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1.  Extracorporeal Lung Support Technologies – Bridge to Recovery and Bridge to Lung Transplantation in Adult Patients 
Executive Summary
For cases of acute respiratory distress syndrome (ARDS) and progressive chronic respiratory failure, the first choice or treatment is mechanical ventilation. For decades, this method has been used to support critically ill patients in respiratory failure. Despite its life-saving potential, however, several experimental and clinical studies have suggested that ventilator-induced lung injury can adversely affect the lungs and patient outcomes. Current opinion is that by reducing the pressure and volume of gas delivered to the lungs during mechanical ventilation, the stress applied to the lungs is eased, enabling them to rest and recover. In addition, mechanical ventilation may fail to provide adequate gas exchange, thus patients may suffer from severe hypoxia and hypercapnea. For these reasons, extracorporeal lung support technologies may play an important role in the clinical management of patients with lung failure, allowing not only the transfer of oxygen and carbon dioxide (CO2) but also buying the lungs the time needed to rest and heal.
Objective
The objective of this analysis was to assess the effectiveness, safety, and cost-effectiveness of extracorporeal lung support technologies in the improvement of pulmonary gas exchange and the survival of adult patients with acute pulmonary failure and those with end-stage chronic progressive lung disease as a bridge to lung transplantation (LTx). The application of these technologies in primary graft dysfunction (PGD) after LTx is beyond the scope of this review and is not discussed.
Clinical Applications of Extracorporeal Lung Support
Extracorporeal lung support technologies [i.e., Interventional Lung Assist (ILA) and extracorporeal membrane oxygenation (ECMO)] have been advocated for use in the treatment of patients with respiratory failure. These techniques do not treat the underlying lung condition; rather, they improve gas exchange while enabling the implantation of a protective ventilation strategy to prevent further damage to the lung tissues imposed by the ventilator. As such, extracorporeal lung support technologies have been used in three major lung failure case types:
As a bridge to recovery in acute lung failure – for patients with injured or diseased lungs to give their lungs time to heal and regain normal physiologic function.
As a bridge to LTx – for patients with irreversible end stage lung disease requiring LTx.
As a bridge to recovery after LTx – used as lung support for patients with PGD or severe hypoxemia.
Ex-Vivo Lung Perfusion and Assessment
Recently, the evaluation and reconditioning of donor lungs ex-vivo has been introduced into clinical practice as a method of improving the rate of donor lung utilization. Generally, about 15% to 20% of donor lungs are suitable for LTx, but these figures may increase with the use of ex-vivo lung perfusion. The ex-vivo evaluation and reconditioning of donor lungs is currently performed at the Toronto General Hospital (TGH) and preliminary results have been encouraging (Personal communication, clinical expert, December 17, 2009). If its effectiveness is confirmed, the use of the technique could lead to further expansion of donor organ pools and improvements in post-LTx outcomes.
Extracorporeal Lung support Technologies
ECMO
The ECMO system consists of a centrifugal pump, a membrane oxygenator, inlet and outlet cannulas, and tubing. The exchange of oxygen and CO2 then takes place in the oxygenator, which delivers the reoxygenated blood back into one of the patient’s veins or arteries. Additional ports may be added for haemodialysis or ultrafiltration.
Two different techniques may be used to introduce ECMO: venoarterial and venovenous. In the venoarterial technique, cannulation is through either the femoral artery and the femoral vein, or through the carotid artery and the internal jugular vein. In the venovenous technique cannulation is through both femoral veins or a femoral vein and internal jugular vein; one cannula acts as inflow or arterial line, and the other as an outflow or venous line. Venovenous ECMO will not provide adequate support if a patient has pulmonary hypertension or right heart failure. Problems associated with cannulation during the procedure include bleeding around the cannulation site and limb ischemia distal to the cannulation site.
ILA
Interventional Lung Assist (ILA) is used to remove excess CO2 from the blood of patients in respiratory failure. The system is characterized by a novel, low-resistance gas exchange device with a diffusion membrane composed of polymethylpentene (PMP) fibres. These fibres are woven into a complex configuration that maximizes the exchange of oxygen and CO2 by simple diffusion. The system is also designed to operate without the help of an external pump, though one can be added if higher blood flow is required. The device is then applied across an arteriovenous shunt between the femoral artery and femoral vein. Depending on the size of the arterial cannula used and the mean systemic arterial pressure, a blood flow of up to 2.5 L/min can be achieved (up to 5.5 L/min with an external pump). The cannulation is performed after intravenous administration of heparin.
Recently, the first commercially available extracorporeal membrane ventilator (NovaLung GmbH, Hechingen, Germany) was approved for clinical use by Health Canada for patients in respiratory failure. The system has been used in more than 2,000 patients with various indications in Europe, and was used for the first time in North America at the Toronto General Hospital in 2006.
Evidence-Based Analysis
The research questions addressed in this report are:
Does ILA/ECMO facilitate gas exchange in the lungs of patients with severe respiratory failure?
Does ILA/ECMO improve the survival rate of patients with respiratory failure caused by a range of underlying conditions including patients awaiting LTx?
What are the possible serious adverse events associated with ILA/ECMO therapy?
To address these questions, a systematic literature search was performed on September 28, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to September 28, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Studies in which ILA/ECMO was used as a bridge to recovery or bridge to LTx
Studies containing information relevant to the effectiveness and safety of the procedure
Studies including at least five patients
Exclusion Criteria
Studies reporting the use of ILA/ECMO for inter-hospital transfers of critically ill patients
Studies reporting the use of ILA/ECMO in patients during or after LTx
Animal or laboratory studies
Case reports
Outcomes of Interest
Reduction in partial pressure of CO2
Correction of respiratory acidosis
Improvement in partial pressure of oxygen
Improvement in patient survival
Frequency and severity of adverse events
The search yielded 107 citations in Medline and 107 citations in EMBASE. After reviewing the information provided in the titles and abstracts, eight citations were found to meet the study inclusion criteria. One study was then excluded because of an overlap in the study population with a previous study. Reference checking did not produce any additional studies for inclusion. Seven case series studies, all conducted in Germany, were thus included in this review (see Table 1).
Also included is the recently published CESAR trial, a multicentre RCT in the UK in which ECMO was compared with conventional intensive care management. The results of the CESAR trial were published when this review was initiated. In the absence of any other recent RCT on ECMO, the results of this trial were considered for this assessment and no further searches were conducted. A literature search was then conducted for application of ECMO as bridge to LTx patients (January, 1, 2005 to current). A total of 127 citations on this topic were identified and reviewed but none were found to have examined the use of ECMO as bridge to LTx.
Quality of Evidence
To grade the quality of evidence, the grading system formulated by the GRADE working group and adopted by MAS was applied. The GRADE system classifies the quality of a body of evidence as high, moderate, low, or very low according to four key elements: study design, study quality, consistency across studies, and directness.
