Clinical trial NCT04074265
Conditions: Cerebral Palsy Hip Dysplasia Pain, Postoperative
Keywords: cerebral palsy randomized controlled trial pediatric pain management perioperative medicine
Sponsor: University of California, Los Angeles
Start date: 2019-12-01; Completion date: 2023-04-30
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Pain management in pediatric patients presents a difficult challenge. Unlike adults, pediatric patients often cannot communicate their pain management needs clearly. Adequate pain control after surgery is pivotal for these patients in order to prevent negative physiologic and psychologic complications and to improve surgical outcomes. There is an ongoing shift away from the use of opioids in the post-operative setting due to both their negative side effects and their high potential for dependence and abuse.

A variety of new techniques of multimodal pain management have been developed and utilized in elective orthopaedic procedures. Injection of local anesthetics is becoming a widely popular technique utilized in adult arthroplasty. This technique blocks pain directly at the site of injection, and therefore can improve post-operative pain while minimizing side effects. Evidence has demonstrated this technique to be both safe and effective, resulting in reduced opioid consumption post-operatively. However, this technique has not been studied for use in pediatric patients, a population in which reduced narcotic use is equally, if not more important than in adult patients.

This study is a prospective, randomized controlled trial with 2 parallel arms. The goal of this study is to assess the efficacy of a surgical-site pain injection administered in pediatric patients with cerebral palsy undergoing major hip surgery. Patients who are scheduled to undergo surgery will be randomized to either intervention (injection of a pain cocktail) or placebo (injection of normal saline). The pain cocktail includes three medications: ropivacaine (a local anesthetic), ketorolac (an anti-inflammatory medication), and epinephrine (a medication to constrict blood vessels and increase the duration of action of any co-administered medications). A surgeon who is blinded to treatment group will administer the injection at the end of the procedure, prior to the patient waking from anesthesia. The injection is in addition to our typical multi-modal pain control protocol, which includes epidural anesthesia, acetaminophen, anti-inflammatories, oral narcotics and anti-spasmodic agents. Patients will then be monitored post-operatively and pain medication consumption (both while in the hospital post-operatively and for the first two weeks following discharge), patient-reported and/or nurse-recorded pain scores, length of hospital stay, and adverse effects will be recorded. At the first post-operative visit, patients' parents will be asked to complete a survey designed to assess parent satisfaction with their child's pain management after surgery. Patients, parents, and surgeons will be blinded to treatment group allocation. Data will be collected while the patient is in the hospital, after surgery (average duration 3-4 days), and at the first post-operative visit two to three weeks after surgery.

Detailed description:
With the ongoing opioid epidemic in the United States, there has been a shift toward the use of non-opioid alternatives for pain control in the post-operative period. The development of a multimodal approach to pain management has seen a rise in the use of local anesthesia, whether as a peripheral nerve block or as an peri/intra-articular injection. These techniques have shown to be very effective in the adult population for improving pain and reducing the need for opioid consumption post-operatively. However, these techniques have yet to be studied in the pediatric population. The purpose of this study is to examine the efficacy of a local anesthetic injection post-operatively in pediatric patients with cerebral palsy undergoing major surgery as part of a multi-modal pain control protocol. The investigators hypothesize that peri-articular injection of a pain cocktail containing a mix of local anesthetic, anti-inflammatory medication, and epinephrine at the end of surgery will result in decreased opioid use in the immediate peri-operative period in pediatric patients with cerebral palsy undergoing proximal femoral osteotomy when compared to an injection of normal saline. The investigators also hypothesize that the pain injection will result in decreased mean pain scores post-operatively, shorter hospital stays and improved parent satisfaction when compared to normal saline injection. With this study, the investigators hope to provide evidence to support the use of a minimally invasive, safe-to-use pain injection that will reduce the need for opioids in pediatric patients undergoing orthopaedic procedures.

Study Design:

This study is a prospective, randomized controlled trial with 2 parallel arms. Patients will be randomly assigned to the 2 treatment groups: surgical-site injection with ropivacaine, ketorolac, and epinephrine, or surgical-site injection with normal saline. Randomization will be performed via random number generator and will be carried out by a research associate who will not participate in study recruitment or outcomes assessment. Allocations will be concealed on a password-protected database accessible only to the research associate. Patients, surgeons, and nursing staff who perform post-operative assessments will be blinded to treatment allocation.

