Non Invasive Ventilation in Acute Cardiogenic Pulmonary Edema

Non-Invasive Ventilation in Acute cardiogenic Pulmonary Edema. Gray, A et al. NEJM, 2008. 359: 142-51. (or here on pubmed)

The “3 interventions in Cardiogenic Pulmonary oedema trial (3CPO)” trail was a multicentre, open, prospective randomised trial. 1069 patients were randomised over 4 years in 23 different centres in the UK. 3 treatment arms, all targeted to achieve sats >92%. 1: Oxygen, 2: CPAP 5-15cmH20 and 3: BiPAP 8-20/4-10.

Previous trials have suggested a reduction in intubation rates and a mortality benefit for CPAP or NIV, but some concerns over an increased MI rate with NIV.

Primary end point were 7 day mortality, secondary end points included intubation rates, 30 day mortality, dyspnoea and various physiological end points. The trial was 80% powered to detect a 6% mortality difference with 1200 patients (so almost there).

Methodology encouragingly reflected usual UK practise in that NIV/CPAP therapy was considered only for severe pulmonary oedema requiring evidence of type II respiratory failure. The managed to recruit approx 60% of eligible patients, which may reflect some fairly lax consent policies.

Results – no significant difference in primary end points (mortality), minor significant difference in relief of respiratory distress and physiological end points.

Some comments on the trial

  1. The intervention had to be implemented for a minimum of only 2 hours, which may be too short for a mortality benefit to be manifest, and presumably assumes that ventilatory therapy works only by buying time for pharmacological therapy to bite. Perhaps effects mediated by changing respiratory and myocardial workloads rather than just gas exchange would take longer?
  2. Patients were mostly elderly (79+-9) and female (55%), and only 20% of patients had evidence of MI, the majority having myocardial ischemia. Whilst probably representing our population, I think care should be used when applying the results to younger, male patients with definite MI.
  3. There was substantial cross over between arms, with approx 15% of patients changing groups. The statistics were analysed correctly on an intention to treat basis, but this may be enough to mask a true positive effect?
  4. Only 8 patients were intubated during the trial. No treatment can reduce an intubation rate that is essentially zero in this patient population! The authors point out their mortality rate was high at 9.8% vs. 6.5% in European databases, and 4% in the ADHERE database. The authors attribute this to an older, female study population but we must consider the possibility that survival may be greater where invasive ventilation is employed more readily (as in previous positive trials where intubation rates were higher). I am not suggesting that we fill our ICUs with 80yr olds with critically poor ventricles, but there may be a place for short periods of ventilation in selected patients with potential for myocardial recovery. And it may be that NIPPV exerts the majority of its survival benefit in the patient sub-groups not admitted to UK ICUs.
  5. The authors suggest that NIV/CPAP still has a place as an adjuvant to pharmacology and to relive respiratory distress. I think the above comments raise enough doubt in my mind for NIPPV to keep its place in the armoury for cardiogenic pulmonary oedema for the time being, but I’ll admit that my own anecdotal experience of NIV in this setting might be swaying my opinion! Open to the floor…….

Dr. Dan Harvey


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