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 Table of Contents  
Year : 2017  |  Volume : 130  |  Issue : 5  |  Page : 505-507

Application of Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure: Situations, Issues, and Trends

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020; Beijing Institute of Respiratory Medicine, Beijing 100020; Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing 100020; Beijing Engineering Research Center for Diagnosis and Treatment of Respiratory and Critical Care Medicine (Beijing Chao-Yang Hospital), Beijing 100020, China

Date of Submission20-Nov-2016
Date of Web Publication20-Feb-2017

Correspondence Address:
Prof. Bing Sun
Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0366-6999.200548

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Keywords: Acute Respiratory Distress Syndrome; Acute Respiratory Failure; Extracorporeal Membrane Oxygenation

How to cite this article:
Li XY, Sun B. Application of Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure: Situations, Issues, and Trends. Chin Med J 2017;130:505-7

How to cite this URL:
Li XY, Sun B. Application of Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure: Situations, Issues, and Trends. Chin Med J [serial online] 2017 [cited 2018 Nov 13];130:505-7. Available from: http://www.cmj.org/text.asp?2017/130/5/505/200548

Extracorporeal membrane oxygenation (ECMO) is a type of extracorporeal life support (ECLS), and technological advances have expanded the use of this technique from the confines of the operating room by producing a compact system that could revolutionize the treatment of different types of respiratory failure.[1] The use of ECMO for severe acute respiratory failure (ARF) has evolved over the past two decades, and venovenous-ECMO (VV-ECMO) has been found to be safe and successful, especially during the H1N1 influenza epidemic, with good survival rates. ECMO has been used as salvage or rescue therapy for acute respiratory distress syndrome (ARDS) by providing oxygenation, CO2 removal, or both. It is not curative for ARDS and is used mainly as a bridge until the lungs recover from the underlying disease or as a bridge to lung transplantation for severe irreversible lung diseases.

  Evolution of Extracorporeal Membrane Oxygenation for Acute Respiratory Failure Top

Three major prospective trials of ECMO have been conducted in the past 40 years in patients with severe ARF. However, because the initial study sponsored by Zapol et al.[2] using venoarterial-ECMO in 1979 and the Morris trial [3] performed in 1994 were both disappointing, the use of ECMO in adults has exhibited a different trajectory. The CESAR trial, which was a randomized multicenter trial comparing conventional ventilation to ECMO for 180 severe ARF patients published in 2009, showed a significantly higher rate of disability-free survival at 6 months, 63% in patients referred for an ECMO protocol versus 47% in the conventional care group.[4] A further surge in the use of ECMO occurred during the H1N1 influenza pandemic in 2009, which caused a significant mortality in otherwise healthy young people due to ARDS, in whom conventional ventilation was often not successful.[5] The ongoing randomized Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome trial will likely provide more concrete answers regarding the effectiveness of ECMO in severe ARDS patients (ClinicalTrials.gov Identifier: NCT01470703).[6]

Although ECMO has been performed for many years in our country, it has mainly been used for cardiac support; the increased use of ECMO as a rescue therapy for ARF due to H1N1 influenza began in 2009 and increased in 2013 due to the H7N9 influenza outbreak.[7],[8],[9] Although the number of hospitals that have performed VV-ECMO for ARF rescue is increasing rapidly, the quantity in each center is limited, and no unified registration network exists in our country. This situation hinders the standardization and management of ECMO and leads to poor outcomes. However, VV-ECMO has been used for the treatment of more than 80 cases of severe ARF in our center, with a survival rate of more than 70% in the last 2 years, which is similar to that of larger ECMO centers abroad.[10],[11]

  Noticeable Problems during Extracorporeal Membrane Oxygenation Top

When to initiate extracorporeal membrane oxygenation

We are also faced with much confusion, such as when ECMO initiation is appropriate and how to manage and prevent complications. According to the Extracorporeal Life Support Organization (ELSO) registry data, over 16,430 adult patients have received ECLS as of July 2016. Of these, the need for respiratory support accounted for 10,601 cases (47%) followed by cardiac support in 9052 (40%) cases, and 2885 cases (13%) involved extracorporeal cardiopulmonary resuscitation.[12]

The common indications for the use of VV-ECMO in patients with ARDS include profound refractory hypoxemic respiratory failure with or without hypercapnia despite maximal ventilator support and the inability to tolerate lung protective strategies.[13] The ELSO guidelines, which we followed, recommend transfer to specialized ECMO centers when the mortality risk is 50% or higher, and transfer is indicated when mortality is equal to or exceeds 80%.[14] However, physicians are now often faced with the dilemma of when to initiate and terminate therapy. This can prove to be ethically challenging. The optimal timing for the initiation of ECMO also remains unclear, which makes the entire process challenging for physicians.

