Variation in the Effect of Dexamethasone Associated With Axillary Plexus on the Occurrence of Rebound Pain

Study Overview
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Brief Summary
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The study will evaluate pain and recovery after a single injection axillary plexus block combined with an intravenous dose of 0.1 mg/kg dexamethasone in ambulatory patients undergoing upper extremity bone surgery. The investigators will try to identify the risk factors involved in a decrease in the efficacy of dexamethaxone for the prevention of RP. The hypotheses are that : The interindividual variability may modulate the preventive effect on rebound pain after axillary block, of pre-incisional administration of an anti-inflammatory dose of dexamethasone (0.1 mg/kg max 10 mg). Patients with increased preoperative anxiety or underlying catastrophizing will experience more postoperative pain as the axillary PNB dissipates. Elevated preoperative salivary lipocortin 1 and cortisol levels result in a lesser preventive effect of dexamethasone on the development of rebound pain.

Detailed Description
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The use of a peripheral nerve block (PNB) through local anesthetics administered may exacerbate the acute inflammatory process induced by the surgical trauma, which may cause rebound pain once the block is lifted, also called Rebound pain (RP). The administration of a dose of Dexamethasone (DEXA) IV as an adjuvant, to optimize the effectiveness of PNB by increasing the duration of PNB , is already a validated practice in anesthesia. In addition the well known analgesic effects of DEXA on postoperative pain (dose> 0.1 mg/kg) seem to contribute to the decrease in RP occurring in the first 24 hours after surgery . These protective properties of DEXA with respect to this phenomenon of hyperalgesia could be explained, among other things, by its modulatory actions on the inflammatory reaction and inhibitory actions on cyclooxygenase as well as its effect on the production of specific mediators such as cytokines. However, even if DEXA can reduce the onset of RP in some patients, its efficacy seems to be variable and inconsistent between individuals, as suggested by the results of a retrospective observational study . It can thus be assumed that some individuals are less sensitive to the preventive administration of DEXA and this for different reasons that it would be interesting to better understand . Objectives:The primary objective will be to identify factors predisposing to variations in the efficacy of DEXA on the occurrence of RP by characterizing the basal stress state of the patient, the level of anxiety and pre-existing catastrophism, as well as the basal thresholds of Lipocortin 1 and cortisol and the basal inflammatory degree (CR high sensitivity) The secondary objective will be to evaluate the interindividual variability of the preventive efficacy of pre-incisional systemic administration of an anti-inflammatory dose of DEXA (0.1 mg/kg, 10 mg maximum) on the occurrence of RP during axillary block removal. Method: Patients scheduled for elective upper extremity surgery will receive an axillary nerve block. An intravenous injection of DEXA 0.1mg/kg preoperatively will be offered to all patients included in the study. The PNB will be performed under real-time ultrasound guidance by a competent anesthesiologist using a local anesthetic solution of MEPIVACAINE 1%, for volumes administered varying between 15 and 30 ml (maximum 400 mg, 5-6 mg/Kg). The intensity, the neuropathic or catastrophic character of the pain as well as the preoperative anxiety will be collected through specific questionnaires (APAIS /Catastrophisation /CSI /NLR...). In addition, salivary samples of free cortisol and Lipocortin 1 and blood samples (CRP hs and NLR) will be collected before the PNB is performed. All patients will receive, if necessary, an adapted analgesia in the postoperative period and in the recovery room. Patients will be discharged with a standardized analgesic treatment. Patients will be followed up according to the study protocol established in the PACU (recovery room) at D1 to D4 D30 and at 3 months postoperatively (by telephone calls).

Official Title
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Evaluation of Intraoperative Dexamethasone Efficacy to Prevent Rebound Pain Phenomenon According to Individual Patient Characteristics

Conditions
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Adjuvants, Anesthesia, Brachial Plexus Anesthesia

Intervention / Treatment
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* Other: upper extremity bone surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any ambulatory upper limb bone surgery carried out under axillary PNB Patient aged between 18 and 75 yrs old Exclusion Criteria: Refusal to participate Contraindication to the use of Dexamethasone Patient with corticoids intake for various reasons Contraindication to regular use of postoperative analgesics like non-steroidal anti-inflammatory drugs and paracetamol Pregnant woman Diabetic patient Vascular patient Cognitive disorders Inability to answer perioperative questionnaires (language problem)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| ambulatory upper limb bone surgery carried out under axillary PNB<br>Patients will receive a slow intravenous injection of 0.1mg/kg max 10 mg intravenous dexamethasone in a 2cc syringe (5 mg/cc dexamethasone) after PNB is performed, prior to tourniquet placement and the start of surgery. | Other: upper extremity bone surgery<br>* any ambulatory upper limb bone surgery carried out under axillary PNB<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of sexe on the efficacy of DEXA on the occurrence of RP | - Sexe (male ,female), | Through study completion, an average of 1 year | 
| Impact of BMI on the efficacy of DEXA on the occurrence of RP | - Body mass index BMI (combination of weight measurement in Kilograms and height in meters to obtain BMI in kg/m^2), | Through study completion, an average of 1 year | 
| Impact of preoperative anxiety levels on the efficacy of DEXA on the occurrence of RP | - Preoperative anxiety levels (APAIS scale). The score can range from 6 (no anxiety) to 30 (very anxious). | Through study completion, an average of 1 year | 
| Impact of preoperative levels of pre-existing catastrophizin on the efficacy of DEXA on the occurrence of RP | - Preoperative levels of pre-existing catastrophizing .(13 items scored from 0 to 4) | Through study completion, an average of 1 year | 
| Impact of preoperative levels of central sensitization on the efficacy of DEXA on the occurrence of RP | - Preoperative levels of central sensitization index (CSI) (9 questions) | Through study completion, an average of 1 year | 
| Impact of baseline levels of Lipocortin 1 and cortisol on the efficacy of DEXA on the occurrence of RP | - Baseline levels of Lipocortin 1 and cortisol (salivary assays in nmol/L) and measurements of blood mediators of inflammation, C-Réactive Proteine (CRP) value (in milligrams/liter) and NLR value (neutrophil to lymphocyte ratio) . | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inter-individual variability of preventive efficacy of DEXA | The investigators wish to demonstrate inter-individual variability in the incidence of pain rebound despite systemic pre-incisional preventive administration of an anti-inflammatory dose of DEXA (0.1 mg/kg, 10 mg maximum) for all patients included in the study. | Through study completion, an average of 1 year |