A 42-year-old male with no significant past medical history presented to the emergency department (ED) with severe abdominal pain. Work-up revealed acute pancreatitis due to alcohol consumption. He disclosed being a binge drinker. Gallbladder disease, the most common cause of acute pancreatitis, was ruled out with imaging and laboratory studies. The patient was admitted to the hospital and treated according to the standard of care for management of acute pancreatitis which included aggressive fluid resuscitation and pain management. On hospital day 3, he developed mild shortness of breath. Although the etiology of his respiratory symptoms was initially unclear, upon further inquiry, he recalled several episodes of vomiting prior to arrival in the ED. Your suspicion for aspiration and possible aspiration pneumonia are raised. The patient is placed on supplemental oxygen via nasal cannula with no improvement. High flow nasal cannula (HFNC) is ordered and initiated with significant improvement in respiratory symptoms. He has a mild non-productive cough and low-grade fever. A chest x-ray revealed mild vascular congestion and a possible right middle lobe opacity. He is pan-cultured and started empirically on antibiotics to cover aspiration pneumonia, he is also given diuretics for suspected volume overload. Overnight, he became tachypneic with respiratory rate in the 40s and increased work of breathing. Peripheral oxygen saturation (SpO₂) was 82% despite titration of fraction of inspired oxygen (FiO₂) to 100% on HFNC. He was intubated, placed on mechanical ventilation and transferred to the ICU for management. A chest x-ray following intubation revealed diffuse bilateral infiltrates. He was initially placed on standard ventilatory settings with brief improvement but, over the next several hours, it became increasingly difficult to oxygenate him despite titration of FiO₂ to 85% on the ventilator. He was given an additional dose of intravenous (IV) diuretic with no improvement. An arterial blood gas (ABG) revealed arterial oxygen of 70mmHg and a repeat CXR revealed progression of diffuse bilateral infiltrates. Acute respiratory distress syndrome (ARDS) was suspected and ARDS specific ventilatory strategies were initiated.

Does this scenario sound familiar? Scary? Both? Respiratory symptoms are something we see daily across healthcare settings. Depending on your role, you may be the first person to recognize a critical change in respiratory status. Understanding the potential continuum of respiratory decompensation is essential to ensure safe management of our patients. Respiratory failure is one of the most common conditions treated in intensive care units (ICUs). The etiology and presentation of respiratory failure can vary widely and may include acute respiratory infection (i.e. bacterial or viral pneumonia), acute exacerbations of chronic respiratory conditions (i.e. COPD, asthma), congestive heart failure (i.e. cardiogenic pulmonary edema), or upper/lower airway obstruction (i.e. angioedema, foreign body). ARDS is a life-threatening complication of respiratory failure associated with high morbidity and mortality. It is characterized by an acute onset, diffuse, inflammatory lung injury leading to increased vascular permeability, increased lung weight and loss of aerated lung tissues (Ranieri et al., 2012) causing severe hypoxemia. Annually, ARDS affects close to 200,000 individuals and is responsible for 74,500 deaths in the United States (Rubenfeld et al., 2005).

Is this ARDS? Diagnosing and Classifying ARDS

Distinguishing ARDS from other forms of respiratory failure can be a challenge. There are several conditions placing one at risk for the development of ARDS. The most common risk factor, sepsis, from either a pulmonary or non-pulmonary source, accounts for 79% of ARDS cases (Rubenfeld et al., 2005). Other risk factors include aspiration, toxic inhalation, lung contusion/trauma, acute pancreatitis, blood product transfusion, near drowning, burn injury/smoke inhalation and cardiopulmonary bypass (Howell & Davis, 2018; Rubenfeld et al., 2005). The presence of any of these conditions in the setting of an acute change in respiratory status should raise your suspicion for ARDS. 