Results
Trials on ILA
Of the seven studies identified, six involved patients with ARDS caused by a range of underlying conditions; the seventh included only patients awaiting LTx. All studies reported the rate of gas exchange and respiratory mechanics before ILA and for up to 7 days of ILA therapy. Four studies reported the means and standard deviations of blood gas transfer and arterial blood pH, which were used for meta-analysis.
Fischer et al. reported their first experience on the use of ILA as a bridge to LTx. In their study, 12 patients at high urgency status for LTx, who also had severe ventilation refractory hypercapnea and respiratory acidosis, were connected to ILA prior to LTx. Seven patients had a systemic infection or sepsis prior to ILA insertion. Six hours after initiation of ILA, the partial pressure of CO2 in arterial blood significantly decreased (P < .05) and arterial blood pH significantly improved (P < .05) and remained stable for one week (last time point reported). The partial pressure of oxygen in arterial blood improved from 71 mmHg to 83 mmHg 6 hours after insertion of ILA. The ratio of PaO2/FiO2 improved from 135 at baseline to 168 at 24 hours after insertion of ILA but returned to baseline values in the following week.
Trials on ECMO
The UK-based CESAR trial was conducted to assess the effectiveness and cost of ECMO therapy for severe, acute respiratory failure. The trial protocol were published in 2006 and details of the methods used for the economic evaluation were published in 2008. The study itself was a pragmatic trial (similar to a UK trial of neonatal ECMO), in which best standard practice was compared with an ECMO protocol. The trial involved 180 patients with acute but potentially reversible respiratory failure, with each also having a Murray score of ≥ 3.0 or uncompensated hypercapnea at a pH of < 7.2. Enrolled patients were randomized in a 1:1 ratio to receive either conventional ventilation treatment or ECMO while on ventilator. Conventional management included intermittent positive pressure ventilation, high frequency oscillatory ventilation, or both. As a pragmatic trial, a specific management protocol was not followed; rather the treatment centres were advised to follow a low volume low pressure ventilation strategy. A tidal volume of 4 to 8 mL/kg body weight and a plateau pressure of < 30 cm H2O were recommended.
Conclusions
ILA
Bridge to recovery
No RCTs or observational studies compared ILA to other treatment modalities.
Case series have shown that ILA therapy results in significant CO2 removal from arterial blood and correction of respiratory acidosis, as well as an improvement in oxygen transfer.
ILA therapy enabled a lowering of respiratory settings to protect the lungs without causing a negative impact on arterial blood CO2 and arterial blood pH.
The impact of ILA on patient long-term survival cannot be determined through the studies reviewed.
In-hospital mortality across studies ranged from 20% to 65%.
Ischemic complications were the most frequent adverse events following ILA therapy.
Leg amputation is a rare but possible outcome of ILA therapy, having occurred in about 0.9% of patients in these case series. New techniques involving the insertion of additional cannula into the femoral artery to perfuse the leg may lower this rate.
Bridge to LTx
The results of one case series (n=12) showed that ILA effectively removes CO2 from arterial blood and corrects respiratory acidosis in patients with ventilation refractory hypercapnea awaiting a LTx
Eight of the 12 patients (67%) awaiting a LTx were successfully transplanted and one-year survival for those transplanted was 80%
Since all studies are case series, the grade of the evidence for these observations is classified as “LOW”.
ECMO
Bridge to recovery
Based on the results of a pragmatic trial and an intention to treat analysis, referral of patient to an ECMO based centre significantly improves patient survival without disability compared to conventional ventilation. The results of CESAR trial showed that:
For patients with information about disability, survival without severe disability was significantly higher in ECMO arm
Assuming that the three patients in the conventional ventilation arm who did not have information about severe disability were all disabled, the results were also significant.
Assuming that none of these patients were disabled, the results were at borderline significance
A greater, though not statistically significant, proportion of patients in ECMO arm survived.
The rate of serious adverse events was higher among patients in ECMO group
The grade of evidence for the above observations is classified as “HIGH”.
Bridge to LTx
No studies fitting the inclusion criteria were identified.
There is no accurate data on the use of ECMO in patients awaiting LTx.
Economic Analysis
The objective of the economic analysis was to determine the costs associated with extracorporeal lung support technologies for bridge to LTx in adults. A literature search was conducted for which the target population was adults eligible for extracorporeal lung support. The primary analytic perspective was that of the Ministry of Health and Long-Term Care (MOHLTC). Articles published in English and fitting the following inclusion criteria were reviewed:
Full economic evaluations including cost-effectiveness analyses (CEA), cost-utility analyses (CUA), cost-benefit analyses (CBA);
Economic evaluations reporting incremental cost-effectiveness ratios (ICER) i.e. cost per quality adjusted life year (QALY), life years gained (LYG), or cost per event avoided; and
Studies in patients eligible for lung support technologies for to lung transplantation.
The search yielded no articles reporting comparative economic analyses.
Resource Use and Costs
Costs associated with both ILA and ECMO (outlined in Table ES-1) were obtained from the University Health Network (UHN) case costing initiative (personal communication, UHN, January 2010). Consultation with a clinical expert in the field was also conducted to verify resource utilization. The consultant was situated at the UHN in Toronto. The UHN has one ECMO machine, which cost approximately $100,000. The system is 18 years old and is used an average of 3 to 4 times a year with 35 procedures being performed over the last 9 years. The disposable cost per patient associated with ECMO is, on average, $2,200. There is a maintenance cost associated with the machine (not reported by the UHN), which is currently absorbed by the hospital’s biomedical engineering department.
The average capital cost of an ILA device is $7,100 per device, per patient, while the average cost of the reusable pump $65,000. The UHN has performed 16 of these procedures over the last 2.5 years. Similarly, there is a maintenance cost not that was reported by UHN but is absorbed by the hospital’s biomedical engineering department.
Resources Associated with Extracorporeal Lung Support Technologies
Hospital costs associated with ILA were based on the average cost incurred by the hospital for 11 cases performed in the FY 07/08 (personal communication, UHN, January 2010). The resources incurred with this hospital procedure included:
Device and disposables
OR transplant
Surgical ICU
Laboratory work
Medical imaging
Pharmacy
Clinical nutrition
Physiotherapy
Occupational therapy
Speech and language pathology
Social work
The average length of stay in hospital was 61 days for ILA (range: 5 to 164 days) and the average direct cost was $186,000 per case (range: $19,000 to $552,000). This procedure has a high staffing requirement to monitor patients in hospital, driving up the average cost per case.
PMCID: PMC3415698  PMID: 23074408
2.  Extracorporeal Rescue for Early and Late Graft Failure after Cardiac Transplantation: Short Result and Long-Term Followup 
The Scientific World Journal  2013;2013:364236.
