Respiratory Failure


Respiratory failure is characterized by a reduction in function of the lungs due to lung disease or a skeletal or neuromuscular disorder. It occurs when gas exchange at the lungs is significantly impaired to cause a drop in blood levels of oxygen(hypoxemia) occurring with or without an increase in carbon dioxide levels (hypercapnia). It's usually defined in terms of the gas tensions in the arterial blood, respiratory rate and evidence of increased work of breathing[1]. Respiratory failure can be acute, chronic or acute on chronic.[2] It's a major cause of mortality and morbidity and mortality rates increase with age and presence of co-morbidities.

Respiratory Physiology

The respiratory system can be said to consist of two parts: the lung- gas exchanging organ and the respiratory pump- ventilates the lungs. The respiratory pumps consists of the chest wall- respiratory muscles, the respiratory controllers in the CNS and the pathways that connect the central controllers with the respiratory muscles i.e the spinal and peripheral nerves. The act of respiration engages three processes: transfer of oxygen across the alveolus, transfer of oxygen to the tissues and removal of carbon dioxide from the blood into the alveolus and then the environment. The alveolar capillary unit of the lungs are primarily where respiration takes place with exchange of oxygen and carbon dioxide between alveolar gas and blood. Oxygen reversibly binds with hemoglobin after diffusing into the blood. At steady state, rate of carbon dioxide production equals rate of elimination by the lungs. Optimally ventilated alveoli that are not well perfused have a large ventilation to perfusion(V/Q) ratio and are called high V/Q units. High V/Q units act like dead space. Optimally perfused but not adequately ventilated alveoli are called low V/Q units and they act like shunt.

Classification of Respiratory Failure

Respiratory failure is classified mechanically based on pathophysiologic derangement in respiratory failure. This classifies RF into 4 types:

  1. Type I (Hypoxemic) Respiratory Failure: this is caused by intrinsic lung disease that interferes with oxygen transfer in the lungs. The resulting hypoxemia is from increased shunt fraction, ventilation/perfusion(V/Q) mismatch or a combination of the two. It's characterized by an arterial oxygen tension(PaO2) < 60mmHg(on room air) with a normal or low arterial carbon dioxide tension(PaCO2). It is the most common form of respiratory failure and it can be associated with most acute diseases of the lungs that involve fluid filling or collapse of alveolar units. Hypoxaemia resulting from V/Q mismatch or diffusion abnormality can easily be corrected with supplemental oxygen, This is in contrast to hypoxaemia induced purely by increased shunt, it is refractory to supplemental oxygen. Common causes include: acute respiratory distress syndrome(ARDS), COPD, pneumonia, pulmonary edema, pulmonary fibrosis, asthma, pneumothorax, pulmonary embolism, pulmonary hypertension,
  2. Type II (Hypercapnic) Respiratory Failure: is characterized by alveolar hypoventilation and increased carbon dioxide pressure(PaCO2). It is caused by loss of CNS drive, impaired neuromuscular competence, excessive dead space or increased mechanical load. Arterial carbon dioxide pressure PaCO2 is > 50mmHg. Commonly caused by myasthenia gravis, head injuries, polyneuropathies, muscular dystrophy, kyphoscoliosis, flail chest, obesity hypoventilation syndrome, advanced chronic bronchitis and emphysema.
  3. Type III Respiratory Failure: typically occurs in the perioperative period when factors that reduce functional residual capacity(FRC) combine with causes of increased closing volume to produce atelectasis. Commonly caused by inadequate post-operative analgesia, obesity, ascites and excessive airway secretions.
  4. Type IV Respiratory Failure: results from hypoperfusion of respiratory muscles in patients in shock. Patients are usually intubated and ventilated in the process of resuscitation for shock. Commonly caused by cardiogenic shock, septic shock and hypovolemic shock.

Respiratory failure can be further classified as acute- develops over minutes to hours with pH < 7.3 or chronic-develops over several days or longer which allows time for renal compensation and increase bicarbonate concentration. pH is usually slightly decreased. Arterial blood gases are not sufficient to clearly distinguish between acute and chronic respiratory failure. Abrupt changes in mental status suggest an acute RF while clinical markers of chronic hypoxemia such as polycythemia or cor pulmonale.

Mechanism of Injury / Pathological Process

Generally, failure of the lung caused by a variety of lung disease leads failure of gas exchange manifested by hypoxemia whilst failure of the pump results in ventilatory failure manifested as hypercapnia. Lung diseases may result in muscle fatigue and ventilatory failure through an imbalance between demands and supplies. Likewise, patients with diseases that involve the ventilatory pump and present with hypercapnia are typically characterized by inability to cough and possibly atelectasis. This aggravates V/Q mismatch resulting in hypoxaemia.

Type I Respiratory Failure

Four pathophysiological mechanisms accounts for hypoxaemia in a variety of diseases and this includes: ventilation/perfusion(V/Q) mismatch, increased shunt, diffusion impairment and alveolar hypoventilation.[3]

  • V/Q mismatch(low V/Q), which is the most common mechanism develops when there are lung regions with a greater reduction in ventilation than in perfusion.
  • In shunt, there is a bypass of ventilated alveoli by intrapulmonary or intracardiac deoxygenated mixed venous blood resulting in venous admixture.
  • Diffusion pathway for oxygen from the alveolar space to the pulmonary capillaries can be increased by diseases which in turn decreases capillary surface area prevents complete equilibrium of alveolar oxygen with pulmonary capillary blood.
  • In underlying pulmonary disease, there is broadening of the alveolar/arterial gradient- either due to V/Q mismatch or shunt or diffusion impairment results in severe hypoxemia while for hypoxaemia accompanying hypoventilation(without underlying pulmonary disease) the alveolar/arterial gradient is normal

Type II Respiratory Failure

Pump failure leading to hypercapnia is caused by three major factors which includes: inadequate output of the respiratory centers controlling the muscles, mechanical defect in the chest wall, excessive inspiratory load

  • Inadequate output of the respiratory centers controlling the muscles results in an insufficient respiratory drive for the demand or the respiratory centers my reflexively modify their output to prevent respiratory muscle injury and avoid fatigue. Insufficient activation from the CNS either temporarily- from anesthesia, drug overdose or permanently- diseases of the medulla results in inadequate respiratory efforts and hypoventilation ensues.
  • Mechanical defects in the chest wall as in flail chest, diseases of the nerves (Guillain-Barre syndrome) and anterior horn cells(poliomyelitis) or diseases of the respiratory muscles(myopathies)
  • Excessive inspiratory load fatigues the inspiratory muscles- they are unable to generate an adequate pleural pressure even though there is an adequate respiratory drive and an intact chest wall. Factors that increase inspiratory muscle energy demand and/or decrease energy supplies predisposes respiratory muscles to fatigue.


Respiratory failure occurs when there is a dysfunction of one or more of the components of the respiratory system. The etiology of respiratory failure can be grouped according to the primary abnormality and the individual components of the respiratory system.

  • Central nervous system dysfunction:
    • Drug overdose- narcotics/sedatives
    • Brain-stem lesion
    • Metabolic disorders- myxedema, chronic metabolic acidosis
    • Central hypoventilation
  • Chest wall dysfunction
    • Kyphoscoliosis
    • Obesity
  • Alveolar dysfunction:
    • Pulmonary edema- cardiogenic & non-cardiogenic
    • pneumonia
    • Pulmonary hemorrhage
  • Pulmonary circulation dysfunction

Clinical Presentation

Presentation of respiratory failure is dependent on the underlying cause and associated hypoxemia or hypercapnia. Common presentations include:

  • Dyspnoea
  • Tachypnoea
  • Restlessness
  • Confusion
  • Anxiety
  • Cyanosis- central
  • Tachycardia
  • Pulmonary hypertension
  • Loss of consciousness

Signs and symptoms of RF Type I (Hypoxemia) include[4]:

  • Dyspnea, irritability
  • Confusion, fits, somnolence
  • Tachycardia, arrhythmia
  • Tachypnea
  • Cyanosis

Signs and symptoms of RF Type II (Hypercapnia) include[4]:

  • Change of behavior
  • headache
  • Coma
  • Warm extremities
  • Astrexis
  • Papilloedema

Symptoms and signs of the underlying disease[4]:


Fever, cough, sputum production, chest pain in cases of pneumonia.

History of sepsis, polytrauma, burn, or blood transfusions before the onset of acute respiratory failure may point to acute respiratory distress syndrome

Diagnostic Procedures

A combination of medical history, physical findings, laboratory investigations, and imaging are used to establish the diagnosis of respiratory failure.

