Extra-corporeal carbon dioxide removal (ECCO2R) devices are new additional tools for the treatment of severe hypercapnic respiratory failure.
Since the 80’s year the ECCO2R has been proposed to treat the patients with ARDS in order to reduce the workload of the injured lungs, but the technology was lacking to support the clinicians ideas .
In the last decade the improvements of the materials and devices of extracorporeal support re-opened the way for a real clinical application of the ECCO2R in ARDS patients and in chronic hypercapnic patients, as a “respiratory” dialysis strategy for avoiding intubation in this patients .
The technical distinctive characteristic of the ECCO2R system is low blood flow (250-1000 ml/min), making them less complex devices if compared to veno-venous extra-corporeal membrane oxygenation (VV ECMO); in facts, vascular access can be smaller and adverse events are infrequent.
On the other hand, low blood flow limits gas exchange capability: ECCO2R devices are able to remove up to 40-50% of CO2 production, thanks to the steep slope of CO2 dissociation curve, but are poorly efficient in improving oxygenation (maximum 10%), because of the sigmoidal shape of oxygen-haemoglobin dissociation curve.
While VV ECMO can completely replace gas exchange function, ECCO2R is indicated when only CO2 removal or respiratory acidosis control are required; oxygenation has to be provided by native lungs.
Two kinds of ECCO2R can be distinguished, depending on cannulation site.
Artero-venous devices (iLA – Novalung) are pump-less systems exploiting artero-venous pressure gradient and therefore depending on patient’s cardiac output; required blood flow ranges from 1L/min to 30% of cardiac output and removes around 50% of CO2 production.
Veno-venous devices present many advantages: first they don’t depend on patient’s hemodynamic and blood flow can be controlled independently; second, they require lower blood flow (250-550 ml/min), entailing minimal hemodynamic impact and implying smaller cannulae; finally, they are free of arterial cannulation complications, such as lower limb ischemia.
Two kinds of pumps can also be distinguished: roller, the most frequent, and centrifugal, the less frequent.
The two main clinical indications for ECCO2R are COPD exacerbations and ARDS patients. COPD patients present in general with hypercarbic respiratory failure; ECCO2R can help in PaCO2 control and respiratory acidosis correction, integrating non-invasive ventilation (NIV) and preventing its failure, which remains frequent (15-26%) despite continuous improvement in its application. In addition, these patients are known to be difficult to wean: extracorporeal CO2 removal can help in the weaning process, from both invasive and non-invasive ventilation .
ECCO2R could appear conversely inappropriate in hypoxemic respiratory distress as ARDS; by the way, those patients require protective ventilation, potentially inducing hypercarbia and respiratory acidosis that, although tolerated, can be a limitating factor. Extracorporeal CO2 removal could allow a more protective ventilation and therefore contribute to avoid more invasive extra-corporeal support, such as VV ECMO 
Among veno-venous systems, in our institution we experienced Hemolung – ALung Technologies, Pittsburgh. This system is minimally invasive thanks to a specific venous double-lumen 15F cannula, very similar to dialysis catheters, than can be placed percutaneously in femoral or internal jugular vein.
ALung peculiarities include a centrifugal pump, less traumatic for blood flow higher than 200 ml/min, a relatively small membrane surface (0.59 m2) and sweep gases provided under negative pressure and cyclically purged.
CO2 removal is measured sampling expired CO2 of the artificial lung and automatically displayed on the monitor.
Its safety and applicability has been tested in a pilot study conducted by Burki et al on COPD exacerbations ; although the small sample did not allow any certain conclusion, Hemolung seemed to help in avoiding intubation in NIV-failure high-risk patients and in weaning them from both non-invasive and invasive ventilation.
No trial or case series are reported on Hemolung appliacations in ARDS.
We successfully applied Hemolung with no complications to both COPD and ARDS patients with the following goals: combined to NIV to prevent re-intubation in a COPD exacerbation and later to wean the patient from NIV; to allow protective ventilation in a mild ARDS patient and to help in weaning him from mechanical ventilation; to allow protective ventilation and weaning from ECMO in a severe ARDS patient.
In all patients, the 15F Hemolung specific double-lumen cannula was placed percutaneously in a femoral vein; cannulation did not require any specific training and was reported by the operators to be as difficult as for standard hemodialysis catheters (Fig. 1)
Fig 1: X-ray of cannula position
Mean length of Hemolung support was 5±1 days; no adverse events were reported.
ECCO2R device performances were evaluated in terms of blood flow and CO2 removal. Average blood flow was 373±70 ml/min the first day and was not significantly modified when Hemolung support was interrupted (365±33 ml/min; p=0.9). Mean CO2 removal was 82±10 ml/min the first day and didn’t present any significant variation the last day of ECCO2R (80±15 ml/min; p=0.8).
All patients presented hypercarbia before extra-corporeal support started (mean PaCO2 60.6±3.7 mmHg); we remarked a reduction in PaCO2 since the first day (49.7±2.5 mmHg), although not statistically significant (p=0.076).
No conclusions can be drawn on pH control since none of the patients presented acidosis before ECCO2R (mean pH 7.4±0.1).
Anticoagulation target was ACT 160-180’’ and was achieved with an initial bolus of heparin 80 U/kg and mean maintain dose of 18 UI/kg*h.
In particularly an emblematic case is a 48 yo man who developed ARDS secondary to abdominal sepsis. That patients was initially treated with continuous positive airways pressure for mild hypoxemia in the ward, he was admitted to our ICU for clinical and radiological decline. Protective mechanical ventilation was started, inducing immediate important increase in PaCO2. Extracorporeal CO2 removal was therefore considered on the second day of mechanical ventilation.
The extracorporeal support lasted 5 days, with no adverse events.
Hemolung allowing since the first day a reduction of peak pressure (from 33 to 29 cmH2O), protective mechanical ventilation was maintained with no complications for 3 days. Clinical picture rapidly improved and the patient was weaned from mechanical ventilation on the forth day and from ECCO2R on the fifth day.
As reported in the table 1, Alung performances in terms of blood flow and CO2 removal remained stable during the entire length of extracorporeal support; PaCO2 was reduced since the first day and remained stable until weaning from extracorporeal device.
Tab 1. Hemolung performances in terms of blood flow (BF) and CO2 removal during extracorporeal support and PaCO2 reduction.
Hemolung is a new ECCO2R device with high performance, characterized by a specific double-lumen 15 Fr catheter, a centrifugeal pump and a small surface membrane.
In our experience, it could be applied safely to both COPD exacerbation and ARDS patients to control hypercarbia and respiratory acidosis, with no adverse event or specific management difficulties.
Although studies on wider sample are required, ECCO2R system is a promising new tool for the support of acute respiratory distress.
- “Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study” Gattinoni L, Kolobow T, Tomlinson T, et al. Anesth Analg. 1978; 57:470-7.
- “Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations” Karagiannidis C, Kampe KA, Sipmann FS, Larsson A, Hedenstierna G, Windisch W, Mueller T. Crit Care. 2014 Jun 17;18(3)
- “Extracorporeal CO2 Removal in Hypercapnic Patients At Risk of Noninvasive Ventilation Failure: A Matched Cohort Study With Historical Control” Del Sorbo L1, Pisani L, Filippini C, Fanelli V, Fasano L, Terragni P, Dell’Amore A, Urbino R, Mascia L, Evangelista A, Antro C, D’Amato R, Sucre MJ, Simonetti U, Persico P, Nava S, Ranieri VM Crit Care Med. 2014 Sep 16
- “Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study.” Bein T, Weber-Carstens S, Goldmann A, Müller T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, Philipp A, Wernecke KD, Lubnow M, Slutsky AS. Intensive Care Med. 2013 May;39(5):847-56
- “A novel extracorporeal CO2 removal system. Results of a pilot study of hypercapnic respiratory failure in patients with COPD” Burki NK, Mani RK, Herth FJF, Schmidt W, Teschler H, Bonin F, Becker H, Randerath WJ, Stieglitz S, Hagmeyer L, Priegnitz C, Pfeifer M, Blaas SH, Putensen C, Theuerkauf N, Quintel M, Moerer O. Chest. 2013; 143(3):678-686.