Burns, Sedation
Conditions
Keywords
pediatric, burn, sedation
Brief summary
Dexmedetomidine is a sedative drug approved for adult patients, intubated, in intensive care units. We are studying whether this drug is cardiovascularly safe in pediatric patients who have recently been burned.
Detailed description
This is an ascending dose study evaluating the cardiovascular safety of dexmedetomidine bolus/infusions in acutely burned pediatric patients. The study entails a bolus of dexmedetomidine, followed by 2 hours of increasing infusion doses. Cardiovascular parameters including EKG, heart rate, oxygen saturation, blood pressure, are recorded.
Interventions
DRUGDexmedetomidine
Dexmedetomidine bolus 1 ug/kg over 10 minutes, followed by ascending infusion as follows: Dexmedetomidine \[in ug/kg/hr\], each for 15 minutes: 0.7, 1.0, 1.3, 1.6, 1.9, 2.2, 2.5.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* pediatric patient * \>25% total body surface area (tbsa) burn and \< 90% tbsa * opioid requirements \> 0.1 mg/kg/hour of morphine (or equivalent) * midazolam requirement \> 0.1 mg/kg/hour * treatment team determined that patient should be started on dexmedetomidine
Exclusion criteria
* hemodynamically unstable patients (epinephrine \> 1.0 ug/kg/min, levophed \> 0.75 ug/kg/min, dopamine \> 10 ug/kg/min) * pregnant patients * patients with history of heart block * patients with congenital heart disease * patients with significant hepatic dysfunction * patients with urine output \< 0.5 ml/kg/hour \[averaged\] over past 24 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Mean Arterial Pressure (MAP) | 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration | Looking at hemodynamic response to dexmedetomidine. Mean arterial pressure primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Arrhythmias. | 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration | Presence of arrhythmias was studied using a 3 lead realtime EKG throughout study. |
| Oxygen Saturation | 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration | Pulse oximetry was used to measure oxygen saturation. |
| Heart Rate | 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration | Heart Rate recorded off EKG in beats per minute |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ascending Dose Study Ascending doses of dexmedetomidine (as per protocol)
Dexmedetomidine: Dexmedetomidine bolus 1 ug/kg over 10 minutes, followed by ascending infusion as follows: Dexmedetomidine \[in ug/kg/hr\], each for 15 minutes: 0.7, 1.0, 1.3, 1.6, 1.9, 2.2, 2.5. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Dexmedetomidine 0.7 mcg/kg/hr Infusion | Physician Decision | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dexmedetomidine 1.6 mcg.kg.hr Infusion | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Ascending Dose Study |
|---|---|
| Age, Categorical <=18 years | 8 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Central Venous Pressure | 10.4 millimeters of mercury (mm Hg) STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fluid intake-Fluid output | 88.7 ml/kg/24 hours STANDARD_DEVIATION 71.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
| Time after injury in days | 19.7 days STANDARD_DEVIATION 10.3 |
| Total Body Surface Area Burned | 58.3 percentage of surface STANDARD_DEVIATION 15.2 |
| Weight | 33.5 kilograms STANDARD_DEVIATION 23.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 1 / 8 | 2 / 7 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 2 |
Outcome results
Primary
Percent Change in Mean Arterial Pressure (MAP)
Looking at hemodynamic response to dexmedetomidine. Mean arterial pressure primary outcome measure.
Time frame: 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration
Population: Acutely burned pediatric patients intubated with burns \>=20% between 2 and 19 years of age requiring escalating doses of morphine and midazolam
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Dexmedetomidine Bolus 1 mcg/kg Over 10 Min IV | Percent Change in Mean Arterial Pressure (MAP) | 26.7 % change | Standard Deviation 7.5 |
| Cohort 2: Dexmedetomidine Bolus + 0.7 mcg/kg/hr Infusion | Percent Change in Mean Arterial Pressure (MAP) | 30.8 % change | Standard Deviation 10.2 |
