Chest Wall Block After Sternotomy: Randomized Controlled Trial in Cardiac Surgery: (PABLOS Study)

Study Overview
=================
Brief Summary
-----------------
The main objective is to compare the effectiveness of LocoRegional Anesthesia (LRA) (bilateral transverse thoracic block or bilateral parasternal block) in addition to standard management compared to standard management alone (general anesthesia without LRA) on the FQoR-15 (French Quality of Recovery - 15 score) at H+24 after cardiac surgery by sternotomy.This is a phase III monocentric superiority study , comparative, with three parallel groups, randomized with a ratio (1:1:1), controlled versus standard management, single-blind.

Detailed Description
-----------------
Each year, more than one million patients worldwide undergo cardiac surgery via sternotomy. Postoperative pain is frequent in this context, affecting 49% of patients at rest and 78% during mobilization. This pain is associated with many avoidable post-operative complications. Nowadays, ERAS (Enhanced Rehabilitation After Surgery) protocols are increasingly developed in order to optimize post-operative rehabilitation. The management of postoperative pain is one of their main challenges and is based in particular on the use of locoregional anesthesia (LRA) with the aim of sparing morphine. Several LRAs have been described in cardiac surgery in recent years, and they are increasingly used in routine clinical practice. Transverse thoracic block and parasternal block are the main peripheral LRA techniques proposed for surgical procedures with sternotomy. Transverse chest block was first described in cardiac surgery in 2015 ; and the parasternal block in 2018. These techniques are spreading in current clinical practice because of their simplicity of implementation, their safety and their supposed effectiveness. The parasternal block is more recent, and presents a more superficial injection plane than the transverse thoracic block. Thus, it is theoretically as effective as the transverse thoracic and less at risk of complications. The main objective of this study is to compare the effectiveness of LRA (bilateral transverse thoracic block or bilateral parasternal block) in addition to standard management compared to standard management alone (general anesthesia without LRA) on the quality of early postoperative recovery after heart surgery by sternotomy. The primary endpoint is the postoperative recovery score in the French version, FQoR-15 (French Quality of Recovery - 15 score), performed at H+24. The FQoR-15 is currently one of the most reliable and reproducible tools for assessing the quality of postoperative rehabilitation. This instrument is one of the recommended endpoints for the evaluation of patient comfort, according to a recent consensus of international experts. This study is a phase III study of superiority, monocentric, comparative, with three parallel groups, randomized with a ratio (1:1:1), controlled versus standard care, single-blind. of inclusion is 254 patients included and randomized. The patient is pre-included during the pre-anaesthetic visit, the day before his scheduled surgery. He receives oral and written information, and provides his written consent to participate in this study, the follow-up will be 30 days. Depending on the randomization, the patient receives one of the following three treatments: bilateral transverse thoracic block followed by standard analgesic management; a bilateral parasternal block followed by standard analgesic treatment; standard analgesic treatment alone (without LRA). Bilateral parasternal block or transverse thoracic block are performed ultrasound-guided, at the end of surgery in the operating room. Once in the desired plane depending on the randomisation (transverse or parasternal), a volume of 20 ml of ropivacaine at 2 mg/ml is injected on each side of the sternum. The rest of the pain management is identical in the three groups according to the habits of the department. If the hypotheses on the effectiveness of parasternal block and/or transverse thoracic block are confirmed, postoperative recovery in the interventional arms will be improved. This will confirm the value of performing an LRA postoperatively.

Official Title
-----------------
Chest Wall Block After Sternotomy: Randomized Controlled Trial in Cardiac Surgery: (PABLOS Study)

Conditions
-----------------
Pain, Postoperative, Cardiac Surgery

Intervention / Treatment
-----------------
* Drug: LRA Loco-regional anesthesia
* Procedure: Standardized post-operative analgesia protocol


