Preemptive Infiltration With Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy

• ClinicalTrials.gov Identifier: NCT04153396
• Recruitment Status: Completed
• First Posted: November 6, 2019
• Last Update Posted: March 14, 2023
• Sponsor: Beijing Tiantan Hospital
• Information provided by (Responsible Party): Fang Luo, Beijing Tiantan Hospital

Tracking Information

• First Submitted Date: November 4, 2019
• First Posted Date: November 6, 2019
• Last Update Posted Date: March 14, 2023
• Actual Study Start Date: September 1, 2021
• Actual Primary Completion Date: December 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2019)

The cumulative butorphanol dose during the 48 hours after surgery via the PCA device. [ Time Frame: Within 48 hours after the operation ]

All participates will receive an electronic intravenous patient-controlled analgesia (PCA) device. Participates will be advised to push the analgesic demand button if they feel pain.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2023)

• The Visual Analogue Scale (VAS) during movement (VASm) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours and 72 hours, and 1 week, 2 weeks, 4 weeks, 6 weeks and 3 months and 6 months after surgery. ]
  The pain will be assessed by the visual analogue scale (VAS) scores: an 11-point VAS score during movement (VASm) will be recorded (0 indicates no pain, 10 indicates the most severe pain imaginable, a higher score means worse pain)
• The Visual Analogue Scale (VAS) at rest (VASr) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours and 72 hours, and 1 week, 2 weeks, 4 weeks, 6 weeks and 3 months and 6 months after surgery. ]
  The pain will be assessed by the visual analogue scale (VAS) scores: an 11-point VAS score at rest (VASr) will be recorded (0 indicates no pain, 10 indicates the most severe pain imaginable, a higher score means worse pain)
• The total times that participants press patient-controlled analgesia button [ Time Frame: Within 48 hours after the operation ]
  The total times that participants press patient-controlled analgesia button including effective presses and ineffective presses.
• The first analgesia demand on the PCA device [ Time Frame: Within 48 hours postoperatively ]
  The time from the end of the surgery to the first administration of analgesia via the PCA device
• Patient Satisfaction Score (PSS) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 4 weeks, 6 weeks, 3 months and 6 months after surgery ]
  The Patient Satisfaction Score (PSS): 0 for unsatisfactory, and 10 for very satisfied
• The Postoperative Nausea and Vomiting (PONV) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours after surgery ]
  The Postoperative Nausea and Vomiting (PONV) will be measured using an ordinal scale, with 0 indicating no nausea; 1, mild nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting.
• Ramsay Sedation Scale (RSS) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours after surgery ]
  The Ramsay Sedation Scale (RSS): A 6-point scale will be used to assess sedation levels, with 1 indicating agitated, anxious; 2, cooperative; 3, only responds to commands; 4, strong response to glabellar tapping or noisy stimulants; 5, weak response to glabellar tapping or noisy stimulants; 6, no response.
• The World Health Organization Quality of Life-BREF (WHOQOL-BREF) scores [ Time Frame: At 6 months postoperatively ]
  The World Health Organization Quality of Life-BREF (WHOQOL-BREF) scores will be used to obtain scores for four domains related to quality of life: physical health (7 items), psychological (6 items), social relationships (3items) and environment (8items). It will also include two stand-alone questions on overall quality of life and satisfaction with health. Each question will be rated on a scale of 1-5 with higher scores signifying better quality of life.
• The Oswestry Disability Index (ODI) [ Time Frame: Preoperatively and at 4 weeks, 6 weeks and 3 months, 6 months after surgery. ]
  Functional disability will be assessed by the Oswestry Disability Index. It includes 10 questions about pain and activities of daily living. Each item has five response categories from no pain related disability (0), to the worst possible pain disability (100). The ODI has been reported to be the most widely used and validated outcome measure in spinal surgery.
• Patient Scar Assessment and the Observer Scar Assessment Scale (POSAS) [ Time Frame: At 6 months postoperatively ]
  The Patient and Observer Scar Assessment Scale includes subjective symptoms of pain and pruritus and consists of 2 numerical scales: The Patient Scar Assessment Scale and the Observer Scar Assessment Scale. It assesses vascularity, pigmentation, thickness, relief, pliability, surface area and overall opinion for a scar on a score of 1 (normal skin) to 10 (worst scar imaginable). and it incorporates patient assessments of pain, itching, color, stiffness, thickness, relief and overall opinion. Participants were asked to rate the severity of their scar compared to normal skin. The overall opinion scale score ranged from 1 (normal skin) to 10 (very different from normal skin)

Original Secondary Outcome Measures (submitted: November 4, 2019)

