What are the notable trials related to the use of sodium bicarbonate (NaHCO3) in critical care settings, such as cardiac arrest and severe metabolic acidosis?

Famous Trials Related to Sodium Bicarbonate Use

Cardiac Arrest Trials

The most notable finding across cardiac arrest trials is that sodium bicarbonate administration does not improve return of spontaneous circulation (ROSC) or survival outcomes, and may actually worsen results. 1

Key Negative Findings

• Multiple studies from 1962-2023 demonstrated that sodium bicarbonate was associated with lower rates of ROSC and worse overall outcomes in conventional cardiac arrest scenarios. 1 This systematic review of 372 records spanning six decades found consistent evidence against routine use.

• A 2018 prospective, double-blind, randomized placebo-controlled pilot trial (NCT02303548) specifically examined patients with severe metabolic acidosis (pH <7.1 or bicarbonate <10 mEq/L) during prolonged CPR. 2 This trial enrolled 50 out-of-hospital cardiac arrest patients who failed to achieve ROSC after 10 minutes of CPR. While sodium bicarbonate significantly improved pH (6.99 vs. 6.90, P=0.038) and bicarbonate levels (21.0 vs. 8.0 mEq/L, P=0.007), it showed no benefit in sustained ROSC (4.0% vs. 16.0%, P=0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, P=1.000). 2

Guideline Consensus Against Routine Use

• The 2010 International Consensus on Cardiopulmonary Resuscitation (published in Circulation) found no randomized controlled trials evaluating sodium bicarbonate in cardiac arrest, with evidence limited to case series and animal studies (Level of Evidence 5). 3 This represents the highest-quality guideline evidence available, establishing that routine bicarbonate use lacks support.

• The American Heart Association issued a Class III recommendation (Level of Evidence B) against routine sodium bicarbonate use in cardiac arrest, citing multiple studies showing no benefit or association with poor outcomes. 4 The guideline specifically notes that bicarbonate administration may compromise coronary perfusion pressure by reducing systemic vascular resistance. 4

Specific Indications Where Trials Support Use

Tricyclic Antidepressant and Sodium Channel Blocker Toxicity

The strongest evidence for sodium bicarbonate use comes from toxicology scenarios, particularly tricyclic antidepressant overdose with cardiac conduction abnormalities. 3

• Evidence from 2 case series (LOE 5) and 6 animal studies (LOE 5) supports sodium bicarbonate as the mainstay therapy for tricyclic-induced cardiac conduction abnormalities with wide QRS complexes. 3 The 2010 International Consensus recommends sodium bicarbonate bolus therapy in the post-arrest period for patients with tricyclic-associated cardiotoxicity. 3

• The American Heart Association provides a Class I recommendation (Level B-NR) for hypertonic sodium bicarbonate (1000 mEq/L) as IV bolus for life-threatening cardiotoxicity from tricyclic and tetracyclic antidepressant poisoning. 5 This represents the highest strength of recommendation in guideline methodology.

Severe Metabolic Acidosis Trials

The evidence for sodium bicarbonate in severe metabolic acidosis remains limited and controversial, with most high-quality trials showing no benefit. 6

• Two blinded randomized controlled trials comparing equimolar saline versus bicarbonate in lactic acidosis patients showed no difference in hemodynamic variables or vasopressor requirements. 5 This directly contradicts the theoretical benefits of bicarbonate therapy.

• The Surviving Sepsis Campaign explicitly recommends against sodium bicarbonate therapy for hypoperfusion-induced lactic acidemia when pH ≥7.15, based on these negative trial results. 5

Diabetic Ketoacidosis Studies

Recent data from multiple trials demonstrate that sodium bicarbonate in diabetic ketoacidosis does not improve patient outcomes and may cause harm, particularly in pediatric patients. 6

• The American Diabetes Association restricts bicarbonate use to only those DKA patients with pH <6.9, based on trials showing no benefit at higher pH levels. 5 For pH 6.9-7.0, only 50 mmol is recommended; for pH <6.9,100 mmol is recommended. 5

Contrast-Induced Nephropathy Prevention Trials

Multiple trials have examined isotonic sodium bicarbonate versus isotonic saline for preventing contrast-associated acute kidney injury, with conflicting results. 5

• The most recent high-quality trial in critically ill patients found no significant difference between isotonic bicarbonate and isotonic saline, with contrast-associated AKI occurring in 35.1% of bicarbonate patients versus 33.3% of saline patients (p=0.81). 5 This represents the highest-quality evidence in this indication.

• KDIGO guidelines acknowledge isotonic bicarbonate as an acceptable alternative to isotonic saline for high-risk patients (eGFR <60 mL/min/1.73m²), though evidence remains conflicting. 5

Rhabdomyolysis Studies

Available evidence suggests that alkalinization of urine with sodium bicarbonate in rhabdomyolysis does not improve patient-centered outcomes. 6 Despite theoretical benefits for preventing myoglobin precipitation, clinical trials have failed to demonstrate improved outcomes. 6

Common Pitfalls in Trial Interpretation

• Many clinicians misinterpret the correction of arterial blood gas parameters as evidence of clinical benefit, when trials consistently show that pH improvement does not translate to improved ROSC, survival, or neurologic outcomes. 2 The 2018 pilot trial exemplifies this disconnect perfectly. 2

• The lack of large randomized controlled trials in most indications means that much of the "evidence" consists of case series and animal studies (Level of Evidence 5), which should not guide routine clinical practice. 3

• Trials have documented multiple adverse effects including paradoxical intracellular acidosis, hypernatremia, hyperosmolarity, decreased ionized calcium, and catecholamine inactivation, which may explain why bicarbonate fails to improve outcomes despite correcting pH. 4, 7