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1.  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
2.  Mechanical Circulatory Support of the Critically Ill Child Awaiting Heart Transplantation 
Current Cardiology Reviews  2010;6(1):46-53.
The majority of children awaiting heart transplantation require inotropic support, mechanical ventilation, and/or extracorporeal membrane oxygenation (ECMO) support. Unfortunately, due to the limited pool of organs, many of these children do not survive to transplant. Mechanical circulatory support of the failing heart in pediatrics is a new and rapidly developing field world-wide. It is utilized in children with acute congestive heart failure associated with congenital heart disease, cardiomyopathy, and myocarditis, both as a bridge to transplantation and as a bridge to myocardial recovery. The current arsenal of mechanical assist devices available for children is limited to ECMO, intra-aortic balloon counterpulsation, centrifugal pump ventricular assist devices, the DeBakey ventricular assist device Child; the Thoratec ventricular assist device; and the Berlin Heart. In the spring of 2004, five contracts were awarded by the National Heart, Lung and Blood Institute to support preclinical development for a range of pediatric ventricular assist devices and similar circulatory support systems. The support of early development efforts provided by this program is expected to yield several devices that will be ready for clinical trials within the next few years. Our work reviews the current international experience with mechanical circulatory support in children and summarizes our own experience since 2005 with the Berlin Heart, comparing the indications for use, length of support, and outcome between these modalities.
doi:10.2174/157340310790231617
PMCID: PMC2845794  PMID: 21286278
Ventricular assist device; heart failure; heart transplantation.
3.  Neonatal congenital diaphragmatic hernia and extracorporeal membrane oxygenation. 
OBJECTIVE: To describe the outcome of infants with congenital diaphragmatic hernia (CDH) presenting early who were referred for possible extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective descriptive study. SETTING: Neonatal Intensive Care Unit of the Royal Alexandra Hospital, Edmonton. PATIENTS: Fifteen infants referred to our program since its introduction, in February 1989; 13 received ECMO. The criterion for ECMO was the presence of an oxygen index of more than 40 on three occasions within 2 hours. INTERVENTION: ECMO was performed by means of cannulation of the right carotid artery and jugular vein for 111.0 hours on average. RESULTS: In 5 of the 13 infants who underwent ECMO the procedure was performed after surgical repair; all were successfully weaned off ECMO, and the cannula was removed without incident. In the remaining eight ECMO was started before surgical repair; of the six who received it during repair four ultimately survived. None of the previously described predictors of outcome for CDH, including diagnosis before 25 weeks' gestation (in six cases), were useful in determining the survival of the patients. Bleeding was the most common complication and cause of death. CONCLUSION: ECMO is associated with survival in infants with CDH who fail to respond to conventional therapy and who have a poor prognosis according to previously established criteria.
PMCID: PMC1488456  PMID: 1737314
4.  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
5.  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
6.  Motor performance in five-year-old extracorporeal membrane oxygenation survivors: a population-based study 
Critical Care  2009;13(2):R47.
Introduction
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a cardio-pulmonary bypass technique to provide life support in acute reversible cardio-respiratory failure when conventional management is not successful. Most neonates receiving ECMO suffer from meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), sepsis or persistent pulmonary hypertension (PPH). In five-year-old children who underwent VA-ECMO therapy as neonates, we assessed motor performance related to growth, intelligence and behaviour, and the association with the primary diagnosis.
Methods
In a prospective population-based study (n = 224) 174 five-year-old survivors born between 1993 and 2000 and treated in the two designated ECMO centres in the Netherlands (Radboud University Medical Centre Nijmegen and Sophia Children's Hospital, Erasmus MC – University Medical Center Rotterdam) were invited to undergo follow-up assessment including a paediatric assessment, the movement assessment battery for children (MABC), the revised Amsterdam intelligence test (RAKIT) and the child behaviour checklist (CBCL).
