The use of CRRT in ECMO patients

The Egyptian Journal of Critical Care Medicine 6 (2018) 95–100

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Original article

The use of CRRT in ECMO patients Marlice Van Dyk 1,2 Netcare Unitas Hospital, Cnr Clifton Avenue and Cantonments Road, Centurion, Pretoria, South Africa

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Article history: Received 3 December 2018 Accepted 11 December 2018 Available online 15 December 2018 Keywords: ECMO Continuous renal replacement therapy Acute kidney injury

a b s t r a c t Extracorporeal life support (ECLS) is an effective therapy used for patients who are severely hypoxic as well as those with cardiogenic shock. Many of these patients require continuous renal replacement therapy (CRRT) as they are too unstable for intermittent haemodialysis. Prognosis of patients who are on ECMO tends to do worse if they develop acute renal failure during the ECMO run resulting in the requirement for dialysis. According to the ELSO registry, the mortality of patients requiring renal replacement therapy (RRT) on ECLS is increased. There are various ways to connect a CRRT circuit onto an ECMO circuit. Each method has its advantages and disadvantages. Separate access for CRRT is recommended. Ó 2018 The Egyptian College of Critical Care Physicians. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Extracorporeal membrane oxygenation (ECMO) is the use of mechanical devices to support the heart and/or lung function in patients with severe cardiac and/or respiratory failure. In these cases, the ECLS is a last line therapy. However, it is also possible to use this modality for patients with reversible cardiac and/or respiratory failure. An ECMO circuit consists of the following:    

a venous access cannula that drains the venous blood, a small volume centrifugal pump, an oxygenator, an ultrasound sensor to measure the rate of blood flow as well as to act as a bubble detector,  a return line to the patient and  a return (arterial) cannula either back to the internal jugular vein or femoral vein in case of VV-ECMO or the aorta in case of VA-ECMO. Modern membrane oxygenators provide optimal gas exchange, attenuates injury to blood and reduce resistance. There is a hydrophobic gas-permeable membrane incorporated into the inlet

1 Netcare Unitas Hospital, Cnr Clifton Avenue and Cantonment Road, Centurion, Pretoria, South Africa. 2 Personal Assistant: Sarah MacDonald. E-mail address: [email protected] Peer review under responsibility of The Egyptian College of Critical Care Physicians.

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port of the oxygenator that enables gas evacuation and prevents leaks, facilitating priming of the circuit, de-aeration and elimination of air in the circuit. There are also two Luer Lock adaptors on both the inlet and outlet ports of the oxygenator, used for priming as well as monitoring of transmembrane gradients [1]. Most ECMO circuits are coated with an anticoagulant, often heparin, which assists in extending the life of the oxygenator. Despite this, numerous patients require anticoagulation treatment where a continuous infusion of unfractionated heparin is used. Repeat monitoring of anticoagulation in the system can be done in various ways. Namely activated clotting time (ACT), partial thromboplastin time (PTT), Anti X-levels, thromboelastography (TEG) and Fibrinogen [1]. Acute kidney injury is also common in patients receiving ECMO, with multiple predisposing factors present for patients to develop AKI. These can be sub-divided into patient and circuit related causes. Pre-treatment patient factors that lead to AKI are hypoperfusion, loss of autoregulation, hypoxia, nephrotoxic drugs and systemic inflammation. Other reasons for CRRT include acid-base and electrolyte disturbances, and fluid overload. Two singlecentre studies showed an AKI incidence of more than 80% with 50% of those patients requiring renal replacement therapy within the first week of the ECMO run [2]. ECMO-related factors that predispose patients to AKI can be divided into: Haemodynamic factors (Blood flow alterations, loss of pulsatile flow), Hormonal factors (Renin-angiotensinaldosterone dysregulation, ANP downregulation) ECMO-related systemic inflammation (Blood shear stress, exposure to an artificial membrane, blood/air interface), Organ crosstalk (cardio-renal syndrome, lung/kidney interactions), and circuit-related factors

https://doi.org/10.1016/j.ejccm.2018.12.006 2090-7303/Ó 2018 The Egyptian College of Critical Care Physicians. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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(high myoglobin, activation of coagulation cascade, and haemolysis) [3]. The most common reasons for starting dialysis on ECMO was fluid overload (43%), prevention of fluid overload (16%), AKI (35%), and electrolyte disturbances (4%) [4]. The early introduction of CRRT may prevent fluid overload and is often used in clinical practice. A study by Michael Wolf et al. showed that early CVVH in paediatric cardiac patients requiring ECMO is associated with increased mortality [5]. This may be related to underlying patient factors rather than the ECMO support. Fluid overload on day 2 in ECMO treated patients are positively associated with worse mortality at day 90 [6]. The most commonly used RRT modality in ECMO patients is CRRT. CRRT encompass the following modalities: Slow continuous venovenous ultrafiltration (SCUF), Continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD), and continuous veno-venous hemodiafiltration (CVVHDF) [1].