Management during extracorporeal membrane oxygenation

The daily care of an ECMO patient is a complex multidisciplinary task. Similar to other critically ill patients, ECMO-supported patients must be re-evaluated for the primary disease, which can lead to Intensive Care Unit (ICU) admission, and for the possible development and treatment of other organ failures. The complex relationship between the patient and the ECMO circuit sometimes makes patient assessment difficult. Other tasks include monitoring of the ECMO circuit and the prevention of complications.

Very little is known about the optimum ventilator settings while using VV-ECMO. The new “ultra-lung protective strategy” adopted the use of even lower tidal volumes and pressures to minimize ventilator-induced lung injury.[15] An important dilemma in these patients is the question, “Should we let the lungs collapse or should we try to keep them open?” The details such as the mode of ventilation, breath type, respiratory rate, positive end-expiratory pressure (PEEP), and FiO2 are still unknown. A study of new ventilation strategies guided by transpulmonary pressure in ECMO to determine the optimal PEEP to limit atelectrauma is ongoing in our center (ClinicalTrials.gov Identifier: NCT02439151).[16] Our previous study found that, compared to the traditional “lung rest” strategy, the transpulmonary pressure-guided ventilation strategy can better maintain lung volume to limit atelectasis and provide more effective lung protection.

Another method includes potentially extubating patients while on ECMO, the so-called “awake ECMO” mode,[17] thereby avoiding the damaging effects of ventilator-induced lung injury and the risk of ventilator-associated pneumonia. Patients undergoing this method will require minimal to no sedation and can ambulate, participate in physical therapy, and remain on ECMO until the lungs recover.

The potential benefit of ECMO can be offset by numerous complications. Bleeding is one of the major and most dreaded complications, with an incidence ranging between 10% and 30%. Intracranial hemorrhage is the most serious and potentially fatal bleeding complication, occurring in approximately 10–15% of ARDS patients on ECMO. These potential complications require close monitoring and necessitate the presence of a specially trained ICU team who are constantly available to troubleshoot the system at the bedside 24 h a day.[18]

Heparin is the most commonly used anticoagulant in EMCO. Targets for anticoagulation are monitored using different methods such as the activated partial thromboplastin time, anti-Xa activity, activated clotting time, anti-Xa levels, and viscoelastic tests (Thromboelastography [TEG ®] or rotational thromboelastometry).[19] However, the most reliable technique for monitoring anticoagulation and the ideal range of anticoagulation to prevent thrombosis or bleeding are both unknown. It is noteworthy that novel centrifugal pumps, polymethylpentene oxygenators, and heparin-coated circuits ensure fewer clotting challenges. Large cannulas with higher flows also reduce the risk of thrombosis.

  Expansion and Standardization Top

Recently, the increasing application of ECMO in ARF patients has expanded the clinical practice of ECMO in our country. However, blind expansion in every hospital is not appropriate. Centralization of patients to a few selected, specifically equipped centers and establishing a registration network to share resources may help improve clinical management by physicians and the outcome of patients, which should be our primary effort. Moreover, the CESAR trial indeed indicated that significantly more patients with severe ARDS survived without severe disability if they were transferred to a single ECMO center compared with patients who were managed conventionally at remote hospitals.[4] ECMO instituted at referral centers allows stabilization of an unstable patient, otherwise unmovable, and thus a safer transportation to the targeted destination. Nevertheless, adding an ECMO system makes transportation more complex, requiring a specialized multidisciplinary ECMO team, trained and equipped to stabilize patients at the referring hospital, to apply and manage ECMO, and to assist patients during transportation up to the treatment center. Besides, as ECMO is an expensive investment and advanced technology life support modality; introduction of a qualification assessment system should be recommended in large medical centers.

Several questions remain to be considered when planning a national or regional ECMO network with structured interhospital transport. Interhospital transportation of critically ill patients to referral centers is required when local resources and technology are insufficient for adequate management. The process requires a specialized team and resources dedicated to retrieval. Therefore, as ECMO is an invasive, intensive form of support; it requires considerable institutional commitment. Consequently, its use is advocated only in those patients who are believed to be at substantial risk of death.

