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Clinical review: Extracorporeal membrane oxygenation


The H1N1 flu pandemic led to a wider use of extracorporeal membrane oxygenation (ECMO), proving its power in hypoxemic emergencies. The results obtained during this pandemic, more than any randomized trial, led to the worldwide acceptance of the use of membrane lungs. Moreover, as centers that applied this technique as rescue therapy for refractory hypoxemia recognized its strength and limited technical challenges, the indications for ECMO have recently been extended. Indications for veno-venous ECMO currently include respiratory support as a bridge to lung transplantation, correction of lung hyperinflation during chronic obstructive pulmonary disease exacerbation and respiratory support in patients with the acute respiratory distress syndrome, possibly also without mechanical ventilation. The current enthusiasm for ECMO in its various aspects should not, however, obscure the consideration of the potential complications associated with this life-saving technique, primarily brain hemorrhage


Extracorporeal membrane oxygenation (ECMO) is a temporary artificial extracorporeal support of the respiratory system and/or cardiac system used for the treatment of cardiopulmonary failure refractory to conventional therapies. More than 1,000 papers on ECMO published between January 2009 and May 2011 (PubMed search) clearly indicate a renewed interest in the technique, initially triggered by the CESAR trial publication [1] and the recent H1N1 flu pandemic. Indeed, during the pandemic the number of patients with acute respiratory distress syndrome (ARDS) who were not safely treatable with current clinical settings of mechanical ventilation (6 to 8 ml/kg tidal volume normalized on ideal body weight and plateau pressure lower than 30 to 35 cmH2O) and who therefore received extracorporeal respiratory support appeared to be greatly increased. After providing a brief background and some technical notes, we will review the most important and recent findings related to the technique, its application and future applications.

Long-term ECMO, as support for severe respiratory failure, was first successfully used in 1972 in an adult patient with post-traumatic respiratory failure [2]. A few years later, at the University of California, Bartlett and colleagues successfully treated a newborn with ECMO [3]. The enthusiasm for this new technique led to a randomized trial sponsored by the National Institutes of Health that compared venous-arterial ECMO with conventional mechanical respiratory support in severe ARDS [4]. After randomization of 90 patients the trial was stopped for futility because the mortality in both groups was around 90%. However, one should note that the greatest concern for mechanical ventilation, at that time, was the high fraction of inspired oxygen and not the high ventilator pressure/volume; that is, nonphysiological stress and strain. In this ECMO trial, therefore, the only difference in mechanical ventilation settings between treatment and control patients was a lower FiO2 in the group that received the extracorporeal support. Moreover, the ECMO technology at these times was very primitive, with consistent risks for the patients due to high priming volumes of the extracorporeal circuits and elevated bleeding risks associated with systemic anti-coagulation. The limitations of this trial passed mostly unrecognized, however, and the discouraging results therefore led to the ECMO technique being abandoned worldwide.

During the same years, Kolobow was developing a new membrane lung optimized for carbon dioxide (CO2) removal as a possible application in patients with chronic obstructive pulmonary disease. While testing this new device in spontaneously breathing animals, however, we observed when part of the metabolically produced CO2 was removed by the membrane lung that the ventilation of the animals proportionally decreased to maintain a constant blood partial pressure of CO2 [5]. Artificial CO2 removal could therefore be a powerful and valuable tool to control the respiratory drive up to complete apnea [6]. Indeed, the focus of extracorporeal support was shifted from oxygenation to CO2 removal, aiming to provide lung rest to allow better healing. The hypothesis of limiting potential harmful stimuli was based uniquely on common sense, however, since concepts such as baby lung [7], atelectrauma [8], and so forth, were still unknown.

The first applications in humans of the concept of lung rest were reported in 1980 [9]. Soon after this experience a larger series of patients treated with extracorporeal CO2 removal and low-frequency positive-pressure ventilation was described by the same authors [10]. However, a small randomized trial conducted in the United States at the beginning of the 1990s failed to show an outcome advantage of additional extracorporeal support as com-pared with conventional mechanical ventilatory support [11]. Despite this lack of evidence, a few centers around Europe continued to provide veno-venous extracorporeal support in selected series of patients, usually as a last resort [12]. In contrast, in the United States Bartlett and colleagues continued to provide extracorporeal support with standard mechanical ventilation, with more liberal indications and with encouraging results [13, 14].

A renewed interest in this technique arose after the publication of the CESAR trial, which clearly showed an improvement in the death rate and severe disability 6 months after randomization, when patients with severe respiratory failure were treated with extracorporeal support in an expert high-case-volume center compared with nonspecialized hospital care [1]. Moreover, although not the primary outcome, an actual difference in survival of around 25% was observed for patients considered for ECMO treatment at 28 days, the primary outcome of most ARDS literature. However, the final explosion of the application of this extracorporeal support was due to the use of ECMO as a rescue therapy in Australia and New Zealand during the H1N1 influenza pandemic [15]. This increased use is also probably due to several technical improvements, which allowed a simpler and safer use of the technique. Among these innovations we can mention the introduction of nonporous hollow fiber devices, characterized by low resistance to blood flow, and poly-methylpentene fibers that, combined with nonthrombogenic coatings, decrease the need for platelet transfusion and continuous heparin infusion. Moreover, recently introduced wire-reinforced walls of vascular access devices allow very thin cannula walls, reducing resistance to blood flow.

As the acronym ECMO includes several techniques with different aims, a brief reminder of the artificial lung's physiology is indicated to fully understand the different approaches, before discussing the latest reports on the topic.

Physiology of the artificial lung


The amount of oxygen provided via artificial lung is a direct function of the blood flow. The blood flow required during veno-venous bypass to achieve acceptable arterial oxygenation is usually between 3 and 6 l/minute, partially depending on the cardiac output of the patient, on the hemoglobin concentration and on saturation. Of note, the gas flow required to fully oxygenate the incoming blood through the artificial lung may be quite low. For example, if we consider an entering hemoglobin saturation of 60% (with 3 l/minute extracorporeal blood flow, 10 g/dl hemoglobin concentration, 40 mmHg partial pressure of oxygen in venous blood and approximately 85 ml/l oxygen content), to reach 100% saturation we would need 200 ml/minute oxygen. Providing 0.2 l/minute pure oxygen to a highly efficient membrane lung would therefore theoretically be sufficient. This underlines the fact that what is of primary importance for artificial oxygenation is the extracorporeal blood flow passing through the membrane lung, and not its ventilation.

The effects of the oxygen supplied by the membrane lung on systemic oxygenation depend on the type of cannulation and on the possible changes induced by the artificial oxygenation on the function of the native lung. In a veno-venous circuit the artificial lung is in series with the natural lung. The improvement in arterial oxygenation, in this case, is due to the increased oxygen saturation of the blood flowing through shunt regions of the natural lung. Great improvements from oxygenation can therefore not be expected. Moreover, with this type of vascular access, as blood with high oxygen saturation reaches the pulmonary artery, the shunt fraction of the natural lung usually increases due to the loss of hypoxic vasoconstriction [16]. Despite this, the veno-venous approach with high flow, even with very high shunt in the natural lung, provides vital arterial oxygenation.

The veno-arterial approach, mostly used for cardiac support, implies the drainage of venous blood, its oxygenation and the subsequent input in the arterial tree through a cannulated artery. The improvement of systemic oxygenation with this technique is much better as compared with the veno-venous approach because the artificially oxygenated blood mixes with arterial blood and directly perfuses distal organs. Moreover, in this type of cannulation - the artificial lung being in parallel with the natural lung - there is no loss of hypoxic vaso-constriction, because no highly oxygenated blood enters the pulmonary artery. Despite the unique ability to also provide cardiac support, this type of cannulation is characterized by major disadvantages. First, an artery - typically the femoral artery - has to be cannulated with a large vascular catheter. This greatly increases the risk of ischemia of the inferior limb. Moreover, the aim of extracorporeal oxygenation (that is, to provide adequate oxygen supply to vital organs such as the brain and the heart) cannot be guaranteed through veno-arterial support if the input of oxygenated blood is performed distal to the great vessels; that is, through the femoral artery [16].

Carbon dioxide removal

The removal of CO2 is primarily a function of the flow of fresh gas. Theoretically it is possible to remove all of the metabolically produced CO2 (rate of elimination of CO2 about 200 to 250 ml/minute) from 0.5 to 1 l/minute venous blood due to its high CO2 content (1 l of venous blood at partial pressure of CO2 45 mmHg and pH 7.38, in standard conditions, contains about 500 ml CO2). In this regard, the local acidification of entering blood may further enhance CO2 removal [17]. In the artificial lung, therefore, while high extracorporeal blood flow is required and low gas flow is sufficient for oxygenation, for CO2 removal very low extracorporeal blood flow is sufficient and high gas flow is required.

The extracorporeal CO2 removal allows the lungs to be put to rest, abolishing totally or partially the need for ventilation [18]. Indeed, if the main purpose of the application of the artificial lung is to allow lung rest and a gentle ventilation of the baby lung, low extracorporeal blood flows are sufficient [19]. In general, lower blood flow is feasible with smaller endovascular catheters and is associated with lower technical difficulties and complications. The approach of arterio-venous bypass with a pumpless device allows consistent CO2 removal at the price of an arterio-venous fistula [2022]. Low-flow CO2 removal systems coupled to or uncoupled from hemo-filtration may remove 20 to 30% of the rate of metabolically produced CO2 [2326]. With artificial lungs actually available, total CO2 clearance requires a blood flow in the order of 1 to 2 l/minute. Moreover, it is conceivable and desirable that, in the near future, regional anticoagulation (for example, with sodium citrate) will be available and will therefore greatly reduce the risk for bleeding due to systemic heparin infusion [27].

The H1N1 flu pandemic

The rebirth of extracorporeal respiratory support is primarily due to its use as a rescue therapy for life-threatening hypoxemia in Australia and New Zealand during the H1N1 flu pandemic [15]. The proper choice for such a purpose was therefore a veno-venous bypass with large-bore drainage catheters to allow high blood flows. The overall survival rate in this selected population was higher than 70%. After this report and in light of results from the CESAR trial [1], an impressive number of centers started to use this technique despite some scientists having expressed some doubt on the scientific evidence of its outcome advantages. The only evidence that led to the application of ECMO was the presence of moribund, severely hypoxemic patients that did not benefit from maximal mechanical ventilatory support [2832]. Interestingly this technique was applied in Europe, the United States, South America, Canada and Asia, spreading as the H1N1 pandemic [3338]. More than 1,000 papers were published from 2009 to May 2011; however, most articles were not related to the use of ECMO in H1N1 flu but referred for other indications, such as lung hyperinflation, cardiac failure or severe respiratory failure not caused by H1N1.

Extracorporeal support is a tool to buy time, maintaining life while awaiting improvement of the underlying disease. Therefore, it is theoretically crucial to take advantage of the extracorporeal support to minimize or, even better, to abolish the possible harm caused by an injurious mechanical ventilation. Extracorporeal CO2 removal, in fact, partially or totally abolishes the need for ventilation, allowing one to apply a gentle ventilatory approach. It would therefore be interesting to know how mechanical ventilation was performed during extracorporeal support in the latest published studies. Surprisingly, however, the details on settings of mechanical ventilators are difficult to retrieve because when some mention of mechanical ventilation is made the information is limited to a general agreement with ARDS Net-work suggestions [39]. Some papers specified more details, which are still in line with lung-protective strategies aiming for a further reduction of tidal volume (for example, 3 to 5 ml/kg ideal body weight) while maintaining relative high mean airway pressure by high positive end-expiratory pressure (PEEP). In this scenario, however, we may find extreme differences [15, 36, 4042]. As an example, in several centers in Italy it was not uncommon to observe very low tidal volumes with the respiratory rate limited to 7 or 8 breaths/minute and a high mean airway pressure related to high PEEP application. On the other hand, in other units - for example at the Karolinska Institute of Stockholm - the patients are kept awake with 5 cmH2O PEEP and ventilated with pressure support of 20 to 25 cmH2O (personal communication, Dr Palmér, Section Manager of the ECMO Center, Karolinska Institute, Stockholm, Sweden). In our ICU in Milan, patients were treated initially with high PEEP, above 15 cmH2O, and low-frequency ventilation [34]. To date, however, it is impossible to claim the superiority of a given treatment of the native lung during extracorporeal respiratory support as no studies are available on the topic. This lack of studies is primarily due to the scarcity of the patient population. However, it is important to emphasize - at least with regard to H1N1 patients - that the survival rate ranged from 56 to 79% throughout the centers, independent of the applied strategy of mechanical ventilation [15, 33, 34, 36].