Results
Twenty-two percent of the children died before the age of five, 86% (n = 149) of the survivors were assessed. Normal development in all domains was found in 49% of children. Severe disabilities were present in 13%, and another 9% had impaired motor development combined with cognitive and/or behavioural problems. Chi-squared tests showed adverse outcome in MABC scores (P < 0.001) compared with the reference population in children with CDH, sepsis and PPH, but not in children with MAS. Compared with the Dutch population height, body mass index (BMI) and weight for height were lower in the CDH group (P < 0.001). RAKIT and CBCL scores did not differ from the reference population. Total MABC scores, socio-economic status, growth and CBCL scores were not related to each other, but negative motor outcome was related to lower intelligence quotient (IQ) scores (r = 0.48, P < 0.001).
Conclusions
The ECMO population is highly at risk for developmental problems, most prominently in the motor domain. Adverse outcome differs between the primary diagnosis groups. Objective evaluation of long-term developmental problems associated with this highly invasive technology is necessary to determine best evidence-based practice. The ideal follow-up programme requires an interdisciplinary team, the use of normal-referenced tests and an international consensus on timing and actual outcome measurements.
doi:10.1186/cc7770
PMCID: PMC2689491  PMID: 19341476
7.  Plasma Concentrations of Inflammatory Cytokines Rise Rapidly during ECMO-related SIRS due to the Release of Pre-formed Stores in the Intestine 
Background
Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically-ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a ‘cytokine storm’, leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS.
Methods
Three-week-old previously-healthy piglets were subjected to venoarterial ECMO for up to 8 hours. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (polymerase chain reaction/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity.
Results
Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. TNF-α and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 hours of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells.
Conclusions
TNF-α and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately following the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may play an important pathophysiological role in ECMO-related SIRS.
doi:10.1038/labinvest.2009.119
PMCID: PMC2799549  PMID: 19901912
ECMO; venoarterial; neonate; SIRS; mast cells; intestine; CRP; cytokines
8.  Clinical review: Extracorporeal membrane oxygenation 
Critical Care  2011;15(6):243.
The H1N1 flu pandemic led to a wider use of extracorporeal membrane oxygenation (ECMO), proving its power in hypoxemic emergencies. The results obtained during this pandemic, more than any randomized trial, led to the worldwide acceptance of the use of membrane lungs. Moreover, as centers that applied this technique as rescue therapy for refractory hypoxemia recognized its strength and limited technical challenges, the indications for ECMO have recently been extended. Indications for veno-venous ECMO currently include respiratory support as a bridge to lung transplantation, correction of lung hyperinflation during chronic obstructive pulmonary disease exacerbation and respiratory support in patients with the acute respiratory distress syndrome, possibly also without mechanical ventilation. The current enthusiasm for ECMO in its various aspects should not, however, obscure the consideration of the potential complications associated with this life-saving technique, primarily brain hemorrhage
doi:10.1186/cc10490
PMCID: PMC3388693  PMID: 22188792
9.  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
10.  Pediatric Cardiovascular Drug Dosing in Critically Ill Children and Extracorporeal Membrane Oxygenation 
Cardiovascular disease in children is common and results in significant morbidity and mortality. The sickest children with cardiovascular disease may require support with extracorporeal membrane oxygenation (ECMO) which provides life-saving assistance for children with refractory cardiorespiratory failure. Many classes of cardiovascular drugs are used in children, but very few of these agents have been well studied in children. The knowledge gap is even more pronounced in children supported with ECMO. Pharmacokinetic (PK) data collected to date (primarily from antibiotics and sedatives) suggest that the ECMO circuit has the potential to significantly alter the pharmacokinetics of drugs including changes in clearance and volume of distribution. Of all cardiovascular drugs administered to children supported by ECMO, only 11 have been partially studied and reported in the medical literature. Esmolol, amiodarone, nesiritide, bumetanide, sildenafil, and prostaglandin E1 appear to require dosing modifications in children supported by ECMO, while it appears that hydralazine, nicardipine, furosemide, epinephrine, and dopamine can be dosed similarly to children not supported by ECMO. However, trials evaluating the PK of these drugs in patients supported by ECMO are extremely limited (i.e. case reports) and therefore definitive dosing recommendations are not plausible. Research efforts should focus on evaluating the PK of drugs in patients on ECMO in order to avoid therapeutic failures or unnecessary toxicities.
