Preemptive Co-infiltration of Dexamethasone Palmitate With Ropivacaine for Postoperative Pain in Major Spinal Surgery

Study Overview
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Brief Summary
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Patients undergoing major spinal surgery usually experience moderate-to-severe postoperative pain. Inadequate pain control may lead to severe complications. Dexamethasone as an adjunctive infiltration to local anesthesia (LA) presented a superior analgesic benefit compared with LA alone in various types of surgeries. However, a recent meta-analysis showed that the additional analgesic effect of dexamethasone in incision/wound infiltration was only statistically significant, but not clinically significant, and the overall benefits were marginal. Compared with dexamethasone, dexamethasone palmitate emulsion (DXP) is a targeted lipo-steroid with stronger anti-inflammatory effect, longer-acting duration and fewer adverse effects. To date, no studies have evaluated the additive analgesia effects of DXP on incision infiltration in major spinal surgery. The purpose of this trial is to determine whether preemptive co-infiltration of DXP emulsion and ropivacaine in surgical incision will further reduce postoperative opioid requirements and pain score after spinal surgery than that of ropivacaine alone.

Official Title
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Preemptive Co-infiltration of Dexamethasone Palmitate Emulsion With Ropivacaine for Postoperative Pain in Patients Undergoing Major Spinal Surgery

