This study will investigate how different types of routine sedation may affect patient's breathing whilst on a ventilator in the Intensive Care Unit (ICU). There are different approaches to sedation which may have advantages and disadvantages. During the study patients will receive both intravenous and inhaled volatile sedation (similar to anaesthetic 'gases' used for general anaesthesia) and the drive to breath, breathing efforts and function of the lung will be assessed.

It is routine for patients to be sedated for their comfort and safety whilst on a ventilator in the Intensive Care Unit (ICU). Conventionally sedatives are given intravenously, however inhaled volatile sedation is becoming more popular. Inhaled sedation has recently been approved by the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom (UK).

Whilst being on a ventilator can be life-saving, it can cause potential problems. It is important that the patient interacts well with the ventilator and that their own breathing efforts are well regulated. There is evidence that inhaled sedation can specifically help the lungs when patients have the Acute Respiratory Distress Syndrome (ARDS) and in particular, inhaled sedation does not appear to suppress patient's own breathing as much as conventional sedation. Greater spontaneous breathing by the patient is usually positive but needs to be carefully understood to ensure it is not excessive or damaging to the patient's already injured lungs.

This study of 20 patients is designed to carefully measure the impact of inhaled sedation on the patient's breathing and lung function, in comparison to intravenous sedation. Measurements will be taken whilst on intravenous sedation before the patient is switched to an equivalent level of inhaled sedation for six hours, when the measurements will be repeated. Finally, the patient will go back to their original intravenous sedation and the measurements taken again. This is called a 'cross-over' study and is a good way to evaluate the effect of the drug.

Inclusion Criteria:

• Adult patients admitted to the Intensive Care Unit (ICU)
• ARDS
• Invasive mechanical ventilation (IMV)
• Spontaneous breathing in pressures support mode (PSV) for less than or equal to 48 hours
• Sedated with intravenous sedation (ie. propofol and / or midazolam and fentanyl or alternate short acting opioid)
• Anticipated to remain on IMV and PSV and with a stable sedation score for a further 24 hours without planned sedation interruption / spontaneous breathing trial or other significant change in the level of ventilator support
• Not receiving / anticipated to receive paralysis
• In supine position

Exclusion Criteria:

• Personal or family history of malignant hyperpyrexia
• Known or suspected elevated intracranial pressure
• High dose vasopressors (ie. Noradrenaline > 0.3mcg/kg/min or equivalent)
• Contra-indication to oesophageal balloon (i.e. oesophageal / upper gastro-intestinal pathology)
• Pregnancy
• High dose oral sedatives (e.g. benzodiazepines) or opioids (e.g. oxycodone / oral morphine) which may affect respiratory drive

None, open label, physiological study