We may therefore ask ourselves what we learned after this impressive utilization of extracorporeal support. First, extensive use of this technique all over the world in H1N1 patients confirmed that extracorporeal support is associated with high survival rates in severe hypoxemic patients. Moreover, we learned that these moribund patients may start time-buying extracorporeal respiratory support in the hospital of origin and thereafter be safely transferred to the referral ECMO centers. This practice has been clearly documented in Scandinavia [42, 43] as well as in Italy [44].


Acute respiratory distress syndrome

After these considerations we may now discuss the actual indications for ECMO. The choice of the technique, which may vary from low-flow bypass with CO2 removal to high-flow ECMO with total oxygenation support, depends on the patient's situation and the physician's preference.

Extracorporeal assistance as a rescue therapy

If the aim is the treatment of life-threatening hypoxemia, the clear-cut indication is high-flow veno-venous ECMO. If the patient presents with severe cardiac failure, however, veno-arterial ECMO must be used. The obvious question is whether these types of treatment are associated with a better outcome.

The recently published CESAR trial provided some clues in this regard [1]. Many physicians, however, were not fully convinced by the investigators' approach [4547]. In fact, this pragmatic study really tested the differences in outcome between a specialized center with high-volume activity and single centers with low-volume activity. Despite these limitations the study strongly indicated that treatment with extracorporeal support may increase the survival rate in a selected population of patients with ARDS. We may ask ourselves why, after over 30 years, a classical, adequately powered randomized trial has not been conducted in these severely hypoxemic patients. To test a possible mortality difference of 10% between the ECMO and control arms would require enrollment of about 1,000 patients (with 90% power using a cutoff value for statistical significance of 0.05). Given that the enrollment rate of previous large randomized trials on severe ARDS [4851] was approximately 0.3 patients/unit/month and that only one-third of these patients could have met the criteria for ECMO application - that is, severe refractory hypoxemia (partial pressure of oxygen <100 mmHg despite 100% FiO2) [52] - 20 ECMO centers would take over 40 years to complete the study (the CESAR trial took about 8 years). It therefore seems to us that a classical randomized trial is not feasible.

Despite this, there seems a high likelihood that extracorporeal support has saved the lives of some extremely severe patients. ECMO seems to be indicated in this type of patient because the risks from complications of the technique seem irrelevant when almost certain death can be predicted. The question is different when severe hypoxemia is still manageable with more conventional approaches (high PEEP, high-frequency oscillatory ventilation, 100% FiO2, nitric oxide, and so forth). In these patients, the possible benefits of extracorporeal support have to be balanced with the only lethal complication of ECMO, which is intracranial hemorrhage. Unfortunately there are few data to predict with reasonable confidence the incidence of intracranial hemorrhage in adults [53]. According to the Italian ECMOnet experience, intracranial hemorrhage occurred in one patient out of 49 (personal communication, Dr Patroniti, San Gerardo Hospital, Monza, Italy). In our experience, however, the incidence was about 5% and this complication occurred both in subjects treated for hematologic malignancy and in patients with no predictable cause of increased bleeding susceptibility. Any time we consider a patient for ECMO we must therefore keep in mind this unpredictable and lethal complication.

Extracorporeal assistance to provide lung rest

If the aim of applying the artificial lung is not to assure oxygenation during hypoxemic emergency but to assure complete lung rest or to allow a protective lung strategy, CO2 removal is indicated. A technique that solely removes CO2 is applied in arterio-venous bypass [22]. With this technique the extracorporeal blood flow is low and oxygen transfer negligible, the input blood in the oxygenator being arterial and therefore already highly saturated. In our opinion, however, in ARDS patients it is safe to remove CO2 using devices that also allow the performance of blood flows up to 2 to 2.5 l/minute. In this way, if needed, not only may lung rest be provided but also oxygenation maintained, in case of natural lung function deterioration.

Extracorporeal assistance for indications other than ARDS

Increased confidence in using extracorporeal assistance led to use of the technique in different clinical conditions. Although outside the aim of the present review, the following conditions should be noted.

Bridge to lung transplant

Extracorporeal assistance has been successfully used as a bridge to lung transplant in patients with terminal chronic obstructive pulmonary disease or cystic fibrosis. Of note, there is an increased tendency to maintain those patients awake, and spontaneously breathing, without the need for intubation [54].

Lung hyperinflation

Lung hyperinflation is common during chronic obstructive pulmonary disease exacerbation or during status asthmaticus. In this condition, when noninvasive mechanical ventilation fails, extracorporeal support may be applied. The primary aim is to remove CO2, therefore reducing spontaneous ventilation and allowing progressive lung deflation [55].

