ECLS for ARDS/Acute Respiratory Failure

There is a subset of patients for whom conservative medical management is not enough to support the patient in severe ARDS. ECMO/ECLS can partially or fully bypass the lungs to support gas exchange and facilitate lung-protective ventilation. Interestingly, ECLS may promote "ultra-lung-protective" ventilation by mitigating VILI and facilitating even further reductions in mechanical ventilation intensity.

ECLS Background

See ECLS. Essentially, can be either ECMO or ECCO2-R. ECMO can be wither venovenous (VV-ECMO) or veno-arterial (VA-ECMO) if cardiac support is required. - oxygenation is blood flow rate dependent - CO2 clearance is gas flow rate dependent (i.e. "sweep flow")

ECMO Centres

• centres with >30 cases per year have lower mortality than lower-volume (<6 cases yearly)

Major Complications of ECMO

• bleeding (major cause of M&M)
  • most common sites: cannulation site, GI, lung, CNS
  • 23% rate of bleeding complications in VV ECMO
• thrombosis
  • occurs in 25% of patients
• mechanical complications of the cannular or circuit
  • includes cannulation site bleeding, vascular injury, DVT, limb ischemia, air embolism, circuit failure from clot accumulation on the membrane lung
• Neurologic complications occur in 10% of patients - ischemic and hemorrhagic stroke are the most common

Clinical Use for ARDS

• NO role for routine ECCO2R in ARDS
• VV-ECMO has now shifted from being reserved for patients as a salvage therapy to prevent death from refractory gas exchange to and early adjunct to lung-protective ventilation in patients with severe ARDS when conventional evidence-based strategies (fluid balance, proning, neuromuscular blockade, steroids) are failing
  • due to costs/risks, ECMO has to be selected well for the right patient.
  • Poorer outcomes are associated with older age, immunocompromised status, number of failing organs, duration of pre-ECMO IMV, and severity of impairment in lung compliance
  • paucity of long-term data in patients receiving ECMO
    • CESAR: 6-month QOL same or better compared to CMV

Evidence - VV-ECMO

The CESAR (2009) trial was a landmark trial that looked at the application of modern VV-ECMO in patients with severe and potentially reversible respiratory failure refractory to conventional management.

• Intervention: transfer to ECMO centre for ECMO consideration
• Control: management of respiratory failure without ECMO
• Results: 63% survival without death or severe disability at 6 months vs 47%
  • only 75% of those transferred received ECMO (bias towards null)
  • NNT 6 for primary outcome
• limitations
  • lack of mandated lung protective ventilation in control group (70% only) compared to intervention group (93%) -- bias towards positive

The 2009 H1N1 pandemic provided anecdotal observational data that suggested improved survival rates in patients with severe viral-related ARDS.

The EOLIA (2018) multicentre trial randomly assigned patients with very severe ARDS to immediate VV-ECMO within 7 days of mechanical ventilation or conventional mechanical ventilation alone.

• Investigators were also encouraged to use NMB and prone positioning prior to randomization.
• Very severe ARDS: PF < 50 for 3 hours, PF/80 for 6 hours, or pH 7.25 with PaCO2 > 50 for 6 hours
• Primary outcome: 60-day mortality was lower in the ECMO group but the difference was not statistically significant (35% vs. 46%, p value 0.09)
• Secondary outcome: death or cross-over to ECMO occured in 58% (control) vs 35% (intervention), P<0.001
  • cross-over group (28% of control group) had very high mortality, 57%
• Adverse events: similar except for greated transfusions in ECMO group

Evidence for ECCO2R

Traditional ARDSNet-informed lung-protective ventilation (Vt < 4-8 ml/kg PBW and Pplat < 30 cm H2O) may be still injurious in 1/3 of patients with severe ARDS. ECCO2R can lower the intensity of mechanical ventilation by enhancing CO2 removal, lowering mechanical ventilation requirements.

Three RCTs have examined ECCO2R in this setting: 1. Morris et al - no difference for ECCO2R vs CMV in 40 patients with severe ARDS 2. Xtravent-study - ECCO2R + 3 mL/kg Vt vs standard of care --> no difference in 60-day VFD/death outcome 3. Protective Ventilation with Veno-venous Lung Assist in Respiratory Failure (REST) trial - ECCO2R did not improve 90-day mortality and VFD at 28 days, but did increase bleeding and ICH compared to control.

References

1. Munshi L, Brodie D, Fan E. Extracorporeal Support for Acute Respiratory Distress Syndrome in Adults. NEJM Evidence. 2022;1(10):EVIDra2200128. doi:10.1056/EVIDra2200128
2. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374:1351-63.
3. Combes A, Hajage D, Capellier G et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018; 378:1965-1975