RESEARCH PROTOCOL

Aims and Objectives 

The aim of the project is to evaluate whether non invasive ventilation, in the form of continuous positive airway pressure (CPAP) compared with bag and mask ventilation, reduces mortality, length of hospital stay and overall symptoms for patients suffering severe acute cardiogenic pulmonary edema (ACPE) in the pre-hospital setting.

Research Plan, Methods, Techniques

Design: randomised controlled trial

Study Population
Patients >18 years of age with sudden onset severe respiratory distress, increased work of breathing and in respiratory failure, crackles on auscultation and
history or risk of cardiogenic pulmonary edema (ACPE), with hypoxaemia and perceived need for ventilatory assistance. Patients attended to and transported by the Tasmanian Ambulance Service in the southern region would be included.

Intervention
CPAP versus assisted bag valve mask ventilation (All other treatments constant)

Outcomes: 
Primary – Mortality from Cardiovascular causes

Secondary - Length of hospital stay, invasive ventilation requirements, blood gases (pH, pCO2, pO2)- taken within 30 minutes of arrival to hospital

Power/recruitment:

A total sample size of 74 participants (37 in each of two equal-sized groups) would provide 80% power to detect a 17.8% absolute reduction in mortality, from 23.2% in the control arm to 5.4% in the CPAP arm. Power calculations for the primary outcome measure is based on the findings of Hubble et al (2006).  

Estimated recruitment based of retrospective review over 1 year approximately 50-60 patients/year therefore N= 75-80. 

Trial length: 18 months

Anticipated start date: June 1st, 2009

Methods
Study Design
A randomised, controlled, parallel-group trial with two treatment arms:
1.	a control arm using standard inspired positive pressure ventilation  with high flow oxygen with a bag-valve-mask assisting patients’ ventilations (bagging)
2.	an active arm using a continuous positive airway pressure (CPAP) device (Whisperflow) with oxygen supplied at 28-33%. 
All subjects initially received standard therapy according to Ambulance Tasmania (AT) guidelines
·	initial high flow oxygen
·	nitroglycerine sublingual in increasing incremental doses from 400 mcg to 1600 mcg increasing every 5 minutes as long as systolic blood pressure was greater than 100 mm/Hg as the primary therapy
·	furosemide 40 mg IV for severe respiratory distress with a transport time greater than 20 minutes
·	1-2 mg morphine IV as an anxiolytic. 

Research Benefits 

This study will advance our understanding. The findings of this study will directly impact patient care and inform the development of guidelines/protocols for appropriate treatment in prehospital care of ACPE.