributable mortality of stage 3 AKI is 16.1% (95% CI 8.2-23.8%) 5
• Hospital mortality odds ratios increase progressively: stage 1 OR=1.73, stage 2 OR=1.88, stage 3 OR=2.89 6

Why BICAR-ICU 2 Focuses on This Population

Mechanistic Rationale

• The majority of excess mortality risk associated with severe AKI is attenuated by metabolic acidosis and cumulative fluid balance 6
• Approximately 70% of excess mortality in stage 3 AKI is explained by AKI-related complications, particularly metabolic acidosis 6
• Sodium bicarbonate may improve outcomes specifically when metabolic acidosis is present (OR 0.70,95% CI 0.53-0.92) 6

Study Status

• BICAR-ICU 2 is an ongoing trial designed to definitively answer whether sodium bicarbonate improves 90-day survival in this high-risk subgroup 1
• The trial uses 4.2% sodium bicarbonate infusion titrated to maintain pH ≥7.30 1
• Results are not yet published, so direct mortality comparison between trials cannot be made at this time 1

Important Clinical Caveats

• The BICAR-ICU 1 subgroup finding was hypothesis-generating, not definitive evidence, which is why BICAR-ICU 2 was designed 1
• Long-term quality of life remains significantly impaired in survivors regardless of bicarbonate therapy, particularly in physical domains 2
• Neither stage 1 AKI nor transient AKI showed increased mortality in matched analyses, emphasizing the importance of AKI severity and persistence 5
• The incidence of AKI in ICU patients exceeds 50%, with increasing severity directly correlating with mortality risk 7