Why No O's: Part 2 of 3
The Guidelines for Emergency Cardiac Care (ECC) in 2000 and 2005 recommended against supplemental oxygen for patients with saturations above 90 percent. The current 2010 ECC Guidelines There is insufficient evidence to support [oxygen’s] routine use in uncomplicated ACS. If the patient is dyspneic, hypoxemic or has obvious signs of heart failure, providers should titrate therapy, based on monitoring of oxyhemoglobin saturation, to 94% (Class I, LOE C).
What is new are prehospital research studies comparing outcomes of patients treated without oxygen or with oxygen titrated to saturations versus patients routinely given high flow oxygen. These data are frightening; they invariably show impressive patient harm from even short periods of hyperoxia. We’ve known since 1999 that oxygen worsened survival in patients with minor to moderate strokes and made no difference for patients with severe stroke. In fact, the American Heart Association recommended in 1994 against supplemental oxygen for non-hypoxemic stroke patients.
The dangers from giving oxygen to neonates have also been long appreciated. The most compelling outcome studies of 7 neonates published in 2004 and repeated in 2007 showed a significant increase in mortality of depressed newborns resuscitated with oxygen (13%) versus room air (8%). This led to the current neonatal resuscitation recommendations for use of room air positive pressure ventilation. In 2002, a study of 5,549 trauma patients in Texas showed prehospital supplemental oxygen administration nearly doubled mortality.
A Tasmanian study of prehospital difficulty breathing patients published in 2010 compared patients treated with oxygen titrated to saturations of 88 to 92 percent to patients treated with non-rebreather oxygen masks. It showed a reduction in deaths during subsequent hospitalization of 78 percent in COPD patients and 58 percent in all patients. New studies are showing a troubling pattern of worse outcomes associated with hyperoxia post cardiac 10 arrest.
It has been our traditional practice to give high concentrations of oxygen to patients with chest pain and MI, for reasons no better than “this is how we’ve always done it.” As Israeli physician Chaim Lotan said at a conference in 2011, “We have been brainwashed into using oxygen” even though recent data suggests it has harmful effects that are mediated primarily by coronary artery vasoconstriction. “Before I started looking into the data,” Lotan said, “I didn’t understand how much damage we were causing by giving oxygen.” Why would oxygen worsen patient outcomes? One mechanism may be absorption atelectasis. Oxygen shares alveolar space with other gases, principally Nitrogen. Nitrogen is poorly soluble in plasma, and thus remains in high concentration in alveolar gas. If the proximal airways are obstructed, for example by mucus plugs, the gases in the alveoli gradually empty into the blood along the concentration gradient, and are not replenished: the alveoli collapse, a process known as atelectasis. This is limited by the sluggish diffusion of Nitrogen. If nitrogen is replaced by another gas, that is if it is actively “washed out” of the lung by either breathing high concentrations of oxygen, or combining oxygen with more soluble nitrous oxide in anesthesia, the process of absorption atelectasis is accelerated. It is important to realize that alveoli in dependent regions, with low V/Q ratios, are particularly vulnerable to collapse. This condition permits blood to pass from the right side of the heart to the left side without meeting air for gas exchange of oxygen and carbon dioxide.
Two studies addressed the degree of atelectasis formation with maintenance ventilation with varying fractions of inspired oxygen. Edmark et al5 performed an observational study with a historical cohort using data from their 2003 research.4 They found that preoxygenation and maintenance with 80% oxygen resulted in a slower onset, but eventually equal degree of atelectasis formation over time compared with preoxygenation with 100% oxygen.5 The researchers drew this conclusion by comparing ventilation with 80% oxygen for 45 minutes and ventilation with 100% oxygen for 14 minutes.
In the second study, Agarwal et al performed a more rigorous research study using a comparative experimental design and including 27 subjects. They found that maintenance ventilation with 40% oxygen resulted in significantly lower atelectasis than maintenance with 100% oxygen.
Gas laws mandate that increases in the concentration of one gas will displace or lower the concentration of others. Room air normally contains 21 percent oxygen, 78 percent nitrogen, and less than 1 percent carbon dioxide and other gases. Nitrogen, the most abundant room air gas, is responsible for secretion of surfactant, the chemical that prevents collapse of the alveoli at end expiration. Premature infants often are not developed sufficiently to produce surfactant and require endotracheal administration of animal surfactant. “Washout” of nitrogen in adult lungs occurs when high concentration oxygen is administered. This “washout” may be desirable temporarily in patients being preoxygenated for rapid- or delayed-sequence intubation, but over time atelectasis may occur and this is not good. Once intubation is accomplished, a natural mixture of gases must be allowed to reconstitute in the lungs to avoid collapse of alveoli and atelectasis. Lower concentrations of nitrogen can lead to decreased surfactant production with subsequent atelectasis and collapse of alveoli, significantly impeding oxygen exchange.
In fact, it is true that 100% oxygen given by non-rebreather reduces coronary artery flow by 30% after 5 minutes. It also reduces the effects of vasodilators, such as nitroglycerin. Researchers in New Zealand led by Meme Wijesinghe found evidence, while limited, which suggests that routine use of high-flow oxygen in uncomplicated MI may result in a greater infarct size and possibly increase the risk of mortality.5 These authors concluded it is well-established that arterial oxygen tension is a major determinant of coronary artery blood flow and that high-flow oxygen therapy can cause a reduction in cardiac output and stroke volume. Potentially harmful mechanisms include the paradoxical effect of oxygen in reducing coronary artery blood flow and increasing coronary vascular resistance, measured by intracoronary Doppler ultrasonography (McNulty 2005;McNulty 2007); reduced stroke volume and cardiac output (Milone 1999); other adverse hemodynamic consequences, such as increased vascular resistance from hyperoxia; and reperfusion injury from increased oxygen free radicals (Rousseau 2005). Nitric oxide (NO) has a number of important physiological actions in the cardiovascular system. In the heart, NO plays role in keeping the vessels patent via vasodilation and prevention of platelet aggregation. It also plays an important role in regulating the force and rate of contraction. The hyperoxia-induced vasoconstriction is primarily the consequence of reduced bioavailability of nitric oxide caused by elevated oxidative stress and increased displacement of nitrogen. Many different and often contradictory effects of NO or on myocardial function have been reported which, until relatively recently, have been difficult to make sense of. However, there is now an emerging consensus that NO generally acts to fine tune and optimize cardiac pump function. It was shown that even after discontinuing the administration of oxygen this increased tendency towards vasoconstriction continued for up to 15 minutes. They concluded there is insufficient evidence to support the routine use of high-flow oxygen in the treatment of uncomplicated MI, and that it may increase mortality.
The final part of this blog posting will take a look at the latest guidelines in regards to oxygen administration. All references will be available following that posting.
Author Bill Young is the program director of the EKU Emergency Medical program. He will receive his doctorate in Educational Leadership this May. CAAHEP-accredited since 1978, EKU offers top quality degree programs in emergency medical care.
Published on March 31, 2016