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Dexamethasone palmitate emulsion(DXP) plus ropivacaine
* Drug: Ropivacaine alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-64 years; Patients scheduled for elective laminoplasty or laminectomy with no more than 3 levels under general anesthesia American Society of Anesthesiologists (ASA) physical status of I-III; Anticipated full recovery and cooperation within 2 hours postoperatively. Exclusion Criteria: History of spinal surgery; Inability to use a patient-controlled analgesia (PCA) pump or comprehend the pain visual analog scale (VAS); Body mass index (BMI)<15kg/m2 or >35kg/m2; Peri-incisional infection; History of diabetes mellitus and other metabolic diseases; History of severe cardiopulmonary, hepatic or renal dysfunction; Preoperative coagulation abnormalities (activated partial thromboplastin time greater than 1.5 times normal value); History of allergies to any of the study drugs; History of alcohol or drugs abuse (more than 2 weeks), or use of any analgesic within 24h before surgery; Use of systemic steroids within 1 week before surgery; History of psychiatric disorders, chronic neck or back pain; History of radiation therapy and chemotherapy or with a high probability of such treatment postoperatively; Pregnant or breastfeeding; Refusal to sign informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The dexamethasone palmitate emulsion(DXP) plus ropivacaine group<br>The local infiltration solution in the dexamethasone palmitate emulsion(DXP) plus ropivacaine group will consist of dexamethasone palmitate emulsion(DXP) and ropivacaine. | Drug: Dexamethasone palmitate emulsion(DXP) plus ropivacaine<br>* The local infiltration solution in the dexamethasone palmitate emulsion(DXP) plus ropivacaine group will consist of ropivacaine and dexamethasone palmitate emulsion(DXP). For local infiltration, a total of 30mL solution will be prepared for each group, which will include 2mL of DXP(4mg per 1mL) added to 20.5 mL of saline and 7.5mL of 1% ropivacaine added to 15mL of saline for Group A . The surgeon will perform incision infiltration before the skin incision. A total of 10 mL of solution will be injected into each level. The study solution will be injected into the entire thickness of the planned incision site. The epidural space and intrathecal space will not be infiltrated.<br>* Other names: DXP plus ropivacaine;|
| Active Comparator: The ropivacaine alone group<br>The local infiltration solution in the ropivacaine alone group will consist of ropivacaine alone. | Drug: Ropivacaine alone<br>* The local infiltration solution in the ropivacaine alone group will consist of ropivacaine alone. For local infiltration, a total of 30mL solution will be prepared for each group, which will include 7.5mL of ropivacaine added to 22.5mL of saline for Group B . The surgeon will perform incision infiltration before the skin incision. A total of 10 mL of solution will be injected into each level. The study solution will be injected into the entire thickness of the planned incision site. The epidural space and intrathecal space will not be infiltrated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative consumption of sufentanil within 24 hours after spinal surgery via the PCA pump. | All participates will receive an electronic intravenous patient-controlled analgesia (PCA) pump. Participates will be advised to push the analgesic demand button if they feel pain. | Within 24 hours after spinal surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative consumption of sufentanil via PCA pump between 24 hours and 48 hours postoperatively. | Patients will use PCA device for pain management within the the first 48 hours after surgery. When the patients feel pain, the PCA button will be pressed. When the patients feel no pain, the PCA button will not be pressed. The PCA pump will provide a bolus of 2μg sufentanil with a 10 minutes lock-out time, and the maximum dose of sufentanil will be limited to 8μg/h. | Between 24 hours and 48 hours after spinal surgery | 
| Number of patients without PCA press button | Patients will use PCA device for postoperative analgesia. When the patients feel pain, the PCA button will be pressed. When the patients feel no pain, the PCA button will not be pressed. The PCA pump will provide a bolus of 2μg sufentanil with a 10 minutes lock-out time, and the maximum dose of sufentanil will be limited to 8μg/h. | Within 48 hours after spinal surgery | 
| The time of first PCA demand | The first time that the participants press PCA button. | Within 48 hours after spinal surgery | 
| The total number of PCA presses including both valid and invalid presses | The total number that participants press PCA button including valid and invalid presses | Within 48 hours after spinal surgery | 
| Postoperative visual analogue scale (VAS) score during movement(VASm) | The pain will be assessed by VAS scores during movement (0 indicates no pain, 10 indicates the most severe pain imaginable, a higher score means worse pain) | At 2 hours, 4 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 3 weeks, 1 month and 3 months postoperatively | 
| Postoperative VAS score at rest(VASr) | The pain will be assessed by VAS scores at rest (0 indicates no pain, 10 indicates the most severe pain imaginable, a higher score means worse pain) | At 2 hours, 4 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 3 weeks, 1 month and 3 months postoperatively | 
| Total consumption of Tylenol as supplementary analgesia | During the initial postoperative 48 hours, when VAS>4 (either VASm or VASr) after pressing button four times with PCA pump for pain relief, patients will be treated for supplementary analgesia with oral Tylenol (Mallinckrodt Inc.), a combination of 5mg of oxycodone hydrochloride and 325mg paracetamol per tablet at a minimum interval of 6 hours. After the initial postoperative 48 hours, patients will be allowed to take oral Tylenol as needed (dose as previously described), until the end of the study (3-months follow-up). | Four separate postoperative periods ( 0- postoperative 48 hours, postoperative 48 hours-postoperative 2 weeks, postoperative 2 weeks-postoperative 1 month, and postoperative 1 month-postoperative 3 months) | 
| Patient Satisfaction Score (PSS) with pain relief | 4 scales; never, sometimes, usually or always | At 48 hours, 72 hours, 1 week, 2 weeks, 3 weeks 1 month and 3 months postoperatively | 
| Postoperative nausea and vomiting (PONV) score | 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. | At 2 hours, 4 hours, 24 hours, 48 hours and 72 hours postoperatively | 
| Ramsay Sedation Scale (RSS) | 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. | At 2 hours, 4 hours, 24 hours, 48 hours and 72 hours postoperatively | 
| Patient Scar Assessment and the Observer Scar Assessment Scale (POSAS) | The POSAS consists of an Observer and a Patient Scale and includes a comprehensive list of items, based on clinically relevant scar characteristics. The observer scores six items: vascularization, pigmentation, thickness, surface roughness, pliability, and surface area. The patient scores six items: pain, pruritus, color, thickness, relief, and pliability. All included items are scored on the same polytomous 10-point scale, in which a score of 1 is given when the scar characteristic is comparable to normal skin and a score of 10 reflects the worst imaginable scar. All items are summed to give a total scar score, and therefore, a higher score represents a poorer scar quality. | At 2 weeks, 1 month and 3 months postoperatively | 
| Rate of steroid-related side effects and complications | Steroid-related side effects (hyperglycemia, gastrointestinal bleeding, gastritis, etc.) or complications including any cardiac, respiratory, renal, neurologic, or infection complications occured during the hospitalization | Through the whole follow-up, an average of 3 months | 
| Readmission rate within 3 months after spine surgery; | Patients readmitted within 3 months after spine surgery | Through the whole follow-up, within 3 months after spine surgery | 
| Length of Postoperative Anesthesia Care Unit (PACU) stay | Time from arrival at PACU after tracheal extubation to transfer from PACU to the surgical ward (modified Aldrete score ≥9). | Approximately 30 minutes to 2 hours after surgery | 
| Duration of hospitalization after surgery | Duration of hospitalization after surgery (time required from the end of surgery to discharge from the hospital). | Approximately 1-2 weeks after surgery | 
| Total consumption of remifentanil during surgery | Total remifentanil dosages during surgery | During surgery | 
| Total consumption of loxoprofen | Pain management will be provided via the sufentanil PCA device for the first 48 hours following surgery. After that, patients will switch to taking oral loxoprofen 60 mg at a minimum interval of 8 hours and a maximum 180mg per day as needed until discharge. | From postoperative 48 hours to approximately 1-2 weeks after surgery |