About this course:
This course reviews the epidemiology, pathophysiology, and risk factors associated with acute respiratory distress syndrome (ARDS). It also covers the clinical manifestations, diagnosis and evaluation, and supportive management strategies for ARDS.
Acute Respiratory Distress Syndrome
This course reviews the epidemiology, pathophysiology, and risk factors associated with acute respiratory distress syndrome (ARDS). It also covers the clinical manifestations, diagnosis and evaluation, and supportive management strategies for ARDS.
Upon completion of this module, learners should be able to:
- review the epidemiology of and risk factors for ARDS
- describe the pathophysiology and clinical manifestations associated with ARDS
- describe the evidence-based guidelines for the diagnosis and evaluation of ARDS
- discuss the various supportive management strategies for ARDS
- discuss the pathophysiology of mechanical ventilation and the recommended ventilator strategies for managing patients with ARDS
Healthcare providers (HCPs) are responsible for offering high-quality, evidence-based care to optimize patient outcomes. As new treatments emerge, people are living longer, healthier lives. As the US population ages, more people live with chronic health conditions. Since more people are managing complex chronic conditions, increasing numbers of patients are admitted to intensive care units (ICUs). Traditionally, HCPs working with critically ill patients have focused on stabilizing immediate, life-threatening cardiopulmonary symptoms. As survival from critical illness has improved, the medical focus has shifted to preventing the sequelae of critical illness, including neuromuscular weakness, cognitive impairment, psychological disorders, and chronic respiratory disorders. Critically ill patients are often admitted to ICUs so that HCPs can effectively manage physiological responses to illness. Acute respiratory distress syndrome (ARDS) is a distinct type of respiratory failure characterized by poor oxygenation and stiff (non-compliant) lungs. ARDS typically occurs in patients who are already critically ill due to a major injury or another disease and is associated with capillary endothelial injury and diffuse alveolar damage. Mechanical ventilation (MV) is an important aspect of managing patients with ARDS, but mortality remains high despite significant advances in treatment. HCPs caring for patients with critically ill patients must be familiar with the pathophysiology, risk factors, and clinical manifestations of ARDS. In addition, HCPs should understand the criteria for ARDS diagnosis and treatment strategies, including the use of MV (Dirkes & Kozlowski, 2019; Hyzy & McSparron, 2022).
The National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP, 2022) defines chronic diseases as conditions that last more than 1 year, require ongoing medical attention, and/or limit activities of daily living (ADLs). Chronic disease is the leading cause of death and disability in the US. An estimated 6 out of 10 American adults have at least one chronic disease, and 4 out of 10 have two or more chronic diseases. Chronic conditions such as heart disease, cancer, chronic lung disease, diabetes mellitus (DM), Alzheimer's disease, and chronic kidney disease (CKD) significantly contribute to the $4.1 trillion spent on US healthcare costs annually (NCCDPHP, 2022).
The current life expectancy for adults in the US is 77.0 years (Centers for Disease Control and Prevention [CDC], 2022). More advanced medical treatments will be necessary as the population lives longer with complex chronic conditions. More than 5 million patients are admitted to ICUs in the US annually for intensive or invasive monitoring, including airway, breathing, or circulation support; stabilization of acute or life-threatening medical problems; and comprehensive management of an injury or illness (Society of Critical Care Medicine [SCCM], n.d.). Although the ICU patient population is heterogeneous, the most common indications for admission include cardiac, respiratory, and neurological conditions. Respiratory failure with ventilator support is among the top 5 reasons for adult ICU admissions. In addition, the most common technical support required in an ICU is MV, accounting for 20% to 40% of admissions in the US. Annual critical care costs have increased by 92% between 2000 and 2010, rising from $56 billion to $108 billion. ICU costs per day were estimated to be $4,300, with some variation depending on the treatment modalities (SCCM, n.d.). The number of patients admitted to the ICU for respiratory support rose further due to the coronavirus (COVID-19) pandemic, with rates of MV among these patients ranging from 29% to 89% across countries (Wunsch, 2020).
Acute Respiratory Distress Syndrome
A distinctive type of acute hypoxemic respiratory failure was first recognized in the 1960s. In 1967, Ashbaugh and colleagues presented a case series of 12 patients who developed respiratory failure after various clinical insults. These patients presented with hypoxemia and decreased lung compliance but did not respond to traditional respiratory treatment. Instead, these patients often required MV with positive end-expiratory pressure (PEEP) to combat atelectasis and hypoxemia. ARDS was initially named adult respiratory distress syndrome until it was discovered that it could also occur in children. ARDS also replaced other names, including shock lung, wet lung, acute lung injury (ALI), noncardiac pulmonary edema, and stiff lung. In 1994, during an American-European Consensus Conference, it was established that ALI and ARDS would be distinguished based on the severity of the patient's hypoxemia, with ARDS representing a higher level of hypoxemia. The level of hypoxemia would be evaluated with objective data using the partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio. This definition was essential to assist HCPs in determining the correct diagnosis to guide treatment options and tools for prevention and continued research. This definition was updated in 2011 and is known as the Berlin definition, which categorizes patients with ARDS into three categories. These categories include mild, moderate, and severe ARDS, with specific parameters for HCPs to utilize in the diagnostic process. The Berlin definition of ARDS is currently the most accepted definition that was initially formulated by the European Society of Intensive Care Medicine (ESICM) and endorsed by the American Thoracic Society (ATS) and the SCCM (Banavasi et al., 2021; Ignatavicius et al., 2018; Siegel, 2022b).
The estimated incidence of ARDS ranges from 62.4 to 78.9 cases per 100,000 person-years in the US. It is estimated that ARDS affects nearly 3 million people globally each year, with some variation based on geographical location. Within the US, ARDS affects approximately 200,000 people annually, resulting in 74,500 deaths. Approximately 25% of ARDS cases are initially classified as mild, while 75% are moderate or severe. However, as many as 33% of the mild cases will progress to moderate or severe ARDS. In a multicenter, international study of 30,000 ICUs, the researchers found that nearly 10% of ICU admissions and 23% of patients requiring MV met the criteria for ARDS. Approximately 80% of patients with ARDS will require MV, and mortality rates vary based on the severity of the ARDS (e.g., 27% for mild, 32% for moderate, and 45% for severe disease; Banavasi et al., 2021; Diamond et al., 2022; Siegel, 2022b).
In 2019, an outbreak of COVID-19 caused significant morbidity and mortality related to severe respiratory distress, similar to ARDS. Many patients diagnosed with COVID-19 require ICU care due to the rapid progression of respiratory symptoms; older adults and those with comorbidities are at higher risk of death. Although significant research has taken place over the last few years, there are still many unknowns about COVID-19. More specifically, researchers are finding that although COVID-19
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HCPs caring for patients with ARDS and those requiring MV must understand the following concepts (Hinkle & Cheever, 2018; Mora Caprio & Mora, 2022):
- Ventilation is the movement and exchange of gases (oxygen and carbon dioxide) between the lungs and the atmosphere. A ventilator forces oxygen into the lungs while carbon dioxide is removed from the body during exhalation. During MV, the carbon dioxide level in the blood can be modified by changing the tidal volume (TV) or respiratory rate (RR).
- Oxygenation of mechanically ventilated patients, which boosts the oxygen supply to the lungs, can be achieved by increasing the fraction of inspired oxygen (FiO2) or the PEEP.
- TV is the volume of air moved in and out of the lungs with each respiratory cycle.
- PEEP refers to the positive pressure applied by the ventilator at the end of each respiratory cycle. In mechanically ventilated patients, the pressure will remain greater than the atmospheric pressure to prevent the alveoli from collapsing.
- FiO2 is the percentage of oxygen in the air mixture that the ventilator delivers to a patient.
- Flow refers to the speed at which the ventilator delivers breaths, measured in liters per minute (LPM).
- Compliance is the elasticity and expandability of the lungs and chest wall determined by the change in volume divided by the change in pressure.
- Hypoxia refers to the lack of oxygen and decreased PaO2.
- Hypercarbia refers to the elevated carbon dioxide or partial pressure of carbon dioxide (PaCO2)
The respiratory system facilitates life-sustaining processes, including oxygen transport, respiration, ventilation, and gas exchange. Human cells rely on the oxidation of carbohydrates, fats, and proteins to produce energy. Without a continuous supply of oxygen, cells in the brain, heart, and other essential organs cannot survive. Oxygen is transported to, and carbon dioxide is removed from, the circulating blood through the thin walls of the capillaries. Oxygen diffuses through capillary walls to the interstitial fluid and eventually to the cells. Carbon dioxide diffuses in the opposite direction from the cells to the blood. After these tissue capillary exchanges, blood enters the systemic venous circulation and travels to the pulmonary circulation. The oxygen concentration in the alveoli is higher than the concentration in the blood; therefore, oxygen diffuses from the alveoli to the blood. Similarly, carbon dioxide has a higher concentration in the blood than in the alveoli, so it diffuses from the blood to the alveoli (see Figure 1; Hinkle & Cheever, 2018).
Human Gas Exchange
(Medic Tests, 2021)
Ventilation requires movement of the walls of the thoracic cage and the diaphragm—the movements of the thoracic cage and diaphragm alternate by increasing and decreasing the chest's capacity. When the chest capacity increases, air enters the trachea, passes through the bronchi and bronchioles, and inflates the alveoli in the lungs (inspiration). As the thoracic cavity expands, the pressure inside the thorax is lower than the atmospheric pressure; air flows from a region of higher to lower pressure. During expiration, the diaphragm relaxes and the lungs recoil, decreasing the size of the thoracic cavity. As the pressure in the alveoli increases, air flows from the lungs to the atmosphere. The inspiratory phase of respiration requires active energy, while the expiratory phase is passive (Hinkle & Cheever, 2018).
In addition to air pressure variances, airway resistance, lung compliance, and lung volumes can also impact ventilation. The size or diameter of the airway, lung volumes, and airflow velocity determine airway resistance. Any process that changes the diameter of the airway will affect airway resistance and airflow rate. With increased airway resistance, a more significant respiratory effort will be required to achieve normal ventilation. Compliance allows the thoracic cavity to expand (change in volume) based on air pressure variances. Alveolar surface tension and the amount of connective tissue and water in the lungs determine lung compliance. Standard compliance allows the lungs and thorax to stretch easily when pressure is applied. Increased compliance occurs when the lungs have lost their elastic recoil and become permanently overextended (e.g., COPD). Decreased compliance occurs when the lungs become stiff, requiring increased energy expenditure by the patient to achieve normal ventilation levels. ARDS, pulmonary edema, pleural effusion, morbid obesity, pneumothorax, and pulmonary fibrosis are associated with decreased lung compliance (Hinkle & Cheever, 2018).
