Oxygen or nitrogen: which is the lesser of two evils?

Ever since it was discovered in the 1770s, the risks and benefits of oxygen have been hotly debated (1). The article by Young, “Hyperoxia—A Review of Risk and Benefits,” the author addresses this important question: What is the optimal oxygen management strategy for cardiopulmonary bypass (CPB)? Surprisingly, after 60 years of clinical experience, there is still disagreement on the optimal partial pressure of oxygen during CPB. Perhaps this is because this simple question is complicated by variables such as the common use of iatrogenic anemia and the frequent infusion of gaseous microemboli (GME) during CPB. The author details the risks of high oxygen tension from the standpoint of potential detrimental effects on cardiovascular function, the generation of oxygen free radical species, and the adverse effects to the lungs and other organs during perfusion or on reperfusion. The author also mentions several possible benefits to using hyperoxia, including ischemic preconditioning of the myocardium, favorable effects on the longevity of GME, and a possible safety margin in that tissue stores of oxygen will be greater should oxygenation or blood flow become temporarily disrupted during surgery. He further reviews the evidence related to postoperative surgical site infection, nausea, and vomiting and decides that there is insufficient evidence to suggest hyperoxia confers any benefit in these areas. His conclusion is that hyperoxia is probably harmful and should be avoided unless the risk of GME is thought to be significant: the benefits of hyperoxia then outweighing the risks. Given that iatrogenic anemia is commonly used and it is well established that GME are prevalent during CPB, one could argue that a hyperoxia strategy should be used on all cases, at least at critical times, to enhance tissue oxygenation and attenuate and resolve GME in patients undergoing cardiac surgery. Membrane oxygenators have been in common use for over two decades. However, during the 30 years prior, bubble oxygenators were the dominant device. The main concern in those days was the excessive hemolysis caused by the bubbles, which resulted in increased renal and coagulation problems. Hyperoxia (95% O2 + 5% CO2 or 97% O2 + 3%CO2) was a necessity when using a bubbler. No nitrogen could be usedduring bubble oxygenation becauseof the very real risk of nitrogen emboli being pumped into the patient. Even after being defoamed by a separate cardiotomy reservoir, the frothy effluent from the ventricular vent and field suckerswas diverted to theoxygenbubble columnwhere any nitrogen was quickly off-gassed. GME, composed primarily of oxygen, exiting the venous reservoir were addressed with the development of purged arterial filters.A reduction of the “sweep (bubble) gas” flow could lower the paO2 in the blood and bubbles emanating from the oxygenator, but only at the risk of CO2 retention above acceptable levels. It was not until the advent of the membrane oxygenator that lower FiO2 values could be used with the reassurance (which we now know is false reassurance) that nitrogenous GME would not be entering the patient. Cavitation of blood containing normal oxygen and nitrogen levels by mechanical heart valves after implantation generates bubbles that can be detected in the brain using transcranial Doppler ultrasound (2). These bubbles are mainly nitrogenous. Nitrogen is less soluble in water than oxygen. So during excessive turbulence, temperature changes, or pressure changes, nitrogen is the first gas to come out of the solution. (Ask any knowledgeable diver about the physiology of the bends.) We know these bubbles are mainly nitrogen because when the nitrogen in the patient’s blood is off-gassed by breathing 100% oxygen, the cavitated bubbles go away. In one study, the administration of 100% oxygen by facemask reduced the cavitation generation of GME by 98% (3). Oxygen constrains the cavitation process of mechanical heart valves and speeds up the dissolution of gas bubbles generated by cavitation because those residual bubbles are mainly oxygen. By comparison, blood is constantly cavitated into nitrogenous GME to a much greater degree within the CPB pump: from the tips of the venous cannula, the ventricular vent cannula and the field suckers all the way through to the tip of the aortic cannula and beyond. Interventions by the perfusionist and surgeon further contribute to the embolic problem (4). Oxygen or nitrogen bubbles can damage the intimal lining of the capillaries that they enter and the best solution would be to prevent or eliminate GME entirely. However, with the current state-of-the-art technology, this is not practical to do with any consistency. Many perfusion articles over the years have documented these bubbles and have attested to the difficulty of detecting, preventing, and mechanically removing them despite improvements in circuit design (5). The next best thing is to change the nitrogen in GME to oxygen. This dissipates them much more rapidly. However, there are few references to suggest the use of hyperoxia to mitigate the dangers of nitrogenous GME during CPB (6). Evidence is not fact, although the evidence we choose to believe guides much of what we do. Contradictory evidence is only evidence that the facts are not fully known.