ARDS

Definition

Berlin definition (2012) establishes the definition and three risk strata (mild, moderate, severe ARDS) based on the degree of hypoxemia as assessed at a minimum PEEP. These stages are associated with mortality risk and duration of mechanical ventilation.

Stages of ARDS

General Principles of ARDS Management

• Excellent overall critical care management of these patients, underlying medical and surgical disorders, minimizing procedures and iatrogenic complications, standard "bundled care" (VTE ppx, GIB ppx, PADIS, CLABSI)
• Recognition of nosocomial infection
• Adequate nutrition via enteral route = when feasible

Care facet	Routine recommendations
Mechanical Ventilation	Low tidal volume, low pressure, high PEEP, minimize FiO2, optimize PaO2
Proning	Do in severe ARDS
ECMO	Rescue therapy
Fluid Management	Minimize LA filling pressures aggressively using fluid restriction and diuretics
Early Neuromuscular Blockade	Do not routinely do
Steroids	Do not routinely give

Mechanical Ventilation in ARDS

In general, these patients require mechanical ventilation due to increased WOB and progressive hypoxemia.

Minimizing Ventilator-Induced Lung Injury

Injury can arise from "volutrauma", "atelectrauma" which lead to inflammation and alveolar injury. Low VT ventilation (6 mL/kg PBW) and low airway pressures (Pplateau < 30 cm H2O) were shown in ARDSNet to reduce mortality by 40%, and these strategies are now commonly used/standard of care.

Optimize PEEP

Reduced compliance means that end-expiration alveolar collase can occur without increases in end-expiratory pressures. Increase/optimize PEEP to minimize FiO2 and optimize PaO2, there is no consensus on how to do this. See Optimizing PEEP for more details.

Prone Positioning

Only one major trial has been conducted that looks at proning as a strategy in ARDS. Theoretically this improves V:Q mismatch by improving airflow to the most perfused areas of the lung (basilar segments), reduces work of breathing by respiratory muscles, and improves compliance (reduced diaphragmatic pressures on the lungs).

Other Strategies in Mechanical Ventilation

• Recruitment maneuvers and the concept of "open lung ventilation" can increase PEEP and oxygenation but have not been shown to reduce mortality.
  • ART trial (2017)
  • PHARLAP (2019)
• Alternate ventilation modes such as APRV and HFOV have not proven beneficial in ARDS.
• ECMO improves mortality and may serve as rescue therapy (conventional view), but newer trials and evidence suggest that it may serve also as an adjunct to early refractory very severe ARDS (i.e. PF < 80) -- see ECLS for ARDS.

Steroids in ARDS

Based on the 2017 and 2019 guidelines for ARDS, few studies have shown significant mortality benefit. They not support the routine use of glucocorticoids in ARDS.

However, in 2020 the ARDSNet group published the first dexamethasone trial of ARDS, the DEXA-ARDS trial, in the Lancet. This study showed that in early moderate to severe ARDS (PF < 200 despite PEEP 10+ and FiO2 50%+), ten days of dexamethasone (20 mg for five days then 10 mg for five days) in addition to lung-protective ventilation decreased 60-day mortality by 15% absolute difference (21% vs 36%), increased ventilator-free days at 28 days by 4.8 days. Less proning was needed for dexamethasone arm. There were no significant adverse effects compared to control with respect to hyperglycemia, new infections in the ICU, or barotrauma. N=277, and this trial was stopped early for efficacy.

Oxygen Targets in ARDS

Conventional oxygenation targets for ICU patients has a lot of current evidence, but current evidence (see Oxygen Targets in the ICU) suggests a conservative target (PaO2 70-100 mmHg; SpO1 90-96%) as opposed to more liberal targets, using the minimum FiO2 required, for most intubated critically ill patients.

The LOCO2 (2020) RCT in NEJM specifically looked at patients with ARDS and compared oxygenation targets of PaO2 55-70 mmHg vs. 90-105 mmHg, or their equivalent saturations (SpO2 88-92% vs. 96%+).

• Trend towards increased mortality (34.3% vs 26.5%) in the conservative group, nonsignificant.
• Increased number of episodes of mesenteric ischemia in the conservative oxygen group.
• stopped early for futility

Fluid Management in ARDS

The pathophysiology of ARDS leads to a propensity to have increased interstitial and alveolar protein-rich fluid that worsens inflammation and oxygenation. Consequently one would imagine that it is important to maintain low left atrial filling pressure to minimize pulmonary edema, preserve oxygenation and lung compliance, improve pulmonary mechanics, shorten ICU stay and duration of mechanical ventilation.

