Acute respiratory failure (ARF) and acute respiratory distress syndrome (ARDS) are critical conditions associated with high mortality. Current management strategies are evolving toward personalized care.

By Bill Pruitt, MBA, RRT, CPFT, FAARC


Management of acute respiratory failure (ARF) has continued to utilize invasive mechanical ventilation and noninvasive respiratory support (NRS) using high-flow oxygen therapy (HFOT), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) using bilevel pressure settings as primary therapies, but there is increased interest in various monitoring approaches and a more personalized care plan. Acute respiratory distress syndrome (ARDS) is also shifting to more patient-specific, personalized care and the definition of ARDS is being defined further. 

Recent guideline updates have come out from several medical groups concerning ARDS so many aspects of care are continuing to evolve but some recommendations have stayed in place for the past several years. This article will review the current approaches to caring for patients with ARF and ARDS and explore what may be coming as research continues.

Acute Respiratory Failure (ARF)

ARF is categorized as either hypoxemic or hypercapnic or mixed. Hypoxemic ARF is characterized by having a PaO2 <60 mmHg or SaO2 <88%. Hypercapnic ARF is characterized by having a PaCO2 >45 mmHg and a pH <7.35. Hypoxemic ARF can be caused by issues such as V/Q mismatch, shunt, decreased ventilation, diffusion limitation, or low inspired oxygen tension (ie, high altitude’s effect on barometric pressure). Hypercapnic ARF can be caused by alveolar hypoventilation, increased deadspace, or increased CO2 production.1 

Patients with mixed ARF have both hypoxemia and hypercapnia occurring. In all of these cases, NRS is used to decrease the work of breathing, relieve dyspnea, improve oxygenation, and attempt to avoid the need to intubate and initiate invasive mechanical ventilation.2

Hypercapnic ARF is subdivided into three possibilities: won’t breathe, can’t breathe, or can’t breathe enough. Those in the first group (won’t breathe) have a neurological issue (ie, a stroke) or may have a depressed respiratory drive due to a drug or alcohol overdose. Those in the other two groups (can’t breathe or can’t breathe enough) have hypercapnic ARF due to neuromuscular disorders, chest wall disease, pleural disease, or obstructive lung disease (COPD).1

Choices in Treatment for ARF

In hypoxemic ARF, oxygen therapy is used to increase oxygenation. If possible, O2 is delivered by simple nasal cannula (up to a flow of 6 LPM), air-entrainment (venturi) mask, or non-rebreather mask. These devices allow for quick application with the least amount of extra capital equipment and carry the lowest cost. However, if these devices are not effective and the patient does not respond quickly with an increased PaO2 (or SaO2), HFOT is often the next step in providing supplemental oxygen. In cases involving acute cardiogenic pulmonary edema, CPAP or NIV will be the preferred approach for providing supplemental oxygen. For hypoxemic ARF in COPD patients, NIV tends to be the preferred approach.1

In hypercapnic ARF, NIV is the primary choice for treatment, provided that two conditions are met. First, the patient must be breathing spontaneously. Second, the patient must be able to protect their airway and able to remove the NIV interface if they begin vomiting to avoid aspiration. Some patients may not be candidates or may not tolerate NIV; in these cases HFOT has been shown to be a possible alternative.1 Note that in patients with COPD who have chronic CO2 retention and chronic low oxygenation, there is physiologic pulmonary vasoconstriction due to the hypoxia. Supplying too much supplemental oxygen in these patients can alter the vasoconstriction and result in increased dead space ventilation. In these cases, the target range for SpO2 should be decreased to 88-92% and these patients should be carefully monitored.1 

Use of NIV may bring about patient self-inflicted lung injury (P-SILI) in those with severe ARF where increased damage to the lung occurs as a result of excessive spontaneous respiratory efforts.2-4 In treating hypoxic, hypercapnic, and mixed ARF using HFOT, CPAP, and/or NIV, the therapy should show acceptable results (improved respiratory rate, improved oxygenation, decreased work of breathing, relief of dyspnea, and improved CO2 clearance) within one to four hours of initiation. During this time, if the patient’s condition has shown no improvement or has worsened, intubation and initiation of mechanical ventilation needs to occur.1