Cardiac failure

There is much experience providing extracorporeal assistance during cardiogenic shock. In this condition the approach is obviously venous-arterial, providing not only respiratory but also cardiac assistance.


Recent events moved the spots of scientific interest once again on extracorporeal techniques of respiratory support. Since the first experiences with ECMO, technology has hugely evolved, making extracorporeal respiratory support safer and more cost-effective. Indeed, extracorporeal respiratory support is now an attractive strategy for the treatment of any type of respiratory failure in addition to, or even as an alternative to, mechanical ventilation.



acute respiratory distress syndrome


carbon dioxide


extracorporeal membrane oxygenation


inspired oxygen fraction


positive end-expiratory pressure.


  1. 1.

    Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D: 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: 1351-1363. 10.1016/S0140-6736(09)61069-2

    Article  PubMed  Google Scholar 

  2. 2.

    Hill JD, O'Brien TG, Murray JJ, Dontigny L, Bramson ML, Osborn JJ, Gerbode F: Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972, 286: 629-634. 10.1056/NEJM197203232861204

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Bartlett RH, Gazzaniga AB, Jefferies MR, Huxtable RF, Haiduc NJ, Fong SW: Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy. Trans Am Soc Artif Intern Organs 1976, 22: 80-93.

    CAS  PubMed  Google Scholar 

  4. 4.

    Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, Morris AH, Peirce EC, Thomas AN, Proctor HJ, Drinker PA, Pratt PC, Bagniewski A, Miller RG Jr: Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979, 242: 2193-2196. 10.1001/jama.1979.03300200023016

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Kolobow T, Gattinoni L, Tomlinson T, White D, Pierce J, Iapichino G: The carbon dioxide membrane lung (CDML): a new concept. Trans Am Soc Artif Intern Organs 1977, 23: 17-21.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Kolobow T, Gattinoni L, Tomlinson TA, Pierce JE: Control of breathing using an extracorporeal membrane lung. Anesthesiology 1977, 46: 138-141. 10.1097/00000542-197702000-00012

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Gattinoni L, Pesenti A: The concept of 'baby lung'. Intensive Care Med 2005, 31: 776-784. 10.1007/s00134-005-2627-z

    Article  PubMed  Google Scholar 

  8. 8.

    Muscedere JG, Mullen JB, Gan K, Slutsky AS: Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994, 149: 1327-1334.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Gattinoni L, Agostoni A, Pesenti A, Pelizzola A, Rossi GP, Langer M, Vesconi S, Uziel L, Fox U, Longoni F, Kolobow T, Damia G: Treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of CO 2 . Lancet 1980, 2: 292-294.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Gattinoni L, Pesenti A, Mascheroni D, Marcolin R, Fumagalli R, Rossi F, Iapichino G, Romagnoli G, Uziel L, Agostoni A: Low-frequency positivepressure ventilation with extracorporeal CO 2 removal in severe acute respiratory failure. JAMA 1986, 256: 881-886. 10.1001/jama.1986.03380070087025

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr, Weaver LK, Dean NC, Thomas F, East TD, Pace NL, Suchyta MR, Beck E, Bombino M, Sittig DF, Bohm S, Hoff mann B, Becks H, Butler S, Pearl J, Rasmusson B: Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO 2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994, 149: 295-305.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Lewandowski K, Rossaint R, Pappert D, Gerlach H, Slama KJ, Weidemann H, Frey DJ, Hoffmann O, Keske U, Falke KJ: High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med 1997, 23: 819-835. 10.1007/s001340050418

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Kolla S, Awad SS, Rich PB, Schreiner RJ, Hirschl RB, Bartlett RH: Extracorporeal life support for 100 adult patients with severe respiratory failure. Ann Surg 1997, 226: 544-564. 10.1097/00000658-199710000-00015

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  14. 14.

    Bartlett RH, Roloff DW, Custer JR, Younger JG, Hirschl RB: Extracorporeal life support: the University of Michigan experience. JAMA 2000, 283: 904-908. 10.1001/jama.283.7.904

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, Forrest P, Gattas D, Granger E, Herkes R, Jackson A, McGuinness S, Nair P, Pellegrino V, Pettila V, Plunkett B, Pye R, Torzillo P, Webb S, Wilson M, Ziegenfuss M: Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 2009, 302: 1888-1895.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Lamy M, Eberhart RC, Fallat RJ, Dietrich HP, Ratliff J, Hill JD: Effects of extracorporeal membrane oxygenation (ECMO) on pulmonary hemodynamics, gas exchange and prognose. Trans Am Soc Artif Intern Organs 1975, 21: 188-198.

