BACKGROUND: Extravasation is the unintentional injection or leakage of fluids into the perivascular or subcutaneous space resulting in potential tissue injury. In this 2-part prospective, controlled study, we assessed the safety of subcutaneously injected sodium bicarbonate in rats first. In the second part, the diagnostic utility of using IV diluted sodium bicarbonate to confirm placement of IV catheters in endotracheally intubated and ventilated rats and patients was tested. Diluted sodium bicarbonate was created using undiluted standard 8.4% (1 mEq/mL) sodium bicarbonate mixed in a 1:1 ratio with sterile water to achieve a final diluted concentration of 4.2% (0.5 mEq/mL). METHODS: Sodium bicarbonate (8.4% and 4.2%) was injected subcutaneously into 10 rats, and skin samples were evaluated. The hemodynamic and ventilatory effects of IV bicarbonate (2 mL/kg) in ventilated rats were measured. Subsequently, in 20 ASA physical status I and II mechanically ventilated patients, the effects of 50 mL of diluted 4.2% sodium bicarbonate or 0.9% normal saline, injected in a randomized order, were analyzed. RESULTS: Part 1: Undiluted (8.4%) subcutaneous sodium bicarbonate resulted in a small area of skin necrosis in 10% of skin samples (3 of 30) taken from rats. Minimal effects (mild scale crust and foci of regenerative epidermis beneath) were detected when a diluted solution was used. In ventilated rats, IV injection of diluted bicarbonate caused a significant increase in end-tidal carbon dioxide, whereas subcutaneous injection had no effect. In humans, diluted bicarbonate resulted in an end-tidal carbon dioxide increase (mean of 38 ± 5 to 45 ± 7 mm Hg) within 7 breaths. Injected normal saline did not result in any changes. Sodium bicarbonate was easily differentiated from normal saline injection by anesthesiologists observing the change in end-tidal carbon dioxide concentrations immediately after injection. CONCLUSION: The injection of diluted sodium bicarbonate (in mechanically ventilated patients) can be used to reliably identify the correct location of an IV catheter by an increase in the exhaled carbon dioxide concentration. Although we found no skin damage with 4.2% (0.5 mEq/mL) sodium bicarbonate, safety and efficacy should be further evaluated in future studies.