COVID-19-associated hypoxemia

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For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rija Gul, M.B.B.S.

Synonyms and keywords:

Overview

COVID-19 emerged as a pandemic, after its outbreak in Wuhan, China in December 2019. It is caused by a new type of Coronavirus, which binds to ACE-2 receptors on Type 2 pneumocytes in the lower respiratory tract. The clinical presentation of patients with COVID-19 varies from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Hypoxemia is present with an increased A-a gradient. Hypoxemia is diagnosed by Pa02<60mmHg in a sample of Arterial Blood Gas. Mechanisms involved in hypoxemia are widely reported to be due to ventilation perfusion mismatch and intrapulmonary shunting. Diffusion impairment can cause hypoxemia during recovery period due to fibrosis in the lungs. Older age, male sex, hypertension and dyspnea have been identified as risk factors for development of hypoxemia in COVID-19. Complications of hypoxemia include acute respiratory failure and multi-organ failure. Treatment is based on oxygen supplementation to keep target Spo2> 90%.

Historical Perspective

  • In December 2019, novel coronavirus outbreak occurred in Wuhan, China[1]
  • On 11th March 2020, it was declared as Pandemic by WHO.

Classification

  • There is no established system for the classification of COVID-19 associated hypoxemia.

Pathophysiology

Mechanisms of Hypoxemia in COVID-19

Ventilation Perfusion Mismatch

Intrapulmonary Shunt

Diffusion Impairment

  • A study was conducted in China to measure DLCO of discharged patients. The researchers concluded that the decrease in DLCO correlated with the severity of pneumonia on admission.[6]

Causes

The table below describes the most common causes of hypoxemia in COVID-19:

Common Causes of Hypoxemia in COVID-19
Pulmonary causes Cardiac causes
Pneumonia Myocardial Infarction
Non cardiogenic Pulmonary Edema Myocarditis
Pulmonary Hypertension Heart Failure
Pulmonary embolism Cardiogenic Shock
Super imposed bacterial infection Arrhythmia

Differentiating COVID-19-associated hypoxemia from other Diseases

  • COVID-19-associated hypoxemia should be differentiated from other potential causes of hypoxemia.
  • Dyspnea is not a prominent feature of hypoxemia due to COVID-19 in contrast to other diseases causing hypoxemia[4]
  • This can be explained by areas of well preserved lung compliance surrounding the damaged tissue.[7]
  • It is important to differentiate COVID-19 associated pneumonia from Community acquired pneumonia, as both can present with hypoxemia and pulmonary infection.[8]
Covid-19 Pneumonia Community Acquired pneumonia
Sars-Cov2 Viral/ Bacterial pathogens e.g Streptococcus Pneumonia, Influenza
Pneumonia develops after 6 days of infective symptoms Rapid development of symptoms of pneumonia
Malaise is a prominent feature Malaise is not a prominent feature
Extra Pulmonary symptoms are present ( anosmia, headache, myalgia) Pulmonary symptoms are more prominent ( Productive cough, fever)
Radiology shows Basal atelectasis / Bilateral peripheral Ground Glass opacities Radiology shows Lobar Consolidation

Epidemiology and Demographics

  • COVID-19 is seen more commonly in men.
  • 80% of patients with Coronavirus disease develop a respiratory infection.[9]
  • According to a study conducted in Hubei, China, 5%-25% of patients admitted in hospital for COVID-19 needed ICU admission. Of the patients admitted in ICU, 60%-70% developed ARDS.[10]
  • There is no geographical association of hypoxemia in COVID-19.

Risk Factors

  • According to a study conducted in Wuhan, China, the following risk factors were identified in patients presenting with hypoxemia (Spo2< 90%):[11]

Natural History, Complications, and Prognosis

Complications

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Laboratory Findings

Electrocardiogram

X-Ray

  • Chest x-ray demonstrates multi-lobar infiltrates[7]
  • To view the x-ray finidings on COVID-19, click here.

Echocardiography or Ultrasound

CT Scan

  • Computed Tomography shows consolidation and bilateral ground-glass opacities located peripherally.
  • To view the CT scan findings on COVID-19, click here.

MRI

Other Imaging Findings

  • To view other imaging findings on COVID-19, click here.

Other Diagnostic Studies

  • To view other diagnostic studies for COVID-19, click here.

Treatment

Treatment of Hypoxemia due to COVID-19

Overview

  • Hypoxia due to COVID-19 warrants hospital admission.
  • Oxygen target should be Spo2>90%.
  • Some centres have suggested to restrict oxygen supplementation by High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (Bipap, CPAP) as they generate aerosol and pose a threat to the healthcare workers.[18]
  • Invasive mechanical Ventilation by early intubation is recommended for hypoxemia not responding to Non-Invasive Ventilation.