doi:10.1097/FJC.0b013e318213aac2
PMCID: PMC3155009  PMID: 21346597
cardiovascular agents; extracorporeal membrane oxygenation; pharmacology; pharmacokinetics
11.  Extracorporeal Membrane Oxygenation Causes Loss of Intestinal Epithelial Barrier in the Newborn Piglet 
Pediatric research  2010;68(2):128-133.
Extracorporeal membrane oxygenation (ECMO) is an important life-support system used in neonates and young children with intractable cardiorespiratory failure. In this study, we used our porcine neonatal model of venoarterial ECMO to investigate whether ECMO causes gut barrier dysfunction. We subjected 3-week-old previously-healthy piglets to venoarterial ECMO for up to 8 hours and evaluated gut mucosal permeability, bacterial translocation, plasma levels of bacterial products, and ultrastructural changes in gut epithelium. We also measured plasma lipopolysaccharide (LPS) levels in a small cohort of human neonates receiving ECMO. In our porcine model, ECMO caused a rapid increase in gut mucosal permeability within the first 2 hours of treatment, leading to a 6–10 fold rise in circulating bacterial products. These changes in barrier function were associated with cytoskeletal condensation in epithelial cells, which was explained by phosphorylation of a myosin II regulatory light chain. In support of these findings, we also detected elevated plasma LPS levels in human neonates receiving ECMO, indicating a similar loss of gut barrier function in these infants. Based on these data, we conclude that ECMO is an independent cause of gut barrier dysfunction, and that bacterial translocation may be an important contributor to ECMO-related inflammation.
doi:10.1203/PDR.0b013e3181e4c9f8
PMCID: PMC2914515  PMID: 20442689
12.  Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age 
Critical Care  2006;10(5):R127.
Introduction
Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made.
Methods
Five-year-old neonatal venoarterial-ECMO survivors from the two designated ECMO centres in The Netherlands (Erasmus MC – Sophia Children's Hospital in Rotterdam, and University Medical Center Nijmegen) were assessed within the framework of an extensive follow-up programme. The protocol included medical assessment, neuromotor assessment, and psychological assessment by means of parent and teacher questionnaires.
Results
Seventeen of the 98 children included in the analysis (17%) were found to have neurological deficits. Six of those 17 (6% of the total) showed major disability. Two of those six children had a chromosomal abnormality. Three were mentally retarded and profoundly impaired. The sixth child had a right-sided hemiplegia. These six children did not undergo neuromotor assessment. Twenty-four of the remaining 92 children (26%) showed motor difficulties: 15% actually had a motor problem and 11% were at risk for this. Cognitive delay was identified in 11 children (14%). The mean IQ score was within the normal range (IQ = 100.5).
Conclusion
Neonatal ECMO in The Netherlands was found to be associated with considerable morbidity at five years of age. It appeared feasible to have as many as 87% of survivors participate in follow-up assessment, due to cooperation between two centres and small travelling distances. Objective evaluation of the long-term morbidity associated with the application of this highly invasive technology in the immediate neonatal period requires an interdisciplinary follow-up programme with nationwide consensus on timing and actual testing protocol.
doi:10.1186/cc5039
PMCID: PMC1751085  PMID: 16961935
13.  Extracorporeal membrane oxygenation for severe acute respiratory failure 
Critical Care  2000;4(3):156-168.
