Pulmonology

Acute Respiratory Distress Syndrome

  • Clinicals
  • Pulmonology
  • 2020-09-12 09:29:25
  • 11 minutes, 3 seconds

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) also known as noncardiogenic pulmonary oedema is an inflammatory disease process of the lungs caused by permeability pulmonary oedema resulting from endothelial damage due to a cascade of inflammatory events in response to direct or indirect insult.

It is characterized by severe hypoxemia, reduced lung compliance and bilateral radiographic infiltrates.

ARDS is not a single entity but represents the severe end of a spectrum of acute lung injury due to many different insults. Therefore ARDS is a complication rather than cause.

Causes of acute respiratory distress syndrome

There are many causes of pro-inflammatory mediator release sufficient to cause ARDS and there may be more than one present.

The common causes in order of prevalence are:

  • Sepsis/pneumonia; secondary risk factors for developing ARDS, when septic, are alcoholism and cigarette smoking
  • Gastric aspiration
  • Trauma/burns, via sepsis, lung trauma, smoke inhalation, fat emboli, and possibly direct effects of large amounts of necrotic tissue.

Less common causes

  • Transfusion-related acute lung injury (TRALI), caused by any blood transfusion.
  • Transplanted lung, worse if the lung poorly preserved
  • Post-bone marrow transplant as bone marrow recovers
  • Drug overdose, e.g. tricyclic antidepressants, opiates, cocaine, aspirin
  • Acute pancreatitis
  • Near drowning
  • Following upper airway obstruction

Pathogenesis of Acute Respiratory Distress Syndrome

In most situations, pulmonary oedema arises as a result of increased pulmonary capillary pressure (e.g. left ventricular failure) but in ARDS it arises because of increased alveolar-capillary permeability.

Pressure pulmonary oedema

In the normal situation, the hydrostatic pressure and the osmotic pressure exerted by the plasma proteins are in a state of equilibrium between the pulmonary capillaries and lung alveoli.

The most common cause of pulmonary oedema is an increase in hydrostatic pressure and this typically occurs secondary to elevated left atrial pressure from left ventricular failure (e.g. after myocardial infarction). Volume overload may also increase pulmonary capillary pressure and this may arise from excessive intravenous fluid administration or fluid retention (e.g. renal failure).

Reduced osmotic pressure may contribute to pulmonary oedema and this occurs in hypoproteinaemic states for example in patients having nephrotic syndrome with renal protein loss.

In the early stages of pulmonary oedema, there is an increase in the fluid content of the interstitial space between the capillaries and alveoli but as the condition deteriorates flooding of the alveoli occurs.

Permeability pulmonary oedema

In acute respiratory distress syndrome, a cascade of inflammatory events arises over a period of hours from a focus of tissue damage.

These inflammatory events cause damage to the alveoli, either by locally produced pro-inflammatory mediators, or remotely produced pro-inflammatory mediators arriving in the lungs via the pulmonary artery.

The change in pulmonary capillary permeability allows fluid and protein leakage into the alveolar spaces with pulmonary infiltrates. The alveolar surfactant is diluted with loss of its stabilizing effect, resulting in diffuse alveolar collapse and stiff lungs.

In the ARDS lung, an influx of protein-rich oedema fluid into the air spaces occurs as a consequence of increased permeability of the alveolar-capillary barrier.

Specifically, activated neutrophils aggregate and adhere to endothelial cells, releasing various toxins, oxygen radicals and mediators like histamine and kinins.

This systemic inflammatory response may be initiated by a variety of injuries or illnesses and gives rise to acute lung injury as one of its earliest manifestations, with the development of endothelial damage and increased alveolar-capillary permeability.

The normal alveolar epithelium has two types of cells. The type I cells makeup 90% of the alveolar surface area and are easily injured.

The type II cells make up the remaining 10% of the alveolar surface area and are more resistant to injury; their functions include surfactant production, ion transport, and proliferation and differentiation to type I cells after injury.

The alveoli become filled with a protein-rich exudate containing abundant neutrophils and other inflammatory cells and the airspaces show a rim of proteinaceous material known as the hyaline membrane.

The characteristic feature of permeability pulmonary oedema in ARDS is that the pulmonary capillary wedge pressure is not elevated.

The measurement of pulmonary capillary wedge pressure reflects left atrial pressure and in ARDS it is typically 18 mmHg, whereas in cardiogenic pulmonary oedema it is elevated.

What are the effects of loss of epithelial integrity in ARDS?

