Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation (INASED)

Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation : INASED Study

The objective of the study is to determine the impact on the frequency of occurrence of delirium of an early inhaled sedation strategy (from induction in rapid sequence if intubation in intensive care, or from admission if intubated in pre -hospital) by Isoflurane using an ANACONDA ™ type system, compared to a conventional intravenous sedation strategy.

Study Overview

• Status: Recruiting
• Conditions: Prevention of Delirium
• Intervention / Treatment: Drug: Propofol + analgesic drug; Drug: Isoflurane + analgesic drug

Detailed Description

Sedation-analgesia is used in most patients treated with mechanical ventilation (MV). The usual benzodiazepine and morphine sedation reduces pain and anxiety and allows tolerance of invasive procedures in intensive care. These molecules, used as part of the sedation titration protocol or the daily sedation stop protocol, have improved patient outcomes.

Although necessary, these drugs, by mechanisms still uncertain, would promote the occurrence of resuscitation delirium. Delirium itself responsible for worsening morbidity and mortality (increase in the duration of MV, increase in the length of hospital stay, discussed increase in mortality, long-term cognitive sequelae).

This finding favored the use of new drugs in the sedation strategies of patients on MV. Dexmedetomidine has for example reduced the number of days of delirium, the number of days of coma and even mortality in septic patients. Its large-scale use has however been questioned by a recent study.

Halogenated gases have been used for a long time in anesthesia. Their pharmacodynamics, their positive and adverse effects, their therapeutic margins are well known. Thanks to technical innovations they can be used on resuscitation respirators. Several studies on targeted populations have shown the feasibility and the benefits of this use, in particular, the absence of accumulation, the absence of tachyphylaxis, the broad therapeutic range, the small interindividual variation, the rapidity of efficacy and the speed of awakening. Safety in use for the staff in charge of the patient is established. In addition, their potential neuroprotective effect would make it an anesthetic of choice in the prevention of resuscitation delirium.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre Bailly, MD; Phone Number: +33 02 98 34 71 81; Email: pierre.bailly@chu-brest.fr

Study Locations

• France
  • Bourges, France, 18000
    • Recruiting
    • CH Bourges
    • Contact: Marie-Catherine BESSE, MD; Email: marie-catherine.besse@ch-bourges.fr
  • Brest, France, 29200
    • Recruiting
    • CHU de Brest
    • Contact: Pierre Bailly, MD; Phone Number: +33 02 98 34 71 81; Email: pierre.bailly@chu-brest.fr
  • Corbeil-Essonnes, France, 91106
    • Recruiting
    • CH Corbeil Essonnes
    • Contact: Billiou Cecilia, MD; Phone Number: 0161693519; Email: cecilia.billiou@chsf.fr
  • Le Mans, France, 72039
    • Recruiting
    • CH Le Mans
    • Contact: Christophe GUITTON, Dr; Phone Number: +33 02 53 04 04 42; Email: cguitton@ch-lemans.fr
  • Lorient, France, 56322
    • Recruiting
    • GHBS Lorient
    • Contact: Guillaume GRILLET, Dr; Email: g.grillet@ghbs.bzh
  • Melun, France, 77000
    • Recruiting
    • CH Melun
    • Contact: Sandie MAZERAND, MD; Phone Number: +33 0181742641; Email: sandie.mazerand@ghsif.fr
  • Montpellier, France, 34295
    • Suspended
    • CHU Montpellier
  • Morlaix, France, 29672
    • Recruiting
    • CH Morlaix
    • Contact: Pierre-Yves EGRETEAU, Dr; Phone Number: +33 02 98 62 60 95; Email: pyegreteau@ch-morlaix.fr
  • Poitiers, France, 86021
    • Recruiting
    • CHU Poitiers
    • Contact: Arnaud THILLE, Pr; Phone Number: +33 05 49 44 43 67; Email: arnaud.thille@chu-poitiers.fr
  • Rennes, France, 35033
    • Recruiting
    • CHU Rennes
    • Contact: Florian REIZINE, Dr; Email: florian.reizine@chu-rennes.fr
  • Tours, France, 37044
    • Recruiting
    • Chu Tours
    • Contact: Stephan EHRMANN, Pr; Phone Number: +33 06 71 10 33 02; Email: stephan.ehrmann@univ-tours.fr
  • Tours, France, 37044
    • Not yet recruiting
    • CHU Tours - Réanimation Chirurgicale
    • Contact: Mathilde BARBAZ; Phone Number: 07.62.12.70.34
    • Contact: Email: mathildebarbaz@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged 18 and over
• Patient requiring mechanical ventilation for at least 24 hours
• The patient requires continuous and immediate sedation for more comfort, safety and to facilitate the administration of survival measures.
• Consent obtained from patient or relative

