Diaphragmatic Paralysis Comparison Between Local Anesthetic Volumen Doses After Interscalene Block (REDOLEV-2019)

Diaphragmatic Paralysis After Interscalene Brachial Plexus Block: A Randomized, Double-blinded, Unicenter and Controlled Clinical Trial to Reduce the Dose of Levobupivacaine 0,25% 20 ml to 10 ml Undergoing Arthroscopic Shoulder Surgery

Arthroscopic shoulder surgery involves dynamic and severe postoperative pain. Interscalene brachial plexus block (IBPB) provides adequate analgesia but the spread of local anaesthetics administered causes a phrenic nerve block which entrains a non-negligible incidence of Hemidiaphragmatic paralysis acute (HDPA).

This is a comparative, prospective, Unicenter, double-blind, two-arm, randomized and controlled clinical trial. 48 patients will be included.

This RCT would demonstrate a low volume dose IBPB decrease the HDPA after IBPB in patients undergoing SAS, by using spirometry and ultrasound and it will not provide inferior postoperative analgesia according to opioid requirements of postoperative PCA in comparison to standard volume dose used in current practice.

Study Overview

• Status: Completed
• Conditions: Brachial Plexus Block; Diaphragmatic Paralysis
• Intervention / Treatment: Procedure: Interscalene brachial plexus block; Drug: Levobupivacaine Hydrochloride 2.5 MG/ML

Detailed Description

Arthroscopic shoulder surgery involves dynamic and severe postoperative pain. Interscalene brachial plexus block (IBPB) provides adequate analgesia but the spread of local anaesthetics administered causes a phrenic nerve block which entrains a non-negligible incidence of Hemidiaphragmatic paralysis acute (HDPA).

The primary study objective is to determine the HDPA diagnosed by using diaphragmatic thickness index in Ultrasound (US) after Low Volume (10 mL) versus Standard Volume (20 mL) of Levobupivacaine 0,25% for IBPB. Secondary end-points are 1) HDPA diagnosed by using FVC and FEV1 in spirometry, 2) HDPA diagnosed by using diaphragmatic excursion in US, 3) postoperative pain regarding time to first analgesic consumption and 24-hour cumulative total consumption of Patient-controlled analgesia (PCA) pump of Morphine IV and (4) postoperative harms between two trial-arms.

This study is a comparative, prospective, Unicenter, double-blind and two-arm RCT. 48 patients will be included.

This RCT would demonstrate a low volume dose IBPB decrease the HDPA after IBPB in patients undergoing SAS, by using spirometry and ultrasound and it will not provide inferior postoperative analgesia according to opioid requirements of postoperative PCA in comparison to standard volume dose used in current practice.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Zaragoza, Spain, 50012
    • Hospital Universitario Miguel Servet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 to 80 years.
• ASA I-III.
• Scheduled for shoulder arthroscopic shoulder surgery and interscalene brachial plexus block.

Exclusion Criteria:

