Inhaled mannitol improves sputum clearance in intubated patients

Dry powder mannitol is administered by aerosol to stable intubated patients using a standard technique of manual hyperinflation. Mannitol is a naturally occurring sugar alcohol and osmotic agent that has been shown to improve sputum clearance and health status when delivered as a dry powder aerosol to patients with bronchiectasis and cystic fibrosis. The mechanisms of action include cough stimulation, improving innate mucociliary clearance by optimizing cilia efficiency and altering sputum rheology. it is postulated that if mannitol can be effectively delivered to the airways of intubated patients in intensive care, clearance of secretions can be optimized. The technology to generate the powder aerosol using an inline device, incorporated into the ventilation circuit is not yet available but we have demonstrated that the powder can be delivered to the end of the endotracheal tube in vitro using a hand held bag, valve and delivery device. Delivering an aerosol by bag and valve to ventilated patients is a standard technique for the administration of nebulised aerosols. This is a similar technique to manual hyperinflation with a bag and valve, a standard technique of hand ventilating intubated patients which has been shown to improve oxygenation and sputum clearance. This study uses this technique to disperse and deliver the mannitol to the airways via an endotracheal or tracheostomy tube. Manual Hyperinflation (as per hospital Manual Hyperinflation procedure)- using a Mayo disposable bag with safety pressure release valve. A two handed deflation of bag, in synchrony with inspiratory effort. Using flow curves obtained while performing normal manual hyperinflation and reproducing the technique in vitro has demonstrated that the dose delivered to the distal end of the endotracheal tube is up to 62% of the nominal dose and to the end of the tracheostomy tube is up to 73%. This is comparable to the estimated dose delivered to the airway of unventilated patients (300mg) nominal dose to bronchiectasis patients and 40% is respirable. Dry powder mannitol 160mg (4 X 40mg capsules) dose to approximate 120mg to the airways. If no clinical effect is seen at the time of interim analysis (after 10 patients) the dose will be increased to 4 X 80mg capsules (approx. 200mg delivered to the airways). Patients will receive one dose per day for 4 consecutive days - study drug on alternate days and placebo on the other days. It takes less than 15 minutes to deliver the total dose. Eligible and consented patient will be randomised to group A and receive active agent (dry powder mannitol) on Day 1 , or group B and receive placebo (empty capsules ) on Day 1. The patient will be monitored during and after the aerosol delivery procedure in Intensive Care Unit for 1 hour by the patients nurse, criticlal care consultant, experienced Intensive Care nurse or physiotherapist delivering the aerosol. After that hour, there will be the standard one Intensive Care nurse to one patient allocation while in Intensive Care Unit. Then monitored by health professionals while in hospital. The duration of the wash-out period is 75 minutes.