Gas exchange depends on pulmonary diffusion and perfusion. Pulmonary diffusion is how oxygen and carbon dioxide are exchanged in the body due to the differences in gas concentrations in the alveoli and capillaries. The alveolar-capillary membrane is ideal for diffusion due to its large, thin surface area, allowing for gas exchange from areas of high concentration to low concentration. Pulmonary perfusion refers to the blood flow through the pulmonary vasculature and is determined by pulmonary artery pressure, gravity, and alveolar pressure. Blood is pumped into the lungs by the right ventricle through the pulmonary artery. The pulmonary artery supplies both lungs by dividing into the right and left branches. The normal range for systolic blood pressure in the pulmonary artery is about 20 to 30 mm Hg, and the diastolic pressure is 5 to 15 mm Hg, making pulmonary circulation a low-pressure system. Due to these lower pressures, the pulmonary vasculature can accommodate varying amounts of blood flow. Alveolar pressure also influences perfusion, as pulmonary capillaries lie between adjacent alveoli. Therefore, if the alveolar pressure is high, the capillaries are squeezed, impacting perfusion (Hinkle & Cheever, 2018).
Adequate gas exchange depends on effective ventilation and perfusion, resulting in an adequate ventilation-perfusion (V/Q) ratio. Four V/Q states can occur in the lungs: normal V/Q ratio, low V/Q ratio, high V/Q ratio, and absence of ventilation and perfusion. In a healthy lung, the V/Q ratio is 1:1, indicating equal amounts of blood and gas moving through the alveoli. Low V/Q ratios (shunt) happen when perfusion exceeds ventilation. When blood bypasses the alveoli without gas exchange, shunting results in hypoxia. Low V/Q ratios can occur with obstruction of the distal airways (e.g., tumor, atelectasis, pneumonia, or mucus plug). High V/Q ratios (dead space) develop when ventilation exceeds perfusion, resulting in an inadequate blood supply for gas exchange in the alveoli (e.g., pulmonary emboli [PE], pulmonary infarction, cardiogenic shock). A silent unit occurs in the absence of ventilation and perfusion caused by blockages (e.g., pneumothorax, ARDS; Hinkle & Cheever, 2018).
Neurologic Control of Ventilation
Ventilation control depends on the neuronal network in the brainstem, which controls the activities of the motor neurons that innervate the respiratory muscles. The inspiratory and expiratory centers in the medulla oblongata and pons control the rate and depth of ventilation. The pneumotaxic center in the upper pons controls the respiration pattern, while the apneustic center in the lower pons stimulates the inspiratory medullary center to promote deep inspiration. In addition, various groups of receptor sites in the brain assist with respiratory control. Central chemoreceptors within the medulla respond to chemical changes in cerebrospinal fluid (CSF). An increase or decrease in pH triggers these receptors, resulting in a change in the rate and depth of respiration. Peripheral chemoreceptors from the aorta to the arch and in the carotid arteries respond to changes in PaO2, followed by changes in PaCO2 and pH. Within the lungs, various receptors—including stretch, irritant, and juxtacapillary mechanoreceptors—respond to changes in resistance by altering breathing patterns. Proprioceptors in the muscles and chest wall react to body movements such as range of motion (ROM) exercises, stimulating an increase in ventilation. Finally, baroreceptors in the aorta and carotid bodies respond to changes in arterial blood pressure, causing reflex hypoventilation or hyperventilation (Hinkle & Cheever, 2018).
Pathophysiology of Acute Respiratory Distress Syndrome
Healthy lung function requires dry, patent alveoli that are closely situated by well-perfused capillaries. The normal pulmonary capillary endothelium is selectively permeable, allowing a small amount into the interstitium. Hydrostatic and oncotic forces control fluid movement while preventing alveolar edema. ARDS involves the activation and dysregulation of multiple overlapping and interacting injury response pathways, coagulation, and inflammation in the lungs and systemically. These pathways are critical to the body's normal response to injury or infection, but excessive or diffuse activation is harmful. The degree to which the specific pathways are involved and the degree of lung versus systemic involvement can vary, making ARDS complex and heterogeneous (Diamond et al., 2022; Patel, 2022; Siegel, 2022b).
ARDS progresses through different phases, starting with alveolar-capillary damage, known as the exudative phase. During this early phase of ARDS, pulmonary or systemic inflammation causes the release of cytokines and other proinflammatory molecules. The cytokines activate alveolar macrophages and recruit neutrophils to the lungs. This process releases oxidants, leukotrienes, platelet-activating factors, and proteases, damaging the capillary and alveolar endothelium and disrupting the barrier between the capillaries and the airspaces. The barrier disruption allows fluid, protein, and cellular debris to flood the airspace and interstitium, leading to disruption of surfactant, airspace collapse, V/Q mismatch, pulmonary hypertension, and shunting. When the airspaces are flooded or collapsed, no inspired gas can enter, leaving blood with a mixed venous oxygen content to perfuse the alveoli regardless of how high the FiO2 is. These changes lead to impaired gas exchange, decreased lung compliance, and pulmonary hypertension. The second phase of ARDS is known as the proliferative phase, characterized by improved lung function and healing. Finally, the fibrotic phase indicates the end of the acute disease process. For patients with COVID-19, research has shown that injury to the alveolar epithelial cells is the predominant cause of COVID-19 ARDS and that endothelial cells are less damaged, causing less exudate (Diamond et al., 2022; Li & Ma, 2020; Patel, 2022; Siegel, 2022b).
