basics of extracorporeal life support for acute ... · the “nuts and bolts” of extracorporeal...

QU A R T E R LY EV I D E N C E-B A S E D RE V I E W S O N CUR R E N T TO P I C S I N

CR I T I C A L CA R E ME D I C I N E B Y L E A D I N G CA N A D I A N CO N T E N T EX P E R T S

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Acknowledgements:

Canadian Institutes of Health ResearchPublic Health Agency of Canada

John Granton, MDChair, Canadian Critical Care Society

John Marshall, MDChair, Canadian Critical Care Trials Group

Margaret Herridge, MDEditor, Critical Care Rounds

Basics of Extracorporeal Life Supportfor Acute Respiratory Failure: Now and Moving Forward BY EDDY FAN , MD , FRCPC , AND ANNE -MAR I E GUERGUER I AN , MD , PHD

In patients with acute respiratory failure (ARF) associated with severe, life-threateninghypoxemia and/or hypercapnia, there is often a tenuous balance between the ability tomaintain sufficient gas exchange to support adequate tissue perfusion and the ability touse a ventilatory strategy that will protect the injured lung from further harm (ie, ven-tilator-associated lung injury). Theoretically, if the cause of acute respiratory distresssyndrome is reversible, extracorporeal life support (ECLS) methods such as extracor-poreal membrane oxygenation may allow the most “lung-protective” ventilatorystrategy possible as it allows the dissociation of mechanical ventilation and gasexchange. This issue of Critical Care Rounds summarizes the contemporary knowledge,clinical evidence, experience, and opinions about the use of ECLS for critically illpatients with ARF. By the end of the paper, the reader should understand the basicprinciples involved in supporting an ARF patient with ECLS, the indications whenusing ECLS as a bridge to recovery, the considerations, expected complications, anduncertainty that remains.

Extracorporeal membrane oxygenation (ECMO) refers to the prolonged extrathoracic deviceconfiguration used for respiratory, cardiac, or cardiopulmonary support, with components thatsupport blood flow and gas exchange.1 By permitting control of oxygenation and carbon dioxide(CO2) removal through an extracorporeal system, the severely injured lungs can be supportedwith lower pressures and minimal tidal volumes, theoretically reducing the risk for ventilator-associated lung injury (VALI). These potential benefits need to be weighed against the poten-tial risks associated with ECMO therapy, particularly risks of bleeding secondary to the needfor anticoagulation, infection given the need for invasive vascular catheterization, for exposureto blood products, and the systemic inflammatory response associated with exposure to extra-corporeal therapy.2-6

The “Nuts and Bolts” of Extracorporeal SupportGas exchange and blood flow support

The overarching objective of ECMO is to maintain oxygen (O2) delivery while mini-mizing O2 consumption, with a view of minimizing ongoing injury and acidosis. Veno-arterial(VA-ECMO) support is used for both cardiac and pulmonary support where veno-venous(VV-ECMO) configuration is used for pulmonary support. O2 delivery is proportional toblood flow delivered by the circuit and O2 content of arterial blood, influenced most by hemo-globin O2 concentration over dissolved O2. Depending on the configuration of the mechanicalsystem, contributions from intrinsic cardiac and pulmonary function may be also useful forpatient’s physiology and condition.7 Basic mechanical support requires a blood flow pump, amembrane oxygenator for oxygenation and CO2 removal, a heat exchanger, and cannulas toconnect the patient for systemic blood drainage and reinfusion (or return). The rate of bloodflow is limited by circuit and patient factors. The circuit factors include the size of the venousdrainage cannula and the arterial and/or venous return cannula, the size of tubing, and mem-brane lung resistance, contributing most to the circuit factors. The patient factors include thepatient’s size, intravascular volume, and vascular systemic resistance (in V-A support) and pul-monary resistance (in V-V support).

While both VA- and VV-ECMO may be used for acute respiratory failure (ARF), VV-ECMO should be the mode of choice in patients with severe ARF in the absence of overt

®

The editorial content of Critical Care Rounds is determinedsolely by the Canadian CriticalCare Society.

Dr. Fan is an Assistant Professor ofMedicine, Interdepartmental Division ofCritical Care Medicine, University ofToronto, and an Intensivist, TorontoGeneral and Mount Sinai hospitals,Toronto, Ontario. Dr. Guerguerian isan Assistant Professor of Medicine,Interdepartmental Division of CriticalCare Medicine, University of Toronto,and a Staff Physician in Critical CareMedicine at The Hospital for SickChildren, Toronto, Ontario.

Disclosure: Dr. Fan is a site investigatorfor the Extracorporeal MembraneOxygenation for Severe Acute RespiratoryDistress Syndrome (EOLIA) study.Dr. Guerguerian is the Medical Director ofthe ECMO Program at the Hospital forSick Children.

cardiac dysfunction and/or refractory shock in order tominimize arterial vascular-related complications. Echocar-diography should be performed prior to initiatingVV-ECMO, to exclude severe left ventricular dysfunctionthat may require VA-ECMO support (eg, severe pneu-monia with sepsis-induced cardiac dysfunction) and evaluate for the presence of a right-to-left shunt. Impor-tantly, acute right heart failure secondary to pulmonaryhypertension from acute respiratory distress syndrome(ARDS) is not an absolute indication for VA-ECMOsupport in most cases, since delivery of oxygenated bloodto the pulmonary circulation will ameliorate reversiblehypoxia-induced pulmonary vasoconstriction and reducepulmonary artery pressures in the hours followingVV-ECMO initiation.1,8,9

Membrane lungs

Modern membranes consist of multiple polymethyl -pentene (PMP) hollow fibres measuring <0.5 mm in diam-eter, which allow the diffusion of gas but not liquid.2-6,10

These PMP membranes have a number of advantages overolder silicone membrane oxygenators, including longerduration of operation (average 12 versus 5-7 days),7,11

lower consumption of blood products, more effective gasexchange, lower resistance to blood flow, and smallerpriming volumes (<300 mL).12,13 These devices have alsobeen specially coated to render them more biocompatibleand more resistant to thrombosis.

