Goal-Directed Sedation in Mechanically Ventilated Infants and Children

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Pfizer
• Treatments: Dexmedetomidine; Midazolam

Criteria

Inclusion Criteria:

• Patients will be eligible for enrollment if they are 1) aged ≥ 6 months and < 11 years, 2) admitted to the pediatric ICU at Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV), and 3) on mechanical ventilation (MV) requiring sedation. Pre-pubescent children (<11 years) are typically different from older children who often behave physiologically more similar to adults. Pre-pubescent children are more likely to be admitted to the PICU and are undergoing a steeper curve of neurocognitive maturation. Therefore, these patients may be at greatest risk for worse brain dysfunction.

Exclusion Criteria: Patients will be excluded (i.e., not approached for consent) if any one is present:

1. Receiving continuous sedation for > 48 hours prior to screening

2. Rapidly resolving respiratory failure at screening, with planned immediate liberation from MV.

3. Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability) on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive status prior to critical illness.

4. Clinically significant 2nd or 3rd degree heart block or bradycardia < 60 beats per minute.

5. Benzodiazepine dependency with ongoing medical requirement of continuous benzodiazepine (infusion).

6. Inability to co-enroll with another study.

7. Expected death or care plan for withdrawal of support measures within 24 hours of enrollment.

8. Bilateral vision loss.

9. Inability to understand English or deafness 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 that particular language.

10. Documented allergy to either dexmedetomidine or midazolam.

11. Medical requirement of continuous (infusion) neuromuscular blockade administration that is planned ongoing for at least 48 hours at time of screening.

12. Inability to start the informed consent process within the 48 hours from the time that all inclusion criteria were met (possible reasons):

1. Attending physician refusal

2. 48-hour period of eligibility was exceeded before the patient was screened

3. Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) refusal

4. Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) unavailable

5. 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.