The effects that may arise due to loss of epithelial integrity include:

  1. Under normal conditions, the epithelial barrier is much less permeable than the endothelial barrier; thus epithelial injury can contribute to alveolar flooding.
  2. The loss of epithelial integrity and injury to type II cells serve to disrupt normal epithelial fluid transport, impairing the removal of oedema fluid from the alveolar space.
  3. Injury to type II cells reduces the production and turnover of surfactant.
  4. Loss of epithelial barrier can lead to sepsis in patients with bacterial pneumonia.
  5. In severe alveolar epithelium injury, pulmonary fibrosis can develop.

Phases of acute respiratory distress syndrome

Phase 1 is the early period of alveolar damage and hypoxaemia with pulmonary infiltration.

Phase 2 develops after a week or so as the pulmonary infiltrates resolve, and on histology seems to be associated with an increase in type II pneumocytes, myofibroblasts, and early collagen formation.

Phase 3 if the patient survives, is the fibrotic stage that leaves the lung with cysts, deranged micro-architecture, and much fibrosis on histology.

Clinical features of acute respiratory distress syndrome

Acute respiratory distress syndrome develops in response to a variety of injuries or illnesses that affect the lungs either directly (e.g. aspiration of gastric contents, severe pneumonia, lung contusion) or indirectly (e.g. systemic sepsis, major trauma, pancreatitis).

About 12–48 hours after an initiating event the patient develops respiratory distress with increasing dyspnoea and tachypnoea.

Arterial blood gases show deteriorating hypoxaemia that responds poorly to oxygen therapy.

Diffuse bilateral infiltrates develop on chest X-ray in the absence of evidence of cardiogenic pulmonary oedema.

ARDS is the most severe end of the spectrum of acute lung injury and is characterised by the following features:

A history of an initiating injury or illness

  • Hypoxaemia refractory to oxygen therapy. In ARDS Po2/Fio2 is < 26 kPa (200 mmHg);
  • Bilateral diffuse infiltrates on chest X-ray;
  • No evidence of cardiogenic pulmonary oedema (e.g. pulmonary capillary wedge pressure < 18 mmHg).
  • Coarse crackles in the chest

Patients who subsequently develop ARDS may appear deceptively well in the initial stages of their illness. Early recognition and careful observation of at-risk patients is of crucial importance in detecting the signs of deterioration and in identifying the need for intensive therapy unit (ITU) care.

Certain warning signs are applicable in a wide variety of clinical circumstances because there is often a common physiological pathway of deterioration in the severely ill that can be detected by simple observations of the pulse rate, respiratory rate, blood pressure, temperature, urine output and level of consciousness.

Arterial blood gas measurements provide useful additional information about gas exchange and the metabolic state of the patient.

Treatment of acute respiratory distress syndrome

The treatment of ARDS consists of optimal management of the initiating illness or injury combined with supportive care directed at preserving adequate oxygenation, maintaining optimal haemodynamic function and compensating for multiorgan failure; which often supervenes.

Treatment of initiating illness

Prompt and complete treatment of the initiating injury or illness is essential. This includes rapid resuscitation with correction of hypotension in patients with multiple trauma for example, and eradication of any source of sepsis (e.g. intra-abdominal abscess or ischaemic bowel post-surgery).

Respiratory support

Characteristically, the hypoxaemia of ARDS is refractory to oxygen therapy because of shunting of blood through areas of the lung that are not being ventilated as a result of the alveoli being filled with a proteinaceous exudate and undergoing atelectasis.

Continuous positive airway pressure(CPAP) can be applied via a tight-fitting nasal mask to prevent alveolar atelectasis and thereby reduce ventilation/perfusion mismatch and the work of breathing. However, endotracheal intubation and mechanical ventilation rapidly become necessary and the patient may need to be transferred to a specialist ITU with expertise and facilities for treating ARDS.

Intermittent positive pressure ventilation mechanically inflates the lungs, delivering oxygen-enriched air at a set tidal volume and rate. Adjustments in the volume, inflation pressure, rate and percentage oxygen are made to achieve adequate ventilation.

A positive end-expiratory pressure(PEEP) of 5–15 cmH2O is usually applied at the end of the expiratory cycle to prevent the collapse of the alveoli. High airway pressures may be generated in ventilating the non-compliant stiff lungs in ARDS and this can reduce cardiac output and carries the risk of barotrauma (e.g. pneumothorax).

High ventilation pressures combined with high oxygen concentrations may themselves result in microvascular damage that perpetuates the problem of permeability pulmonary oedema (‘ventilator lung/oxygen toxicity’).

Permissive hypercapnia is a technique that allows the patient to have a high Paco2 level (e.g. 10 kPa; 75 mmHg) in order to reduce the alveolar ventilation and to avoid excessive airway pressure.

Inverse ratio ventilation prolongs the inspiratory phase of ventilation such that it is longer than the expiratory phase allowing the tidal volume to be delivered over a longer time at a lower pressure. However, this may cause progressive air trapping.