Fresh (sweep) gas flows (air-O2-CO2) through thelumen of the hollow fibres, facilitating CO2 eliminationand oxygenation of the blood running through the mem-brane. CO2 is more effectively exchanged than O2, due tothe greater solubility of CO2 leading to more rapid diffu-sion (Fick law) and the linear shape of the CO2 dissocia-tion curve (as compared the sigmoid shape of the O2

dissociation curve). Thus, the patient’s partial pressure ofarterial CO2 (PaCO2) is mainly determined by the sweepgas flow rate, whereas the main determinant of PaO2 isblood flow through the circuit. For instance, effectiveCO2 clearance can be achieved with low blood flow rates(eg, 10-15 mL/kg/min) while effective oxygenationrequires much higher flow rates (eg, 50-100 mL/kg/min),depending on the cardiac output and the amount of recir-culation.10

Centrifugal pumps

Blood flow through an ECMO circuit is driven by apump. Centrifugal pumps are most frequently used, whilepulsatile and roller pumps also exist. Centrifugal pumpshave a number of advantages over roller pumps includingsmaller priming volumes, are simple to use and maintain,have no requirement for gravity drainage or venous reser-voirs, and are useful for prolonged ECMO runs, as well asfor intra- or inter-hospital transport. The continuous nega-tive pressure created by the centrifugal pump can causecavitation and hemolysis in the venous line and requirescontinuous monitoring and ongoing vigilance (patient’sintravascular volume status, venous line size, and pumpspeed) to minimize the risk of air emboli.

Vascular access

For VV-ECMO, either a single- or multi-vesselapproach is possible. For example, in the double-vesselapproach, a large single lumen multi-perforated drainagecannula can be inserted in the femoral vein and advanced tothe cavo-atrial junction. The return cannula is a single-stage catheter inserted in the right internal jugular vein tothe superior vena cava. Bicaval dual-lumen cannulae areavailable, and can be inserted through the right internaljugular vein and positioned to allow drainage from proximal(superior vena cava) and distal (inferior vena cava) ports andreturn oxygenated blood via a second lumen into the rightatrium and across the tricuspid valve.14 Proper positioningof these bicaval catheters typically requires experienced cli-nicians with real-time fluoroscopic and/or echocardio-graphic (transesophageal or transthoracic) guidance.15

If VA-ECMO is required, the drainage cannula canbe inserted in the jugular vein and oxygenated blood maybe returned, either through the femoral artery or thecarotid artery. Jugular vein-to-femoral artery configura-tion provides adequate distal perfusion, but may notprovide adequate oxygenation of the aortic arch becauseof desaturated blood coming from the lungs to the pulmonary veins (and may be associated with coronaryand aortic arch desaturation). Adding another returnvenous cannula may be helpful (veno-veno-arterial). Thecarotid artery cannulation most often used in neonatesand young children can be done with an open surgicalapproach. The femoral artery cannulation site used inlarger children and adults inserted either by open or per-cutaneous approach usually requires a distal perfusioncannula (or graft) to ensure distal limb perfusion.1 If leftventricular dysfunction is associated with distension thatcannot be overcome with dialing an increased blood flowto the circuit, it will be associated with left atrial hyper-tension, pulmonary edema and may require venting withballoon atrial septostomy.1

Pumpless support devices and extracorporeal CO2 removal (ECCO2R)

The use of a membrane lung connected as a pumplessarteriovenous (AV) shunt for extracorporeal gas exchangesignificantly reduces the complexity of conventionalECMO. The use of a membrane as a pumpless AV shunt,with a simplified circuit, allows for less intensive moni-toring, lower costs, and decreased risk of complicationsfrom the use of a centrifugal pump. It is used primarily forECCO2R.16 One such recent device resembles a modernhollow-fibre PMP membrane with extremely low resist-ance which can be used with a patient mean perfusionpressure of 60-80 mmHg, from femoral artery to vein,allowing blood flows of approximately 1.0–2.5 L/min.17

Vascular access is obtained via the femoral artery and veinusing smaller cannulae (eg, 13-21 F arterial and 19-21 Fvenous) than typically used in ECMO. Oxygenation by thisdevice is limited (<10%–20%) due to relative quantity ofblood inflow to the membrane compared to the patient’sintrinsic arterial blood oxygenation.16

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An important consequence of pressure- and volume-limited ventilatory strategies which have become the stan-dard of care for the management of patients with ARDS18

may be the development of significant hypercapnia andrespiratory acidosis, which can result in hemodynamicinstability and challenges with end-organ perfusion. Theuse of ECCO2R has been described as both an adjunct toboth conventional and alternative modes of ventilation (eg,high-frequency oscillation) to help control respiratory aci-dosis,19-21 and perhaps permit further reductions in tidalvolumes and airway pressures to enhance lung protectionin these patients.22 A number of reports have described theuse of interventional lung assist, including status asth-maticus,23 ARDS,17 and bridge to lung transplant.24-27

Anticoagulation, bleeding, and life-threatening hemorrhage

Standard unfractionated heparin is the main anticoag-ulant used when supporting patients on ECMO. Anticoag-ulation primary targets vary between institutions: somefavour activated clotting times (ACTs), activated partialthromboplastin time (aPTT), or heparin anti-Xa factorlevels. Bedside ACTs are most often used to titrate antico-agulation as the test can be measured on whole bloodsamples quickly, with the ACT target usually set at 180–200 seconds. Because ACTs offer crude assessments, anti-coagulation monitoring (when used) is supplemented byongoing assessment of aPTT and heparin anti-Xa factorlevels, platelet counts (>100 000 per dL), and factorsinvolved in coagulation such as antithrombin III, fib-rinogen (>1.5), and international normalized ratio. Antico-agulation goals should be set daily based on individualpatient risk of bleeding and clotting.

