Impact of Lidocaine Administration on Postoperative Complications During Lung Resection Surgery

Impact of the Administration of Intravenous or Paravertebral Lidocaine in Continuous Perfusion During the Intraoperative Period of Lung Resection Surgery on the Appearance of Postoperative Complications

The purpose of this study is to analyze the impact of the intravenous (IV) or paravertebral (PV) lidocaine administration during the intraoperative period of lung resection surgery on the appearance of postoperative complications. We design a randomized, controlled and blinded study to be performed in 153 patients with 3 arms: 1) Lidocaine IV + PV saline 2) saline IV + PV lidocaine, 3) remifentanil IV + PV saline. Perioperative analysis of inflammatory biomarkers in bronchoalveolar lavage and serum. Follow-up of the postoperative course, especially the appearance of postoperative complications according to the revised Clavien-Dindo classification for thoracic surgery, as well as other relevant clinical results.

Study Overview

• Status: Completed
• Conditions: Lung Diseases; Postoperative Complications; Lung Inflammation; Lung Injury, Acute
• Intervention / Treatment: Drug: Lidocaine; Drug: Remifentanil

Detailed Description

Postoperative pulmonary complications continue to be one of the main causes of morbidity, mortality and increase in hospital stay in patients undergoing surgical procedures requiring anesthesia. Its incidence in lung resection surgery is greater than in other non-cardiac major surgeries due to damage of structures related to respiratory function.

Furthermore, during lung resection surgery there is an exaggerated pulmonary inflammatory response related to the use of one-lung ventilation and / or the lung damage produced by the collapse of the operated lung as well as the surgical manipulation itself.

Recently, in a clinical trial on 180 patients (NCT 02168751), our researcher group observed that the attenuation of the pulmonary inflammatory response through the use of halogenated anesthetic agents, was related to a decrease in the appearance of postoperative pulmonary complications after lung resection surgery. In addition, the presence, in bronchoalveolar lavages, of elevated levels of tumor necrosis factor-alpha, interleukine(IL)-6 and the IL-6 / IL10 ratio were independent predictors of the risk of developing postoperative pulmonary complications.

Lidocaine is a local anesthetic that blocks nerve conduction by blocking sodium channels. In addition it has been known for experimental and clinical studies of its immunomodulatory properties.

Clinical studies performed in different surgeries show that a continuous intravenous infusion of lidocaine during surgery is associated with a lower inflammatory response assessed by monitoring plasma cytokines, as well as less postoperative pain, a shorter duration of postoperative paralytic ileus and a early hospital discharge.

Currently, there is no clinical study that has evaluated the role of intravenous lidocaine on the pulmonary inflammatory response and the subsequent lung damage that inevitably occurs during lung resection surgery with periods of one lung ventilation.

Currently, some experts are proposing the replacement of thoracic epidural and paravertebral analgesia by the intravenous infusion of lidocaine and minor analgesics, for fast-track programs, based on their analgesic and anti-inflammatory capacity and on avoiding the risks inherent in the insertion of an epidural or paravertebral catheter.

Hypothesis: The administration of intravenous or paravertebral lidocaine during lung resection surgery attenuates the exaggerated inflammatory response that inevitably occurs in this surgical intervention. The lower expression of pro-inflammatory mediators will be associated with a lower rate of postoperative complications that are related to the perioperative inflammatory process.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañón

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients of both sexes undergoing lung resection surgery at the Thoracic Surgery Service at the Gregorio Maranón hospital.
• Patients who voluntarily accept to participate in the study and sign the informed consent
• Age> 18 years and legally capable
• Scheduled surgery.
• Functional respiratory tests with forced expiratory volume at one second > 50% or forced vital capacity > 50% preoperatively performed on these patients routinely.
• Not having been on chronic treatment with oral corticosteroids or immunosuppressants three months before surgery.
• Patients without previous history of liver disease.

Exclusion Criteria:

• Pregnancy and lactation
• Known hypersensitivity to amide-type local anesthetics.
• Transfusion of blood products in the previous 10 days.
• Impossibility of performing mechanical ventilation for pulmonary protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lidocaine IV; Group 1: intravenous lidocaine and paravertebral saline (SF). In this group during intraoperative anesthetic maintenance, a continuous intravenous infusion of lidocaine at 1.5mg/kg/h until the end of surgery and perfusion of 0.9% SF through the intraoperative paravertebral catheter at a rate of 0.1ml/kg/h will be administered.	Drug: Lidocaine; Intravenous or paravertebral lidocaine; Other Names: Lignocaine; N-(2,6-dimethylphenyl)-N2,N2-diethylglycinamide
EXPERIMENTAL: Lidocaine PV; Group 2: intravenous SF and paravertebral lidocaine. During anesthesia maintenance, a continuous intravenous infusion of 0.9% SF and an infusion of 2% lidocaine will be administered through the intraoperative paravertebral catheter at a rate of 0.1 ml/kg/h.	Drug: Lidocaine; Intravenous or paravertebral lidocaine; Other Names: Lignocaine; N-(2,6-dimethylphenyl)-N2,N2-diethylglycinamide
ACTIVE_COMPARATOR: no lidocaine; Group 3: intravenous remifentanil and paravertebral SF. During the maintenance of anesthesia, a continuous intravenous infusion of remifentanil at a rate of 0.1 mg/kg/min until the end of surgery and an infusion of 0.9% SF through the intraoperative paravertebral catheter at a rate of 0.1 ml / kg / h.	Drug: Remifentanil; intravenous remifentanil; Other Names: methyl 1-(2-methoxycarbonylethyl)-4-(phenyl-propanoyl-amino)-piperidine-4-carboxylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications	to compare the proportion of patients included in the different scales of the Clavien-Dindo classification of postoperative complications reviewed for thoracic surgery in the three groups of patients. Patients will be followed from the day of hospital admission until hospital discharge and up to 30 days after the surgery	up to 30 days after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gas exchange	Compare the gas exchange (PaO2 / FiO2) at 24 hours after the intervention between the three groups of the study.	24 hours
Differences between three groups in Inflammatory biomarkers (IL 1, IL 2, IL 6, IL 8, IL 10, TNF alpha, MCP-1) measure in serum and bronchoalveolar lavage during 24 hours after the surgery.	To evaluate the effect of intravenous lidocaine on the inflammatory response in lung resection surgery by measuring the inflammatory biomarkers (Interleukin(IL) 1, IL 2, IL 6, IL8, IL 10, tumor necrosis factor alfa and monocyte chemoattractant protein) in serum and in bronchoalveolar lavage, compared to the other two groups of patients. Blood samples are taken at the beginning of the surgery, at the end of the one lung ventilation, and at 24 hours postoperatively. Bronchoalveolar lavage is done just before the beginning of one lung ventilation and at the end of one lung ventilation	up to 24 hours of intervention
Analgesic requirements of opioids in the first 24 hours after the surgery	To compare the analgesic requirements of opioids in the immediate postoperative period (first 24 hours after the surgery) between the three groups of the study. When patients will be admitted in the postoperative care Unit a patient controlled analgesia pump of intravenous morphine 0,1% (bolus of 1mg) will be connected. The total dose of morphine self-administered by the patient in the first 24 hours after surgery will be recorded.	24 hours
Special Care Units stay	To compare the average stay (measure in hours) in Special Care Units among the three groups of the study	up to 30 days after intervention
Hospital stay	To compare the average hospital stay (measure in days) among the three groups of the study	up to 30 days after intervention
Re-admissions in Special Care Units	To compare the number of re-admissions in Special Care Units among the three groups of the study in the 30 days after the intervention.	up to 30 days after intervention
Postoperative cognitive dysfunction measure by mini mental state examination	To analyze the incidence of postoperative cognitive dysfunction (POCD) in the three groups by comparing the mini mental state examination performed at admission and 3 days after the intervention.	up to 3 days after intervention
Neuro-inflammatory response measure by the synthesis of protein S-100 beta in serum	To evaluated the neuro-inflammatory response by the synthesis of protein S-100 beta measured in serum in the first 24 hours postoperatively in the three groups of patients. Blood samples are taken at the beginning of the surgery, at the end of the one lung ventilation, and at 24 hours postoperatively	up to 24 hours after intervention
Neuro-inflammatory response measure by the synthesis of neuronal specific enolase in serum	To evaluated the neuro-inflammatory response by the synthesis of neuronal specific enolase measured in serum in the first 24 hours postoperatively in the three groups of patients. Blood samples are taken at the beginning of the surgery, at the end of the one lung ventilation, and at 24 hours postoperatively	up to 24 hours after intervention
Neuro-inflammatory response measure by the synthesis of glial fibrillary acidic protein	To evaluated the neuro-inflammatory response by the synthesis of glial fibrillary acidic protein measured in serum in the first 24 hours postoperatively in the three groups of patients. Blood samples are taken at the beginning of the surgery, at the end of the one lung ventilation, and at 24 hours postoperatively	up to 24 hours after intervention

Collaborators and Investigators

• Sponsor: Francisco Andres de la Gala
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Francisco de la Gala, MD PhD, Hospital Gregorio Marañón

Publications and helpful links

General Publications

• De la Gala F, Pineiro P, Reyes A, Simon C, Vara E, Rancan L, Huerta LJ, Gonzalez G, Benito C, Munoz M, Grande P, Paredes SD, Aznar PT, Perez A, Martinez D, Higuero F, Sanz D, De Miguel JP, Cruz P, Olmedilla L, Lopez Gil E, Duque P, Sanchez-Pedrosa G, Valle M, Garutti I. Effect of intraoperative paravertebral or intravenous lidocaine versus control during lung resection surgery on postoperative complications: A randomized controlled trial. Trials. 2019 Nov 6;20(1):622. doi: 10.1186/s13063-019-3677-9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 28, 2019
• Primary Completion (ACTUAL): June 2, 2021
• Study Completion (ACTUAL): July 2, 2021

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (ACTUAL): April 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: lidocaine; thoracic surgery; postoperative complications
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Wounds and Injuries; Thoracic Injuries; Lung Diseases; Inflammation; Pneumonia; Postoperative Complications; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Remifentanil; Lidocaine; Piperidine
• Other Study ID Numbers: IGMFGG-2016

Drug and device information, study documents

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