Spastic Cerebral Palsy
Conditions
Keywords
extended-release epidural morphine, DepoDur, Spastic Cerebral Palsy
Brief summary
The purpose of this proposal is to improve the investigators' current Selective Dorsal Rhizotomy (SDR) analgesia protocol by eliminating or minimizing the use of fentanyl in the post-operative period. Children undergoing SDR for spastic cerebral palsy have significant post-operative pain. The procedure requires dissection of the lumbar back musculature and removal of the L1 lamina (the bony posterior part of the vertebra). The majority of the operation is intradural, and a water-tight dural closure at the termination of the operation is critical in order to prevent leakage of cerebrospinal fluid (CSF) from the wound. In fact, these children must remain flat on their back for 48 hours to allow the dural incision to heal prior to mobilization. Thus, adequate pain control is essential not only for patient comfort, but also to prevent agitation and additional stress on the dural closure. Currently, the investigators' patients undergoing SDR are treated for 48 hours with scheduled intravenous (IV) narcotic (continuous fentanyl infusion at 0.5-2.0 μg/kg/hour) in addition to the sedative/muscle relaxant Valium (0.2 mg/kg IV every 4 hours for 24 hours, then every 6 hours for 24 hours). The IV fentanyl, and to a lesser degree Valium, carries a real risk of hypotension and respiratory depression and requires frequent dose adjustments to achieve adequate analgesia. By improving the current SDR analgesia protocol, the investigators hope to maximize patient safety and comfort while maintaining the effectiveness of the operation by minimizing the risk of CSF leak.
Detailed description
improve the investigators' current Selective Dorsal Rhizotomy (SDR) analgesia protocol by eliminating or minimizing the use of fentanyl in the post-operative period. Children undergoing SDR for spastic cerebral palsy have significant post-operative pain. The procedure requires dissection of the lumbar back musculature and removal of the L1 lamina (the bony posterior part of the vertebra). The majority of the operation is intradural, and a water-tight dural closure at the termination of the operation is critical in order to prevent leakage of cerebrospinal fluid (CSF) from the wound. In fact, these children must remain flat on their back for 48 hours to allow the dural incision to heal prior to mobilization. Thus, adequate pain control is essential not only for patient comfort, but also to prevent agitation and additional stress on the dural closure. Currently, the investigators' patients undergoing SDR are treated for 48 hours with scheduled intravenous (IV) narcotic (continuous fentanyl infusion at 0.5-2.0 μg/kg/hour) in addition to the sedative/muscle relaxant Valium (0.2 mg/kg IV every 4 hours for 24 hours, then every 6 hours for 24 hours). The IV fentanyl, and to a lesser degree Valium, carries a real risk of hypotension and respiratory depression and requires frequent dose adjustments to achieve adequate analgesia. By improving the current SDR analgesia protocol, the investigators hope to maximize patient safety and comfort while maintaining the effectiveness of the operation by minimizing the risk of CSF leak.
Interventions
DRUGExtended-release Epidural morphine (EREM) 80
After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Epidural DepoDur (80μg/kg) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter.
DRUGExtended-release Epidural Morphine (EREM) 120
After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Epidural DepoDur (120μg/kg) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter.