Monitoring Patients with ARF

Approaches to monitoring patients receiving NRS to treat ARF is evolving and the newer approaches have allowed for more patient-specific treatment and personalized care plan. Conventional monitoring includes respiratory rate, tidal volume and minute ventilation, blood gas results (for pH, PaO2, SaO2, and PaCO2), and pulse oximetry (for heart rate and SpO2).2 Note that there are some inherent issues related to pulse oximetry tied to darker skin tones that may cause questionable results.1-2 Monitoring respiratory effort is helping to avoid P-SILI and is performed by measuring changes in esophageal pressure (ΔPes), changes in pressure at the nares (ΔPnose, which approximates ΔPes), and changes in central venous pressure (ΔCVP).2 Composite scores are also being used in monitoring the patient’s response to NRS. One is the HACOR score, which uses heart rate, acidosis, consciousness, oxygenation, and respiratory rate. Another is the ROX score, which uses the SpO2/FiO2 to RR ratio.2 A low ROX and/or high HACOR score indicates that the patient should be considered for changing to invasive mechanical ventilation.4 Ultrasound of the lungs (LUS) is being used to quantify lung aeration and movement of the diaphragm.2-3 Electrical impedance tomography (EIT) also helps evaluate lung aeration and provides a non-invasive indirect measurement of tidal volume.2 

Acute Respiratory Distress Syndrome (ARDS)

ARDS is a life-threatening condition that is characterized by severe refractory hypoxemia and inflammatory injury to the lungs and results in non-cardiogenic pulmonary edema, decreased lung compliance, and reduced clearance of carbon dioxide.5 ARDS is a heterogenous condition where small parts of the lungs are still functioning properly while other more extensive parts are damaged, full of fluid, collapsed and non-functioning. This description has led to the term “baby lung” as only a small portion of the lungs are still fairly normal. The official published definition of ARDS has been revised six times, starting with the first definition in 1967 (by Ashbaugh et al). Revisions were released in 1988 (Murray), 1994 ( from the AECC), 2012 (the Berlin definition), 2023 (from the ESICM), and 2024 (the New Global Definition).5-6 As these revisions are made, the definition is adapting to a more global approach and refinements are helping to uncover and confirm cases of ARDS.

Pathology and Classification of ARDS

In terms of pathology, ARDS is seen in three phases: 

  1. The acute (or exudative) phase (occurring in the first six days) shows the development of either interstitial or alveolar edema containing inflammatory and red blood cells. The endothelium and epithelium are damaged and hyaline membranes appear in the alveoli. 
  2. The subacute (or proliferative) phase (occurring between 7 to 14 days) has the edema reabsorbed, proliferation of alveolar type II epithelial cells, infiltration of fibroblasts, and the deposition of collagen fibers. 
  3. The last phase is the chronic (or fibrotic) phase (occurring after 14 days) which shows a clearing of neutrophils and an influx of alveolar mononuclear cells and macrophages into the alveoli, along with marked fibrosis.5 

Further descriptions of ARDS classify the syndrome based on the source/cause of the inflammatory insult. This divides ARDS into either direct (or pulmonary) or indirect (or extrapulmonary) ARDS. Direct sources include issues such as pneumonia, aspiration, toxic gas inhalation, ventilator-induced lung injury (VILI), lung contusion/trauma, etc. Indirect sources include nonpulmonary sepsis, blood transfusion, pancreatitis, trauma (nonpulmonary) burns, cardiopulmonary bypass, noncardiogenic shock, etc.5 Recently, two subphenotypes of ARDS have been identified: hyperinflammatory and hypo-inflammatory.3 Patients with hyper-inflammatory ARDS have more issues with coagulation, endothelial activation, inflammation, organ dysfunction, shock, sepsis, metabolic acidosis, and higher mortality compared to those with hypo-inflammatory ARDS.5-6 

With the advent of subphenotypes, researchers can predict the severity of the disease and use the distinctions to direct choices in treatment. Note, it has been uncovered that ARDS associated with COVID-19 has nearly normal lung compliance while exhibiting profound refractory hypoxemia, and an increased risk for thrombosis formation compared with the other cases/types of ARDS.7 

Management of ARDS and Ventilator Settings

The main supportive approach for ARDS is invasive mechanical ventilation, using a lung-protective strategy of low tidal volume (4-8 mL/kg predicted body weight) and keeping plateau pressure less than 30 cmH2O.7 Application of positive end expiratory pressure (PEEP) has evolved in the recommendations to using a higher level than earlier approaches and is usually in the range of 10 to 20 cmH2O.7 (Although, according to the ATS update from 2024: “The optimal strategy for setting PEEP in patients with ARDS remains uncertain.”)8 Use of esophageal pressure monitoring to estimate transpulmonary pressure and electrical impedance tomography to assess regional distribution of ventilation have allowed for more personalized PEEP settings.3,7 In addition, using higher PEEP without lung recruitment maneuvers (LRM) in moderate to severe cases has been recommended in the ATS update on management of ARDS, published in early 2024.8 

Another recent approach in managing the patient-ventilator systems involves driving pressure (calculated by Plateau pressure, PEEP). Driving pressure can be used as a surrogate for the strain applied to the lungs. The goal is to keep driving pressure <14 cmH2O to minimize strain on the lung tissues.7 Prone positioning has become a frequent approach for cases of moderate to severe ARDS (those with a PaO2/FiO2 ratio less than 150 mmHg) with application occurring early in the care plan and maintained for >12 to 16 hours each day.7

Other Recommendations in ARDS Management

Use of neuromuscular blocking agents (NMBA): The 2024 ATS update recommends using NMBA early in the treatment of patients with severe ARDS (during the first 48 hours and in those with a PaO2/FiO2 ratio less than 100 mmHg). There was no recommendation made concerning later administration of NMBA or in those with less severe ARDS.8

Use of Corticosteroids

The use of corticosteroids has received a conditional recommendation in the ATS 2024 update, which advises that there is considerable variation in support from research as to the dosing, timing, and duration of use. The panel recognized that corticosteroids given after 14 days of mechanical ventilation increased risk of harm, that the regimen chosen should be tailored to the specific condition, and that use of corticosteroids should be discontinued at extubation.8

Use of Venovenous Extracorporeal Membrane Oxygenation (vvECMO)

The ATS 2024 update recommended using vvECMO but only after other less invasive strategies had been utilized, and it should be used in patients who meet certain criteria. The strategies include lung protective ventilation, higher PEEP, use of NMBA, and prone positioning. The patient criteria for consideration include those who have “reversible etiologies of respiratory failure and very severe hypoxemia (PaO2/FiO2 ratio <80mmHg) or hypercapnia (pH <7.25 with PaCO2 >60mmHg) despite optimal conventional management, who are early in their ARDS course, and have few risk factors for futility of treatment.” Also, these patients should be transferred to a high-volume EMCO center (>30 patients a year) to maximize the chances of success.3,8

Use of Artificial Intelligence (Ai):

Ai is increasingly used in several areas to support diagnosis and management of ARDS. It is being used in predicting outcomes, scoring patients using various scoring systems, analyzing images and waveforms, early detection of sepsis, optimizing treatment protocols, and assisting in clinical documentation.3 As noted in the 3rd Respiratory Failure and Mechanical Ventilation Conference in Berlin in 2024 regarding Ai: “By complementing expert knowledge, it offers high potential for diagnosis decision support and optimization in clinical settings. To bridge the gap between Ai model development and real-world clinical outcomes it is fundamental to have homogenized big data landscapes, robust reporting guidelines, and actionable Ai solutions tailored to clinical settings.”3

Conclusions

ARDS is a very complex syndrome that involves making the right choices in treatment and allowing for change over time. It calls for careful monitoring, clear strategies, and flexibility in management. Despite all the research, protocols, and guidelines, ARDS still carries a high instance of morbidity and mortality. Advancements on several fronts are bringing more personalized treatment plans and refinements in what approaches and strategies provide better patient outcomes. Respiratory therapists are key personnel in caring for these patients and must stay up-to-date on research and recommendations in order to provide the best patient care.

RT

Bill Pruitt, MBA, RRT, CPFT, FAARC, is a writer, lecturer, and consultant. He has over 40 years of experience in respiratory care and has over 20 years teaching at the University of South Alabama in the department of Cardiorespiratory Care. After retiring from teaching, he continues to provide guest lectures and write professionally. For more information, contact [email protected].


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