Historical Appreciation of Brain Vulnerability from Pure Hypoxemia

By Eelco F. M. Wijdicks
First Online: 23 February 2021

Even more now than in the recent past, neurointensivists are asked to evaluate the effects of hypoxemia on the brain. The SARS-CoV-2 pandemic, characterized by widespread transmission and admitting patients by the thousands, requires aggressive management of profound hypoxemia. Many patients are initially in what has been called “silent hypoxemia.” A thoughtful explanation of why ‘silence’ is expected rather than unusual has been provided by Tobin et al., who emphasizes to recognize well-established physiology principles [1]. Hypoxia increases depth and rate of breathing but the carotid artery baroreceptors are set at quite low levels. Patients seldom experience dyspnea with moderate hypoxemia. This is further illustrated by the experience of climbers, in whom oxygen saturations of < 65% for prolonged periods may “dull the mind” but do not always increase the sensation of dyspnea [2]. Clinically, only a severely hypoxemic (< 50%) patient is tachypneic (assuming no further blunting effect from hypercarbia or enhancing effect from fever) and restless. The gradual hypotension and rising PaCO2 are eventually more crucial factors in declining consciousness than hypoxemia alone.

Neurologists will have to anticipate an increasing number of intensive care consults during and even long after the SARS-CoV-2 pandemic is over. Specifically there will be questions about whether the brain can tolerate prolonged hypoxemia. Early neuropathology studies in SARS-CoV-2 have not found major brain damage due to hypoxemia. In a recent autopsy study of 43 patients between ages 51 and 94 years, 6 (14%) patients had new ischemic infarctions most likely due to thromboembolic events but no evidence of anoxic-ischemic injury in the examined frontal cortices [3].

Hypoxemia was already sub-classified in the 1920s [4], and it is important to distinguish between anoxic anoxia (reduced hemoglobin saturation due to pulmonary disease), anemic anoxia (reduced hemoglobin, but normal saturation in carbon monoxide poisoning), stagnant anoxia (normal hemoglobin saturation but reduced cerebral blood flow due to shock), and other less common forms. There is no question that profound hypoxemia may damage the brain, but when it does, there is often associated severe hypotension from vasodilatation (or briefly no pulse); hence, the commonly used moniker hypoxic-ischemic brain injury.

Already in the 1940’s alterations in cerebral metabolism after hypoxemia have been studied by Gurdjian et al. [5]. Cerebral lactic acid rose when the oxygen content of the inspired air fell to a critical level of 11 to 13 percent. As the oxygen percentage further decreased to a critical level of 7 percent, they noted phosphocreatine break down. A return to room air was followed by an extremely rapid re-synthesis of phosphocreatine, but lactic acid levels fell much more slowly.

Historically, from where did the data originate connecting hypoxemia with brain damage? What are the lessons for today?


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