• The Visual Analogue Scale (VAS) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours and 72 hours, and 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 3 months and 6 months after surgery. ]
  The pain will be assessed by VAS scores
• The total times that participants press patient-controlled analgesia button [ Time Frame: Within 48 hours after the operation ]
  The total times that participants press patient-controlled analgesia button including effective presses and ineffective presses.
• The first analgesia demand on the PCA device [ Time Frame: Within 48 hours postoperatively ]
  The time from the end of the surgery to the first administration of analgesia via the PCA device
• Patient Satisfaction Score (PSS） [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 1 month, 3 months and 6 months after surgery ]
  0 for unsatisfactory, and 10 for very satisfied
• The Postoperative Nausea and Vomiting（PONV） [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours after surgery ]
  PONV will be measured using an ordinal scale, with 0 indicating no nausea; 1, mild nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting.
• Ramsay Sedation Scale (RSS) [ Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours, 48 hours after surgery ]
  RSS: A 6-point scale will be used to assess sedation levels, with 1 indicating agitated, anxious; 2, cooperative; 3, only responds to commands; 4, strong response to glabellar tapping or noisy stimulants; 5, weak response to glabellar tapping or noisy stimulants; 6, no response.
• The World Health Organization Quality of Life-BREF (WHOQOL-BREF) scores [ Time Frame: At 6 months postoperatively ]
  The WHOQOL-BREF scores will be used to obtain scores for four domains related to quality of life: physical health (7 items), psychological (6 items), social relationships (3items) and environment (8items). It will also include two stand-alone questions on overall quality of life and satisfaction with health. Each question will be rated on a scale of 1-5 with higher scores signifying better quality of life.
• The Oswestry Disability Index (ODI) [ Time Frame: Preoperatively and at 4 weeks, 6 weeks and 3 months, 6 months after surgery. ]
  Functional disability will be assessed by the ODI. It includes 10 questions about pain and activities of daily living. Each item has five response categories from no pain related disability (0), to the worst possible pain disability (100). The ODI has been reported to be the most widely used and validated outcome measure in spinal surgery.
• Patient Scar Assessment and the Observer Scar Assessment Scale (POSAS) [ Time Frame: At 6 months postoperatively ]
  The POSAS scores is comprised of 2 numerical scales. It is comprised of subjective symptoms of pain and pruritus.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Preemptive Infiltration With Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy
• Official Title: Preemptive Infiltration With Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy (PRE-EASE)
• Brief Summary: Laminoplasty and laminectomy have been used for decades for the treatment of intraspinal space occupying lesions, spinal stenosis, disc herniation, injuries, etc. After these procedures, patients often experience severe postoperative pain at the surgical site. However, current methods of pain control are mostly insufficient. At present, several pain controlling methods are available, to reduce postoperative pain after laminoplasty or laminectomy. Methods for systemic administration include: oral analgesics, intermittent intravenous, intramuscular injections, patient- controlled intravenous analgesia, etc. However, the aforementioned methods may have a lot of side effects, and are usually used after the occurrence of pain and the analgesic effects are sometimes inadequate. Topical administration options use a lower dose of drugs and therefore have less systemic side effects. Pre-emptive injection of local anesthetics can significantly reduce postoperative pain during rest and movement, however, the analgesic effect is maintained for a relatively short period of time. It is necessary to use more cases to explore the other compatibility of drugs with longer duration of action and stronger analgesic effect. Betamethasone as the stereoisomer of dexamethasone is a long-acting corticosteroid, which has long lasting anti-inflammatory properties. Whether betamethasone combined with local anesthetic for laminoplasty or laminectomy has better short-term and long-term effects than the local anesthetic alone has not been reported yet. Therefore, a prospective, randomized, controlled, blinded-endpoint study is needed to compare the postoperative analgesic efficacy of preemptive wound infilteration of ropivacaine alone and betamethasone plus ropivacaine for laminectomy or laminoplasty.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Prevention

Condition

• Pain, Postoperative
• Neurosurgery

Intervention

• Drug: The Treatment group
  The local infiltration solution in the treatment group will consist of betamethasone and ropivacaine. For local infiltration, a total of 30 ml solution will be prepared for each group, which will include 0.5ml of compound betamethasone injection(betamethasone propionate 5mg and betamethasone sodium phosphate 2mg per 1ml) added to 14.5ml of saline and 15ml of 1% ropivacaine. The surgeon will perform wound infiltration after induction of anesthesia and before surgery. A total of 10 ml of solution will be injected into each level. The study solution will be injected into the subcutaneous tissue, paravertebral muscles, along with the posterior area around the spinous process, lamina, transverse process and the facet joints, along both sides of the planned incision. The epidural space and intrathecal space will not be infiltrated.
• Drug: The Control group
  The local infiltration solution in the control group will consist of ropivacaine. For local infiltration, a total of 30 ml solution will be prepared for each group, which will include 15ml of ropivacaine added to 15 ml of saline for the Control group. The surgeon will perform wound infiltration after induction of anesthesia and before surgery. A total of 10 ml of solution will be injected into each level. The study solution will be injected into the subcutaneous tissue, paravertebral muscles, along with the posterior area around the spinous process, lamina, transverse process and the facet joints, along both sides of the planned incision. The epidural space and intrathecal space will not be infiltrated.

