Effect of Intravenous Lidocaine on BIS-guided Propofol Requirements During General Anesthesia

Study Overview
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Brief Summary
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The purpose of this randomized clinical trial is to evaluate the interaction of lidocaine infusion initiated and maintained during surgery, on propofol requirements during general anesthesia.

Detailed Description
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Use of intravenous lidocaine as a coadjuvant agent during general anesthesia has increased. Lidocaine infusion during and after abdominal surgery decreases postoperative pain and reduces ileus duration, reducing patient´s hospital stay and opioid consumption. Intravenous lidocaine´s effect on other intravenous anesthetics is unclear, and there are no present studies evaluating its interaction on hypnotic anesthetic requirements when using a BIS (Bispectral Index) monitor to maintain an adequate depth of anesthesia. We therefore decided to conduct a randomized controlled trial to evaluate the interaction of systemic lidocaine infusion, initiated and maintained during surgery, on propofol requirements and anesthetic depth as measured by BIS.

Official Title
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Estimation of the Effect of Intravenous Lidocaine on BIS-guided Propofol Requirements During General Anesthesia

Conditions
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Intravenous Anesthetic Interaction Unrecognized Condition

Intervention / Treatment
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* Drug: Intravenous lidocaine infusion
* Other: Placebo (0.9% saline infusion)
* Drug: Propofol 1% (intravenous infusion)
* Procedure: Placement of arterial line


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA I-II patients, Between 20 and 65 years of age Programed for elective laparoscopic cholecystectomy Eligible for total intravenous anesthesia with propofol Exclusion Criteria: Unwillingness to participate in the study Adverse reactions to the drugs used in the study Use of medications that interfere in local anesthetic metabolism History of liver disease, kidney failure, hypoalbuminemia, hypocalcemia or hypophosphatemia History of drug or alcohol abuse Chronic use of benzodiazepines

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous lidocaine infusion<br>Intravenous lidocaine infusion during total intravenous anesthesia with propofol administered by target controlled infusion | Drug: Intravenous lidocaine infusion<br>* Once the dose of propofol required for general anesthesia is stabilized for 5 minutes with BIS values between 40 and 50, lidocaine 1% infusion is begun in a bolus of 1.5mg/kg for 5 minutes and then infused at 2 mg/kg/hr until the end of surgery (last skin suture is made).<br>Drug: Propofol 1% (intravenous infusion)<br>* Propofol is administered according to a widely-accepted pharmacokinetic model, initially dosed to a target controlled infusion (TCI) of 4.5 micrograms/ml, and titrated by step increases of 0.5 every minute until loss of conscience is obtained and BIS values are less than 50. During the maintenance phase of anesthesia propofol TCI is actively titrated to maintain BIS values between 40 and 50. If BIS is out of this range for more than 10 seconds, propofol is adjusted in 0.5 ug/mc to maintain BIS values in the predetermined limits.<br>Procedure: Placement of arterial line<br>* An arterial line was placed in the anesthetised patient´s right arm by the investigator and arterial samples were obtained every 10 minutes since initiation of the study infusion to determine plasmatic lidocaine and propofol levels (if the infusion was saline the samples were not analyzed). The arterial line was removed before the end of surgery.<br>|
| Placebo Comparator: Intravenous 0.9% saline infusion<br>Intravenous 0.9% saline infusion during total intravenous anesthesia with propofol administered by target controlled infusion | Other: Placebo (0.9% saline infusion)<br>* Once the dose of propofol required for general anesthesia is stabilized for 5 minutes with BIS values between 40 and 50, 0.9% saline infusion is begun in a bolus of 1.5mg/kg for 5 minutes and then infused at 2 mg/kg/hr until the end of surgery (last skin suture is made).<br>Drug: Propofol 1% (intravenous infusion)<br>* Propofol is administered according to a widely-accepted pharmacokinetic model, initially dosed to a target controlled infusion (TCI) of 4.5 micrograms/ml, and titrated by step increases of 0.5 every minute until loss of conscience is obtained and BIS values are less than 50. During the maintenance phase of anesthesia propofol TCI is actively titrated to maintain BIS values between 40 and 50. If BIS is out of this range for more than 10 seconds, propofol is adjusted in 0.5 ug/mc to maintain BIS values in the predetermined limits.<br>Procedure: Placement of arterial line<br>* An arterial line was placed in the anesthetised patient´s right arm by the investigator and arterial samples were obtained every 10 minutes since initiation of the study infusion to determine plasmatic lidocaine and propofol levels (if the infusion was saline the samples were not analyzed). The arterial line was removed before the end of surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total propofol requirements during bispectral index guided general anesthesia | During and after elective laparoscopic cholecystectomy. Patients' anesthetic depth will be monitored during the intra-operative period using a BIS monitor. Patients' follow up considers the immediate post-operative period at the recovery room (PACU), and it will continue until patients' discharge from the hospital (average 3 days postoperatively). | DAY 1. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate effect of intravenous lidocaine infusion on waking time after general anesthesia | Immediately after elective laparoscopic cholecystectomy, during PACU stay. Patients' follow up considers the immediate post-operative period at the recovery room (PACU), and it will continue until patients' discharge from the hospital (average 3 days postoperatively). | DAY 1. |