Hemorrhage remains one of the most frequent andlife-threatening complications associated with the use ofECMO. The 2011 Extracorporeal Life Support Organiza-tion (ELSO) annual reports suggest that cannula site andsurgical site bleeding are most often reported in childrenand adults supported for respiratory reasons, followed bygastric, pulmonary, and neurological; in the neonatal agegroup, gastric bleeding is rarely reported, and neurologicalbleeding are more often reported. In patients withbleeding, solving surgical bleeding remains a primarystrategy. When faced with nonsurgical bleeding, someinstitutions will follow strict anticoagulation protocols28

with lower heparin dose delivery approaches andincreasing blood flow, while others will suggest addingtranexamic acid29 or aminocaproic acid;30-32 however, a ran-domized, controlled trial (RCT) of the use of the latterapproach did not show benefit.31 When life-threateninghemorrhage is unresponsive to surgical manipulations ordecreasing heparin delivery, the clinician may need to con-template premature separation from ECMO. If separatingfrom ECMO is impossible and hemorrhage persists afterreplacing blood products, different approaches can be con-sidered,1 none of which are efficacious in all patients.Whenever these approaches are being used, the teamshould be prepared for a circuit failure and immediatecircuit replacement.

Extracorporeal Support for ARF

The ELSO collects voluntary reporting from over 150institutions in 3 age groups (neonatal, pediatric, adult) and3 reasons for ECMO support (respiratory, cardiac, andextracorporeal cardiopulmonary resuscitation). As of July2011, the number of patients reported to the ELSO reg-istry for respiratory indication since 1990 were 24 770neonatal, 5009 pediatric, and 2620 adult, and survival tohospital discharge was 75%, 56%, and 55%, respectively.

Neonatal and pediatric considerations – focusing on timing and long-term outcomes

ECMO has been used in neonatal (infants <1 month ofage) and pediatric populations for acute respiratory failurefor over 40 years. The most common indications in thefirst month of life are meconium aspiration, pneumoniaand sepsis with persistent pulmonary hypertension of thenewborn, and pulmonary insufficiency with congenitaldiaphragmatic hernia; these conditions are characterizedwith increased pulmonary vascular resistance with orwithout an additional hypoxemia with right-to-leftshunting. Two RCTs in neonates comparing ECMO to“conventional” care have been conducted;33,34 the morerecent was stopped early because of favourable outcome inthe group allocated to ECMO support (Table 1). Morerecently with the introduction of inhaled nitric oxide andhigh-frequency oscillation, the “conventional” treatmenthas evolved, and there has been a consistent decline inreports of neonates supported for these indications to theELSO registry since the mid-1990s. For pediatric ECMO,practice is based on evidence from the ELSO case seriesregistry and on the experience of institutions that reportcase series or nonrandomized comparisons. Pneumoniaand/or ARDS are the main reasons for using ECMO inrespiratory failure and bridge to recovery.35-37 Septic shockwith low cardiac output with or without respiratory failureis another indication.38,39 Given the challenges associatedwith pediatric RCTs, the field is focused on identifying theoptimal “timing” of initiation of extracorporeal life support(ECLS) – ie, “not too early but not too late” – in childrenwith reversible ARF refractory to conventional support. Inconditions where the deterioration is rapid and severe andpre-ECLS exposure to mechanical ventilation is limited induration and magnitude (eg, severe asthma or severeinfluenza pneumonia), ECMO is offered to bridge pedi-atric patients to recovery. However, with increasing dura-tion and intensity of pre-ECLS mechanical ventilation,40

many clinicians become concerned that the prognosis ofsome pediatric patients may not be modifiable withECMO; eg, oncology patients with ARF in the context ofbone marrow transplantation. The neonatal and pediatricfields evaluate the severity of ARF and the indication forECMO by using the oxygenation index (OI), which is cal-culated as the product of the mean airway pressure andfraction of inspired O2 (FiO2), divided by the PaO2. Inpediatrics, ECMO will be considered upon an OI ≥40maintained for more than 4 hours. Although an OI of 40has neither been validated to indicate ARF refractory to


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mechanical ventilation nor to be of prognostic significance,it remains a clinically meaningful metric to pediatric inten-sive care specialists to indicate severe respiratory failuredespite therapy. Neonatal and pediatric survivors havereached adulthood, but contemporary longer-term func-tional respiratory or mental health outcomes of these earlycohorts are rare, and their generalizability to patients in2012 would be limited. Regardless, ECMO programs needto anticipate that survivors require follow-up for pro-longed periods of time, given the impact on respiratoryfunction, neurological function, and growth.41 Some pedi-atric patients with severe ARF not supported with ECMO(eg, congenital diaphragmatic hernia) also show evidenceof impaired function in similar domains, which makes itdifficult to discern between the disease and therapeuticfactors.

Adult considerations – evidence and indications

The first RCT of ECMO for ARF in adults, publishedin 1979, found dismal rates of survival, with mortality>90% in both groups (Table 2).42 Importantly, the patientsreceived mechanical ventilation for averages of 7 and 10days prior to being randomized to the control or ECMOgroups, respectively. Interestingly, as the authors note, 7 ofthe 8 surviving patients underwent mechanical ventilationfor ≤7 days before entering the study, in stark contrast tothe 4% survival in either group for those receiving >7 daysof mechanical ventilation prior to study entry. Finally,among the 8 survivors, 7 had no limitations in their activi-ties and normal pulmonary function tests 6 months afterhospital discharge. As a result, interest in ECMO foradults with ARF waned for years. In 1994, a second RCTwas performed using ECCO2R in conjunction with analternative mode of ventilation (pressure-controlledinverse-ratio ventilation [PC-IRV]) which focused on opti-mizing oxygenation.43 The rationale for this study was anencouraging report of 77% survival among severe ARDSpatients in Milan supported with PC-IRV, followed if nec-essary by low-frequency positive pressure ventilation(LFPPV)-ECCO2R.44 Importantly, half of the survivors

recovered following PC-IRV, without ever having receivedLFPPV-ECCO2R. This study also demonstrated no signif-icant difference in mortality between ECCO2R-treatedand non-ECCO2R-treated groups, and led the authors toconclude that “we do not recommend extracorporeal lifesupport as a therapy for ARDS.” However, neither studycompared ECMO to a pressure- and volume-limited ven-tilation strategy, which has now become the standard ofcare for patients with ARDS. Indeed, despite the goal ofutilizing LFPPV-ECCO2R to allow “lung rest”, the meanpeak inspiratory pressure among new therapy patients was49.5 cm H2O (while trying to achieve a tidal volume of3.5–4.5 mL/kg predicted body weight).