Objectives. Graft failure after heart transplantation led to poor outcomes. We tried to analyze the outcomes of extracorporeal membrane oxygenation (ECMO) rescue in graft survival after transplantation. Methods. A retrospective review of 385 consecutive heart transplants revealed 46 patients of graft failure requiring ECMO rescue (48 episodes). The pretransplant and ECMO-related variables were evaluated. Results. The median age was 37.7 ± 18.8 years, and the median support time was 155 ± 145 hours. Success rate was 47.9% (23/48). Pretransplant ECMO use was 25% (12/48) and they had 58.3% mortality. The success rate in “early” graft failures was 51.4% (18/35) and 50% for “late” graft failure. The ischemic time with graft failure (178 ± 70 min) was significantly longer than that without graft failure. Preoperative status and the longer ischemic time may be the major factors for failure. Long-term 5-year survival demonstrated significant survival difference between graft failure and nongraft failure. No survival difference was shown between “early” and “late” graft failure. Conclusions. Graft failure still carried high mortality if advanced circulatory support was required. Early graft failure and late graft failure had similar outcomes. Further investigation of the risk factors shows that ECMO does play a role of rescue in catastrophic conditions.
doi:10.1155/2013/364236
PMCID: PMC3817658  PMID: 24228000
3.  Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study 
Critical Care  2013;17(2):R73.
Introduction
Mortality of patients on extracorporeal membrane oxygenation (ECMO) remains high. The objectives of this study were to assess the factors associated with outcome of patients undergoing ECMO in a large ECMO referral centre and to compare veno-arterial ECMO (VA ECMO) with veno-venous ECMO (VV ECMO).
Methods
We reviewed a prospectively obtained ECMO database and patients' medical records between January 2005 and June 2011. Demographic characteristics, illness severity at admission, ECMO indication, organ failure scores before ECMO and the ECMO mode and configuration were recorded. Bleeding, neurological, vascular and infectious complications that occurred on ECMO were also collected. Demographic, illness, ECMO support descriptors and complications associated with hospital mortality were analysed.
Results
ECMO was initiated 158 times in 151 patients. VA ECMO (66.5%) was twice as common as VV ECMO (33.5%) with a median duration significantly shorter than for VV ECMO (7 days (first and third quartiles: 5; 10 days) versus 10 days (first and third quartiles: 6; 16 days)). The most frequent complications during ECMO support were bleeding and bloodstream infections regardless of ECMO type. More than 70% of the ECMO episodes were successfully weaned in each ECMO group. The overall mortality was 37.3% (37.1% for the patients who underwent VA ECMO, and 37.7% for the patients who underwent VV ECMO). Haemorrhagic events, assessed by the total of red blood cell units received during ECMO, were associated with hospital mortality for both ECMO types.
Conclusions
Among neurologic, vascular, infectious and bleeding events that occurred on ECMO, bleeding was the most frequent and had a significant impact on mortality. Further studies are needed to better investigate bleeding and coagulopathy in these patients. Interventions that reduce these complications may improve outcome.
doi:10.1186/cc12681
PMCID: PMC4056036  PMID: 23594433
4.  Factors influencing the outcome of paediatric cardiac surgical patients during extracorporeal circulatory support 
Background
Veno-arterial extracorporeal membrane oxygenation (ECMO) is a common modality of circulatory assist device used in children. We assessed the outcome of children who had ECMO following repair of congenital cardiac defects (CCD) and identified the risk factors associated with hospital mortality.
Methods
From April 1990 to December 2003, 53 patients required ECMO following surgical correction of CCD. Retrospectively collected data was analyzed with univariate and multivariate logistic regression analysis.
Results
Median age and weight of the patients were 150 days and 5.4 kgs respectively. The indications for ECMO were low cardiac output in 16, failure to wean cardiopulmonary bypass in 13, cardiac arrest in 10 and cardio-respiratory failure in 14 patients. The mean duration of ECMO was 143 hours. Weaning off from ECMO was successful in 66% and of these 83% were survival to hospital-discharge. 37.7% of patients were alive for the mean follow-up period of 75 months. On univariate analysis, arrhythmias, ECMO duration >168 hours, bleeding complications, renal replacement therapy on ECMO, arrhythmias and cardiac arrest after ECMO were associated with hospital mortality.
On multivariate analysis, abnormal neurology, bleeding complications and arrhythmias after ECMO were associated with hospital mortality. Extra and intra-thoracic cannulations were used in 79% and 21% of patients respectively and extra-thoracic cannulation had significantly less bleeding complications (p = 0.031).
Conclusion
ECMO provides an effective circulatory support following surgical repair of CCD in children. Extra-thoracic cannulation is associated with less bleeding complications. Abnormal neurology, bleeding complications on ECMO and arrhythmias after ECMO are poor prognostic indicators for hospital survival.
doi:10.1186/1749-8090-2-4
PMCID: PMC1797039  PMID: 17217529
5.  Extracorporeal membrane oxygenation for pediatric respiratory failure: History, development and current status 
Extracorporeal membrane oxygenation (ECMO) is currently used to support patients of all ages with acute severe respiratory failure non-responsive to conventional treatments, and although initial use was almost exclusively in neonates, use for this age group is decreasing while use in older children remains stable (300-500 cases annually) and support for adults is increasing. Recent advances in technology include: refinement of double lumen veno-venous (VV) cannulas to support a large range of patient size, pumps with lower prime volumes, more efficient oxygenators, changes in circuit configuration to decrease turbulent flow and hemolysis. Veno-arterial (VA) mode of support remains the predominant type used; however, VV support has lower risk of central nervous injury and mortality. Key to successful survival is implementation of ECMO before irreversible organ injury develops, unless support with ECMO is used as a bridge to transplant. Among pediatric patients treated with ECMO mortality varies by pulmonary diagnosis, underlying condition, other non-pulmonary organ dysfunction as well as patient age, but has remained relatively unchanged overall (43%) over the past several decades. Additional risk factors associated with death include prolonged use of mechanical ventilation (> 2 wk) prior to ECMO, use of VA ECMO, older patient age, prolonged ECMO support as well as complications during ECMO. Medical evidence regarding daily patient management specifically related to ECMO is scant, it usually mirrors care recommended for similar patients treated without ECMO. Linkage of the Extracorporeal Life Support Organization dataset with other databases and collaborative research networks will be required to address this knowledge deficit as most centers treat only a few pediatric respiratory failure patients each year.
doi:10.5492/wjccm.v2.i4.29
PMCID: PMC3953872  PMID: 24701414
Respiratory failure; Pediatrics; Extracorporeal life support; Veno-arterial; Veno-venous
6.  Extracorporeal life support as bridge to lung transplantation: a systematic review 
Critical Care  2015;19(1):19.
