Neurological Events and Unforeseen Risks After Locoregional-anesthesia (NEURAL)

This is a multicenter, prospective, observational study aimed at determining the incidence of neurological and non-neurological complications following locoregional anesthesia procedures. The study will collect data on events such as nerve injury, hematoma, pneumothorax, and local anesthetic systemic toxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: Regional Anesthesia; Regional Anesthesia Block
• Intervention / Treatment: Other: Observational assessment after regional anesthesia

Detailed Description

Locoregional anesthesia is generally considered safe, but rare neurological and systemic complications have been reported. Current data on the true incidence of these complications are limited and often derived from small sample sizes or registries. The NEURAL study aims to fill this knowledge gap by prospectively collecting data on complications following single-shot nerve blocks in the upper limb, lower limb, and fascial plane. In addition to incidence, the study will investigate potential risk factors for these complications.

• Study Type: Observational
• Enrollment (Estimated): 3396

Contacts and Locations

• Study Contact: Name: Cristina Cacciagrano Clinical Reasearch Office SIAARTI; Phone Number: +39 06 4452816; Email: ricerca@siaarti.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) undergoing single-shot locoregional anesthesia of the upper limb, lower limb, or fascial blocks.

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Scheduled to undergo a single-shot nerve or fascial plane block.
• Ability to provide written informed consent.

Exclusion Criteria:

• Performance of more than one single-shot nerve or fascial plane block within the same anatomical region or sensory distribution during the same procedure.
• Use of continuous nerve or fascial plane catheter-based anesthesia.
• Presence of a language barrier that, in the investigator's judgment, would prevent adequate follow-up.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Single group of enrolled patients; Adult patients (≥18 years) undergoing single-shot upper limb, lower limb, or fascial plane regional anesthesia. All participants meeting inclusion criteria and providing informed consent will be enrolled consecutively.

Other: Observational assessment after regional anesthesia; Adult patients undergoing single-shot regional anesthesia, including: Upper limb blocks - interscalene, superior trunk, supraclavicular, infraclavicular (coracoid, retroclavicular, costoclavicular), suprascapular (anterior, posterior), axillary, and superficial/intermediate/deep cervical plexus blocks. Lower limb blocks - lumbar, sacral, fascia iliaca (supra/infrainguinal), adductor canal, PENG, femoral, femoral triangle, sciatic (anterior, transgluteal, infragluteal, popliteal), nerve to vastus medialis, genicular, IPACK, common peroneal, ankle, and pudendal blocks. Fascial plane blocks - rectus sheath, ilioinguinal/iliohypogastric, TAP (standard/subcostal/midaxillary), ESP, serratus anterior (deep/superficial), parasternal intercostal (superficial/deep), interpectoral, transversalis fascia, rhomboid intercostal, retrolaminar, quadratus lumborum (anterior/lateral/posterior), paravertebral, intertransverse process, and pectoserratus blocks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Composite Complications Following Single-Shot Locoregional Anesthesia	Incidence of any major complication - including nerve injury, hematoma requiring medical intervention, pneumothorax, or local anesthetic systemic toxicity (LAST) - following single-shot locoregional anesthesia. The rate is calculated as the number of procedures with at least one complication divided by the total number of procedures performed.	From the time of the locoregional anesthesia procedure up to 30 days post-procedure (periprocedural and early postoperative period, with follow-up at 24 hours, 48 hours, 15 days, and 30 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Complications in Upper Limb Nerve Blocks	Incidence of each complication type (nerve injury, hematoma, pneumothorax, LAST) following upper limb single-shot nerve blocks. Calculated as the number of events divided by the total number of upper limb procedures	From the procedure to 30 days post-procedure.
Incidence of Complications in Fascial Plane Blocks	Incidence of each complication type (nerve injury, hematoma, pneumothorax, LAST) following fascial plane single-shot blocks.	From the procedure to 30 days post-procedure.
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Age	Measured in years	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Gender	Using a dichotomic male/female framework	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Body Mass Index	Calculated dividing a person's weight in kilograms by the square of their height in meters (BMI = weight ÷ height²) (kg/cm²)	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Presence of comorbidities	Hypertension, diabetes, and central or peripheral neuropathies each expressed dichotomically as "Yes" (present) or "No" (absent).	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Use of anticoagulant or antiplatelet therapy	Use of anticogulants and/or antiplatetets drugs expressed as a Yes or No	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Use of sedative during the block procedure	Use of any sedative agents during the block procedure reported as a Yes or No	Periprocedural
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Pain at injection	Reported pain during the injection of local anesthetics expressed as a Yes or No	Baseline
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Ultrasound guidance	Use of ultrasound guidance to perform the block, measured with a "Yes" or "No" variable	Periprocedural
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Local anesthetic used to perform the block	Name, volume(ml) and dose(mg) of the local anesthetic used to perform the block	Periprocedural
(Predictor of Complications in Upper Limb, Lower Limb or Fascial Plane Blocks) Adjuvants used to perform the block	Name, volume(ml) and dose(mcg) of the adjuvants used to perform the block	Periprocedural

