Annales Franc¸aises d’Anesthe´sie et de Re´animation 33 (2014) 492–494
Monothematic meeting of Sfar
Extracorporeal membrane oxygenation in adults for severe acute respiratory failure§,§§ Oxyge´nation extracorporelle lors d’un syndrome de de´tresse respiratoire aigue¨ H. Roze´ a,*,b, B. Repusseau a,b, A. Ouattara a,b a Service d’anesthe´sie-re´animation II, unite´ de re´animation polyvalente de la Maison du Haut-Le´veˆque, hoˆpital Haut-Le´veˆque, CHU de Bordeaux, avenue Magellan, 33600 Pessac, France b Inserm, adaptation cardiovasculaire a` l’ische´mie, U1034, universite´ Bordeaux, 33600 Pessac, France
A R T I C L E I N F O
A B S T R A C T
Available online 13 August 2014
The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS. ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
Keywords: Refractory hypoxemia ECMO ARDS
R E´ S U M E´
Mots cle´s : Hypoxe´mie re´fractaire ECMO SDRA
L’objectif de cette revue est d’examiner les indications des membranes d’oxyge´nation extracorporelle (ECMO) lors d’un syndrome de de´tresse respiratoire aigue¨ (SDRA). Le recours a` cette technique d’oxyge´nation a augmente´ de manie`re significative a` travers le monde depuis la pande´mie grippale H1N1. Le but de l’ECMO est de maintenir un niveau acceptable d’oxyge´nation, ainsi que de controˆler l’acidose respiratoire sous ventilation protectrice. Cet enthousiasme pour l’ECMO ne doit pas faire ne´gliger les complications potentielles associe´es a` la technique. Avant d’e´largir le recours a` l’ECMO, de nouvelles e´tudes devront tester l’efficacite´ d’une utilisation pre´coce ou d’une e´puration du CO2 en comple´ment ou a` la place de la ventilation me´canique lors d’un SDRA se´ve`re. ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
1. Introduction Extracorporeal membrane oxygenation (ECMO) is proposed for patients with severe-acute respiratory distress syndrome (ARDS), § Article presented at Monothematic meeting of Sfar (Socie´te´ franc¸aise d’anesthe´sie et de reanimation): ‘‘Perioperative ventilation’’, Paris, May 21, 2014. §§ This article is published under the responsibility of the Scientific Committee of the ‘‘Journe´e Monothe´matique 2014’’ de la Sfar. The editorial board of the Annales franc¸aises d’anesthe´sie et de re´animation was not involved in the conception and validation of its content. * Corresponding author. E-mail address: [email protected] (H. Roze´).
which may be defined as not being effectively and/or safely treated by current clinical types of mechanical ventilation. ECMO offers artificial temporary and respiratory support that should be maintained until the patient recovers from severe respiratory failure. It is a tool to buy time and to allow recovery from the underlying disease. The first successful report on ECMO for respiratory failure was described in 1972 [1]. This new technique led to an unsuccessful randomized study using veno-arterial ECMO in ARDS [2]. At that time, ECMO technology was primitive and knowledge about ventilation-induced lung injury was limited. Despite this lack of evidence, few centres continued to provide ECMO in selected
http://dx.doi.org/10.1016/j.annfar.2014.07.008 0750-7658/ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
H. Roze´ et al. / Annales Franc¸aises d’Anesthe´sie et de Re´animation 33 (2014) 492–494
patients [3]. Renewed interest arose with encouraging results from the randomized CESAR trial, which demonstrated improved outcomes from referral to an ECMO-centre for ARDS [4]. ECMO was proposed in 2009 as a rescue therapy for severe ARDS during the H1N1 influenza pandemic, and had good outcomes [5–8]. 2. Indications for ECMO The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. It has been used in various other severe conditions apart from ARDS, such as primary graft dysfunction after lung transplantation [9], lung trauma [10], and pulmonary embolism [11]. The decision to initiate ECMO requires several criteria that must be discussed: these include assessment of arterial blood gases, optimization of ARDS treatment, multiorgan failure, comorbidities, a prognosis before acute respiratory failure, duration of mechanical ventilation, treatment of aetiology of ARDS. 3. ECMO and oxygenation The actual main reason to initiate ECMO is severe hypoxemia, so the question is, what is severe hypoxemia in an ARDS patient? Human tolerance to chronic severe hypoxia has been studied at high altitudes. Severe oxygen deprivation at extreme altitudes can only be tolerated because there is enormously increased ventilation, which protects the alveolar PO2 against the reduced inspiration [12]. Nevertheless, the mean values of PaO2 and PaCO2 in four subjects at 8400 m were 24.6 mmHg (3.28 kPa) and 13.3 mmHg (1.77 kPa), respectively [13]. The climbers’ mean arterial saturation of haemoglobin was 50% with a mean arterial oxygen content of 150 mL/L. Alveolar hyperventilation results in very low arterial PaCO2, which causes severe respiratory alkalosis. This has the advantage of increasing the oxygen-affinity of haemoglobin and accelerating oxygen loading by the pulmonary capillaries under diffusionlimited conditions. These climbers reached the summit of Mount Everest after 60 days to an elevation of > 2500 m: this time-period allowed haemoglobin to increase up to 20 g/dL. The level of arterial oxygenation in these climbers at 8400 m was equivalent to an intensive care patient with a PaO2 of 60 mmHg, a SaO2 of 90% and Hg of 7 g/dL. Of course, a comparison cannot be made between expert climbers and severe intensive-care patients regarding comorbidities, ARDS and other organ dysfunctions. However, this highlights the fact that the highest level of acceptable hypoxemia in ARDS patients is still unknown. Other measurements, such as low venous oxygen saturation and hyper-lactatemia are probably helpful when a decision of whether or not to conduct ECMO is made. However, mean arterial lactatemia was 2.9 mmol/L prior to ECMO in the French ECMO H1N1 study [7]. Numerous patients had normal levels of lactatemia; this suggests that anaerobic metabolism was not contributing substantially to energy production at these levels of hypoxemia in sedated patient. An alternative or additional explanation is the possibility of increased lactate use as an energy source [14]. It is possible that hypoxemia in severe ARDS is responsible for long-term cognitive and psychiatric morbidity [15]. There is also impairment of central nervous system function at high altitudes, which persists following a return to sea level. It is possible that climbers who ventilate most at high altitudes have the most impairment to the central nervous system, presumably because of the more severe cerebral vasoconstriction. Before considering ECMO, it is crucial to ensure that ventilator and non-ventilator treatments for ARDS have been optimized, as was conducted during the H1N1 influenza pandemic in 2009
493
[16,17]. Moreover, Grasso et al. [18] demonstrated that the use of transpulmonary pressure, as opposed to airway pressure, could offer the opportunity to safely increase positive end-expiratory pressure (PEEP) and improve oxygenation, thereby avoiding unnecessary ECMO. The French Re´seau europe´en de recherche en ventilation artificielle (REVA) group proposed that the indications for ECMO in cases of refractory hypoxemia were defined by a PaO2/FiO2 of < 50 mmHg, despite a high PEEP (10–20 cmH2O) and high FiO2 (> 80%) ventilation. Refractory hypoxemia must persist for a few hours as this situation can improve rapidly within 12 hours and, thus, ECMO could be avoided. The REVA group also proposed ECMO in cases of ARDS that had a low compliance, if plateau pressure was > 35 cmH2O, and despite a reduction in tidal volume (VT) of 4 mL/kg of predicted body weight. Adjunctive therapies for ARDS, including the prone position, were highly recommended [19]. Severe comorbidities and multiple-organ failure (SOFA score > 15) were considered as contraindications for the use of ECMO for this group. The Extracorporeal Life-Support Organization (ELSO) proposes that ECMO should be considered in hypoxic respiratory failure when the risk of mortality is 50%. Refractory hypoxemia in this group is defined by a PaO2/FiO2 of < 150 mmHg with FiO2 > 90%, and/or a Murray score of 2–3. The ELSO considered that ECMO is indicated when the risk of mortality exceeds 80%, that is when PaO2/FiO2 is < 80, when FiO2 is > 90% and the Murray score is 3–4. ELSO’s consideration regarding ECMO in ARDS is different from the REVA group. In the Berlin definition of ARDS, ECMO is proposed as a rescue therapy for severe hypoxemia when PaO2/FiO2 is < 50 [20]. ECMO is considered when plateau-pressure exceeds 32 cmH2O, when FiO2 approaches 100%, and arterial oxygen saturation falls below 90%, and/or pH drops below 7.2. The initiation of ECMO is easier when the risks from complications of the technique seem irrelevant, i.e. when almost certain death can be predicted. The question is different when severe hypoxemia is still manageable with a high PEEP, a prone position, 100% FiO2 and nitric oxide. The absolute risk of a plateau pressure > 30–32 cmH2O, compared to all the risk factors associated