    CAS  PubMed  Google Scholar 

  17. 17.

    Zanella A, Patroniti N, Isgro S, Albertini M, Costanzi M, Pirrone F, Scaravilli V, Vergnano B, Pesenti A: Blood acidification enhances carbon dioxide removal of membrane lung: an experimental study. Intensive Care Med 2009, 35: 1484-1487. 10.1007/s00134-009-1513-5

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Kolobow T, Gattinoni L, Tomlinson T, Pierce JE: An alternative to breathing. J Thorac Cardiovasc Surg 1978, 75: 261-266.

    CAS  PubMed  Google Scholar 

  19. 19.

    Brunet F, Mira JP, Dhainaut JF, Dall'ava-Santucci J: Efficacy of low-frequency positive-pressure ventilation-extracorporeal CO 2 removal. Am J Respir Crit Care Med 1995, 151: 1269-1270.

    CAS  PubMed  Google Scholar 

  20. 20.

    Ohtake S, Kawashima Y, Hirose H, Matsuda H, Nakano S, Kaku K, Okuda A: Experimental evaluation of pumpless arteriovenous ECMO with polypropylene hollow fiber membrane oxygenator for partial respiratory support. Trans Am Soc Artif Intern Organs 1983, 29: 237-241.

    CAS  PubMed  Google Scholar 

  21. 21.

    Bein T, Scherer MN, Philipp A, Weber F, Woertgen C: Pumpless extracorporeal lung assist (pECLA) in patients with acute respiratory distress syndrome and severe brain injury. J Trauma 2005, 58: 1294-1297. 10.1097/01.TA.0000173275.06947.5C

    Article  PubMed  Google Scholar 

  22. 22.

    Bein T, Weber F, Philipp A, Prasser C, Pfeifer M, Schmid FX, Butz B, Birnbaum D, Taeger K, Schlitt HJ: A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia. Crit Care Med 2006, 34: 1372-1377. 10.1097/01.CCM.0000215111.85483.BD

    Article  PubMed  Google Scholar 

  23. 23.

    Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, Faggiano C, Quintel M, Gattinoni L, Ranieri VM: Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology 2009, 111: 826-835. 10.1097/ALN.0b013e3181b764d2

    Article  PubMed  Google Scholar 

  24. 24.

    Livigni S, Maio M, Ferretti E, Longobardo A, Potenza R, Rivalta L, Selvaggi P, Vergano M, Bertolini G: Efficacy and safety of a low-flow veno-venous carbon dioxide removal device: results of an experimental study in adult sheep. Crit Care 2006, 10: R151. 10.1186/cc5082

    PubMed Central  Article  PubMed  Google Scholar 

  25. 25.

    Ruberto F, Pugliese F, D'Alio A, Perrella S, D'Auria B, Ianni S, Anile M, Venuta F, Coloni GF, Pietropaoli P: Extracorporeal removal CO 2 using a venovenous, low-flow system (Decapsmart) in a lung transplanted patient: a case report. Transplant Proc 2009, 41: 1412-1414. 10.1016/j.transproceed.2009.03.048

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Batchinsky AI, Jordan BS, Regn D, Necsoiu C, Federspiel WJ, Morris MJ, Cancio LC: Respiratory dialysis: reduction in dependence on mechanical ventilation by venovenous extracorporeal CO 2 removal. Crit Care Med 2011, 39: 1382-1387. 10.1097/CCM.0b013e31820eda45

    Article  PubMed  Google Scholar 

  27. 27.

    Cardenas VJ Jr, Miller L, Lynch JE, Anderson MJ, Zwischenberger JB: Percutaneous venovenous CO 2 removal with regional anticoagulation in an ovine model. ASAIO J 2006, 52: 467-470. 10.1097/01.mat.0000227743.07743.5d

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Mitchell MD, Mikkelsen ME, Umscheid CA, Lee I, Fuchs BD, Halpern SD: A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic. Crit Care Med 2010, 38: 1398-1404. 10.1097/CCM.0b013e3181de45db

    PubMed Central  Article  PubMed  Google Scholar 

  29. 29.

