ECCO₂R therapy in the ICU: consensus of a European round table meeting

The ECCO₂R therapy Expert Round Table Meeting was held in Brussels in July 2019 and was attended by 14 clinicians who regularly provide ECCO₂R therapy in hospitals across Europe in order to provide a European perspective on ECCO₂R therapy. Each attendee was a senior clinician/intensivist invited based on their experience delivering ECCO₂R therapy, with and without continuous renal replacement therapy, using different devices. The attendees had direct clinical experience with a wide range of ECCO₂R devices, including ALung, iLA, Prismalung and PALP (the later had been removed from the market at the time of the meeting due to loss of the distribution agreement). In addition, several of the attendees are principal investigators in recently completed or ongoing clinical trials, including randomised controlled trials such as REST and SUPERNOVA. Conflict of interest declarations for the attendees can be found at the end of the manuscript.

The meeting objectives were to better define and understand the application of ECCO₂R therapy in key indications (ARDS and ae-COPD), to identify patient selection criteria and when to initiate and stop/wean patients from treatment and to determine points of consensus and differences in clinical practice in those centres represented at the meeting. A non-systematic search of MEDLINE, ClinicalTrials.​gov and other sites was performed to identify key studies and trials to support the development of the questions and the content of the meeting.

A modified Delphi-based method (Fig. 1) was used to collate the clinicians’ views in three rounds of questioning [24]. The meeting questions as well as the pre-meeting and post-meeting questionnaires were developed by JG and KH before being reviewed and approved by AC. JG and KH were present as Baxter employees and moderators, but were not permitted to provide answers or responses, either to the survey questions or during the meeting. Round 1 data were collected via an interactive PDF questionnaire circulated in advance of the meeting, and results were analysed anonymously. Round 2 data were collected during the meeting, attendees were divided into 4 subgroups and the questions were presented by an independent facilitator. Open questions were used to encourage freedom of response, and the meeting was designed to allow the attendees adequate time to consider and respond to the questions based on their experience. Attendees could respond to the questions either through anonymous electronic voting or by inputting responses into a microcomputer, with responses collected and discussed openly by the group. Round 3 was a second interactive PDF questionnaire, circulated post-meeting, designed to follow up on discussion points raised at the face-to-face meeting, with results analysed anonymously. Details on the process for information gathering and the questions are provided in Additional file 1.

Target values for ventilation parameters of interest—criteria for initiation of ECCO₂R therapy and treatment targets for ECCO₂R therapy in both ARDS and ae-COPD—were collected during the three rounds of questioning. These values were subsequently evaluated for consensus. To facilitate the analysis of the responses for certain questions, a scoring system was employed. Participants were asked to score their responses in order of importance, giving them a score (e.g. from 1 to 8, depending on the number of variables). Scores were then combined to give a total score for each parameter, with higher scores indicating a higher perceived importance. To determine whether a consensus was reached or not based on participant responses to the questions, a threshold of ≥ 80% of participants in agreement was used to define if consensus was reached, a level that has been used in previous analyses [25]. Majority agreement indicates that ≥ 50% of participants agreed, but consensus level was not reached, and no agreement means that < 50% of participants agreed. The report was drafted by an independent medical writing company (SciMentum, Nucleus Global) and paid for by Baxter in line with Good Publication Practice 3. The various drafts were reviewed and approved by AC before being reviewed by the full author team. All authors provided their approval to submit and meet the ICMJE criteria for authorship.

Twelve clinicians completed the pre-meeting survey: eight worked in Combined Surgical and Medical intensive care units (ICUs), while the others were employed in Medical ICUs (n = 2), Surgical ICUs (n = 2) and Cardiac Surgery ICUs (n = 2); respondents could be employed at more than one type of centre. ICUs had a median of 20 beds/unit and 400–2000 admissions/year. Extracorporeal membrane oxygenation (ECMO) experience of participants ranged from 0 to 80 veno-venous ECMO procedures/year and 0 to 220 veno-arterial ECMO procedures/year.