Introduction
Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at a high risk of death. Extracorporeal membrane oxygenation (ECMO) has been proposed as an alternative bridging strategy to mechanical ventilation. The aim of this study was to assess the current evidence regarding how the ECMO bridge influences patients’ survival and length of hospital stay.
Methods
We performed a systematic review by searching PubMed, EMBASE and the bibliographies of retrieved articles. Three reviewers independently screened citation titles and abstracts and agreement was reached by consensus. We selected studies enrolling patients who received ECMO with the intention to bridge lung transplant. We included randomized controlled trials (RCTs), case–control studies and case series with ten or more patients. Outcomes of interest included survival and length of hospital stay. Quantitative data summaries were made when feasible.
Results
We identified 82 studies, of which 14 were included in the final analysis. All 14 were retrospective studies which enrolled 441 patients in total. Because of the broad heterogeneity among the studies we did not perform a meta-analysis. The mortality rate of patients on ECMO before lung transplant and the one-year survival ranged from 10% to 50% and 50% to 90%, respectively. The intensive care and hospital length of stay ranged between a median of 15 to 47 days and 22 to 47 days, respectively. There was a general paucity of high-quality data and significant heterogeneity among studies in the enrolled patients and technology used, which confounded analysis.
Conclusions
In most of the studies, patients on ECMO while awaiting lung transplantation also received invasive mechanical ventilation. Therefore, whether ECMO as an alternative, rather than an adjunction, to invasive mechanical ventilation is a better bridging strategy to lung transplantation still remains an unresolved issue. ECMO support as a bridge for these patients could provide acceptable one-year survival. Future studies are needed to investigate ECMO as part of an algorithm of care for patients with end-stage lung disease.
doi:10.1186/s13054-014-0686-7
PMCID: PMC4302424
7.  Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation 
Objective
To determine if, in children, plasma glial fibrillary acidic protein (GFAP) is associated with brain injury during extracorporeal membrane oxygenation (ECMO) and with mortality.
Design
Prospective, observational study.
Setting
Pediatric intensive care unit in an urban tertiary care academic center.
Patients
Neonatal and pediatric ECMO patients (n=22).
Interventions
Serial blood sampling for GFAP measurements.
Measurements and Main Results
Prospective patients age 1 day-18 years who required ECMO from April 2008 to August 2009 were studied. GFAP was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5-16 years) and 59 NICU infants without neurologic injury. In controls, the median GFAP concentration was 0.055 ng/mL (IQR: 0-0.092 ng/mL) and the 95th percentile of GFAP was 0.436ng/mL. In ECMO patients, plasma GFAP was measured at 6, 12 and every 24 hours after cannulation. We enrolled 22 children who underwent ECMO. Median age was 7 days (IQR, 2 days-9 years), and primary ECMO indication was: cardiac failure, 6/22 (27.3%), respiratory failure, 12/22 (54.5%), ECPR, 3/22 (13.6%), and sepsis, 1/22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the ECMO group, peak GFAP levels were higher in children with brain injury than those without (median, 5.9 vs 0.09ng/mL, p=0.04) and in non-survivors compared to survivors to discharge (median, 5.9 vs 0.09ng/mL, p=0.04). The odds ratio (OR) for brain injury for GFAP >0.436ng/mL vs normal was 11.5 (95%CI: 1.3-98.3) and the OR for mortality was 13.6 (95%CI: 1.7-108.5).
Conclusions
High GFAP during ECMO is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of ECMO patients to improve outcomes and benchmark new therapies.
doi:10.1097/PCC.0b013e3181fe3ec7
PMCID: PMC3686089  PMID: 21057367
ECMO; extracorporeal membrane oxygenation; GFAP; glial fibrillary acidic protein; biochemical marker; intracranial hemorrhage
8.  Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure 
Critical Care  2014;18(1):R20.
Introduction
Acute respiratory failure (ARF) is the main reason for intensive care unit (ICU) admissions in patients with hematologic malignancies (HMs). We report the first series of adult patients with ARF and HMs treated with extracorporeal membrane oxygenation (ECMO).
Methods
This is a retrospective cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n = 5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10), thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and transfusion-related acute lung injury (n = 1). Diagnosis of HM was established during ECMO in four patients, and five first received (immuno-) chemotherapy on ECMO.
Results
Before ECMO, the PaO2/FiO2 ratio was 60 (53 to 65), (3.3 to 3.7). Three patients received venoarterial ECMO because of acute circulatory failure in addition to ARF; all other patients received venovenous ECMO. All patients needed vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months); five patients were in complete remission, one in partial remission, and one had relapsed.
Conclusions
ECMO therapy is feasible in selected patients with HMs and ARF and can be associated with long-term disease-free survival.
doi:10.1186/cc13701
PMCID: PMC4055976  PMID: 24443905
9.  Short-term outcomes of cadaveric lung transplantation in ventilator-dependent patients 
Critical Care  2009;13(4):R129.
Introduction
Survival after cadaveric lung transplantation (LTx) in respiratory failure recipients who were already dependent on ventilation support prior to transplantation is poor, with a relatively high rate of surgical mortality and morbidity. In this study, we sought to describe the short-term outcomes of bilateral sequential LTx (BSLTx) under extracorporeal membrane oxygenation (ECMO) support in a consecutive series of preoperative respiratory failure patients.
Methods
Between July 2006 and July 2008, we performed BSLTx under venoarterious (VA) ECMO support in 10 respiratory failure patients with various lung diseases. Prior to transplantation, 6 patients depended on invasive mechanical ventilation support and the others (40%) needed noninvasive positive pressure ventilation to maintain adequate gas exchange. Their mean age was 40.9 years and the mean observation period was 16.4 months.
Results
Except for 1 ECMO circuit that had been set up in the intensive care unit for pulmonary crisis 5 days prior to transplantation, most ECMO (90%) circuits were set up in the operating theater prior to pneumonectomy of native lung during transplantation. Patients were successfully weaned off ECMO circuits immediately after transplantation in 8 cases, and within 1 day (1/10 patients) and after 9 days (1/10 patients) due to severe reperfusion lung edema following transplantation. The mean duration of ECMO support in those successfully weaned off in the operating theater (n = 8) was 7.8 hours. The average duration of intensive care unit stay (n = 10) was 43.1 days (range, 35 to 162 days) and hospital stay (n = 10) was 70 days (range, 20 to 86 days). Although 4 patients (40%) had different degrees of complicated postoperative courses unrelated to ECMO, all patients were discharged home postoperatively. The mean forced vital capacity and the forced expiratory volume in 1 second both increased significantly postoperatively. The cumulative survival rates at 3 months and at 12 months post-transplantation were 100% and 90%.