    Park PK, Dalton HJ, Bartlett RH: Point: Efficacy of extracorporeal membrane oxygenation in 2009 influenza A(H1N1): sufficient evidence? Chest 2010, 138: 776-778. 10.1378/chest.10-1791

    Article  PubMed  Google Scholar 

  30. 30.

    Morris AH, Hirshberg E, Miller RR, Statler KD, Hite RD: Counterpoint: Efficacy of extracorporeal membrane oxygenation in 2009 influenza A(H1N1): sufficient evidence? Chest 2010, 138: 778-781. 10.1378/chest.10-1792

    Article  PubMed  Google Scholar 

  31. 31.

    MacLaren G: Evidence and experience in extracorporeal membrane oxygenation. Chest 2011, 139: 965-966.

    Article  PubMed  Google Scholar 

  32. 32.

    Hubmayr RD, Farmer JC: Should we 'rescue' patients with 2009 influenza A(H1N1) and lung injury from conventional mechanical ventilation? Chest 2010, 137: 745-747. 10.1378/chest.09-2915

    Article  PubMed  Google Scholar 

  33. 33.

    Roch A, Lepaul-Ercole R, Grisoli D, Bessereau J, Brissy O, Castanier M, Dizier S, Forel JM, Guervilly C, Gariboldi V, Collart F, Michelet P, Perrin G, Charrel R, Papazian L: Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study. Intensive Care Med 2010, 36: 1899-1905. 10.1007/s00134-010-2021-3

    Article  PubMed  Google Scholar 

  34. 34.

    Norfolk SG, Hollingsworth CL, Wolfe CR, Govert JA, Que LG, Cheifetz IM, Hollingsworth JW: Rescue therapy in adult and pediatric patients with pH1N1 influenza infection: a tertiary center intensive care unit experience from April to October 2009. Crit Care Med 2010, 38: 2103-2107. 10.1097/CCM.0b013e3181f268f1

    PubMed Central  Article  PubMed  Google Scholar 

  35. 35.

    Ugarte S, Arancibia F, Soto R: Influenza A pandemics: clinical and organizational aspects: the experience in Chile. Crit Care Med 2010, 38: e133-e137.

    Article  PubMed  Google Scholar 

  36. 36.

    Freed DH, Henzler D, White CW, Fowler R, Zarychanski R, Hutchison J, Arora RC, Manji RA, Legare JF, Drews T, Veroukis S, Kesselman M, Guerguerian AM, Kumar A: Extracorporeal lung support for patients who had severe respiratory failure secondary to influenza A (H1N1) 2009 infection in Canada. Can J Anaesth 2010, 57: 240-247. 10.1007/s12630-009-9253-0

    Article  PubMed  Google Scholar 

  37. 37.

    Kao TM, Wu UI, Chen YC: Rapid diagnostic tests and severity of illness in pandemic (H1N1) 2009, Taiwan. Emerg Infect Dis 2010, 16: 1181-1183.

    PubMed Central  Article  PubMed  Google Scholar 

  38. 38.

    Liong T, Lee KL, Poon YS, Lam SY, Chan CP, Yue CS, Chu CM, Yuen KY, Law KI: The first novel influenza A (H1N1) fatality despite antiviral treatment and extracorporeal membrane oxygenation in Hong Kong. Hong Kong Med J 2009, 15: 381-384.

    CAS  PubMed  Google Scholar 

  39. 39.

    Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308.

  40. 40.

    Cianchi G, Bonizzoli M, Pasquini A, Bonacchi M, Zagli G, Ciapetti M, Sani G, Batacchi S, Biondi S, Bernardo P, Lazzeri C, Giovannini V, Azzi A, Abbate R, Gensini G, Peris A: Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center. BMC Pulm Med 2011, 11: 2. 10.1186/1471-2466-11-2

    PubMed Central  Article  PubMed  Google Scholar 

  41. 41.

    Dominguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, de la TA, Poblano-Morales M, Baltazar-Torres JA, Bautista E, Martinez A, Martinez MA, Rivero E, Valdez R, Ruiz-Palacios G, Hernandez M, Stewart TE, Fowler RA: Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 2009, 302: 1880-1887. 10.1001/jama.2009.1536

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Holzgraefe B, Broome M, Kalzen H, Konrad D, Palmer K, Frenckner B: Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure. Minerva Anestesiol 2010, 76: 1043-1051.

