Sodium Bicarbonate for Metabolic Acidosis in the Intensive Care Unit (SODa-BIC) trial

Sodium Bicarbonate for Metabolic Acidosis in the Intensive Care Unit (SODa-BIC) trial

The SODa-BIC Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. NEJM 2026; doi: 10.1056/NEJMoa2600526

Clinical Question

• In critically ill adults with metabolic acidosis (pH < 7.30) receiving vasopressors, does sodium bicarbonate decrease the risk of major adverse kidney events within 30 days compared with placebo?

 

Background

• Metabolic acidosis disrupts normal cellular and organ function through effects on haemodynamics, oxygen delivery, and metabolic regulation
• Persistent acidosis increases risk of acute kidney injury and renal replacement therapy (RRT), which are associated with longer ICU stay and increased mortality
• There is conflicting evidence regarding sodium bicarbonate in metabolic acidosis

 

• A recent large target trial emulation performed in Australia found a statistically significant reduction in mortality

• BICAR-ICU found no difference in primary composite outcome of mortality or organ failure, except in a subgroup of patients with moderate-to-severe kidney injury
• BICAR-ICU 2 found no mortality benefit in a cohort of patients with moderate-to-severe AKI
• Both BICAR-ICU and BICAR-ICU2 found a reduction in RRT use in bicarbonate group

 

Design

• Multi-centre, randomised, double-blinded trial
• Eligible patients assigned in 1:1 ratio into sodium bicarbonate or placebo group
• Permuted block randomisation of varying sizes with computer generated allocation sequence
• Stratification by centre, pH (<7.25 or >7.25), and creatinine level (<150 or >150 mmol/L)

 

Setting

• 55 ICUs across seven countries (Australia, New Zealand, Japan, India, Oman, Saudi Arabia, Brazil)
• Enrolment from April 2023 to December 2025

 

Population

• Inclusion:
  • Adult’s age >18 years admitted into the ICU receiving a continuous vasopressor infusion to maintain a MAP > 65mmHg (or as determined by treating clinician) AND
  • Dedicated line (central or peripheral) AND
  • Metabolic acidosis within last 2hr before randomisation: pH <7.30 AND Base excess ≤ 4mEq/L AND PaC02 ≤ 45mmHg (non-intubated) or ≤50mmHg (intubated)
• Exclusion:
  • Clinically significant digestive or urinary tract loss of sodium bicarbonate
  • Diabetic ketoacidosis
  • CKD with an eGFR <30 mL/min
  • Receiving sodium bicarbonate at the time of randomisation
  • Currently receiving RRT (acute or chronic) or planned to start RRT in the next 3 h
  • Severe dysnatraemia (serum Na 155 mEq/L or <120 mEq/L),
  • Hypokalaemia (serum K <2.5 mEq/L)
  • Pulmonary oedema with PaO2/FiO2 <100
  • Hypocalcaemia (iCa <0.8mmol/L)
  • Drug overdose or intoxication
  • Pregnancy or breastfeeding
  • Considered to be at high risk of cerebral oedema by the treating clinician
  • Death is deemed to be inevitable due to the current acute illness
  • Patients with a life expectancy <30 days due to a chronic or underlying medical condition
• Patient characteristics between bicarbonate and placebo groups generally well balanced
  • Age – 65.0 vs 68.0
  • APACHE score on ICU admission – 21 vs 22
  • Median pH at eligibility – 7.26 vs 7.26
  • Median Base Excess – -9.2 vs -8.8
  • Median Bicarbonate – 17.0 vs 18.0 mmol/L
  • Median Creatinine – 1.46 vs 1.42 mg/dl
  • Acute Kidney Injury – 46.5% vs 45.8%

 

Intervention

• Administration of 8.4% Sodium Bicarbonate infusion (600mEq/L)
  • Aim to achieve and maintain arterial blood gas pH ≥7.30 and ≤7.35 and BE ≥ 0 using pre-defined changes to rate of fluid administration depending on pH
  • Infusion duration for 5hr to achieve/maintain target pH, unless initiation of RRT, patient dies, or is discharged from ICU

Control

• Infusion of 5% dextrose solution

 

Management common to both groups

• Intervention/comparator to start within 1 hour of randomisation
• Other aspects of care are determined by the treating clinical team, including the use of additional fluid therapy, vasopressors, and other organ support modalities.
• Open-label bicarbonate may be considered if pH <7.10, HC03 < 8 mmol/L, BE < -15mEq/L, severe hyperkalaemia (K>7.0 mmol/L) in presence of pH <7.10 or after the 5-hour intervention period

 

Outcome

Primary outcome

• Death, use of renal-replacement therapy, or persistent renal dysfunction, within 30 days: sodium bicarbonate vs placebo
  • No significant difference: 98 of 244 patients (40.2%) vs 100 of 254 patients (39.4%)
  • Adjusted difference 1.2 percentage points; 95% CI, −7.1 to 9.4; P=0.78
  • Secondary outcomes
  • No statistically significant difference in the following secondary outcomes: sodium bicarbonate vs placebo
• In hospital death by day 30: 62 (25.4%) vs 61 (24.0%)
• RRT within 30 days: 41 (16.8%) vs 53 (20.9%)
• Persistent renal dysfunction within 30 days (>200% baseline): 34 (14.0%) vs 46 (18.3%)
• RRT dependence at day 30: 14 (5.7%) vs 23 (9.1%)
• In-ICU death by day 30: 49 (20.1%) vs 56 (22.0%)
• In-hospital death by day 90: 64 (26.2%) vs 65 (25.6%)

 

• Physiological outcomes: sodium bicarbonate v placebo
  • Recurrence of metabolic acidosis: 78 (32.0%) vs 141 (55.7%)
  • AKI: 156 (64.5%) vs 162 (64.8%)

 

• Adverse Effects
  • 4 (1.6%) in bicarbonate vs 0 in placebo, P=0.06
  • All involved hypokalaemia K <3.0mmol/L

 

Authors’ Conclusions

The use of sodium bicarbonate for correction of metabolic acidosis in adult patients in the ICU receiving a vasopressor infusion to treat hypotension DID NOT result in a lower risk of major adverse kidney events within 30 days. Secondary outcomes regarding in-hospital death, persistent renal dysfunction, and renal-replacement therapy dependence appeared to be similar in the two groups.

 

Strengths

• Inclusion of patients with mild-moderate metabolic acidosis pH <7.30 unlike BICAR-ICU 1 and 2 which included only patients with severe metabolic acidosis pH <7.20
• Double-blinded study, in contrast to open-label BICAR-ICU trials
• International RCT encompassing seven countries

Weaknesses

• Patients required to be on a vasopressor – excluded patients without shock
• High exclusion rate with 2422 of 3060 patients screened being excluded – reduction in generalisability to certain sub-groups

 

The Bottom Line

• In ICU patients with a metabolic acidosis and pH <7.30, the use of sodium bicarbonate did not result in a reduction in death from any cause, receipt of renal-replacement therapy, or persistent renal dysfunction at 30 days
• Sodium bicarbonate for metabolic acidosis in the ICU should remain a clinician-directed therapy, used selectively to achieve targeted physiological goals based on the hemodynamic and metabolic impact of acidosis.

 

External Links

• article https://www.nejm.org/doi/full/10.1056/NEJMoa2600526

 

Meta data:

Summary author: Rockie Kang

Summary date: 20^th May 2026

Peer-review editor: Aniket Nadkarni