Table 3 Relevant clinical studies on ECCO₂R in ARDS

ECCO₂R in ARDS

 Augy et al. 31452899

Multicenter, observational, prospective, cohort study

70

VV configuration via a double-lumen 15.5-Fr venovenous catheter (either right jugular or femoral site) or a double-lumen 18 Fr (right jugular site) or 24 Fr (femoral site) or Novaport Twin (18, 22, or 24 Fr) catheters

430

Not reported

PLP based on siloxane layer; 0.59 (ALung Hemolung RAS) or PMP; 1.3 (Novalung iLA activve)

5 days

Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V_T was observed in ARDS patients, from 5.9 to 4.1 ml/kg (p < 0.001). A reduction in PaCO₂ values was observed in AE-COPD patients, from 67.5 to 51 mmHg (p < 0.001). Median duration of ECCO₂R was 5 days (IQR 3–8). Reasons for ECCO₂R discontinuation were improvement (n = 33), ECCO₂R-related complications (n = 18), the limitation of life-sustaining therapies or decision measures (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which were ECCO₂R related

 Grasselli et al. 31425258

Retrospective study

11

VV configuration via a single double-lumen catheter 13 Fr (femoral or jugular)

333

Not reported

PMP; 1.8 (ProLUNG® ESTOR)

7 days

Twenty-four hours of ECCO₂R treatment reduced arterial PaCO₂ from 63 ± 12 to 54 ± 11 mmHg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). All four ARDS patients were invasively ventilated at the initiation of treatment, no one was extubated and they all died. Among the seven patients with an exacerbation of COPD, four were managed with noninvasive ventilation via ECCO₂R, while three were extubated after starting ECCO2R. None of these seven patients was intubated or reintubated after ECCO2R and five (71%) survived to hospital discharge

 Karagiannidis et al. 31014366

Physiological study

20

VV configuration via a 19 Fr/38 cm femoral-draining cannula and a 17 Fr/15 cm inlet-flow cannula (Maquet, Rastatt, Germany)

2000–3000

0–10

PMP; 1.3 (Maquet HLS CardioHelp)

Not reported

Patients supported by NIV-NAVA were studied during stepwise weaning of ECCO₂R. Based on dyspnea, tolerance, and blood gases, weaning from ECCO₂R was successful in 12 patients and failed in 8 patients. Respiratory drive increased to 19 ± 10 μV and 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO₂ and pH values stable. Eventually, 19 patients were discharged, while one patient died. Mortality at 90 days and 180 days was 15% and 25%, respectively

 Schmidt et al. 29743094

Prospective study

20

A 13-Fr hemodialysis venous catheter (Gamcath™®; Gambro-Baxter)

420

10

PMP, 0.32 (PrismaLung®; Gambro-Baxter)

31 h

Twenty patients with mild (n = 8) or moderate (n = 12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP was adjusted to reach 23 ≤ P_plat ≤ 25 cmH₂O. While VT was reduced from 6 to 4 ml/kg and P_plat was maintained at < 25 cmH₂O, PEEP was significantly increased from 13.4 ± 3.6 cmH₂O at baseline to 15.0 ± 3.4 cmH₂O, and the driving pressure was significantly reduced from 13.0 ± 4.8 to 7.9 ± 3.2 cmH₂O (both p < 0.05). The PaO₂/FiO₂ ratio and respiratory system compliance were not modified. Mild respiratory acidosis occurred, with mean PaCO₂ increasing from 43 ± 8 to 53 ± 9 mmHg and mean pH decreasing from 7.39 ± 0.1 to 7.32 ± 0.10 from baseline to 4 ml/kg VT, respectively. Day 28 mortality was 15%

 Peperstraete et al. 29179681

Prospective pilot study

10

A 13.5-Fr double-lumen catheter (Niagara™, Bard)

300–500

0–7

PMP; 0.67 (Lilliput 2, LivaNova)