Extracorporeal membrane oxygenation (ECMO) is a technique for providing life support, in case the natural lungs are failing and are not able to maintain a sufficient oxygenation of the body's organ systems. ECMO technique was an adaptation of conventional cardiopulmonary bypass technique and introduced into treatment of severe acute respiratory distress syndrome (ARDS) in the 1970s. The intial reports of the use of ECMO in ARDS patients were quite enthusiastic, however, in the following years it became clear that ECMO was only of benefit in newborns with acute respiratory failure. In neonates treated with ECMO, survival rates of 80% could be achieved. In adult patients with ARDS, two large randomized controlled trials (RCTs) published in 1979 and 1994 failed to show an advantage of ECMO over convential treatment, survival rates were only 10% and 33%, respectively, in the ECMO groups. Since then, ECMO technology as well as conventional treatment of adult ARDS have undergone further improvements. In conventional treatment lung-protective ventilation strategies were introduced and ECMO was made safer by applying heparin-coated equipment, membranes and tubings. Many ECMO centres now use these advanced ECMO technology and report survival rates in excess of 50% in uncontrolled data collections. The question, however, of whether the improved ECMO can really challenge the advanced conventional treatment of adult ARDS is unanswered and will need evaluation by a future RCT.
doi:10.1186/cc689
PMCID: PMC137254  PMID: 11094500
acute respiratory distress syndrome; adults; children; complications; extracorporeal membrane oxygenation; follow up; history; lung protective mechanical ventilation; mortality rates; technology
14.  Physical Therapy Management of a Patient on Portable Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation: A Case Report 
Introduction
Although the life expectancy for patients with cystic fibrosis (CF) has increased dramatically in the preceding decades, often the final therapeutic option for patients with end-stage CF is lung transplantation. Prior to transplantation, patients with severe disease may require mechanical ventilation. Those refractory to mechanical ventilation may require extracorporeal membrane oxygenation (ECMO). The purpose of this case report is to describe the physical therapy management of a patient who received ECMO as a bridge to lung transplantation.
Case Presentation
A 16-year-old girl with severe acute respiratory failure due to a CF exacerbation eventually required ECMO to maintain adequate gas exchange. While on ECMO, she received physical therapy interventions ranging from therapeutic exercise, manual therapy, and integumentary protection techniques in addition to airway clearance techniques. Prior to her transplant, she was standing multiple times per day with moderate assistance, was sitting on the edge-of-bed, as well as taking steps to transfer to/from a chair. She successfully received a bilateral lung transplant after 8 days on ECMO.
Conclusion
Physical therapy interventions, including out-of-bed mobility, can be safely provided to patients on portable ECMO as a bridge to lung transplantation. These interventions were focused on preventing the negative sequelae of bed rest, increasing her strength and endurance, as well as improving her level of consciousness and psychological well being in preparation for lung transplantation.
PMCID: PMC3286498  PMID: 22807653
extracorporeal membrane oxygenation; lung transplantation; physical therapy; exercise
15.  Neonatal ECMO Study of Temperature (NEST) - a randomised controlled trial 
BMC Pediatrics  2010;10:24.
Background
Existing evidence indicates that once mature neonates with severe cardio-respiratory failure become eligible for Extra Corporeal Membrane Oxygenation (ECMO) their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a multi-centre randomised controlled trial designed to test whether, in neonates requiring ECMO, cooling to 34°C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Infants allocated to the control group will receive ECMO at 37°C throughout their course, which is currently standard practice around the world. Health status of both groups will be assessed formally at 2 years corrected age.
Methods/Design
All infants recruited to the study will be cared for in one of the four United Kingdom (UK) ECMO centres. Babies who are thought to be eligible will be assessed by the treating clinician who will confirm eligibility, ensure that consent has been obtained and then randomise the baby using a web based system, based at the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit. Trial registration.
Babies allocated ECMO without cooling will receive ECMO at 37°C ± 0.2°C. Babies allocated ECMO with cooling will be managed at 34°C ± 0.2°C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling will be 48 hours. Rewarming (to 37°C) will occur at a rate of no more than 0.5°C per hour. All other aspects of ECMO management will be identical. Primary outcome: Cognitive score from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at age of 2 years (24 - 27 months).