High-frequency jet ventilation is a technique whereby small volumes are delivered as an injected jet of gas at high frequencies (e.g. 100–300/min).

Ventilation of the patient in the prone posture may be beneficial as it reduces gravity-dependent fluid deposition and atelectasis.

Extracorporeal membrane oxygenation (ECMO) involves the diversion of the patient’s circulation through an artificial external membrane to provide oxygen and remove carbon dioxide.

Nursing patients in a semi-recumbent position at 45 degrees reduces the incidence of ventilator-associated pneumonia.

Optimising haemodynamic function

Reducing the pulmonary artery pressure may help to reduce the degree of pulmonary capillary leak. This is achieved by avoiding excessive fluid administration, by judicious use of diuretics and by use of drugs that act as vasodilators of the pulmonary arteries.

Treatment is sometimes guided by the use of a balloon-tipped pulmonary artery catheter (Swan–Ganz) that measures pulmonary artery pressures, pulmonary capillary wedge pressure (reflecting left atrial pressure) and cardiac output (using a thermal dilution technique).

Haemodynamic management essentially consists of achieving an optimal balance between a low pulmonary artery pressure to reduce fluid leak to the alveoli, an adequate systemic blood pressure to maintain perfusion of tissues and organs (e.g. kidneys) with a satisfactory cardiac output and optimal oxygen delivery to tissues (oxygen delivery is a function of the haemoglobin level, oxygen saturation of blood and cardiac output).

Most drugs used to vasodilate the pulmonary arteries, such as nitrates or calcium antagonists, also cause systemic vasodilatation with hypotension and impaired organ perfusion.

Inotropes and vasopressor agents, such as dobutamine or norepinephrine (noradrenaline) may be needed to maintain systemic blood pressure and cardiac output particularly in patients with the sepsis syndrome (caused by septicaemia or peritonitis, for example) in which sepsis is associated with systemic vasodilatation.

Inhaled nitric oxide (NO) may be used as a selective pulmonary artery vasodilator. Because it is given by inhalation it is selectively distributed to ventilated regions of the lung where it produces vasodilatation. This vasodilatation to ventilated alveoli may significantly improve ventilation/perfusion matching with improved gas exchange.

NO is rapidly inactivated by haemoglobin preventing a systemic action. It is necessary to monitor the level of inspired gas, nitrogen dioxide (NO2) and methaemoglobin to avoid toxicity.

Nebulised prostacyclin is a vasodilator with similar effects to NO but less risk of toxicity.

General management

Correction of anaemia by blood transfusions improves oxygen carriage in the blood and oxygen delivery to the tissues.

Nutritional support (e.g. by enteral feeding via a jejunostomy) is crucial in maintaining the patient’s overall fitness in the face of critical illness, and correction of hypoalbuminaemia improves the osmotic pressure of the plasma reducing fluid leak from the circulation.

The ventilated patient with ARDS is particularly vulnerable to hospital-acquired pneumonia and bronchoalveolar lavage may be helpful in identifying pathogens.

Multiorgan failure often complicates ARDS requiring further specific interventions (e.g. dialysis for renal failure).

Anti-inflammatory therapies

A key target for potential treatment is the cascade of inflammatory events arising from the tissue damage resulting from the initiating illness. Unfortunately, these events are poorly understood and no anti-inflammatory drug has yet achieved an established role in treating ARDS.

Corticosteroids have not been beneficial.

Ibuprofen has been used in an attempt to reduce neutrophil activation and pentoxifylline has been used because of its action in reducing the production of interleukin-1.

Haemofiltration is a procedure primarily used to control fluid balance but it may have an additional beneficial effect in patients with sepsis by removal of endotoxins.

Recombinant human activated protein C has an anti-inflammatory effect by blocking the production of cytokines and cell adhesion and by inhibiting thrombin production. This drug has been shown to reduce mortality when used early in the treatment of patients with severe sepsis and multiple organ failure.

Complications of ARDS 

  • The high ventilation pressures lead to barotrauma: pneumothorax, surgical emphysema, pneumomediastinum.
  • Pneumothorax may be lethal, but difficult to detect on a CXR in the supine patient
  • Nosocomial infections occur in about half the patients, making surveillance bronchoalveolar lavage important
  • Myopathy associated with long-term neuromuscular blockade, high steroid doses, and poor glycaemic control
  • Non-specific problems of venous thromboembolism, GI haemorrhage, inadequate nutrition.

References:
author

Daniel Ogera

Medical educator, passionate about simplifying difficult medical concepts for easier understanding and mastery by nursing and medical students.

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  • Topic:Clinicals
  • Duration:11 minutes, 3 seconds
  • Subtopic:Pulmonology

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