CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure

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Peek, G. J., Clemens, F., Elbourne, D., Firmin, R., Hardy, P., Hibbert, C., Killer, H., Mugford, M., Thalanany, M., Tiruvoipati, R., Truesdale, A., … Wilson, A. (2006). CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC health services research6, 163. doi:10.1186/1472-6963-6-163.

Link to Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766357/

Clinical Question

Is extracorporeal membrane oxygenation (ECMO) a safe, efficacious and cost-effective treatment compared with conventional ventilation for the management of severe adult respiratory failure?

  • Type of Trial: RCT

  • Blinding: Non-blinded to clinicians although researchers were blinded at 6 month follow up

  • Setting: 92 conventional tertiary ICU’s and 11 referral hospitals in the UK from July 2001 - August 2006; Glenfield Hospital, Leicester was the only center where ECMO treatment took place

  • Intention to treat analysis: yes


  • Population:

    • 180 patients with severe but potentially reversible respiratory failure as defined by Murray Score of 3 or more, uncompensated hypercapnia with pH<7.2 despite optimal vent settings, age 18-65

    • Primary cause of respiratory failure was pneumonia (2/3rds of patients)

      • Excluded if:

        • PIP>30 cmH20 and/or FiO2>0.8 for more than 7 days; signs of intracranial bleeding; contraindications to heparin; planned limitation of support

  • Intervention:

    • Transfer to ECMO specialist centre and consideration for ECMO treatment

      • all patients randomised for consideration of ECMO were transferred by Glenfield’s own specialist retrieval team.

      • no patient was transferred on ECMO

    • If patients were haemodynamically stable, a standard protocol was used – pressure restricted   mechanical ventilation at 30cmH2O, titrated optimal PEEP, FiO2 adjusted to maintain SaO2 > 90%, diuresis, PCV 40%, prone positioning

      • Low-volume low-pressure ventilation 84 patients (93%)

    • If patient did not respond within 12 hours they received cannulation and ECMO according to published institutional protocols

    • Non-responders = FiO2 > 0.9 to maintain SpO2 > 90%, respiratory or metabolic acidosis pH < 7.2) or was haemodynamically unstable

    • ECMO:

      • was done in the veno-venous mode with percutaneous cannulation

      • Servo-controlled roller pumps (stockert, Freiburg, Germany) and poly-methyl pentene oxygenators (Medos Medizintechink, Stolbeerg, Germany) were used

      • was continued until lung recovery or apparently irreversible multiorgan failure

  • Control:

    • Continued conventional ventilation (pressure control mode with Siemens Servo 300 ventilators) or high-frequency oscillatory ventilation, or both

      • Low-volume low-pressure ventilation 63 patients (70%)

  • Outcome:

    • Primary outcome: Death or severe disability at 6 months after randomization

      • Severe disability: defined as confinement to bed and inability to wash and dress alone

      • 63% in ECMO vs 47% in conventional ventilation group, p=0.03, NNT 7

        • Death < 6 months or before discharge: 57 patients (63%) in ECMO vs. 45 patients (50%) in the conventional ventilation group (p=0.07)

    • Secondary outcomes:

      • Use of HFOV of jet ventilation - 7% in intervention vs 14% in control (p=0.21)

      • Prone ventilation - 4% in intervention vs 42% in control (p=0.58)

      • Use of steroids - 84% in intervention vs 64% in control (p=0.001)

      • Use of MARS - 17% in intervention vs 0% in control (p=<0.0001)

      • Nitric oxide and CVVHF: no difference

      • ICU LOS - 24d in intervention vs 13d in control

      • 5 patients in ECMO group died, 3 before they could be transferred and 2 died in transit


Recommend transferring adult patients with severe but potentially reversible respiratory failure, whose Murray score > 3 or who have a pH < 7.2 on optimum conventional management, to a center where ECMO-based management is available


  • Early assignment to treatment groups

  • Incorporation of transport risk into trial design

  • Robust economic analysis

  • 6 month follow up testing was done in patients’ home by trained researchers who were blinded to treatment allocation. Patient and their relatives were instructed not to reveal which treatment had been used. A scarf was used to cover the neck to mask cannulation status


  • This study was more about treatment in a single specialist centre with the potential for ECMO treatment versus standard based UK treatment rather than ECMO vs. conventional ventilation

  • Only 76% in the ECMO group actually received ECMO

  • Perhaps it would have been better if patients were randomised at the point they arrived at Glenfield. The pragmatic decision not to do this is understandable

  • Lack of a management protocol for patients randomised to conventional ventilation. 93% in intervention group vs. 70% in control group were treated with lung protective ventilation, p<0.0001

  • Health evaluation data representation confusing.  On first glance, 33% of patients in the ECMO group reported no problems with mobility vs. 21% of patients in the conventional ventilation group. However the data is misleading. 40 of the 90 patients in the conventional ventilation group had follow up information available = 44%. 19 had no problems with mobility. This is represented as 19 of 90 patients (21%) rather than 19 of 40 (48%). The ECMO group would be 53% (30 of 57 patients). An ARR of 5% looks less impressive than 12% particularly when up to 24% of patients in the ECMO group never received this treatment.

  • Intention to treat analysis is useful only when there is minimal data lost to follow up. Full follow up information was only available in 58% and 36% of the patients in the ECMO group and conventional ventilation group respectively

Take Note

  • ECMO is an option; but this study does not show that ECMO is better than conventional ventilation

  • There is incomplete follow up data with nearly half of the patients and 24% of the patients in the ECMO group not actually receiving ECMO



Rachel MulderComment