Acute Respiratory Failure

Acute respiratory failure is a clinical condition where the lungs are unable to perform adequate gas exchange, resulting in insufficient oxygen (O₂) supply to the body and/or inability to eliminate enough carbon dioxide (CO₂) from the blood. This leads to hypoxemia, hypercapnia, or a combination of both, and can rapidly become life-threatening if not treated promptly¹.

The condition is identified through two key arterial blood gas values:

PaO₂ (arterial oxygen pressure):This is the amount of oxygen dissolved in the blood. In respiratory failure, PaO₂ falls below 60 mmHg, meaning that the blood does not contain enough oxygen to meet the body’s needs.

PaCO₂ (arterial carbon dioxide pressure):This is the amount of carbon dioxide in the blood. In some types of respiratory failure, PaCO₂ rises above 50 mmHg, which shows that the lungs are unable to eliminate CO₂. This can lead to severe CO₂ intoxication in the body.

Respiratory failure is divided into two main types based on blood gas values (levels of O₂ and CO₂):

Type 1 – hypoxemic respiratory failure:

Here, PaO₂ is below 60 mmHg, while PaCO₂ is normal or low. This type occurs because gas exchange at the alveolar–capillary membrane level is impaired. Examples of conditions that cause type 1 respiratory failure include pulmonary edema (fluid in the lungs, either heart failure–related or not), acute respiratory distress syndrome (ARDS), severe pneumonia, and COVID-19.¹

Type 2 – hypercapnic respiratory failure:

Here, PaCO₂ is elevated, i.e., above 50 mmHg, often in combination with low oxygen levels. This happens because the respiratory pump does not function properly. The cause is often airway obstruction (e.g., COPD – chronic obstructive pulmonary disease) or musculoskeletal problems such as chest wall deformities, neurological diseases, or weakness of the respiratory muscles.

Pathophysiology: underlying mechanisms

Respiratory failure can occur through several mechanisms that impair gas exchange in the lungs:

Hypoventilation:

Here, both PaCO₂ and PaO₂ and the difference between alveolar and arterial oxygen pressure (A–a gradient) are normal. This often occurs when the central nervous system is suppressed, for example by opioid use, so that the respiratory center in the brain is affected and breathing becomes too weak.¹

Ventilation/perfusion disturbance (V/Q mismatch):

This is the most common cause of hypoxemia (too little oxygen in the blood). It occurs when airflow (ventilation) and blood flow (perfusion) in the lungs are not balanced. The V/Q ratio describes how much air reaches the alveoli and how much blood passes through the capillaries. If this balance is disturbed, oxygenation of the blood becomes impaired. Providing 100% oxygen will usually correct hypoxemia if it is due to V/Q mismatch.¹

Shunt:

Shunt means that blood flows through the lung without encountering air, because the alveoli are not ventilated. Thus, the blood remains deoxygenated even with 100% oxygen supplementation. This leads to persistent hypoxemia and is seen in conditions such as pulmonary edema, pneumonia, and atelectasis (collapse of lung tissue).²

Types of respiratory failure and causal mechanisms

Type I (hypoxemic) respiratory failure:

This type is characterized by low oxygen content in the blood and normal or low CO₂. It occurs when the lungs have damaged tissue that can no longer oxygenate the blood effectively. Typical causes include pulmonary edema, pneumonia, ARDS, and idiopathic pulmonary fibrosis (IPF). In these patients, healthy lung tissue is often still able to eliminate CO₂, because the body requires less functioning lung tissue to remove CO₂ than to absorb O₂.³

Type II (hypercapnic) respiratory failure:

Here, both low oxygen levels and high CO₂ levels are found in the blood. This occurs when alveolar ventilation becomes too poor, causing CO₂ to accumulate. Typical causes are muscle weakness (e.g., Guillain-Barré syndrome), chest wall deformities, or brain injury (e.g., heroin overdose). COPD is a very common cause. Reduced ventilation is due either to low respiratory drive or increased airway resistance. As a result, CO₂ builds up in the blood, and respiratory acidosis develops which – if untreated – can lead to severe organ failure due to the combination of hypoxemia and hypercapnia.⁴

Epidemiology

The exact prevalence of respiratory failure is difficult to determine, since it is not a disease in itself but a syndrome that can arise as a result of many different conditions². Nevertheless, respiratory failure accounts for a large proportion of both illness and death, especially among the elderly and individuals with underlying chronic diseases such as chronic obstructive pulmonary disease (COPD) and heart disease. The risk of respiratory failure increases markedly with age, and acute respiratory failure is a very common cause of hospital admission to intensive care units.

Although treatment options have improved in recent years, respiratory failure remains a significant public health challenge. A sharp increase in the number of cases is expected, partly because the prevalence of COPD is projected to rise by 23% from 2020 to 2050, especially among women and in low- and middle-income countries. This will likely result in more people developing respiratory failure as a complication⁵.

Etiology

Respiratory failure can be caused by diseases of the lungs (pulmonary causes) as well as diseases outside the lungs (extrapulmonary causes). The most common main groups are:

Central neurological causes:

Depression of the central nervous system can lead to respiratory failure by weakening or eliminating the respiratory drive. This may occur with severe head injury, stroke, overdose of narcotics or sedatives, severe central nervous system infections (such as encephalitis), or degenerative diseases such as Parkinson’s disease or ALS⁶.

