Atrial Septal Defect, Bidirectional Cavopulmonary Anastomosis, Cardiac Transplant, Patent Ductus Arterious
Conditions
Keywords
Dexmedetomidine, Congenital heart disease, pharmacokinetics, pharmacodynamics, pediatric, Bidirectional cavopulmonary anastomosis, Fontan physiology, Cardiac transplant
Brief summary
The purpose of this study is to examine the pharmacokinetics, pharmacodynamics, and pharmacogenomics of dexmedetomidine in the following three pediatric patient populations: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect.
Detailed description
While opioid analgesia is currently the mainstream for management of pain in the perioperative setting, it often leads to significant morbidity, including opioid tolerance and hyperalgesia. Looking at ways to decrease the need for opioids with the use of adjunct medications allows for the long-term goal of decreasing physiologic tolerance in children. This is especially relevant in the pediatric congenital heart population. Dexmedetomidine is in a class of drugs known as alpha-2 agonists and is known to provide analgesia, attenuate opioid tolerance and inhibit the sympathetic stress response. While there are numerous published case studies of dexmedetomidine validating its effectiveness and safety, the pharmacologic and pharmacodynamic profile has not been established. This study will examine the hemodynamics, pharmacokinetics, and pharmacogenomics of dexmedetomidine in patients with congenital heart disease. The dose-ranging effect of dexmedetomidine will also be investigated. The three groups being studied will be: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect. Comparison: Compare both invasive and noninvasive hemodynamic parameters at baseline sevoflurane and during maintenance dosing on dexmedetomidine. The pharmacokinetics of dexmedetomidine in the pediatric population following escalating loading doses and continuous infusion at timed intervals will be estimated. The efficacy of dexmedetomidine will be estimated by the amount of rescue doses of propofol that are given.
Interventions
DRUGDexmedetomidine
Dexmedetomidine load of 1 microgram/kilogram over 10 minutes, followed by a 1 microgram/kilogram/hour infusion during the time of catheterization
Sponsors
Children's National Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* age is birth to 18 years * \> or = 6 kg. * American Society of Anesthesiology (ASA) I, II, or III * undergone prior cardiac transplant, Fontan or has a patent ductus arterious or atrial septal defect. * scheduled for cardiac catheterization
Exclusion criteria
* subject or family history of malignant hyperthermia * known hepatic disorder determined by history physical exam or laboratory tests * pregnant or lactating female * receiving inotropic agents or has a pacemaker * weighs less than 6 kg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Up to 24 hours following cardiac catheterization | Non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%.The 95% confidence interval was normalized by subtracting the baseline values. Bispectral Index: monitors electroencephalographic and electromyographic parameters to monitor the depth of anesthesia. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from cardiology outpatient clinic. The study is anticipating to enroll 104 patients.
Pre-assignment details
74 subjects assessed for eligibility, 9 were excluded; 12 did not meet inclusion criteria; 12 refused to enroll; resulting in 41 subjects enrolled
Participants by arm
| Arm | Count |
|---|---|
| Normal Physiology | 26 |
| Cardiac Transplant | 9 |
| Fontan Physiology | 6 |
| Total | 41 |
Baseline characteristics
| Characteristic | Normal Physiology | Cardiac Transplant | Fontan Physiology | Total |
|---|---|---|---|---|
| Age, Continuous | 4.3 years STANDARD_DEVIATION 4 | 11 years STANDARD_DEVIATION 4.5 | 5.5 years STANDARD_DEVIATION 3.3 | 6.9 years STANDARD_DEVIATION 6.2 |
| American Society of Anesthesiology (ASA) physical status classification ASA 1 | 18 participants | 0 participants | 0 participants | 18 participants |
| American Society of Anesthesiology (ASA) physical status classification ASA 2 | 8 participants | 9 participants | 0 participants | 17 participants |
| American Society of Anesthesiology (ASA) physical status classification ASA 3 | 0 participants | 0 participants | 6 participants | 6 participants |
| Primary diagnosis ASD | 10 participants | 0 participants | 0 participants | 10 participants |
| Primary diagnosis Cardiomyopathy | 0 participants | 4 participants | 0 participants | 4 participants |
| Primary diagnosis DORV | 0 participants | 0 participants | 1 participants | 1 participants |
| Primary diagnosis Ebstein's anomaly | 0 participants | 0 participants | 1 participants | 1 participants |
| Primary diagnosis HLHS | 0 participants | 2 participants | 2 participants | 4 participants |
| Primary diagnosis PA with IVS | 0 participants | 2 participants | 0 participants | 2 participants |
| Primary diagnosis PDA | 16 participants | 0 participants | 0 participants | 16 participants |
| Primary diagnosis Tricuspid Atresia | 0 participants | 0 participants | 2 participants | 2 participants |
| Primary diagnosis Unbalanced AVC | 0 participants | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 17 Participants | 3 Participants | 2 Participants | 22 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 4 Participants | 19 Participants |
| Weight (kg) | 19.1 kg STANDARD_DEVIATION 14.3 | 35.2 kg STANDARD_DEVIATION 17.8 | 21.4 kg STANDARD_DEVIATION 8.7 | 27.3 kg STANDARD_DEVIATION 13.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 6 | 0 / 26 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 26 |
Outcome results
Primary
Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine.
Non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%.The 95% confidence interval was normalized by subtracting the baseline values. Bispectral Index: monitors electroencephalographic and electromyographic parameters to monitor the depth of anesthesia.
Time frame: Up to 24 hours following cardiac catheterization
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Normal Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Mean Pressure | 0.23 percentage of change from baseline |
| Normal Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Diastolic Pressure | 0.23 percentage of change from baseline |
| Normal Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Heart Rate | -0.14 percentage of change from baseline |
| Normal Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Systolic Pressure | 0.15 percentage of change from baseline |
| Normal Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Bispectral Index | 0.04 percentage of change from baseline |
| Cardiac Transplant | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Diastolic Pressure | 0.19 percentage of change from baseline |
| Cardiac Transplant | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Heart Rate | -0.16 percentage of change from baseline |
| Cardiac Transplant | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Systolic Pressure | 0.18 percentage of change from baseline |
| Cardiac Transplant | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Mean Pressure | 0.16 percentage of change from baseline |
| Cardiac Transplant | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Bispectral Index | 0.16 percentage of change from baseline |
| Fontan Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Bispectral Index | -0.14 percentage of change from baseline |
| Fontan Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Mean Pressure | 0.08 percentage of change from baseline |
| Fontan Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Heart Rate | -0.21 percentage of change from baseline |
| Fontan Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Diastolic Pressure | 0.09 percentage of change from baseline |
| Fontan Physiology | Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Systolic Pressure | 0.22 percentage of change from baseline |
p-value: 0.05t-test, 2 sided