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

Spastic Cerebral Palsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00955877
• Other study ID #: DeporDur2009
• Status: Terminated
• Phase: N/A
• Start date: March 2010
• Est. completion date: January 2015

Study information

• Verified date: June 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 12 Years

Eligibility

Inclusion Criteria:

• Receiving selective dorsal rhizotomy (SDR)

• Willingness to Participate

Exclusion Criteria:

• Known Morphine Allergy

• Inability to speak and read the English language

Related Conditions & MeSH terms

• Cerebral Palsy
• Muscle Spasticity
• Spastic Cerebral Palsy

Intervention

Drug:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	St. Louis Children's Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (22)

Carvalho B, Riley E, Cohen SE, Gambling D, Palmer C, Huffnagle HJ, Polley L, Muir H, Segal S, Lihou C, Manvelian G; DepoSur 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):1150-8. — View 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. — View 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. — View 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. Review. — View Citation

Gambling D, Hughes T, Martin G, Horton W, Manvelian G. 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):1065-74. — View Citation

Grether JK, Cummins SK, Nelson KB. The California Cerebral Palsy Project. Paediatr Perinat Epidemiol. 1992 Jul;6(3):339-51. — View 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. Review. — View 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. — View 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. — View Citation

Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994 Jan 20;330(3):188-95. Review. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. Review. — View 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. Erratum in: Dev Med Child Neurol 1997 Nov;39(11):inside back cov. — View Citation

Steinbok P. Outcomes after selective dorsal rhizotomy for spastic cerebral palsy. Childs Nerv Syst. 2001 Jan;17(1-2):1-18. Review. — View Citation

Taft LT. Cerebral palsy. Pediatr Rev. 1995 Nov;16(11):411-8; quiz 418. Review. — View 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. — View Citation

Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 1988 Jan-Feb;14(1):9-17. — View 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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	48 hour post-operative period
Primary	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	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
Secondary	Number of Participants With Hemodynamic Instability 48hrs Post op	Number of Participants with Hemodynamic Instability 48hrs post operation	48 hour post-operative period
Secondary	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
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.	After the Foley catheter has been removed on post-operative day #1 for a 48 hour follow-up period
Secondary	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
Secondary	Number of Participants With Pruritis Within 48hrs Post op	Number of participants with pruritis within 48hrs post operation	48 hour post-operative period
Secondary	Number of Participants That Were Given Codeine 48hr Post Surgery	Number of participants that were given codeine 48hr post surgery	48hr post surgery
Secondary	Number of Participants That Were Given Zofran 48hr Post Surgery	Number of participants that were given Zofran 48hr post surgery	48hr post surgery
Secondary	Number of Participants That Were Bradycardia Within 48hr Post Surgery	Number of participants that were bradycardia within 48hr post surgery	48hr post surgery