    CAS  PubMed  Google Scholar 

  43. 43.

    Linden V, Palmer K, Reinhard J, Westman R, Ehren H, Granholm T, Frenckner B: Inter-hospital transportation of patients with severe acute respiratory failure on extracorporeal membrane oxygenation - national and international experience. Intensive Care Med 2001, 27: 1643-1648. 10.1007/s001340101060

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Patroniti N, Zangrillo A, Pappalardo F, Peris A, Cianchi G, Braschi A, Iotti GA, Arcadipane A, Panarello G, Ranieri VM, Terragni P, Antonelli M, Gattinoni L, Oleari F, Pesenti A: The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med 2011, 37: 1447-1457. 10.1007/s00134-011-2301-6

    Article  PubMed  Google Scholar 

  45. 45.

    Zwischenberger JB, Lynch JE: Will CESAR answer the adult ECMO debate? Lancet 2009, 374: 1307-1308. 10.1016/S0140-6736(09)61630-5

    Article  PubMed  Google Scholar 

  46. 46.

    Wallace DJ, Milbrandt EB, Boujoukos A: Ave, CESAR, morituri te salutant! (Hail, CESAR, those who are about to die salute you!). Crit Care 2010, 14: 308. 10.1186/cc8946

    PubMed Central  Article  PubMed  Google Scholar 

  47. 47.

    Brindley PG, Cave D, Lequier L: BEST evidence in critical care medicine. Extracorporeal membrane oxygenation (ECMO) in severe adult respiratory distress syndrome. Can J Anaesth 2010, 57: 273-275. 10.1007/s12630-009-9242-3

    Article  PubMed  Google Scholar 

  48. 48.

    Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L, Latini R: Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001, 345: 568-573. 10.1056/NEJMoa010043

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Guerin C, Gaillard S, Lemasson S, Ayzac L, Girard R, Beuret P, Palmier B, Le QV, Sirodot M, Rosselli S, Cadiergue V, Sainty JM, Barbe P, Combourieu E, Debatty D, Rouffineau J, Ezingeard E, Millet O, Guelon D, Rodriguez L, Martin O, Renault A, Sibille JP, Kaidomar M: Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004, 292: 2379-2387. 10.1001/jama.292.19.2379

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Mancebo J, Fernandez R, Blanch L, Rialp G, Gordo F, Ferrer M, Rodriguez F, Garro P, Ricart P, Vallverdu I, Gich I, Castano J, Saura P, Dominguez G, Bonet A, Albert RK: A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2006, 173: 1233-1239. 10.1164/rccm.200503-353OC

    Article  PubMed  Google Scholar 

  51. 51.

    Taccone P, Pesenti A, Latini R, Polli F, Vagginelli F, Mietto C, Caspani L, Raimondi F, Bordone G, Iapichino G, Mancebo J, Guerin C, Ayzac L, Blanch L, Fumagalli R, Tognoni G, Gattinoni L: Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA 2009, 302: 1977-1984. 10.1001/jama.2009.1614

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall JR, Morris A, Spragg R: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149: 818-824.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Kasirajan V, Smedira NG, McCarthy JF, Casselman F, Boparai N, McCarthy PM: Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 1999, 15: 508-514. 10.1016/S1010-7940(99)00061-5

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Olsson KM, Simon A, Strueber M, Hadem J, Wiesner O, Gottlieb J, Fuehner T, Fischer S, Warnecke G, Kuhn C, Haverich A, Welte T, Hoeper MM: Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation. Am J Transplant 2010, 10: 2173-2178. 10.1111/j.1600-6143.2010.03192.x

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Crotti S, Lissoni A, Tubiolo D, Azzari S, Tarsia P, Caspani ML, Gattinoni L: Artificial lung as an alternative to mechanical ventilation in COPD exacerbation. Eur Resp J 2012, in press.

    Google Scholar 

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Correspondence to Luciano Gattinoni.

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Gattinoni, L., Carlesso, E. & Langer, T. Clinical review: Extracorporeal membrane oxygenation. Crit Care 15, 243 (2011).

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  • Acute Respiratory Distress Syndrome
  • Chronic Obstructive Pulmonary Disease Exacerbation
  • Severe Respiratory Failure
  • Artificial Lung
  • Lung Hyperinflation