Ropivacaine Pharmacokinetics in ESP Blocks

• Conditions: Local Anesthetic Systemic Toxicity; Pain; Quality of Recovery

• Registration Number: NCT04807504
• Lead Sponsor: Thomas Jefferson University

Brief Summary

This is a pharmacokinetic study to determine risk of local anesthetic systemic toxicity of ropivacaine when used in erector spinae plane blocks for thoracic surgery. Through serial blood sampling and the use of NONMEM population pharmacokinetic analysis this risk will be determined for the study population and other populations as well. Pain and quality of recovery will also be assessed.The erector spinae plane (ESP) block was first described in 2016 as a novel fascial plane block that provided analgesia for thoracic neuropathic pain. Since then hundreds of articles have been published that have reported use of the ESP block for indications such as rib fractures, breast surgery, abdominal surgery, and even shoulder surgery. It has also been studied in thoracic surgery and clinical experience confirms that patients undergoing video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracic surgery experience satisfactory analgesia with ESP blocks. Because the block location is further from the neuraxis than both epidural and paravertebral blocks, ESP blocks have been suggested as a safer alternative to these older blocks but safety data have not yet been generated. In particular, the risk of local anesthetic systemic toxicity (LAST) has not been studied in ESP blocks. While the pharmacokinetics of ropivacaine used for thoracic paravertebral blocks have been established, similar studies have yet to be performed for the newer ESP block. Of particular concern for ESP blocks are two factors not present in some other blocks with established safety: 1). significant intercostal spread has been noted in anatomical studies, which could put patients at risk for LAST and 2). some of the proposed dosing regimens involve the intermittent injection of large bolus doses of local anesthetic. While measurement of arterial plasma levels is useful and necessary to study the safety of ropivacaine given in ESP blocks, the measurements alone do not allow for prediction of plasma levels that would occur in populations as a whole. Nonmem is a population pharmacokinetic application that provides estimates of mean parameters and residual variability in pharmacokinetic values across populations and has been shown to generate better estimates than the two-stage approach. Nonmem will be used in this study to predict pharmacokinetics in populations with different characteristics than the one being studied here, which would create generalizable results.

Detailed Description

The erector spinae plane (ESP) block was first described in 2016 as a novel fascial plane block that provided analgesia for thoracic neuropathic pain. Since then hundreds of articles have been published that have reported use of the ESP block for indications such as rib fractures, breast surgery, abdominal surgery, and even shoulder surgery. It has also been studied in thoracic surgery and our clinical experience confirms that patients undergoing video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracic surgery experience satisfactory analgesia with ESP blocks. Because the block location is further from the neuraxis than both epidural and paravertebral blocks, ESP blocks have been suggested as a safer alternative to these older blocks but safety data have not yet been generated. In particular, the risk of local anesthetic systemic toxicity (LAST) has not been studied in ESP blocks. While the pharmacokinetics of ropivacaine used for thoracic paravertebral blocks have been established, similar studies have yet to be performed for the newer ESP block. Of particular concern for ESP blocks are two factors not present in some other blocks with established safety: 1). significant intercostal spread has been noted in anatomical studies, which could put patients at risk for LAST and 2). some of the proposed dosing regimens involve the intermittent injection of large bolus doses of local anesthetic. While measurement of arterial plasma levels is useful and necessary to study the safety of ropivacaine given in ESP blocks, the measurements alone do not allow for prediction of plasma levels that would occur in populations as a whole. Nonmem is a population pharmacokinetic application that provides estimates of mean parameters and residual variability in pharmacokinetic values across populations and has been shown to generate better estimates than the two-stage approach. Nonmem will be used in this study to predict pharmacokinetics in populations with different characteristics than the one being studied here, which would create generalizable results.

Study Timeline

• Study First Submitted: 2021-03-17
• Study First Submitted QC: 2021-03-17
• Study First Posted: 2021-03-19
• Study Start: 2021-03-26
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-03
• Last Update Posted: 2022-06-06
• Primary Completion: 2022-11
• Study Completion: 2022-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• undergoing robotic or video-assisted thoracic surgery
• able to speak English

Exclusion Criteria

• active liver disease
• active renal disease
• ropivacaine allergy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean maximum plasma concentration of ropivacaine	24 hours

Secondary Outcome Measures

Name	Time	Method
Opioid consumption	24 hours	Mean amount of opioids consumed in morphine milligram equivalents
Sensory levels	12 hours	Mean number of dermatomes blocked after erector spinae plane block
Quality of recovery	24 hours	The mean quality of recovery 15 survey scores (0-150 where 0 is worst quality of recovery and 150 is best)
Mean pain scores	24 hours	Numerical rating scale pain scores (0-10 where 0 is no pain and 10 is worst pain imaginable)

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States