There has been renewed interest in ECMO as astrategy for managing severe ARDS in adults. A case seriesfrom Australia and New Zealand reported on the use ofVV-ECMO for severe influenza-associated ARDS in 61patients during the H1N1 pandemic with a survival of79%.45 While these results rejuvenated interest in the useof ECMO as rescue therapy for patients with severeARDS, the results remain confounded by indication (ie,age, severity of illness, pre-existing comorbidities) andshould be considered hypothesis-generating. In an attemptto address some limitations of a case series, investigatorsfrom the UK Swine Flu Triage Study (SwiFT) comparedhospital mortality for 75 patients referred, accepted, andtransferred to ECMO centres in the United Kingdom forH1N1-related ARDS with 75 carefully matched non-ECMO-referred patients.46 ECMO-referred patients hadsignificantly lower hospital mortality (24.0% versus50.7%) than matched non-ECMO referred patients (rela-tive risk 0.47; 95% confidence interval 0.31-0.72). Thisresult was consistent across 3 different strategies formatching patients and robust to a number of well-plannedsensitivity analyses.

Finally, the Conventional Ventilatory Support versusExtracorporeal Membrane Oxygenation for Severe AdultRespiratory Failure (CESAR) trial randomized patientswith severe, potentially reversible ARF, to either considera-tion for ECMO with transportation to a single ECMO


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Table 1: Comparative studies of ECLS in neonates or children with ARF

RCT N Patient characteristics (n) Mortality Other considerations

O’Rourke, 198934 39 • ECMO (29) vs. CMT (10)

• Severe PPHN and respiratoryfailure

• 85% likelihood of dying

3% vs. 40%(P<0.05)

• Phase I mortality:– 4/10 CMT vs. 0/9 ECMO– No further babies randomized to CMT (as planned)

• Phase II mortality:– 1/20 ECMO

UK CollaborativeECMO Trial Group,199633

185 • ECMO + MV (93) vs. usualcare (92)

• Severe ARF with OI ≥40– Majority had PPHN secondary to meconiumaspiration

32% vs. 59%(P=0.0005)

• Patients randomized to ECMO group were transferred to 1 of 5 referral centres

• Only 84% of patients randomized toECMO group were placed on ECMO

• Trial was stopped early for efficacy

ECLS = extracorporeal life support; ARF = acute respiratory failure; RCT = randomized, controlled trial; ECMO = extracorporeal membraneoxygenation; CMT = conventional medical therapy; PPHN = persistent pulmonary hypertension of the newborn; MV = mechanical ventilation;OI = oxygenation index

centre, or continued therapy with the best standard practice; ie, conventional pressure- and volume-limitedmechanical ventilation. In this trial, only 75% of thepatients randomized to consideration for treatment byECMO actually received this therapy. This clinical trialdemonstrated a significantly greater survival at 6 monthswithout disability in patients randomized to considerationfor ECMO (relative risk 0.69; 95% confidence interval0.05-0.97).47 However, it is difficult to separate the effectof ECMO alone, as compared to differences in overallcare, upon transfer to a specialized centre for patients ran-domized to consideration for ECMO, on the difference inoutcome between groups. Indeed, if only 2 additionalpatients had not suffered death or disability in the controlgroup, the difference in the primary outcome would nolonger be statistically significant.48 These methodologicallimitations should be addressed in the EOLIA (ECMO torescue Lung Injury in severe ARDS; ClinicalTrials.govNCT01470703) trial, an ongoing international, multi-centre RCT that will compare VV-ECMO in every patientrandomized to this group to a modern protocolized lungprotective ventilation strategy in the control group.49

Given the lack of high-quality comparative evidence,formal guidelines for the use of ECMO in patients withsevere ARF vary from centre to centre, and across jurisdic-tions.10,50 In general, for patients with severe ARF refrac-tory to conventional mechanical ventilation, and especiallythose who may have failed other rescue therapies, transfer

to a centre that is capable of providing adult ECMO (andother advanced therapies) may be potentially life-saving.51

Most adult ECMO centres would consider initiatingECMO for ARF in patients with refractory and persistenthypoxemia (eg, PaO2/FiO2 < 50 mmHg on FiO2 >80%despite high levels of positive end-expiratory pressure[PEEP]), hypercapnia (eg, PaCO2 >100 mm Hg with pH<7.25 and PaO2/FiO2 <100 mm Hg), or for specific condi-tions (eg, bridge to lung transplantation). Perhaps the onlyabsolute contraindication to ECMO therapy would be anycondition that precludes the use of any anticoagulation.50

Relative contraindications may include patients who havealready received high-pressure ventilation (end-inspiratoryplateau pressure >30 cm H2O) or high FiO2 (>80%) formore than 7 days, have limited vascular access (sites and/orsize for ECMO cannulae), or comorbidities (eg, incurablemetastatic malignancy) and/or organ failure that would beindicative of an unfavourable prognosis. However, as ourexperience, understanding, and the technology associatedwith ECMO therapy improves, so too will the indicationsand contraindications for the use of ECMO in patientswith ARF (Table 3).

