COVID-19-associated respiratory failure
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords:
Overview
The most devastating complication of SARS-CoV-2 is acute hypoxaemic respiratory failure which requires mechanical ventilation. There can be multiple causes that can lead to acute hypoxemic respiratory failure ranging from pulmonary edema , vascular occlusion, ventilation/perfusion mismatch and haemoglobinopathies. The most important pathology is usually acute respiratory distress syndrome ( ARDS) that eventually leads to hypoxaemic respiratory failure in patients that are not maintaining oxygen saturation. The difference between COVID related ARDS and the usual ARDS is the injury site which is mainly the respiratory system involving the alveolar epithelial cells. Usually the clinical symptoms don't correlate with the severity of imaging and laboratory findings. Lung compliance maybe normal in some patients. The patients that progress towards acute respiratory failure are usually managed by mechanical intubation with tidal volume target of 6mL/kg PBW.
Historical Perspective
- In December 2019, an outbreak of coronavirus disease (COVID-19) broke out in Wuhan,China.
- COVID-19 was a clustering pneumonia like illness which affected patients that rapidly developed ARDS.
- ARDS was one of the most important cause of hospital and ICU admission due to COVID.
- Many autopsies studies reported ARDS to be the cause of death in patients dying due to respiratory complications of COVID
Classification
Respiratory failure can be classified in two types. The respiratory failure that primarily occurs in COVID-19 patients is type 1 respiratory failure which is hypoxemic respiratory failure.
| Hypoxemic Respiratory Failure (Type 1) | Hypercapnic Respiratory Failure (Type 2) |
|---|---|
| PaO2 is lower than 60 mmHg | PaCO2 is greater than 50 mmHg |
| Most common form of respiratory failure | Mostly seen in COPD patients |
| Can involve any condition that involves fluid filling or collapse of alveolar units
Proposed respiratory failure that occurs in COVID-19 patients that experience respiratory distress |
Other Etiologies may include
|
Pathophysiology
- After the infection of the SARS-CoV-2 virus, Type II pneumocytes release inflammatory cytokines that recruit macrophages.
- Macrophages further release cytokines that cause vasodilation and allow more neutrophils and macrophages to come to the site of injury.
- Fluid starts accumulating into the alveolus which leads to dilution of surfactant.
- SARS-CoV propagates within type II cells and releases a large number of viral particles. The type II pneumocytes undergo apoptosis and die. This results in a self-replicating pulmonary toxin as the released viral particles infect type II cells in adjacent units.
- Normally, type II cells are the precursor cells for type I cells.
- This postulated sequence of events has been further supported by the murine model of influenza pneumonia.
- The pathological result of SARS and COVID-19 is diffuse alveolar damage in which there is the development of fibrin hyaline membranes and formation of a few multinucleated giant cells. This aberrant wound healing may lead to further scarring and fibrosis which is more severe than other forms of ARDS.
- Recovery will require a vigorous innate and acquired immune response and epithelial regeneration.
- Elderly individuals are particularly susceptible because of their diminished immune response and inability to regenerate damaged epithelium quickly. Due to reduced mucociliary clearance, it may allow the virus to spread to the gas exchange units of the lung more readily.
- The respiratory failure resulting as a complication of ARDS is due to the result of the acute systemic inflammatory response which is caused by the direct or indirect insults to the lungs.
- In the early exudative stage of ARDS, there occurs the development of diffuse alveolar damage with the destruction of epithelial cells and endothelial cells.
- There are two mechanisms which can lead ARDS or any other pathology to respiratory failure in COVID-19
| V/Q Mismatch | Development of Shunt |
|---|---|
|
|
Causes
Airspace filling in acute hypoxemic respiratory failure (AHRF) is due to
- Elevated alveolar capillary hydrostatic pressure
- Increased alveolar capillary permeability such as COVID-19 predisposing to acute respiratory distress syndrome (ARDS)
- Hemorrhage into alveoli or inflammatory exudates
Differentiating COVID-19-associated respiratory failure from other Diseases
The ARDS and subsequent respiratory failure caused by COVID-19 can be differentiated by other diseases through following factors [1]
- Timing of Onset : According to Berlin Criteria of ARDS , the onset must be within 1 week of clinical insult buy various reported onsets of COVID-19 related ARDS had mean onset time of 8-12 days from ARDS. It is therefore suggested that there should be caution against development of ARDS in COVID-19 patients with the course of more than week.
- Respiratory system compliance : Not all the cases of acute respiratory failure caused by COVID-19 were ARDS.The typical CT findings of the COVID-19 affected patient showed bilateral ground-glass shadow with a peripheral lung distribution. Although there were consolidation and exudation, this was not the typical "ARDS picture".Lung compliance might be relatively normal in some COVID-19-related ARDS patients who met ARDS Berlin criteria which is inconsistent with ARDS caused by other factors.In addition, the lung compliance was relatively high in some COVID-19-related ARDS patients, which was inconsistent with the severity of hypoxemia.