Risk Factors for ARDS
Many factors may increase the risk of ARDS, including infectious and non-infectious triggers. These triggers can cause injury to the lung directly due to local inflammation or indirectly due to systemic inflammation and injury mediators. More than 60 possible causes of ARDS have been identified, and other causes will likely emerge over time. Sepsis (i.e., pulmonary and non-pulmonary) is the most common cause of ARDS, with pulmonary sepsis (i.e., pneumonia) being the most prevalent cause (60% of ARDS cases). Among the non-infectious triggers, the more common causes of ARDS include aspiration of gastric contents, pancreatitis, and severe traumatic injuries that result in hypovolemic shock or multiple blood transfusions. However, with advancements in MV, transfusion strategies, and the use of crystalloids for fluid resuscitation, the number of ARDS cases resulting from a traumatic injury has decreased. Alcohol use, cigarette smoking, and exposure to air pollutants are common indirect factors that increase the risk of ARDS. Some genetic components have also been shown to minimally increase the risk of ARDS, specifically the haptoglobin variant Hp-2, more common in European ancestry. More recently, there has been an increase in acute lung injuries related to e-cigarettes, vaping, and drug-induced ARDS (i.e., chemotherapeutic agents and immunotherapies; Bos & Ware, 2022; National Heart, Lung, and Blood Institute [NHLBI], 2022; Patel, 2022; Siegel, 2022b). Less common causes of direct and indirect lung injuries can be found in Table 1.
Less Common Direct and Indirect Causes of Acute Lung Injuries
(Bos & Ware, 2022; NHLBI, 2022; Patel, 2022; Siegel, 2022b)
The lung injury prediction score (LIPS) can identify patients at low risk for developing ARDS but may not be as accurate in identifying high-risk patients. The LIPS is a sum of points assigned for various predisposing conditions for ARDS, with a score less than 4 indicating low risk and a score greater than 4 indicating a high risk. In a prospective cohort study of 5,584 patients, the LIPS had a negative predictive value (i.e., the percent of patients with a LIPS score less than 4 that developed ARDS) of 97%. However, for scores greater than 4, the LIPS had a sensitivity of 68% and a specificity of 78%. More recent studies have found that a high LIPS score, combined with a high C-reactive protein (CRP) level, may increase the accuracy of predicting patients at high risk for ARDS (Ahmed et al., 2020; Siegel, 2022b).
Patients with ARDS can present with clinical manifestations of ARDS in addition to features associated with the inciting event. However, based on the numerous potential inciting events, manifestations of ARDS can often be non-specific, making diagnosis challenging. HCPs should be aware of various clinical findings associated with ARDS since prompt recognition and treatment is critical to reducing morbidity and mortality. The characteristic features of ARDS include dyspnea and hypoxemia that progressively worsens within 6 to 72 hours of the inciting event. Symptoms can quickly progress from mild shortness of breath to severe respiratory distress within 12 to 24 hours, often requiring MV to prevent hypoxia. Patients may also report restlessness, anxiety, fast breathing or heart rate, coughing, and fatigue. Physical exam findings may include acute confusion, cyanosis, diaphoresis, tachypnea, tachycardia, and diffuse crackles. Patients often maintain low oxygen saturation levels despite 100% oxygen administration (Diamond et al., 2022; Patel, 2022; Siegel, 2022a).
In many cases, the underlying cause will be easily identified as pneumonia or sepsis. Clinical features associated with pneumonia or sepsis may include fever, hypotension, leukocytosis, lobar consolidation, and lactic acidosis. However, in other cases, the causative factor may be more challenging to determine. HCPs should ask the patient or family member about potential recent exposures that could help identify the causative agent. More specifically, HCPs should inquire about recent trauma, smoke or other toxic inhalation, sick contacts, and environmental exposures. In addition, HCPs should also ask about a history of asthma, cancer, cardiac dysfunction, pulmonary fibrosis, stem cell transplant, recent surgeries, smoking history, illicit drug use, or changes in prescription medications (Diamond et al., 2022; Patel, 2022; Siegel, 2022a).
Evaluation and Diagnosis
ARDS can be challenging to diagnose and often masquerades as another disorder or disease initially, making prompt treatment difficult. HCPs should start with a medical history, focusing on previous respiratory conditions, heart disease, recent infections, or recent travel that could have resulted in some contamination and other relevant information. The HCP should complete a thorough physical assessment looking carefully for any signs of change in fluid status or inflammatory response. Examination of the abdomen should include tenderness, distention, or absent bowel sounds. A thorough skin assessment should also be completed, looking for rashes, wounds, burns, or track marks (Diamond et al., 2022; Siegel, 2022a).
Laboratory and Diagnostic Testing
Laboratory testing for patients with suspected ARDS should include a complete blood count (CBC) with differential, comprehensive metabolic profile (CMP), serum magnesium, calcium, and phosphorous levels, liver function tests, coagulation studies, and arterial blood gas (ABG) analysis. Other laboratory tests that may be indicated to evaluate for common etiologies include troponin, CRP, D-dimer, lactate levels, brain natriuretic peptide (BNP; for cardiogenic pulmonary edema), and lipase (for pancreatitis; Diamond et al., 2022; Siegel, 2022a).
In addition to laboratory testing, all patients with suspected ARDS should have a chest radiograph. Abnormal imaging is critical for diagnosing ARDS and evaluating various etiologies (e.g., pneumonia). Although not necessary to diagnose ARDS, a computed tomography (CT) of the chest may be helpful for a more comprehensive pulmonary evaluation for pneumothorax, pleural effusion, barotrauma, or mediastinal lymphadenopathy. An electrocardiogram (ECG) should be performed to evaluate for cardiac dysfunction, such as arrhythmias or ischemia. A sputum or endotracheal aspirate should be collected and sent for gram stain and culture (Diamond et al., 2022; Siegel, 2022a).