Principles of Patient Management DuringExtracorporeal SupportMechanical ventilation during ECMO

The optimal ventilatory settings for patients with ARFreceiving ECMO are unknown. Since nearly complete gas


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Table 2: Comparative studies of ECLS in adults with ARF

RCT N Patient characteristics (n) Mortality Other considerations

Zapol 197942 90 • VA ECMO + MV (48) vs. MV only (42)

• 57% with infectious pneumonia

• Fast entry: PaO2/FiO2 <50 mmHg for≥2 hours

• Slow entry: PaO2/FiO2 <83 mmHg for>12 hours and shunt fraction >30%(after 48 hours in ICU)

90% vs. 92%(P=0.84)

• MV not protocolized in either group

• Overall barotrauma rate 45%

• RBC/FFP transfusion rate 2.5 L/dayvs. 1.0 L/day

Morris 199443 40 • ECCO2R + MV (21) vs. MV only (19)

• ARDS patients– 60% with infectious pneumonia

• Fast entry: PaO2/FiO2 <50 mmHg for≥2 hours

• Slow entry: PaO2/FiO2 <83 mmHg for>12 hours and shunt fraction >30%(after 48 hours in ICU)

67% vs. 58%(P=0.80))

• Unconventional MV in ECCO2Rgroup (PC-IRV followed by LFPPV)

• Overall barotrauma rate 68%

• Non-CNS hemorrhage 21 vs. 0

• RBC transfusion rate 1.8 L/day vs.0.2 L/day

CESAR 200947 180 • VV ECMO + MV (90) vs. usual care (90)

• ARDS patients – 60% with pneumonia

• Reversible respiratory failure

• Murray score ≥ 3.0

37% vs. 50%(P=0.07)

• Patients randomized to ECMO group were transferred to a referral centre

• Only 68 (75%) of patients randomized to ECMO group wereplaced on ECMO

• Conventional management for control patients was not protocolized

VA = veno-arterial; PaO2 = partial pressure of arterial oxygen; FiO2 = fraction of inspired oxygen; ICU = intensive care unit; RBC = red blood cell;FFP = fresh frozen plasma; ECCO2R = extracorporeal carbon dioxide removal; ARDS = acute respiratory distress syndrome; PC-IRV = pressure-controlled inverse ratio ventilation; LFPPV = low-frequency positive pressure ventilation; CNS = central nervous system; VV = veno-venous

exchange support may be provided by VV-ECMO, thecontribution to gas exchange from ongoing ventilation ofthe lungs with moderate to high pressures and/or volumesis likely to be limited. Thus, ventilatory support may bedecreased to provide “lung rest”, in keeping with the prin-ciples of pressure- and volume-limited ventilation inpatients with ARDS and its association with improved out-comes.18 For instance, the initial ventilator settings appliedin the CESAR trial47 were pressure-controlled ventilationfor a peak inspiratory pressure 20–25 cm H2O, PEEP of10–15 cm H2O, set respiratory rate of 10 breaths perminute, and FiO2 of 30%. Due to the reduction in venti-lator settings, delivered tidal volumes may be ≤4 mL/kg ofpredicted body weight, which may further enhance lungprotection and lead to improved outcomes.22,52 Childrenare rapidly managed with spontaneous breathing(eg, PEEP 8–10 cm H2O and peak inspiratory pressure20 cm H2O), and cared for awake with analgesia, low levelsof sedation, and parental presence. In adults, as patientsimprove, spontaneous breathing may be allowed (eg, pres-sure support ventilation) and patients with adequate gasexchange may even be extubated while supported byECMO.

Rehabilitation and mobilization

Many adult patients receiving invasive mechanical ven-tilation for ARF require sedation and analgesia to facilitatepatient-ventilator synchrony, comfort, and reduce O2 con-sumption. However, an important consequence of thesemedications, along with endotracheal intubation andmechanical ventilation and the requirement for other formsof organ support (eg, vasopressors, renal replacementtherapy), is enforced bed rest and immobility for thesepatients while in the intensive care unit (ICU). Coupledwith their underlying critical illness, this state of immobilitycan lead to profound ICU-acquired weakness, which maycontribute to persistent and significant decrements in phys-ical function and quality of life among survivors.53

Early rehabilitation among mechanically ventilatedpatients with ARF can lead to improved functional out-comes at hospital discharge.54 However, numerous real orperceived barriers (such as over-sedation, delirium, endo-tracheal intubation, and ARDS) may limit early delivery ofthis therapy in the course of illness.55,56 A potential advan-tage of earlier ECLS therapy for patients with severe ARFmay be the ability to facilitate earlier rehabilitation, some-thing that has traditionally not been provided to thesepatients during their ICU stay.57,58 As patients on ECLSmay require far less ventilatory support, and may not beintubated in some cases, their requirements for sedationand analgesia may be greatly reduced, allowing for rela-tively awake and cooperative patients who may be able toparticipate in rehabilitation while in the ICU. Moreover,the miniaturization of ECLS components and simplifica-tion of the system allows patients to be mobilized andambulate. A group recently reported on their institutionalexperience (26 patients) with a novel strategy of “awakeECMO” in nonintubated patients, representing their pre-ferred bridging strategy for patients with end-stage respi-ratory failure who are awaiting lung transplantation.59

Patients in the awake ECMO could participate in rehabili-tation and had significantly shorter postoperative durationof mechanical ventilation (14 versus 37 days; P=0.04) and atrend towards shorter postoperative hospital stay (38versus 67 days; P=0.06) as compared to a historical controlgroup of patients bridged to lung transplantation withmechanical ventilation. Survival at 6 months amongpatients who survived to transplantation in both group wassignificantly greater in the awake ECMO group (80 versus50%; P=0.02). While promising, the results from this ret-rospective cohort study will require confirmation in aprospective RCT applied to ARF.60

Challenges, Controversies, and Future Directions

In 2012, the intent of ECLS is to replace all, or com-ponents of, organ function until recovery of function or


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Table 3: Indications, contraindications, and considerations for ECLS for ARF in children and adults

PEEP = positive end-expiratory pressure

Children Adults

Indications/considerations

• Potentially reversible cause forrespiratory failure

• OI ≥40 maintained for morethan 4 hours

• Potentially reversible cause for respiratory failure

• Refractory and persistent hypoxemia (eg, PaO2/FiO2

<50 mm Hg on FiO2 >80% despite high levels of PEEP)

• Refractory hypercapnia (eg, PaCO2 >100 mm Hg with pH<7.25 and PaO2/FiO2 <100 mm Hg)

• Can consider in specific conditions (eg, massive pulmonaryembolism, bridge to lung transplantation)

Considerations or contraindications

• Any condition that precludesthe use of anticoagulation

• Patients who have alreadyreceived high-pressureventilation for more than14 days

• Limited vascular access (sitesand/or size for ECMO cannulae)

• Any condition that precludes the use of anticoagulation

• Patients who have already received high-pressure ventilation(end-inspiratory plateau pressure >30 cm H2O) or high FiO2

(>80%) for more than 7 days

• Limited vascular access (sites and/or size for ECMO cannulae)

• Comorbidities (eg, incurable metastatic malignancy) and/ormultiorgan failure that would limit potential of overallbenefit from ECMO

until replacement of the organ with a transplant or until adecision can be formalized for the management of thepatient. In the critically ill patient who develops ARF andECLS becomes a consideration, the questions that shouldimmediately come to mind to best tailor the approachinclude the following: • Does the patient have a disease or process causing lung

failure and/or heart failure? This determines the modeof support.