| Cohort 3: Dexmedetomidine 1.0 mcg/kg/hr Infusion | Percent Change in Mean Arterial Pressure (MAP) | 26.5 % change | Standard Deviation 10.5 |
| Cohort 4: Dexmedetomidine Infusion 1.3 mcg/kg/hr | Percent Change in Mean Arterial Pressure (MAP) | 24.5 % change | Standard Deviation 13.8 |
| Cohort 5: Dexmedetomidine 1.6 mcg/kg/hr Infusion | Percent Change in Mean Arterial Pressure (MAP) | 25.5 % change | Standard Deviation 12.5 |
| Cohort 6: Dexmedetomidine 1.9 mcg/kg/hr | Percent Change in Mean Arterial Pressure (MAP) | 18 % change | Standard Deviation 8.7 |
| Cohort 7: Dexmedetomidine 2.2 mcg/kg/hr | Percent Change in Mean Arterial Pressure (MAP) | 15 % change | Standard Deviation 7 |
| Cohort 8: Dexmedetomidine 2.5 mcg/kg/hr | Percent Change in Mean Arterial Pressure (MAP) | 15.6 % change | Standard Deviation 8 |
Secondary
Heart Rate
Heart Rate recorded off EKG in beats per minute
Time frame: 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Dexmedetomidine Bolus 1 mcg/kg Over 10 Min IV | Heart Rate | 125.6 heart beats per minute | Standard Deviation 16.6 |
| Cohort 2: Dexmedetomidine Bolus + 0.7 mcg/kg/hr Infusion | Heart Rate | 122 heart beats per minute | Standard Deviation 15.8 |
| Cohort 3: Dexmedetomidine 1.0 mcg/kg/hr Infusion | Heart Rate | 127.5 heart beats per minute | Standard Deviation 11.9 |
| Cohort 4: Dexmedetomidine Infusion 1.3 mcg/kg/hr | Heart Rate | 125.5 heart beats per minute | Standard Deviation 17.2 |
| Cohort 5: Dexmedetomidine 1.6 mcg/kg/hr Infusion | Heart Rate | 122.8 heart beats per minute | Standard Deviation 17.8 |
| Cohort 6: Dexmedetomidine 1.9 mcg/kg/hr | Heart Rate | 129.7 heart beats per minute | Standard Deviation 11.6 |
| Cohort 7: Dexmedetomidine 2.2 mcg/kg/hr | Heart Rate | 132.3 heart beats per minute | Standard Deviation 17.9 |
| Cohort 8: Dexmedetomidine 2.5 mcg/kg/hr | Heart Rate | 125 heart beats per minute | Standard Deviation 8.9 |
Secondary
Oxygen Saturation
Pulse oximetry was used to measure oxygen saturation.
Time frame: 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Dexmedetomidine Bolus 1 mcg/kg Over 10 Min IV | Oxygen Saturation | 99.8 Percent of Hemoglobin Saturated | Standard Deviation 0.5 |
| Cohort 2: Dexmedetomidine Bolus + 0.7 mcg/kg/hr Infusion | Oxygen Saturation | 99.5 Percent of Hemoglobin Saturated | Standard Deviation 0.8 |
| Cohort 3: Dexmedetomidine 1.0 mcg/kg/hr Infusion | Oxygen Saturation | 99.5 Percent of Hemoglobin Saturated | Standard Deviation 0.8 |
| Cohort 4: Dexmedetomidine Infusion 1.3 mcg/kg/hr | Oxygen Saturation | 98.6 Percent of Hemoglobin Saturated | Standard Deviation 1.1 |
| Cohort 5: Dexmedetomidine 1.6 mcg/kg/hr Infusion | Oxygen Saturation | 98.6 Percent of Hemoglobin Saturated | Standard Deviation 1.1 |
| Cohort 6: Dexmedetomidine 1.9 mcg/kg/hr | Oxygen Saturation | 98.6 Percent of Hemoglobin Saturated | Standard Deviation 1.3 |
| Cohort 7: Dexmedetomidine 2.2 mcg/kg/hr | Oxygen Saturation | 99.3 Percent of Hemoglobin Saturated | Standard Deviation 1.5 |
| Cohort 8: Dexmedetomidine 2.5 mcg/kg/hr | Oxygen Saturation | 99.5 Percent of Hemoglobin Saturated | Standard Deviation 0.6 |
Secondary
Presence of Arrhythmias.
Presence of arrhythmias was studied using a 3 lead realtime EKG throughout study.
Time frame: 10, 25, 40, 55, 70, 85, 100, 115 minutes after dexmedetomidine bolus administration
Population: EKG was analyzed on each participant looking for presence of arrhythmias. None were detected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Dexmedetomidine Bolus 1 mcg/kg Over 10 Min IV | Presence of Arrhythmias. | 0 Participants |
| Cohort 2: Dexmedetomidine Bolus + 0.7 mcg/kg/hr Infusion | Presence of Arrhythmias. | 0 Participants |
| Cohort 3: Dexmedetomidine 1.0 mcg/kg/hr Infusion | Presence of Arrhythmias. | 0 Participants |
| Cohort 4: Dexmedetomidine Infusion 1.3 mcg/kg/hr | Presence of Arrhythmias. | 0 Participants |
| Cohort 5: Dexmedetomidine 1.6 mcg/kg/hr Infusion | Presence of Arrhythmias. | 0 Participants |
| Cohort 6: Dexmedetomidine 1.9 mcg/kg/hr | Presence of Arrhythmias. | 0 Participants |
| Cohort 7: Dexmedetomidine 2.2 mcg/kg/hr | Presence of Arrhythmias. | 0 Participants |
| Cohort 8: Dexmedetomidine 2.5 mcg/kg/hr | Presence of Arrhythmias. | 0 Participants |