The setup of a renal replacement system on either VA- or VVECMO is performed in the same manner and can be divided into either patient or circuit access. Within these two access methods, there are three main modalities for combining CRRT and ECMO. Each of these having their various advantages and disadvantages. The first method to be discussed relates to patient access methods. 1. Separate vascular access and CRRT machine Most commonly additional vascular access points are used. This option provides the advantage of no interference with either the systemic or ECMO haemodynamic while having the ultrafiltration controlled by the CRRT machine [1,7]. Two possible disadvantages are present in this model. Firstly, due to the anticoagulation used for the ECMO and the introduction of a large cannula for CRRT, the risk of bleeding during insertion and multiple other complications are elevated. Additionally, the use of additional access sites might be required

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Hemofilter

Centrifugal Pump Oxygenator Fig. 1. Hemofilter inflow line connected after the centrifugal pump returning to the ECMO circuit before the pump [1].

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CVP Opon 2 Opon 1

hemoconcentrator

Centrifugal Pump Oxygenator Fig. 2. Hemoconcentrator filter inflow line connected to the ECMO circuit before the oxygenator. Option 1 has the return limb connected post-oxygenator here Option 2 has the return limb connected to the CVP line [1].

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for additional ECMO support, or the additional access points may be compromised [7]. 2. The ‘‘in-line technique.” This technique incorporates the hemodiafilter into the ECMO circuit (Fig. 1), thereby making use of the ECMO pump to force the blood through the hemodiafilter. Although an easy technique, this has several problems, mainly the use of external infusion pumps which is less accurate. SCUF is the most commonly used modality for in-line RRT [1]. Fig. 2 below indicates an example of a patient on VA-ECMO where the in-line hemoconcentrator for fluid management is used due to no viable venous access being available. Initially

(Option 1), the return limb was connected to the Luer Lock connection post-oxygenator with a high risk of air bubbles and/or clots. The circuit was subsequently adjusted to have the return limb connected to the patients’ CVP line (Option 2). Thereby creating a shunt but was deemed to be a safer option. Fig. 3 provides a practical example of this modality. 3. Combining ECMO and CRRT Using a dedicated CRRT machine is the most precise and safest method of delivering dialysis in ICU. The CRRT circuit can be combined with the ECMO circuit in various ways however the machine’s pressure alarms may be a problem when combing a high flow and a low flow extracorporeal circuit.

Fig. 3. Practical example of Option 2 of the in-line technique as discussed above.

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CRRT Opon 2

CRRT Opon 1

Centrifugal Pump Oxygenator Fig. 4. Connecting a CRRT machine to the ECMO circuit. Option 1 has the inlet of CRRT circuit connected to the venous line of the ECMO, before the pump. Option 2 CRRT circuit is connected to the high-pressure part of the ECMO circuit post pump. Both options have the CRRT outlet return to the venous line of the ECMO circuit pre-pump [1].

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The CRRT can be connected to the venous line of the ECMO circuit with the dialysis inflow either before or after the centrifugal pump as indicated in Fig. 4. If the CRRT outlet line is connected before the ECMO pump (Option 1), the CRRT returns into the negative pressure part of the ECMO circuit. These negative pressures range from 20 to 100 mm Hg. Often the CRRT machine will alarm indicating low arterial pressures and automatically stops the machine. Overriding these limits leads to very low negative pressure, haemolysis and micro-embolisation [1]. Complications for the ECMO circuit of connecting the CRRT to the negative pressure side are increased risk of air emboli and also increased risk of clotting of the ECMO pump. If ECMO flows are high, the venous pressure may be very low. Factors determining the access or venous pressure include the size of the access cannula, volume status of the patient, and intrathoracic pressures.

An alternative option for combining the two circuits is to connect the CRRT machine to the ECMO circuit between the pump and the oxygenator (Fig. 5). The inflow for the CRRT circuit is connected to the venous line, just after the ECMO pump and the outflow is returned to the ECMO circuit just before the oxygenator [1]. In this scenario, additional connectors need to be attached to the ECMO circuit for the CRRT machine to be connected. This generates very high pressures on both the inlet and outlet lines on the CRRT machine as well as leading to an increased risk of thrombus formation around these connectors. The advantage of this modality is the use of the oxygenator as an air bubble trap as well as reducing the risk of air entering the centrifugal pump. The third option, as indicated by Fig. 6 below is to connect the inlet line for the CRRT machine to the arterial line, near to the return cannula of the ECMO circuit. With the outlet line returning

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Centrifugal Pump Oxygenator Fig. 5. Connecting the inflow of the CRRT machine to the venous line after the pump (in close proximity) and outflow to the venous line closer to the oxygenator (just before the oxygenator) [1].