with ECMO, remains unknown. Similarly, we do not know how to balance the risk of injury from over-distension of the lungs versus the risk of lung underrecruitment in patients with severe hypoxemic ARDS [21]. Indeed, once the patients are on ECMO, tidal volume is significantly reduced by almost half [22], which leads to significant reduction in plateau pressure [7] and derecruitment as PEEP remains stable [23]. It can take a long time for some patients to re-open their lungs: Pham et al. found a significant increase in the length of mechanical ventilation after matching ECMO patients with similar non-ECMO patients according to a propensity score [7]. Lastly, the possible benefits of extracorporeal support have to be balanced by the only lethal complication of ECMO, which is intracranial haemorrhage: if this complication occurs, then we will have to ask ourselves whether ECMO was absolutely necessary or not [24]. There is no absolute contraindication for ECMO: all cases have to be discussed and, probably, indications and the limits will change according to future results from studies on the indications and outcomes of ECMO for ARDS. For example, the PRESERVE score has been proposed to help in deciding whether to initiate ECMO [22]. This score was based on 144 patients requiring ECMO for ARDS in three French ECMO centres. Age, immunosuppression, SOFA score > 12, mechanical ventilation for > 6 days prior to ECMO, PEEP of < 10 cmH2O, plateau pressure of > 30 cmH2O and noprone position were associated with a poor outcome. In this study, the patients had severe ARDS with a PaO2/FiO2 of 53, PaCO2 of 63 mmHg and a plateau pressure of 32 cmH2O. A prone position and nitric oxide were both used in more than 80% of cases. The mortality rate in this study, regarding H1N1 patients, was low at
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17% compared to other studies [5,7]. This might be because of patient selection but also because these centres had been using ECMO for years before the H1N1 influenza pandemic [6]. 4. ECMO and CO2 removal ECMO can also be proposed as a tool to reduce ventilatorinduced lung injury in ARDS by reducing VT to an extremely low value. A VT of 6 mL/kg of predicted body weight (PBW) and a maximum plateau pressure of 30 cmH2O represent the gold standards for mechanical ventilation in ARDS patients [25]. However, recent studies with computed tomography scans of the chest show that about one-third of patients with severe ARDS, although ventilated with a tidal volume of 6 mL/kg of PBW and a limited plateau pressure of 30 cmH2O, had evidence of alveolar over-distension [26,27]. If hyperinflation plays a role in the pathogenesis of ventilator-induced lung injury, then one may wonder whether a lower VT of 6 mL/kg PBW is low enough [28]. An experimental study demonstrated a reduction of alveolar epithelial injury and pulmonary oedema when VT was reduced from 6 to 3 mL/kg in rats [29]. Such a reduction in VT requires extracorporeal removal of CO2 in order to limit respiratory acidosis. In this situation, extracorporeal blood flow is low: around 1 L/min [30]. Recent clinical studies have found interesting results regarding the feasibility and safety of a super-protective ventilator strategy using extracorporeal removal of CO2 in ARDS [31,32]. Larger studies are required to assess the effects on mortality. 5. Conclusion The use of ECMO for ARDS remains controversial with conflicting data regarding its impact on survival compared to conventional treatments. The goal of ECMO is to maintain safe levels of oxygenation and control respiratory acidosis under protective ventilation. Its role as a salvage therapy is accepted, but it could also be proposed to treat any type of respiratory failure in addition to mechanical ventilation. Further studies are required before such practices are adopted. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Hill JD, O’Brien TG, Murray JJ, Dontigny L, Bramson ML, Osborn JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972;286:629–34. [2] 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. [3] Bartlett RH, Roloff DW, Custer JR, Younger JG, Hirschl RB. Extracorporeal life support: the University of Michigan experience. JAMA 2000;283:904–8. [4] 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. [5] Australia, New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators, Davies A, Jones D, Bailey M, Beca J, Bellomo R, et al. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA 2009;302:1888–95. [6] Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011;306:1659–68.
