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

Giles J Peek, Felicity Clemens, Diana Elbourne, Richard Firmin, Pollyanna Hardy, Clare Hibbert, Hilliary Killer, Miranda Mugford, Mariamma Thalanany, Ravin Tiruvoipati, Ann Truesdale, Andrew Wilson, Giles J Peek, Felicity Clemens, Diana Elbourne, Richard Firmin, Pollyanna Hardy, Clare Hibbert, Hilliary Killer, Miranda Mugford, Mariamma Thalanany, Ravin Tiruvoipati, Ann Truesdale, Andrew Wilson

Abstract

Background: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising.

Methods/design: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months.

Discussion: Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

Figures

Figure 1
Figure 1
organisation of the trial.

References

    1. Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, Morris AH, Peirce EC, Thomas AN, Proctor HJ, Drinker PA, Pratt PC, Bagniewski A, Miller RG. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA. 1979;242:2193–2196. doi: 10.1001/jama.242.20.2193.
    1. Vasilyev S, Schaap RN, Mortensen JD. Hospital survival rates of patients with acute respiratory failure in modern respiratory intensive care units. An international, multicenter, prospective survey. Chest. 1995;107:1083–1088.
    1. Gerlach H, Pappert D, Lewandowski K, Rossaint R, Falke KJ. Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome [see comments] Intensive Care Medicine. 1993;19:443–449. doi: 10.1007/BF01711084.
    1. Rossaint R, Gerlach H, Schmidt-Ruhnke H, Pappert D, Lewandowski K, Steudel W, Falke K. Efficacy of inhaled nitric oxide in patients with severe ARDS. Chest. 1995;107:1107–1115.
    1. Pappert D, Rossaint R, Slama K, Gruning T, Falke KJ. Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome. Chest. 1994;106:1511–1516.
    1. Anonymous UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. UK Collaborative ECMO Trail Group. Lancet. 1996;348:75–82. doi: 10.1016/S0140-6736(96)04100-1.
    1. Anonymous The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age. Pediatrics. 1998;101:E1.
    1. Green TP, Timmons OD, Fackler JC, Moler FW, Thompson AE, Sweeney MF. The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Critical Care Medicine. 1996;24:323–329. doi: 10.1097/00003246-199602000-00023.
    1. Peek GJ, Moore HM, Moore N, Sosnowski AW, Firmin RK. Extracorporeal Membrane Oxygenation for Adult Respiratory Failure. Chest. 1997;112:759–764.
    1. Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF, Weaver LK, Dean NC, Thomas F, East TD, Pace NL. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome [see comments] [published erratum appears in Am J Respir Crit Care Med 1994 Mar;149(3 Pt 1):838] American Journal of Respiratory & Critical Care Medicine. 1994;149:295–305.
    1. Peevy KJ, Hernandez LA, Moise AA, Parker JC. Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern. Critical Care Medicine. 1990;18:634–637. doi: 10.1097/00003246-199006000-00012.
    1. Parker JC, Hernandez LA, Peevy KJ. Mechanisms of ventilator-induced lung injury. [Review] [105 refs] Critical Care Medicine. 1993;21:131–143.
    1. Kolla S, Awad SS, Rich PB, Schreiner RJ, Hirschl RB, Bartlett RH. Extracorporeal life support for 100 adult patients with severe respiratory failure. Annals of Surgery. 1997;226:544–64. doi: 10.1097/00000658-199710000-00015. discussion 565–6.
    1. Anonymous . ECMO, Extracorporeal cardiopulmonary support in critical care. Ann Arbor: ELSO; 1995.
    1. Abel SJ, Finney SJ, Brett SJ, Keogh BF, Morgan CJ, Evans TW. Reduced mortality in association with the acute respiratory distress syndrome (ARDS) Thorax. 1998;53:292–294.
    1. Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome [published erratum appears in Am Rev Respir Dis 1989 Apr; 139(4):1065] American Review of Respiratory Disease. 1988;138:720–723.
    1. Moreno R, Vincent JL, Matos R, Medonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Medicine. 1999;25:686–696. doi: 10.1007/s001340050931.
    1. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takla J, Suter PM, Sprung CL, Colardyn F, Belcher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine [see comments] Critical Care Medicine. 1998;26:1793–1800.
    1. The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine. 2000;342:1301–1308. doi: 10.1056/NEJM200005043421801.
    1. Ware JE. SF-36 health survey-manual and interpretation guide. Boston: Nimrod Press; 1993.
    1. Williams A. EuroQol – A new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199–208. doi: 10.1016/0168-8510(90)90421-9.
    1. Jones PW, Quirk FH, Bevestock CH, Littlejohns P. A Self-complete Measure of Health Status for Chronic Airflow Limitation. American Review of Respiratory Disease. 2006;145:1321–1327.
    1. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 2006;67:361–370.
    1. Folstein MF, Folstein SE. 'Mini-mental state' A practical method for grading the cognitive state of patients for the clinician. J of Psychiatric Res. 1975;12:189–98. doi: 10.1016/0022-3956(75)90026-6.
    1. Williams SJ. Measuring health status? A review of the sickness impact and functional limitations profile. Health Care Anal. 2006;4:273–283.
    1. Robinson BC. Validation of a caregiver strain index. J Gerontol. 1993;38:344–8.
    1. Hibbert CL, Coates E, Brazier J, Morris J. Development of Healthcare Resource Groups for adult critical care. Report for the NHS Information Authority. 2004.
    1. Mugford M, Thalanany M, Hibbert C, Coates L, Truesdale A, Robertson S, (on behalf of the CESAR Trial Group) Methods for the economic evaluation alongside a national, multicentre trial in the UK: CESAR. Discussed at HESG Newcastle June 30th 2005 by Stavros Petrou. Copy ofpaper available from Miranda Mugford, University of East Anglia, Norwich UK

Source: PubMed

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