Conclusions
Although BSLTx in this critical population has varied surgical complications and prolonged length of postoperative ICU and hospital stays, all the patients observed in this study could tolerate the transplant procedures under VA ECMO support with promising pulmonary function and satisfactory short-term outcome.
doi:10.1186/cc7989
PMCID: PMC2750186  PMID: 19660110
10.  Recovery of renal function and survival after continuous renal replacement therapy during extracorporeal membrane oxygenation 
Objective
To assess the outcome of pediatric patients supported by concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT).
Design, Setting, and Patients
Acute kidney injury (AKI) is associated with mortality in ECMO patients. CRRT on ECMO provides an efficient and potentially beneficial method of AKI management. Concern that concomitant CRRT use increases the risk of developing anuria and chronic renal failure (CRF) limits its use in some centers. We hypothesized that development of CRF is rare with concurrent ECMO and CRRT. Outcomes of 154 ECMO/CRRT patients cared for over 10 years at a referral pediatric medical center were evaluated.
Measurements and Main Results
Among 68 ECMO/CRRT survivors (44%), 45 were assigned a pRIFLE score at CRRT initiation. Seventeen patients (38%) met criteria for Risk, 15 (33%) for Injury, and 10 (22%) for Failure. Two Failure patients later met End stage criteria. Of all survivors, 18 (26%) required ongoing RRT (15 CVVH, 2 peritoneal dialysis, 1 intermittent hemodialysis) following ECMO discontinuation. Renal recovery occurred in 65 of 68 (96%) before discharge. One neonatal patient had sepsis-induced renal injury on transfer, but normal creatinine one month later. Two pediatric patients with vasculitis and primary renal disease at presentation (both meeting Failure criteria) developed end-stage renal disease. One received peritoneal dialysis and subsequent renal transplant. The other has diminished function without need for renal replacement therapy.
Conclusion
In the absence of primary renal disease, CRF did not occur following concurrent use of CRRT with ECMO. Concern for precipitating CRF by using CRRT during ECMO is not substantiated by this large single center experience. Consistent with previous reports, mortality is higher in patients receiving concomitant CRRT and ECMO compared to those receiving ECMO alone. Mortality is similar to patients requiring CRRT who are not on ECMO. Additional studies are warranted to determine the optimal role of CRRT use in ECMO patients.
doi:10.1097/PCC.0b013e3181e2a596
PMCID: PMC4054600  PMID: 20453702
ECMO; ECLS; CVVH; CRRT; Outcome; Chronic Renal Failure
11.  Cardiac ECMO for biventricular hearts after paediatric open heart surgery 
Heart  2004;90(5):545-551.
Objective: To delineate predictors of hospital survival in a large series of children with biventricular physiology supported with extracorporeal membrane oxygenation (ECMO) after open heart surgery.
Results: 81 children were placed on ECMO after open heart surgery. 58% (47 of 81) were transferred directly from cardiopulmonary bypass to ECMO. Hospital survival was 49% (40 of 81) but there were seven late deaths among these survivors (18%). Factors that improved the odds of survival were initiation of ECMO in theatre (64% survival (30 of 47)) rather than the cardiac intensive care unit (29% survival (10 of 34)) and initiation of ECMO for reactive pulmonary hypertension. Important adverse factors for hospital survival were serious mechanical ECMO circuit problems, renal support, residual lesions, and duration of ECMO.
Conclusions: Hospital survival of children with biventricular physiology who require cardiac ECMO is similar to that found in series that include univentricular hearts, suggesting that successful cardiac ECMO is critically dependent on the identification of hearts with reversible ventricular dysfunction. In our experience of postoperative cardiac ECMO, the higher survival of patients cannulated in the operating room than in the cardiac intensive care unit is due to early effective support preventing prolonged hypoperfusion and the avoidance of a catastrophic cardiac arrest.
doi:10.1136/hrt.2002.003509
PMCID: PMC1768194  PMID: 15084554
congenital heart surgery; ECMO; extracorporeal membrane oxygenation; ventricular dysfunction
12.  Prediction of mortality in adult patients with severe acute lung failure receiving veno-venous extracorporeal membrane oxygenation: a prospective observational study 
Critical Care  2014;18(2):R67.
Introduction
Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.
Methods
Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models.
Results
In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and hemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.
Conclusions
While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
doi:10.1186/cc13824
PMCID: PMC4057201  PMID: 24716510
13.  Local Experience with Extracorporeal Membrane Oxygentaion in Children with Acute Fulminant Myocarditis 
PLoS ONE  2013;8(12):e82258.
To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in children with acute fulminant myocarditis, we retrospectively analyzed the data of five children with acute fulminant myocarditis in the intensive care unit (ICU) at the Affiliated Children’s Hospital, Zhejiang University from February 2009 to November 2012. The study group included two boys and three girls ranging in age from 9 to 13 years (median 10 years). Body weight ranged from 25 to 33 kg (mean 29.6 kg). They underwent extracorporeal membrane oxygenation (ECMO) through a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40–142 h). Extracorporeal circulation was established in all five children. After treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were greatly improved in the four children who survived. These four children were successfully weaned from ECMO and discharged from hospital machine-free, for a survival rate of 80% (4/5). One child died still dependent on the machine. Cause of death was irrecoverable cardiac function and multiple organ failure. Complications during ECMO included three cases of suture bleeding, one case of acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia. During the follow-up period of 4–50 months, the four surviving children recovered with normal cardiac function and no abnormal functions of other organs. The application of ECMO in acute fulminant myocarditis, even in local centers that experience low incidence of this disease, remains an effective approach. Larger studies to determine optimal timing of placement on ECMO to guide local centers are warranted.
doi:10.1371/journal.pone.0082258
PMCID: PMC3857228  PMID: 24349238
14.  Developmental outcome in newborn infants treated for acute respiratory failure with extracorporeal membrane oxygenation: present experience 
Objective
To describe the later health status of newborn infants who received extracorporeal membrane oxygenation (ECMO) for acute respiratory failure in the era after the UK ECMO trial.
Design
Prospective follow up study of newborn infants who received ECMO at a single centre between January 1997 and January 2001.
Setting
Departments of ECMO and Paediatric Intensive Care, University Hospitals of Leicester.
Patients
All babies who received ECMO within 14 days of birth.
Interventions
Neurodevelopment screening using the schedule for growing skills‐II (SGS‐II) assessment tool.
Main outcome measures
Survival at 12 months of age by disease and functional development at follow up.
Results
A total of 145 neonates received ECMO for treatment of respiratory failure. Of these, 108 (75%) were alive at 1 year of age. There were no deaths in children treated for respiratory failure secondary to meconium aspiration syndrome (73/145). Ninety three (86% of survivors) infants attended a follow up visit at 11–19 months postnatal age. Eighty two were classed as normal, seven as having “impairment”, and four as having “severe disability”.