[7] Pham T, Combes A, Roze´ H, Chevret S, Mercat A, Roch A, et al. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2013;187:276–85. [8] 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. [9] Hartwig MG, Appel 3rd JZ, Cantu 3rd E, Simsir S, Lin SS, Hsieh C-C, et al. Improved results treating lung allograft failure with venovenous extracorporeal membrane oxygenation. Ann Thorac Surg 2005;80:1872–9. [10] Cordell-Smith JA, Roberts N, Peek GJ, Firmin RK. Traumatic lung injury treated by extracorporeal membrane oxygenation (ECMO). Injury 2006;37:29–32. [11] Maggio P, Hemmila M, Haft J, Bartlett R. Extracorporeal life support for massive pulmonary embolism. J Trauma 2007;62:570–6. [12] West JB. Tolerance to severe hypoxia: lessons from Mt Everest. Acta Anaesthesiol Scand Suppl 1990;94:18–23. [13] Grocott MPW, Martin DS, Levett DZH, McMorrow R, Windsor J, Montgomery HE, et al. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009;360:140–9. [14] Cerretelli P, Samaja M. Acid-base balance at exercise in normoxia and in chronic hypoxia. Revisiting the ‘‘lactate paradox’’. Eur J Appl Physiol 2003;90:431–48. [15] Mikkelsen ME, Christie JD, Lanken PN, Biester RC, Thompson BT, Bellamy SL, et al. The adult respiratory distress syndrome cognitive outcomes study: longterm neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med 2012;185:1307–15. [16] Napolitano LM, Park PK, Raghavendran K, Bartlett RH. Nonventilatory strategies for patients with life-threatening 2009 H1N1 influenza and severe respiratory failure. Crit Care Med 2010;38:e74–90. [17] Ramsey CD, Funk D, Miller 3rd RR, Kumar A. Ventilator management for hypoxemic respiratory failure attributable to H1N1 novel swine origin influenza virus. Crit Care Med 2010;38:e58–65. [18] Grasso S, Terragni P, Birocco A, Urbino R, Del Sorbo L, Filippini C, et al. ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure. Intensive Care Med 2012;38:395–403. [19] Gue´rin C, Reignier J, Richard J-C, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159–68. [20] Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012;38:1573–82. [21] Hubmayr RD, Farmer JC. Should we ‘‘rescue’’ patients with 2009 influenza A(H1N1) and lung injury from conventional mechanical ventilation? Chest 2010;137:745–7. [22] Schmidt M, Zogheib E, Roze´ H, Repesse X, Lebreton G, Luyt C-E, et al. The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intensive Care Med 2013;39:1704–13. [23] Richard JC, Maggiore SM, Jonson B, Mancebo J, Lemaire F, Brochard L. Influence of tidal volume on alveolar recruitment. Respective role of PEEP and a recruitment maneuver. Am J Respir Crit Care Med 2001;163:1609–13. [24] Australia, New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators, Davies A, Jones D, Bailey M, Beca J, Bellomo R, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA 2009;302:1888–95. [25] The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–8. [26] Hager DN, Krishnan JA, Hayden DL, Brower RG, ARDS Clinical Trials Network. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 2005;172:1241–5. [27] Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007;175:160–6. [28] Slutsky AS. Lung injury caused by mechanical ventilation. Chest 1999;116:9S– 15S. [29] Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA. Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 2002;165:242–9. [30] Terragni P, Maiolo G, Ranieri VM. Role and potentials of low-flow CO(2) removal system in mechanical ventilation. Curr Opin Crit Care 2012;18:93–8. [31] Bein T, Weber-Carstens S, Goldmann A, Mu¨ller T, Staudinger T, Brederlau J, et al. Lower tidal volume strategy ( 3 mL/kg) combined with extracorporeal CO2 removal versus ‘‘conventional’’ protective ventilation (6 mL/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med 2013;39:847–56. [32] Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, et al. Tidal volume lower than 6 mL/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology 2009;111:826–35.