  Conclusion Top

Overall, the application of VV-ECMO for ARF in the mainland of China is still in the development phase. Based on the above-mentioned standardized management experience and shared resources, we can implement a system that is consistent with that of the international community.

  References Top

Allen S, Holena D, McCunn M, Kohl B, Sarani B. A review of the fundamental principles and evidence base in the use of extracorporeal membrane oxygenation (ECMO) in critically ill adult patients. J Intensive Care Med 2011;26:13-26. doi: 10.1177/0885066610384061.  Back to cited text no. 1
Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979;242:2193-6. doi: 10.1001/jama.1979.03300200023016.  Back to cited text no. 2
Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr., Weaver LK, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994;149(2 Pt 1):295-305. doi: 10.1164/ajrccm.149.2.8306022.  Back to cited text no. 3
Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): A multicentre randomised controlled trial. Lancet 2009;374:1351-63. doi: 10.1016/S0140-6736(09)61069-2.  Back to cited text no. 4
Patroniti N, Zangrillo A, Pappalardo F, Peris A, Cianchi G, Braschi A, et al. The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: Preparation for severe respiratory emergency outbreaks. Intensive Care Med 2011;37:1447-57. doi: 10.1007/s00134-011-2301-6.  Back to cited text no. 5
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA). Available from: https://www.clinicaltrials.gov/ct2/show/NCT01470703. [Last accessed on 2016 Oct 30].  Back to cited text no. 6
Zhan QY, Sun B, Tong ZH, Guo LM, Xu L, Zhu X, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome caused by novel 2009 influenza A (H1N1) virus (in Chinese). Natl Med J China 2011;91:3262-6. doi: 10.3760/cma.j.issn.0376-2491.2011.46.007.  Back to cited text no. 7
Hu Y, Lu S, Song Z, Wang W, Hao P, Li J, et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet 2013;381:2273-9. doi: 10.1016/S0140-6736(13)61125-3.  Back to cited text no. 8
Huang L, Li T, Xu L, Hu XM, Duan DW, Li ZB, et al. Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data. Chin Med J 2016;129:1688-95. doi: 10.4103/0366-6999.185871.  Back to cited text no. 9
[PUBMED]  [Full text]  
Sun B, Wang CT, Wu J, Li XY, He HY, Zhang CY, et al. The experience of extracorporeal membrane oxygenation for severe acute respiratory failure in adults (in Chinese). Chin J Tuberc Respir Dis 2012;35:804-8. doi: 10.3760/cma.j.issn.1001-0939.2012.11.004.  Back to cited text no. 10
Sun B, He H, Wang Z, Qu J, Li X, Ban C, et al. Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: A prospective observational study. Crit Care 2014;18:456. doi: 10.1186/s13054-014-0456-6.  Back to cited text no. 11
Extracorporeal Life Support Registry Report. Available from: https://www.elso.org/Registry/Statistics/InternationalSummary.aspx. [Last accessed on 2016 Oct 30].  Back to cited text no. 12
Sen A, Callisen HE, Alwardt CM, Larson JS, Lowell AA, Libricz SL, et al. Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives. Ann Card Anaesth 2016;19:97-111. doi: 10.4103/0971-9784.173027.  Back to cited text no. 13
[PUBMED]  [Full text]  
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Costa EL, Amato MB. Ultra-protective tidal volume: How low should we go? Crit Care 2013;17:127. doi: 10.1186/cc12556.  Back to cited text no. 15
Applied Research of New Lung Ventilation Strategies Guided by Transpulmonary Pressure in Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02439151. [Last accessed on 2016 Oct 30].  Back to cited text no. 16
Langer T, Santini A, Bottino N, Crotti S, Batchinsky AI, Pesenti A, et al. “Awake” extracorporeal membrane oxygenation (ECMO): Pathophysiology, technical considerations, and clinical pioneering. Crit Care 2016;20:150. doi: 10.1186/s13054-016-1329-y.  Back to cited text no. 17
Anand S, Jayakumar D, Aronow WS, Chandy D. Role of extracorporeal membrane oxygenation in adult respiratory failure: An overview. Hosp Pract 2016;44:76-85. doi: 10.1080/21548331.2016.1151325.  Back to cited text no. 18
Esper SA, Levy JH, Waters JH, Welsby IJ. Extracorporeal membrane oxygenation in the adult: A review of anticoagulation monitoring and transfusion. Anesth Analg 2014;118:731-43. doi: 10.1213/ANE.0000000000000115.  Back to cited text no. 19

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