Efficacy of non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: The 3CPO trial.

Austria, Vienna, 2 September 2007:

Acute cardiogenic pulmonary oedema, or “fluid on the lung”, is a common, extremely distressing and often fatal condition that is a major consumer of health care resources. The aim of the 3CPO trial was to establish whether high-pressure oxygen, given by a simple facemask, could help reduce the death rate in patients with this condition.

The 3CPO trial, led by Dr Alasdair Gray, was undertaken over three years in 26 Emergency Departments across the UK and recruited over 1,000 patients with this severe life-threatening condition. The study established that administering oxygen at high pressure (so-called non-invasive ventilation) did speed up the recovery of these patients irrespective of how this was performed. However, non-invasive ventilation did not influence whether the patient ultimately died. This first major large scale clinical trial has demonstrated that non-invasive ventilation is a useful treatment to alleviate distress and improve breathing in patients with “fluid on the lung” but that it does not improve their subsequent chances of survival.

The Disease

This trial addressed the very serious and potentially fatal condition of acute cardiogenic pulmonary oedema or “fluid on the lung”. In this condition, the heart suddenly fails to pump blood effectively around the body. This causes a build up of blood behind the heart leading to an increase in pressure that floods the lungs with fluid. The patient experiences extreme breathlessness and distress, and may rapidly deteriorate such that they need to go onto a ventilator. This is a devastating condition that kills 1 in 6 sufferers, and accounts for 15-20,000 hospital admissions per year in the UK and 6.5 million hospital days in the US. Thus, this is a serious,
potentially fatal condition that has a major impact on health care provision.

The Treatment

The main treatment of this condition focuses on using oxygen and drugs to clear the lung of fluid and help the heart recover. Numerous small studies of 20-50 patients have suggested that increasing the pressure of oxygen may help improve the outcome of this condition. Rather than inserting a tube into the lung, this can be achieved by applying a tightly fitting facemask with oxygen blown in at pressure, so-called non-invasive ventilation. This can be performed by using a constant pressure (continuous positive pressure ventilation or CPAP) or at low pressure when breathing out and high pressure when breathing in (non-invasive intermittent positive pressure ventilation, NIPPV).
 
The purpose of the 3CPO trial was to determine whether non-invasive ventilation can improve the death rate of this condition, and which method (CPAP or NIPPV) should be used, as this has not been established . Since the study started, several papers have suggested that the total evidence to date indicates non-invasive ventilation should halve the rate of death in this condition.

The Trial

The trial was funded by the National Health Service Health Technology Assessment Programme of the Department of Health, England. It was conducted over the last 3 years and was based in the Emergency Departments of 26 centres throughout the United Kingdom. Patients went into the trial immediately on arrival at the hospital and were only eligible if they were very breathless and had evidence that the body was struggling to cope (the blood had become acidic).

The Results

At the close of the trial, 1,069 patients were recruited and received either standard oxygen (367 patients), CPAP (346 patients) or NIPPV (356 patients). In comparison to standard oxygen treatment, both forms of non-invasive ventilation produced better rates of recovery with a more rapid fall in the breathing and heart rate as well as a quicker resolution of the acidity in the blood. However, the death rate did not differ (see Figure). There were no differences in responses according to which type of treatment (CPAP or NIPPV) was used.

The Implications

This is the first large scale clinical trial to test whether giving oxygen at high pressure can help patients with this serious life threatening condition. It has shown that, irrespective of the method of administration, non-invasive ventilation helps patients to recover more quickly in the first few hours of their illness but that this does not improve their subsequent chances of survival.