Participation Criteria
=================
Eligibility Criteria
-----------------
Pre-inclusion criteria : Adult patient (≥18 years old); Patient having scheduled cardiac surgery with a sternotomy performed at the CHU d'Angers; Patient having signed a consent; French-speaking patient, able to understand and answer a questionnaire; Affiliated patient or beneficiary of a social security scheme. Criteria for confirming inclusion Hemodynamic stability at the end of surgery; Absence of bleeding justifying immediate revision surgery. Non-inclusion criteria Known hypersensitivity to amide-bonded local anesthetics; Operation for cardiac revision surgery, including sternotomy REDUX (revision surgery); Emergency surgery; Surgery in a septic context (Endocarditis, Intravascular device infection); Weight less than 30kg; Severe psychiatric or cognitive impairment interfering with assessment by questionnaires; Pregnant, breastfeeding or parturient woman; Person deprived of liberty by judicial or administrative decision; A person undergoing psychiatric treatment under duress; Person subject to a measure of legal protection; Inclusion in another interventional study modifying postoperative pain management.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study phase III, superiority study, monocentric, comparative, with three parallel groups, randomized with a ratio (1:1:1), controlled versus standard care, single-blind
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TTP group (= Transversus Thoracic Plane block = Deep PIP = Deep parasternal intercostal plane block)<br>At the end of the surgery, realisation of a bilateral transverse thoracic block. (20ml of Naropeine 0.2%, each side) Followed by standard analgesic treatment. | Drug: LRA Loco-regional anesthesia<br>* Bilateral parasternal block or transverse thoracic block are performed ultrasound-guided, at the end of surgery in the operating room. Once in the desired plane depending on the randomisation (transverse or parasternal), a volume of 20 ml of ropivacaine at 2 mg/ml is injected on each side of the sternum. The intervention (TTP or PSB) is performed by the anesthetist-resuscitator investigator.<br>* Other names: 40ml Ropivacaine 0.2%;Procedure: Standardized post-operative analgesia protocol<br>* The pain management protocol in intensive care is as follows: paracetamol 1g x 4 per day systematically (apart from the usual contraindications), IV then PO; PCA (Patient Controlled Analgesia) with oxycodone or morphine: 1mg bolus, 7min refractory period, maximum 4h dose 20mg. The PCA is usually maintained until 24-48h after the intervention then relayed by oxycodone 5mg every 4h if EVA > 3 sublingual and addition of oxycodone LP 10mg x 2 per day if daily intake on PCA > 20mg. Remedy molecules in case of ineffective analgesia: ketoprofen 100mg q12h IV, or 50mg q8h PO; nefopam 20mg every 6h IV or PO; ketamine 1 to 1.5 mg/kg/24H IVSE.<br>|
| Experimental: PSB group (=ParaSternal Block = Superficial PIP = Superficial parasternal intercostal plane block)<br>At the end of the surgery, realisation of a bilateral parasternal block (20ml of Naropeine 0.2%, each side). Followed by standard analgesic treatment. | Drug: LRA Loco-regional anesthesia<br>* Bilateral parasternal block or transverse thoracic block are performed ultrasound-guided, at the end of surgery in the operating room. Once in the desired plane depending on the randomisation (transverse or parasternal), a volume of 20 ml of ropivacaine at 2 mg/ml is injected on each side of the sternum. The intervention (TTP or PSB) is performed by the anesthetist-resuscitator investigator.<br>* Other names: 40ml Ropivacaine 0.2%;Procedure: Standardized post-operative analgesia protocol<br>* The pain management protocol in intensive care is as follows: paracetamol 1g x 4 per day systematically (apart from the usual contraindications), IV then PO; PCA (Patient Controlled Analgesia) with oxycodone or morphine: 1mg bolus, 7min refractory period, maximum 4h dose 20mg. The PCA is usually maintained until 24-48h after the intervention then relayed by oxycodone 5mg every 4h if EVA > 3 sublingual and addition of oxycodone LP 10mg x 2 per day if daily intake on PCA > 20mg. Remedy molecules in case of ineffective analgesia: ketoprofen 100mg q12h IV, or 50mg q8h PO; nefopam 20mg every 6h IV or PO; ketamine 1 to 1.5 mg/kg/24H IVSE.<br>|
