Key Point

For patients with severe but potentially reversible respiratory failure, extracorporeal membrane oxygenation is associated with better rates of survival without severe disability than is conventional ventilation.

HONOLULU—Final results from the CESAR (Conventional Ventilatory Support versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure) trial were presented by Giles J. Peek, MD, of the University of Leicester, Glenfield, United Kingdom, at a session of the Society of Critical Care MedicineÕs 37th Critical Care Congress.

NONPROTOCOLIZED STUDY APPROACH

According to Dr. Peek, the hypothesis of the trial was that the use of extracorporeal membrane oxygenation (ECMO) in patients with severe but potentially reversible respiratory failure would increase the rate of intact survivalÑthat is, survival without severe disabilityÑat six months.

From July 2001 until August 2006, the CESAR trial investigators recruited patients ages 18 to 65 with severe but potentially reversible respiratory failure from treatment centers and hospitals across the UK. Patients with a Murray score higher than 3.0 or uncompensated hypercapnia with a pH less than 7.2 were included, while those who had been treated with high pressure and/or high fraction of inspired oxygen ventilation of 80% for more than seven days were excluded.

Other exclusion criteria were intracranial bleeding, any other contraindication to limited heparinization, or patients who were moribund and had any contraindication to continuation of active treatment.

With 90 patients in each arm, participants were randomized to either ECMO or conventional treatment. The arms were similar with regard to patient age bracket, duration of high pressure ventilation, and number of organs failing, as well as by diagnostic groupÑsince outcomes may differ according to primary diagnosis, with ARDS having a worse prognosis in obstetric patients than in other groups. All ECMO treatment was done at the center in Glenfield, while conventional treatment was done at a number of ICUs in the UK.

ÒThis was a pragmatic trial, so we didnÕt protocolize the conventional treatment. The intensivists could use any type of management they felt appropriate, but we did recommend the NIH ARDS strategy,Ó Dr. Peek said.

The primary outcome measure was death or severe disability at six months after randomization. The mean age of the total patient population was 40, and more than half were men. The median duration of ventilation prior to randomization was 35 hours, and the median duration of high pressure ventilation was 28 hoursÑapproximately the same in both groups.

Most patients had acute hypoxia at study entry, and only a small number had uncompensated hypercapnia. The mean APACHE score in both groups was 20, although Dr. Peek noted that it was difficult to get these scores, as it is not standard practice in the UK to obtain them.

A significant number of patients had multiple organ failureÑ28 in the ECMO group and 27 in the conventional treatment group. ÒThe idea that ECMO is only for single system failure isnÕt borne out by previous experience, nor is it borne out by data from this trial,Ó Dr. Peek said.

RIGHT CARE

Of the 90 patients originally randomized to ECMO, 68 received treatment, with a mean time of 6.1 hours between randomization and initiation of ECMO. The mean duration of ECMO was nine days. Most of the 22 patients who did not receive ECMO appeared to improve clinically with conventional care, while approximately 23% died before treatment could be initiated. Steroid use was greater in the ECMO arm than in the conventional treatment arm.

For the primary outcome of intact survival at six months, the ECMO arm experienced a significant survival benefitÑ63% of patients versus 47% of patients in the conventional treatment arm. The difference was significant regardless of the stratification criteria, including number of organs failing and the age range.

Although it was not a study end point, Dr. Peek noted that there was a high mortality rate in the conventional arm. ÒThe patients in the conventional arm died much more quickly than in the ECMO arm,Ó he said. There was one ECMO-related death because of a cannulation problem.

ÒECMO increases survival of patients with potentially reversible respiratory failure. I believe the reason survival is higher in the ECMO arm is that ECMO allows you to do lung-protective ventilation,Ó Dr. Peek concluded.

ÒYou get one extra survivor for every six patients treated. So I would suggest to you that this is the right care, right now.Ó

—Laurel McKee Ranger

Suggested Reading
Bayrakci B, Josephson C, Fackler J. Oxygenation index for extracorporeal membrane oxygenation: is there predictive significance? J Artif Organs. 2007;10(1):6-9.
Frenckner B, Radell P. Respiratory failure and extracorporeal membrane oxygenation. Semin Pediatr Surg. 2008;17(1):34-41.
Iglesias M, Martinez E, Badia JR, Macchiarini P. Extrapulmonary ventilation for unresponsive severe acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg. 2008;85(1):237-244.

Return to table of contents