Extracorporeal membrane oxygenation (ECMO) is a respiratory-support technique that has existed since the 1970s but has been utilized primarily with severe neonatal respiratory failure. In early trials, ECMO therapy had been unsuccessful with adults, but over the years, the technology, protocols, and reported outcomes began to improve. As result, the United Kingdom’s health ministry decided to sponsor a randomized clinical and economic trial to evaluate ECMO for adults.
The trial, known as CESAR (Conventional Versus ECMO for Severe Adult Respiratory Failure), randomly selected adults with severe respiratory failure to receive either ECMO or traditional ventilation. After 6 months, the patients’ health and cost of health care were evaluated. Preliminary results were announced early in 2008 and suggest that ECMO is more effective than conventional ventilation therapy—but also more expensive. Nevertheless, CESAR researchers believe that better economic results will be possible in the future.
The Genesis of the CESAR Trial
Early ECMO adult patients with severe respiratory illnesses had poor to mixed results in various clinical trials,1-7 but as protocols and ECMO technology developed throughout the years, researchers began to reconsider ECMO for adults with severe respiratory failure.
Ravindranath Tiruvoipati, FRCSEd (Fellow of the Royal College of Surgeons of Edinburgh), is a research fellow for the CESAR trial. He says, “Toward the mid 90s, ECMO was at a state where the results were very good compared to previous studies, as well as compared to the current level of conventional treatment in managing patients with severe respiratory failure. But we weren’t sure whether it was just by observation that we were picking patients who would survive anyway, or ECMO was really helpful in reducing the mortality.”
Lead by Giles Peek, MD, researchers sought funding and created the CESAR, a randomized clinical and economic trial that ultimately involved 180 patients and 70 medical centers throughout the United Kingdom. (See sidebar for patient protocols.)
The CESAR researchers’ main hypothesis was that for patients with severe but potentially reversible respiratory failure, ECMO would a) increase the rate of survival without severe disability by 6 months after the randomization, and b) would be cost-effective compared to conventional ventilator therapy.
Tiruvoipati says that while standard ventilator treatment for adults with severe respiratory failure is effective, it does have its risks and complications. “There are inherent hazards by using ventilator machines, which can cause things like barotrauma and volutrauma and oxygen toxicity.”
Tiruvoipati likens ECMO’s restorative abilities to the way a broken bone is treated.
“It’s a simple physiology,” Tiruvoipati says. “If you have a broken leg, we splint it up and fix it so that the broken bone heals. Similarly, when the lungs are broken, what they need is rest and not high pressures and high oxygen content, which can damage them further.”
Of course, ECMO also has its own risks. Tiruvoipati notes, “ECMO is more invasive than mechanical ventilation. With ECMO, you have to put cannulas into the patient, and usually we use large veins to take the blood out to the oxygenator and return oxygenated blood to the patients. That can be associated with some complications, such as injury to blood vessels. Having said that, in 90 patients randomized to ECMO, only one patient had a complication that can be related to ECMO.”
|source: www.cesar-trial.org. Adapted with permission.8
|source: [removed]www.cesar-trial.org/Summary[/removed] Protocol. Adapted with permission.8
The CESAR trial’s peer-reviewed conclusions are to be published sometime in 2009, but Tiruvoipati reports that CESAR’s results are promising for ECMO.
“The clinical results are very clear,” Tiruvoipati reports. “We found that ECMO significantly improved the overall survival without physical disability at 6 months of randomization.”
Results from the ECMO patients’ lung function tests and respiratory symptoms were about the same as those of the patients randomized to ventilation, however. Tiruvoipati was surprised by those results. He says, “I was expecting that the lung function might be better in patients randomized to ECMO because we had protected their lungs from further ventilator-induced lung injury. But there wasn’t a statistically significant difference between the ECMO group and the standard management group.”
Similarly, based on the Quality Adjusted Life Year (QALY) score, the assessment of the ECMO patients’ quality of life showed some gain in QALYs.
Tiruvoipati suspects that ECMO’s QALY score could improve over time. “I’m not sure how significant, statistically, that score is at 6 months,” he says. “There is some evidence that the quality of life of patients that CESAR evaluated [for ECMO] could get better. Improvement continues for 1 or 2 years, so looking at these patients after 1 or 2 years might clarify this issue further.”
The economic results were not as promising for ECMO compared to conventional ventilation treatment. The cost of treating patients with ECMO was almost double. However, Tiruvoipati believes that ECMO is still a financially viable alternative—at least for United Kingdom health care costs—because expenses would be lower in nontrial circumstances. Tiruvoipati hopes that with improving technology, the ECMO expenses can be minimized in the future.
CESAR’s Impact in the United Kingdom—and Beyond?
Tiruvoipati reports that the CESAR trial work is already making a significant impact in the United Kingdom. He says, “Before, many intensivists were skeptical [about] whether ECMO treatment works. … In fact, during the trial, some treating physicians were reluctant to send patients to the CESAR trial because they weren’t sure whether it works. But since this trial has been presented [at medical conferences], I think that skepticism has gone down markedly.”
Tiruvoipati hopes that once the paper is published in an undisclosed but prominent peer-reviewed international journal later this year, it will make a further impact in the United States and other countries.
Beyond 6 Months
While the 6-month CESAR trial’s work is finished, Tiruvoipati says that the CESAR researchers are considering monitoring the participating patients and continuing to evaluate their quality of life.
Another goal is to improve the existing standards in transporting patients to a central ECMO facility. Tiruvoipati says, “One of the problems in this trial was that the patients were very sick to be transported from the base hospital to the ECMO center. In fact, we lost two patients while they were being transported and three patients died before the transport team could even get to them.”
In the future, Tiruvoipati hopes to use a special ECMO team who would travel to the participating hospital with a mobile ECMO machine, place the patients on ECMO, and then transfer them on ECMO to the central hospital. He suspects that such a practice would further improve ECMO results.
Tiruvoipati is also optimistic that ECMO will develop further. “Like any other technology, it’s going to improve over time,” he says. “I assume it will be more user-friendly and the complications of the extracorporeal system will be minimized with further advances in the equipment and the way we run the circuit. ECMO started in the 1970s and has improved quite remarkably over the last few decades, but there’s still a lot of room for it to be improved further.”
Tor Valenza is a staff writer for RT. For further information, contact [email protected].
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