Venturi Mask

  • SpO2< 93%-94%
  • Respiratory rate > 28-30 breaths per minute.
  • Deliver oxygen via 40% Venturi mask.
  • If a response is seen in 5-10 minutes, continue treatment for the next 6 hours.
  • NIV is recommended if there is no improvement.

High Flow Nasal Oxygenation(HFNO)

  • Use is recommended in a negative pressure environment due to aerosol generation.
  • Apply if SpO2< 92%.
  • No response to Oxygen delivery is observed via nasal cannula, face mask or Venturi mask.
  • Use Oxygen flow of 30-50L/min.
  • Keep FiO2 between 50%-70%.

Non Invasive Ventilation

  • Used when dyspnea/ hypoxemia does not improve within 1 hour of HFNO used at 50L/min and FiO2>70%.
  • Recommended to use pressure setting of 8-10cm Hg and FiO2of 60%.
  • Monitor with hourly Arterial Blood Gas sampling.
  • Use for 4-6 hours, allowing 1-hour break for feeding.

Invasive Mechanical ventilation

  • Performed in patients with severe hypoxemia ( Pa02/FiO2 <200) and failure of NIV.
  • Rapid Sequence intubation is preferred to avoid aerosolisation by Bag mask ventilation.
  • Lung protective Ventilation is used in patients with severe ARDS.
  • Tidal Volume at 4-6ml/kg of body weight.
  • Plateau Pressure(Pplat) < 30cm H2O.
  • High Positive End Expiratory Pressure (PEEP) is recommended to keep driving pressure (Pplat-PEEP)<14cm H2O.

Prone Position

  • Recommended in severe ARDS (PaO2/FiO2 <150) along with Invasive Mechanical ventilation.
  • Recommended for a total duration of 12-16 hours daily.
  • Not recommended for infants less than 6 months of age.
  • It decreases Va/Q mismatch by eliminating gravitational forces exerted on lung portion by mediastinal structures, allowing maximum lung recruitment when positive pressure mechanical ventilation is applied.[19]
  • Meta analysis have shown that Prone positioning can decrease mortality when used for long duration within intial 48hours in severe ARDS.[20]
  • In a pilot study performed in New York emergency, awake proning was associated with improved oxygen saturations in non intubated patients.[21]
  • Position should be changed every 2 hours to prevent pressure ulcer formation.

Extra Corporeal Membrane Oxygenation

  • Used in refractory hypoxemic respiratory failure.
  • PaO2/Fio2 < 50mmHg for more than 1 hour.
  • PaO2/FiO2 < 80mmHg for more than 2 hours.
  • Arterial Blood Gas indicating pH <7.2 persisting for more than 1 hour, due to uncompensated respiratory acidosis.
  • It is has shown improved clinical outcome in severe COVID-19.[22]

Prevention

Primary Prevention

  • Infection with COVID-19 can be prevented by practicing the following:
    • Social distancing
    • Frequent hand washing
    • Personal Hygiene
    • Wearing mask
    • Use of Personal Protective equipment by healthcare workers[7]