Study Arms

• Experimental: The Treatment Group
  The local infiltration solution in the treatment group will consist of betamethasone and ropivacaine.
  Intervention: Drug: The Treatment group
• Active Comparator: The Control group
  The local infiltration solution in the control group will consist of ropivacaine.
  Intervention: Drug: The Control group

Publications *

• Itoh T, Tsuji H. Technical improvements and results of laminoplasty for compressive myelopathy in the cervical spine. Spine (Phila Pa 1976). 1985 Oct;10(8):729-36. doi: 10.1097/00007632-198510000-00007.
• Takayasu M, Takagi T, Nishizawa T, Osuka K, Nakajima T, Yoshida J. Bilateral open-door cervical expansive laminoplasty with hydroxyapatite spacers and titanium screws. J Neurosurg. 2002 Jan;96(1 Suppl):22-8. doi: 10.3171/spi.2002.96.1.0022.
• Gurbet A, Bekar A, Bilgin H, Ozdemir N, Kuytu T. Preemptive wound infiltration in lumbar laminectomy for postoperative pain: comparison of bupivacaine and levobupivacaine. Turk Neurosurg. 2014;24(1):48-53. doi: 10.5137/1019-5149.JTN.8431-13.0.
• Ersayli DT, Gurbet A, Bekar A, Uckunkaya N, Bilgin H. Effects of perioperatively administered bupivacaine and bupivacaine-methylprednisolone on pain after lumbar discectomy. Spine (Phila Pa 1976). 2006 Sep 1;31(19):2221-6. doi: 10.1097/01.brs.0000232801.19965.a0.
• Hetland ML, Ostergaard M, Ejbjerg B, Jacobsen S, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Svendsen A, Pedersen JK, Skjodt H, Ellingsen T, Lindegaard H, Podenphant J, Horslev-Petersen K; CIMESTRA study group. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP. Ann Rheum Dis. 2012 Jun;71(6):851-6. doi: 10.1136/annrheumdis-2011-200632. Epub 2012 Feb 1. Erratum In: Ann Rheum Dis. 2012 Nov;71(11):1918.
• Watanabe K, Tokumine J, Yorozu T, Moriyama K, Sakamoto H, Inoue T. Particulate-steroid betamethasone added to ropivacaine in interscalene brachial plexus block for arthroscopic rotator cuff repair improves postoperative analgesia. BMC Anesthesiol. 2016 Oct 4;16(1):84. doi: 10.1186/s12871-016-0251-9.
• Cherian MN, Mathews MP, Chandy MJ. Local wound infiltration with bupivacaine in lumbar laminectomy. Surg Neurol. 1997 Feb;47(2):120-2; discussion 122-3. doi: 10.1016/s0090-3019(96)00255-8.
• Shrestha N, Wu L, Wang X, Jia W, Luo F. Preemptive Infiltration with Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy (PRE-EASE): study protocol for a randomized controlled trial. Trials. 2020 May 5;21(1):381. doi: 10.1186/s13063-020-04308-z.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 4, 2019): 116
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 3, 2022
• Actual Primary Completion Date: December 3, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients scheduled for surgery under general anaesthesia for laminectomy or laminoplasty;
• American Society of Anaesthesiologists (ASA) classification of I or II;
• Age 18 to 64 years;
• Participates with an anticipated full recovery within 2 hours postoperatively.

Exclusion Criteria:

• Patient refusal;
• Participants who cannot use a patient-controlled analgesia (PCA) device and cannot understand the instructions of a Visual Analogue Score (VAS);
• Previous history of spinal surgery;
• Allergy to opioids, betamethasone or ropivacaine;
• Peri-incisional infection;
• History of stroke or a major neurological deficit;
• Trauma, deformity;
• Psychological problems;
• Extreme body mass index (BMI) (< 15 or > 35);
• History of excessive alcohol or drug abuse, chronic opioid use (more than 2 weeks), or use of drugs with confirmed or suspected sedative or analgesic effects;
• Patients using systemic steroids;
• Pregnant or breastfeeding;
• Preoperative Glasgow Coma Scale < 15;
• Participants who have received radiation therapy or chemotherapy preoperatively, or with a high probability to require a postoperative radiation therapy or chemotherapy according to the preoperative imaging.
• Not able to give written informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04153396
• Other Study ID Numbers: KY 2019-112-02-1
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Fang Luo, Beijing Tiantan Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Beijing Tiantan Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fang Luo, M.D.; Beijing Tiantan Hospital

• PRS Account: Beijing Tiantan Hospital
• Verification Date: March 2023