Abstract Body: Background: Hypoxemia is a leading cause of cardiac arrest and is associated with poor outcomes. Emergency treatments that do not rely on the failing lung are limited. We developed a novel method to produce oxygen nano- and microbubbles in saline without a carrier or shell that may be suitable for intravenous administration.

Hypothesis: We hypothesized that oxygen nano- and microbubbles in saline will increase oxyhemoglobin saturation (SO₂) in a dose-dependent manner when infused in a desaturated blood circuit.

Aims: To evaluate oxygen transfer to blood following administration of two oxygen-saline mixtures and measure bubble size distribution.

Methods: Oxygen gas was dissolved in saline at a ratio of 1:1 or 3:1 by volume at 1 atm in an accumulator pressurized to 100 atm. The pressurized mixture was released through a custom orifice to atmospheric pressure, causing nucleation of oxygen nano- and microbubbles. The mixture was infused directly into a heparinized ex vivo circuit containing 1L of venous blood from Yorkshire swine. The 1:1 mixture infused for up to 6 minutes (n=8); 3:1 infused for 3 minutes (n=9). The primary outcome was change in SO₂ at 10 minutes measured with continuous oximetry and timed blood gas analysis. Secondary outcomes were partial pressure of oxygen and hemolysis. Bubble size distribution was measured with optical imaging and laser diffraction.

Results: Starting hemoglobin was 8.3±0.2 mg/dL. Following infusion, SO₂ increased by 26±5% for 1:1 and 49±2% for 3:1 (P<0.01, Figure). Partial pressure of oxygen increased by 21±5 mmHg for 1:1 and 368±92 mmHg for 3:1 (P<0.01). Mean fluid volume delivered was 472±65 mL for 1:1 and 414±28 mL for 3:1. Mean flow rate was 1.5±0.2 mL/s for 1:1 and 2.3±0.2 mL/s for 3:1. Both mixtures caused hemolysis and platelet activation. In a 1:1 sample, mean nanobubble size was 59±13 nm and median microbubble size was 13.6 (IQR 11.2, 16.6) µm.

Conclusions: We demonstrated that an infusion of oxygen nano- and microbubbles in saline improves oxygenation in a desaturated blood circuit. An oxygen to saline ratio of 3:1 was more effective than 1:1. Hyperoxemia appears to be dose-dependent. The impact of oxygen content, flow rate, bubble size distribution, and blood age on hemolysis and platelet activation requires further study. Animal studies are necessary to investigate clinical safety endpoints and efficiency while oxygen metabolism is ongoing.