Peripheral nervous system disorders:

Diseases affecting nerves, respiratory muscles, or the chest wall, such as Guillain-Barré syndrome and myasthenia gravis, can cause weakness of the respiratory muscles and thereby respiratory failure.

Airway obstruction:

Both upper and lower airway obstruction can lead to respiratory failure, for example during COPD exacerbation or severe asthma attack. Such conditions make it difficult to move air in and out of the lungs.

Alveolar changes:

Injury or disease of the alveoli – the small air sacs in the lungs – can cause type 1 (hypoxemic) respiratory failure, as seen in pulmonary edema and severe pneumonia².

Clinical picture

The symptoms and findings of respiratory failure depend on the underlying cause, and whether the patient has hypoxemia, hypercapnia, or both.

Common symptoms include:

• Shortness of breath (dyspnea)

• Rapid breathing (tachypnea)

• Restlessness or agitation

• Confusion

• Anxiety

• Central cyanosis (blue lips, tongue, mucous membranes)

• Rapid pulse (tachycardia)

• High blood pressure in the pulmonary circulation (pulmonary hypertension)

• Loss of consciousness

Signs and symptoms of type 1 (hypoxemic) respiratory failure:⁷

• Shortness of breath and irritability

• Confusion, seizures, drowsiness

• Rapid pulse and cardiac arrhythmias

• Rapid breathing

• Cyanosis (bluish discoloration)

Signs and symptoms of type 2 (hypercapnic) respiratory failure:⁷

• Behavioral changes

• Headache

• Coma

• Warm hands/feet

• Asterixis (flapping tremor)

• Papilledema (swelling of the optic disc)

Symptoms of the underlying disease:

• Fever, cough, sputum, and chest pain (in pneumonia)

• History of sepsis, major trauma, burns, or blood transfusions may suggest acute respiratory distress syndrome (ARDS)

Clinical findings

Certain clinical findings can provide clues to the underlying cause of respiratory failure:

• Low blood pressure together with signs of poor circulation suggests severe sepsis or pulmonary embolism.

• High blood pressure with poor circulation suggests heart failure and pulmonary edema.

• Wheezing and stridor suggest airway obstruction.

• Rapid pulse and arrhythmias can be both a cause and a consequence of heart failure.

• Elevated jugular venous pressure indicates right-sided heart failure.

• Low respiratory rate (< 12 breaths/min) in an awake patient with hypoxemia/hypercarbia and acidosis suggests neurological failure.

• Paradoxical breathing movement (the abdomen and chest move in opposite directions) indicates muscle weakness.

Investigations

• Arterial blood gases (ABG): Measure oxygen and CO₂ directly, and are used to classify the type of respiratory failure.

• Renal and liver function tests: Can reveal both the cause of and complications from respiratory failure.

• Pulmonary function tests: Show whether obstruction, restriction, or impaired diffusion is present.

  • Normal FEV1 and FVC, but reduced ventilatory control → may suggest a central neurological cause.

  • Reduced FEV1/FVC ratio → obstructive lung disease.

  • Reduced FEV1 and FVC, but normal ratio → restrictive lung disease.

• ECG: Detects arrhythmias or cardiac strain.

• Chest X-ray: Identifies changes in lung tissue, chest wall, and pleura.

Other tests to identify underlying causes:

• Complete blood count (CBC)

• Microbiology (blood, urine, sputum cultures)

• Electrolytes and thyroid function tests

• Echocardiography

• Bronchoscopy

Complications

Respiratory failure can lead to a range of serious complications affecting multiple organ systems:

Lungs:

• Pulmonary embolism

• Pulmonary fibrosis

• Complications related to mechanical ventilation (e.g., barotrauma)

Cardiovascular system:

• Hypotension

• Reduced cardiac output

• Cor pulmonale (right-sided heart failure)

• Arrhythmias

• Myocardial infarction

• Pericarditis

Gastrointestinal system:

• Gastrointestinal bleeding

• Abdominal distension

• Ileus

• Diarrhea

• Free air in the abdomen (pneumoperitoneum)

• Stress ulcers, common in critically ill patients

Infections:

• Nosocomial infections such as pneumonia, urinary tract infections, and catheter-related sepsis, particularly in patients on mechanical ventilation.

Kidneys:

• Acute kidney injury

• Electrolyte and acid–base disturbances

Nutrition:

• Malnutrition

• Complications from tube feeding or parenteral nutrition (e.g., abdominal distension, diarrhea)

Treatment

Treatment of respiratory failure includes both supportive measures and targeted management of the underlying cause. The primary goal is to ensure a patent airway, adequate ventilation, and correction of abnormal blood gases.

Supportive measures focus on maintaining airway patency, ensuring adequate ventilation (movement of air in and out of the lungs), and correcting abnormal blood gases (low O₂, high CO₂).