Monothematic meeting of Sfar
Extracorporeal membrane oxygenation in adults for severe acute respiratory failure§,§§ Oxyge´nation extracorporelle lors d’un syndrome de de´tresse respiratoire aigue¨ H. Roze´ a,*,b, B. Repusseau a,b, A. Ouattara a,b a Service d’anesthe´sie-re´animation II, unite´ de re´animation polyvalente de la Maison du Haut-Le´veˆque, hoˆpital Haut-Le´veˆque, CHU de Bordeaux, avenue Magellan, 33600 Pessac, France b Inserm, adaptation cardiovasculaire a` l’ische´mie, U1034, universite´ Bordeaux, 33600 Pessac, France
A R T I C L E I N F O
A B S T R A C T
Available online 13 August 2014
The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS. ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
Keywords: Refractory hypoxemia ECMO ARDS
R E´ S U M E´
Mots cle´s : Hypoxe´mie re´fractaire ECMO SDRA
L’objectif de cette revue est d’examiner les indications des membranes d’oxyge´nation extracorporelle (ECMO) lors d’un syndrome de de´tresse respiratoire aigue¨ (SDRA). Le recours a` cette technique d’oxyge´nation a augmente´ de manie`re significative a` travers le monde depuis la pande´mie grippale H1N1. Le but de l’ECMO est de maintenir un niveau acceptable d’oxyge´nation, ainsi que de controˆler l’acidose respiratoire sous ventilation protectrice. Cet enthousiasme pour l’ECMO ne doit pas faire ne´gliger les complications potentielles associe´es a` la technique. Avant d’e´largir le recours a` l’ECMO, de nouvelles e´tudes devront tester l’efficacite´ d’une utilisation pre´coce ou d’une e´puration du CO2 en comple´ment ou a` la place de la ventilation me´canique lors d’un SDRA se´ve`re. ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Publie´ par Elsevier Masson SAS. Tous droits re´serve´s.
1. Introduction Extracorporeal membrane oxygenation (ECMO) is proposed for patients with severe-acute respiratory distress syndrome (ARDS), § Article presented at Monothematic meeting of Sfar (Socie´te´ franc¸aise d’anesthe´sie et de reanimation): ‘‘Perioperative ventilation’’, Paris, May 21, 2014. §§ This article is published under the responsibility of the Scientific Committee of the ‘‘Journe´e Monothe´matique 2014’’ de la Sfar. The editorial board of the Annales franc¸aises d’anesthe´sie et de re´animation was not involved in the conception and validation of its content. * Corresponding author. E-mail address: [email protected] (H. Roze´).
which may be defined as not being effectively and/or safely treated by current clinical types of mechanical ventilation. ECMO offers artificial temporary and respiratory support that should be maintained until the patient recovers from severe respiratory failure. It is a tool to buy time and to allow recovery from the underlying disease. The first successful report on ECMO for respiratory failure was described in 1972 [1]. This new technique led to an unsuccessful randomized study using veno-arterial ECMO in ARDS [2]. At that time, ECMO technology was primitive and knowledge about ventilation-induced lung injury was limited. Despite this lack of evidence, few centres continued to provide ECMO in selected
http://dx.doi.org/10.1016/j.annfar.2014.07.008 0750-7658/ß 2014 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
H. Roze´ et al. / Annales Franc¸aises d’Anesthe´sie et de Re´animation 33 (2014) 492–494
patients [3]. Renewed interest arose with encouraging results from the randomized CESAR trial, which demonstrated improved outcomes from referral to an ECMO-centre for ARDS [4]. ECMO was proposed in 2009 as a rescue therapy for severe ARDS during the H1N1 influenza pandemic, and had good outcomes [5–8]. 2. Indications for ECMO The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. It has been used in various other severe conditions apart from ARDS, such as primary graft dysfunction after lung transplantation [9], lung trauma [10], and pulmonary embolism [11]. The decision to initiate ECMO requires several criteria that must be discussed: these include assessment of arterial blood gases, optimization of ARDS treatment, multiorgan failure, comorbidities, a prognosis before acute respiratory failure, duration of mechanical ventilation, treatment of aetiology of ARDS. 3. ECMO and oxygenation The actual main reason to initiate ECMO is severe hypoxemia, so the question is, what is severe hypoxemia in an ARDS patient? Human tolerance to chronic severe hypoxia has been studied at high altitudes. Severe oxygen deprivation at extreme altitudes can only be tolerated because there is enormously increased ventilation, which protects the alveolar PO2 against the reduced inspiration [12]. Nevertheless, the mean values