Collaborators and Investigators

• Sponsor: Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva
• Investigators: Principal Investigator: Alessandro De Cassai Prof., MD, UOC Istituto di Anestesia e Rianimazione, Azienda Ospedale Università di Padova

Publications and helpful links

General Publications

• Neal JM, Barrington MJ, Brull R, Hadzic A, Hebl JR, Horlocker TT, Huntoon MA, Kopp SL, Rathmell JP, Watson JC. The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015. Reg Anesth Pain Med. 2015 Sep-Oct;40(5):401-30. doi: 10.1097/AAP.0000000000000286.
• Gitman M, Fettiplace MR, Weinberg GL, Neal JM, Barrington MJ. Local Anesthetic Systemic Toxicity: A Narrative Literature Review and Clinical Update on Prevention, Diagnosis, and Management. Plast Reconstr Surg. 2019 Sep;144(3):783-795. doi: 10.1097/PRS.0000000000005989.
• McLeod GA, Sadler A, Hales TG. Traumatic needle damage to nerves during regional anesthesia: presentation of a novel mechanotransduction hypothesis. Reg Anesth Pain Med. 2022 Jul 25:rapm-2022-103583. doi: 10.1136/rapm-2022-103583. Online ahead of print.
• El-Boghdadly K, Wolmarans M, Stengel AD, Albrecht E, Chin KJ, Elsharkawy H, Kopp S, Mariano ER, Xu JL, Adhikary S, Altiparmak B, Barrington MJ, Bloc S, Blanco R, Boretsky K, Borglum J, Breebaart M, Burckett-St Laurent D, Capdevila X, Carvalho B, Chuan A, Coppens S, Costache I, Dam M, Egeler C, Fajardo M, Gadsden J, Gautier PE, Grant SA, Hadzic A, Hebbard P, Hernandez N, Hogg R, Holtz M, Johnson RL, Karmakar MK, Kessler P, Kwofie K, Lobo C, Ludwin D, MacFarlane A, McDonnell J, McLeod G, Merjavy P, Moran E, O'Donnell BD, Parras T, Pawa A, Perlas A, Rojas Gomez MF, Sala-Blanch X, Saporito A, Sinha SK, Soffin EM, Thottungal A, Tsui BCH, Tulgar S, Turbitt L, Uppal V, van Geffen GJ, Volk T, Elkassabany NM. Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of abdominal wall, paraspinal, and chest wall blocks. Reg Anesth Pain Med. 2021 Jul;46(7):571-580. doi: 10.1136/rapm-2020-102451.
• El-Boghdadly K, Albrecht E, Wolmarans M, Mariano ER, Kopp S, Perlas A, Thottungal A, Gadsden J, Tulgar S, Adhikary S, Aguirre J, Agur AMR, Altiparmak B, Barrington MJ, Bedforth N, Blanco R, Bloc S, Boretsky K, Bowness J, Breebaart M, Burckett-St Laurent D, Carvalho B, Chelly JE, Chin KJ, Chuan A, Coppens S, Costache I, Dam M, Desmet M, Dhir S, Egeler C, Elsharkawy H, Bendtsen TF, Fox B, Franco CD, Gautier PE, Grant SA, Grape S, Guheen C, Harbell MW, Hebbard P, Hernandez N, Hogg RMG, Holtz M, Ihnatsenka B, Ilfeld BM, Ip VHY, Johnson RL, Kalagara H, Kessler P, Kwofie MK, Le-Wendling L, Lirk P, Lobo C, Ludwin D, Macfarlane AJR, Makris A, McCartney C, McDonnell J, McLeod GA, Memtsoudis SG, Merjavy P, Moran EML, Nader A, Neal JM, Niazi AU, Njathi-Ori C, O'Donnell BD, Oldman M, Orebaugh SL, Parras T, Pawa A, Peng P, Porter S, Pulos BP, Sala-Blanch X, Saporito A, Sauter AR, Schwenk ES, Sebastian MP, Sidhu N, Sinha SK, Soffin EM, Stimpson J, Tang R, Tsui BCH, Turbitt L, Uppal V, van Geffen GJ, Vermeylen K, Vlassakov K, Volk T, Xu JL, Elkassabany NM. Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of upper and lower limb nerve blocks. Reg Anesth Pain Med. 2024 Nov 4;49(11):782-792. doi: 10.1136/rapm-2023-104884.
• Long B, Chavez S, Gottlieb M, Montrief T, Brady WJ. Local anesthetic systemic toxicity: A narrative review for emergency clinicians. Am J Emerg Med. 2022 Sep;59:42-48. doi: 10.1016/j.ajem.2022.06.017. Epub 2022 Jun 13.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 2, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Toxicity; Pneumothorax; Nerve Injury; Local Anesthetic Systemic; Upper limb block; Lower limb block; Fascial plane block
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Pneumothorax
• Other Study ID Numbers: NEURAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No