Discussion
For the primary analysis, children will be analysed in the groups to which they are assigned, comparing the outcome of all babies allocated to "ECMO with cooling" with all those allocated to "ECMO" alone, regardless of deviation from the protocol or treatment received. For the primary outcome the analysis will compare the mean scores for each group of surviving babies. The rationale for this choice of primary analysis is to give a fair representation of the average ability of assessable children, accepting the limitation that excluding deaths might impose.
The consistency of the effect of cooling on the group of babies recruited to the trial will be explored to see whether cooling is of particular help, or not, to specific subgroups of infants, using the statistical test of interaction. Therefore pre-specified subgroup analyses include: (i) whether the ECMO is veno-arterial or veno-venous; (ii) whether the child's oxygenation index at the time of recruitment is <60 or ≥ 60; (iii) initial aEEG pattern shown on the cerebral function monitor, and (iv) primary diagnostic group.
Trial Registration
Current Controlled Trials ISRCTN72635512.
doi:10.1186/1471-2431-10-24
PMCID: PMC2865456  PMID: 20403176
16.  Outcomes of Venovenous Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome in Adults 
Background
Despite improved managements for acute respiratory distress syndrome (ARDS), its mortality remains high. Extracorporeal membrane oxygenation (ECMO) has emerged as the final option for the treatment of ARDS unresponsive to conventional measures. This study describes our experiences of venovenous ECMO support for the treatment of ARDS.
Materials and Methods
Between 2007 and 2010, 56 patients (aged 56.6±13.4 years, 43 males) received venovenous ECMO for the treatment of ARDS. The detailed clinical records were retrospectively reviewed.
Results
Before the institution of ECMO support, 35 patients (55.4%) required nitric oxide inhalation, 35 patients (55.4%) received continuous renal replacement therapy, and 20 patients (35.7%) were in shock status. The median duration of ECMO support was 164 hours (range, 5 to 1,413 hours). 27 (48%) patients could be successfully weaned from ECMO. Of them, 7 (13%) survived to discharge. On logistic regression analysis, a requirement for higher inspiratory pressure before ECMO support was the only significant factor that could predict ECMO weaning failure.
Conclusion
The outcome of venovenous ECMO support for the treatment of ARDS was suboptimal. Further improvements in outcomes should be made through the accumulation of experience and establishment of a standardized protocol for the management of ECMO.
doi:10.5090/kjtcs.2012.45.2.91
PMCID: PMC3322191  PMID: 22500278
Acute respiratory distress syndrome; Extracorporeal membrane oxygenation
17.  Extracorporeal circulatory systems in the interhospital transfer of critically ill patients: experience of a single institution 
Annals of Saudi Medicine  2009;29(2):110-114.
BACKGROUND AND OBJECTIVES:
Critically ill patients with acute circulatory failure cannot be moved to other institutions unless stabilized by mechanical support systems. Extracorporeal heart and lung assist systems are increasingly used as a bridge to end-organ recovery or transplantation, and as an ultimate rescue tool in cardiopulmonary resuscitation.
PATIENTS AND METHODS:
From July 2001 to April 2008, we had 38 requests for extracorporeal support for interhospital transfer carried out by the air medical service. Respiratory failure was present in 29 patients, who were provided with pumpless extracorporeal lung assist (PECLA) or veno-venous extracorporeal membrane oxygenation (ECMO). Cardiac failure dominated in 9 patients, who underwent implantation of extracorporeal life support (ECLS). Underlying diseases were acute respiratory distress syndrome in 15 patients, pneumonia in 7, prior lung transplant status in 4, cardiogenic shock in 7, and septic shock in 4.
RESULTS:
All assist systems were connected via peripheral vessels by the Seldinger technique. Transport was uneventful in all cases with no technical failures. On arrival at the specialized care hospital, two patients had leg ischemia and underwent relocation of the arterial cannula. After a mean (SD) support of 5.1 (3.0) days for PECLA, 3.5 (2.9) days for ECLS, and 7.3 (5.8) days for ECMO, 60%, 66%, and 66% of patients, respectively, could be successfully weaned from the systems. Discharge rates were 45% for PECLA, 44% for ECLS, and 56% for ECMO.
