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

Prevention of Delirium Clinical Trial

— INASED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04341350
• Other study ID #: INASED (29BRC19.0280)
• Status: Recruiting
• Phase: N/A
• Start date: August 6, 2020
• Est. completion date: August 2025

Study information

• Verified date: January 2024
• Source: University Hospital, Brest
• Contact: Pierre Bailly, MD
• Phone: 02 98 34 71 81
• Email: pierre.bailly[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: August 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Prevention of Delirium

Intervention

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
• 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.

Locations

Country	Name	City	State
France	CH Bourges	Bourges
France	CHU de Brest	Brest
France	CH Corbeil Essonnes	Corbeil-Essonnes
France	CH Le Mans	Le Mans
France	GHBS Lorient	Lorient
France	CH Melun	Melun
France	CHU Montpellier	Montpellier
France	CH Morlaix	Morlaix
France	CHU Poitiers	Poitiers
France	CHU Rennes	Rennes
France	CHU Tours	Tours
France	CHU Tours - Réanimation Chirurgicale	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of a delirium in intensive care	Occurrence of delirium in intensive care will be observed (yes / no)	28 days
Secondary	Mortality in intensive care	Mortality in intensive care will be observed	Throuh exit from the intensive care unit, an average of 28 days
Secondary	Mortality at day 28	Mortality at day 28 will be observed	28 days
Secondary	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.
Secondary	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
Secondary	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
Secondary	Cumulative dose anesthetics drugs	Cumulative dose anesthetics drugs will be observed	Throuh exit from the intensive care unit, an average of 28 days
Secondary	Duration of anesthetics drugs	Duration of anesthetics drugs will be observed	Throuh exit from the intensive care unit, an average of 28 days
Secondary	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
Secondary	Ventilation free days at 28 days following randomisation	Ventilation free days at 28 days following randomisation will be observed	28 days
Secondary	Incidence of delirium	Incidence of delirium will be observed	28 days
Secondary	Duration of delirium	Duration of delirium will be observed	28 days
Secondary	Length of ICU stay	Length of ICU stay will be calculated	Throuh exit from the intensive care unit, an average of 28 days
Secondary	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
Secondary	Self aggressive act	Self aggressive act will be observed	Throuh exit from the intensive care unit, an average of 28 days
Secondary	Hetero-aggressive act	Hetero-aggressive act will be observed	Throuh exit from the intensive care unit, an average of 28 days
Secondary	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.