1. Correction of hypoxemia (low oxygen)

The aim is to achieve adequate tissue oxygenation, usually defined as an arterial oxygen pressure (PaO₂) around 60 mmHg or oxygen saturation (SaO₂) around 90%. Excess oxygen must be avoided, since uncontrolled oxygen therapy can lead to oxygen toxicity and CO₂ narcosis (CO₂ buildup due to suppression of the respiratory drive). Oxygen should therefore always be given in the lowest dose that provides adequate saturation.

Oxygen delivery methods:

• Nasal cannula

• Simple face mask or non-rebreather mask

• High-flow nasal cannula for severe failure

• Extracorporeal membrane oxygenation (ECMO) may be considered in the most critical cases, where blood is oxygenated outside the body.

2. Correction of hypercapnia and respiratory acidosis

This is achieved by treating the underlying cause or supporting ventilation so that the body can eliminate CO₂. Often, a combination of medications, physiotherapy, and mechanical support is required.

3. Ventilatory support

The aim of ventilatory support is to:

• Correct hypoxemia (low oxygen)

• Correct acute respiratory acidosis (CO₂ retention with acidic blood pH)

• Rest the respiratory muscles

Non-invasive ventilatory support (NIV/NIPPV)

This is respiratory support without the need for intubation. It is used in patients with mild to moderate respiratory failure who are awake, have a patent airway, and preserved cough reflex. Non-invasive ventilation has been shown to reduce complications, ICU length of stay, and mortality, especially in acute exacerbations of COPD. The success of treatment depends strongly on the underlying cause.

Invasive ventilatory support

This involves intubation, where a tube is placed in the trachea and the patient is connected to a mechanical ventilator. It is indicated when hypoxemia persists despite maximal oxygen therapy, or if the patient develops altered consciousness due to CO₂ retention. Invasive ventilation carries potential complications, including aspiration (stomach contents entering the airways), dental injury, barotrauma (pressure-related lung damage), and tracheal injury.

Permissive hypercapnia

This is a strategy where higher CO₂ levels in the blood are tolerated to protect the lungs from ventilator-induced injury, particularly in acute lung injury (ALI/ARDS) and in patients with COPD. Here, lower minute ventilation is accepted to avoid excessive lung pressures (auto-PEEP). This approach has been associated with improved survival in selected patient groups, such as children with severe ARDS.

Physiotherapy

Physiotherapeutic management aims to maximize lung function, strengthen the respiratory pump, and improve quality of life.

In mechanically ventilated patients, early physiotherapy has been shown to enhance quality of life and prevent complications such as muscle weakness, reduced mobility, and ventilator dependency. The main indications for physiotherapy are secretion retention in the lungs and atelectasis (collapse of lung tissue).

Appropriate timing and type of physiotherapy can improve gas exchange, prevent disease progression, and in some cases reduce the need for invasive ventilation.

Interventions

Positioning:

Different body positions are used to improve ventilation/perfusion ratio (V/Q), promote mucus clearance, increase lung volume, and reduce work of breathing.

• Prone position: Especially in ARDS to improve oxygenation.

• Side-lying: Diseased lung up to increase lung volume in the healthy lung.

• Semi-sitting position (45°): Reduces risk of aspiration.

• Upright position: Improves lung volume, often used during ventilator weaning.

Postural drainage and percussion:

Uses gravity to drain secretions from the lungs, often combined with gentle chest percussion/vibration.

Suctioning:

Indicated when the patient cannot clear secretions independently, for example when “sawtooth pattern” is observed on ventilator curves and/or gurgling sounds over the trachea.

Manual hyperinflation:

Technique where the lungs are artificially inflated to reopen collapsed areas and loosen mucus.

Active cycle of breathing technique (ACBT) and manual techniques:

Includes rhythmic breathing, deep inspirations, coughing, and manual vibrations to loosen and clear secretions.

Active/passive movement exercises:

Reduce risk of immobility-related complications and improve oxygen transport.

Inspiratory muscle training:

Strengthens inspiratory muscles and facilitates ventilator weaning. Research shows it improves physical performance, especially in patients with reduced capacity, and benefits are also documented in advanced lung disease.

Early mobilization:

Getting out of bed early improves function, mobility, and quality of life.

Differential diagnoses

Conditions that may cause similar symptoms and/or blood gas abnormalities, and must be considered when respiratory failure is suspected:

• Acute respiratory distress syndrome (ARDS)

• Angina pectoris

• Aspiration pneumonitis (inhalation of gastric contents)

• Asthma

• Atelectasis (lung collapse)

• Cardiogenic shock

• Obstructive sleep apnea

• Myocardial infarction

• Pulmonary embolism

Prognosis

Respiratory failure generally carries a poor prognosis, but advances in ventilatory support and airway management have improved survival in recent years. The outcome depends primarily on the underlying cause.

Mortality in ARDS is around 40–45 % and has remained stable over time. Younger patients (< 60 years) have better survival than older adults. About two-thirds of ARDS survivors continue to have impaired lung function one year or more after the event.

In COPD with acute respiratory failure, overall mortality has decreased from 26 % to 10 % in recent years. Patients with hypercapnic respiratory failure have higher mortality, particularly when accompanied by malnutrition and multiple comorbidities.

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