Surgical Procedure:

Patients undergoing unilateral or bilateral hip proximal femoral osteotomies will be included in the study. All patients will be treated with standard-of-care techniques chosen by the treating surgeon. The addition of pelvic osteotomies and/or soft tissue procedures will be at the discretion of the treating surgeon and will not exclude the patient from the study. Written consent will be obtained for all patients prior to the surgical procedure. Parental consent will be obtained, in addition to patient assent for all patients of appropriate age and intellectual capability. All patients will have a general anesthetic with a lumbar epidural. No preemptive scheduled analgesic regimen will be employed. All medications administered during induction and maintenance of anesthesia will be managed by the anesthesiologist and titrated at their discretion.

The local anesthetic group will be injected with a cocktail totaling 40 milliliters (mL) (20mL on each side) that will be composed of ropivicaine 2mg/mL (3mg/kg), epinephrine 1mg/mL (0.5mg), ketorolac 30mg/mL (0.5mg/kg). The control group will receive 40mL of 0.9% sodium chloride solution. The injection will be performed while the patient is still under general anesthesia, following wound closure, and will be injected evenly between the deep and superficial tissues in an extra-articular pattern (no injection of the synovium or capsule). All injections will be performed using a 20-gauge needle. All medications will be obtained from the hospital pharmacy. All injections will be prepared by an operating room nurse under the supervision of a research assistant, and placed in an unlabeled syringe to allow for blinding of the surgeon administering the injection.

Post-Operative Protocol:

The epidural anesthesia will be started at the discretion of the attending anesthesiologist either before or on-arrival to the post-anesthesia care unit. Any additional medications administered during the immediate post-operative period in the post-anesthesia care unit will be prescribed by the attending anesthesiologist and will not be standardized. Beginning when the patient leaves the post-anesthesia care unit, all patients will be given the following pain regimen: acetaminophen (15mg/kg PO or per g-tube every 6 hours around the clock), ketorolac (0.5mg/kg IV every 8 hours for 3 doses) followed by ibuprofen (10mg/kg PO or per g-tube every 8 hours as needed for mild pain (pain score 1-3)), diazepam (0.1mg/kg PO or per g-tube every 6 hours around the clock for 36 hours followed by every 6 hours as needed for muscle spasms), and oxycodone (0.1mg/kg PO or per g-tube every 6 hours as needed for severe pain (pain score 7-10)). Nurses will be instructed to offer this as-needed medication to patients at standardized intervals every 4 hours when performing pain assessments. Additional medication for pain may be administered if the protocol does not result in adequate pain relief, at the discretion of the treating physician. The epidural will be titrated by the acute pain anesthesiology team for inadequate pain control, and all epidurals will be discontinued the morning of post-operative day two. All patients will be discharged on a standardized medication regimen as follows: diazepam (0.1mg/kg PO or per g-tube every 6 hours for 14 days), oxycodone (0.5mg/kg PO or per g-tube every 6 hours as needed for severe pain, 20 doses), acetaminophen (15mg/kg PO or per g-tube every 6 hours for 14 days), and ibuprofen (10mg/kg PO or per g-tube every 8 hours for 14 days). Inpatient and outpatient narcotic consumption will be recorded as morphine equivalents per kilogram, to allow adjustment for the weight-based dosing used in pediatric patients.

All other aspects of post-operative care, including (but not limited to) physical therapy, weight bearing status, mobilization, and bracing will be decided on a case-by-case basis by the treating surgeon.

Data Collection and Protection:

Data will be collected by approved research personnel via access to the medical record. Personal identifying information collected will include name, date of birth, medical record number, and telephone number. All data will be labeled with a code that can be linked to this personal identifying information. Data will be collected only from the hospitalization following the surgical procedure and from the first post-operative visit. This data will include: narcotic consumption, pain scores, complications or adverse events, and re-admission in the immediate post-operative period (first two weeks post-operatively). All data will be stored on a secure, encrypted data storage device or password protected and encrypted internet-based storage device.

