Down Syndrome Autonomic Nervous System Induction Bradycardia (DANSIB)

Finding the Contribution of the Autonomic Nervous System During Perioperative Events in Children With Down Syndrome

Children with Down syndrome (DS) often experience dangerously low heart rates on induction of anesthesia for routine procedures and this occurs at 10 times the rate of non-DS patients. Given that the cardiac output of children is heart rate dependent, bradycardia is especially perilous in this population.

Historically, individuals with DS were not expected to survive beyond childhood; consequently, correction of congenital anomalies, e.g. cardiac defects, was not frequently offered. Fortunately, today individuals with DS live into adulthood and surgical correction of anomalies is universally offered. Thus, increasing numbers of children with DS are exposed to anesthesia and at risk for this hemodynamic catastrophe. It is medically unacceptable and an autonomic nervous system mechanism will be sought.

Study Overview

• Status: Completed
• Conditions: Bradycardia; Down Syndrome
• Intervention / Treatment: Other: Monitoring patients undergoing surgery to look for association between ANS activity and bradycardia

• Study Type: Observational
• Enrollment (Actual): 195

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 8 years (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population will be children age 1 month to 8 years undergoing otolaryngologic surgery with anesthesia.

Description

Inclusion Criteria:

• Patients who are overtly healthy as determined by medical evaluation including lack of diagnosis of Down Syndrome and children with Down Syndrome

Exclusion Criteria:

1. Contraindication to adhesive placement, eg, epidermolysis bullosa
2. Patient or parent refusal
3. Opioids
4. Heart rate altering therapy such as beta blockers
5. During the study period, participants will abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, tea, cola drinks, and chocolate) for [6 hours] before the start of the anesthetic.
6. Participants will be assumed not to be using tobacco or alcohol during the study period due to their young age.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Down Syndrome patients undergoing otolaryngologic surgery with anesthesia	Other: Monitoring patients undergoing surgery to look for association between ANS activity and bradycardia; Use of an Ambulatory Monitoring System from Vuije University (VU-AMS) to record autonomic and cardiovascular activity of patients undergoing otolaryngologic surgery with anesthesia. This monitoring device will provide data of ANS activity and normoxic bradycardia among patients with Down Syndrome. This data will be compared to data from patients without Down Syndrome.
Non-Down Syndrome patients undergoing otolaryngologic surgery with anesthesia	Other: Monitoring patients undergoing surgery to look for association between ANS activity and bradycardia; Use of an Ambulatory Monitoring System from Vuije University (VU-AMS) to record autonomic and cardiovascular activity of patients undergoing otolaryngologic surgery with anesthesia. This monitoring device will provide data of ANS activity and normoxic bradycardia among patients with Down Syndrome. This data will be compared to data from patients without Down Syndrome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory feasibility of VU-AMS monitor on patients with Down Syndrome	Subjects will be observed for monitor use coming to the hospital for surgery. The two outcomes will be binary: wearing the device or not. We anticipate that 50% of subjects will be wearing the VU-AMS monitor on entry to the hospital on the day of surgery.	Immediately upon entry into Same Day Surgery patient room
Ambulatory feasibility of VU-AMS monitor on patients without Down Syndrome	Subjects will be observed for monitor use coming to the hospital for surgery. The two outcomes will be binary: wearing the device or not. We anticipate that 50% of subjects will be wearing the VU-AMS monitor on entry to the hospital on the day of surgery.	Immediately upon entry into Same Day Surgery patient room
Operating room feasibility of VU-AMS monitor on patients with Down Syndrome	Subjects will be observed for monitor use throughout surgery. We anticipate that 80% of subjects will wear the VU-AMS in the operating room	Immediately prior to mask induction with sevoflurane
Operating room feasibility of VU-AMS monitor on patients without Down Syndrome	Subjects will be observed for monitor use throughout surgery. We anticipate that 80% of subjects will wear the VU-AMS in the operating room	Immediately prior to mask induction with sevoflurane
Autonomic data including pre-ejection period and respiratory sinus arrhythmia among patients with Down Syndrome	Among subjects who become bradycardic with induction of anesthesia, we expect that the pre-ejection period will increase by 20%	Beginning at time of bradycardia and continuing for the next 300 seconds.
Autonomic data including pre-ejection period and respiratory sinus arrhythmia among patients without Down Syndrome	Among subjects who become bradycardic with induction of anesthesia, we expect that the pre-ejection period will increase by 20%	Beginning at time of bradycardia and continuing for the next 300 seconds.

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Jamie Sinton, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): December 12, 2023
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Bradycardia; Down Syndrome
• Other Study ID Numbers: 2021-0643; R21HL162572 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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