• Is this disease or process reversible in a reasonableamount of time? The indication is bridge to recovery.

• If this disease or process is irreversible with recovery ofthe organ, is transplantation an option? The indicationis bridge to transplantation.

Approximately one-half of patients supported withECMO for ARF survive, which directly implies that theother half does not. End-of-life care in patients supportedby ECMO or shortly after separation from ECMO addstechnology and some complexity to the process, andremains particularly challenging for patients and their fam-ilies. Patients can be diagnosed with brain death while onECMO or they may die of cardiopulmonary failure fol-lowing a decision to wean off or separate from ECMO.For those who continue on ECMO, which provides con-tinuous resuscitation through ongoing gas exchangeand/or cardiovascular support, what would a previous “donot resuscitate” (DNR) order mean?61 With increasingadvances in life support technology, the challenge ofunderstanding when to consider, and how to discuss, lim-iting ECLS with patients and their caregivers will be ofparamount importance.62

Over the next decade, we anticipate that the field willmove forward dramatically because of the innovativeopportunities targeting neuroprotection63 and rehabilita-tion57-59,64,65 during intervals of care supported with ECLSwhile allowing failing organs to recover. An expandedunderstanding of long-term outcomes in patients sup-ported with ECLS, including any potential neurocognitiveand/or neuropsychiatric morbidity, is needed. In particular,the role of hypoxemia as an important risk factor for long-term neuropsychiatric impairment in patients with ARDS66

may inform optimal timing for in the initiation of ECLS inhypoxemic ARDS patients failing conventional therapiesand the physiological (eg, oxygenation) targets for thosereceiving ECLS support. Novel anticoagulationapproaches and modulation of inflammation will allow forbleeding-related deaths to become a complication of thepast and thrombotic complications will be manageable.Preclinical discoveries applicable to lung injury and repairmay allow for in vivo or ex vivo organ restoration usingallo- and autotransplantation.67 Finally, as technology andexperience making ECLS simpler, easier, and more com-monplace in our ICUs, perhaps we will eventually moveaway from using mechanical ventilation for gas exchangefor patients with ARF.68

Conclusions

Advances in ECLS technology have made the provi-sion of this therapy to patients with ARF safer and easierthan ever before. For neonates and pediatric patients

requiring ECLS, contraindications have yielded the placeto considerations on a case-by-case basis. In adults,improvements in short-term outcomes of carefully selectedARF patients supported with ECLS are promising, butthey require confirmation in large RCTs. Moreover, theoptimal timing, mode, and patient population for thistherapy remain controversial. Until these are better delin-eated in future studies, patients who require, or are beingconsidered, for ECLS should be transferred to centreswith expertise in management of ARF and the use of theseand other advanced therapies.

ReferencesAnnich G. Lynch W. MacLaren G. Wilson J. Bartlett R, eds. ECMO1.Extracorporeal Cardiopulmonary Support in Critical Care. 4th ed. Ann Arbor(MI): ELSO; 2012.Peek GJ, Firmin RK. The inflammatory and coagulative response to pro-2.longed extracorporeal membrane oxygenation. ASAIO J. 1999;45(4):250-263.Hirthler M, Simoni J, Dickson M. Elevated levels of endotoxin, oxygen-3.derived free radicals, and cytokines during extracorporeal membrane oxy-genation. J Pediatr Surg. 1992;27(9):1199-1202.Kawahito K, Misawa Y, Fuse K. Extracorporeal membrane oxygenation sup-4.port and cytokines. Ann Thorac Surg. 1998;65(4):1192-1193.McILwain RB, Timpa JG, Kurundkar AR, et al. Plasma concentrations of5.inflammatory cytokines rise rapidly during ECMO-related SIRS due to therelease of preformed stores in the intestine. Lab Invest. 2010;90(1):128-139.Yamamoto T, Terajima K, Kato K, et al. Transient leukocytopenia associat-6.ed with a steep surge of pro-inflammatory cytokines in a patient with severecardiogenic pulmonary edema. Intern Med. 2006;45(20):1153-1155.Duncan BW, ed. Mechanical Support for Cardiac and Respiratory Failure in7.Pediatric Patients. New York (NY): Marcel Dekker, Inc; 2001.Heiss KF, Clark RH, Cornish JD, et al. Preferential use of venovenous extra-8.corporeal membrane oxygenation for congenital diaphragmatic hernia.J Pediatr Surg. 1995;30(3):416-419.MacLaren G, Combes A, Bartlett RH. Contemporary extracorporeal mem-9.brane oxygenation for adult respiratory failure: life support in the new era.Intensive Care Med. 2012;38(2):210-220.Combes A, Bacchetta M, Brodie D, Müller T, Pellegrino V. Extracorporeal10.membrane oxygenation for respiratory failure in adults. Curr Opin Crit Care.2012;18(1):99-104.Janes E, Lawler P. New methods of oxygenation. Curr Anaesth Crit Care.11.1993;(4):182-188.Peek GJ, Killer HM, Reeves R, Sosnowski AW, Firmin RK. Early experience12.with a polymethyl pentene oxygenator for adult extracorporeal life support.ASAIO J. 2002;48(5):480-482.Khoshbin E, Roberts N, Harvey C, et al. Poly-methyl pentene oxygenators13.have improved gas exchange capability and reduced transfusion require-ments in adult extracorporeal membrane oxygenation. ASAIO J. 2005;51(3):281-287.Javidfar J, Brodie D, Wang D, et al. Use of bicaval dual-lumen catheter for14.adult venovenous extracorporeal membrane oxygenation. Ann Thorac Surg.2011;91(6):1763-1768.Tabak B, Elliott CL, Mahnke CB, Tanaka LY, Ogino MT. Transthoracic15.echocardiography visualization of bicaval dual lumen catheters for veno-venous extracorporeal membrane oxygenation. J Clin Ultrasound. 2012;40(3):183-186.Lynch JE, Hayes D, Zwischenberger JB. Extracorporeal CO(2) Removal in16.ARDS. Crit Care Clin. 2011;27(3):609-625.Bein T, Weber F, Philipp A, et al. A new pumpless extracorporeal interven-17.tional lung assist in critical hypoxemia/hypercapnia. Crit Care Med.2006;34(5):1372-1377.Fan E, Needham DM, Stewart TE. Ventilatory management of acute lung18.injury and acute respiratory distress syndrome. JAMA. 2005;294(22):2889-2896.Kredel M, Brederlau J, Wunder C, et al. High-frequency oscillatory ventila-19.tion with and without arteriovenous extracorporeal lung assist in patientswith severe respiratory failure. J Crit Care. 2012;27(2):182-191.Brederlau J, Muellenbach R, Kredel M, et al. Combination of arteriovenous20.extracorporeal lung assist and high-frequency oscillatory ventilation in aporcine model of lavage-induced acute lung injury: a randomized controlledtrial. J Trauma. 2007;62(2):336-346.Muellenbach RM, Kredel M, Wilhelm J, et al. High-frequency oscillation21.combined with arteriovenous extracorporeal lung assist reduces lung injury.Exp Lung Res. 2010;36(3):148-158.Terragni PP, del Sorbo L, Mascia L, et al. Tidal volume lower than 6 ml/kg22.enhances lung protection: role of extracorporeal carbon dioxide removal.Anesthesiology. 2009;111(4):826-835.