References

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  2. Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L (June 2020). "COVID-19 pneumonia: different respiratory treatments for different phenotypes?". Intensive Care Med. 46 (6): 1099–1102. doi:10.1007/s00134-020-06033-2. PMC 7154064 Check |pmc= value (help). PMID 32291463 Check |pmid= value (help).
  3. Mekontso Dessap, Armand; Boissier, Florence; Leon, Rusel; Carreira, Serge; Roche Campo, Ferran; Lemaire, François; Brochard, Laurent (2010). "Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome*". Critical Care Medicine. 38 (9): 1786–1792. doi:10.1097/CCM.0b013e3181eaa9c8. ISSN 0090-3493.
  4. 4.0 4.1 Fisher HK (June 2020). "Hypoxemia in COVID-19 patients: An hypothesis". Med. Hypotheses. 143: 110022. doi:10.1016/j.mehy.2020.110022. PMC 7308039 Check |pmc= value (help). PMID 32634734 Check |pmid= value (help).
  5. George, Peter M; Wells, Athol U; Jenkins, R Gisli (2020). "Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy". The Lancet Respiratory Medicine. doi:10.1016/S2213-2600(20)30225-3. ISSN 2213-2600.
  6. Mo, Xiaoneng; Jian, Wenhua; Su, Zhuquan; Chen, Mu; Peng, Hui; Peng, Ping; Lei, Chunliang; Chen, Ruchong; Zhong, Nanshan; Li, Shiyue (2020). "Abnormal pulmonary function in COVID-19 patients at time of hospital discharge". European Respiratory Journal. 55 (6): 2001217. doi:10.1183/13993003.01217-2020. ISSN 0903-1936.
  7. 7.0 7.1 7.2 Dondorp, Arjen M.; Hayat, Muhammad; Aryal, Diptesh; Beane, Abi; Schultz, Marcus J. (2020). "Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings". The American Journal of Tropical Medicine and Hygiene. 102 (6): 1191–1197. doi:10.4269/ajtmh.20-0283. ISSN 0002-9637.
  8. Lipman, Marc; Chambers, Rachel C; Singer, Mervyn; Brown, Jeremy Stuart (2020). "SARS-CoV-2 pandemic: clinical picture of COVID-19 and implications for research". Thorax: thoraxjnl-2020–215024. doi:10.1136/thoraxjnl-2020-215024. ISSN 0040-6376.
  9. . doi:10.1161/CIRCULATIONAHA.120.047915Circulation. Missing or empty |title= (help)
  10. Greenland, John R.; Michelow, Marilyn D.; Wang, Linlin; London, Martin J. (2020). "COVID-19 Infection". Anesthesiology. 132 (6): 1346–1361. doi:10.1097/ALN.0000000000003303. ISSN 0003-3022.
  11. Xie, Jiang; Covassin, Naima; Fan, Zhengyang; Singh, Prachi; Gao, Wei; Li, Guangxi; Kara, Tomas; Somers, Virend K. (2020). "Association Between Hypoxemia and Mortality in Patients With COVID-19". Mayo Clinic Proceedings. 95 (6): 1138–1147. doi:10.1016/j.mayocp.2020.04.006. ISSN 0025-6196.
  12. Greenland JR, Michelow MD, Wang L, London MJ (June 2020). "COVID-19 Infection: Implications for Perioperative and Critical Care Physicians". Anesthesiology. 132 (6): 1346–1361. doi:10.1097/ALN.0000000000003303. PMC 7155909 Check |pmc= value (help). PMID 32195698 Check |pmid= value (help).
  13. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y (May 2020). "Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study". Lancet Respir Med. 8 (5): 475–481. doi:10.1016/S2213-2600(20)30079-5. PMC 7102538 Check |pmc= value (help). PMID 32105632 Check |pmid= value (help).
  14. Pan F, Yang L, Li Y, Liang B, Li L, Ye T, Li L, Liu D, Gui S, Hu Y, Zheng C (2020). "Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study". Int J Med Sci. 17 (9): 1281–1292. doi:10.7150/ijms.46614. PMC 7294915 Check |pmc= value (help). PMID 32547323 Check |pmid= value (help).
  15. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (March 2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).
  16. . doi:10.1016/ S1473-3099(20)30367-4 Check |doi= value (help). Missing or empty |title= (help)
  17. 17.0 17.1 Ullah, Waqas; Saeed, Rehan; Sarwar, Usman; Patel, Rajesh; Fischman, David L. (2020). "COVID-19 Complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure". JACC: Case Reports. doi:10.1016/j.jaccas.2020.04.008. ISSN 2666-0849.
  18. Kluge S, Janssens U, Welte T, Weber-Carstens S, Marx G, Karagiannidis C (April 2020). "German recommendations for critically ill patients with COVID‑19". Med Klin Intensivmed Notfmed. doi:10.1007/s00063-020-00689-w. PMC 7155395 Check |pmc= value (help). PMID 32291505 Check |pmid= value (help).
  19. Lindahl S (August 2020). "Using the prone position could help to combat the development of fast hypoxia in some patients with COVID-19". Acta Paediatr. 109 (8): 1539–1544. doi:10.1111/apa.15382. PMC 7301016 Check |pmc= value (help). PMID 32484966 Check |pmid= value (help). Vancouver style error: initials (help)
  20. Mora-Arteaga, J.A.; Bernal-Ramírez, O.J.; Rodríguez, S.J. (2015). "The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis". Medicina Intensiva (English Edition). 39 (6): 359–372. doi:10.1016/j.medine.2014.11.004. ISSN 2173-5727.
  21. Caputo ND, Strayer RJ, Levitan R (May 2020). "Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED's Experience During the COVID-19 Pandemic". Acad Emerg Med. 27 (5): 375–378. doi:10.1111/acem.13994. PMC 7264594 Check |pmc= value (help). PMID 32320506 Check |pmid= value (help).
  22. Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, Zhang Z, Lu Y, Chen N, Clifford SP, Huang J (May 2020). "Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 in Shanghai, China". ASAIO J. 66 (5): 475–481. doi:10.1097/MAT.0000000000001172. PMC 7273861 Check |pmc= value (help). PMID 32243266 Check |pmid= value (help).


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