17th January 2024

Acute Respiratory Distress Syndrome

Background

Acute respiratory distress syndrome (ARDS) is defined by the acute onset of lung inflammation, causing a diffuse, non-cardiogenic pulmonary oedema and respiratory failure. Due to the nature of the diagnostic criteria, it is almost exclusively a diagnosis made and managed in a critical care setting.

Epidemiology

There are various estimates for the prevalence of ARDS, ranging from 1 case per 100,000 to 79 per 100,000. One large, multi-centre study projected incidence as 86 per 100,000 person-years. Prevalence in the intensive care patient population is thought to be around 10%, rising to 23% in the mechanically ventilated patient group. Mortality from ARDS is estimated to be around 40%, increasing depending on severity group. It can affect many different patient groups, but incidence increases with age (1).

Pathophysiology

ARDS is an umbrella term encompassing multiple different disease processes leading to a distinct clinical syndrome. The most common causes are sepsis, pneumonia (including COVID-19 pneumonitis), aspiration, trauma, pancreatitis and transfusion of blood products. All causes of ARDS result in an increased vascular endothelial permeability, allowing for accumulation of protein-rich fluid in the alveolar spaces. This initiates the release of pro-inflammatory cytokines, such as Tumour Necrosis Factor (TNF), IL-1 and IL-6, creating a further cycle of damage, whereby neutrophils are recruited to accumulate in the alveolar spaces, and toxic free radical production causes extensive oxidative cell damage. This diffuse alveolar damage results in impaired gas exchange, reduced lung compliance and pulmonary hypertension (2).

The pathophysiology of ARDS can be divided into three distinct stages (3):

• Early exudative stage – the acute reaction to lung injury from various sources, involving inflammation and alveolar oedema. This lasts for around 7-10 days.
• Fibroproliferative stage – remodelling of the alveolar cell walls with fibroblastic invasion and collagen deposition, reducing compliance.
• Fibrotic stage – not all patients progress to this final stage. It involves the complete destruction of the alveolar architecture, with cyst formation and further fibrosis.

Presentation

Signs and symptoms

Symptoms of ARDS can be non-specific but include shortness of breath, dry cough, fever, confusion, myalgia, dizziness and fatigue. Patients may often have many of the above symptoms due to their underlying diagnosis, so regular and close monitoring is key in early identification of progression to ARDS. On examination, features include tachypnoea, tachycardia, diffuse crepitations on auscultation and cyanosis, depending on severity. Signs of acute pulmonary oedema, such as raised JVP and peripheral oedema, should be absent.

Diagnosis

To diagnose ARDS, the following clinical and radiographic criteria need to be met (4):

• Acute onset time of <1 week
• Bilateral opacities on chest x-ray
• Arterial to inspired oxygen ratio (PₐO2/FᵢO2) of ≤300 on positive end-expiratory pressure (PEEP) or continuous positive airways pressure (CPAP) of ≥5cm H2O
• Presentation cannot be fully explained by cardiac failure or fluid overload

ARDS can be stratified by severity according to oxygenation defined by PₐO2/FiO2 ratio:

• Mild – PₐO2/FᵢO2 200-300mmHg
• Moderate – 100-199mmHg
• Severe – <100mmHg

Investigations

Often, the diagnosis of ARDS can be made on the basis of basic clinical and chest x-ray findings, and the priority should be initiating supportive management in a timely fashion. However, there is still an important role in continuing investigations alongside supportive care, both to differentiate between ARDS and acute pulmonary oedema and to establish the underlying cause. Some of the below investigations can be useful in certain situations:

• Chest x-ray – an essential investigation, as diffuse pulmonary infiltrates on a plain radiograph, are part of the diagnostic criteria for ARDS.
• Lung ultrasound – increasingly, point of care lung ultrasound use in critical care can be used to make the radiological diagnosis in the place of x-ray, looking for B-lines associated with an irregular pleural morphology with spared areas (5).
• Arterial blood gas monitoring – frequent ABG monitoring helps determine the PaO2 to FiO2 ratio for both diagnosis and to determine progression and oxygen requirements.
• Transthoracic echocardiogram (TTE) – the role of TTE here is to rule out the differential diagnosis of pulmonary oedema due to left ventricular dysfunction and/or valvular disease.
• Bronchoscopy – useful where the underlying aetiology is unclear, as samples can be taken and sent for culture, biochemistry and cytology testing.
• Lung biopsy – this is a very invasive test and not routinely done for all patients; however, biopsy can be a useful investigation where there is a lot of diagnostic uncertainty regarding aetiology of the ARDS. Histopathologically, the diagnosis of ARDS can be confirmed by the appearance of diffuse alveolar damage (DAD).

Image Source: Wikimedia Commons (2017). ARDSSevere, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:ARDSSevere.png (Accessed: 6 June 2022).

Differential diagnoses

Pulmonary oedema

Cardiogenic pulmonary oedema is the most important differential for ARDS, and when severe, can have an almost identical appearance on chest x-ray. Whilst both can be associated with progressive shortness of breath and worsening oxygen requirement, certain signs on examination can help differentiate the two. A raised JVP, presence of a third heart sound and peripheral oedema are all present in pulmonary oedema but not in ARDS. There also may be clues in the history, such as a recent acute coronary syndrome or known pre-existing valvular disease. It is important to distinguish the two, as pulmonary oedema can respond well to the timely initiation of IV diuretics.

Pulmonary haemorrhage

Diffuse alveolar haemorrhage can have a similar radiological appearance to ARDS. Clinically, remain clinically suspicious of pulmonary haemorrhage with any patient presenting with haemoptysis or a very acute onset breathlessness.

Pulmonary vasculitis 

Conditions such as granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) can present with bilateral infiltrates on chest x-ray and a similar symptom profile to ARDS. However, patients can also have evidence of multi-system involvement, such as vasculitic skin rash and renal impairment. Differentiate this patient group by sending off an autoimmune screen, including ANA, ANCA and double-stranded DNA (dsDNA).

Lymphangitic carcinomatosis 

In patients with disseminated malignancy presenting with unexplained worsening shortness of breath and dry cough suspect pulmonary lymphangitis, where the lymphatic channels in the lungs are infiltrated by malignant cells. Presentation is often too indolent here to meet the diagnostic criteria for ARDS (3).

Management

The management of ARDS is largely supportive whilst treating the underlying condition. The vast majority of patients with ARDS require mechanical ventilatory support. The main principles of supportive management are as follows:

• Lung protective ventilation – the ventilation approach evidenced to produce the best mortality outcomes involves using lower tidal volumes of 6-8mL/kg to avoid barotrauma, as tolerated to maintain O2 saturations of 88-95%, with permissive hypercapnia.
• Venous thromboembolism prophylaxis with low molecular weight heparin
• Stress ulcer prophylaxis with a proton pump inhibitor, e.g., omeprazole
• Nutritional support with NG feeding (6)

References

• Confalonieri M, Salton F, Fabiano F. Acute respiratory distress syndrome. European Respiratory Review. 2017;26(144):160116.
• Pierrakos. Acute Respiratory Distress Syndrome: Pathophysiology and Therapeutic Options. Journal of Clinical Medicine Research. 2012;4(1).
• UpToDate [Internet]. www.uptodate.com. [cited 2022 Jun 4]. Available from: https://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-diagnosis-and-complications-in-adults
• Acute Respiratory Distress Syndrome Definitions • LITFL [Internet]. Life in the Fast Lane • LITFL • Medical Blog. 2019. Available from: https://litfl.com/acute-respiratory-distress-syndrome-definitions/
• Corradi F, Brusasco C, Pelosi P. Chest ultrasound in acute respiratory distress syndrome. Current Opinion in Critical Care. 2014 Feb;20(1):98–103.
• Saguil A, Fargo M. Acute Respiratory Distress Syndrome: Diagnosis and Management. American Family Physician [Internet]. 2012 Feb 15 [cited 2022 Jun 5];85(4):352–8. Available from: https://www.aafp.org/pubs/afp/issues/2012/0215/p352.html