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Elliot SC, Paramasivam K, Oram J, Bodenham AR, Howell SJ, Mallick A.23.Pumpless extracorporeal carbon dioxide removal for life-threatening asthma.Crit Care Med. 2007;35(3):945-948.Fischer S, Simon AR, Welte T, et al. Bridge to lung transplantation with the24.novel pumpless interventional lung assist device NovaLung. J ThoracCardiovasc Surg. 2006;131(3):719-723.Fischer S, Hoeper MM, Tomaszek S, et al. Bridge to lung transplantation25.with the extracorporeal membrane ventilator Novalung in the veno-venousmode: the initial Hannover experience. ASAIO J. 2007;53(2):168-170.Strueber M, Hoeper MM, Fischer S, et al. Bridge to thoracic organ trans-26.plantation in patients with pulmonary arterial hypertension using a pumplesslung assist device. Am J Transplant. 2009;9(4):853-857.Cypel M, Keshavjee S. Extracorporeal life support as a bridge to lung trans-27.plantation. Clin Chest Med. 2011;32(2):245–251.Muensterer OJ, Laney D, Georgeson KE. Survival time of ECMO circuits28.on and off bleeding protocol: is there a higher risk of circuit clotting? Eur JPediatr Surg. 2011;21(1):30-32.van der Staak FH, de Haan AF, Geven WB, Festen C. Surgical repair of con-29.genital diaphragmatic hernia during extracorporeal membrane oxygenation:hemorrhagic complications and the effect of tranexamic acid. J Pediatr Surg.1997;32(4):594-599.Wilson JM, Bower LK, Fackler JC, Beals DA, Bergus BO, Kevy SV.30.Aminocaproic acid decreases the incidence of intracranial hemorrhage and otherhemorrhagic complications of ECMO. J Pediatr Surg. 1993;28(4):536-540.Horwitz JR, Cofer BR, Warner BW, Cheu HW, Lally KP. A multicenter trial31.of 6-aminocaproic acid (Amicar) in the prevention of bleeding in infants onECMO. J Pediatr. Surg. 1998;33(11):1610-1613.Downard CD, Betit P, Chang RW, Garza JJ, Arnold JH, Wilson JM. Impact32.of AMICAR on hemorrhagic complications of ECMO: a ten-year review.J Pediatr Surg. 2003;38(8):1212-1216.UK collaborative randomised trial of neonatal extracorporeal membrane33.oxygenation. UK Collaborative ECMO Trail Group. Lancet. 1996;348(9020):75-82.O’Rourke PP, Crone RK, Vacanti JP, et al. Extracorporeal membrane oxy-34.genation and conventional medical therapy in neonates with persistent pul-monary hypertension of the newborn: a prospective randomized study.Pediatrics. 1989;84(6):957-963.Turner DA, Cheifetz IM. Pediatric acute respiratory failure: areas of debate35.in the pediatric critical care setting. Expert Rev Respir Med. 2011;5(1):65-73.Skinner SC, Iocono JA, Ballard HO, et al. Improved survival in venovenous36.vs venoarterial extracorporeal membrane oxygenation for pediatric noncar-diac sepsis patients: a study of the Extracorporeal Life Support Organizationregistry. J. Pediatr. Surg. 2012;47(1):63-67.Smalley N, MacLaren G, Best D, Paul E, Butt W. Outcomes in children37.with refractory pneumonia supported with extracorporeal membrane oxy-genation. Intensive Care Med. 2012;38(6):1001-1007.MacLaren G, Butt W, Best D, Donath S. Central extracorporeal membrane38.oxygenation for refractory pediatric septic shock. Pediatr Crit Care Med.2011;12(2):133-136.MacLaren G, Butt W, Best D, Donath S, Taylor A. Extracorporeal mem-39.brane oxygenation for refractory septic shock in children: one institution’sexperience. Pediatr Crit Care Med. 2007;8(5):447-451.Domico MB, Ridout DA, Bronicki R, et al. The impact of mechanical ven-40.tilation time before initiation of extracorporeal life support on survival inpediatric respiratory failure: a review of the Extracorporeal Life SupportRegistry. Pediatr Crit Care Med. 2012;13(1):16-21.Nijhuis-van der Sanden MWG, van der Cammen-van Zijp MHM, Janssen41.AJWM, et al. Motor performance in five-year-old extracorporeal membraneoxygenation survivors: a population-based study. Critical care (London,England). 2009;13(2):R47.Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane oxygena-42.tion in severe acute respiratory failure. A randomized prospective study.JAMA. 1979;242(20):2193-2196.Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of43.pressure-controlled inverse ratio ventilation and extracorporeal CO2removal for adult respiratory distress syndrome. Am J Respir Crit Care Med.1994;149(2 Pt 1):295-305.Gattinoni L, Pesenti A, Caspani ML, et al. The role of total static lung com-44.pliance in the management of severe ARDS unresponsive to conventionaltreatment. Intensive Care Med. 1984;10(3):121-126.