Arms: arm 1: This group will be injected with a cocktail totaling 40mL (20mL on each side) that will be composed of ropivicaine 2mg/mL (3mg/kg), epinephrine 1mg/mL (0.5mg), ketorolac 30mg/mL (0.5mg/kg). arm 2: The control group will receive an injection of 40mL of 0.9% sodium chloride solution.
Interventions: intervention 1: Ropivacaine injection intervention 2: normal saline
Intervention descriptions: intervention 1: Injection containing a mix of the above medications will be performed while the patient is still under general anesthesia, following wound closure, and will be injected evenly between the deep and superficial tissues in an extra-articular pattern (no injection of the synovium or capsule). intervention 2: Injection containing normal saline will be performed while the patient is still under general anesthesia, following wound closure, and will be injected evenly between the deep and superficial tissues in an extra-articular pattern (no injection of the synovium or capsule).

Protocol documents:
Prot_SAP_001.pdf: 
Official Title: Efficacy of a Peri-Operative Surgical-Site, 
Multimodal Drug Injection in Pediatric Patients with Cerebral 
Palsy Undergoing Hip Surgery: A Randomized Controlled Trial.  
NCT: NCT04074265 
Date of Document: 1/4/2024 
 
 


Study Title:  
Efficacy of a Peri-Operative Surgical-Site, Multimodal Drug Injection in Pediatric Patients with 
Cerebral Palsy Undergoing Hip Surgery: A Randomized Controlled Trial.  
Study Design:  
This study is a prospective, randomized controlled trial with 2 parallel arms. Patients will be 
randomly assigned to the 2 treatment groups: surgical-site injection with ropivacaine, ketorolac, 
and epinephrine, or surgical-site injection with normal saline. Randomization will be performed 
via random number generator and will be carried out by a research associate who will not 
participate in study recruitment or outcomes assessment. Allocations will be concealed on a 
password-protected database accessible only to the research associate. Patients, surgeons, and 
nursing staff who perform post-operative assessments will be blinded to treatment allocation.  
Participants:  
Patients will be eligible to be included in this study if they are under the age of 18 years, have a 
known diagnosis of cerebral palsy, and are scheduled to undergo surgery of the proximal femur 
(specifically, unilateral or bilateral proximal femoral osteotomy for hip dysplasia). Patients will 
be recruited from both UCLA/Orthopaedic Institute for Children and Lurie Children’s Hospital 
of Chicago. Patients and parents/guardians will be asked at their pre-operative clinic visit if they 
would like to participate in the study. They will be provided with the informed consent form at 
their pre-operative visit in order to allow them time to review the information prior to signing 
consent. Informed consent for the study will then be obtained in the pre-operative holding area 
prior to surgery. Patients will be excluded from the study if they have ongoing pre-operative 
opioid use, or a history of an allergic reaction to any of the components of the pain injection.  
Surgical Procedure:  
Patients undergoing unilateral or bilateral hip proximal femoral osteotomies will be included in 
the study. All patients will be treated with standard-of-care techniques chosen by the treating 
surgeon. The addition of pelvic osteotomies and/or soft tissue procedures will be at the discretion 
of the treating surgeon and will not exclude the patient from the study. Written consent will be 
obtained for all patients prior to the surgical procedure. Parental consent will be obtained, in 
addition to patient assent for all patients of appropriate age and intellectual capability. All 
patients will have a general anesthetic with a lumbar epidural. No preemptive scheduled 
analgesic regimen will be employed. All medications administered during induction and 
maintenance of anesthesia will be managed by the anesthesiologist and titrated at their discretion.  
The local anesthetic group will be injected with ropivacaine 2mg/mL (3mg/kg), epinephrine 
1mg/mL (0.5mg), and ketorolac 30mg/mL (0.5mg/kg). If bilateral hips are involved, the total 
amount will be split evenly between the two sides. The control group will receive equivalent 
volumes of 0.9% sodium chloride solution (these volumes will be calculated based on the 
volumes of medication the patient would have received had they been assigned to the cocktail 
group). The injections will be performed while the patient is still under general anesthesia,  


following wound closure, and medications will be injected evenly between the deep and 
superficial tissues in an extra-articular pattern (no injection of the synovium or capsule). All 
injections will be performed using a 20-gauge needle. The injection medications will be placed 
in a sterile cup. The surgical technician will fill syringes from the labeled cup, which will be 
handed to the surgeon for immediate administration.  
Post-Operative Protocol:  
The epidural anesthesia will be started at the discretion of the attending anesthesiologist either 
before or on-arrival to the post-anesthesia care unit. Any additional medications administered 
during the immediate post-operative period in the post-anesthesia care unit will be prescribed by 
the attending anesthesiologist and will not be standardized. Beginning when the patient leaves 
the post-anesthesia care unit, all patients will be given the following pain regimen: 
acetaminophen (15mg/kg PO or per g-tube every 6 hours around the clock), ketorolac (0.5mg/kg 
IV every 8 hours for 3 doses) followed by ibuprofen (10mg/kg PO or per g-tube every 8 hours as 
needed for mild pain (pain score 1-3)), diazepam (0.1mg/kg PO or per g-tube every 6 hours 
around the clock for 36 hours followed by every 6 hours as needed for muscle spasms), and 
oxycodone (0.1mg/kg PO or per g-tube every 6 hours as needed for severe pain (pain score 7- 
10)). Nurses will be instructed to offer this as-needed medication to patients at standardized 
intervals every 4 hours when performing pain assessments. Additional medication for pain may 
be administered if the protocol does not result in adequate pain relief, at the discretion of the 
treating physician. The epidural will be titrated by the acute pain anesthesiology team for 
inadequate pain control, and all epidurals will be discontinued the morning of post-operative day 
two. All patients will be discharged on a standardized medication regimen as follows: diazepam 
(0.1mg/kg PO or per g-tube every 6 hours for 14 days), oxycodone (0.1mg/kg PO or per g-tube 
every 6 hours as needed for severe pain, 20 doses), acetaminophen (15mg/kg PO or per g-tube 
every 6 hours for 14 days), and ibuprofen (10mg/kg PO or per g-tube every 8 hours for 14 days). 
Inpatient and outpatient narcotic consumption will be recorded as morphine equivalents.  
All other aspects of post-operative care, including (but not limited to) physical therapy, weight 
bearing status, mobilization, and bracing will be decided on a case-by-case basis by the treating 
surgeon.  
Data Collection and Protection:  
Data will be collected by IRB-approved research personnel via access to the medical record. 
Personal identifying information collected will include name, date of birth, medical record 
number, and telephone number. All data will be labeled with a code that can be linked to this 
personal identifying information. Data will be collected only from the hospitalization following 
the surgical procedure and from the first post-operative visit. This data will include: narcotic 
consumption, pain scores, complications or adverse events, and re-admission in the immediate 
post-operative period (first two weeks post-operatively). All data will be stored on a secure, 
encrypted data storage device or password protected and encrypted internet-based storage device.  
Outcome Measures:  


The primary outcome measure will be total narcotic consumption in the first 48 hours after 
surgery. Narcotic consumption will be recorded in the medical record while in the post- 
anesthesia care unit and while inpatient and will be converted into morphine equivalents 
according to a conversion table. The secondary outcome will be pain scores during inpatient 
hospitalization following the surgical procedure. Pain score assessments will be completed in the 
post-anesthesia care unit, and every 4 hours following the surgical procedure. Scores will be 
collected by nursing staff on the inpatient ward who are blinded to treatment allocation and 
recorded in the electronic medical record. The type of pain score collection will vary based on 
patient age and level of intellectual disability. In verbal children, either the VAS or FACES pain 
scale will be employed. In non-verbal children, the FLACC scale will be employed.  
Additional secondary outcome measures will include total narcotic consumption following 
hospital discharge, length of stay, parent satisfaction scores, and complications. Patients will be 
instructed to bring their medications with them to their first post-operative visit, and outpatient 
narcotic use will be recorded based on amount of medication remaining. This will also be 
converted into morphine equivalents according to the same conversion table. Parent satisfaction 
scores will be based on a standardized questionnaire taken by parents in person at the first post- 
operative clinic visit aimed to assess their satisfaction with their child’s pain management peri- 
operatively.  
Statistical Analysis Plan  
Outcome measures will be analyzed using a two-tailed t-test or a non-parametric Mann-Whitney 
test for quantitative variables; a Fischer exact test was used for categorical variables. Further, 
while a t-test will be utilized to demonstrate differences in narcotic consumption and average 
pain scores during discrete, comparable, clinically-relevant measures of time, mixed effects 
modeling will be utilized to further analyze narcotic consumption and pain scores over time. 
Statistical significance will be defined as p<0.05.