Ards: Symptoms, Types, Causes and Treatment

Acute Respiratory Distress Syndrome (ARDS) is a serious, life-threatening condition characterized by sudden and severe respiratory failure. It can develop rapidly in critically ill patients, often leading to high morbidity and mortality rates. Understanding the symptoms, types, causes, and treatments of ARDS is crucial for early detection, effective management, and improved outcomes. This article synthesizes current research to provide a comprehensive overview of ARDS, ensuring readers have access to the most up-to-date, evidence-based information.

Symptoms of Ards

When it comes to ARDS, the symptoms can be both obvious and subtle, making early recognition a challenge. Patients often present with acute shortness of breath, rapid breathing, and low oxygen levels, but survivors also experience lingering effects long after leaving the intensive care unit. These effects include fatigue, depression, and memory problems, which can impact quality of life and the ability to return to everyday activities. Recognizing both the acute and long-term symptoms is vital for timely intervention and holistic care.

Symptom	Description	Persistence/Onset	Source(s)
Hypoxemia	Low blood oxygen	Acute onset	9 11 14
Dyspnea	Severe shortness of breath	Acute onset	9 11 14
Fatigue	Persistent tiredness	Months to years	3
Depression	Mood disturbance	Months to years	1 2 3
Memory Issues	Cognitive dysfunction	Months to years	1 2 3

Table 1: Key Symptoms

Acute Symptoms

The hallmark symptoms of ARDS typically appear rapidly and can worsen within hours to days. These include:

• Severe shortness of breath (dyspnea): Patients experience difficulty breathing, often requiring supplemental oxygen or mechanical ventilation.
• Hypoxemia: Markedly low levels of oxygen in the blood, which do not improve significantly with standard oxygen therapy.
• Rapid breathing (tachypnea): Breathing becomes fast and shallow as the body attempts to compensate for low oxygen levels.
• Other signs: Cyanosis (bluish skin), confusion, and low blood pressure can also occur as the condition progresses 9 11 14.

Persistent and Long-term Symptoms

Survivors of ARDS often face a range of ongoing symptoms that can last for months or even years:

• Fatigue: Approximately two-thirds of ARDS survivors report ongoing fatigue—more prevalent than physical impairment, anxiety, or depression in the first year after illness 3.
• Depression: Moderate to severe depressive symptoms are common, affecting up to 41% within two years post-ICU, though this can decrease over time 1 2.
• Memory and cognitive dysfunction: Problems with memory and thinking skills affect a minority but can be significant for those impacted 1 2 3.

These persistent symptoms can hinder return to work and daily functioning, highlighting the importance of post-ICU care and mental health support.

Types of Ards

Although ARDS is traditionally viewed as a single clinical entity, research over the past decade has revealed significant biological and clinical heterogeneity within this syndrome. Scientists have identified distinct ARDS subtypes—also known as "phenotypes" or "endotypes"—that differ in their biological markers, clinical features, and responses to treatment. Understanding these types is key to advancing personalized medicine for ARDS patients.

Type	Defining Feature	Clinical Relevance	Source(s)
Hyperinflammatory	High inflammation markers	Higher mortality, different treatment response	4 6 7 8
Hypoinflammatory	Lower inflammation markers	Lower mortality, standard treatment	4 6 7 8
COVID-19-related	Unique compliance/hypoxemia	Different pathophysiology	5

Table 2: Main ARDS Types

Classic ARDS Subtypes

Hyperinflammatory vs. Hypoinflammatory Phenotypes

• Hyperinflammatory phenotype:
  • Marked by elevated inflammatory biomarkers (e.g., interleukins, TNF receptors).
  • Associated with higher mortality and organ dysfunction.
  • May respond differently to treatments such as higher PEEP (positive end-expiratory pressure) and fluid management strategies 4 6 7 8.
• Hypoinflammatory phenotype:
  • Lower levels of inflammation.
  • Lower mortality and more favorable prognosis.
  • Standard supportive care may be sufficient 4 6 7 8.

These subtypes can be identified using machine learning models that analyze routine clinical data at the bedside, making it possible to stratify patients for personalized management 7 8.

COVID-19 and Other Specific ARDS Types

• COVID-19-related ARDS:
  • Shares many features of classical ARDS but exhibits unique characteristics, such as severe hypoxemia despite relatively preserved lung mechanics in some patients.
  • May be divided into “type 1” (non-ARDS phenotype, high compliance, severe hypoxemia) and “type 2” (classic ARDS phenotype) 5.
• Biological endotypes:
  • Emerging research also suggests further subgroups based on gene expression and immune cell activation, supporting the need for individualized therapies 6.

Causes of Ards

Understanding what triggers ARDS is crucial for prevention and early management. ARDS is not a disease in itself but a final common pathway of lung injury from various direct and indirect insults. These causes initiate a cascade of immune responses, leading to widespread inflammation and damage to the lung's delicate tissues.

Cause	Description	Mechanism/Trigger	Source(s)
Sepsis	Systemic infection	Neutrophil activation	9 10 11
Pneumonia	Lung infection	Direct lung injury	9 13
Aspiration	Inhalation of gastric contents	Chemical injury	9
Trauma	Physical injury to body/lungs	Indirect lung injury	9
COVID-19	SARS-CoV-2 viral infection	Cytokine storm, direct viral effect	5 12

Table 3: Main Causes of ARDS

Direct Lung Injury

• Pneumonia: Infection of the lung tissue, whether bacterial, viral (such as influenza or COVID-19), or fungal, can directly injure the alveoli 9 13.
• Aspiration: Inhalation of stomach contents or other foreign material causes chemical burns and inflammation in the airways and alveoli 9.
• COVID-19: SARS-CoV-2 can trigger severe lung inflammation and ARDS, sometimes directly through viral proteins that damage cells and induce cytokine storms 5 12.