Additional testing may be required when acute cardiogenic pulmonary edema is suspected since it can mimic ARDS. Most HCPs will use the combination of clinical assessment and BNP or N-terminal proBNP (NT-proBNP), with or without transthoracic echocardiography (TEE), to confirm or exclude acute cardiogenic pulmonary edema. Since acute cardiogenic pulmonary edema is usually due to left ventricular systolic or diastolic dysfunction, clinical features can include crackles, murmurs, S3/S4 gallops, raised jugular venous pressure, and lower extremity edema. A BNP or NT-proBNP can be obtained, but this test alone is not a reliable indicator for distinguishing ARDS from acute cardiogenic pulmonary edema. TEE may be performed when a diagnosis of acute cardiogenic pulmonary edema cannot be excluded by clinical evaluation, laboratory findings, or imaging but is not routinely performed in patients with low suspicion of acute cardiogenic pulmonary edema. In rare cases, when the diagnosis and etiology of ARDS remain unclear, additional testing may be performed, including an echocardiogram, heart catheterization, or bronchoscopy (Diamond et al., 2022; Siegel, 2022a).
For most patients, ARDS is a clinical diagnosis, as histopathology (i.e., diffuse alveolar damage) obtained through a lung biopsy is rarely performed. The Berlin Definition of ARDS is the gold standard for diagnosis. It should be used once acute cardiogenic pulmonary edema and other causes of hypoxemic respiratory failure and bilateral lung infiltrates are excluded (Diamond et al., 2022; Gorman et al., 2022; Siegel, 2022a).
Histopathologic Diagnosis and Staging
Patients with ARDS typically progress through three pathologic stages: early exudative, fibroproliferative, and fibrotic. Although histopathological samples are not routinely collected for diagnosis of ARDS, they are obtained in certain circumstances and, more commonly, post-mortem. The early exudative stage occurs in the first 7 to 10 days. It is characterized by diffuse alveolar damage, evidenced by interstitial edema, type II cell hyperplasia, acute and chronic inflammation, and hyaline membrane formation. The fibroproliferative stage occurs after 7 to 10 days. It is characterized by the resolution of pulmonary edema and the proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early collagen deposition. The fibroproliferative phase may vary in length, but it is estimated to be between 2 and 3 weeks. For patients that survive, the final stage is the fibrotic stage, characterized by the obliteration of normal lung architecture, fibrosis, and cyst formation. The severity of the disease determines the degree of fibrosis (Gorman et al., 2022; Siegel, 2022a).
Clinical Course of ARDS
For patients with ARDS, the first few days are characterized by hypoxemia that requires moderate to high concentrations of inspired oxygen and PEEP. The patient will have persistent bilateral alveolar infiltrates and diffuse crackles. For most patients, these first few days are usually the most tenuous. Mortality in patients with ARDS is not usually due to respiratory function but rather sepsis or multiorgan failure. For patients who survive, the subsequent days are characterized by diminishing infiltrates and improved oxygenation, allowing for weaning to begin. Some patients will have persistent hypoxemia and remain ventilator-dependent, which signifies the fibroproliferative phase. These patients will have low lung compliance, high dead space, pulmonary hypertension, and persistent hypoxemia. Finally, the fibrous stage will begin for patients who survive the fibroproliferative phase. This stage is characterized by a gradual improvement in hypoxemia and pulmonary infiltrates over weeks to months. Cardiopulmonary function generally returns to baseline by 6 to 12 months (Gorman et al., 2022; Siegel, 2022a).
Treatment Strategies for ARDS
ARDS can be difficult to manage, with high mortality rates that are dependent on numerous factors, including the severity of the disease, age, and comorbidities. MV and other supportive therapies remain the recommended strategies for managing ARDS. Treatment goals include increasing oxygen delivery, decreasing oxygen consumption, and avoiding further injury. Most patients will require invasive MV (i.e., via an endotracheal tube or tracheostomy), particularly those with moderate or severe ARDS. Noninvasive ventilation (NIV; via a mask or nasal cannula) may be appropriate for some patients with mild or early ARDS (Patel, 2022; Siegel & Siemieniuk, 2022).
NIV should only be used for patients who are hemodynamically stable and easily oxygenated. These patients require frequent evaluation by an HCP to identify the early signs that intubation is needed. Mild ARDS can be treated with 70% to 100% oxygen delivered noninvasively using a non-rebreather face mask. However, since the COVID-19 pandemic, high-flow nasal cannula (HFNC) and noninvasive positive pressure ventilation (NIPPV) use have increased. These strategies may prevent endotracheal intubation and the complications associated with MV. However, if excessive spontaneous breathing effort is needed, there is a risk of self-inflicted lung injury. In a clinical trial that compared HFNC, face mask NIPPV, and standard oxygen, researchers found that HFNC was more effective at preventing intubation in patients with a PaO2/FiO2 <200. In addition, there was a higher 90-day mortality rate with standard oxygen and face mask NIPPV compared to HFNC. Researchers hypothesized that the face mask NIPPV has a higher mortality rate due to excessive TV that can worsen lung injury. NIV should be used cautiously because delayed intubation can increase mortality in moderate to severe ARDS. MV should be considered if oxygen saturation falls below 90% with NIV (Patel, 2022; Siegel & Siemieniuk, 2022).
