Happy or Silent Hypoxia in COVID-19–A Misnomer Born in the Pandemic Era

Abstract

Early in the pandemic era of COVID-19 the term "happy or silent hypoxia" was introduced to describe patients with COVID-19 who presented with severe hypoxemia and absence of dyspnea (Couzin-Frankel, 2020;Guan et al., 2020). The absence of dyspnea despite severe hypoxemia was considered to be a "paradox" and unique to COVID-19 (Archer et al., 2020;Ferenchick and Ferenchick, 2020). As such the term "happy or silent hypoxia" has been received wide attention by the press and social media and even described as a silent killer in COVID-19 (Levitan, 2020). Although scientific evidence is lacking, central nervous system viral invasion has been put forward to explain this "paradox" (Nouri-Vaskeh et al., 2020;Gopal et al., 2021;Tavčar et al., 2021). Nevertheless, basic principles of respiratory system physiology dictate that the absence of dyspnea despite severe hypoxemia is not specifically linked to COVID-19 but to other lung diseases as well (Tobin et al., 2020). The aim of our article is to present information about the responses to both acute and sustained hypoxia and provide an analysis of control of breathing physiology that could explain the absence of dyspnea despite severe hypoxemia. Specifically, we apply in hypoxemic patients with COVID-19 our currently published analysis (Vaporidi et al., 2020) that relates arterial carbon dioxide levels with respiratory centers response to this stimulus, contrasting the brain's responses to the patient's ability to generate effective alveolar ventilation. This analysis may facilitate comprehension of the pathophysiology of dyspnea in hypoxemic patients with COVID-19.

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

“…A fall in oxygen saturation (hypoxemia) and higher respiratory rate (tachypnea) are associated with increased mortality risk in COVID-19 patients [ 91 , 92 ]. Hypoxia can occur even without dyspnea, and this phenomenon is called silent hypoxia [ 93 , 94 ]. Hypoxic cells produce larger amounts of aldehydes and ROS, leading to an even greater molecular modification of albumin [ 95 ].…”

Treatment experience of post-COVID cognitive impairment (clinical observation)

“…Появление «тихой» гипоксии ученые объясняют целой комбинацией биологических механизмов: аномальным перераспределением крови между поврежденной и интактной тканью легких со снижением притока к здоровой, обогащенной кислородом ткани и увеличением притока к поврежденной ткани с последующим снижением насыщения кислородом циркулирующей крови; микротромбообразованием внутри легочных сосудов и нарушением соотношения объема воздуха и кровотока, необходимого легким для нормального функционирования [24]. Опасность такой гипоксии заключается в способности «тихо» наносить ущерб органам и тканям, особенно чувствительным к гипоксии (гиппокамп), недооценки кислородного голодания головного мозга и возможности развития неврологических нарушений [25]. У наблюдаемого пациента гипоксия с чертами «тихой» гипоксии послужила поводом для госпитализации и оказания респираторной поддержки.…”

Respiratory Drive, Dyspnea, and Silent Hypoxemia: A Physiological Review in the Context of COVID-19

“…The response is directly stimulated by decreased P aO 2 tension or hypotension ("stagnant hypoxia"), not by S aO 2 . 40 And in contrast to the stimulatory effects of acute hypercapnia on central respiratory drive, brain stem hypoxia exerts a directly depressant effect. 22 The ventilatory threshold to hypoxemia occurs when P aO 2 sensed in the carotid bodies is # 60 mm Hg.…”

“…22 The ventilatory threshold to hypoxemia occurs when P aO 2 sensed in the carotid bodies is # 60 mm Hg. [40][41][42] The responses to acute hypoxemia (referred to as hypoxic ventilatory response) include tachypnea, hyperventilation, tachycardia, and elevated cardiac output, all of which rise proportionally as the severity of hypoxemia increases from mild to profound. [42][43][44][45] Furthermore, the magnitude of the hypoxic ventilatory response is mediated by the corresponding P aCO 2 .…”

“…It bears repeating that unless P aO 2 is 45 mm Hg hypoxemia alone often does not induce dyspnea, particularly when P aCO 2 is < 40 mm Hg. 8,40 A study examining how acute hypercapnia generates breathlessness in normal subjects found that by increasing P ETCO 2 from 39-43 mm Hg only a slight sensation of breathlessness was experienced. 87 In contrast, breathlessness intensified rapidly as P ETCO 2 rose to 45-48 mm Hg, becoming intolerable at 50 mm Hg.…”