• Age <18 and >80 years.
• Pregnancy.
• Exclusión to perform IBPB or spirometry.
• Allergy to amide group local anaesthetics, opioids or nonsteroidal anti-inflammatory drugs.
• Background of Pulmonary diseases (chronic obstructive pulmonary disease (COPD) and moderate, severe or not well-controlled asthma), diaphragmatic paralysis or neurological disease with diaphragmatic dysfunction, brachial plexus neuropathy or chronic opioid consumption (more than 3-months consumption or more than oral Morphine 1 mg 1-month).
• Coagulation disorders (INR>3, TTPA > 35 y AP <50%).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard Volume Dose; 24 patients will be included in the Standard Volume Dose arm. 20 ml Levobupivacaine Hydrochloride 2.5 MG/ML will be administered in the Interscalene brachial plexus block before the arthroscopic shoulder surgery.	Procedure: Interscalene brachial plexus block; Interscalene brachial plexus block is a locorregional anaesthesia technique which is indicated in shoulder and upper arm surgery. The goal of this block is to place the needle in the tissue space between the anterior and middle scalene muscles and inject local anesthetic until the spread around the brachial plexus is documented by ultrasound.; Other Names: MeSH Unique ID: D065527; CIE-10 code 3E0T3CZ; Interscalene block; Drug: Levobupivacaine Hydrochloride 2.5 MG/ML; Levobupivacaine Hydrochloride 2.5 MG/ML is an anesthestic product intended for epidural, intradural and perineural administration. Levobupivacaine is chemically described as (S)-l-butyl-2-piperidylformo-2',6'-xylidide hydrochloride. It is a white crystalline powder with a molecular formula of C18H28N2O. HCl, with a molecular weight 324.9. FDA approval: NDA-20997 (1999).; Other Names: Chirocaine® 2.5 MG/ML
EXPERIMENTAL: Low Volume Dose; 24 patients will be included in the Low Volume Dose arm. 10 ml Levobupivacaine Hydrochloride 2.5 MG/ML will be administered in the Interscalene brachial plexus block before the arthroscopic shoulder surgery.	Procedure: Interscalene brachial plexus block; Interscalene brachial plexus block is a locorregional anaesthesia technique which is indicated in shoulder and upper arm surgery. The goal of this block is to place the needle in the tissue space between the anterior and middle scalene muscles and inject local anesthetic until the spread around the brachial plexus is documented by ultrasound.; Other Names: MeSH Unique ID: D065527; CIE-10 code 3E0T3CZ; Interscalene block; Drug: Levobupivacaine Hydrochloride 2.5 MG/ML; Levobupivacaine Hydrochloride 2.5 MG/ML is an anesthestic product intended for epidural, intradural and perineural administration. Levobupivacaine is chemically described as (S)-l-butyl-2-piperidylformo-2',6'-xylidide hydrochloride. It is a white crystalline powder with a molecular formula of C18H28N2O. HCl, with a molecular weight 324.9. FDA approval: NDA-20997 (1999).; Other Names: Chirocaine® 2.5 MG/ML

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Diaphragmatic Thickness Ratio at 4 hours	The primary outcome is the difference in the proportion of patients with Hemidiaphragmatic paralysis acute (HDPA) according to diaphragmatic thickness ratio (DTR) in ultrasounds between the Treatment and Control groups. DTR will be the result of Inspiratory Diaphragmatic Thickness and Expiratory Diaphragmatic Thickness. The ratio will be defined by DTR=IDT/EDT. HDPA after IBPB at 4 hours will be diagnosed with a DTR<1.2.	Before (Baseline) and 4-hour after interscalene brachial plexus block

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline FVC at 4 hours and 24 hours	This secondary outcome is the difference in the proportion of patients with Hemidiaphragmatic paralysis acute (HDPA) according to Forced Vital Capacity (FVC) in spirometry. HDPA will be diagnosed with a CVF diminution of >20%.	Before (Baseline), 4-hour and 24-hour after interscalene brachial plexus block
Change from Baseline FEV1 at 4 hours and 24 hours	This secondary outcome is the difference in the proportion of patients with Hemidiaphragmatic paralysis acute (HDPA) according to forced expiratory volume in one second (FEV1) in spirometry. HDPA will be diagnosed with a FEV1 diminution of >20%.	Before (Baseline), 4-hour and 24-hour after interscalene brachial plexus block
Change from Baseline Diaphragmatic excursion at 4 hours and 24 hours	This secondary outcome is the difference in the proportion of patients with Hemidiaphragmatic paralysis acute (HDPA) according to Diaphragmatic excursion expressed as number of intercostal spaces and motion type. HDPA will be diagnosed with a reduction of >25% number of intercostal spaces or a paradoxal or nule diaphragmatic motion.	Before (Baseline), 4-hour and 24-hour after interscalene brachial plexus block
Postoperative IV morphine consumption	This secondary outcome is the postoperative 24-hour cumulative IV morphine consumption (mg) of Patient controlled analgesia (PCA) pump.	From 4-hour to 24-hour after interscalene brachial plexus block
Postoperative time to first analgesic consumption	This secondary outcome is the time to first analgesic consumption (minutes) of Patient controlled analgesia (PCA) pump.	From 4-hour to 24-hour after interscalene brachial plexus block
Incidence and frequency of Serious Adverse Events (SAE)	This secondary outcome is the incidence, frequency and severity of Serious Adverse Events (SAE) as assessed by CTCAE v4.0 in the two study groups	From performing the interscalene brachial plexus block to finish the 24-hour postoperative follow-up