Most patients with ARDS will require MV to improve oxygenation and reduce oxygen demand by relaxing the respiratory muscles. Normal respiratory function works as a negative-pressure system. During inspiration, the diaphragm moves downward, creating negative pressure in the pleural cavity. This negative intrathoracic pressure decreases right atrial (RA) pressure, which creates a pulling effect on the inferior vena cava (IVC), resulting in increased venous return. Conversely, MV alters normal respiratory function by pushing air into the upper airways and alveoli, creating positive pressure in the thoracic cavity. This positive intrathoracic pressure increases RA pressure and decreases venous return, reducing preload (i.e., the force stretching the cardiac muscle before constriction). With less blood reaching the right ventricle and, subsequently, the left ventricle, cardiac output decreases. With decreased cardiac output and preload, mean arterial pressure (MAP) will drop if there is no compensatory increase in systemic vascular resistance (SVR). In addition, the positive pressure generated by MV can significantly reduce a patient's work of breathing (WOB). This reduction in WOB allows blood flow to be redistributed to more critical organs, limits carbon dioxide and lactate generation, and improves acidosis (see Figure 2; King Han, 2022; Mora Carpio & Mora, 2022).
HCPs who manage MV patients must understand lung pressures and lung compliance. Healthy lung compliance in adults is approximately 100 mL/cm H2O. Therefore, when positive-pressure ventilation delivers 500 mL of air to a healthy lung, a 5 cm H2O increase in alveolar pressure will occur. Various respiratory disorders can significantly impact lung compliance. For example, any respiratory disorder that destroys the lung parenchyma (e.g., COPD) can increase lung compliance. Conversely, ARDS, pneumonia, pulmonary fibrosis, and pulmonary edema can cause stiffening of the lungs, resulting in decreased lung compliance. Stiffening can increase the risk of barotrauma during MV, where small increases in volume can lead to significant increases in pressure. HCPs should understand two pressure types when managing a patient receiving MV: peak pressure and plateau pressure. Peak pressure measures airway resistance and is achieved when air is pushed into the lungs during inspiration. Plateau pressure is a static pressure achieved at the end of full inspiration, measuring alveolar pressure and lung compliance. Normal plateau pressure is below 30 cm H2O, and higher pressures increase the likelihood of barotrauma (Mora Carpio & Mora, 2022).
Biology of Ventilation
The American Thoracic Society (ATS), the European Society of Intensive Care Medicine, and the SCCM published a clinical practice guideline on using MV in adults with ARDS (Fan et al., 2017). Ventilator settings are particularly important for patients with ARDS, as evidence suggests that some strategies can exacerbate alveolar damage and perpetuate lung injury. Therefore, a low TV or lung-protective approach is recommended using a volume-limited assist control mode (AC). AC ventilation is a volume-controlled mode that sets a fixed TV that the ventilator will deliver at set intervals or when the patient initiates a breath (Diamond et al., 2022; Fan et al., 2017; Patel, 2022; Siegel & Hyzy, 2022). The NHLBI ARDS Clinical Network Mechanical Ventilation Protocol (ARDSnet) is a low TV approach, which includes the following recommendations:
- TV from 4 to 8 mL/kg of ideal body weight
- respiratory rate up to 35 breaths per minute (bpm)
- SpO2 between 88% and 95%
- plateau pressure less than 30 cm H2O
- pH between 7.30 and 7.45
- inspiratory-to-expiratory time ratio less than 1
- PEEP should be high enough to maintain open alveoli and minimize FiO2 until a plateau pressure of 28 to 30 cm H2O is reached; PEEP is typically set at 5 cm H2O, and FiO2 is set to 1 and weaned soon after to target oxygen saturation (Diamond et al., 2022; Fan et al., 2017; Patel, 2022; Siegel & Hyzy, 2022)
Conventional MV strategies for ARDS focused on normalizing ABG values. However, more recent research has shown that low TVs reduce mortality. Low TVs require an increased respiratory rate (up to 35 bpm) to ensure adequate alveolar ventilation and carbon dioxide removal. These settings can increase the risk of respiratory acidosis, which is generally well tolerated when the pH remains ≥ 7.15 (ideally between 7.30 and 7.45). If the pH drops below 7.15, a bicarbonate infusion may be beneficial. Oxygen saturation levels between 88% and 95% are recommended to limit oxygen toxicity. Low TV and hypercarbia can cause dyspnea, causing ventilator dyssynchrony. Ventilator dyssynchrony can lead to increased WOB, discomfort, and poor gas exchange. HCPs should administer analgesics (Fentanyl or Morphine) and a sedative (e.g., propofol [Diprivan]). PEEP improves oxygenation in patients with ARDS by increasing the volume of aerated lung through alveolar recruitment. This allows for a decrease in FiO2 to prevent oxygen toxicity. HCPs should titrate the PEEP, using the least amount necessary to ensure adequate oxygenation on a non-toxic FiO2. For most patients with ARDS, this level of PEEP will be between 8 and 15 cm H2O; however, some patients with severe ARDS may require PEEP levels greater than 20 cm H2O. These patients should be monitored closely for oxygen toxicity (Diamond et al., 2022; Fan et al., 2017; Patel, 2022; Siegel & Hyzy, 2022).
Other Supportive Measures
After the initiation of low TV ventilation, HCPs should monitor the patient's clinical response, including vital signs, lung sounds, ABG analysis, and plateau pressure. Adjustments to the ventilator settings should be made as needed. For patients that improve with low TV ventilation, HCPs should attempt weaning as tolerated, specifically reducing the PEEP and FiO2. If the patient tolerates the initial weaning process, switching to a partial-assist or spontaneous ventilator mode can be considered. The weaning process will vary but could take as little as 24 to 48 hours or days to weeks in other individuals. HCPs should initiate medical therapies to address the underlying etiology of ARDS (Siegel & Hyzy, 2022).