of PaO2 and PaCO2 in four subjects at 8400 m were 24.6 mmHg (3.28 kPa) and 13.3 mmHg (1.77 kPa), respectively [13]. The climbers’ mean arterial saturation of haemoglobin was 50% with a mean arterial oxygen content of 150 mL/L. Alveolar hyperventilation results in very low arterial PaCO2, which causes severe respiratory alkalosis. This has the advantage of increasing the oxygen-affinity of haemoglobin and accelerating oxygen loading by the pulmonary capillaries under diffusionlimited conditions. These climbers reached the summit of Mount Everest after 60 days to an elevation of > 2500 m: this time-period allowed haemoglobin to increase up to 20 g/dL. The level of arterial oxygenation in these climbers at 8400 m was equivalent to an intensive care patient with a PaO2 of 60 mmHg, a SaO2 of 90% and Hg of 7 g/dL. Of course, a comparison cannot be made between expert climbers and severe intensive-care patients regarding comorbidities, ARDS and other organ dysfunctions. However, this highlights the fact that the highest level of acceptable hypoxemia in ARDS patients is still unknown. Other measurements, such as low venous oxygen saturation and hyper-lactatemia are probably helpful when a decision of whether or not to conduct ECMO is made. However, mean arterial lactatemia was 2.9 mmol/L prior to ECMO in the French ECMO H1N1 study [7]. Numerous patients had normal levels of lactatemia; this suggests that anaerobic metabolism was not contributing substantially to energy production at these levels of hypoxemia in sedated patient. An alternative or additional explanation is the possibility of increased lactate use as an energy source [14]. It is possible that hypoxemia in severe ARDS is responsible for long-term cognitive and psychiatric morbidity [15]. There is also impairment of central nervous system function at high altitudes, which persists following a return to sea level. It is possible that climbers who ventilate most at high altitudes have the most impairment to the central nervous system, presumably because of the more severe cerebral vasoconstriction. Before considering ECMO, it is crucial to ensure that ventilator and non-ventilator treatments for ARDS have been optimized, as was conducted during the H1N1 influenza pandemic in 2009
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[16,17]. Moreover, Grasso et al. [18] demonstrated that the use of transpulmonary pressure, as opposed to airway pressure, could offer the opportunity to safely increase positive end-expiratory pressure (PEEP) and improve oxygenation, thereby avoiding unnecessary ECMO. The French Re´seau europe´en de recherche en ventilation artificielle (REVA) group proposed that the indications for ECMO in cases of refractory hypoxemia were defined by a PaO2/FiO2 of < 50 mmHg, despite a high PEEP (10–20 cmH2O) and high FiO2 (> 80%) ventilation. Refractory hypoxemia must persist for a few hours as this situation can improve rapidly within 12 hours and, thus, ECMO could be avoided. The REVA group also proposed ECMO in cases of ARDS that had a low compliance, if plateau pressure was > 35 cmH2O, and despite a reduction in tidal volume (VT) of 4 mL/kg of predicted body weight. Adjunctive therapies for ARDS, including the prone position, were highly recommended [19]. Severe comorbidities and multiple-organ failure (SOFA score > 15) were considered as contraindications for the use of ECMO for this group. The Extracorporeal Life-Support Organization (ELSO) proposes that ECMO should be considered in hypoxic respiratory failure when the risk of mortality is 50%. Refractory hypoxemia in this group is defined by a PaO2/FiO2 of < 150 mmHg with FiO2 > 90%, and/or a Murray score of 2–3. The ELSO considered that ECMO is indicated when the risk of mortality exceeds 80%, that is when PaO2/FiO2 is < 80, when FiO2 is > 90% and the Murray score is 3–4. ELSO’s consideration regarding ECMO in ARDS is different from the REVA group. In the Berlin definition of ARDS, ECMO is proposed as a rescue therapy for severe hypoxemia when PaO2/FiO2 is < 50 [20]. ECMO is considered when plateau-pressure exceeds 32 cmH2O, when FiO2 approaches 100%, and arterial oxygen saturation falls below 90%, and/or pH drops below 7.2. The initiation of ECMO is easier when the risks from complications of the technique seem irrelevant, i.e. when almost certain death can be predicted. The question is different when severe hypoxemia is still manageable with a high PEEP, a prone position, 100% FiO2 and nitric oxide. The absolute risk of a plateau pressure > 30–32 cmH2O, compared to all the risk factors associated with ECMO, remains