Although it was obvious the above patient was in severe respiratory distress, ARDS was not always first in the differential diagnosis. In this particular patient, initial concern was for volume overload and aspiration pneumonia. In accordance with established definitions of ARDS, to diagnose ARDS, a patient must not only have an acute change in clinical condition, a high oxygen requirement, and diffuse bilateral infiltrates on radiographic studies, but the clinician must also rule out other conditions that could account for these respiratory findings.

There have been several definitions of ARDS since it was first described in the 1960s. The term acute lung injury, which had been used in past definitions, is no longer an accepted term in respect to the description or definitions of ARDS. The most current definition, developed by the ARDS definition task force in 2012 are termed the Berlin criteria (Ranieri et al., 2012). The Berlin criteria require the presence of the following 4 criteria to diagnose ARDS:

1. The onset of respiratory symptoms beginning within one week of a known clinical insult, or patient must have new or worsening symptoms during the past week;
2. the presence of bilateral opacities on either chest x-ray or chest CT scan consistent with pulmonary edema and are not explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules;
3. respiratory failure that cannot be fully explained by cardiac failure or fluid overload (consider echocardiogram or cardiac assessment if no other ARDS risk factors); and
4. the presence of a moderate to severe impairment of oxygenation, as defined by the PaO₂/ FiO₂ ratio ≤ 300 (Raineri et al. 2012).

 ARDS is classified according to the degree of hypoxemia as follows:

• Mild - PaO2/FiO2 ratio of 201-300
• Moderate - PaO2/FiO2 ratio of 101-200
• Severe - PaO2/FiO2 ratio £ 100 (Ranieri et al. 2012)

Looking back at our patient’s clinical history, he meets criteria for ARDS. His respiratory symptoms came on acutely, his clinical insult was pancreatitis and possible aspiration, he had the radiologic findings of diffuse bilateral opacities, and although he did receive aggressive fluid resuscitation, respiratory symptoms continued to deteriorate despite diuresis. Finally, he had a severe impairment in oxygenation. Based on his PaO2 of 75mmHg and FiO2 of 85%, his PaO2/FiO2 ratio was ≤ 100 classifying him as having severe ARDS.

What is actually happening in ARDS?

The pathophysiology involved in the development of ARDS is complex and may vary depending on the mechanism of injury. Furthermore, there are three phases in the progression of ARDS, the exudative phase, the proliferative phase and the fibrotic phase. These phases have distinct histopathologic and clinical features that go beyond the depth of this blog, but it is important to be aware of terminology surrounding ARDS. In general, the clinical sequelae of ARDS are related to increased vascular permeability and these distinct histopathologic changes in each phase of ARDS (Howell & Davis, 2018). The hallmark multifocal opacities are the results of tissue damage in the alveoli mediated by neutrophil, macrophage, and dendritic cell activation. Due to an overall inflammatory state with increased vascular permeability and release of inflammatory cytokines, a protein rich fluid accumulates in the alveoli resulting in impaired gas exchange (Han & Mallampalli, 2015) and subsequent hypoxia. This alveolar damage increases physiologic dead space (remember dead space? ventilation that does not participate in gas exchange; think of it as the fluid accumulating in alveoli, blocking the blood’s access to absorb oxygen) and decreased lung compliance (elasticity of lungs) leading to the “stiff” lung often described in ARDS (the fluid accumulation makes is difficult for alveoli to inflate).

Treatment of ARDS

Despite the high morbidity and mortality associated with ARDS, there are limited evidence-based therapies known to reduce mortality. Treatment remains largely supportive and primarily involves mechanical ventilatory support which, unfortunately, can further potentiate lung injury. In 2017, updated treatment strategies were published jointly by the American Thoracic Society, the European Society of Intensive Care Medicine and the Society of Critical Care Medicine. The following treatment recommendations were made (Fan et al., 2017):