Many patients respond well to low TV ventilation, while others experience refractory hypoxemia (i.e., PaO2/FiO2 <150 mmHg). Signs of refractory hypoxemia can include ventilator dyssynchrony, high plateau pressures (i.e., ≥ 30 cm H2O), or worsening hypoxemia. HCPs should be aware that abrupt changes in airway pressures could indicate a pneumothorax or obstructed endotracheal tube. When refractory hypoxemia occurs, HCPs should target the suspected reason for the intolerance to low TV ventilation. For some patients, additional supportive therapies may be indicated, such as conservative fluid management, considering an alternative diagnosis, evaluating for complications of ARDS or MV (e.g., PE or ventilator-associated pneumonia [VAP]), and treating ventilator dyssynchrony. Other options include switching ventilator modes (i.e., pressure limited or increasing the inspiratory to expiratory ratio; Siegel & Hyzy, 2022; Siegel & Siemieniuk, 2022). Other supportive measures for refractory hypoxemia can include (Fan et al., 2017; Patel, 2022; Siegel & Hyzy, 2022; Siegel & Siemieniuk, 2022):
- General measures that decrease oxygen consumption should be implemented to improve arterial oxygen saturation. Pain, anxiety, increased WOB, and fever can all increase oxygen consumption. HCPs should consider anti-pyretic, analgesics, sedatives, and paralytics when appropriate.
- Conservative fluid management should be considered for patients with refractory hypoxemia. ARDS can increase vascular permeability leading to pulmonary edema. HCPs should consider fluid restrictions and/or diuresis for patients with fluid overload. This is a delicate balance between ensuring adequate circulating volume to preserve end-organ perfusion while lowering preload and fluid in the lungs.
- Treat ventilator dyssynchrony, which can increase WOB, discomfort, poor gas exchange, and lead to prolonged mechanical ventilation (PMV). Ventilator dyssynchrony can occur in 25% of patients receiving MV, leading to an increased need for sedation and/or a neuromuscular blockade. HCPs should review ventilator settings and consider minor trigger sensitivity and inspiratory flow adjustments.
- Prone positioning ventilation involves ventilating the patient with low TV ventilation while in the prone position. This strategy can improve oxygenation in patients with moderate to severe ARDS by allowing the recruitment of nonventilated lung regions and decreasing the risk of ventilator-induced lung injury (VILI). The clinical practice guidelines for MV in ARDS patients recommend prone positioning for more than 12 hours per day for severe ARDS. Prone positioning should be initiated early (within 7 days) to maximize the success of this strategy. If patients do not respond after a short trial of prone positioning (i.e., 6 to 8 hours or up to 20 hours), they are unlikely to improve with this strategy.
- High PEEP can be used for patients with refractory hypoxemia, which may help to open collapsed alveoli resulting in decreased alveolar over-distention. If the alveoli remain open throughout the respiratory cycle, cyclic atelectasis is reduced, decreasing the risk of VILI. Fan and colleagues (2017) recommend that adults with moderate to severe ARDS receive high PEEP when low PEEP is insufficient.
- Recruitment maneuvers are a brief application of a high level of PEEP or CPAP, which recruits non-gas exchanging parts of the lung to become involved in gas exchange. These maneuvers can be performed independently or as part of an open lung ventilation approach (i.e., a strategy that combines low TV ventilation with recruitment and subsequent titration of applied PEEP). Fan and colleagues (2017) recommend that adult patients with ARDS receive recruitment maneuvers; however, little guidance is given regarding the method, timing, and optimal patient population. Recruitment maneuvers are more often used in patients with moderate to severe ARDS.
- Pharmacological therapies may be beneficial in patients with severe ARDS. Neuromuscular blockades can improve oxygenation but remain controversial because of the risk of prolonged neuromuscular weakness. The impact of glucocorticoid administration on ARDS remains uncertain. Some studies have found that early administration of glucocorticoids in moderate to severe ARDS may reduce mortality. Glucocorticoids should be considered for patients with ARDS triggered by a steroid-responsive process (e.g., acute eosinophilic pneumonia, community-acquired pneumonia, or refractory sepsis) or patients with early (within 14 days of onset) refractory hypoxemia despite standard therapies. Inhaled pulmonary vasodilators (e.g., nitric oxide [INOmax], prostacyclin [Flolan], prostaglandin E1 [Prostasol]) may improve oxygenation in patients with refractory hypoxemia by selectively dilating vessels that perfuse well-ventilated lung regions, improving V/Q matching and ameliorating pulmonary hypertension. These agents act locally and have short half-lives with very few systemic effects. Studies have found that neither of these agents is superior to the other; however, nitric oxide is associated with the risk of renal impairment.
- Extracorporeal membrane oxygenation (ECMO) has been more frequently used as a rescue therapy for improving oxygenation. ECMO is a system that drains blood from a large central vein, pumping it through a gas exchange device that oxygenates the blood and removes carbon dioxide. The blood is then reinfused back into a large central vein or artery. Fan and colleagues (2017) recommend that additional evidence is needed to make a definitive clinical recommendation for ECMO in severe ARDS patients. ECMO should be reserved for patients with severe ARDS that have failed prone ventilation, high PEEP, and recruitment maneuvers. Early application (i.e., within 7 days) is critical to successful outcomes with ECMO.
