Endovenous Lidocaine and Serum Cytokines Concentration

Effect of Endovenous Lidocaine on Analgesia and Serum Cytokines Concentration: Randomized and Double-blind Trial

Ineffective treatment of postoperative pain may cause organic damage and chronic pain. Nevertheless, opioids, the leading drugs used for this purpose, present side effects that sometimes restrict their usability. In a multimodal context, new postoperative analgesia techniques have been developed focusing in the reduction of opioid use and their adverse effects, as well as postoperative chronic pain prevention. In this background, continuous intravenous infusion of lidocaine during perioperative period has shown to be promising. This trial aimed to compare postoperative analgesia, opioid consumption, duration of ileus and length of hospital stay and IL-1, IL-6, IL-10, α TNF and γ IFN levels in patients undergoing to laparoscopic cholecystectomies who received intravenous lidocaine in comparison to a control group. Intravenous lidocaine in the perioperative period of laparoscopic cholecystectomies was not able to reduce postoperative pain, opioid consumption, and duration of ileus or length of hospital stay. However, its anti-inflammatory effect was evidenced by the significant changes in the studied cytokines.

Study Overview

• Status: Completed
• Conditions: Cholelithiasis
• Intervention / Treatment: Drug: Lidocaine; Drug: Saline solution

Detailed Description

Forty-four patients undergoing laparoscopic cholecystectomy, under general anesthesia, were randomly allocated in two groups. The first group received intravenous lidocaine infusion during the procedure until one hour postoperatively; meanwhile the second group received intravenous saline for the same period of time. The intervention was double-blind. In the postoperative period, both groups received dipyrone and morphine PCA. Pain was assessed by Visual Numeric Scale (VNS) at rest and when coughing at 1st, 2nd, 4th, 12th e 24th hour after the end of the surgery. Blood samples for cytokines measurement were taken at the end of procedure and 24 hours later. The total morphine PCA demand, the time for the first flatus and the length of hospital stay were also recorded and compared.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age over 18 years and
• physical status according to the American Society of Anesthesiologists (ASA) I and II

Exclusion Criteria:

• patients older than 75 years,
• patients with heart disease,

• patients with history of:

  • kidney failure,
  • liver failure,
  • psychiatric disorder,
  • chronic use of opioids or medications that could cause induction of liver enzymes (anticonvulsants).
• the presentation of adverse effects during the intervention or postoperative complications, and the conversion to open surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Lidocaine; Group treated with lidocaine solution	Drug: Lidocaine; Lidocaine was administered in bolus of 1.5 mg.kg-1 at the start of the procedure and maintained at a dose of 3 mg.kg-1.h-1 until one hour after the end of the procedure. Solution of 0,3% lidocaine was used, so that the infusion rate was equal to the weight of the patient.; Other Names: Lidocaine hydrochloride; Xilocayne
PLACEBO_COMPARATOR: Placebo; Group treated with saline solution	Drug: Saline solution; Saline solution was administered in bolus of 1.5 mg.kg-1 at the start of the procedure and maintained at a dose of 3 mg.kg-1.h-1 until one hour after the end of the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome was pain intensity as assessed by visual analogical scale (VAS) scores	The primary endpoint was the effect of lidocaine on postoperative pain within the first 24 hours. Three interns who participante of the study applied VNS to measure the intensity of pain at rest and when coughing 1, 2, 4, 12 and 24 hours after surgery.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary outcome was measure of citokynes IL-1 levels	A blood sample was collected by the author or by the anesthetist of the procedure to measure IL-1, IL-6, IL-10, TNF α and IFN γ levels immediately at the end of the surgery and 24 hours after. The difference of these markers between the two groups also featured secondary outcome. The samples were centrifuged and the serum was separated in Eppendorfs and then frozen at - 70 Celsius degrees, for posterior simultaneous analysis. The biochemical responsible for this analysis also did not have contact with the group to which participants belonged.	24 hours.
The secondary outcome was measure of citokynes IL-6 levels	The primary endpoint was the effect of lidocaine on postoperative pain within the first 24 hours. Three interns who participante of the study applied VNS to measure the intensity of pain at rest and when coughing 1, 2, 4, 12 and 24 hours after surgery.	24 hours
The secondary outcome was measure of citokynes IL-10 levels	The primary endpoint was the effect of lidocaine on postoperative pain within the first 24 hours. Three interns who participante of the study applied VNS to measure the intensity of pain at rest and when coughing 1, 2, 4, 12 and 24 hours after surgery.	24 hours
The secondary outcome was measure of citokynes TNF levels	The primary endpoint was the effect of lidocaine on postoperative pain within the first 24 hours. Three interns who participante of the study applied VNS to measure the intensity of pain at rest and when coughing 1, 2, 4, 12 and 24 hours after surgery.	24 hours
The secondary outcome was measure of citokynes IFN γ levels	The primary endpoint was the effect of lidocaine on postoperative pain within the first 24 hours. Three interns who participante of the study applied VNS to measure the intensity of pain at rest and when coughing 1, 2, 4, 12 and 24 hours after surgery.	24 hours

Collaborators and Investigators

• Sponsor: Universidade Federal de Santa Maria
• Collaborators: Universidade Federal de Santa Catarina

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (ESTIMATE): February 16, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 16, 2015
• Last Update Submitted That Met QC Criteria: February 9, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Cytokines; cholelithiasis; under general anesthesia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Calculi; Gallstones; Cholelithiasis; Cholecystolithiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: LIDOCAINE X CYTOCINES