Conclusions
Most newborn infants with acute respiratory failure treated with ECMO will have a normal neurodevelopment screening assessment at 11–19 months of postnatal age. There is no evidence to suggest that changes in neonatal practice since the UK ECMO trial have led to changes in outcome of infants undergoing ECMO therapy.
doi:10.1136/adc.2004.066290
PMCID: PMC2672642  PMID: 16159956
development; outcome; respiratory; extracorporeal membrane oygenation; lung
15.  Neurodevelopmental outcome after neonatal extracorporeal membrane oxygenation. 
OBJECTIVE: To determine the neurodevelopmental outcome of neonates who underwent extracorporeal membrane oxygenation (ECMO group) and similarly critically ill newborns with a lower Oxygenation Index who underwent conventional treatment (comparison group), and to determine whether factors such as the underlying diagnosis and the distance transported from outlying areas affect outcome. DESIGN: Multicentre prospective longitudinal comparative outcome study. SETTING: An ECMO centre providing services to all of western Canada and four tertiary care neonatal follow-up clinics. SUBJECTS: All neonates who received treatment between February 1989 and January 1992 at the Western Canadian Regional ECMO Center and who were alive at 2 years of age; 38 (95%) of the 40 surviving ECMO-treated subjects and 26 (87%) of the 30 surviving comparison subjects were available for follow-up. INTERVENTIONS: ECMO or conventional therapy for respiratory failure. OUTCOME MEASURES: Neurodevelopmental disability (one or more of cerebral palsy, visual or hearing loss, seizures, severe cognitive disability), and mental and performance developmental indexes of the Bayley Scales of Infant Development. RESULTS: Six (16%) of the ECMO-treated children had neurodevelopmental disabilities at 2 years of age, as compared with 1 (4%) of the comparison subjects; the difference was not statistically significant. The mean mental developmental index (91.8 [standard deviation (SD) 19.5] v. 100.5 [SD 25.4]) and the mean performance developmental index (87.2 [SD 20.0] v. 96.4 [SD 20.9]) did not differ significantly between the ECMO group and the comparison group respectively. Among the ECMO-treated subjects those whose underlying diagnosis was sepsis had the lowest Bayley indexes, significantly lower than those whose underlying diagnosis was meconium aspiration syndrome. The distance transported did not affect outcome. CONCLUSIONS: Neurodevelopmental disability and delay occurred in both groups. The underlying diagnosis appears to affect outcome, whereas distance transported does not. These findings support early transfer for ECMO of critically ill neonates with respiratory failure who do not respond to conventional treatment. Larger multicentre studies involving long-term follow-up are needed to confirm these findings.
PMCID: PMC1338020  PMID: 7540105
16.  Concurrent treatment with a tumor necrosis factor-alpha inhibitor and veno-venous extracorporeal membrane oxygenation in a post-hematopoietic stem cell transplant patient with idiopathic pneumonia syndrome: a case report 
Idiopathic pneumonia syndrome (IPS) is a fatal non-infectious respiratory complication that develops after hematopoietic stem cell transplantation (HSCT). Because of the poor prognosis of post-HSCT patients with IPS requiring mechanical ventilatory support, performing extracorporeal membrane oxygenation (ECMO) has been regarded as relatively contraindicated in these patients. A tumor necrosis factor-alpha inhibitor, etanercept, has been reported to be a promising treatment option for post-HSCT patients with IPS; however, the phase III clinical trial of etanercept has recently been terminated without definitive conclusion. If post-HSCT patients with IPS really benefit from etanercept, mechanical ventilation (MV)-dependent IPS patients might be worth receiving ECMO treatment in line with the protective lung strategy. We therefore performed veno-venous ECMO (VV-ECMO), which substantially acted as an extracorporeal carbon dioxide removal, on a 56-year-old post-HSCT male with severe MV-dependent IPS due to graft-versus-host disease. Although a serious bleeding complication due to post-HSCT thrombocytopenia occurred, the VV-ECMO was continued for 11 days. The patient successfully entered remission of the IPS and was finally extubated on the 12th MV day. However, the patient soon complained of dyspnea, probably due to cytomegalovirus infection and/or exacerbation of the IPS, and was reintubated after 3 days of extubation. The patient then rapidly developed irreversible type II respiratory failure despite the administration of etanercept and an anti-cytomegalovirus agent and died on the eighth re-MV day. The autopsy findings of the patient revealed diffuse alveolar damage and alveolar hemorrhage, accompanied with bronchitis obliterans in his lungs, as well as whole body cytomegalovirus infection, which were compatible with the clinical diagnosis of the patient. We think that the legitimacy of this treatment strategy is dependent on the overall prognosis of IPS, which is influenced by the complications induced by immunosuppressants and ECMO, especially infections and bleeding.
Electronic supplementary material
The online version of this article (doi:10.1186/s40560-014-0048-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s40560-014-0048-1
PMCID: PMC4336281
Idiopathic pneumonia syndrome; Extracorporeal membrane oxygenation; Extracorporeal carbon dioxide removal; Tumor necrosis factor-alpha inhibitor; Etanercept; Hematopoietic stem cell transplantation; Graft-versus-host disease
17.  Extracorporeal membrane oxygenation 
F1000Prime Reports  2013;5:55.
Extracorporeal membrane oxygenation (ECMO) is an advanced form of life support technology whereby venous blood is oxygenated outside of the body and returned to the patient. ECMO was initially used as last-resort rescue therapy for patients with severe respiratory failure. Over the last four decades, it has developed into a safe, standard therapy for newborns with progressive cardiorespiratory failure, as a resuscitation therapy after cardiac arrest, and in combination with other treatments such as hypothermia and various blood filtration therapies. ECMO has also become routine for children and adults with all forms of cardiogenic shock and is also routine in early graft failure after transplantation. The one area of ongoing debate is the role of ECMO in adults with hypoxemic respiratory failure. As ECMO equipment becomes safer, earlier use improves patient outcomes. Several modifications of the two basic venovenous and venoarterial ECMO systems are now occurring, as are many minor variations in cannulation strategies and systems of care for patients receiving ECMO. The indications and situations in which ECMO have been tried continue to change, and ECMO for sub-acute and chronic illnesses is now commonplace, as is the use of ECMO in patients with clinical problems previously regarded as contraindications, such as sepsis, malignancy, and immunosuppression.
doi:10.12703/P5-55
PMCID: PMC3876455  PMID: 24404382
18.  Preoperative extracorporeal membrane oxygenation as a bridge to cardiac surgery in children with congenital heart disease 
The Annals of thoracic surgery  2009;88(4):1306-1311.
Background
The efficacy of extracorporeal membrane oxygenation (ECMO) in bridging children with unrepaired heart defects to a definitive or palliative surgical procedure has been rarely reported. The goal of this study is to report our institutional experience with ECMO used to provide preoperative stabilization after acute cardiac or respiratory failure in patients with congenital heart disease before cardiac surgery.
