ISO-DRIVE: Volatile Sedation for Patients With the Acute Respiratory Distress Syndrome

Sponsor

Guy's and St Thomas' NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06014138

Collaborator

Sedana Medical (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome Mechanical Ventilation Complication Sedation Complication	Drug: Propofol Drug: Isoflurane	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Prospective, cross-over trial design comparing intravenous versus inhaled volatile sedationProspective, cross-over trial design comparing intravenous versus inhaled volatile sedation

Masking:

None (Open Label)

Masking Description:

None, open label, physiological study

Primary Purpose:

Basic Science

Official Title:

Effect of Volatile Sedation on Spontaneous Breathing During Mechanical Ventilation for Patients With the Acute Respiratory Distress Syndrome

Anticipated Study Start Date :

Sep 30, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Conventional intravenous sedation Conventional intravenous sedation (e.g. propofol) with short acting opioid, titrated to a clinically prescribed sedation score. Period of observation will be 2 hours pre-cross over and 2 hours post cross over.	Drug: Propofol Standard care, propofol sedation - 2 hour periods of observation before and after inhaled volatile sedation
Active Comparator: Inhaled volatile sedation Inhaled volatile sedation (Isoflurane) delivered via the AnaConDa device for a 6 hour period (2 hours washout of intravenous sedation / wash-in of volatile to achieve stable baseline, followed by 4 hours of observations at steady state) titrated to an equivalent sedation score. During this period opioid infusion should be maintained at baseline level unless clinical indication for titration of dose.	Drug: Isoflurane Inhaled volatile sedation for 6 hours - 2 hours wash in / wash out, followed by 4 hours of observations

Arm

Intervention/Treatment

Active Comparator: Conventional intravenous sedation

Conventional intravenous sedation (e.g. propofol) with short acting opioid, titrated to a clinically prescribed sedation score. Period of observation will be 2 hours pre-cross over and 2 hours post cross over.

Drug: Propofol

Standard care, propofol sedation - 2 hour periods of observation before and after inhaled volatile sedation

Active Comparator: Inhaled volatile sedation

Inhaled volatile sedation (Isoflurane) delivered via the AnaConDa device for a 6 hour period (2 hours washout of intravenous sedation / wash-in of volatile to achieve stable baseline, followed by 4 hours of observations at steady state) titrated to an equivalent sedation score. During this period opioid infusion should be maintained at baseline level unless clinical indication for titration of dose.

Drug: Isoflurane

Inhaled volatile sedation for 6 hours - 2 hours wash in / wash out, followed by 4 hours of observations

Outcome Measures

Primary Outcome Measures

Respiratory drive (P0.1) [8 hours]
Negative pressure in the first 100milliseconds of inspiration (P0.1) - Physiological parameter

Secondary Outcome Measures

Respiratory effort (Pmus) [8 hours]
End expiratory occlusion pressure (Pmus) - Physiological parameter
Respiratory effort (PMI) [8 hours]
Pressure Muscle Index (PMI) - Physiological parameter
Respiratory effort (Oesophageal pressure swings) [8 hours]
Oesophageal pressure swings - Physiological parameter
Gas exchange (PaO2:FiO2 ratio) [8 hours]
Ratio of arterial partial pressure of oxygen to fractional inspired concentration of oxygen (PaO2:FiO2) - Physiological parameter
Gas exchange (pulmonary shunt fraction (Qs/Qt)) [8 hours]
Pulmonary shunt fraction (Qs/Qt) - Physiological parameter
Gas exchange ( ratio of ventilatory 'dead space' to tidal volume (Vd/Vt)) [8 hours]
ratio of ventilatory 'dead space' to tidal volume (Vd/Vt) - Physiological parameter
Gas exchange (volume of carbon dioxide breathed out (VCO2)) [8 hours]
volume of carbon dioxide breathed out (VCO2) - Physiological parameter

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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