Acute lung injury (
ALI) is a diffuse heterogeneous
lungThe lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
injury characterized by
hypoxemia Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...
, non cardiogenic
pulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the heart to remove fluid from the lung circulation or a direct injury to the lung parenchyma...
, low lung compliance and widespread
capillaryCapillaries are the smallest of a body's blood vessels and are part of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
leakage. ALI is caused by any stimulus of local or systemic
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
, principally
sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
.
Acute Lung Injury (ALI) and Acute Respiratory Distress SyndromeAcute respiratory distress syndrome , also known as respiratory distress syndrome or adult respiratory distress syndrome is a serious reaction to various forms of injuries to the lung....
(ARDS) are defined as:
- Bilateral pulmonary infiltrates on chest x-ray
- Pulmonary Capillary Wedge Pressure <
- PaO2/FiO2* <300 = ALI
- PaO2/FiO2 <200 = ARDS
Primary ALI is caused by a direct injury to the lung (e.g.
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Acute lung injury (
ALI) is a diffuse heterogeneous
lungThe lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
injury characterized by
hypoxemia Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...
, non cardiogenic
pulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the heart to remove fluid from the lung circulation or a direct injury to the lung parenchyma...
, low lung compliance and widespread
capillaryCapillaries are the smallest of a body's blood vessels and are part of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
leakage. ALI is caused by any stimulus of local or systemic
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
, principally
sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
.
Acute Lung Injury (ALI) and Acute Respiratory Distress SyndromeAcute respiratory distress syndrome , also known as respiratory distress syndrome or adult respiratory distress syndrome is a serious reaction to various forms of injuries to the lung....
(ARDS) are defined as:
- Bilateral pulmonary infiltrates on chest x-ray
- Pulmonary Capillary Wedge Pressure <
- PaO2/FiO2* <300 = ALI
- PaO2/FiO2 <200 = ARDS
Primary ALI is caused by a direct injury to the lung (e.g. pneumoniaPneumonia is an inflammatory illness of the lung. Frequently, it is described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid ....
). Secondary ALI is caused by an indirect insult (e.g. pancreatitisPancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden while chronic pancreatitis "is characterized by recurring or persistent abdominal pain with or without steatorrhea or diabetes mellitus."...
). There are two stages – the acute phase characterized by disruption of the alveolar-capillary interface, leakage of protein rich fluid into the interstitium and alveolar space and extensive release of cytokineCytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
s and migration of neutrophils. A later reparative phase is characterized by fibroproliferation, and organization of lung tissue.
The patient has low lung volumesLung volumes refer to physical differences in lung volume, while lung capacities represent different combinations of lung volumes, usually in relation to inhalation and exhalation....
, atelectasisAtelectasis is a medical condition in which the lungs are not fully inflated. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation....
, loss of compliance, ventilation-perfusion mismatch (increased deadspace) and right to left shunt.
Clinical features are - severe dyspnea, tachypnea and resistant hypoxemia. There are two diagnoses to be made: the syndrome of Acute Lung Injury and the underlying cause. ALI is a clinical diagnosis. There are probably two forms of ALI – primary ALI, caused by a direct injury to the lung, and secondary ALI, caused by an indirect injury to the lung. The cornerstone of treatment is to keep the PaO2 > , without causing injury to the lungs with excessive O2 or volutrauma.
Pressure controlPressure Control Ventilation also Pressure Control is a controlled mode of ventilation. The ventilator delivers a flow to maintain the preset pressure at a preset respiratory rate over a preset inspiratory time....
ventilation (PC) is more versatile than volume control: but a volume limited strategy should be used. A number of adjunct therapies are available, none have proven effective. Of these, inhaled nitric oxide and prone positioning are most frequently used. Current ventilation strategies involve using low tidal volumes with or without high levels of PEEP. The open lung approach attempts to optimize lung mechanics and minimize phasic damage by strategically placing PEEP above Pflex. Ventilator induced lung injury is caused by volutrauma and excessive use of oxygen.
SteroidA steroid is a terpenoid lipid characterized by its sterane core and additional functional groups. The core is a carbon structure of four fused rings: three cyclohexane rings and one cyclopentane ring. The steroids vary by the functional groups attached to these rings and the oxidation state of the...
s may have a role in chronic ARDS in patients, without infection, with high O2 requirements days to weeks into the disease process.
Pathology
The core pathologyPathology is the study and diagnosis of disease through examination of organs, tissues, bodily fluids, and whole bodies...
is disruption of the capillary-endothelial interface: this actually refers to two separate barriers – the endotheliumThe endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary...
and the basement membrane of the alveolus. In the acute phase of ALI, there is increased permeability of this barrier, and protein rich fluid leaks out of the capillaries. There are two types of alveolar epithelial cells – Type 1 pneumocytes represent 90% of the cell surface area, and are easily damaged. Type 2 pneumocytes are more resistant to damage, which is important as these cells produce surfactant, transport ions and proliferate and differentiate into Type 1 cells.
The damage to the endothelium and the alveolar epithelium results in the creation of an open interface between the lung and the blood, facilitating the spread of micro-organisms from the lung systemically, stoking up a systemic inflammatory response. Moreover, the injury to epithelial cells handicaps the lung’s ability to pump fluid out of airspaces. Fluid filled airspaces, loss of surfactant, microvascular thrombosis and disorganized repair (which leads to fibrosis) reduces resting lung volumes (decreased compliance), increasing ventilation-perfusion mismatch, right to left shunt and the work of breathing. In addition, lymphatic drainage of lung units appears to be curtailed – stunned by the acute injury: this contributes to the build up of extravascular fluid.