Methods
A retrospective review of the ECMO database at Children's Hospital Boston was undertaken. Children with unrepaired congenital heart disease supported with ECMO for acute cardiac or respiratory failure as bridge to a definitive or palliative cardiac surgical procedure were identified. Data collection included patient demographics, indication for ECMO, details regarding ECMO course and complications, and survival to hospital discharge.
Results
Twenty-six patients (18 male, 8 female) with congenital heart disease were bridged to surgical palliation or anatomic repair with ECMO. Median age and weight at ECMO cannulation were, respectively, 0.12 months (range, 0 to 193) and 4 kg (range, 1.8 to 67 kg). Sixteen patients (62%) survived to hospital discharge. Variables associated with mortality included inability to decannulate from ECMO after surgery (p = 0.02) and longer total duration of ECMO (p = 0.02). No difference in outcomes was found between patients with single and biventricular anatomy.
Conclusions
Extracorporeal membrane oxygenation, used as a bridge to surgery, represents a useful modality to rescue patients with failing circulation and unrepaired complex heart defects.
doi:10.1016/j.athoracsur.2009.06.074
PMCID: PMC4249921  PMID: 19766826
19.  Effects of intra-aortic balloon pump on cerebral blood flow during peripheral venoarterial extracorporeal membrane oxygenation support 
Background
The addition of an intra-aortic balloon pump (IABP) during peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) support has been shown to improve coronary bypass graft flows and cardiac function in refractory cardiogenic shock after cardiac surgery. The purpose of this study was to evaluate the impact of additional IABP support on the cerebral blood flow (CBF) in patients with peripheral VA ECMO following cardiac procedures.
Methods
Twelve patients (mean age 60.40 ± 9.80 years) received VA ECMO combined with IABP support for postcardiotomy cardiogenic shock after coronary artery bypass grafting. The mean CBF in the bilateral middle cerebral arteries was measured with and without IABP counterpulsation by transcranial Doppler. The patients provided their control values. The mean CBF data were divided into two groups (pulsatile pressure greater than 10 mmHg, P group; pulsatile pressure less than 10 mmHg, N group) based on whether the patients experienced cardiac stun. The mean cerebral blood flow in VA ECMO (IABP turned off) alone and VA ECMO with IABP support were compared using the paired t test.
Results
All of the patients were successfully weaned from VA ECMO, and eight patients survived to discharge. The addition of IABP to VA ECMO did not change the mean CBF (251.47 ± 79.28 ml/min vs. 251.30 ± 79.47 ml/min, P = 0.96). The mean CBF was higher in VA ECMO alone than in VA ECMO combined with IABP support in the N group (257.68 ± 97.21 ml/min vs. 239.47 ± 95.60, P = 0.00). The addition of IABP to VA ECMO support increased the mean CBF values significantly compared with VA ECMO alone (261.68 ± 82.45 ml/min vs. 244.43 ± 45.85 ml/min, P = 0.00) in the P group.
Conclusion
These results demonstrate that an IABP significantly changes the CBF during peripheral VA ECMO, depending on the antegrade blood flow by spontaneous cardiac function. The addition of an IABP to VA ECMO support decreased the CBF during cardiac stun, and it increased CBF without cardiac stun.
doi:10.1186/1479-5876-12-106
PMCID: PMC4006449  PMID: 24766774
Intra-aortic balloon pump; Venoarterial extracorporeal membrane oxygenation; Cerebral blood flow; Transcranial doppler ultrasound
20.  Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study 
Critical Care  2013;17(4):R151.
Introduction
Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support.
Methods
This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage.
Results
Of 242 patients included, 179 (74%) survived. Median age at the start of ECMO was 39 hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk, 55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only 71 (46%) patients of all 153 AKI patients improved by at least one RIFLE category. With regression analysis, it was found that nitric oxide ventilation (P = 0.04) and younger age at the start of ECMO (P = 0.004) were significant predictors of AKI. Survival until intensive care unit discharge was significantly lower for patients in the Failure category (35%) as compared with the Non-AKI (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no significant differences were found between the three latter RIFLE categories.
Conclusions
Two thirds of neonates receiving ECMO had AKI, with a significantly increased mortality risk for patients in the Failure category. As AKI during childhood may predispose to chronic kidney disease in adulthood, long-term monitoring of kidney function after ECMO is warranted.
doi:10.1186/cc12830
PMCID: PMC4057448  PMID: 23883698
Critical care; acute kidney injury; extracorporeal membrane oxygenation (ECMO); RIFLE; serum creatinine
21.  Extracorporeal membrane oxygenation in near-drowning patients with cardiac or pulmonary failure 
Background
The aim of this study was to determine the early outcomes of using extracorporeal membrane oxygenation (ECMO) in near-drowning patients with cardiac or pulmonary failure.
Methods
This study was based on data from 9 patients including 2 children (mean age 33; 8 males, 1 female) who received ECMO after near-drowning between 2008 and 2013. Veno-arterial or veno-arteriovenous ECMO was used in 2 patients with sustained cardiac arrest and veno-venous ECMO was used in 7 patients with severe acute respiratory distress syndrome (ARDS). The means of the partial arterial oxygen pressure (PaO2), Murray score, sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS-II) prior to ECMO were 59.7 ± 9.9 mmHg on 100% oxygen, 3.5 ± 0.6, 11.4 ± 1.9, and 73.0 ± 9.2, respectively.
Results
The PaO2 mean improved to 182 ± 152 mmHg within 2 h post-ECMO. The mean of SOFA score and SAPS-II decreased significantly to 8.6 ± 3.2 (p = 0.013) and 46.4 ± 5.1 (p = 0.008), respectively, at 24 h post-ECMO with mean flow rate of 3.9 ± 0.8 l/min. ECMO was weaned at a mean duration of 188 (range, 43–672) h in all patients. Seven patients were discharged home without neurological sequelae, while 2 patients who had hypoxic brain damage died after further referral. The overall survival with favourable neurological outcomes at 3 months was 77.8%. There were no complications related to ECMO.
Conclusions
ECMO was safe and effective for patients with ongoing cardiac arrest or ARDS after a near-drowning incident and can be used as a resuscitative strategy in near-drowning patients with cardiac or pulmonary failure resistant to conventional ventilator therapy.
doi:10.1186/s13049-014-0077-8
PMCID: PMC4269952  PMID: 25496812
Drowning; Near-drowning; Extracorporeal membrane oxygenation; Cardiac or pulmonary failure; Acute respiratory distress syndrome
22.  Predicting outcome in ex-premature infants supported with extracorporeal membrane oxygenation for acute hypoxic respiratory failure 
Objective: To identify predictors of outcome in ex-premature infants supported with extracorporeal membrane oxygenation (ECMO) for acute hypoxic respiratory failure.
