Ropivacaine Plasma Concentrations After Fascial Blocks in Elective Cardio-thoracic and Abdominal Surgery

Ropivacaine Plasma Concentrations After Fascial Blocks in Elective Cardio-thoracic and Abdominal Surgery: an Observational, Monocentric Study

Primary aim: observe the incidence of systemic toxicity from local anesthetic (LAST) after performing fascial blocks in patients undergoing elective cardio-thoracic and abdominal surgery.

Secondary aim: describe the pharmacokinetic profile of the local anesthetic (ropivacaine) and assess peri-procedural complications, post-operative pain and opiate consumption in the first 24 hours.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain; Regional Anesthesia Morbidity; Local Anesthetic Toxicity
• Intervention / Treatment: Procedure: Fascial block

Detailed Description

Loco-regional anesthesia (LRA) procedures have acquired, in recent years, increasing importance in the peri-operative control of pain in the field of cardio-thoracic and abdominal surgery. To date, they are recognized as part of the multimodal analgesia underlying the Enhanced Recovery After Surgery (ERAS) protocols as they have demonstrated a better efficacy in post-operative pain control than the use of opiates alone and allow a significant reduction in the use of opioids in the postoperative period.

The advent of ultrasound-guided LRA procedures has led to the development of numerous fascial blocks, which involve the injection, at the level of the muscle-fascial planes, of an abundant volume of low-concentration local anesthetic to allow spread to adjacent nerve structures. The fascial blocks represent a valid alternative to epidural analgesia for the control of postoperative pain in the thoracoabdominal area, as they are characterized by a rapid learning curve and a lower risk of periprocedural complications compared to neuraxial anesthesia procedures.

The main chest wall nerve blocks used in clinical practice include the pectoral nerve block (PECS1 and PECS2) and serrate anterior plane block (SAP) at the level of the anterior chest wall; the spinal erector plane (ESP) block and the paravertebral block at the level of the posterior thoracic wall.

LRA techniques also play a fundamental role in the field of abdominal surgery, especially in the context of multimodal analgesia, aiming to reduce consumption and, consequently, the secondary side effects of the use of opioids.

In the case of laparotomic major abdominal surgery, the use of epidural analgesia has been shown to be effective in reducing post-operative pain, opioid consumption, and recovery of gastrointestinal function, but has not shown a significant reduction in the duration of hospitalization and of post-operative complications.

Subarachnoid analgesia is mainly indicated in laparoscopic abdominal surgery. Numerous studies have shown an efficacy similar to epidural anesthesia in controlling pain and reducing opioid consumption as well as allowing early patient mobilization and a shorter length of hospital stay.

The transverse abdominal plane (TAP) block has a rapid learning curve and has been shown to be effective in controlling postoperative analgesia, reducing opioids consumption and reducing hospital stay.

The lumbar square (QoL) block has a greater efficacy than other abdominal wall blocks on the visceral component of pain. A recent meta-analysis demonstrated greater efficacy than TAP in the control of post-operative pain and guarantees a longer duration of analgesia.

The effectiveness of the anesthetic depends on its local action at the level of the nervous structures "wetted" by the drug; a variable amount of local anesthetic undergoes systemic absorption and might be responsible for part of the analgesic effect, but above all for the possible appearance of systemic side effects.10 The amount of drug redistributing in the blood depends on the total dose of the drug administered, the route of administration, and the vascularity of the injection site.

Ropivacaine is a long-acting amide local anesthetic frequently used in LRA procedures. Unlike other drugs of the same family, the levorotatory enantiomer S-Ropivacaine is characterized by reduced lipophilicity and this determines a lower risk of toxicity to the Central Nervous System (CNS) and cardiovascular system (CVS). The drug exhibits high plasma protein binding (α1-acid glycoprotein), linear absorption kinetics, hepatic metabolism, and renal elimination.

Systemic toxicity from Local anesthetic (LAST) represents a complication of local anesthetic administration and is directly dependent on the plasma concentration of the drug. The signs and symptoms of LAST occur progressively and mainly affect the CNS (visual disturbances, perioral hypoaesthesia, dizziness, euphoria, muscle stiffness, spasms, convulsions) and the CVS system (hypotension, bradycardia, arrhythmias, cardiac arrest).

The study aims to observe the onset of local anesthetic toxicity (LAST) after performing fascial blocks in patients undergoing elective cardiothoracic and abdominal surgery.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Luca Brazzi, Professor; Phone Number: (+39) 011 633 5505; Email: luca.brazzi@unito.it

Study Locations

• Italy
  • Turin, Italy, 10100
    • Recruiting
    • AOU Citta della Salute e della Scienza di Torino
    • Contact: Luca Brazzi, PhD; Phone Number: +39 011 6335501; Email: luca.brazzi@unito.it
    • Principal Investigator: Edoardo Ceraolo, MD
    • Sub-Investigator: Giulio L Rosboch, MD
    • Sub-Investigator: Giorgia Montrucchio, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study involves the enrollment of patients who will undergo elective cardio-thoracic and / or abdominal surgery at the A.O.U. Città della Salute e della Scienza of Turin, with clinical indications for the execution of band blocks for analgesic purposes.

Description

Inclusion Criteria:

• Patients undergoing elective cardio-thoracic and abdominal surgery with indications for the execution of fascial block
• Signature of the informed consent form.

Exclusion Criteria:

• Lack of informed consent form.
• Previous neuropsychiatric pathologies or neuropathies of the back / trunk
• Severe renal insufficiency (GFR <30ml / min)
• Severe hepatic insufficiency or alteration of liver enzymes
• Contraindications to LRA procedures (injection site infection, coagulopathy, allergy / hypersensitivity to local anesthetics)
• Pregnancy
• Hypoalbuminemia
• Hospitalization in intensive care and / or post-operative sedation> 24 hours

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study Cohort; Patients undergoing fascial blocks in elective cardio-thoracic and abdominal surgery.

