Assessment of Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion

Study Overview
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Brief Summary
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The aim of the study is the assessment of the systemic absorption of local anesthetics during continuous epidural infusion for postoperative pain control.

Detailed Description
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In literature the systemic toxicity of bupivacaine is widely demonstrated, like the minor toxicity of levobupivacaine and ropivacaine at the same anesthetic potency. The are actually no studies in humans confronting levobupivacaine and ropivacaine under the aspect of efficacy and toxicity.The aim of the study is the assessment of the systemic absorption of local anesthetics during continuous epidural infusion for postoperative pain control. Primary outcome: Assessment of the plasmatic equimolar concentrations of levobupivacaine and ropivacaine during continuous epidural infusion Secondary outcome: Assessment of the safety level of the local anesthetic (major difference between haematic concentration of the local anesthetic and neuro-cardiotoxic dose). Difference of the analgesic efficacy between levobupivacaine and ropivacaine. Differences in collateral effects due to the local anesthetic: hypotension and sensitive block. Prospective randomized double-blinded clinical trial

Official Title
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Prospective Randomized Double-blinded Study of Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion

Conditions
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Anesthesia, Surgery

Intervention / Treatment
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* Drug: local anesthetic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA I or ASA II Scheduled for major surgery written informed consent Exclusion Criteria: ASA III, IV Emergency surgery Recovery in intensive care unit after surgery habitual opioid consumption cognitive or mental alterations coagulopathy piastrinemia < 100.000/mm3

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: levobupivacaine<br> | Drug: local anesthetic<br>* postoperative 48h epidural continuous infusion, ropivacaine 0,2% (250ml)+ sufentanil 0,75mcg/ml levobupivacaine 0,125% (250ml)+ sufentanil 0,75mcg/ml<br>* Other names: Naropina;|
| Other: ropivacaine<br> | Drug: local anesthetic<br>* postoperative 48h epidural continuous infusion, ropivacaine 0,2% (250ml)+ sufentanil 0,75mcg/ml levobupivacaine 0,125% (250ml)+ sufentanil 0,75mcg/ml<br>* Other names: Naropina;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of the local anesthetics in study | Assessment of the equivalence of the systemic exposition of levobupivacaine and ropivacaine during 48h continuous epidural infusion with in a range of 15%.Blood samples (8) will be taken for farmacological assessment of local anesthetic plasma concentrations at time (hours) 0,+3h,+6h,+12h,+24h,+48h,+54h,+60h | during 60h after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the pharmacological profile of the local anesthetics in study | Assessment of the therapeutic index (plasma concentration of the local anesthetics in study compared to those described in literature to be related to toxic effects). | during 60h after surgery | 
| Difference between the to groups (at least 25%) in terms of pain control (1 episode of VAS>4) |  | Pain control (VAS, VASm, rescue dose) during the 72 h postsurgery | 
| Difference at least 20% in presentation of collateral effects between the two groups |  | Continuous assessment during the 72 h post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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local anesthetic, epidural, pharmacokinetics, plasmatic concentration, epidural continuous infusion