Analysis of the Round 1 pre-meeting survey responses revealed that ARDS was considered the primary indication for ECCO₂R therapy by 7 participants, while 3 participants considered ae-COPD to be the primary indication. Severe asthma was also mentioned as another potential ECCO₂R indication, although less frequently. The median number of ARDS admissions (as per the Berlin definition [26]) was 60 patients per centre per year, with some centres admitting up to 500 patients per year. While the most common criteria stated in the pre-meeting responses for initiating ECCO₂R therapy in patients with ARDS were to manage hypercapnia with acidosis, although specific criteria varied across the ICUs, likewise, weaning criteria shared at Round 1 varied significantly, with no clearly consistent management pattern being identified between centres. However, most participants (92%) indicated that they would place patients with ARDS in the prone position when using ECCO₂R therapy. The number of ae-COPD admissions ranged from 0 to 250 patients per centre per year (median 50). Participants indicated that ECCO₂R therapy was predominantly initiated to prevent intubation in patients at risk of NIV failure or to facilitate extubation in patients who had been intubated after NIV failure.

During the Expert Round Table Meeting and post-meeting survey (Rounds 2 and 3, respectively), the group considered the ventilation parameters for implementation of a lung protective ventilation (LPV) strategy in all patients with ARDS and agreed upon the following targets: driving pressure, 10–14 cmH₂O; positive end-expiratory pressure (PEEP), 10–14 cmH₂O; P_plat, 25–29 cmH₂O; and respiratory rate either 20–25 or 25–30 breaths/min, although most of the group would target a respiratory rate of 25 breaths/min. There was some variation in responses among the group when asked about target pH, with half of participants opting for a target pH value of 7.25–7.30, while others indicated the target should be > 7.30 (n = 4), < 7.25–7.30 (n = 2) or < 7.20 (n = 1). Finally, the panellists thought V_T should be set at 6.0 mL/kg of predicted body weight (PBW), although 6.1–7.0 or 7.1–8.0 mL/kg PBW were also considered to be reasonable targets. When asked in the post-meeting survey (Round 3) about the preferred ventilation mode used for patients with ARDS undergoing LPV, the group were split with respect to pressure control (pressure assist) (n = 8) and flow control (volume assist) (n = 6) modes of ventilation. These recommendations agreed with the most recent guidelines for the ventilation management of patients with ARDS [27, 28].

There was consensus among the group (91% [2 participants were unavailable for this question, 11 of n = 12/14 voted in favour]) that the primary treatment goal of ECCO₂R therapy for patients with ARDS was to apply UPLV via managing CO₂ levels. For initiating ECCO₂R therapy in patients with ARDS, driving pressure (≥ 14 cmH₂O) followed by P_plat (≥ 25 cmH₂O) was considered the most important criteria, and this was confirmed in the post-meeting survey (Tables 1 and 2). Additional key parameters included pH (< 7.25), reducing V_T to < 6 mL/kg PBW, PaCO₂ (> 60–80 mmHg), respiratory rate (≥ 25 to > 30 breaths/min), PaO₂/FiO₂ (100–200) and PEEP (combined findings from Rounds 2 and 3).

Participants were evenly split during the meeting on the primary rationale for ECCO₂R therapy, being rescue therapy in patients with ARDS undergoing injurious MV, i.e. those with very high plateau and driving pressures despite reduced V_T and PEEP (n = 7), or to facilitate UPLV to prevent the deleterious effects of MV in patients already undergoing LPV (n = 7). Based on the results of the post-meeting survey, a consensus was reached among the group (12/14, 86% of participants) that ECCO₂R was a strategy they would consider selecting for rescue in patients with ARDS. Typical characteristics for initiating ECCO₂R in a rescue situation obtained as part of the post-meeting survey are summarised in Table 2. A majority (10/14, 71% of participants) indicated that they would select ECCO₂R as a means of facilitating UPLV for patients with ARDS, and typical characteristics for selecting patients are summarised in Table 2.

For both potential indications, patients would not be considered suitable for an ECCO₂R strategy if they met the indications for ECMO, such as severe or refractory ARDS [29] and presence of severe right heart failure (ECMO may be a more adequate treatment for these patients), in cases where anticoagulation is contraindicated and for those with major comorbidities and/or predicted survival of < 1 year.

