| Article Access Statistics|
| Viewed||10210 |
| Printed||34 |
| Emailed||0 |
| PDF Downloaded||36 |
| Comments ||[Add] |
Click on image for details.
|Year : 2020 | Volume
| Issue : 5 | Page : 1261-1262
Silent Hypoxemia in COVID-19: Dangerous, If Gone Undetected
Ravindra K Garg, Ravi Uniyal, Shweta Pandey
Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
|Date of Web Publication||27-Oct-2020|
Dr. Ravindra K Garg
Department of Neurology, King George Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Garg RK, Uniyal R, Pandey S. Silent Hypoxemia in COVID-19: Dangerous, If Gone Undetected. Neurol India 2020;68:1261-2
The coronavirus disease-2019 (COVID-19) is primarily a disease of the respiratory system and is caused by a newly discovered Coronavirus “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).” Current data from the World Health Organization indicate that so far 14 043 176 confirmed cases worldwide have been reported. The total number of death stands at 597 583 cases. India currently ranks third, after the USA and Brazil with a number of confirmed COVID-19 cases as 1077618 and 26816 deaths. COVID-19 may be asymptomatic or it may cause a variety of clinical manifestations mostly in form of mild upper respiratory tract infection symptoms. Fever, dry cough, and shortness of breath are common symptoms. A subset of cases develops hypoxemia because of acute respiratory distress syndrome (ARDS), which in many cases culminates in multiple organ failure and subsequent death. Patients with comorbidities, like diabetes, hypertension, renal failure, and systemic malignancies are more vulnerable to severe COVID-19 and deaths. Severely ill patients are generally treated in intensive care units and many of them require mechanical ventilation.
The SARS-CoV-2, in advanced stages, can characteristically cause ARDS and pneumonia resulting in hypoxemic respiratory failure. ARDS is clinically identified if the patient fulfills one or more of the following criteria; breathing rate of 30 or more per minute, oxygen saturation level of 92% or less and/or a ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) of 300 mm Hg or less. The lungs of patients with Covid-19 demonstrate distinctive pathological features. Covid-19 associated lung injury is characterized by extensive endothelial cell damage (endothelialitis) and widespread thrombosis with microangiopathy. Interstitial inflammatory cell infiltration along with lung edema on chest imaging manifests with characteristic ground-glass opacities.
The key component of the pathogenesis of severe COVID-19 is a cytokine storm. In cytokine storm, very high levels of pro-inflammatory cytokines orchestrate wide-spread tissue destruction because of endothelial cell dysfunction, disseminated intravascular coagulation and capillary leakage. COVID-19 is associated with a distinct type of coagulopathy, which is characterized by elevated D-dimers and an enhanced risk of thrombo-embolic events.
The SARS-CoV-2 virus has a propensity to affect several other body organs, including the central nervous system. The SARS-CoV-2 virus has neurotropic potential and can enter in the neuronal cells via angiotensin-converting enzyme-2 receptor. Loss of smell and loss of taste are early signs of COVID-19. Other common neurological complications include encephalitis, encephalopathy, myelitis, Guillain–Barre syndrome, myalgia, rhabdomyolysis, and critical care myopathy.
The current review by Machado and many other reports have indicated that viral invasion of brainstem and damage of the respiratory regulation centers can also lead to acute neurogenic respiratory failure, which is characterized by “happy hypoxemia or silent hypoxemia”. The phenomenon of silent hypoxemia in COVID-19 is characterized with a lack of dyspnea despite a low level of blood oxygen saturation, measured on pulse oximetry. Instead, many such patients have tachypnea and tachycardia. It has been hypothesized that damaged brainstem respiratory centers fail to respond to low oxygen levels in the blood and patients fail to experience compensatory dysnoea.,, There are many other clinical correlates of involvement of brainstem respiratory system. Experts think that as a consequence of damage to brainstem respiratory center many times is not possible to wean off such patients from mechanical ventilation. In severe Covid-19, there is always an enhanced risk of acute respiratory arrests during intensive care management because of damage of the brainstem respiratory center.
Dysfunction of brainstem respiratory center is currently the most plausible reason for silent hypoxemia. The respiratory center is localized in the medulla oblongata and pons. The SARS-CoV-2 virus via retrograde transmission from olfactory can spread to brainstem. Viral transmission generally considered to take place via trans-synaptic route. In medulla oblongata the SARS-CoV-2 virus affects the pre-Bötzinger nucleus, which acts as center for respiratory control. Alternatively, the SARS-CoV-2 virus spread to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors present in the lungs and other parts of lower respiratory system.,
In alternative hypothesis, destruction of the pulmonary C-fibers, carrying nociceptive stimulus necessary to maintain respiratory drive to brain, can also be responsible of lack of dysnoea in these patients. The pulmonary C-fibers are afferent neurons, which carry varied nociceptive stimulus from the alveolar membrane to brainstem. The afferent sensations are carried to brainstem nucleus of the tractus solitarius via vagal and glossopharyngeal nerves. The nucleus tractus solitarius is component of the regulatory processes related to cardiorespiratory functions. The SARS-CoV-2 virus or cytokine storm can destroy pulmonary C-fibers.
In conclusion, brainstem involvement plays a crucial role in the pathogenesis of respiratory failure. Unrecognized silent hypoxemia contributes to high death rates in 19 patients. The long intensive care unit stay of severe Covid-19 patients is possibly because of a lack of central respiratory drive, resulting in failures in mechanic ventilation weaning. Experts working in intensive care units need to be always alert as sudden unexpected respiratory arrest can take place. Timely intubation needs to be done.
| » References|| |
Machado C, DeFina PA, Chinchilla M, Machado Y, Machado Y. Brainstem Dysfunction in SARS-COV-2 Infection can be a Potential Cause of Respiratory Distress. Neurol India 2020;68:989-93. [Full text]
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al
. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N
Engl J Med 2020;383:120-8.
Mosleh W, Chen K, Pfau SE, Vashist A. Endotheliitis and endothelial dysfunction in patients with COVID-19: Its role in thrombosis and adverse outcomes. J Clin Med 2020;9:E1862.
Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med 2020;20:356-60.
González-Duarte A, Norcliffe-Kaufmann L. Is 'happy hypoxia' in COVID-19 a disorder of autonomic interoception? A hypothesis. Clin Auton Res 2020;30:331-3.
Baig AM. Computing the effects of SARS-CoV-2 on respiration regulatory mechanisms in COVID-19. ACS Chem Neurosci 2020;11:2416-21.
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020;92:552-5.
Tan BH, Zhang Y, Gui Y, Wu S, Li YC. The possible impairment of respiratory-related neural loops may be associated with the silent pneumonia induced by SARS-CoV-2. J Med Virol 2020. doi: 10.1002/jmv.26158.