The development of respiratory dysfunction in patients with sepsis lies on a continuum from subclinical disease to overwhelming organ dysfunction. At the worst end is the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI). The definition of ARDS is adapted from the American European Consensus Conference held in 1994:
• PaO2 in mmHg/FIO2 (for example, 0 6 for 60% oxygen) of < 200
• bilateral infiltrates on the chest x ray film
• a pulmonary arterial occlusion pressure of < 18 mmHg.
These criteria show an incidence varying from 5 to 71 per 100 000 people in the USA and accounting for nearly 5 billion dollars' worth of financial support. Morbidity and mortality associated with ALI and ARDS is in excess of 40%. Mortality is often due to unresolved sepsis or multiple organ failure as opposed to progressive respiratory failure. The hallmark of ARDS is alveolar epithelial inflammation, air space flooding with plasma proteins and cellular debris, surfactant depletion and inactivation, and loss of normal endothelial reactivity.
Hypoxaemia in sepsis is caused by extensive right-to-left intrapulmonary shunting of blood, which may account for more than 25% of the total cardiac output (see Figure 4.2). Usually compensation occurs through hypoxaemic vasoconstriction, limiting the amount of shunt by reducing perfusion to poorly ventilated lung units. However, in states of lung injury, hypoxaemic vasoconstriction may be ineffective or even absent. The shunting of blood through non-ventilated lung units accounts for the relative refractory nature of hypoxaemia in ARDS. The hypoxaemia is often out of proportion to initial x ray film findings. Lung compliance is the change in volume for a given change in pressure and is reduced in ARDS because of small airway and alveolar collapse. In early ARDS the volume of functional lung is also reduced by alveolar oedema and surfactant abnormalities. There is also an increase in airway resistance caused by airway secretions, oedema, and mediators that provoke bronchospasm.
As a result of changes in lung compliance in ARDS, greater airway pressures are needed to achieve a given tidal volume. This increases the work of breathing, which is exacerbated by the increased respiratory rate seen in severe sepsis. Hypoxaemia in sepsis therefore results from the following:
• ventilation-perfusion mismatch
• respiratory muscle dysfunction
• decreased thoracic compliance
• increased airway resistance due to bronchoconstriction.
Oxygen delivery is also affected by upper airway obstruction where there is a reduced conscious level, circulatory collapse, metabolic acidosis, and reduced haemoglobin levels.
The pathological changes in ARDS are divided into three phases:
1. the early exudative phase (days 1-5), characterised by oedema and haemorrhage;
2. the fibroproliferative phase (days 6-10), characterised by organisation and repair;
3. the fibrotic phase (after 10 days) characterised by fibrosis.
These times are approximate and characteristic features in each phase often overlap. When the initial signs and symptoms of sepsis first appear, between 28-33% of patients meet the criteria for ARDS.
Since ARDS was first reported, mortality has remained relatively constant at 60-70%. More recent reports suggest that mortality has declined to around 40%. The explanation for this apparent improvement in patient outcome is not clear but could be due to differences in patient populations, changes in ventilation strategies, greater attention to fluid management, improved haemodynamic and nutritional support, improved antibiotics for hospital-acquired infections, or corticosteroid use (small randomised trials have suggested benefit with intravenous corticosteroid therapy in patients with a prolonged fibroproliferative phase of ARDS). No one therapeutic intervention has been proved to be effective in reducing the incidence of respiratory failure in sepsis nor its mortality.
Intubation and mechanical ventilation is considered early in severe sepsis, especially if ARDS is present. The indications for intubation include:
• patient cannot protect own airway;
• correction of refractory hypoxaemia - PaO2 < 8 0 kPA (60 mmHg) - despite maximum oxygen therapy;
• respiratory rate > 35 per minute and vital capacity < 15 ml kg-1 - invasive ventilation alleviates the increased work of breathing allowing blood to be redirected to other vital organs.
Non-invasive ventilation has not been shown to be effective in ARDS, although limited data exist.
Much has been written on the different ventilatory strategies in ARDS, which is beyond the scope of this book. Pressure-controlled inverse ratio ventilation is often used as a means of recruiting non-ventilated lung units. Smaller tidal volumes limit barotrauma and volutrauma. Permissive hypercapnia means that the CO2 is allowed to rise to allow these ventilation strategies. Prone positioning of the patient can improve oxygenation but has not been shown to improve outcome. Finally, fluid balance can be difficult in ARDS because overhydration can be a disadvantage when the lung has leaky capillaries - but cardiac function and organ perfusion also have to be optimised.
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