CONCLUSION:
Our experience proves that minimized extracorporeal assist devices allow safe assistance of patients with isolated or combined heart and lung failure in need of interhospital transfer. Critically ill patients get a chance to reach a center of maximum medical care.
doi:10.4103/0256-4947.51792
PMCID: PMC2813631  PMID: 19318758
18.  Extracorporeal Membrane Oxygenation Using the Tandem Heart System's Catheters 
Texas Heart Institute Journal  2009;36(4):337-341.
We describe the initial—and successful—use of the TandemHeart System's catheters to provide extracorporeal membrane oxygenation (ECMO), in 2 patients. In 1 patient, who was experiencing severe primary respiratory failure, the catheters provided a standard venovenous ECMO circuit. In the other patient, who had severe, acute pulmonary hypertension and right-heart failure, the catheters enabled a novel right atrial-to-left atrial circuit for ECMO. We discuss the potential of the TandemHeart System's catheters to provide novel and possibly superior vascular routes for the delivery of ECMO in different types of cardiopulmonary failure.
PMCID: PMC2720287  PMID: 19693311
Extracorporeal circulation; extracorporeal membrane oxygenation/instrumentation/methods; heart failure/therapy; heart-assist devices; hemodynamics; methods; pneumonia/complications; respiratory insufficiency/therapy; technology assessment, biomedical; treatment outcome
19.  Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation 
Intensive Care Medicine  2010;36(9):1587-1591.
Purpose
In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO.
Methods
Prospective observational study in 20 neonates (0.17–5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms.
Results
Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0–24.1 h). Median interruption duration for midazolam was 16.5 h (6.6–29.6 h), and for morphine was 11.2 h (6.7–39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred.
Conclusions
This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2–3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes.
doi:10.1007/s00134-010-1931-4
PMCID: PMC2921052  PMID: 20508914
Neonate; Extracorporeal membrane oxygenation; Sedation; Daily interruption
20.  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
21.  Bivalirudin-based versus conventional heparin anticoagulation for postcardiotomy extracorporeal membrane oxygenation 
Critical Care  2011;15(6):R275.
Introduction
Extracorporeal membrane oxygenation (ECMO) after cardiac operations (postcardiotomy) is commonly used for the treatment of acute heart failure refractory to drug treatment. Bleeding and thromboembolic events are the most common complications of postcardiotomy ECMO. The present study is a retrospective comparison of the conventional heparin-based anticoagulation protocol with a bivalirudin-based, heparin-free protocol. Endpoints of this study are blood loss, allogeneic blood product use, and costs during the ECMO procedure.
Methods
A retrospective study was undertaken in the setting of cardiac surgery, anesthesia, and intensive care departments of a university research hospital. Twenty-one patients (12 adults and nine children) who underwent postcardiotomy ECMO from 2008 through 2011 were retrospectively analyzed. The first consecutive eight patients were treated with heparin-based anticoagulation (H-group) and the next 13 consecutive patients with bivalirudin-based anticoagulation (B-group). The following parameters were analyzed: standard coagulation profile, thromboelastographic parameters, blood loss, allogeneic blood products use, thromboembolic complications, and costs during the ECMO treatment.
Results
Patients in the B-group had significantly longer activated clotting times, activated partial thromboplastin times, and reaction times at thromboelastography. The platelet count and antithrombin activity were not significantly different, but in the H-group a significantly higher amount of platelet concentrates, fresh frozen plasma, and purified antithrombin were administered. Blood loss was significantly lower in the B-group, and the daily cost of ECMO was significantly lower in pediatric patients treated with bivalirudin. Thromboembolic complications did not differ between groups.
