Delirium in the Intensive Care Unit
Conditions
Keywords
delirium, pediatric, dexmedetomidine, midazolam, intensive care unit
Brief summary
The goal of this clinical trial is to learn if dexmedetomidine can reduce delirium in critically ill children, needing mechanical ventilation for more than 12 hours. The main question it aims to answer is : • Does dexmedetomidine reduce the proportion of children presenting at least one episode of delirium during their intensive care unit (ICU) stay ? Researchers will compare dexmetomidine to midazolam, to see if the use of dexmedetomidine reduces the prevalence of delirium. Participants will be sedated with midazolam or dexmedetomidine, according to randomization arm, and the rest of sedation is determined by the study protocol.
Detailed description
\- In the experimental group, participants will receive dexmedetomidine as primary sedative, with opioids for analgesia in order to reach sedation within the target range evaluated with the COMFORT B scale every 4 hours. The initial dose of dexmedetomidine continuous infusion is 0.7 µg/kg/h with increases of 0.2 µg/kg/h if needed associated to an opioid continuous infusion (sufentanil at 0.2 µg/kg/h or morphine at 40 µg/kg/h). A protocol to adjust level of sedation according to the COMFORT B scale will be followed with maximal doses of 1.4 µg/kg/h for dexmedetomidine, 1.5 µg/kg/h for sufentanil and 300 µg/kg/h for morphine. Other drugs like ketamine up to 2 mg/kg/h, propofol, other opioids, midazolam at bolus or small doses (beginning between 20 µg/kg/h and 0.5 mg/h according to age/weight) are possible and will be reported. \- In the control group, participants with invasive ventilation will receive midazolam as first line therapy with opioids in order to reach sedation within the target sedation range evaluated with the COMFORT B scale every 4 hours. The initial dose of midazolam is 40 µg/kg/h for children \<2 years, 60 µg/kg/h for children after 2 years, and 1 mg/h for children \>40kg associated with sufentanil at 0.2 µg/kg/h or intravenous morphine at 40 µg/kg/h. A protocol to adjust level of sedation according to the COMFORT B scale will be followed with maximal doses of 200 µg/kg/h and 10 mg/h if \>40kg for midazolam and 1.5 µg/kg/h for sufentanil or 300 mcg/kg/h for morphine. Other drugs like ketamine up to 2 mg/kg/h, propofol, other opioids, are possible and noted. In case of failure, addition of dexmedetomidine will be possible only if midazolam is used at maximal doses.
Interventions
DRUGDexmedetomidine
Participants in intervention arm will receive dexmedetomidine as primary sedative. We will assess if there is less delirium in the intervention arm
DRUGMidazolam
participant will receive midazolam as the comparator group
Sponsors
University Hospital, Tours
University Hospital, Angers
University Hospital, Lille
Nantes University Hospital
University Hospital, Strasbourg, France
University Hospital, Marseille
University Hospital, Caen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Children between 1month to 17 years and 6 months * Sedation and analgesia for mechanical ventilation for more than 12 hours * Participants covered by or entitled to French social security * Informed consent, dated and signed, from the participant's legal representative(s). (The emergency inclusion procedure will be used if the legal representative(s) cannot be contacted. When the legal representative(s) and the patient are available and/or able to consent, informed consent from the participant's legal representative(s) * Ability for participant to comply with the requirements of the study * Receiving sedation by benzodiazepines for less than 6 hours at the time of inclusion
Exclusion criteria
* Patients under guardianship, curatorship or legal protection * Pregnant or breastfeeding woman (positive pregnancy test for women of childbearing age) * High-grade heart conduction disorder (Second or third-degree atrioventricular block) * Status epilepticus * Intracranial hypertension * Sedation for more than 6 hours by benzodiazepines at the time of inclusion * Need for paralytic medication (neuromuscular blocker) at admission to PICU * Following cardiac surgery * Palliative care on admission * Significant bradycardia * Severe hepatic dysfunction (CHILD score C or worse) due to the hepatic metabolism of dexmedetomidine * Patient already enrolled in the study previously * Expected duration of invasive mechanical ventilation inferior to 12 hours * Hospitalized in a pediatric intensive care unit without computerized prescription software
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of children with at least one episode of delirium during the ICU stay. | From enrollment to the end of ICU stay, up to 90 days | Surveillance of delirium is part of the routine neurological monitoring in pediatric ICU. CAPD score is an 8-items scale. A score of 9 points or higher indicates the presence of delirium. We will evaluate the proportion of children with at least one CAPD score higher than 9. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sedation efficacy | From enrollment to the end of sedation, up to 90 days | Investigators will assess: * The percentage of sedation scores in the target sedation range evaluated with COMFORT B scale every 4 hours, in each group * Percentage of under-sedation, and adverse events (such as unplanned extubation with reintubation, accidental removal of a central line) * Percentage of over-sedation |
| Duration of delirium | from enrollment to the end of ICU stay, up to 90 days | Investigators will assess the number of days with CAPD score higher than or equal to 9 |
| Adverse events and serious adverse events | From enrollment to the end of ICU stay, up to 90 days | Investigators will record: * Hypotension and/or bradycardia needing an intervention, unplanned extubation * accidental removal of a central line |
| Mechanical ventilation | From enrollment to extubation, for an average of 7 days | Investigators will report the mechanical ventilation time in hours |
| Health economic end points | From enrollment to the end of hospital stay, up to 90 days | Investigators will assess the cumulative doses of IV sedative and analgesic drugs so we can compare: * Difference in the costs of sedative, analgesics and opioids consumed during the paediatric intensive care stay and valued from the hospital perspective; * Difference in the cost of inpatient stays and the cost of stays in intensive care units valued from the healthcare system perspective, over a three month time horizon. |
| Severity of delirium | from enrollement to the end of hospital stay, up to 90 days | Investigators will assess the severity of delirium defined by the need for antipsychotic drugs |
| Need for re-intubation | from enrollment, to the end of hospital stay, up to 90 days | Investigators will report the need for re-intubation post extubation |
| Need for neurological investigations | from enrollement to the end of hospital stay, up to 90 days | Investigators will report the percentage of brain imaging and electroencephalogramm |
| Length of stay | from enrollement to the end of hospital stay, up to 90 days | Investigators will report * Intensive care unit length of stay, in days * Hospital length of stay out of the intensive care unit, in days |
| Mortality | from enrollement, to the end of follow-up, up to 90 days | Investigators will assess: hospital mortality |
| Withdrawal | from enrollement to the end of ICU stay, up to 90 days | Investigators will assess the incidence of iatrogenic withdrawal syndrome, measured with WAT-score (defined by WAT \> 4) |
| Associated sedation | from enrollement, to the end of sedation, up to 90 days | Investigators will assess the daily cumulative weight-adjusted dose of IV sedative agents (benzodiazepine, ketamine, propofol) and opioids required in each group. |
| Duration of sedation | from enrollment, to the end of sedation, up to 90 days | Invesitgators will assess the number of days exposed to sedatives and opioids |
Countries
France
Contacts
CONTACTJulie Chantreuil, Dr
CONTACTLea Savary, Dr
Outcome results
None listed