The Australia and New Zealand Extracorporeal Membrane Oxygenation45.ANZ ECMO Influenza Investigators. Extracorporeal membrane oxygena-tion for 2009 influenza A (H1N1) acute respiratory distress syndrome.JAMA. 2009;302(17):1888-1895.Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal mem-46.brane oxygenation center and mortality among patients with severe 2009influenza A (H1N1). JAMA. 2011;306(15):1659-1668.Peek G, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment47.of conventional ventilatory support versus extracorporeal membrane oxy-genation for severe adult respiratory failure (CESAR): a multicentre ran-domised controlled trial. Lancet. 2009;374(9698):1351–1363.Jones A, Barrett N, Scales D, Beale R. Ventilatory support versus ECMO for48.severe adult respiratory failure. Lancet. 2010;375(9714):550-551.Combes A. Extracorporeal membrane oxygenation (ECMO) pour les syn-49.dromes de détresse respiratoire aiguë (SDRA) sévères. L’essai EOLIA(ECMO to rescue Lung Injury in severe ARDS). Réanimation. 2011;20:49-61.Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in50.Adults. N Engl J Med. 2011;365(20):1905-1914.Pipeling MR, Fan E. Therapies for refractory hypoxemia in acute respirato-51.ry distress syndrome. JAMA. 2010;304(22):2521-2527.Needham DM, Colantuoni E, Mendez-Tellez PA, et al. Lung protective52.mechanical ventilation and two year survival in patients with acute lunginjury: prospective cohort study. BMJ. 2012;344:e2124-e2124.Fan E, Zanni JM, Dennison CR, Lepre SJ, Needham DM. Critical illness53.neuromyopathy and muscle weakness in patients in the intensive care unit.AACN Advanced Critical Care. 2009;20(3):243-253.Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and54.occupational therapy in mechanically ventilated, critically ill patients: a ran-domised controlled trial. Lancet. 2009;373(9678):1874-1882.Pohlman MC, Schweickert WD, Pohlman AS, et al. Feasibility of physical55.and occupational therapy beginning from initiation of mechanical ventila-tion. Crit Care Med. 2010;38(11):2089-2094.Fan E. What is stopping us from early mobility in the intensive care unit?56.Crit Care Med. 2010;38(11):2254-2255.Turner DA, Cheifetz IM, Rehder KJ, et al. Active rehabilitation and physi-57.cal therapy during extracorporeal membrane oxygenation while awaitinglung transplantation: A practical approach. Crit Care Med. 2011;39(12):2593-2598.Garcia JP, Kon ZN, Evans C, et al. Ambulatory veno-venous extracorporeal58.membrane oxygenation: innovation and pitfalls. J Thorac Cardiovasc Surg.2011;142(4):755-761.Fuehner T, Kuehn C, Hadem J, et al. Extracorporeal membrane oxygenation59.in awake patients as bridge to lung transplantation. Am J Respir Crit CareMed. 2012 ;185(7):763-768.del Sorbo L, Ranieri VM, Keshavjee S. Extracorporeal membrane oxygena-60.tion as “bridge” to lung transplantation: what remains in order to make itstandard of care? Am J Respir Crit Care Med. 2012;185(7):699-701.Meltzer EC, Fins JJ. Extracorporeal membrane oxygenation for ARDS in61.adults. N Engl J Med. 2012;366(6):575-576.Lamas D, Rosenbaum L. Freedom from the tyranny of choice—teaching the62.end-of-life conversation. N Engl J Med. 2012;366(18):1655-1657.Wu X, Drabek T, Kochanek PM, et al. Induction of profound hypothermia63.for emergency preservation and resuscitation allows intact survival after car-diac arrest resulting from prolonged lethal hemorrhage and trauma in dogs.Circulation. 2006;113(16):1974-1982.Thiagarajan RR, Teele SA, Teele KP, Beke DM. Physical therapy and reha-64.bilitation issues for patients supported with Extracorporeal MembraneOxygenation. J Pediatr Rehabil Med. 2012;5(1):47-52.Fortenberry JD. Walk this way. Crit Care Med. 2011;39(12):2752-2753.65.Mikkelsen ME, Christie JD, Lanken PN, et al. The adult respiratory distress66.syndrome cognitive outcomes study: long-term neuropsychological functionin survivors of acute lung injury. Am J Respir Crit Care Med. 2012;185(12):1307-1315.Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in67.clinical lung transplantation. N Engl J Med. 2011;364(15):1431-1440.del Sorbo L, Ranieri VM. We do not need mechanical ventilation any more.68.Crit Care Med. 2010;38(10 Suppl):S555-S558.

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© 2012 Canadian Critical Care Society, which is solely responsible for the contents. The opinions expressed in this publication do not necessarily reflect those of the publisher or sponsor,but rather are those of the authoring institution based on the available scientific literature. Publisher: SNELL Medical Communication Inc. in cooperation with the Canadian CriticalCare Society. ®Critical Care Rounds is a registered trademark of SNELL Medical Communication Inc. All rights reserved. The administration of any therapies discussed or referred to inCritical Care Rounds should always be consistent with the recognized prescribing information in Canada. SNELL Medical Communication Inc. is committed to the development ofsuperior Continuing Medical Education.

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