Conclusions
Bivalirudin as the sole anticoagulant can be safely used for postcardiotomy ECMO, with a better coagulation profile, less bleeding, and allogeneic transfusions. No safety issues were raised by this study, and costs are reduced in bivalirudin-treated patients.
doi:10.1186/cc10556
PMCID: PMC3388709  PMID: 22099212
22.  The Microcirculation Is Unchanged in Neonates with Severe Respiratory Failure after the Initiation of ECMO Treatment 
Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcirculation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children's hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1) and within the first 24 hours after initiation of ECMO treatment (T2). Data were compared to data of a ventilated control group (N = 7). Results. At baseline (T1), median functional capillary density (FCD), microvascular flow index (MFI), and heterogeneity index (HI) did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4–4.2] versus 4.3 [2.8–7.4] cm/cm2; P value <0.001). For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure.
doi:10.1155/2012/372956
PMCID: PMC3366207  PMID: 22675619
23.  Intrahospital Transport of Children on Extracorporeal Membrane Oxygenation: Indications, Process, Interventions and Effectiveness 
Objective
Critically ill patients supported with extracorporeal membrane oxygenation (ECMO) are transported within the hospital to the radiology suite, cardiac catheterization suite, operating room, and from one ICU to another. No studies to date have systematically evaluated intra-hospital transport (IHT) while on ECMO. This study aims to evaluate indications, process, interventions, and effectiveness of patients undergoing IHT.
Design
Retrospective cohort analysis.
Setting
Cardiac intensive care unit in a tertiary care children's hospital.
Patients
All patients requiring IHT while on ECMO between January 1996 and March 2007 were included and analyzed in detail.
Measurement and Main Results
A total of 57 IHTs for cardiac catheterization (CC) and head CT scans were analyzed. In 14/20 (70%) of CC patients, a management change occurred as a result of the diagnostic CC. In 10/17 (59%) bedside echo was of limited value in defining the critical problem. In the interventional group the majority of transports were for atrial septostomy. In the head CT group significant pathology was identified, which led to management change. No major complications occurred during these IHTs.
Conclusions
IHT while on ECMO is labor intensive and requiring extensive logistic support, it can be carried out safely in experienced hands and results in important therapeutic and diagnostic yields. To our knowledge this is the first study designed to evaluate safety and efficacy of IHT for patients receiving ECMO support.
doi:10.1097/PCC.0b013e3181b063b2
PMCID: PMC3039026  PMID: 19593245
Extracorporeal membrane oxygenation; intra-hospital transport; cardiac catheterization; CT scan; children
24.  Morbidity and Mortality in Late Preterm Infants with Severe Hypoxic Respiratory Failure on ECMO 
The Journal of pediatrics  2011;159(2):192-198.e3.
Objectives
To evaluate morbidity, mortality, and associated risk factors in late preterm term infants (34 0/7-36 6/7 wk) requiring extra-corporeal membrane oxygenation (ECMO).
Study design
We reviewed a total of 21,218 neonatal ECMO runs in Extracorporeal Life Support Organization (ELSO) registry data from 1986 to 2006. Infants were divided into 3 groups: Late Preterm (34 0/7 to 36 6/7), Early Term (37 0/7 to 38 6/7), and Full Term (39 0/7 to 42 6/7).
Results
There were 14,528 neonatal ECMO runs which met inclusion criteria. Late preterm infants experienced the highest mortality on ECMO (late preterm 26.2%, early term 18%, full term 11.2%. p<0.001) and had longer ECMO runs; they also had higher rates of serious complications. GA was a highly significant predictor for mortality. Late preterm infants with a primary diagnosis of sepsis and PPHN had 3-fold higher risk of mortality on ECMO than those with meconium aspiration.
Conclusion
Late preterm infants treated with ECMO havehigher morbidity and mortality than term infants. This underscores the need for special consideration of this vulnerable population in the diagnosis and treatment of hypoxic respiratory failure.
doi:10.1016/j.jpeds.2011.02.015
PMCID: PMC3134553  PMID: 21459387
Late preterm; near term; early term; preterm birth; late preterm infant; infant mortality; hypoxic respiratory failure; extra corporeal membrane oxygenation (ECMO)
25.  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

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