Congenital Heart Disease
Conditions
Keywords
congenital heart disease, pediatric cardiothoracic surgery
Brief summary
The investigators hypothesize that intermittent bolus doses of morphine and midazolam can provide the same pain control after pediatric cardiothoracic surgery as bolus doses plus infusions while using smaller total doses of both medications. The investigators will randomize patients to receive either morphine/midazolam as needed intermittently or morphine/midazolam drips plus intermittent doses to be received as needed. Pain scores will be recorded and total medications given will be recorded.
Detailed description
Prior to surgery, eligible patients scheduled for surgery will be sent our standard surgery letter (Attachment A) along with our study informational sheet (Attachment B) describing our study. The study informational sheet will have a telephone number to call to set up a phone appointment to discuss the study with the PI should parents have questions not answered on the sheet. During the pre-operative visit, the study will again be discussed with the parents. Our nurse practitioners will be trained on this study and will obtain written consent at this time. If the parents would like to further discuss the study directly with the PI, this will be arranged prior to surgery. The PI will be notified by the NPs of all parents who give permission for their child to participate in the study, and he will notify the on service medical team. On the day of surgery, a computerized order for the study will be entered to notify the pharmacy to randomize the subject to the control or treatment group. Randomization will be stratified based on whether the child has DS, as children with DS are known to have a heightened pain response and require large doses of medication to treat pain. Only the pharmacist will know the random assignment, health care providers and subjects/families will be blinded as to treatment arm. Treatment Group: Intravenous (IV) drip of 0.03 mg/kg/hour morphine and 0.03 mg/kg/hour midazolam Control Group: IV drip of normal saline (NS) at same volume as what the morphine/midazolam drip would be Both Groups Subjects in both the control and treatment group will receive the following post-operative pain control orders that are currently in use in the PSHU: 1. Morphine 0.05 mg/kg/dose IV q 2 hours prn pain score 4 or greater 2. Midazolam 0.05 mg/kg/dose IV q1 hours prn agitation 3. Additional prn doses of morphine and midazolam may be given as determined by the treating team (these doses will be recorded in the EMR) 4. Acetaminophen 30 mg/kg PR x 1 to be given on admission to PSHU post surgery 5. Acetaminophen 15 mg/kg PR q4 hours to be started 4 hours after first dose 6. Acetaminophen 15 mg/kg PO q4 hours to be started after subject starts drinking by mouth and PR doses stopped 7. Ketorolac 0.5 mg/kg/dose IV q 6 hours to start 6-12 hours after surgery when chest tube drainage criteria are met. Will start when chest tube drainage is no longer frankly bloody and if chest tube drainage is less than 3 cc/kg/hour for two hours in a row
Interventions
Continuous morphine/midazolam and 'as needed' doses. Will receive scheduled acetaminophen and ketorolac.
DRUGas needed dosing
morphine and midazolam as needed. Will receive scheduled acetaminophen and ketorolac..
DRUGAcetaminophen
Acetaminophen will be given every 4 hours for a total of 24 hours.
DRUGketorolac
Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
3 Months to 4 Months
Healthy volunteers
No
Inclusion criteria
* Age 3 months - 4 years (48 months) * Anticipated cardiothoracic surgery with midline sternotomy incision * Planned early extubation (e.g. within 3 hours post surgery)
Exclusion criteria
* Presence of renal insufficiency defined as a creatinine greater than 0.8mg/dL on the standard basic metabolic profile sent after surgery or history of chronic renal failure. * Significant development delay that the bedside nurse or treating physician judges would make pain scoring difficult (Down syndrome is not excluded) * History of bleeding disorder or gastrointestinal bleed within the past 2 months. * Presence of chronic hepatic disease or elevation of AST or ALT greater than 250 U/L before or after surgery. * More than 3 previous surgeries with a sternotomy incision (this may alter pain perception). * Children on immunosuppressants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Morphine Dosage | 24 hours | Total dose of morphine used will be recorded for each patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | From date of randomization until the date of first documented progression or date of death from any cause or discharge, whichever came first, assessed up to 100 months | Length of stay will be recorded for each subject. |
Countries
United States
Participant flow
Recruitment details
We enrolled 78, but 18 were excluded after informed consent for the reasons listed below. 30 in each group were assigned and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Continuous Infusion Patients in this group will received morphine/midazolam drips at 0.3 mg/kg/hour each. They will be given doses of morphine 0.05 mg/kg/dose every 2 hours as needed for pain score 4 or more. Midazolam will also be given as needed (0.05 mg/kg/dose every 1 hour)
continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac.
Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours.
ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study. | 30 |
| As Needed Dosing Patients in this arm will be given doses of morphine 0.05 mg/kg/dose every 2 hours as needed for pain score 4 or more. Midazolam will also be given as needed (0.05 mg/kg/dose every 1 hour)
as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group.
Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours.
ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | lab values precluding use of ketorolac | 2 | 2 |
| Overall Study | Physician Decision | 4 | 6 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | required heparin so could not use ketoro | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Continuous Infusion | As Needed Dosing |
|---|---|---|---|
| Age, Continuous | 15.4 months STANDARD_DEVIATION 12.5 | 14.8 months STANDARD_DEVIATION 12.1 | 16 months STANDARD_DEVIATION 12.8 |
| Presence of Down syndrome | 9 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 35 Participants | 17 Participants | 18 Participants |
| Sex: Female, Male Male | 25 Participants | 13 Participants | 12 Participants |
| Surgical complexity scores | 120 units on a scale | 59 units on a scale | 61 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 40 |
| other Total, other adverse events | 3 / 38 | 2 / 40 |
| serious Total, serious adverse events | 0 / 38 | 1 / 40 |
Outcome results
Primary
Total Morphine Dosage
Total dose of morphine used will be recorded for each patient.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous Infusion | Total Morphine Dosage | 0.9 mg/kg | Standard Deviation 0.13 |
| As Needed Dosing | Total Morphine Dosage | 0.23 mg/kg | Standard Deviation 0.14 |
Secondary
Length of Stay
Length of stay will be recorded for each subject.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause or discharge, whichever came first, assessed up to 100 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous Infusion | Length of Stay | 4.9 days | Standard Deviation 2.5 |
| As Needed Dosing | Length of Stay | 8.4 days | Standard Deviation 7.7 |