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

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Neuropathic Pain
• Intervention / Treatment: Drug: Pregabalin; Other: Naive patient

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• France
  • Cesson Sevigne, France, 35510
    • Christophe Aveline, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The investigators will evaluate the postoperative opioid consumption and pain scores in patients scheduled for lumbar spine surgery and taking pregabalin since more than 15 days and compare with preoperative pregabalin-free patient that will receive pregabalin only during surgery.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregabalin patients; 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; 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; Other Names: ATC code: N03AX16
Naive patients; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Christophe Aveline, MD
• Collaborators: Rennes University Hospital
• Investigators: Study Chair: Hélène Beloeil, MD, PhD, Rennes University Hospital; Principal Investigator: Christophe Aveline, MD, Private Hospital Sevigne

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): September 1, 2017
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: July 11, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (ESTIMATE): August 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2018
• Last Update Submitted That Met QC Criteria: March 31, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: chronic pain; pregabalin; oxycodone; multimodal analgesia; lumbar spine surgery
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: SPH-016-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO