Goal-Directed Sedation in Mechanically Ventilated Infants and Children (mini-MENDS)

  • End date
    Jun 22, 2025
  • participants needed
  • sponsor
    Vanderbilt University Medical Center
Updated on 22 August 2023


Ventilated pediatric patients are frequently over-sedated and the majority suffer from delirium, a form of acute brain dysfunction that is an independent predictor of increased risk of dying, length of stay, and costs. Universally prescribed sedative medications-the GABA-ergic benzodiazepines-worsen this brain organ dysfunction and independently prolong duration of ventilation and ICU stay, and the available alternative sedation regimen using dexmedetomidine, an alpha-2 agonist, has been shown to be superior to benzodiazepines in adults, and may mechanistically impact outcomes through positive effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The mini-MENDS trial will compare dexmedetomidine and midazolam, and determine the best sedative medication to reduce delirium and improve duration of ventilation, and functional, psychiatric, and cognitive recovery in our most vulnerable patients-survivors of pediatric critical illness.


The need for mechanical ventilation (MV) following acute respiratory and myocardial failure is the leading cause of admission to the pediatric intensive care unit (PICU). Over 90% of MV pediatric patients receive continuous sedation, most commonly with gamma-aminobutyric acid (GABA) agonist benzodiazepines. Recently, the investigators demonstrated that exposure to the benzodiazepine midazolam contributed to iatrogenic harm in pediatric patients-prolonging PICU length of stay and increasing the prevalence and duration of delirium. Delirium is prevalent in the PICU with rates of up to 30% in older children, over 50% in infants and toddlers, and up to 60-70% in those on MV. Delirium in children is a significant contributor to longer duration of MV, substantial consequential costs, prolonged ICU stay, and mortality. Adult studies have shown that an alternative sedation paradigm using dexmedetomidine, an alpha-2 agonist, decreases the prevalence and duration of delirium, duration of MV, ICU length of stay, cost, and infection rates compared to benzodiazepine-based sedation. Furthermore, the FDA recently published warnings regarding the possible role of anesthetics, including benzodiazepines, on cognitive dysfunction in children. Dexmedetomidine has unique anti-inflammatory and anti-oxidant characteristics that are appealing given the association between inflammation, and endothelial and blood-brain barrier (BBB) injury with prolonged delirium and worse cognitive impairment in adults. To this end, there has been no large pediatric cohort study to examine the relationship between sedative choice and exposure in the ICU (a much longer exposure) with cognitive impairment among pediatric survivors. The investigators, therefore, propose mini-MENDS (Maximizing Efficacy of Goal-Directed Sedation to Reduce Neurological Dysfunction in Mechanically Ventilated Infants and Children STUDY), in which the investigators will determine whether sedation of MV pediatric patients with an alpha-2 agonist (dexmedetomidine) versus a GABA-ergic benzodiazepine (midazolam) will decrease daily prevalence of delirium (Aim 1A) and duration of MV (Aim 1B), will be associated with better functional, psychiatric, and cognitive recovery (Aim 2), and reduced levels of pro-inflammatory cytokines and biomarkers of endothelial and blood brain barrier injury (Aim 3). To accomplish these aims, the investigators will randomize 372 pediatric patients on MV, aged 44 weeks post-menstrual age to 11 years, to receive goal-directed continuous sedation with either dexmedetomidine or midazolam for up to 10 days. Our primary outcome, daily prevalence of delirium, will be objectively measured by trained research nurses who are blinded to intervention arm. Screening for delirium will be completed using the Preschool or Pediatric Confusion Assessment Methods for the ICU (ps/pCAM-ICU), based on developmental age, twice daily for up to 14 days while in the PICU. Cognition, functional status, and parental/patient psychological health will be assessed at enrollment (baseline), hospital discharge (DC), and 6 months following ICU-DC during an in-person evaluation by the pediatric neuropsychiatry team. Blood will be collected on days 1, 3, and 5 post-randomization to measure cytokines, markers of endothelial and BBB injury, and for safety.

Condition Delirium, Critical Illness, Sedation Complication, Executive Dysfunction, Post Traumatic Stress Disorder
Treatment Dexmedetomidine, Midazolam
Clinical Study IdentifierNCT04801589
SponsorVanderbilt University Medical Center
Last Modified on22 August 2023


Yes No Not Sure

Inclusion Criteria

Attending physician refusal
72-hour period of eligibility was exceeded before the patient was enrolled
Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) refusal
Legal Authorized Decision Maker (e.g. legal guardian/power of attorney)
Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) is
non-English speaking and available research staff is not proficient and/or
translation services are not available in that particular language
Adjusted dosing weight is > 50 kg at time of screening

Exclusion Criteria

Patients will be excluded (i.e., not approached for consent) if any one
is present
Rapidly resolving respiratory failure at screening, with planned immediate liberation
Receiving continuous sedation for > 72 hours prior to screening
from MV
Inability to co-enroll with another study
Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability)
Bilateral vision loss
on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive
status prior to critical illness
Documented allergy to either dexmedetomidine or midazolam
Clinically significant 2nd or 3rd degree heart block or bradycardia < 60 beats per
Benzodiazepine dependency with ongoing medical requirement of continuous
benzodiazepine (infusion)
Expected death or care plan for withdrawal of support measures within 24 hours of
Deafness that will preclude delirium evaluation
Inability to understand English that will preclude delirium evaluation. The inability
to understand English in verbal participants will not result in exclusion when the
research staff is proficient and/or translation services are actively available in
Medical requirement of continuous (infusion) neuromuscular blockade administration
that particular language
that is planned ongoing for at least 48 hours at time of screening
Inability to start the informed consent process within the 72 hours from the time that
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