Complications of ARDS
Patients with ARDS are at high risk for complications related to critical illness and MV. More specifically, patients requiring MV are at high risk for complications and poor outcomes, including death. VAP, barotrauma, PE, VILI, and sepsis are ventilator-associated events (VAEs) that can affect patients receiving MV. These complications can result in PMV, prolonged ICU stays, increased healthcare costs, and high mortality. VAE rates for ICUs nationwide are approximately 6.8 events per 1,000 ventilator days. These rates varied substantially by ICU type, with higher rates in trauma, surgery, and neurological units and lower in medical and cardiac units. Although patients are at risk for VAEs until extubation occurs, the highest risk is within the first 2 weeks of MV (specifically days 3 to 7). VAEs are divided into two subcategories to distinguish VAP from other ventilator-associated complications. The overall mortality rate for VAEs is 31%, and patients developing VAEs are twice as likely to die compared to patients who did not develop VAEs (Klompas, 2019).
Prolonged Mechanical Ventilation
PMV increases the risk of pneumonia, barotrauma, tracheal injuries, musculoskeletal deconditioning, and mortality. Strategies such as early mobilization (EM) of patients on MV can help prevent PMV and facilitate the weaning process (Fadila et al., 2021). Prolonged ventilatory dependence can stem from many factors, including respiratory insufficiency, reduced ventilatory capacity, and cardiovascular insufficiency. PMV can lead to diaphragmatic weakness and atrophy, especially when accompanied by passive modes (e.g., AC) of ventilation. Other factors contributing to respiratory muscle weakness include malnutrition, immobility, excessive steroids, sedative medications, and a systemic inflammatory response (SIR) associated with sepsis. Cardiovascular insufficiency (i.e., heart failure [HF]) can also increase the risk of PMV (Fadila et al., 2022). The following risk factors can increase the risk of PMV:
- history of obstructive pulmonary disease (e.g., COPD)
- history of restrictive pulmonary disease (e.g., pulmonary fibrosis, sarcoidosis)
- neuromuscular disorders
- ICU admission due to pneumonia, ARDS, head trauma, and postoperative intracerebral hemorrhage
- abnormal arterial carbon dioxide, serum blood urea nitrogen (BUN), serum creatinine, arterial pH, white blood count (WBC), or body temperature on the first ICU day
- age 85 years and older
- extended inpatient length of stay before ICU admission (Fadila et al., 2022; King Han, 2022)
Barotrauma is an example of a VILI caused by high lung inflation pressure, which leads to high transpulmonary pressure, regional lung over-distention, and air leakage. With ventilation, positive pressure is needed to overcome airway resistance, increase airflow, and overcome lung elasticity. Plateau pressure is commonly used as a representative indicator of transpulmonary pressure, measuring lung over-distention. Careful control of inspiratory pressures is a strategy to limit lung distention and prevent barotrauma. High inspiratory pressures can cause alveolar rupture, pneumothorax, pneumomediastinum, and subcutaneous emphysema due to barotrauma or air leakage (Haribhai & Mahboobi, 2022).
Patients with ARDS are often critically ill and require intensive, prolonged therapies that place them at risk for additional complications. Prolonged bed rest can lead to profound muscle weakness, skin breakdown, and deep vein thrombosis (DVT). Patients with ARDS and prolonged ventilation often experience gastrointestinal bleeding from stress ulcers. Acute delirium can also occur in patients who are critically ill. Since acute delirium is multifactorial, identifying and treating the underlying cause can be challenging. Additional complications can include nosocomial infections, line sepsis, urinary tract infections, antibiotic resistance, renal failure, and nutritional deficiencies. Patients who experience a critical illness can suffer long-term consequences, including anxiety, depression, and post-traumatic stress disorder (PTSD; Diamond et al., 2022; Siegel, 2022a).
The nurse's role in the care and treatment of patients with ARDS is multi-faceted and typically occurs in an ICU. Nurses should assess the patient by collecting a detailed history and performing a physical assessment. The nurse must carefully monitor vital signs, respiratory effort, oxygen saturation levels, and diagnostic studies, contacting the provider with remarkable findings. It is also essential that the nurse keeps the family updated within their scope of practice and patient confidentiality, ensuring not to violate HIPAA. The patient's family may be anxious and apprehensive. Although the nurse will be busy caring for the patient, they must remember to integrate the family into patient care and use open and honest communication (Ignatavicius et al., 2018).
Nurses may also assist with diagnostic procedures such as obtaining sputum specimens, collecting urine samples, and assisting with bronchoscopies. The nurse may need to set up sterile fields for procedures and monitor the patient for anticipated and unexpected events following the procedures. Treatment options include using supplemental oxygen as ordered and observing the effectiveness of the oxygen. The nurse must be prepared to titrate oxygen levels per provider order and change oxygen delivery devices based on arterial blood gases and/or oxygen saturation levels. Nurses should be aware of the various types of oxygen delivery devices, flow rates, and the percentage of oxygen they can deliver through each device, including a nasal cannula, face mask, nonrebreather, and venturi mask (Ignatavicius et al., 2018).
As many patients with ARDS may be placed on MV, nurses must be knowledgeable about ventilators, intubation, and sterile suctioning of the airway. Nurses working in ICUs must be familiar with different types of ventilator modes and settings and how to troubleshoot the problems. Working with respiratory therapy will be essential to deliver the best care for the patient. Since many patients with ARDS have a baseline infection or a high risk of developing an infection, nurses must employ diligent hand hygiene and other measures to prevent infection. Finally, nurses must work collaboratively with other specialty areas such as physical therapy, occupational therapy, respiratory therapy, social work, and other specialties to ensure positive outcomes (Ignatavicius et al., 2018).
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