BY Ruwan Laknath Jayakody
The emergency usage of intravenous oxygen (IVO₂) therapy would be useful in children whenever a certain bridging time is required prior to instituting conventional ventilation and even extracorporeal membrane oxygenation (ECMO), which is a form of life support used for patients with life-threatening heart and/or lung problems, a specialist consultant paediatrician noted.
However, the academic also noted that intravenous oxygen (IVO₂) therapy is unlikely to become a long-term management approach due to clinical limitations imposed by infusion fluid-related requirements and technical problems in producing the required amounts of packaged oxygen.
These observations were made in an editorial titled “IVO₂ administration: Fact or fiction?” which was authored by Sri Lanka Journal of Child Health joint editor and specialist consultant paediatrician Dr. B.J.C. Perera and published in the said journal’s 51st Volume’s Third Issue in September 2022.
Hypoxaemia, a reduction in the amount of oxygen carried in the blood, causes drastic consequences and when extreme, has the potential to even kill humans. The administration of oxygen is the therapeutic manoeuvre that is resorted to in all forms of hypoxaemia. Many maneuvers can alleviate the effects of hypoxaemia, but they are not without their problems and disadvantages. In such a context, it is of interest that some entirely different and innovative initiatives have come into the scenario where oxygen could be directly delivered through the intravenous route.
According to J.A. Gehlbach, K.J. Rehder, M.A. Gentile, D.A. Turner, D.J. Grady, and I.M. Cheifetz’s “IVO₂: A novel method of oxygen delivery in hypoxaemic respiratory failure?”, this could be accomplished by artificially increasing the amount of dissolved oxygen in the blood, and that IVO₂ is a novel method to improve oxygen delivery that involves the intravenous administration of a physiologic solution containing dissolved oxygen at hyperbaric (ambient pressure is greater than sea level atmospheric pressure) concentrations. However, experts agree that while not yet at the stage of clinical testing in the US and Europe, the procedure has been used safely in Asia and that initial laboratory data have been encouraging. These suggest that IVO₂ may have a role in the management of patients with hypoxaemic respiratory failure in the future. Gehlbach et al. however point out that more work needs to be undertaken, including providing clear evidence that such therapy is safe before it can be advocated for general use for hypoxaemic respiratory failure.
A more recent development is the use of nanotechnology to administer IVO₂. In “Oxygen gas-filled microparticles provide IVO₂ delivery”, an injectable foam suspension containing self-assembling, lipid-based microparticles encapsulating a core of pure oxygen gas for intravenous injection is developed and when mixed with human blood in vitro, the oxygen transfer from 70 volume per cent microparticles was complete within four seconds while when the microparticles were infused by intravenous injection into hypoxaemic rabbits, arterial oxygen saturations increased within seconds to near normal levels, only to be followed by a decrease in oxygen tensions after stopping the infusion.
The particles were also infused into rabbits undergoing 15 minutes of complete tracheal occlusion (an innovative approach aimed at driving accelerated lung growth in the most severe forms of diaphragmatic hernia) and here, oxygen microparticles significantly decreased the degree of hypoxaemia in these rabbits, and the incidence of cardiac arrest and organ injury was reduced, when compared to the controls. Therefore, Kheir et al. postulated that administering oxygen directly to the bloodstream could represent a technique for the short-term rescue of profoundly hypoxaemic patients.
More recently, A.K. Vutha, R. Patenaude, A. Cole, R. Kumar, J.N. Kheir, and B.D. Polizzotti’s “A microfluidic device for real-time on-demand IVO₂ delivery” claimed to have perfected a device that can inject oxygen directly into the bloodstream through the intravenous route. There are risks of directly injecting oxygen into the bloodstream as it has the potential to create air bubbles that can block blood vessels (embolisms) which can often even be fatal.
A new technology claims to overcome this with an entirely new procedure using a new device. To prepare the oxygen to be injected into the bloodstream, the oxygen is put into the device along with a fluid containing phospholipid (a type of fat that is found in the linings of human cells). The gas and the fluid are then made to move through nozzles of decreasing size in order to create tiny nanobubbles of oxygen with a phospholipid coating, all smaller than a single red blood cell. These bubbles are coated with the phospholipid membrane similar to that in every cell in the body, which prevents them from merging with other bubbles so as to create larger ones, and in turn, provides a path for the oxygen to diffuse out and into the blood while minimising the likelihood of material-related toxicities, and therefore, as emphasised in “Experimental device would give oxygen by IV”, the phospholipid packaging and tiny size of the bubbles are critical for making the entire manoeuvre safe.
The new emulsion, a fluid full of tiny bubbles, is then injected into the bloodstream. Once the solution is injected, the material dissolves, leading to the release of the packaged oxygen. In vitro experiments on donated human blood have shown that blood oxygen saturation levels could be lifted from 15% to over 95% within just a few minutes. In live rats, the process increased oxygen saturation from 20% to 50% quite rapidly. Hence, it is postulated that these devices allow for the control of the dosage of oxygen delivered and the volume of fluid administered, both of which are vital in the management of critically ill patients.
That said, researchers have not tested the device on humans as the technology is far from ready to be tested on humans. Vutha et al. elaborate: “If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxaemia.”
While this is a significant development, it needs to be taken into consideration that there have not been any in vivo human studies of this procedure as of yet. Injecting oxygen into the body in this manner can become complicated if it is administered in the wrong way or for doubtful indications if too much or too little is added. The team has to test their oxygen injection on larger animals before moving on to human trials.
It is hoped that this new device can be utilised to keep alive people who cannot breathe properly by providing them with oxygen. It can also better prepare the body to be placed on ECMO. The said device could “potentially be integrated into existing ventilators, allowing for the seamless integration into existing clinical workflows”. It is believed that patients who are injected with the solution may regain near normal blood oxygen levels within seconds and that this can in turn drastically reduce the incidence of organ injury and cardiac arrest. Scientists have however opined that the research team needs to make the device more dependable and ensure that it provides at least 10 times more oxygen.
If the procedure is found to be efficacious and safe, the initial use for this initiative would be to buy time by its emergency usage in recalcitrant hypoxaemia before other procedures, particularly ECMO, could be instituted as a definitive long-term management strategy.
How emergency intravenous oxygen therapy can save child lives
21 Sep 2022
How emergency intravenous oxygen therapy can save child lives
21 Sep 2022