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

NCT00955877 | Terminated Results DMC

• 1 other identifier: DeporDur2009
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Spastic Cerebral Palsy

Keywords

extended-release epidural morphine; DepoDur; Spastic Cerebral Palsy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Number of Participants With Respiratory Depression Within 48hrs Post op

  48 hour post-operative period

• Number of Participants With Hemodynamic Instability 48hrs Post op

  48 hour post-operative period

• Number of Participants With CSF Leaks Within 6 Months Post op.

  6 month post-operative period

• 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.

  48 hour post-operative period

Study Arms (3)

DepoDur80

EXPERIMENTAL

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

DepoDur120

EXPERIMENTAL

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

Control

PLACEBO COMPARATOR

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

Interventions

Extended-release Epidural morphine (EREM) 80 DRUG

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.

Also known as: DepoDur

DepoDur80

Extended-release Epidural Morphine (EREM) 120 DRUG

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.

Also known as: DepoDur

DepoDur120

Control: Saline DRUG

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.

Control

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (22)

• 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.

  PMID: 12634632 BACKGROUND

• Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994 Jan 20;330(3):188-95. doi: 10.1056/NEJM199401203300308. No abstract available.

  PMID: 8264743 BACKGROUND

• 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.

  PMID: 1635884 BACKGROUND

• Taft LT. Cerebral palsy. Pediatr Rev. 1995 Nov;16(11):411-8; quiz 418. No abstract available.

  PMID: 8539191 BACKGROUND

• 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.

  PMID: 11219613 BACKGROUND

• 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.

  PMID: 11811645 BACKGROUND

• 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.

  PMID: 9593495 BACKGROUND

• 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.

  PMID: 9112967 BACKGROUND

• 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.

  PMID: 9593493 BACKGROUND

• 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.

  PMID: 8988079 BACKGROUND

• Park TS, Johnston JM. Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Technical note. Neurosurg Focus. 2006 Aug 15;21(2):e7.

  PMID: 16918228 BACKGROUND

• 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.

  PMID: 18986234 BACKGROUND

• 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.

  PMID: 15781524 BACKGROUND

• 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.

  PMID: 15781537 BACKGROUND

• 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.

  PMID: 17578973 BACKGROUND

• 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.

  PMID: 15851890 BACKGROUND

• 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.

  PMID: 16452737 BACKGROUND

• 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.

  PMID: 17319482 BACKGROUND

• 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.

  PMID: 9220806 BACKGROUND

• Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 1988 Jan-Feb;14(1):9-17. No abstract available.

  PMID: 3344163 BACKGROUND

• 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.

  PMID: 8034820 BACKGROUND

• 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.

  PMID: 12923744 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

The study was stopped short as the manufacturer decided to stop drug production; therefore without a complete enrollment, statistical analysis was not performed.

Results Point of Contact

• Title: Diego Morales
• Organization: Washington University in St. Louis School of Medicine

d.morales@wustl.edu

3144544688

Study Officials

• David Limbrick, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2009
• First Posted: August 10, 2009
• Study Start: March 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 11, 2018
• Results First Posted: June 13, 2018

Record last verified: 2018-06

Locations

US (1)