Indirect Lung Injury

• Sepsis: The most common cause, sepsis involves a body-wide infection that leads to inflammatory mediators activating neutrophils and platelets, which then damage the lung’s blood vessels and air sacs 9 10 11.
• Major trauma: Physical injuries, including those that do not involve the chest, can trigger a systemic inflammatory response that leads to ARDS 9.

Pathophysiological Mechanisms

• Inflammatory cascade: The common thread in ARDS pathogenesis is uncontrolled inflammation—neutrophils release reactive oxygen species (ROS), cytokines, and other mediators that disrupt the lung’s endothelial and epithelial barriers, causing fluid leakage into alveoli 10 11.
• Immune dysregulation: Aberrant immune responses, sometimes driven by host proteins or direct viral effects (as in COVID-19), perpetuate lung injury 12 13.
• Protein-homeostasis-system hypothesis: Suggests that both pathogen-derived and host-derived substances can provoke immune reactions leading to ARDS 13.

Treatment of Ards

Treating ARDS is complex and primarily supportive, as no specific cure currently exists. The mainstay of therapy focuses on maintaining adequate oxygenation while minimizing further lung injury. Newer, individualized approaches are emerging as research sheds light on the heterogeneity of ARDS. Below, we summarize both standard and emerging treatments.

Treatment	Main Approach/Tool	Evidence/Notes	Source(s)
Low tidal volume ventilation	Mechanical ventilation strategy	Reduces mortality	9 16 17
Prone positioning	Lying face-down to improve oxygenation	Beneficial in severe ARDS	14 15 17
PEEP optimization	Setting appropriate airway pressure	Individualized, especially for hyperinflammatory phenotype	8 14 17
Fluid management	Negative fluid balance	Improves lung function	14 17
Neuromuscular blockade	Muscle relaxants for ventilation	Used in select cases	14 17
Steroids	Immunomodulation	For select patients	13 17
Cell-based therapy	Mesenchymal stromal cells (MSCs)	Experimental	18

Table 4: Key Treatments for ARDS

Standard Supportive Care

Mechanical Ventilation

• Low tidal volume ventilation: Using smaller breaths (6–8 mL/kg) to reduce ventilator-associated lung injury is a cornerstone of ARDS management and has been shown to reduce mortality 9 16 17.
• PEEP (Positive End-Expiratory Pressure): Helps keep alveoli open, improve oxygenation, and reduce further injury. Higher PEEP levels may benefit patients with more severe or hyperinflammatory ARDS 8 14 17.
• Prone positioning: Placing patients face-down can significantly improve oxygenation and survival in severe ARDS, especially when used early and for prolonged periods 14 15 17.

Fluid Management

• Conservative fluid strategy: Maintaining a negative fluid balance reduces lung edema and improves oxygenation. Hemofiltration may be considered in some cases 14 17.

Adjunctive Therapies

• Neuromuscular blockade: Short-term use in patients with severe ARDS requiring mechanical ventilation can help improve oxygenation and ventilation synchrony 14 17.
• Steroids: Early systemic corticosteroids may reduce excessive immune responses in certain cases, but their use is individualized and based on clinical judgment 13 17.

Emerging and Experimental Therapies

• Cell-based therapies: Mesenchymal stromal cells (MSCs) are being investigated for their anti-inflammatory and reparative properties. Early trials suggest safety, and ongoing research aims to clarify their efficacy, especially in selected ARDS subtypes 18.
• Personalized/phenotype-driven therapy: Identifying ARDS subtypes using clinical or biomarker data may allow for tailored therapies, such as adjusting PEEP or testing immunomodulatory treatments according to individual patient profiles 4 6 7 8.

Infection and Complication Management

• Infection control: Early diagnosis and treatment of underlying infections, including broad-spectrum antibiotics and accurate microbiological sampling, are essential 14.
• Supportive care: Adequate sedation, prevention of secondary complications, and careful weaning from mechanical ventilation are vital aspects of care 14 17.

Conclusion

ARDS remains a critical challenge in intensive care medicine. Early recognition, stratification by ARDS type, and advanced supportive care are essential for improving outcomes. As our understanding of ARDS evolves, so too does the promise of personalized and innovative therapies.

Main Points Covered:

• Symptoms:
  • Acute: severe shortness of breath, rapid breathing, profound hypoxemia.
  • Long-term: fatigue, depression, cognitive impairment 1 2 3 9 11 14.
• Types:
  • Hyperinflammatory and hypoinflammatory phenotypes with differing risks and treatment responses.
  • Unique COVID-19-related ARDS presentations 4 5 6 7 8.
• Causes:
  • Sepsis, pneumonia, aspiration, trauma, and COVID-19 are key triggers.
  • Pathogenesis involves uncontrolled inflammation and immune-mediated damage 9 10 11 12 13.
• Treatment:
  • Mainstay: low tidal volume ventilation, PEEP, prone positioning, fluid management.
  • Adjuncts: steroids, neuromuscular blockers, infection control.
  • Emerging: cell-based therapies and personalized approaches based on ARDS subtypes 8 13 14 15 16 17 18.

The future of ARDS care lies in combining these evidence-based standards with innovative, individualized treatments tailored to each patient's unique disease profile.