Extended-release Epidural Morphine for Acute Post-operative Analgesia Following Selective Dorsal Rhizotomy in Children

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Double-Blinded Placebo Controlled Trial of Epidural, Sustained-relief Morphine for Acute Post-operative Analgesia Following Selective Dorsal Rhizotomy in Children

Conditions
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Spastic Cerebral Palsy

Intervention / Treatment
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* Drug: Extended-release Epidural morphine (EREM) 80
* Drug: Extended-release Epidural Morphine (EREM) 120
* Drug: Control: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Receiving selective dorsal rhizotomy (SDR) Willingness to Participate Exclusion Criteria: Known Morphine Allergy Inability to speak and read the English language

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DepoDur80<br>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. | Drug: Extended-release Epidural morphine (EREM) 80<br>* 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.<br>* Other names: DepoDur;|
| Experimental: DepoDur120<br>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. | Drug: Extended-release Epidural Morphine (EREM) 120<br>* 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.<br>* Other names: DepoDur;|
| Placebo Comparator: Control<br>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. | Drug: Control: Saline<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 hour post-operative period | 
| Quantity of Fentanyl Administered | Mean and standard deviation of total quantity of fentanyl administered (per patient per day) 48hrs post surgery. | 48 hour post-operative period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Respiratory Depression Within 48hrs Post op | Number of participants with respiratory depression within 48hrs post operation | 48 hour post-operative period | 
| Number of Participants With Hemodynamic Instability 48hrs Post op | Number of Participants with Hemodynamic Instability 48hrs post operation | 48 hour post-operative period | 
| Number of Participants With CSF Leaks Within 6 Months Post op. | Number of participants with CSF leaks within 6 months post operation. | 6 month post-operative period | 
| 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. | After the Foley catheter has been removed on post-operative day #1 for a 48 hour follow-up period | 
| Number of Participants With Nausea and/or Vomiting 48hrs Post op. | Number of participants with nausea and or vomiting 48hr post surgery | 48 hour post-operative period | 
| Number of Participants With Pruritis Within 48hrs Post op | Number of participants with pruritis within 48hrs post operation | 48 hour post-operative period | 
| Number of Participants That Were Given Codeine 48hr Post Surgery | Number of participants that were given codeine 48hr post surgery | 48hr post surgery | 
| Number of Participants That Were Given Zofran 48hr Post Surgery | Number of participants that were given Zofran 48hr post surgery | 48hr post surgery | 
| Number of Participants That Were Bradycardia Within 48hr Post Surgery | Number of participants that were bradycardia within 48hr post surgery | 48hr post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extended-release epidural morphine, DepoDur, Spastic Cerebral Palsy