Medical History

This aims to gather information about history of diseases/conditions that could lead to respiratory failure,

Physical Findings

These are signs that suggest a possible underlying cause of respiratory failure include:

  • Hypotension usually with signs of poor perfusion suggest severe sepsis or pulmonary embolus
  • Hypertension usually with signs of poor perfusion suggests cardiogenic pulmonary edema
  • Wheeze & stridor suggest airway obstruction
  • Tachycardia and arrhythmias may be the cause of cardiogenic pulmonary edema
  • Elevated jugular venous pressure suggests right ventricular dysfunction
  • Respiratory rate < 12b/m in spontaneously breathing patient with hypoxia or hypercarbia and acidemia suggest nervous system dysfunction
  • Paradoxical respiratory motion suggest muscular dysfunction

Laboratory Investigations

  • Arterial blood gases- measures oxygen and carbon dioxide levels in the blood
  • Full blood count- may indicate anemia which can contribute to tissue hypoxia; polycythaemia may indicate chronic hypoxaemic respiratory failure; thrombocytopenia may suggest sepsis
  • Renal function tests and liver function tests- may indicate the etiology of respiratory failure or identify complications associated with it.
  • Pulmonary function test- identifies obstruction, restriction, and gas diffusion abnormalities. Normal values for forced expiratory volume in 1 second(FEV1) and forced vital capacity(FVC) suggest a disturbance in respiratory control. Decrease in FEV1 to FVC ratio indicates airflow obstruction. A decrease in FEV1 and FVC and maintenance of FEV1 to FVC ratio suggest restrictive lung disease.
  • Electrocardiography(ECG)- determines if respiratory failure is from a cardiovascular cause, may detect dysrhythmias from hypoxaemia or acidosis
  • Echocardiography- needed when a cardiac cause of acute respiratory failure is suspected. Findings such as left ventricular dilatation, regional/global wall motion abnormalities or severe mitral regurgitation verify the diagnosis of cardiogenic pulmonary edema. Normal heart size and normal systolic and diastolic function in a patient with pulmonary edema suggests acute respiratory distress syndrome
  • Chest radiography- reveals the cause of respiratory failure
  • Serum creatinine kinase with fractionation and troponin I- excludes recent myocardial infarction in a patient with RF. Elevated levels of creatinine kinase with normal troponin I levels may indicate myositis- causes respiratory failure occasionally
  • Thyroid function tests- hypothyroidism may cause chronic hypercapnic respiratory failure


Multiple organ-system complications involving the cardiovascular, pulmonary, gastrointestinal system may occur subsequent to respiratory failure

  • Pulmonary: pulmonary embolism, pulmonary fibrosis, complications secondary to the use of mechanical ventilator
  • Cardiovascular: hypotension, reduced cardiac output, cor pulmonale, arrhythmias, pericarditis and acute myocardial infarction
  • Gastrointestinal: haemorrhage, gastric distention, ileus, diarrhoea, pneumoperitoneum and duodenal ulceration- caused by stress is common in patients with acute respiratory failure
  • Infectious: noscomial- pneumonia, urinary tract infection and catheter-related sepsis. Usually occurs with use of mechanical devices.
  • Renal: acute renal failure, abnormalities of electrolytes and acid-base balance.
  • Nutritional: malnutrition and complications relating to parenteral or enteral nutrition and complications associated with NG tube- abdominal distention and diarrhea


Management of respiratory failure focuses on optimizing oxygen delivery to tissues by ensuring airway management, oxygenation and ventilation(if indicated). Appropriate management of the underlying cause is also an integral component in the management of respiratory failure.

Patent Airway

It’s important the patient is able to maintain, clear and protect the airway. This is dependent on the patient’s level of consciousness as reduced levels of consciousness can result in partial airway obstruction due to loss of muscle tone. Airway can be opened using tilt-chin-lift manoeuvre or inserting an oropharyngeal airway and endotracheal intubation if a patient is unable to clear the airway.


Oxygen is usually given to treat hypoxaemia. Ensuring adequate oxygen delivery to tissues is generally achieved with an arterial oxygen tension (PaO2) of 60mmHg or arterial oxygen saturation (SaO2) greater than 90%. Supplemental oxygen is given via nasal prongs or face mask, although in patients with severe hypoxaemia, intubation and mechanical ventilation are often required. A study by Peek et al found out that survival without disability was significantly higher in patients considered for extracorporeal membrane oxygen(ECMO). Also lifetime quality adjusted life years(QALYs) gained were 10.75 for ECMO group and 7.31 for control group.[5]

Respiratory Support

The goals of ventilatory support include: improve alveolar ventilation, decrease work of breathing and improve gas exchange. It can be done either invasively- using an endotracheal tube (ETT) or tracheostomy tube or non-invasively- using a mask or a similar interface.