- Severity of Hypoxemia :
| Berlin Criteria Of ARDS leading to respiratory failure | COVID-Related ARDS leading to respiratory failure |
|---|---|
ARDS is divided into three stages based on oxygenation index (PaO2/FiO2) on PEEP ≥ 5 cmH2O:[2]
|
COVID-19-related ARDS was divided into three categories based on oxygenation index (PaO2/FiO2) on PEEP ≥ 5 cmH2O [3]
|
Epidemiology and Demographics
- In a sampling of some of the larger epidemiologic studies of patients with COVID-19 to date, rates of invasive mechanical ventilation among patients admitted to ICUs leading to respiratory failure range from 29.1% in one Chinese study [4] to 89.9% in a U.S. study [4] and anywhere from 2.3% of patients admitted to the hospital up to 33.1%.
- The epidemiological data regarding age, gender and race of patients developing ARDS and subsequent respiratory failure is insufficient.
Risk Factors
Comorbidities and other conditions that have been associated with severe illness and progression of ARDS to subsequent failure include
- Cardiovascular disease
- Diabetes mellitus
- Hypertension
- Chronic lung disease such COPD
- Malignancy
- Chronic kidney disease
- Obesity
- Smoking
Screening
There is insufficient evidence to recommend routine screening for COVID associated respiratory failure.
Natural History, Complications, and Prognosis
The development of ARDS and subsequent respiratory failure is a major transition from medical therapy to mechanical ventilation in the management of COVID-19. Various case studies shows the development of respiratory failure an eventual outcome in patients developing moderate to severe symptoms eventually requiring mechanical ventilation.
Complications
The complications that results from mechanical ventilation which is often required in patient developing respiratory failure includes
- Barotrauma
- Ventilation associated lung injury
- Intrinsic positive end expiratory pressure
- Heterogeneous ventilation
- altered V/Q mismatch
- Diaphragmatic muscle atrophy
- Respiratory muscle weakness
Prognosis
- The mortality from COVID-19 appears driven by the presence of severe ARDS and subsequent respiratory failure is approximately 50 percent (range 12 to 78 percent).
- Other risk factors associated with death among critically ill patients include development of severe ARDS and requirement of mechanical ventilation, comorbidities, increased markers of inflammation, worsening lymphopenia,neutrophilia and troponin leak.
Diagnosis
Diagnostic Study of Choice
There are no established criteria for the diagnosis of COVID associated respiratory failure. Caution is observed when a patient develops ARDS and oxygen saturation is maintained with HFNC and non-invasive ventilation. Respiratory failure is set into play when there is SpO2 sat <90% despite maximal supplemental oxygen. Chext X-ray and arterial blood gas measurement is done periodically to check for the development of ARDS.
History and Symptoms
The patient usually has a story of PCR positive COVID-19 and has already developed symptoms of ARDS which include difficulty breathing and failure to maintain oxygen saturation on room air. The patient may also present with restlessness, anxiety, loss of consciousness, rapid and shallow breathing, racing heart , irregular heartbeats,and profuse sweating.
Physical Examination
- Cyanosis can be seen on general physical exam
- Altered level of sensorium or consciousness
- Crackles during chest auscultation worse at lung bases
- Jugular venous distention with high levels of end-expiratory pressure.
Laboratory Findings
An arterial blood gas is mandatory to confirm the diagnosis of respiratory failure.
One needs to document two of the three criteria to formally diagnose acute respiratory failure: pO2 less than 60 mm Hg (or room air oxygen saturation less than or equal to 90%), pCO2 greater than 50 mm Hg with pH less than 7.35, and signs/symptoms of respiratory distress.
Particular lab findings associated with worse prognosis include
- Lymphopenia
- Elevated liver enzymes
- Elevated lactate dehydrogenase
- Elevated inflammatory markers
- Elevated D-dimer (>1 mcg/mL)
- Elevated prothrombin time (PT)
- Elevated troponin
- Elevated creatine phosphokinase (CPK)
Electrocardiogram
There are no ECG findings associated with COVID associated respiratory failure.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with COVID associated respiratory failure.
Chest X-ray
Chest x-ray is done to periodically categorize the severity of ARDS along with arterial blood gases.
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Surgery
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
Primary Prevention
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
OR
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
Secondary Prevention
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
References
- ↑ Li, Xu; Ma, Xiaochun (2020-05-06). "Acute respiratory failure in COVID-19: is it "typical" ARDS?". Critical Care. Springer Science and Business Media LLC. 24 (1). doi:10.1186/s13054-020-02911-9. ISSN 1364-8535.
- ↑ "Acute Respiratory Distress Syndrome". JAMA. American Medical Association (AMA). 307 (23). 2012-06-20. doi:10.1001/jama.2012.5669. ISSN 0098-7484.
- ↑ Phua, Jason; Weng, Li; Ling, Lowell; Egi, Moritoki; Lim, Chae-Man; Divatia, Jigeeshu Vasishtha; Shrestha, Babu Raja; Arabi, Yaseen M; Ng, Jensen; Gomersall, Charles D; Nishimura, Masaji; Koh, Younsuck; Du, Bin (2020). "Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations". The Lancet Respiratory Medicine. Elsevier BV. 8 (5): 506–517. doi:10.1016/s2213-2600(20)30161-2. ISSN 2213-2600.
- ↑ 4.0 4.1 "Mechanical Ventilation in COVID-19: Interpreting the Current Epidemiology". American Journal of Respiratory and Critical Care Medicine. 2020-07-01. Retrieved 2020-07-02.