Methods: Retrospective review of ex-premature infants with acquired acute hypoxic respiratory failure requiring ECMO support in the United Kingdom from 1992 to 2001. Review of follow up questionnaires completed by general practitioners and local paediatricians.
Results: Sixty four ex-premature infants (5–10 each year) received ECMO support, despite increased use of advanced conventional treatments over the decade. The most common infective agent was respiratory syncytial virus (85% of cases). Median birth gestation was 29 weeks and median corrected age at the time of ECMO support was 42 weeks. Median ECMO support duration was relatively long, at 229 hours. Survival to hospital discharge and to 6 months was 80%, remaining similar throughout the period of review. At follow up, 60% had long term neurodisability and 79% had chronic pulmonary problems. Of pre-ECMO factors, baseline oxygen dependence, younger age, and inpatient status were associated with non-survival (p ⩽ 0.05). Of ECMO related factors, patient complications were independently associated with adverse neurodevelopmental outcome and death (p < 0.01).
Conclusions: Survival rates for ex-premature infants after ECMO support are favourable, but patients suffer a high burden of morbidity during intensive care and over the long term. At the time of ECMO referral, baseline oxygen dependence is the most important predictor of death, but no combination of the factors considered was associated with a mortality that would preclude ECMO support.
doi:10.1136/adc.2003.033308
PMCID: PMC1721757  PMID: 15321962
23.  Double lumen bi-cava cannula for veno-venous extracorporeal membrane oxygenation as bridge to lung transplantation in non-intubated patient 
Extracorporeal membrane oxygenation (ECMO) is used for refractory respiratory failure. Normally, ECMO is implanted in intubated patients as a last resort. We report the case of a non-intubated patient who benefited from veno-venous (VV) ECMO. A 35-year old cystic fibrosis man presented a severe respiratory decompensation with refractory hypercapnia. We opted for an ECMO instead of mechanical ventilation (MV). We implanted a double lumen bi-cava cannula (DLC) (Avalon EliteTM) in the right jugular vein. Before ECMO implantation, the patient presented refractory respiratory failure (pH = 7.1, PaO2 = 83 mmHg, PaCO2 = 103 mmHg). We proposed that the patient be placed on the high emergency lung transplantation waiting list after failure to wean him from ECMO. This registration was effective 10 days after ECMO implantation. The patient was grafted the next day. Under ECMO, mean PaO2, PaCO2 and TCA were 80.6 ± 14.2, 53.8 ± 6.4 mmHg and 56.2 ± 9.7 s, respectively. The patient could eat, drink, talk and practice chest physiotherapy. The evolution was uneventful under ECMO. Weaning from ECMO was done in the operating theatre after transplantation. VV ECMO with DLC is safe and feasible in non-intubated patients. It avoids potential complications of MV, and allows respiratory assistance as bridge to transplantation.
doi:10.1093/icvts/ivr046
PMCID: PMC3420286  PMID: 22108944
Extracorporeal membrane oxygenation; Veno-venous extracorporeal membrane oxygenation; Non-intubated patient; Transplantation; Lung transplantation; Bridge to transplantation; Cystic fibrosis
24.  Prognosis in the Patients with Prolonged Extracorporeal Membrane Oxygenation 
Background
Prolonged usage of extracorporeal membrane oxygenation (ECMO) may induce multi-organ failure. This study is aimed to evaluate prognostic factors in the patients with ECMO. Also, the prognosis of ECMO with Kidney Injury Network Scoring system is studied.
Materials and Methods
From May 2005 to July 2011, 172 cases of ECMO were performed. The cases of perioperative use of ECMO were excluded. Renal failure patient and younger than 15 years old one were also excluded. As a result, 26 cases were enrolled in this study. Male patients were 15 (57.7%), and mean age was 56.57±17.03 years old. Demographic data, ECMO parameters, weaning from ECMO, and application of continuous renal replacement therapy are collected and Acute Kidney Injury Network (AKIN) scores were evaluated just before ECMO and day 1, day 2 during application of ECMO.
Results
Venoarterial ECMO was applied in 22 cases (84.6%). The reasons for applications of ECMO were cardiac origin in 21 (80.8%), acute respiratory distress syndrome in 4, and septic shock in 1 case. Successful weaning from ECMO was achieved in 15 cases (57.7%), and survival discharge rate was 9 cases (34.6%). Mean duration of application of ECMO was 111.39±54.06 hours. In univariate analysis, myocarditis was independent risk factors on weaning failure. Using the receiver operating characteristic curve, level of hemoglobin on 24 hours after ECMO, and base excess on 48 hours after ECMO were showed more than 0.7. AKIN score was not matched the prognosis of the patients with ECMO.
Conclusion
In our study, the prognosis of the patients with myocarditis was poor. Hemoglobin level at first 24 hours, and degree of acidosis at 48 hours were useful methods in relating with prognosis of ECMO. AKIN scoring system was not related with the prognosis of the patients. Further study for prognosis and organ injury during application ECMO may be needed.
doi:10.5090/kjtcs.2012.45.4.236
PMCID: PMC3413828  PMID: 22880168
Prognosis; Extracorporeal membrane oxygenation
25.  Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study 
Critical Care  2014;18(1):R38.
Introduction
Critical illness is a well-recognized cause of neuromuscular weakness and impaired physical functioning. Physical therapy (PT) has been demonstrated to be safe and effective for critically ill patients. The impact of such an intervention on patients receiving extracorporeal membrane oxygenation (ECMO) has not been well characterized. We describe the feasibility and impact of active PT on ECMO patients.
Methods
We performed a retrospective cohort study of 100 consecutive patients receiving ECMO in the medical intensive care unit of a university hospital.
Results
Of the 100 patients receiving ECMO, 35 (35%) participated in active PT; 19 as bridge to transplant and 16 as bridge to recovery. Duration of ECMO was 14.3 ± 10.9 days. Patients received 7.2 ± 6.5 PT sessions while on ECMO. During PT sessions, 18 patients (51%) ambulated (median distance 175 feet, range 4 to 2,800) and 9 patients were on vasopressors. Whilst receiving ECMO, 23 patients were liberated from invasive mechanical ventilation. Of the 16 bridge to recovery patients, 14 (88%) survived to discharge; 10 bridge to transplant patients (53%) survived to transplantation, with 9 (90%) surviving to discharge. Of the 23 survivors, 13 (57%) went directly home, 8 (35%) went to acute rehabilitation, and 2 (9%) went to subacute rehabilitation. There were no PT-related complications.
Conclusions
Active PT, including ambulation, can be achieved safely and reliably in ECMO patients when an experienced, multidisciplinary team is utilized. More research is needed to define the barriers to PT and the impact on survival and long-term functional, neurocognitive outcomes in this population.
doi:10.1186/cc13746
PMCID: PMC4056162  PMID: 24571627

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