key: cord-0859782-ezpq0boq authors: Heerdt, Paul M.; Shelley, Ben; Singh, Inderjit title: Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications date: 2021-12-27 journal: Br J Anaesth DOI: 10.1016/j.bja.2021.12.036 sha: da5fb7ee8e3bf4523019a62d496aa36876702e93 doc_id: 859782 cord_uid: ezpq0boq nan assessing perioperative risk. They note that patients suffering from "long COVID" have been reported to exhibit demonstrable abnormalities in several biomarkers as well as cardiac, neurologic, haematologic, renal, hepatic, and endocrine impairment. Based on current evidence, the authors suggest that patients previously experiencing mild COVID-19 but without clear evidence of these sequelae can be regarded as having minimal additional perioperative risk. In this context, the relatively young person who suffered mild COVID-19 a year earlier, complains of exertional fatigue but admits to being sedentary and unfit, and has no objective evidence of cardiopulmonary disease or other organ dysfunction will likely raise little concern. While the morbidity and mortality associated with severe COVID-19 has appropriately received considerable attention, most SARS-CoV-2 infections result in relatively mild, self-limited symptoms not requiring hospitalization. Nonetheless, some of these patients subsequently experience persistent fatigue and reduced exercise capacity that is not attributable to cardiopulmonary impairment diagnosed by conventional means 3 . Several mechanisms have been proposed including anaemia, deconditioning, and red blood cell abnormalities 4 . However, many of the studies describing these mechanisms were conducted in patients following hospitalization and/or within a few months of recovery. A central focus of perioperative management has always been maintenance of systemic oxygen delivery (DO2) and tissue perfusion. Toward this end, research has defined how the fundamental relationships between DO2, tissue oxygen consumption (VO2), and oxygen extraction (EO2) shift from the intraoperative setting where VO2 tends to be reduced, to the postoperative period when VO2 increases 5 . Although a range of postoperative complications has been linked to suboptimal tissue DO2 6 7 , the incidence of these complications appears relatively low in relation to the documented incidence of perioperative hypoxaemia 8 9 , particularly when considered in light of potential coincidence with other common factors such as anaemia, hypovolaemia, and transient hypotension. A contributing factor may be that, as with most physiological systems, evolutionary pressure has yielded compensatory mechanisms J o u r n a l P r e -p r o o f for reduced DO2 to many organs. Under most circumstances, when DO2 is low, VO2 is maintained by augmented EO2 to prevent tissue hypoxia 10 . This compensatory EO2 reserve persists until limits that vary among tissue beds are reached and VO2 becomes DO2-dependent. Ultimately, in the perioperative setting where alterations in regional VO2/DO2 balance occur with regularity it is probable that this EO2 reserve is working continuously 'behind the scenes' for organ protection. But what if this seemingly occult protective mechanism is impaired? Clinical experience imparts heightened suspicion of tissue vulnerability in patients with defined end-organ impairment or risk factors for reduced functional reserve such as aging, smoking, diabetes mellitus, or hypertension. But how does this affect that relatively young person who admits to being sedentary and unfit but has no objective evidence of cardiopulmonary disease, and whose only other notable medical history is mild COVID-19 a year earlier? A recent report proposed the existence of a specific "long COVID phenotype" with exertional intolerance and dyspnoea despite normal pulmonary function 11 , raising the question of whether there is more to this patient than meets the eye. Recently published data indicates that this may well be the case. Singh and colleagues 4 performed invasive cardiopulmonary exercise testing (iCPET) on 10 patients (mean age 48 yr, range: 28 to 79 yr, 9/10 female) with persistent exertional limitation 11 (1) months following mild COVID-19. None of the patients had abnormalities evident on chest computed tomographic imaging, pulmonary function testing, or resting echocardiogram, and all had normal haemoglobin levels. Study results were compared to a matched control group of 10 patients with normal exercise capacity and no history of COVID-19. As shown in table 1, relative to control patients at rest, DO2 was the same for post-COVID-19 patients but VO2 and systemic EO2 were modestly reduced. At peak exercise, when functional reserve mechanisms normally increase both DO2 and EO2, the difference in VO2 and EO2 between control and post-COVID-19 patients was more profound. Importantly, this disparity occurred despite a peak exercise response for heart rate and DO2 that was similar for both groups. These results indicate that exercise capacity was primarily 14 15 . Given the broad heterogeneity of symptoms associated with COVID-19, the complexity of accurately measuring EO2, and the fact that a substantial number of people have undoubtedly experienced mild but undiagnosed SARS-CoV-2 infection 1 , it is difficult (if not impossible) to define the incidence, much less the consequences, of impaired EO2 reserve following mild COVID-19 in the surgical population. Ultimately, we agree with Silvapulle and colleagues 2 , that at present the best approach to perioperative risk assessment in post-COVID-19 patients is tangible, objective evaluation of multiorgan sequelae. Nonetheless, clinicians should be aware that a deficit may exist that can mimic impaired tissue DO2 despite normal cardiopulmonary function and haemoglobin level, and potentially enhance the adverse consequences of perioperative hypoxaemia, anaemia, or impaired tissue perfusion. We are just beginning to learn of the long-term sequelae of even mild COVID-19, underscoring the need to be vigilant to the potential for a broader perioperative impact of prior SARS-CoV-2 infection. The authors declare con conflicts of interest. Data presented as %, mean (SD) or median (IQR). BMI -body mass index; FEV1 -forced expiratory volume in one second; FVC -forced vital capacity; SaO2 -oxygen saturation in arterial blood; DO2oxygen delivery, VO2 -oxygen consumption, EO2 -oxygen extraction ratio. Highlighted rows emphasize differences between groups. Data adapted from reference 4. 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