The FACTT (2006) trial ("Comparison of Two Fluid-Management Strategies in Acute Lung Injury") sought to define the optimal fluid management strategy in ALI/ARDS. It randomized 1,000 patients with ALI/ARDS to liberal (CVP 10-14, +1 L/day on average) or conservative (CVP <4, +0 L/day on average) fluid management strategies. Its results suggest that conservative fluid-management improves lung functional and shortens mechanical ventilation and critical care, without increasing non-pulmonary organ failure. At 60 days, there was no difference between the two groups in mortality.

Neuromuscular Blockade in ARDS

In severe ARDS, sedation alone can be inadequate for the patient-ventilator synchrony required for optimal lung-protective ventilation. Consequently, one would imagine that optimizing compliance and synchrony via Neuromuscular Blockade may improve oxygenation and ventilation, and reduce the risk of barotrauma. Two major trials have been done:

• ACURASYS (2010) was the first landmark study showed a mortality and ventilation-dependence benefit with 48h of cisatracurium in severe ARDS.
  • N=340, early moderate to severe ARDS (PF < 150, PEEP 5+) who were deeply sedated (Ramsey sedation score 6) prior to the intervention
  • Arms:
    • Cisatracurium 15 mg bolus , followed by 37.5 mg/h infusion x 48 hours
    • Placebo
  • Outcomes/Results:
    • 90-day mortality: 32% vs 41% (P=0.04, NNT=11)
    • 90-day days outside of ICU: 48 vs 40 (P=0.03)
    • Reduced barotrauma and PTX: 5% vs 11.7% (P=0.01, NNT=15)
• ROSE (2019) changed the paradigm by showing that use of early (<48h) cisatracurium with moderate to severe ARDS in conjunction with deep sedation protocols did not reduce mortality as compared to usual care (light sedation), and was associated with an increase in ICU-acquired weakness and serious adverse cardiovascular events.
  • N=1006, moderate to severe ARDS (P:F < 150 with PEEP >8)
  • Arms:
    • Early NM blockade - 48 hours of continuous cisatracurium (15 mg bolus, followed by 37.5 mg/h infusion) with deep sedation (RASS -5)
    • Usual care - routine strategy of PRN NMB (15%) with light sedation (RASS -1 to 0)
  • Outcomes:
    • No difference in mortality (43%)
    • Increased ICU-AW (47% vs 28% at 28 days)
    • Increased serious adverse CV events (14 events vs 4 events)
  • Stopped early due to futility

Other Therapies

• Pulmonary surfactants not shown to work.
• Pulmonary vasodilators such as inhaled NO, not shown to work.

References

1. Harrison's Chapter 294 on ARDS
2. Fernando SM, Ferreyro BL, Urner M, Munshi L, Fan E. Diagnosis and management of acute respiratory distress syndrome. CMAJ [Internet]. 2021 May 25 [cited 2021 Dec 8];193(21):E761–8. Available from: https://www.cmaj.ca/content/193/21/E761
3. Papazian L, Aubron C, Brochard L, Chiche J-D, Combes A, Dreyfuss D, et al. Formal guidelines: management of acute respiratory distress syndrome. Annals of Intensive Care [Internet]. 2019 Jun 13 [cited 2021 Dec 8];9(1):69. Available from: https://doi.org/10.1186/s13613-019-0540-9
4. Griffiths MJD, McAuley DF, Perkins GD, Barrett N, Blackwood B, Boyle A, et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respiratory Research [Internet]. 2019 May 1 [cited 2021 Dec 8];6(1):e000420. Available from: https://bmjopenrespres.bmj.com/content/6/1/e000420
5. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, et al. 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. Am J Respir Crit Care Med [Internet]. 2017 May 1 [cited 2021 Dec 8];195(9):1253–63. Available from: https://www.atsjournals.org/doi/full/10.1164/rccm.201703-0548ST
6. Guérin C, Reignier J, Richard J-C, Beuret P, Gacouin A, Boulain T, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. New England Journal of Medicine [Internet]. 2013 Jun 6 [cited 2021 Nov 29];368(23):2159–68. Available from: https://doi.org/10.1056/NEJMoa1214103
7. Slutsky AS, Marco Ranieri V. Mechanical ventilation: lessons from the ARDSNet trial. Respir Res [Internet]. 2000 [cited 2021 Nov 29];1(2):73–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59545/
8. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. New England Journal of Medicine [Internet]. 2000 May 4 [cited 2021 Nov 29];342(18):1301–8. Available from: https://doi.org/10.1056/NEJM200005043421801