Up to 50% of patients requiring extracorporeal membrane oxygenation (ECMO) also suffer from acute kidney injury (AKI) requiring renal replacement therapy (RRT).1 Metabolic disorders and fluid overload are the main indications for RRT in this setting.2,3 Correcting these disorders, especially fluid overload by early RRT may be associated with improved prognosis. Nevertheless, vascular access required for RRT may be challenging, as ECMO circuit occupies vascular two access sites, and an additional access increases the risk of bleeding, vascular and infectious complications.4 Continuous renal replacement therapy (CRRT) lines directly to the ECMO circuit may circumvent these limitations and allow a higher blood flow associated with increased efficiency and circuit life expectancy.5,6 In fact, undetected diminution of blood flow has been described to lower circuit life expectancy.5 Thus, preventing blood flow reduction may facilitate prevention of membrane clotting. This method is technically challenging and pressure levels in different segments of the ECMO circuit may not be compatible with CRRT pressure thresholds.1,7,8 In fact, CRRT devices are manufactured to be connected to central venous pressure ranging from 0 to 20 mm Hg. Pressures in ECMO circuit are markedly negative before the pump (segment A) and positive between the pump and the oxygenator (segment B) (Figure 1). Modifying ECMO blood flow induces variation of these pressures, and consequently modifies pressures in CRRT lines.7 Detection of pressures beyond alarm ranges provokes stop of CRRT device. If pressures are not appropriately managed, iterative stops of session may impair CRRT efficiency.
Technical aspects of direct connection of CRRT device on ECMO circuit have been described in the pediatric population7,9,10 but with little focus on pressure management.7 Some reports of successful connection of CRRT on ECMO exist in adults.1,8,10
Even though, managing pressures in CRRT lines is an identified problem,1,8 this challenging issue has been poorly and not appropriately evaluated.1,8 The problem of high pressures may be circumvented by inhibiting pressure alarms,7 or decreasing ECMO blood flow, but with potential unpredictable consequences.
We report a preliminary experience of management of CRRT lines pressures with the goal to perform RRT in accordance with current guidelines by maintaining CRRT pressures in adequate ranges without modifying ECMO blood flow or inhibiting pressure alarms.
The “Comité d’Evaluation de l’Ethique des projets de Recherche Biomédicale Paris Nord” (Institutional Review Board -IRB 00006477- of HUPNVS, Paris 7 University, AP-HP) reviewed and approved the research project (No. 14–025), waiving the need for informed consent for this retrospective observational study.
Extracorporeal Membrane Oxygenation and Continuous Veno Venous Hemofiltration Equipment
Extracorporeal membrane oxygenation circuits were inserted using a 15 or 17 Fr arterial cannula, and a 25 Fr venous cannula. This relative small size of arterial cannula has been chosen because in our center cannulas are inserted by a percutaneous technique. Extracorporeal membrane oxygenation (Maquet Cardiopulmonary AG) was driven by a centrifugal pump (RotaFlow RF32) with a heparinized circuit (Bioline tubing) and an oxygenator (PLS Quadrox). Continuous renal replacement therapy was performed with an Aquarius machine (Edwards Lifesciences), comprising a membrane (Aquamax HF 19 [Baxter]) and hemofiltration lines (Aqualine [Baxter]). An access for connection is available on each segment of the ECMO circuit. Ranges of pressure alarms of CRRT are as follows: access line (−250; +200 mm Hg); return line (−50; + 350 mm Hg).
Different Options of Connection
Different options of connection have been described in the literature.1,10 The local protocol has been written taking into account these propositions and our recent local experience (Figures 1 and 2).
Continuous Veno Venous Hemofiltration Goals
The goals of continuous veno venous hemofiltration (CVVH) are as follows: blood flow from 200 to 300 ml/min; ultrafiltration (UF) volume > 35 ml/kg/h, and filtration fraction lower than 25%.
Connection of Continuous Veno Venous Hemofiltration Lines to the Extracorporeal Membrane Oxygenation Circuit
We first systematically performed the connection as shown in Figure 1A. To ensure that pressures remain within appropriate ranges, CVVH session is started at half of the prescribed CVVH blood flow and is gradually increased to the target blood flow. The CVVH device may trigger an alarm in case of high ECMO flow rates, but this is not an indication to modify ECMO blood flow. A stepwise management protocol was applied to keep lines in adequate pressure ranges (Figure 2).
Patient and Continuous Veno Venous Hemofiltration Data
Data related to general characteristics, ECMO settings, and CVVH sessions were recorded from charts.
Successful Connection, Efficacy, and Serious Events
Connection without premature clotting was defined as continuous session lasting at least 12 hours without membrane clotting, and with CVVH blood flow within the defined target range.
Efficacy was defined by a 20% decrease of both creatinine and BUN, and an effective UF volume of at least 35 ml/kg/h.8 Serious events were defined as any ECMO dysfunction.
