PK/PD Levobupivacaine With and Without Epinephrine After Ultrasound Guided ESP Block

Pharmacokinetics and Pharmacodynamics for Levobupivacaine With and Without Epinephrine After Ultrasound Guided Erector Spinae Plane Block

Currently there is no standardized management or single technique to manage postoperative pain after Video-assisted thoracic surgery (VATS), there are many options available ranging from intravenous opioids, morphine or fentanyl Patient-controlled analgesia (PCA), peripheral nerve blocks, intercostals, paravertebral and epidural blocks. Erector Spinal Block (ESP), this blocks the ventral and dorsal branch of the unilateral thoracic roots. It corresponds to an interfacial block that produces an extensive multidermatomal sensitive block with a single puncture, covering the anterior, lateral and posterior aspect of the thorax. One of its main advantages would be safety, possible less damage to nerves and pneumothorax, as well as the simplicity of execution of this block. What has positioned it as another analgesic alternative in this type of surgery.

The pharmacokinetic profile that local anesthetics would have when injected into this interfacial compartment has not yet been described, and what the real impact of the use of vasoconstrictor will be in terms of plasma levels and duration of the block.

Our objective is to compare the plasma levels of levobupivacaine achieved after performing an ESP Block with or without epinephrine.

Study Overview

• Status: Unknown
• Conditions: Surgery; Nerve Block; Anesthetic Toxicity; Anesthetics Complications; Bupivacaine Overdose
• Intervention / Treatment: Drug: Levobupivacaine 0.25% with epinephrine 5 ug/ml; Drug: Levobupivacaine 0.25% without epinephrine 5 ug/ml

Detailed Description

Video-assisted thoracic surgery (VATS) is one of the most common procedures performed in thoracic surgery, mainly because it has made it possible to solve many pathologies that previously required a thoracotomy with all the complications that that meant. VATS has been shown to be beneficial for patients, for many reasons such as lower mortality, better postoperative lung function, and shorter stay during hospitalization.

Less invasive procedures such as VATS, where the surgical incision is small and avoids costal resection, produces less postoperative pain when compared to a thoracotomy, this has been objectified by numerous studies that have found lower scores on the numerical verbal scale (NVE) and fewer requirements for pain relievers. Despite the fact that VATS produces less acute postoperative pain (VNS 4-5 on the first postoperative day in VATS vs VNS 6 in thoracotomies), the incidence of chronic postoperative pain ranges from 20 to 47%, which is comparable to thoracotomy, mainly due to damage to the intercostal nerves and inadequate analgesia.

It has been seen that one of the factors associated with the appearance of chronic pain after chest surgery is severe acute pain in the first three postoperative days. Acute pain in VATS is caused by surgical trauma to muscular and bone structures of the thorax, achieving good analgesia is important to maintain adequate respiratory function and avoid complications such as atelectasis, hypoxemia and possible pneumonia.

Currently, there is no standardized management or single technique to manage postoperative pain after VATS, there are many options available ranging from intravenous opioids, morphine or fentanyl Patient-controlled analgesia, peripheral nerve blocks, intercostals, paravertebral and epidural blocks. Each of them with advantages and disadvantages, but without being able to demonstrate a clear superiority between them, both the paravertebral and epidural blocks are the ones that accumulate the most reports in the literature regarding the management of postoperative pain, but at the same time they are not exempt from complications such as technical failure, hypotension and difficulty of the procedure. In addition to documenting a low use of thoracic epidurals in VATS.

At the end of 2016, the description of the Erector Spinal Block (ESP) by Forero was published, it blocks the ventral and dorsal branch of the unilateral thoracic roots. It corresponds to an interfacial block that produces an extensive multidermatomal sensitive block with a single puncture, covering the anterior, lateral and posterior aspect of the thorax. One of its main advantages would be safety, possible less nerve damage and pneumothorax, as well as the simplicity of execution of this block. What has positioned it as another analgesic alternative in this type of surgery.

In ESP, the pharmacokinetic (PK) profile that local anesthetics would have when injected into this interfacial compartment has not yet been described, and what will be the real impact of the use of vasoconstrictor in terms of plasma levels and duration of the block.

Considering the above, it is important to know the pharmacodynamics of levobupivacaine after performing an ESP block with ultrasonography in order to know the risks of toxicity from local anesthetics as well as to clinically characterize this block in patients who will undergo VATS.

The first objective of this study is to compare the plasma levels of levobupivacaine achieved after performing an ESP Block with or without epinephrine. As secondary objectives, it is proposed to characterize the block in terms of duration, pain, opioid requirements in the first 24 hours and adverse events, in both groups.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andrea Araneda, MD; Phone Number: 223543270; Email: andreaaraneda10@yahoo.es

Study Locations

• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 450881
      • Recruiting
      • Pontificia Universidad Catolica de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Indication of VATS
• ASA I-II
• Body mass index (BMI) 20-34 kg / m2

Exclusion Criteria:

• Patients with conversion to thoracotomy
• History of chronic pain
• Drug abuse
• Psychiatric illness
• Allergic to some of the drugs used in the study
• Chronic analgesic users
• History of peripheral neuropathy
• Who refuse the procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I Epi; The ESP will be performed under ultrasound vision at T5 level, with the patient seated. Once the ultrasound image is achieved, a 100 mm, 20 G Stimuplex needle will be punctured and a solution of levobupivacaine 0.25% with epinephrine 5 ug/ml completing a volume of 20 ml.	Drug: Levobupivacaine 0.25% with epinephrine 5 ug/ml; The block will be performed under ultrasound vision at T5 level, with the patient seated. Once the ultrasound image is achieved, a 100 mm, 20 G Stimuplex needle will be punctured and a solution of levobupivacaine 0.25% with epinephrine 5 ug / ml until completing a volume of 20 ml in fractional form.; Other Names: Bupivacaine; ESP
Active Comparator: Group II no Epi; The ESP will be performed under ultrasound vision at T5 level, with the patient seated. Once the ultrasound image is achieved, a 100 mm, 20 G Stimuplex needle will be punctured and a solution of levobupivacaine 0.25% without epinephrine completing a volume of 20 ml.	Drug: Levobupivacaine 0.25% without epinephrine 5 ug/ml; The block will be performed under ultrasound vision at T5 level, with the patient seated. Once the ultrasound image is achieved, a 100 mm, 20 G Stimuplex needle will be punctured and a solution of levobupivacaine 0.25% without epinephrine 5 ug / ml until completing a volume of 20 ml in fractional form.; Other Names: Bupivacaine; ESP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of levobupivacaine	Levobupivacaine plasma levels will be measured using High-performance liquid chromatography.	5, 10, 20, 30, 60, 90 minutes post block.
Changes in plasma levels levobupivacaine of the group I v/s group II	To assess the changes in plasma levels of the group I with epinephrine versus the group II without epinephrine.	5, 10, 20, 30, 60, 90 minutes post block.
Sensitive skin extension	Determine the sensitive skin extension of ESP after its performance using pinprick and temperature discrimination using an alcohol swab.	15 minutes post-block

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Heart rate (bpm)	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Pulse oximetry	% oximetry saturation	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Pain measured	Pain measured by Verbal Numerical Scale (VNS) 0 to 10. 0 = no pain. 10 = worse pain.	Every 15 minutes per 2 hours in the PACU and 12 hrs, 24 hrs, 48 hrs during hospitalization
Hemodynamics	Invasive arterial pressure (mmHg)	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Consumption of morphine or its equivalents	Consumption of morphine or its equivalents (mg/kg/hr)	During the first 48 hours including intraoperative and postoperative

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Investigators: Principal Investigator: Andrea Araneda, MD, Clinician

Publications and helpful links

General Publications

• Corvetto MA, Echevarria GC, De La Fuente N, Mosqueira L, Solari S, Altermatt FR. Comparison of plasma concentrations of levobupivacaine with and without epinephrine for transversus abdominis plane block. Reg Anesth Pain Med. 2012 Nov-Dec;37(6):633-7. doi: 10.1097/AAP.0b013e31826c330a.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Perioperative Care; ESP; Bupivacaine Overdose; VATS surgery
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Drug Overdose; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Bupivacaine; Levobupivacaine; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: 170627010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Procedure performance of ESP in terms of duration and user satisfaction
• IPD Sharing Time Frame: After the paper publication
• IPD Sharing Access Criteria: Researchers and clinicians related to the analgesic management of patients, upon formal request via e-mail to the research director.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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