| Sham Comparator: Control group<br>Standard analgesic treatment alone (without LRA) . | Procedure: Standardized post-operative analgesia protocol<br>* The pain management protocol in intensive care is as follows: paracetamol 1g x 4 per day systematically (apart from the usual contraindications), IV then PO; PCA (Patient Controlled Analgesia) with oxycodone or morphine: 1mg bolus, 7min refractory period, maximum 4h dose 20mg. The PCA is usually maintained until 24-48h after the intervention then relayed by oxycodone 5mg every 4h if EVA > 3 sublingual and addition of oxycodone LP 10mg x 2 per day if daily intake on PCA > 20mg. Remedy molecules in case of ineffective analgesia: ketoprofen 100mg q12h IV, or 50mg q8h PO; nefopam 20mg every 6h IV or PO; ketamine 1 to 1.5 mg/kg/24H IVSE.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FQoR-15 score at 24 hours (French Quality of Recovery-15 score) | Value of the French Quality of Recovery-15 score (minimum value of 0 and maximum value of 150, with a higher score for a better outcome). The QoR-15 questionnaires will be completed by the patient himself whenever possible, who could be helped by a nurse blinded to the assignment group. | 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain (VRS) at rest and mobilisation | Analgesic efficacy at rest and during exercise (cough, physiotherapy session, mobilization) assessed via pain measurements by a simple verbal rating scale (VRS) with 11 items (0: no pain, 10: maximum pain) | 3, 6, 12, 24, 48 , 72 hours after surgery and during the removal of surgical drains | 
| Post-operative consumption of morphine (milligrams) | Amount of opioid consumption, in equivalent of milligrams. | 3, 6, 12 hours after surgery and daily assessed at 24, 48, 72, 96 and 120 hours after surgery | 
| Post-operative consumption of daily non-morphine analgesics (milligrams) | Including Pacetamol, Nefopam, ketoprofene, Ketamine in milligrams. | 24, 48, 72, 96 and 120 hours after surgery | 
| Rate of painful patients | Proportion of patients having had at least one VRS >3 | 24 and 48 hours after surgery | 
| FQoR-15 score at 48 hours | The quality of postoperative recovery reassessed 48 hours after surgery by the FQoR-15; Value of the French Quality of Recovery-15 score (minimum value of 0 and maximum value of 150, with a higher score for a better outcome). The QoR-15 questionnaires will be completed by the patient himself whenever possible, who could be helped by a nurse blinded to the assignment group. | 48 hours after surgery | 
| Rate of patients with at least one complication of LRA | Proportion of patients with at least one complication of LRA: systemic intoxication with local anesthetics within 3 hours after injection, hematoma or infection at the puncture site. | 30 days | 
| Rate of postoperative complications | The proportion of patients with at least one major postoperative complication of cardiac surgery during hospitalization: de novo postoperative atrial fibrillation, revision surgery, respiratory failure, mediastinitis, neurological complication, acute renal failure, gastrointestinal complication, infectious complication with bacteremia, pneumothorax, infectious pneumonitis. | 30 days | 
| Rate of patients return to preoperative weight | Proportion of patient return to announced weight at the pre-anaesthetic consultation (truncating the weight in kg) | Noted at day 3 and 5 after surgery | 
| Rate of patients return to a transit | Proportion of patient return to a transit (including solid or gaseous transit) | Noted at day 3 and 5 after surgery | 
| Extubation time (hours) | Measured in number of hours since arrival in intensive care (between arrival in intensive care and the first attempt at extubation); | Noted at Day 30 | 
| Duration of hospitalization. (days) | The length of stay in post-operative intensive care (between arrival in intensive care and leaving the service) and in the hospital counted in number of days started. | Noted at Day 30 | 
| Rate of readmission to intensive care. | The proportion of patients admitted in the intensive care unit whatever the reason, censored at 30 days. | Noted at Day 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LRA, Block, ERAS, FQOR-15, QOR-15, Transversus thoracic block, Parasternal block, Cardiac surgery, Analgesia, PIP (parasternal intercostal plane block), Régional anesthesia