Non-invasive respiratory support: is ventilatory support without tracheal intubation/ via upper airway. Considered in patients with mild to moderate respiratory failure. Patients should be conscious, have an intact airway and airway protective reflexes. Noninvasive positive pressure ventilation(NIPPV) has been shown to reduce complications, duration of ICU stay and mortality(). It has been suggested that NIPPV is more effective in preventing endotracheal intubation in acute respiratory failure due to COPD than other causes. The etiology of respiratory failure is an important predictor of NIPPV failure.[6]

Invasive respiratory support: indicated in persistent hypoxemia despite receiving maximum oxygen therapy, hypercapnia with impairment of conscious level. Intubation is associated with complications such as aspiration of gastric content, trauma to the teeth, barotraumas, trauma to the trachea etc

  • Permissive hypercapnia[7] - A ventilatory strategy that allows arterial carbon dioxide(PaCO2) to rise by accepting a lower alveolar minute ventilation to avoid the risk of ventilator-associated lung injury in patients with ALI and minimize intrinsic positive end-expiratory pressure (auto PEEP) in patients with COPD thereby protecting the lungs from barotrauma. Permissive hypercapnia could increase survival in immunocompromised children with severe ARDS[8]

Physiotherapy Management

In mechanically ventilated patients, early physiotherapy has been shown to improve quality of life and to prevent ICU-associated complications like de-conditioning, ventilator dependency and respiratory conditions. Main indications for physiotherapy are excessive pulmonary secretions and atelectasis. Timely physical therapy interventions may improve gas exchange and reverse pathological progression thereby avoiding ventilation. Ultimately, physio-therapeutic interventions aim to maximize function in motor, ventilatory and improve quality of life. Interventions include:

  • Positioning:  the use of specific body position aimed at improving ventilation/perfusion(V/Q) matching, promoting mucociliary clearance, improving aeration via increased lung volumes and reducing the work of breathing.[9] These include:
    • Prone: helps to improve V/Q matching, redistribute edema and increase functional residual capacity(FRC)  in patients with acute respiratory distress syndrome. It has been shown to result in oxygenation for 52-92% of patients with severe acute respiratory failure.[10][11]
    • Side-lying: with affected lungs uppermost to improve aeration through increased lung volumes in patients with unilateral lung disease.
    • Semi-recumbent: 450 head-up position serves to prevent the risk of gastroesophageal reflux and aspiration.
    • Upright: helps to improve lung volumes and decrease work of breathing in patients that are being weaned from mechanical ventilator.
  • Postural drainage: uses gravitational effects to facilitate mucociliary clearance
  • Suction: used for clearing secretions when the patient cannot do so independently. Guglielminotti et al recommended a saw-tooth pattern seen on ventilator’s flow-volume loop and/or respiratory sounds over the trachea as good indicators for tracheal suction in a ventilated patient[12]
  • Manual Hyperinflation: aims to re-inflate atelectatic areas of the lung as such improving pulmonary compliance[13] and facilitate the clearance of pulmonary secretions when used with other techniques.
  • Active cycle of breathing technique[14] and  manual techniques such as shaking and vibration to facilitate mucus clearance
  • Limb exercises: passive, active-assisted, active exercises may optimize oxygen transport and reduce the effects of immobility.[9]
  • Inspiratory muscle training: aims to improve inspiratory muscle strength and it facilitates weaning from mechanical ventilation. It has be shown to improve whole body exercise performance, particularly in less fit subjects.[15] The study by Hoffman L et showed positive outcomes with inspiratory muscle training in patients with advanced lung disease.[16]
  • Early mobilisation: improves function, mobility and quality of life[17][18][19]

Differential Diagnosis


Respiratory failure is associated with poor prognosis but advances in mechanical ventilation and airway management have improved prognosis. It is dependent on the underlying cause of respiratory failure. Mortality rates of approximately 40-45% which has remained constant over the years occur with acute respiratory distress syndrome(ARDS)[20][21] with younger patients(< 60 years) having better survival rates. About two-thirds of the patients who survive an episode of ARDS show some impairment of pulmonary function one or more years of post-recovery. For COPD and acute respiratory failure. overall mortality has reportedly declined from 26% to 10%. Also, significant mortality occurs in patients with hypercapnic respiratory failure due to associated co-morbidities and poor nutritional status. Noveanu et al's study show a strong association between preadmission use of beta-blockers and in-hospital and 1-year mortality among patients with acute respiratory failure.[22]


European Respiratory Society/American Thoracic Society Clinical guideline for non-invasive ventilation in acute respiratory failure.


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