Impact of Pregabalin in Chronic Users vs. a Perioperative Limited Prescription on Oxycodone Requirement

Study Overview
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Brief Summary
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Spinal surgery is associated with intense pain and associated to a history of preoperative chronic pain. Pregabalin is licensed to treat chronic neuropathic pain, particularly when high dose of opioid are required. Preoperative pain is associated with high postoperative pain scores and opioid requirement promoting persistent hyperalgesic state. The investigators will evaluate the postoperative opioid consumption and pain scores in patients scheduled for lumbar surgery and taking pregabalin since more than 15 days and compare with preoperative pregabalin-free patient that will receive pregabalin only during surgery.

Detailed Description
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Patients will be prospectively included and compared according their preoperative medication: pregabalin-treated patients (>more than 15 days) for neuropathic pain associated to spinal surgery and pregabalin-free patients for whom pregabalin will be prescribed for 48 hours. Patients will be included without randomization as an observational study. All the patients will receive multimodal analgesia and intraoperative management will be standardized. The main outcome will be the amount of oxycodone during the first 24h after surgery. Other outcomes include pain scores, the quantification of the neuropathic pain diagnostic questionnaire (DN4), nausea and vomiting, length of stay, side-effects of pregabalin and opioid. Patients were also evaluated at three months for pain scores and DN4 score. Postoperative evaluation will be performed in a single-blind manner with investigators not include in the recruitment or the peroperative period.

Official Title
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Postoperative Oxycodone Consumption After Spinal Surgery in Pregabalin-treated Patients Compared to a 48-h Perioperative Administration: a Prospective, Observational Study

Conditions
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Postoperative Pain, Neuropathic Pain

Intervention / Treatment
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* Drug: Pregabalin
* Other: Naive patient


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society Anesthesiologist Physical status (ASA) 1-3 Age ≥18 years old Spinal surgery: discectomy, posterior or transforaminal lumbar interbody fusion limited to 2 levels, lumbar disk prosthesis Able to participate personality, has given free and inform consent in French Affiliated of beneficiary of a system of social security Exclusion Criteria: Age less than 18 years or higher than 85 years old Refusal to participate or provide written consent Surgery with a combined anterior and posterior approach Emergency surgery, reintervention, spine fracture, metastasis Tricyclic antidepressant use Pregabalin use for other indication: other neuropathy, epilepsy, generalized anxiety disorder Pregnancy Lack of understanding of NRS and/or DN4 scores Hypersensibility or contraindication to levobupivacaine, paracetamol, nefopam, ketoprofen and/or oxycodone Participation in another clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregabalin patients<br>Same dose of preoperative pregabalin 1h after surgery associated to paracetamol 1g PO and ketoprofen 100mg PO Intraoperative: nefopam 20mg IV + ketamine 0.3mg/kg IV + dexamethasone 8mg IV Postoperative: morphine titration (PACU if NRS > 3) + paracetamol 1g/6h PO + ketoprofen 100mg/12h PO systematically, oxycodone 5-10mg/12h PO if NRS>3 | Drug: Pregabalin<br>* Pregabalin continued at the same preoperative dose 1h before surgery associated to paracetamol 1g PO and ketoprofen 100mg PO Intraoperative: nefopam 20mg IV + ketamine 0.3mg/kg IV + dexamethasone 8mg IV Postoperative: morphine titration in PACU (NRS > 3) + paracetamol 1g/6h PO + ketoprofen 100mg/12h PO systematically, oxycodone 5-10mg/12h PO if NRS>3<br>* Other names: ATC code: N03AX16;|
| Naive patients<br>Pregabalin 150mg PO initiated 1h before surgery and associated to paracetamol 1g PO and ketoprofen 100mg PO Intraoperative: nefopam 20mg IV + ketamine 0.3mg/kg IV + dexamethasone 8mg IV Postoperative: morphine titration in PACU (NRS > 3) + paracetamol 1g/6h PO + ketoprofen 100mg/12h PO systematically, oxycodone 5-10mg/12h PO if NRS>3 | Other: Naive patient<br>* Pregabalin 150mg PO initiated 1h before surgery Associated to paracetamol 1g PO and ketoprofen 100mg PO Intraoperative: nefopam 20mg IV + ketamine 0.3mg/kg IV + dexamethasone 8mg IV Postoperative: morphine titration in PACU (NRS > 3) + paracetamol 1g/6h PO + ketoprofen 100mg/12h PO systematically, oxycodone 5-10mg/12h PO if NRS>3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxycodone consumption | mg | 24h postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) Pain at rest | NRS: 0 no pain - 10 worst pain | the day before surgery | 
| Numeric Rating Scale (NRS) Pain during walking | NRS: 0 no pain - 10 worst pain | the day before surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 1h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 4h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 8h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 12h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 24h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 48h after surgery | 
| Numeric Rating Scale Pain (NRS) at rest | NRS: 0 no pain - 10 worst pain | 3 months after surgery | 
| Numeric Rating Scale Pain (NRS) during walking | NRS: 0 no pain - 10 worst pain | 12h after surgery | 
| Numeric Rating Scale Pain (NRS) during walking | NRS: 0 no pain - 10 worst pain | 48h after surgery | 
| Numeric Rating Scale Pain (NRS) during walking | NRS: 0 no pain - 10 worst pain | 3 months ater surgery | 
| remifentanil consumption | µg/kg/min | during surgery | 
| Morphine titration | mg | 0-2h after surgery | 
| Oxycodone requirement | mg | 0-48h after surgery | 
| Ondansetron requirement | mg | 0-48h after surgery | 
| DN4 score |  | preoperatively | 
| DN4 score |  | on postoperative day one | 
| DN4 score |  | on postoperative day two | 
| DN4 score |  | three months after surgery | 
| length of stay | days | on postoperative day five | 
| Post Opertive Nausea and vomiting (PONV) | % of patients | 0-48h after surgery | 
| Pregabalin side-effects | diplopia, confusion, dizziness, psychiatric disorders (% of patients) | 0-48h after surgery | 
| Sedation | 1: awake - 2: drowsiness, easily awake by appeal - 3: drowsiness, awake to tactile stimulation - 4: drowsiness, awake by pain | 0-48h after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pain, oxycodone, pregabalin, lumbar spine surgery, multimodal analgesia