Procedure: Fascial block; The end of the drug infusion will be considered the time zero (T0); subsequently blood samples (4ml) will be taken at pre-established time intervals (after 5, 15, 30, 60, 120 and 180 minutes). Blood samples will be collected in test tubes and centrifuged within 1 hour of collection; subsequently they will be stored at a low temperature and transported to the reference analysis laboratory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of systemic toxicity from local anesthetic signs and symptoms.	The typical presentation of LAST usually begins with prodromal symptoms and signs, such as perioral numbness, tinnitus, agitation, dysarthria, and confusion. These may be followed by more severe central nervous system (CNS) derangements such as seizures and coma.	6 hours after surgery
Incidence of systemic toxicity from local anesthetic signs and symptoms.	The typical presentation of LAST usually begins with prodromal symptoms and signs, such as perioral numbness, tinnitus, agitation, dysarthria, and confusion. These may be followed by more severe central nervous system (CNS) derangements such as seizures and coma.	12 hours after surgery
Incidence of systemic toxicity from local anesthetic signs and symptoms.	The typical presentation of LAST usually begins with prodromal symptoms and signs, such as perioral numbness, tinnitus, agitation, dysarthria, and confusion. These may be followed by more severe central nervous system (CNS) derangements such as seizures and coma.	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ropivacaine concentration	Ropivacaine plasma concentration	5 minutes from the fascial block execution
Ropivacaine concentration	Ropivacaine plasma concentration	15 minutes from the fascial block execution
Ropivacaine concentration	Ropivacaine plasma concentration	30 minutes from the fascial block execution
Ropivacaine concentration	Ropivacaine plasma concentration	60 minutes from the fascial block execution
Ropivacaine concentration	Ropivacaine plasma concentration	120 minutes from the fascial block execution
Ropivacaine concentration	Ropivacaine plasma concentration	180 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	5 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	15 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	30 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	60 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	120 minutes from the fascial block execution
Ropivacaine latency time	Ropivacaine maximum plasma concentration and latency time between the execution of the block and the achievement of Cmax	180 minutes from the fascial block execution
Anesthesia effectiveness	Global extension of the anesthetized skin surface, measured by Pinprick test.	Immediately after fascial block
Post-operative pain	Pain after awakening, estimated using the numeric scale for pain assessment (min 0 max 10, 10 equals worst outcome)	0 hours after awakening
Post-operative pain	Pain after awakening, estimated using the numeric scale for pain assessment (min 0 max 10, 10 equals worst outcome)	1 hour after awakening
Post-operative pain	Pain after awakening, estimated using the numeric scale for pain assessment (min 0 max 10, 10 equals worst outcome)	6 hours after awakening
Post-operative pain	Pain after awakening, estimated using the numeric scale for pain assessment (min 0 max 10, 10 equals worst outcome)	12 hours after awakening
Post-operative pain	Pain after awakening, estimated using the numeric scale for pain assessment (min 0 max 10, 10 equals worst outcome)	24 hours after awakening
Opioid requirement	Pain after awakening, estimated using morphine equivalent milligrams	0 hours after awakening
Opioid requirement	Pain after awakening, estimated using morphine equivalent milligrams	1 hour after awakening
Opioid requirement	Pain after awakening, estimated using morphine equivalent milligrams	6 hours after awakening
Opioid requirement	Pain after awakening, estimated using morphine equivalent milligrams	12 hours after awakening
Opioid requirement	Pain after awakening, estimated using morphine equivalent milligrams	24 hours after awakening

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Investigators: Principal Investigator: Edoardo Ceraolo, MD, AOU Citta della Salute e della Scienza di Torino

Publications and helpful links

General Publications

• Nagaraja PS, Ragavendran S, Singh NG, Asai O, Bhavya G, Manjunath N, Rajesh K. Comparison of continuous thoracic epidural analgesia with bilateral erector spinae plane block for perioperative pain management in cardiac surgery. Ann Card Anaesth. 2018 Jul-Sep;21(3):323-327. doi: 10.4103/aca.ACA_16_18.
• Crumley S, Schraag S. The role of local anaesthetic techniques in ERAS protocols for thoracic surgery. J Thorac Dis. 2018 Mar;10(3):1998-2004. doi: 10.21037/jtd.2018.02.48.
• Chin KJ, Versyck B, Pawa A. Ultrasound-guided fascial plane blocks of the chest wall: a state-of-the-art review. Anaesthesia. 2021 Jan;76 Suppl 1:110-126. doi: 10.1111/anae.15276.
• Jack JM, McLellan E, Versyck B, Englesakis MF, Chin KJ. The role of serratus anterior plane and pectoral nerves blocks in cardiac surgery, thoracic surgery and trauma: a qualitative systematic review. Anaesthesia. 2020 Oct;75(10):1372-1385. doi: 10.1111/anae.15000. Epub 2020 Feb 16.
• Hughes MJ, Ventham NT, McNally S, Harrison E, Wigmore S. Analgesia after open abdominal surgery in the setting of enhanced recovery surgery: a systematic review and meta-analysis. JAMA Surg. 2014 Dec;149(12):1224-30. doi: 10.1001/jamasurg.2014.210.
• Leone S, Di Cianni S, Casati A, Fanelli G. Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed. 2008 Aug;79(2):92-105.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: October 19, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: PRAST

Drug and device information, study documents

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