Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine.

Acute respiratory failure can cause profound hypoxaemia that leads to organ injury or death within minutes. When conventional interventions are ineffective, the intravenous administration of oxygen can rescue patients from severe hypoxaemia, but at the risk of microvascular obstruction and of toxicity of the carrier material. Here we describe polymeric microbubbles as carriers of high volumes of oxygen (350-500 ml of oxygen per litre of foam) that are stable in storage yet quickly dissolve following intravenous injection, reverting to their soluble and excretable molecular constituents. In swine with profound hypoxaemia owing to acute and temporary (12 min) upper-airway obstruction, the microbubble-mediated delivery of oxygen led to: the maintenance of critical oxygenation, lowered burdens of cardiac arrest, improved survival, and substantially improved neurologic and kidney function in surviving animals. Our findings underscore the importance of maintaining a critical threshold of oxygenation and the promise of injectable oxygen as a viable therapy in acute and temporary hypoxaemic crises.

Esophageal oxyhemoglobin saturation as a resuscitative metric in hemorrhagic shock.

Background: Mixed venous saturation (SvO2) is considered the gold standard to assess the adequacy of tissue oxygen delivery (DO2) in shock states. However, SvO2 monitoring is challenging as it requires an invasive catheter and frequent blood sampling. Non-invasive methods, including near-infrared spectroscopy, have demonstrated low sensitivity to tissue dysoxia. Methods: We fabricated a new device that uses resonance Raman spectroscopy (RRS) to quantify oxyhemoglobin saturation (ShbO2) in the esophagus (eShbO2), tongue (tShbO2), and liver (hShbO2). In two rat models of hemorrhagic shock, we quantified (1) The correlation of RRS-measured ShbO2 to SvO2 during progressive hemorrhage (n=20) and (2) The value of these metrics to predict near-term mortality in fixed, severe hemorrhage (mean blood pressure =25 mm Hg; n=18). Results: In model 1, eShbO2 (r=0.705, p<0.0001) and tShbO2 (r=0.724, p<0.0001) correlated well with SvO2 and with serum lactic acid (eShbO2-lactate r=0.708, p<0.0001; tShbO2-lactate r=0.830, p<0.0001). hShbO2 correlated poorly with both SvO2 and lactic acid. Using time-matched ShbO2-SvO2 pairs, the performance of ShbO2 to detect severe tissue hypoxia (SvO2<20%) was excellent (AUC 0.843 for eShbO2, 0.879 for tShbO2). In model 2, eShbO2 showed a maximized threshold of 40% with 83% of animals dying within 45 minutes of this cut-off, demonstrating accuracy as a monitoring device. This was similar for tShbO2, with a threshold of 50%, predicting death within 45 minutes in 76% of animals. ShbO2 showed superior sensitivity to invasive monitoring parameters, including MABP<30 mm Hg (sensitivity 59%), pulse pressure<15 mm Hg (sensitivity 50%), and heart rate>220 bpm (sensitivity 39%, p=0.004). Conclusions: eShbO2 represents a new paradigm to assess the adequacy of DO2 to a tissue. It constitutes a promising monitoring method to evaluate tissue oxygen saturation in real time and non-invasively, correlating with SvO2 and time to death. Level of evidence: Level III, therapeutic/care management.

Low-Fouling Zwitterionic Polymeric Colloids as Resuscitation Fluids for Hemorrhagic Shock.

Colloids, known as volume expanders, have been used as resuscitation fluids for hypovolemic shock for decades, as they increase plasma oncotic pressure and expand intravascular volume. However, recent studies show that commonly used synthetic colloids have adverse interactions with human biological systems. In this work, a low-fouling amine(N)-oxide-based zwitterionic polymer as an alternative volume expander with improved biocompatibility and efficacy is designed. It is demonstrated that the polymer possesses antifouling ability, resisting cell interaction and deposition in major organs, and is rapidly cleared via renal filtration and hepatic circulation, reducing the risk of long-term side effects. Furthermore, in vitro and in vivo studies show an absence of adverse effects on hemostasis or any acute safety risks. Finally, it is shown that, in a head-to-head comparison with existing colloids and plasma, the zwitterionic polymer serves as a more potent oncotic agent for restoring intravascular volume in a hemorrhagic shock model. The design of N-oxide-based zwitterionic polymers may lead to the development of alternative fluid therapies to treat hypovolemic shock and to improve fluid management in general.