Exclusion Criteria:

Patient hospitalized for the following reasons for admission:

• Cardiac arrest
• State of refractory epilepticus
• Head trauma

• Stroke

  • Hearing, visual or aphasia disorders before inclusion making it impossible to take the CAM-ICU
  • Sedation started more than 24 hours ago
  • Impairment of cognitive functions and / or dementia
  • Contraindication to halogenated gases (personal or family history of malignant hyperthermia, acute or chronic neuromuscular disease, hepatocellular insufficiency with PT <30%)
  • Severe acute respiratory distress syndrome (ARDS) (Berlin criteria: PaO2 / FiO2 <100 after ventilatory optimisation))
  • PaCO2 at inclusion> 50 mmHg after ventilatory optimisation
  • Patient for whom a procedure of "limitation of active therapies" is envisaged at inclusion
  • Patient under guardianship or curatorship
  • Minor patient
  • Pregnant or breastfeeding woman
  • Patient not affiliated to the social security scheme

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual sedation; Sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug.	Drug: Propofol + analgesic drug; sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioïd adjuncts (acetaminophen, NSAIDs, nefopam), opioïds (per os opioïds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl
Experimental: Inhaled sedation; Sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of an analgesic drug.	Drug: Isoflurane + analgesic drug; sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of a analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioïd adjuncts (acetaminophen, NSAIDs, nefopam), opioïds (per os opioïds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of a delirium in intensive care	Occurrence of delirium in intensive care will be observed (yes / no)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality in intensive care	Mortality in intensive care will be observed	Throuh exit from the intensive care unit, an average of 28 days
Mortality at day 28	Mortality at day 28 will be observed	28 days
Hospital cost per patient	The average cost of hospitalization for each patient will be calculated taking into account their length of hospital stay, examinations carried out and medical treatment taken.	Through study completion, an average of 1 year.
Number of days with vasopressors or inotropic agents	Number of days with vasopressors or inotropic agents will be observed	Throuh exit from the intensive care unit, an average of 28 days
Number of days with sedation	Number of days with sedation will be observed	Throuh exit from the intensive care unit, an average of 28 days
Cumulative dose anesthetics drugs	Cumulative dose anesthetics drugs will be observed	Throuh exit from the intensive care unit, an average of 28 days
Duration of anesthetics drugs	Duration of anesthetics drugs will be observed	Throuh exit from the intensive care unit, an average of 28 days
Maximum dose of vasopressors or inotropic agents	Maximum dose of vasopressors or inotropic agents will be observed	Throuh exit from the intensive care unit, an average of 28 days
Ventilation free days at 28 days following randomisation	Ventilation free days at 28 days following randomisation will be observed	28 days
Incidence of delirium	Incidence of delirium will be observed	28 days
Duration of delirium	Duration of delirium will be observed	28 days
Length of ICU stay	Length of ICU stay will be calculated	Throuh exit from the intensive care unit, an average of 28 days
Requirement of patients physical restraints	Requirement of physical restraints, of patients with unplanned extubation, unplanned catheter, urinary probe or gastric probe removal will be observed	Throuh exit from the intensive care unit, an average of 28 days
Self aggressive act	Self aggressive act will be observed	Throuh exit from the intensive care unit, an average of 28 days
Hetero-aggressive act	Hetero-aggressive act will be observed	Throuh exit from the intensive care unit, an average of 28 days
Evaluation of cognitive functions	Cognitive function will be evaluated at discharge, 3- and 12 months using two kinds of score : Cantab test, combining 6 cognitive evaluations with an iPad during a 45-60 minutes medical consultation; PCLS (Posttraumatic stress disorder Checklist Scale), HADS (Hospital Anxiety and Depression scale), SF36 (medical outcome study short form 36), IADL (instrumental activities of daily living) practised by a clinical research associate	Through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Pierre Bailly, MD, CHRU Brest

Publications and helpful links

General Publications

• Bailly P, Egreteau PY, Ehrmann S, Thille AW, Guitton C, Grillet G, Reizine F, Huet O, Jaber S, Nowak E, L'her E. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial. BMJ Open. 2021 Feb 19;11(2):e042284. doi: 10.1136/bmjopen-2020-042284.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Analgesics; Isoflurane
• Other Study ID Numbers: INASED (29BRC19.0280)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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