DRUGControl: Saline
After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Preservative-free normal saline (2.5 ml) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Receiving selective dorsal rhizotomy (SDR) * Willingness to Participate
Exclusion criteria
* Known Morphine Allergy * Inability to speak and read the English language
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adequacy of Analgesia as Judged by Age-adjusted Pain Scales | 48 hour post-operative period | Mean and standard deviation for standardized, age-appropriate pain scales (per patient per day) 48hrs post surgery. As is standard of care at St. Louis Children's Hospital, pain level was scored based on age using the Face, Legs, Activity, Cry, Consolability (FLACC) for participants aged 0-3, the FACES scale on participants between the age of 3 and 5, numeric pain rating scale (NRS) on participants between the age of 5 and 8 years, or the Individualized Numeric Rating Scale (INRS) for participants greater than or equal to 8 years of age. All four of the scales were ranged from 0-10 scores, with 0 being no pain at all, and 10 being extreme pain. Each patient had two scores given, one at 24hrs and one at 48hrs post surgery. The output was reported as an average of all scores for all patients within each group. |
| Quantity of Fentanyl Administered | 48 hour post-operative period | Mean and standard deviation of total quantity of fentanyl administered (per patient per day) 48hrs post surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With CSF Leaks Within 6 Months Post op. | 6 month post-operative period | Number of participants with CSF leaks within 6 months post operation. |
| Number of Participants That Had Urine Retention for 48hrs Post Foley Catheter Removal. | After the Foley catheter has been removed on post-operative day #1 for a 48 hour follow-up period | Number of participants that had urine retention for 48hrs post foley catheter removal. |
| Number of Participants With Nausea and/or Vomiting 48hrs Post op. | 48 hour post-operative period | Number of participants with nausea and or vomiting 48hr post surgery |
| Number of Participants With Respiratory Depression Within 48hrs Post op | 48 hour post-operative period | Number of participants with respiratory depression within 48hrs post operation |
| Number of Participants That Were Given Codeine 48hr Post Surgery | 48hr post surgery | Number of participants that were given codeine 48hr post surgery |
| Number of Participants That Were Given Zofran 48hr Post Surgery | 48hr post surgery | Number of participants that were given Zofran 48hr post surgery |
| Number of Participants That Were Bradycardia Within 48hr Post Surgery | 48hr post surgery | Number of participants that were bradycardia within 48hr post surgery |
| Number of Participants With Pruritis Within 48hrs Post op | 48 hour post-operative period | Number of participants with pruritis within 48hrs post operation |
| Number of Participants With Hemodynamic Instability 48hrs Post op | 48 hour post-operative period | Number of Participants with Hemodynamic Instability 48hrs post operation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DepoDur80 DepoDur will be administered at 80μg/kg (not to exceed 5 mg total/patient) under direct vision in the L1 laminectomy defect prior to wound closure.
Extended-release Epidural morphine (EREM) 80: After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Epidural DepoDur (80μg/kg) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter. | 6 |
| DepoDur120 DepoDur will be administered at 120μg/kg (not to exceed 10 mg total/patient) under direct vision in the L1 laminectomy defect prior to wound closure.
Extended-release Epidural Morphine (EREM) 120: After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Epidural DepoDur (120μg/kg) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter. | 0 |
| Control Preservative-free normal saline (2.5ml) will be placed in the L1 laminectomy defect and also dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter prior to wound closure.
Control: Saline: After completion of the rhizotomy, the dura will be closed in the standard water-tight fashion with running suture. Preservative-free normal saline (2.5 ml) will be placed under direct vision in the L1 laminectomy defect. It will also be dispensed 1-2 levels above and 1-2 levels below using a flexible angiocatheter. | 7 |
| Total | 13 |
Baseline characteristics
| Characteristic | DepoDur80 | DepoDur120 | Control | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 0 Participants | 7 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 Participants | — | 7 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 0 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 0 | 0 / 7 |
| other Total, other adverse events | 0 / 6 | 0 / 0 | 0 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 0 | 0 / 7 |
Outcome results
Primary
Adequacy of Analgesia as Judged by Age-adjusted Pain Scales
Mean and standard deviation for standardized, age-appropriate pain scales (per patient per day) 48hrs post surgery. As is standard of care at St. Louis Children's Hospital, pain level was scored based on age using the Face, Legs, Activity, Cry, Consolability (FLACC) for participants aged 0-3, the FACES scale on participants between the age of 3 and 5, numeric pain rating scale (NRS) on participants between the age of 5 and 8 years, or the Individualized Numeric Rating Scale (INRS) for participants greater than or equal to 8 years of age. All four of the scales were ranged from 0-10 scores, with 0 being no pain at all, and 10 being extreme pain. Each patient had two scores given, one at 24hrs and one at 48hrs post surgery. The output was reported as an average of all scores for all patients within each group.
