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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; Mechanical Ventilation Complication; Sedation Complication
• Intervention / Treatment: Drug: Propofol; Drug: Isoflurane

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Guy Glover; Phone Number: 00447879696250; Email: guy.glover@gstt.nhs.uk
• Study Contact Backup: Name: Gill Radcliffe; Phone Number: 02071887188; Email: gillian.radcliffe@gstt.nhs.uk

Study Locations

• United Kingdom
  • London
    • London, London, United Kingdom, SE1 9RT
      • Recruiting
      • Guy's & St Thomas' NHS Foundation Trust
      • Contact: Gill Radcliffe; Phone Number: 02071888070; Email: gillian.radcliffe@gstt.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory drive (P0.1)	Negative pressure in the first 100milliseconds of inspiration (P0.1) - Physiological parameter	8 hours

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: Sedana Medical
• Investigators: Principal Investigator: Guy Glover, Guy's and St Thomas' NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome; Organic Chemicals; Ethers; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Methyl Ethers; Propofol; Isoflurane
• Other Study ID Numbers: SMRG_318537

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No