The group considered treatment targets for their patients with ARDS undergoing ECCO₂R. A consensus was reached regarding driving pressure (< 14 cmH₂O) and respiratory rate (< 25 or < 20 breaths/min). There was majority agreement with respect to targets for P_plat (< 25 cmH₂O), pH (> 7.30 [Rounds 2 and 3]), PaCO₂ (< 50 or < 55 mmHg) and V_T (≤ 6 mL/kg PBW). Other target parameters were not proposed by the group (Table 1). The expected average length of time patients with ARDS would remain on ECCO₂R therapy was suggested to be 1–3 days (n = 5) and 4–6 days (n = 9).

Following discussion during the meeting on a protocol for weaning from ECCO₂R in patients with ARDS, a protocol was proposed and reviewed as part of the post-meeting survey (Table 3). The group voted on each step and reached consensus (92% of participants, n = 13) that this proposal was a suitable weaning strategy.

There was consensus during the meeting that patients with ae-COPD who should receive ECCO₂R therapy were those at risk of NIV failure, as well as patients recently initiated on MV after NIV failure to allow for early extubation within 24 h of initiating ECCO₂R therapy. Other patient groups would be considered (e.g. patients on prolonged MV who require weaning from invasive ventilation and patients who are refusing intubation), but a consensus was not reached.

The group agreed that for patients with ae-COPD at risk of NIV failure, ‘no decrease in PaCO₂’ and ‘no decrease in respiratory rate’ while on NIV were both key initiation criteria for ECCO₂R therapy (Table 4). These criteria were considered indicative of NIV failure. Clinical signs of respiratory failure and pH (< 7.25 [n = 5] or 7.25–7.30 [n = 6]) would be considered as initiation criteria by most of the participants. Baseline PaCO₂ and respiratory rate as main triggers were favoured by less than half of participants. For patients with ae-COPD who had already been intubated, criteria for initiating ECCO₂R therapy varied (Table 4).

Factors for excluding patients with ae-COPD from ECCO₂R typically included patients with end-stage disease (the group highlighted that markers for this include severe functional limitation and cachexia); contraindications to anticoagulation; problems with vascular access; patient’s wishes, e.g. refusal to be intubated, except in cases where ECCO₂R therapy represented the last resource accepted by the patient; poor quality of life; and the patient not being a candidate for MV.

Treatment targets for patients with ae-COPD receiving ECCO₂R therapy were, in order of perceived importance (Table 5), comfortable patient, pH (> 7.35/7.30; no consensus on specific pH), respiratory rate (< 20–25 breaths/min), decrease of PaCO₂ by 10–20%, weaning from NIV, decrease in HCO₃⁻ and maintaining haemodynamic stability. Consensus on a weaning protocol for patients with ae-COPD was reached during the meeting (Table 5).

Responses obtained during Round 1 (pre-meeting survey) showed that heparin was the preferred choice of anticoagulant used during ECCO₂R therapy (~ 80% of participants stated that heparin was their anticoagulant of choice). This was confirmed in the post-meeting survey, in which unfractionated heparin was the anticoagulant of choice for the majority (~ 90% of participants). The proposed heparin anticoagulation protocol agreed by the group is shown in Table 6. Lastly, argatroban was the group’s preferred anticoagulant in case of proven heparin-induced thrombocytopenia (HIT).

The findings presented here relate to the experiences of a relatively small number of physicians from centres across Europe; evidence from a larger group of intensivists from multiple regions of the world may be required to support these observations. Certain topics were not covered due to the scope of the meeting. Firstly, the questions covered current practice and did not explore if practices, e.g. inclusion policies of the respective centres, had changed over time. Secondly, certain rarer indications, e.g. lung transplant, were not covered, as the meeting focussed on the broader population of patients requiring ECCO₂R therapy, e.g. patients with ARDS or ae-COPD. These questions could be covered as part of a follow-up meeting. Additionally, while the authors took every opportunity to ensure all relevant major articles were cited, the purpose of the meeting was to understand current practice as opposed to conducting a comprehensive literature analysis. Finally, the experiences outlined are the physicians’ respective personal experiences and are not a replacement for formal guidelines. The reader should consider their patients’ needs and local guidelines when performing ECCO₂R therapy.