Time frame: 48 hour post-operative period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoDur80 | Adequacy of Analgesia as Judged by Age-adjusted Pain Scales | 0.5454 units on a scale | Standard Deviation 1.2136 |
| Control | Adequacy of Analgesia as Judged by Age-adjusted Pain Scales | 1.8571 units on a scale | Standard Deviation 1.8337 |
Primary
Quantity of Fentanyl Administered
Mean and standard deviation of total quantity of fentanyl administered (per patient per day) 48hrs post surgery.
Time frame: 48 hour post-operative period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoDur80 | Quantity of Fentanyl Administered | 11 mcg | Standard Deviation 15.5037 |
| Control | Quantity of Fentanyl Administered | 10.7857 mcg | Standard Deviation 10.6423 |
Secondary
Number of Participants That Had Urine Retention for 48hrs Post Foley Catheter Removal.
Number of participants that had urine retention for 48hrs post foley catheter removal.
Time frame: After the Foley catheter has been removed on post-operative day #1 for a 48 hour follow-up period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants That Had Urine Retention for 48hrs Post Foley Catheter Removal. | 0 Participants |
| Control | Number of Participants That Had Urine Retention for 48hrs Post Foley Catheter Removal. | 0 Participants |
Secondary
Number of Participants That Were Bradycardia Within 48hr Post Surgery
Number of participants that were bradycardia within 48hr post surgery
Time frame: 48hr post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants That Were Bradycardia Within 48hr Post Surgery | 0 Participants |
| DepoDur120 | Number of Participants That Were Bradycardia Within 48hr Post Surgery | 0 Participants |
| Control | Number of Participants That Were Bradycardia Within 48hr Post Surgery | 0 Participants |
Secondary
Number of Participants That Were Given Codeine 48hr Post Surgery
Number of participants that were given codeine 48hr post surgery
Time frame: 48hr post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants That Were Given Codeine 48hr Post Surgery | 1 Participants |
| Control | Number of Participants That Were Given Codeine 48hr Post Surgery | 2 Participants |
Secondary
Number of Participants That Were Given Zofran 48hr Post Surgery
Number of participants that were given Zofran 48hr post surgery
Time frame: 48hr post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants That Were Given Zofran 48hr Post Surgery | 1 Participants |
| Control | Number of Participants That Were Given Zofran 48hr Post Surgery | 1 Participants |
Secondary
Number of Participants With CSF Leaks Within 6 Months Post op.
Number of participants with CSF leaks within 6 months post operation.
Time frame: 6 month post-operative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants With CSF Leaks Within 6 Months Post op. | 0 Participants |
| Control | Number of Participants With CSF Leaks Within 6 Months Post op. | 0 Participants |
Secondary
Number of Participants With Hemodynamic Instability 48hrs Post op
Number of Participants with Hemodynamic Instability 48hrs post operation
Time frame: 48 hour post-operative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants With Hemodynamic Instability 48hrs Post op | 0 Participants |
| Control | Number of Participants With Hemodynamic Instability 48hrs Post op | 0 Participants |
Secondary
Number of Participants With Nausea and/or Vomiting 48hrs Post op.
Number of participants with nausea and or vomiting 48hr post surgery
Time frame: 48 hour post-operative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants With Nausea and/or Vomiting 48hrs Post op. | 6 Participants |
| DepoDur120 | Number of Participants With Nausea and/or Vomiting 48hrs Post op. | 0 Participants |
| Control | Number of Participants With Nausea and/or Vomiting 48hrs Post op. | 6 Participants |
Secondary
Number of Participants With Pruritis Within 48hrs Post op
Number of participants with pruritis within 48hrs post operation
Time frame: 48 hour post-operative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants With Pruritis Within 48hrs Post op | 2 Participants |
| Control | Number of Participants With Pruritis Within 48hrs Post op | 0 Participants |
Secondary
Number of Participants With Respiratory Depression Within 48hrs Post op
Number of participants with respiratory depression within 48hrs post operation
Time frame: 48 hour post-operative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DepoDur80 | Number of Participants With Respiratory Depression Within 48hrs Post op | 0 Participants |
| Control | Number of Participants With Respiratory Depression Within 48hrs Post op | 0 Participants |