Some patients rapidly recover from acute lung injury, and have no permanent sequelae. Prolonged inflammation and destruction of pneumocytes leads to fibroblastic proliferation, hyaline membrane formation and lung fibrosis. This fibrosing alveolitis may become apparent as early as five days after the initial injury. Subsequent recovery may be characterized by reduced physiologic reserve, and increased susceptibility to further lung injuries. Extensive microvascular thrombosis may lead to pulmonary hypertension, myocardial dysfunction and systemic hypotension.
Finally, it is essential to understand that although ALI is a diffuse process, it is also a heterogeneous process, and not all lung units are affected equally: normal and diseased tissue may exist side-by-side.
Acute Lung Injury Treatment
The cornerstone of treatment is to keep the PaO2 > , without causing injury to the lungs with excessive O2 or volutrauma. Pressure control ventilation is more versatile than volume control, although breaths should be volume limited, to prevent stretch injury to the alveoli.
In general tidal volumes should not exceed 6ml/kg and plateau pressure should not exceed 30 cmH2O (2.9 kPa). However tidal volumes of 4ml/kg should be delivered irrespective of airway pressure. The management of patients with respiratory failure goes beyond ventilation strategies, requiring a holistic multisystem approach. Providers are reminded of the ABCDEFG mnemonic.
A = Airway, establish a patient airway, intubate as necessary.
B = Breathing, commence mechanical ventilation and obtain an adequate minute volume to maintain oxygen delivery.
C = Circulation: blood pressure, pulse, intravascular volume – fluid resuscitation and vasopressors as necessary
D = Diagnosis, find the underlying problem and control the source.
E = Empiric therapy, for example antimicrobials for sepsis
FG = Feed the Gut, to prevent villus atrophy and bacterial translocation
The principles of mechanical ventilation are simple:
- Give enough oxygen to keep the PaO2 over preferably, and over at the very least.
- Avoid volutrauma and barotrauma, by keeping the tidal volumes in the 4-6 ml/kg range and the airway plateau pressure below 30-35 cmH2O (2.9–3.4 kPa) (the tidal volume should not be less than 4ml/kg, irrespective of airway pressure).
The PaO2 is a function of the FiO2FiO2, in the field of medicine, is the fraction of inspired oxygen in a gas mixture.The FiO2 is expressed as a number from 0 to 1 .The FiO2 of normal room air is 0.21 ....
, the PEEP level, the mean airway pressure and the minute ventilation. The tidal volume, depending on what mode of ventilation is used, is determined by the pressure control level (in pressure controlled modes) or the tidal volume dialed up on the ventilator (in volume controlled modes).
There is no clear evidence that any particular mode or strategy improves outcome in ALI, except for controlling tidal volumes and airway pressures. What follows is a suggested starting strategy:
- Start with a high FiO2 (use the same FiO2 on the patient following intubation as before).
- Set the CPAP/PEEP level – if the patient has a P/F ratio of 200-300 start with CPAP/PEEP of 5 cmH2O (490 kPa), if the P/F ratio is <200, use a CPAP/PEEP of 10 cmH2O (980 kPa).
- For inspiratory support, use a decelerating flow pattern, with a tidal volume of 5-6 ml/kg, of if pressure control is being used, a pressure limit which gives a tidal volume of 5-6 ml/kg (1).
Please see tutorials on ventilator strategy.
It is important to note that ARDS is a disease of altered lung compliance. This is reduced due to the presence of large quantities of extravascular lung water. However, chest wall compliance may also be low - in patients who are edematous, have had massive fluid resuscitation or have abdominal hypertension. In this situation, the chamber in which the lungs are inflating (the chest), bears more resemblance to a brick wall than a rib cage with muscles. Higher inflation pressures are required to inflate the lungs in these circumstances and higher PEEP is required to maintain FRC.
The choice of mode of ventilation is institution specific. The majority of intensive care units in the United States continue to use volume controlled modes of ventilation to treat ARDS. Severe hypoxemia is managed by increasing mean airway pressure by escalating levels of PEEP and rapid respiratory rates. The logic behind increasing mean airway pressure is that much of the ventilation perfusion mismatch contributing to hypoxia occurs at end expiration (click here for more information). Although the majority cases can be managed in this way, more versatile modes are available, under the pressure control umbrella.
Pressure control modes have the advantage of allowing us manipulate the mean airway pressure by prolonging inspiration, and this may improve oxygenation without increasing peak or plateau pressures . In addition, pressure control may improve gas distribution at the end of inspiration, particularly where different lung units have different resistance patterns (ALI is, after all, a heterogeneous process).
The drawback of prolonging inspiration, and, in effect, inverting the I:E ratio (2:3), is that the patient may experience a lot of discomfort, and requires deep sedation. Further, incomplete expiration tends to reduce CO2 elimination, and the patient will develop “permissive hypercapnia” and respiratory acidosis. As we now know that ventilator induced lung injury causes much more trouble than respiratory acidosis, we do not consider the latter to be a major problem (4). Newer pressure control modes such as BiLevel / Airway Pressure Release ventilation have been developed to address the problem of patient discomfort in inverse ratio ventilation; with some success.
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