unknown. Similarly, we do not know how to balance the risk of injury from over-distension of the lungs versus the risk of lung underrecruitment in patients with severe hypoxemic ARDS [21]. Indeed, once the patients are on ECMO, tidal volume is significantly reduced by almost half [22], which leads to significant reduction in plateau pressure [7] and derecruitment as PEEP remains stable [23]. It can take a long time for some patients to re-open their lungs: Pham et al. found a significant increase in the length of mechanical ventilation after matching ECMO patients with similar non-ECMO patients according to a propensity score [7]. Lastly, the possible benefits of extracorporeal support have to be balanced by the only lethal complication of ECMO, which is intracranial haemorrhage: if this complication occurs, then we will have to ask ourselves whether ECMO was absolutely necessary or not [24]. There is no absolute contraindication for ECMO: all cases have to be discussed and, probably, indications and the limits will change according to future results from studies on the indications and outcomes of ECMO for ARDS. For example, the PRESERVE score has been proposed to help in deciding whether to initiate ECMO [22]. This score was based on 144 patients requiring ECMO for ARDS in three French ECMO centres. Age, immunosuppression, SOFA score > 12, mechanical ventilation for > 6 days prior to ECMO, PEEP of < 10 cmH2O, plateau pressure of > 30 cmH2O and noprone position were associated with a poor outcome. In this study, the patients had severe ARDS with a PaO2/FiO2 of 53, PaCO2 of 63 mmHg and a plateau pressure of 32 cmH2O. A prone position and nitric oxide were both used in more than 80% of cases. The mortality rate in this study, regarding H1N1 patients, was low at
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17% compared to other studies [5,7]. This might be because of patient selection but also because these centres had been using ECMO for years before the H1N1 influenza pandemic [6]. 4. ECMO and CO2 removal ECMO can also be proposed as a tool to reduce ventilatorinduced lung injury in ARDS by reducing VT to an extremely low value. A VT of 6 mL/kg of predicted body weight (PBW) and a maximum plateau pressure of 30 cmH2O represent the gold standards for mechanical ventilation in ARDS patients [25]. However, recent studies with computed tomography scans of the chest show that about one-third of patients with severe ARDS, although ventilated with a tidal volume of 6 mL/kg of PBW and a limited plateau pressure of 30 cmH2O, had evidence of alveolar over-distension [26,27]. If hyperinflation plays a role in the pathogenesis of ventilator-induced lung injury, then one may wonder whether a lower VT of 6 mL/kg PBW is low enough [28]. An experimental study demonstrated a reduction of alveolar epithelial injury and pulmonary oedema when VT was reduced from 6 to 3 mL/kg in rats [29]. Such a reduction in VT requires extracorporeal removal of CO2 in order to limit respiratory acidosis. In this situation, extracorporeal blood flow is low: around 1 L/min [30]. Recent clinical studies have found interesting results regarding the feasibility and safety of a super-protective ventilator strategy using extracorporeal removal of CO2 in ARDS [31,32]. Larger studies are required to assess the effects on mortality. 5. Conclusion The use of ECMO for ARDS remains controversial with conflicting data regarding its impact on survival compared to conventional treatments. The goal of ECMO is to maintain safe levels of oxygenation and control respiratory acidosis under protective ventilation. Its role as a salvage therapy is accepted, but it could also be proposed to treat any type of respiratory failure in addition to mechanical ventilation. Further studies are required before such practices are adopted. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Hill JD, O’Brien TG, Murray JJ, Dontigny L, Bramson ML, Osborn JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972;286:629–34. [2] 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. [3] Bartlett RH, Roloff DW, Custer JR, Younger JG, Hirschl RB. Extracorporeal life support: the University of Michigan experience. JAMA 2000;283:904–8. [4] 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. [5] Australia, New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators, Davies A, Jones D, Bailey M, Beca J, Bellomo R, et al. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA 2009;302:1888–95. [6] Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011;306:1659–68.
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