5 days

ARDS patients on MV, with PaO₂/FiO₂ < 150 mmHg, tidal volume ≤ 8 mL/kg with positive end-expiratory pressure ≥ 5 cmH₂O, FiO₂ titrated to SaO₂ 88–95%, plateau pressure ≥ 28 cmH₂O, and respiratory acidosis (pH < 7.25). After 2 h of ECCO₂R, 6 patients had a ≥ 20% decrease in PaCO₂ (60%); PaCO₂ decreased 28.4% (from 58.4 to 48.7 mmHg, p = 0.005), and pH increased (1.59%, p = 0.005). 6 patients had an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in occurred in 3 patients (30%). These adverse events were judged not to be life threatening

 Hilty et al 28638160

Retrospective study

20

VV configuration via a single double-lumen 13-Fr catheter (femoral or jugular)

300–350

Not reported

PMP; 1.8 (ProLUNG® ESTOR)

1.4–5.2 days

Causes of HRF were severe ARDS (N = 11), COPD (N = 4), chronic lung transplant rejection (N = 3) and cystic fibrosis (N = 2). During the first 8 h of ECCO₂R, PaCO₂ decreased from 10.6 (9.3–12.9) to 7.9 (7.3–9.3) kPa (p < 0.001) and pH increased from 7.23 (7.09–7.40) to 7.36 (7.27–7.41) (p < 0.05). Lung protective tidal volume (4.7 (3.8–6.5) mL/kg) and peak ventilator pressure (28 (27–30) mbar at 24 h) were maintained. Thrombocyte count decreased by 52% (p < 0.01) and fibrinogen decreased by 38% (p < 0.05). Intubation could be avoided in all spontaneously breathing patients. In 4/6 patients, high blood flow extracorporeal circulation was required due to increased oxygen demand. Six of 14 mechanically ventilated patients recovered from respiratory support

 Moss et al. 27195746

Retrospective study

14

VV configuration via a double-lumen 15.5-Fr venovenous catheter (either right jugular or femoral site)

440

9.6

PLP based on siloxane layer; 0.59 (ALung Hemolung RAS)

5 days

A statistically significant improvement in pH (p = 0.012) was demonstrated. Ten patients were discharged from the intensive care unit (ICU) alive. Four complications related to ECCO2R were reported, none of which resulted in serious adverse outcomes

Fanelli et al. 26861596

Prospective pilot study

14

VV configuration via a double-lumen 15.5-Fr venovenous catheter (either right jugular or femoral site)

435

10

PLP based on siloxane layer; 0.59 (ALung Hemolung RAS)

2 h

During the 2-h run-in phase, V_T reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH₂O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life-threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking)

Combes et al. 30790030

Prospective multicenter international phase II study

95

VV configuration via a double-lumen venovenous catheter (either right jugular (57%) or femoral (43%) site)

Catheter size was 15.5 Fr (Hemolung) and 18 Fr (iLA activve and Cardiohelp® HLS 5.0)

300–500 mL/min vs. 800–1000 mL/min

6–10

PLP based on siloxane layer (ALung Hemolung RAS, iLA activve, Novalung, Cardiohelp® HLS 5.0, Getinge)

The proportion of patients who achieved ultraprotective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68–89%) and 82% (78 out of 95 patients; 95% confidence interval 76–88%), respectively. ECCO₂R was maintained for 5 [3–8] days. Six SAEs were reported; two of them were attributed to ECCO₂R (brain hemorrhage and pneumothorax). ECCO₂R-related AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge

Peperstraete et al. 29179681

Paired cohort study with historical control

25

Continuous VV hemofiltration system modified with pulmonary membrane via 14-Fr double-femoral cannula (femoral)

255

8

PLP; 1.35 (Hemodec DecapSmart®)

1–2 h

Significantly higher risk of intubation in the NIV-only group (HR 0.27, 95% CI 0.07–0.98). Thirteen patients experienced adverse events: 3 bleeding, 1 venous perforation and 9 device malfunctions