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Centrifugal Pump Oxygenator Fig. 6. The CRRT inlet is connected to the arterial line of the ECMO circuit near connection with the return cannula of the ECMO and the outlet line of the CRRT circuit to the venous line of the ECMO circuit near connection with the drainage ECMO cannula [1].

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From paent

Return to paent

Centrifugal Pump Oxygenator Fig. 7. The inflow of the CRRT circuit to the arterial (return) line of ECMO just after the oxygenator, the CRRT outflow to the venous line of the ECMO circuit just before the oxygenator [1].

Fig. 8. A CRRT machine connected to the VA-ECMO circuit. Both drainage and return limbs from the CRRT machine was post-oxygenator (connected to standard connections in the circuit).

to the ECMO circuit near the drainage cannula. While this modality provides optimal inflow to the CRRT circuit as well as no resistance to the outflow, it does hinder the patient care due to the two ECLS circuits [1]. The CRRT circuit can also be connected to the existing Luer locks on the inlet and outlet ports of the oxygenator as indicated in Fig. 7 below. This is probably the easiest, least invasive and safest method of delivering CRRT on the ECMO circuit [1,8]. The benefits here relate to the integrated Luer ports which allow for easy connection to the ECMO circuit, the use of the oxygenator as an air bubble and clots trap as well as the ability to monitor the pre- and post-oxygenator pressure readings. The major disadvantage, however, is the implication of the high pressures on the CRRT machine which will result in the alarms triggering the blocking of the flow [1]. Some ECMO circuits come standard with additional connections. This was used in a patient on VA-ECMO that required urgent

dialysis, but where no additional vascular access was possible (Fig. 8). Various options of delivering CRRT on ECMO have been presented. In the author’s opinion, the less intervention into the ECMO circuit the safer. Not only regarding the CRRT machine and alarms but also to maintain the integrity of the ECLS circuit.

Conclusion AKI is the most common complication on ECMO. In this article, the different access methods for CRRT to be performed are discussed. These are namely either directly onto the ECMO circuit or on a separate extracorporeal circuit. While each method provides unique pros and cons, it is of the author’s opinion that separate vascular access is recommended. Thereby providing no interference with either the systemic or ECMO haemodynamic as well as

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allowing the CRRT machine to control the ultrafiltration. Should this option not be feasible a thorough assessment of the advantages and disadvantages of the other modalities should be performed. Meticulous attention should be paid to all aspects of CRRT on ECMO, as these patients have been shown to have higher mortality. References [1] Seczyn´ska B, Królikowski W, Nowak I, Jankowski M, Szułdrzyn´ski K, Szczeklik W. Continuous renal replacement therapy during extracorporeal membrane oxygenation in patients treated in the medical intensive care unit: technical considerations Available from. Ther Apher Dial 2014;18(6):523–34. https:// onlinelibrary.wiley.com/doi/abs/10.1111/1744-9987.12188. [2] Hamdi T, Palmer BF. Review of extracorporeal membrane oxygenation and dialysis-based liver support devices for the use of nephrologists Available from. Am J Nephrol 2017;46(2):139–49. https://www.karger.com/DOI/10.1159/ 000479342. [3] Villa G, Katz N, Ronco C. Extracorporeal membrane oxygenation and the kidney Available from. Cardiorenal Med 2015;6(1):50–60. https://www.karger.com/ DOI/10.1159/000439444.

[4] Fleming GM, Askenazi DJ, Bridges BC, Cooper DS, Paden ML, Selewski DT, et al. A multicenter international survey of renal supportive therapy during ECMO: the kidney intervention during extracorporeal membrane oxygenation (KIDMO) group Available from. ASAIO J 2012;58(4). https://journals.lww.com/ asaiojournal/Fulltext/2012/07000/A_Multicenter_International_Survey_of_Renal. 17.aspx. [5] Wolf MJ, Chanani NK, Heard ML, Kanter KR, Mahle WT. Early renal replacement therapy during pediatric cardiac extracorporeal support increases mortality Available from. Ann Thorac Surg 2013;96(3):917–22. https://doi.org/10.1016/j. athoracsur.2013.05.056. [6] Schmidt M, Bailey M, Kelly J, Hodgson C, Cooper DJ, Scheinkestel C, et al. Impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation Available from. Intensive Care Med 2014, Sep,;40 (9):1256–66. https://doi.org/10.1007/s00134-014-3360-2. [7] Thajudeen B, Daheshpour S, Bijin B. Extracorporeal membrane oxygenation and continuous renal replacement therapy Available from. In: Firstenberg MS, editor. Extracorporeal membrane oxygenation. Rijeka: IntechOpen; 2016. [8] Zhou X-L, Chen Y-H, Wang Q-Y. A new approach combining venoarterial extracorporeal membrane oxygenation and CRRT for adults: a retrospective study Available from. Int J Artif Organs 2017;40(7):345–9. https://doi.org/10. 5301/ijao.5000597.