Prevention of CVVH membrane clotting was performed with unfractionated heparin, in the absence of contraindications.
Results are expressed as median and interquartile range (IQR [25–75]) for continuous variables and number and percentages for dichotomous variables.
Between January 2011 and February 2013, CRRT lines were directly connected to the ECMO circuit in 12 patients (eight venoarterial ECMO and four venovenous ECMO).
Median of ECMO blood flow was 3.55 L/min [3.1–4.8]. Primary indications for RRT were anuric AKI (n = 6), metabolic acidosis (n = 3), and hyperkalemia (n = 2), pulmonary edema (n = 1).
The first attempt of connection was successful in seven patients, (connected as shown in Figure 1A). In three cases, because of high pressures in CRRT access line, this line was connected before ECMO pump (segment A) (Figure 1B). In two other patients, positive pressure in return line was also beyond alarms of pressure ranges, necessitating connecting this line before the pump (segment B) (Figure 1C). In one patient, because of negative return line pressure below the lower limit of alarm, a clamp was tightened to adjust the pressure (Figure 1C). In no patient, a reduction of CRRT blood flow was necessary (fourth step).
Data concerning hemofiltration settings are presented in Table 1. CRRT blood flow was 8% [7–9.75] of ECMO blood flow. Because of contraindications, only five patients received anticoagulation. CRRT was terminated due to death in two cases, transfer to the operating room in two cases, correction of initial disorder in one case, and membrane clotting in the other seven cases. However, no case of premature clotting (within 12 hours) was observed. After excluding deaths and transfers to the operating room, the median circuit life was 27.5 [19.5–33] hours. Evolution of biological parameters is shown in Table 2. Evolution of CRRT pressures after changing CRRT connection are summarized in Table 3.
No air embolism or other events impaired the normal ECMO functioning.
This case series reports the successful management of high CRRT pressures induced by direct connection of CRRT to ECMO circuit, allowing an achievement of RRT goals without inhibiting CRRT pressure alarms or modifying ECMO settings. Despite the scarcity of the literature regarding this issue, we believe that managing high CRRT pressures is a major challenge in the most severe adult patients necessitating very high ECMO blood flow. In one review of Seczynska et al.1, this point is little discussed, but no detailed solution is provided. In one case series in adult, Rubin et al.8 described the successful management of high pressures by connecting access line after pump and oxygenator, and return line before the pump. Nevertheless, manipulating connections after oxygenator exposes to the risk of emboli. Furthermore, only few details about RRT settings and clearance data are provided. They obtained UF rates below current guidelines and practices, and CRRT blood flow was close to the lowest level defined by guidelines.11 In the pediatric study of Santiago, pressure alarms were inhibited. Furthermore, the modality of connection is not provided and this pediatric experience may not be generalized to adults.7
It is also possible to manage high return line pressure by connecting CRRT return line before the pump and access line after the pump, but this option exposes to the drawback of hypothetical air embolism and recirculation.
One of the main factors decreasing the efficacy of CRRT is iterative stops because of unsuitable pressure and membrane clotting.11 Prevention of membrane clotting remains challenging and can be achieved by ensuring high blood flow from 150 to 300 ml/min to maintain a filtration fraction less than 25% with a replacement volume of 35 ml/kg/h.11
The choice of connections applied in our protocol may be controversial, but no data are available in support of either of the different options. The review by Seczynska et al.1 summarized various options. In fact, four issues have to be taken into account: high CRRT pressures, oxygenation membrane shunt, recirculation, risk of air embolism. The clamp used in case of excessive negative pressure in return line has already been proposed in the review of Seczynska et al.1 but there is no report of its successful use in adults.
Median CRRT duration was only 22 hours. This is one of the main limitations of this study, which may limit the applicability of this approach. Nevertheless, this duration is in the range of those found in other studies by Crosswell (14-25H),6 Chua (6–16),12 Baldwin (20H).5 Two explanations may be proposed. First, these surgical patients were mainly managed without anticoagulation. Second, when excluding deaths and transfers to operating room, the median circuit life was 27.5 hours, close to the 29 hours reported by Crosswell et al.6
It would be interesting to evaluate the impact of cannula size on access and return line CVVH pressure. Larger cannulas may be associated with decreased pressure. Our percutaneous technique requires small size ECMO arterial cannula. Central venous pressure (CVP) may be correlated to the patient volemic status, thus potentially impact ECMO line pressures. The role of CVP has not been evaluated because this is not a parameter routinely recorded in our institution.
The challenge of high pressure is underestimated and scarcely addressed in the current literature. We report the successful management of high pressure in CRRT lines induced by the direct connection of CRRT directly on ECMO circuit. Furthermore, this study demonstrates the effective clearance obtained by direct connection of CRRT on ECMO circuit in adults.
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