Institution of extracorporeal membrane oxygenation late after lung transplantation - a futile exercise?

The use of and indications for extracorporeal membrane oxygenation (ECMO) are expanding as its reliability improves with widely varying results reported. A retrospective review of 24 lung transplant recipients who required ECMO support postoperatively was performed with 13 patients requiring ECMO within the first 48 h ("early" group) and 11 requiring ECMO after seven d postoperatively ("late" group). The majority of early ECMO group had primary graft failure patients and the late ECMO group comprised patients with infection or non-specific graft failure. There were significant differences in outcomes between groups, with 10/13 in the early group and 4/11 in the late group successfully weaned from ECMO (p = 0.045). Six of the 13 patients in the early group and none of the late group survived to hospital discharge (p = 0.009). The late ECMO group had a much higher incidence of death owing to complications existing prior to institution of ECMO (essentially uncontrolled infection or organ failure). There were no differences in complications arising during ECMO between groups. Late institution of ECMO in lung transplant recipients for causes other than primary graft failure is associated with such poor survival that its use should be considered only in very select cases.

Augmentation of left ventricular mechanics by recirculation-mediated AAV2/1-SERCA2a gene delivery in experimental heart failure.

AIMS: Down-regulation of sarcoplasmic reticulum calcium ATPase (SERCA2a) is a key molecular abnormality in heart failure (HF), which is not currently addressed by specific pharmacotherapy. We sought to evaluate, in detail, the impact of augmented SERCA2a expression on left ventricular (LV) mechanics in a large animal model of HF. METHODS AND RESULTS: Heart failure was induced in adult sheep by rapid pacing (180 b.p.m.) for 1 month, followed by delivery of adeno-associated virus (AAV) 2/1-SERCA, using a percutaneous, recirculating system for gene delivery over a 10 min period. Left ventricular mechanics was investigated by echocardiography and conductance catheter measurements in sheep receiving AAV2/1-SERCA2a after a further 4 weeks of pacing in comparison with untreated HF controls. Left ventricular function was significantly improved in the AAV2/1-SERCA2a-treated group, despite continued pacing, as measured by fractional shortening (delta absolute FS, control -4.2 ± 1.5% vs. treatment 4.4 ± 1.5%; P < 0.01) and conductance catheterization (delta Ees, control -1.22 ± 0.60 vs. treatment 0.65 ± 0.51; P < 0.05). Western blots showed an increase in SERCA protein in AAV2/1-SERCA2a-treated animals, and an analysis of gene delivery showed no evidence of regional myocardial heterogeneity in the distribution of AAV2/1-SERCA. CONCLUSION: In a large animal model, AAV2/1-mediated SERCA2a gene delivery using percutaneous, recirculating cardiac delivery leads to improved LV function.

Extracorporeal membrane oxygenation in primary graft failure after heart transplantation.

BACKGROUND: The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. METHODS: A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. RESULTS: Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). CONCLUSIONS: Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.

Survey of adult extracorporeal membrane oxygenation (ECMO) practice and attitudes among Australian and New Zealand intensivists.

OBJECTIVE: To gauge use of extracorporeal membrane oxygenation (ECMO) in Australian and New Zealand intensive care units, to investigate attitudes to and experience with ECMO, and to assess interest in contributing to a national database of ECMO use. METHODS: The survey was conducted by email in July 2004. A targeted cohort of ICUs across the two countries was chosen, comprising JFICM (Joint Faculty of Intensive Care Medicine) Approved Training Centres, and large regional and private institutions. Directors of the ICUs were invited to participate in the survey of department demographics, ECMO practice rates and experience, and attitudes to ECMO. The survey was registered (http://clinicaltrials.gov registration number NCT00157144), and local ethics approval was obtained. RESULTS: Response rate was 56% (39/70), with 49% of responses (19/39) from JFICM Approved Training Centres. ECMO practice in responding centres was low, with 69% (27/39) having managed no ECMO patients in the past year, and 62% (24/39) having managed none in the past 3 years. Only one centre had managed more than eight patients in the past year. Individual respondents had limited ECMO experience, with 56% (22/39) having ever managed two or fewer patients. The most common reasons given for not providing ECMO were lack of staff skill/training and lack of access to support services. Cost, high mortality and lack of evidence for ECMO efficacy were not regarded as significant factors preventing its use. Seventy-two per cent (28/39) of respondents supported ECMO use outside a randomised controlled trial, and 49% (19/39) would conduct ECMO at their own institution, while 74% (29/39) felt it a useful tool to facilitate transport to specialist centres. CONCLUSION: ECMO use in Australian and New Zealand ICUs is limited, but there is support for its use among survey respondents. Lack of training and experience with ECMO may be restricting its use.

Thoracotomy in adults while on ECMO is associated with uncontrollable bleeding.

This report details the outcomes of four patients supported by extracorporeal membrane oxygenation (ECMO) who required thoracotomy. All four patients sustained massive bleeding as a result of the operative intervention, which was not controllable in three of the patients who subsequently died. This experience has led us to review the literature of anticoagulation management of patients on ECMO so we can alter our own protocols and allow safer operative intervention in the future.

Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals.

OBJECTIVES: The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart. BACKGROUND: Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems. METHODS: We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad-beta-galactosidase (AdLacZ). RESULTS: Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 +/- 3% to 50 +/- 4%; p < 0.001), whereas a further decline occurred in the AdLacZ group (34 +/- 4% to 27 +/- 3%; p < 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p < 0.05). In conjunction, AdS16E-treated animals showed significant improvement in the expression of PLN and Ca2+-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression. CONCLUSIONS: We report the development of a novel closed-loop system for cardiac gene therapy. Using this approach delivery of AdS16E reversed HF progression in a large animal HF model.

Extracorporeal membrane oxygenation after lung transplantation: evolving technique improves outcomes.

BACKGROUND: Severe pulmonary graft failure (PGF) is the most common cause of death within the first 30 days after lung transplantation. Extracorporeal membrane oxygenation (ECMO) may provide lifesaving temporary support; however, its longer-term efficacy is controversial. METHODS: We reviewed the use of ECMO for severe PGF after lung transplantation, and compared the outcomes between our early (1990 to 1999) and recent (2000 to 2003) experience utilizing improved initiation timing, oxygenator technology, and surgical technique. RESULTS: Ten transplant recipients from a total of 481 (2.1%) were managed for PGF on ECMO by a multidisciplinary team at The Alfred Hospital. Four single-lung, 3 bilateral single-lung, and 3 heart-lung recipients were supported for a mean of 96 hours (range 14 to 212 hours). In the early group (operation from 1990 to 1999, n = 4) ECMO was initiated 21 days (range 7 to 40 days) after lung transplantation and in the recent group (operation from 2000 to 2003, n = 6) after 0 to 2 days (p = 0.01). Radial-arterial blood gas analysis 12 hours after initiation of ECMO showed significantly better oxygenation in the recent group (341 +/- 90 mm Hg) than in the early group (90 +/- 23 mm Hg, p = 0.03). Four deaths occurred as a result of bleeding (two in each group). In the early group only 1 patient was weaned from ECMO but died. In the recent group 3 were successfully weaned and were discharged from the intensive care unit; of these patients, 2 were discharged from hospital. CONCLUSIONS: Extracorporeal membrane oxygenation results have improved with advances in oxygenator technology and surgical techniques. The procedure can allow resolution of early PGF after lung transplantation.