Clinical trial NCT00955877: Extended-release Epidural Morphine for Acute Post-operative Analgesia Following Selective Dorsal Rhizotomy in Children
Official title: Randomized, Double-Blinded Placebo Controlled Trial of Epidural, Sustained-relief Morphine for Acute Post-operative Analgesia Following Selective Dorsal Rhizotomy in Children
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Spastic Cerebral Palsy
Keywords: extended-release epidural morphine
DepoDur
Spastic Cerebral Palsy
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2009-08-10
Enrollment: 13
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Receiving selective dorsal rhizotomy (SDR)
* Willingness to Participate

Exclusion Criteria:

* Known Morphine Allergy
* Inability to speak and read the English language

Primary outcomes:
measure: Adequacy of Analgesia as Judged by Age-adjusted Pain Scales
timeFrame: 48 hour post-operative period
measure: Quantity of Fentanyl Administered
timeFrame: 48 hour post-operative period
Secondary outcomes:
measure: Number of Participants With Respiratory Depression Within 48hrs Post op
timeFrame: 48 hour post-operative period
measure: Number of Participants With Hemodynamic Instability 48hrs Post op
timeFrame: 48 hour post-operative period
measure: Number of Participants With CSF Leaks Within 6 Months Post op.
timeFrame: 6 month post-operative period
measure: Number of Participants That Had Urine Retention for 48hrs Post Foley Catheter Removal.
timeFrame: After the Foley catheter has been removed on post-operative day #1 for a 48 hour follow-up period
measure: Number of Participants With Nausea and/or Vomiting 48hrs Post op.
timeFrame: 48 hour post-operative period
measure: Number of Participants With Pruritis Within 48hrs Post op
timeFrame: 48 hour post-operative period
measure: Number of Participants That Were Given Codeine 48hr Post Surgery
timeFrame: 48hr post surgery
measure: Number of Participants That Were Given Zofran 48hr Post Surgery
timeFrame: 48hr post surgery
measure: Number of Participants That Were Bradycardia Within 48hr Post Surgery
timeFrame: 48hr post surgery
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: David Limbrick, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark SL, Hankins GD. Temporal and demographic trends in cerebral palsy--fact and fiction. Am J Obstet Gynecol. 2003 Mar;188(3):628-33. doi: 10.1067/mob.2003.204.
citation: Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994 Jan 20;330(3):188-95. doi: 10.1056/NEJM199401203300308. No abstract available.
citation: Grether JK, Cummins SK, Nelson KB. The California Cerebral Palsy Project. Paediatr Perinat Epidemiol. 1992 Jul;6(3):339-51. doi: 10.1111/j.1365-3016.1992.tb00774.x.
citation: Taft LT. Cerebral palsy. Pediatr Rev. 1995 Nov;16(11):411-8; quiz 418. No abstract available.
citation: Steinbok P. Outcomes after selective dorsal rhizotomy for spastic cerebral palsy. Childs Nerv Syst. 2001 Jan;17(1-2):1-18. doi: 10.1007/pl00013722.
citation: McLaughlin J, Bjornson K, Temkin N, Steinbok P, Wright V, Reiner A, Roberts T, Drake J, O'Donnell M, Rosenbaum P, Barber J, Ferrel A. Selective dorsal rhizotomy: meta-analysis of three randomized controlled trials. Dev Med Child Neurol. 2002 Jan;44(1):17-25. doi: 10.1017/s0012162201001608.
citation: Wright FV, Sheil EM, Drake JM, Wedge JH, Naumann S. Evaluation of selective dorsal rhizotomy for the reduction of spasticity in cerebral palsy: a randomized controlled tria. Dev Med Child Neurol. 1998 Apr;40(4):239-47. doi: 10.1111/j.1469-8749.1998.tb15456.x.
citation: Steinbok P, Reiner AM, Beauchamp R, Armstrong RW, Cochrane DD, Kestle J. A randomized clinical trial to compare selective posterior rhizotomy plus physiotherapy with physiotherapy alone in children with spastic diplegic cerebral palsy. Dev Med Child Neurol. 1997 Mar;39(3):178-84. doi: 10.1111/j.1469-8749.1997.tb07407.x.
citation: McLaughlin JF, Bjornson KF, Astley SJ, Graubert C, Hays RM, Roberts TS, Price R, Temkin N. Selective dorsal rhizotomy: efficacy and safety in an investigator-masked randomized clinical trial. Dev Med Child Neurol. 1998 Apr;40(4):220-32. doi: 10.1111/j.1469-8749.1998.tb15454.x.
citation: Chicoine MR, Park TS, Kaufman BA. Selective dorsal rhizotomy and rates of orthopedic surgery in children with spastic cerebral palsy. J Neurosurg. 1997 Jan;86(1):34-9. doi: 10.3171/jns.1997.86.1.0034.
citation: Park TS, Johnston JM. Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Technical note. Neurosurg Focus. 2006 Aug 15;21(2):e7.
citation: Hartrick CT, Hartrick KA. Extended-release epidural morphine (DepoDur): review and safety analysis. Expert Rev Neurother. 2008 Nov;8(11):1641-8. doi: 10.1586/14737175.8.11.1641.
citation: Gambling D, Hughes T, Martin G, Horton W, Manvelian G; Single-Dose EREM Study Group. A comparison of Depodur, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. Anesth Analg. 2005 Apr;100(4):1065-1074. doi: 10.1213/01.ANE.0000145009.03574.78.
citation: Carvalho B, Riley E, Cohen SE, Gambling D, Palmer C, Huffnagle HJ, Polley L, Muir H, Segal S, Lihou C, Manvelian G; DepoDur Study Group. Single-dose, sustained-release epidural morphine in the management of postoperative pain after elective cesarean delivery: results of a multicenter randomized controlled study. Anesth Analg. 2005 Apr;100(4):1150-1158. doi: 10.1213/01.ANE.0000149544.58230.FF.
citation: Carvalho B, Roland LM, Chu LF, Campitelli VA 3rd, Riley ET. Single-dose, extended-release epidural morphine (DepoDur) compared to conventional epidural morphine for post-cesarean pain. Anesth Analg. 2007 Jul;105(1):176-83. doi: 10.1213/01.ane.0000265533.13477.26.
citation: Viscusi ER, Martin G, Hartrick CT, Singla N, Manvelian G; EREM Study Group. Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation. Anesthesiology. 2005 May;102(5):1014-22. doi: 10.1097/00000542-200505000-00022.
citation: Hartrick CT, Martin G, Kantor G, Koncelik J, Manvelian G. Evaluation of a single-dose, extended-release epidural morphine formulation for pain after knee arthroplasty. J Bone Joint Surg Am. 2006 Feb;88(2):273-81. doi: 10.2106/JBJS.D.02738.
citation: Martin G, Hartmannsgruber M, Riley E, Manvelian G. Single-dose extended-release epidural morphine for pain after hip arthroplasty. J Opioid Manag. 2006 Jul-Aug;2(4):209-18. doi: 10.5055/jom.2006.0033.
citation: Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.
citation: Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 1988 Jan-Feb;14(1):9-17. No abstract available.
citation: Jensen MP, Turner JA, Romano JM. Correlates of improvement in multidisciplinary treatment of chronic pain. J Consult Clin Psychol. 1994 Feb;62(1):172-9. doi: 10.1037//0022-006x.62.1.172.
citation: Solodiuk J, Curley MA. Pain assessment in nonverbal children with severe cognitive impairments: the Individualized Numeric Rating Scale (INRS). J Pediatr Nurs. 2003 Aug;18(4):295-9. doi: 10.1016/s0882-5963(03)00090-3.