Sodium Bicarbonate for In-Hospital Cardiac Arrest: A Randomized Clinical Trial

Bottom line

In this trial of 779 adults with in-hospital cardiac arrest who had already received epinephrine, sodium bicarbonate (up to 100 mmol) did not significantly improve sustained ROSC, 30-day survival, or favorable 30-day neurologic outcome versus placebo, while alkalosis and hypernatremia were more common with bicarbonate, findings that do not support routine bicarbonate use during in-hospital cardiac arrest.

PICO at a glance

• Population: Adults with in-hospital cardiac arrest who had received at least 1 dose of epinephrine (779 analyzed of 913 randomized; 2913 screened).
• Intervention or exposure: Sodium bicarbonate IV, up to 2 doses of 50 mmol each (maximum 100 mmol), timed to the 1st and 2nd epinephrine doses (per ClinicalTrials.gov NCT05564130).
• Comparator: Volume- and schedule-matched 0.9% NaCl placebo, same 2-dose-maximum timing.
• Outcomes: Primary: sustained ROSC, defined per the trial registry as spontaneous circulation with no further chest compressions needed for at least 20 minutes. Key secondary: 30-day survival; favorable 30-day neurologic outcome (modified Rankin Scale 0-3).
• Study design: BIHCA, a randomized, double-blind, placebo-controlled trial at 21 Danish hospitals.

Clinical question and design

Sodium bicarbonate has been given empirically during cardiac arrest for decades on the rationale that correcting acidosis might improve myocardial contractility and catecholamine responsiveness, yet current ACLS guidance already discourages routine use outside specific indications (severe preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose), a position built mostly on out-of-hospital cardiac arrest data and small or retrospective in-hospital series. BIHCA (Bicarbonate for In-Hospital Cardiac Arrest) is one of the first adequately powered randomized trials to test bicarbonate specifically in in-hospital cardiac arrest (IHCA).

BIHCA was led by Lars Wiuff Andersen (Aarhus University Hospital / Aarhus University). Adults with in-hospital cardiac arrest who had received at least 1 epinephrine dose were enrolled February 6, 2023 through February 11, 2026. Of 2913 screened, 913 were randomized and 779 analyzed, 372 sodium bicarbonate, 407 placebo. Median (IQR) age was 73 (64-79); 502 (64%) were male.

Intervention and outcomes measured

Per the registry (ClinicalTrials.gov NCT05564130), sodium bicarbonate was dosed 50 mL of 1 mmol/mL (50 mmol) as soon as possible after the first epinephrine dose, plus one additional 50-mmol dose after the second epinephrine dose if still in arrest (maximum 2 doses, 100 mmol), matching the abstract's "up to 100 mmol." Placebo was volume- and schedule-matched 0.9% NaCl. The primary outcome, sustained ROSC, was defined as spontaneous circulation with no further chest compressions needed for at least 20 minutes.

Results

Sustained ROSC occurred in 146 of 372 (39%) bicarbonate patients versus 150 of 407 (37%) placebo patients (risk ratio, 1.05; 95% CI, 0.88-1.24; P=.62), not significant. At 30 days, 45 (12%) bicarbonate and 37 (9.1%) placebo patients were alive (RR, 1.25; 95% CI, 0.84-1.88), the interval crosses 1. Favorable 30-day neurologic outcome (mRS 0-3) occurred in 30 (8.1%) versus 22 (5.4%) patients (RR, 1.39; 95% CI, 0.82-2.34), also not significant.

Additional findings

The retained full paper reports the safety outcomes directly. In 779 analyzed in-hospital cardiac-arrest patients, sodium bicarbonate did not improve sustained ROSC (39% versus 37%; RR 1.05, 95% CI 0.88-1.24). Among patients with return of spontaneous circulation or extracorporeal circulation who were evaluable for the prespecified laboratory adverse events (147 bicarbonate; 153 placebo), alkalosis occurred in 52 (35%) versus 31 (20%), and hypernatremia in 62 (42%) versus 44 (29%). Thirty-day survival and favorable neurologic survival were also imprecise and did not demonstrate benefit. This supports avoiding routine bicarbonate for undifferentiated in-hospital cardiac arrest; it does not address indication-specific use.

Uncertainty and limitations

The primary analysis included 779 of 913 randomized patients. The participant flow and exclusions should be considered when interpreting the analysis population. The trial was conducted entirely in Denmark, which may limit generalizability to other resuscitation systems. The reported safety-event proportions use the evaluable laboratory subgroup, not all randomized or analyzed patients.

Literature review and evidence synthesis

BIHCA is among the first large, adequately powered randomized trials to test sodium bicarbonate specifically in in-hospital cardiac arrest, a setting long extrapolated from out-of-hospital resuscitation literature and small or retrospective bicarbonate studies. Current ACLS/AHA guidance (2020 AHA Guidelines for CPR and ECC, Part 3) already discourages routine bicarbonate use outside specific indications; BIHCA's non-significant result in IHCA adds trial-level evidence consistent with that stance rather than overturning it.

How this fits with the broader evidence

BIHCA did not demonstrate a statistically significant improvement with sodium bicarbonate on the primary outcome (sustained ROSC) or on either secondary outcome (30-day survival, favorable neurologic outcome). All three point estimates numerically favored bicarbonate, but every 95% CI crossed the null, meaning the trial cannot rule out either a real benefit or a real harm. This pattern does not support routine use and is consistent with, rather than contradicting, ACLS guidance reserving bicarbonate for specific indications: severe preexisting metabolic acidosis, hyperkalemia, and tricyclic antidepressant overdose. Pharmacists managing code carts and ACLS drug supply should treat BIHCA as reinforcing electrolyte and pH monitoring when bicarbonate is used, and should confirm local protocols reflect this evidence rather than assuming larger empiric doses help.

ACPE UAN: 0683-0000-26-036-H01-P

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Study source: PMID:42273960