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria Aragón
• Collaborators: Hospital Miguel Servet
• Investigators: Principal Investigator: Pablo O Forniés, MD, Hospital Miguel Servet

Publications and helpful links

General Publications

• Lopez Escarraga VM, Dubos Espana K, Castillo Bustos RH, Peidro L, Sastre S, Sala-Blanch X. Diaphragmatic thickness ratio (inspiratory/expiratory) as a diagnostic method of diaphragmatic palsy associated with interescalene block. Rev Esp Anestesiol Reanim (Engl Ed). 2018 Feb;65(2):81-89. doi: 10.1016/j.redar.2017.09.008. Epub 2017 Nov 7. English, Spanish.
• Urmey WF, McDonald M. Hemidiaphragmatic paresis during interscalene brachial plexus block: effects on pulmonary function and chest wall mechanics. Anesth Analg. 1992 Mar;74(3):352-7. doi: 10.1213/00000539-199203000-00006.
• Urmey WF, Talts KH, Sharrock NE. One hundred percent incidence of hemidiaphragmatic paresis associated with interscalene brachial plexus anesthesia as diagnosed by ultrasonography. Anesth Analg. 1991 Apr;72(4):498-503. doi: 10.1213/00000539-199104000-00014.
• Thackeray EM, Swenson JD, Gertsch MC, Phillips KM, Steele JW, Burks RT, Tashjian RZ, Greis PE. Diaphragm function after interscalene brachial plexus block: a double-blind, randomized comparison of 0.25% and 0.125% bupivacaine. J Shoulder Elbow Surg. 2013 Mar;22(3):381-6. doi: 10.1016/j.jse.2012.06.011. Epub 2012 Sep 1.
• Stundner O, Meissnitzer M, Brummett CM, Moser S, Forstner R, Kokofer A, Danninger T, Gerner P, Kirchmair L, Fritsch G. Comparison of tissue distribution, phrenic nerve involvement, and epidural spread in standard- vs low-volume ultrasound-guided interscalene plexus block using contrast magnetic resonance imaging: a randomized, controlled trial. Br J Anaesth. 2016 Mar;116(3):405-12. doi: 10.1093/bja/aev550.
• Oliver-Fornies P, Ortega Lahuerta JP, Gomez Gomez R, Gonzalo Pellicer I, Oliden Gutierrez L, Vinuales Cabeza J, Gallego Ligorit L, Orellana Melgar CE. Diaphragmatic paralysis, respiratory function, and postoperative pain after interscalene brachial plexus block with a reduced dose of 10 ml levobupivacaine 0.25% versus a 20 ml dose in patients undergoing arthroscopic shoulder surgery: study protocol for the randomized controlled double-blind REDOLEV study. Trials. 2021 Apr 19;22(1):287. doi: 10.1186/s13063-021-05216-6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 11, 2020
• Primary Completion (ACTUAL): October 20, 2021
• Study Completion (ACTUAL): October 20, 2021

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (ACTUAL): May 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Ultrasound; Postoperative pain; Diaphragmatic Paralysis; Interscalene Brachial Plexus Block; Arthroscopic shoulder surgery.
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Respiratory Insufficiency; Paralysis; Respiratory Paralysis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Levobupivacaine
• Other Study ID Numbers: REDOLEV-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD will be available on file in storage and on the Internet (URL undecided yet) after finishing the data collection for 25 years at the participating site.
• IPD Sharing Time Frame: Starting in February 2021 for 25 years.
• IPD Sharing Access Criteria: To contact to Study Principal Investigator.; To provide to Study Principal Investigator a request to explain the reason to access to IPD study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No