1. For all patients diagnosed with ARDS:
   • Lower tidal volume mechanical ventilation (4-8 ml/kg predicted body weight) and lower plateau pressures < 30cm H₂O
     • Typical initial tidal volumes for those without ARDS is 6-8mL/kg predicted body weight
     • It is recommended that tidal volume be adjusted to maintain goal plateau pressures
     • Low volume ventilation and lower plateau pressures, sometime referred to as lung protective ventilation strategies are thought to prevent volutrauma (overdistension of alveolar units) and atelectrauma (cyclic changes in nonaerated lung).
   • Prone positioning for > 12 hours/day in those with severe ARDS
     • Involves placing patient in prone position while on ventilator, shifts weight of heart to ventral wall
     • Potentially improves ventilation-perfusion, increasing end-expiratory lung volume, and decreasing VILI by more uniform distribution of tidal volume through lung recruitment and alterations in chest wall mechanics (Gattinoni L, Pesenti A, Carlesso E, 2013).
2. For those with moderate to severe ARDS:
   • Higher PEEP as opposed to lower PEEP
     • In non-ARDS mechanical ventilation, typical initial PEEP is 5; however, PEEP can often be as high as 24 in the treatment of ARDS; increasing PEEP often allows for decreased FiO2
     • higher PEEP may improve alveolar recruitment, reduce lung stress and strain, and prevent atelectrauma (Fan et al. 2017)
   • Recruitment maneuvers (RMs)
     • A transient, sustained increase in airway pressure with goal to open collapsed alveoli
     • Involves applying high PEEP for a specified time and evaluating improvements in oxygenation
       • Example: 30-40 PEEP for 30-40 seconds
   • Both higher PEEP and RMs are thought to decrease atelectasis by improving alveolar recruitment (increasing the number of alveoli participating in tidal ventilation and improve end-expiratory lung volumes.
3. It was noted that further research is necessary on the use of Extra-corporeal Membrane Oxygenation (ECMO) for treatment of refractory ARDS. 
   • Veno-venous ECMO works by pulling blood from the inferior vena-cava through a circuit (outside of the body) which removes carbon dioxide and oxygenated blood returning it to the venous system via internal jugular vein.

What was the outcome for our patient with ARDS? What treatment modalities were implemented?

Continue to Part 2 where we review treatment modalities for ARDS in more detail, specifically the logistics of prone positioning in the treatment of ARDS and the outcome of our patient. Have you encountered a patient with ARDS? Do you have any experience with prone-positioning? Please share your experiences in the management of this challenging complication of respiratory failure.

References:

Fan, E., Del Sorbo, L., Goligher, E.C., Hodgson, C.L., Munshi, L., Walkey, A.J.,…Brochard, L.J. (2017). An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. American Journal of Respiratory and Critical Care Medicine, 195(9), 1253-1263. doi: 10.1164/rccm.201703-0548ST    

Gattinoni L, Pesenti A, Carlesso E. (2013). Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure: impact and clinical fallout through the following 20 years. Intensive Care Medicine, 39(11), 1909–1915. doi: 10.1007/s00134-013-3066-x

Han, S.H. & Mallampalli, R.K. (2015). The Acute Respiratory Distress Syndrome: From Mechanism to Translation. The Journal of Immunology, 194(3), 855-860.  doi: https://doi.org/10.4049/jimmunol.1402513 

Howell, M.D. & Davis, A.M. (2018). Management of ARDs in Adults. JAMA, 319(7), 711-712. doi: 10.1001/jama.2018.0307
 
Ranieri, V.M., Rubenfeld, V.M., Thompson, B.T., Ferguson, N.D., Caldwell, E., Fan, E., Camporota, L. & Slutsky, A.S.; ARDS Definition Task Force. (2012). Acute respiratory distress syndrome: The Berlin Definition.  JAMA, 307(23), 2526-2533. doi: 10.1001/jama.2012.5669
 
Rubenfeld, G.D., Caldwell, E., Peabody, E., Weaver, J., Martin, D.P., Neff, M., Stern, E.J., Hudson, L.D. (2005). Incidence and outcomes of acute lung injury. The New England Journal of Medicine, 353(16), 1685-1693.  doi: 10.1056/NEJMoa050333