Clinical trial NCT06356038: Phrenic Nerve Infiltration: Pulmonary Expansion and Pain Control
Official title: Phrenic Nerve Infiltration: a Good Practice to Combine Pulmonary Expansion and Pain Control in Patients With High-risk of Prolonged Air Leak
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prolonged Air Leak
Post-operative Pain
Keywords: prolonged air leak
phrenic nerve
local anaesthetic
Lead sponsor: Azienda Ospedaliera "Sant'Andrea"
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Between January 2021-2023, 65 consecutive patients at risk for PAL (defined in accordance to "2019 Society of Thoracic Surgery score-criteria of PAL") underwent lung resection (lobectomy or sublobar resection) for malignancy. 5 patients were lost. The remaining have been assigned with a 1:2 randomization into: group A (22 patients), received intra-operative phrenic nerve infiltration with Ropivacaine 10 mg/ml in the peri-neurotic fat on the pericardium and group B (38 patients), did not receive infiltration. Data on hemidiaphragm elevation, air leaks, pain at 24 and 72 hours post-surgery, shoulder pain, length of hospital stay, length of chest tube permanence, were retrospectively collected and compared.The aim of the study is to investigate the effect of intra-operative phrenic nerve infiltration with long acting anesthetic in patients at high risk for PAL, improving pulmonary expansion after surgery, and reducing air leaks, while controlling post-operative pain.

Detailed description: This prospective randomized trial received approbation by the institutional review board (Prot. n. 76 SA/2022 RIF. CE 6682/2022) and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients.

Patients were defined at risk for PAL in accordance with "2019 Society of Thoracic Surgery score-criteria of PAL". This is an aggregate score specifically designed for lung resection, assigning an odd risk to each patient based on the most common predictors for prolonged air leak including: Body Mass Index \<_25.5 kg/m2 (7 points); lobectomy or bilobectomy (6 points); forced expiratory volume in 1 second (FEV1) \</= 70% (5 points); male sex (4 points); right upper lobe (3 points). A total score \> 17 is considered high risk for PAL.

All patients received pre-operative physical examination, routine blood tests, pulmonary functional test (spirometry and arterial blood gas analysis) and cardiac tests according to the personal clinical history. Imaging collection includes Total Body Computed Tomography (CT) and Positron Emission Tomography (PET). Central tumours required bronchoscopy to assess an eventual endobronchial invasion and to obtain histological diagnosis. If N1/N2 staging was clinically suspected, patients underwent Endo-Bronchial Ultra-Sonography (EBUS) with eventual Trans-Bronchial Needle Aspiration (TBNA) or mediastinoscopy.

Exclusion criteria for the study were: wedge resections, pneumonectomy, neoplasms infiltrating diaphragm and/or chest wall, patients with congenital or acquired neurological diseases, chronic pain, osteo-muscular pathologies affecting the shoulder.

All candidate patients for surgery underwent lung resection with a muscle sparing thoracotomy (lateral 5-6 cm incision on the fifth intercostal space), to reduce bias due by different surgical approaches on the post-operative pain.

In group A, patients received the intra-operative infiltration of phrenic nerve by the surgeon who injected 10 ml of Ropivacaine 0.75% (the same procedure routinely adopted in our clinical practice of local analgesia at the level of intercostal spaces) in the peri-neurotic pericardial fat, near the diaphragm. Infiltration is made with a deflated lung, after pulmonary resection and chest tube insertion.

Chest tubes were connected to a pleur-evac device with a system to register air leaks (DrentechTM Palm Evo, Redax).

All patients received Chest X-Rays in post-operative day 1, 3, 5. Pain control was assessed using Numeric Rating Scale (NRS), from 0 (no pain) to 10 (maximum level of pain) at 24-hors and 72-hours from surgery. Even the need for additional antalgic medicaments was registered. All patients started pulmonary rehabilitation programs (mobilization and respiratory exercises) on post-operative day 1.

Data were collected and stored in an Excel database (Microsoft Corp, Redmond, Wash) and were analyzed using statistical package SPSS, version 25.0 (SPSS Software, IBM Corp., Armonk, NY, USA). Data collected were then analyzed and compared between the two groups. Values were expressed as mean ± standard deviation (SD) for continuous variables and as absolute number and percentage in categorical variables. Comparison of categorical variables was performed by c2 test using Fischer exact test. Comparison of qualitative variables was performed by student t-test. Significance was defined as a P value of less than 0.05. The adjusted odd ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate and measure the association using 1000 bootstrapping samples.

Eligibility criteria: Inclusion Criteria:

* patients affected by lung cancer eligible for surgery
* patients with high risk for post-operative prolonged air leaks: Body Mass Index \<_25.5 kg/m2 (7 points); lobectomy or bilobectomy (6 points); forced expiratory volume in 1 second (FEV1) \</= 70% (5 points); male sex (4 points); right upper lobe (3 points). A total score \> 17 is considered high risk for PAL

Exclusion Criteria:

* metastatic desease
* patients not eligible for surgery because low performance status
* pneumonectomy/ wedge resections
* tumors infiltrating phrenic nerve/ diaphragm
* patients with neurological disorders causing chronic pain

Primary outcomes:
measure: rate of pulmonary expansion due by phrenic nerve intra-operative local anaesthetic infiltration
timeFrame: two years
Secondary outcomes:
measure: rate of post-operative pain control after intra-operative phrenic nerve infiltration with local anaesthetic
timeFrame: two years
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Azienda Ospedaliera "Sant'Andrea"
Study officials:
References: