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Impact of Lidocaine Administration on Postoperative Complications During Lung Resection Surgery

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ClinicalTrials.gov Identifier: NCT03905837
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : April 9, 2019
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Francisco Andres de la Gala, Hospital General Universitario Gregorio Marañon

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lung Diseases Lung Inflammation Lung Injury, Acute Postoperative Complications Drug: Lidocaine Drug: Remifentanil Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Unicentric, randomized, blind and controlled phase IV Clinical trial of three parallel groups.

Randomization: Patients will be randomized into three groups (ratio 1: 1: 1): intravenous lidocaine and paravertebral saline (group 1), intravenous and paravertebral saline solution with lidocaine (group 2) and intravenous remifentanil and paravertebral saline solution (group 3) ). The randomization will be carried out through the EPIDAT 3.1 program prior to the recruitment of the first patient and the randomization codes will be kept in a sealed envelope with the number on the outside of the envelope. Patients will be followed from the day of hospital admission until hospital discharge and after 30 days of surgery.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The randomization will be carried out through the EPIDAT 3.1 program. Randomization codes will be obtained prior to the recruitment of the first patient and will be kept in a sealed envelope with numbering on the outside of the envelope. The operating room anesthesiologist will receive the assigned medication from the corresponding group with the only identification of intravenous perfusion and paravertebral perfusion, without having knowledge of the group to which the patient belongs.

Bias control: The anesthesiologist responsible for the intraoperative management of the patient, the physician responsible for postoperative control in the postoperative care unit and the guard physician who will perform the cognitive dysfunction test preoperative and postoperative and the follow up until the month of surgery will be blind to the technique used, as well as those responsible for the analysis of the biological samples.

Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : May 28, 2021
Estimated Study Completion Date : November 28, 2021


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 Name: methyl 1-(2-methoxycarbonylethyl)-4-(phenyl-propanoyl-amino)-piperidine-4-carboxylate




Primary Outcome Measures :
  1. Postoperative complications [ Time Frame: up to 30 days after intervention ]
    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


Secondary Outcome Measures :
  1. gas exchange [ Time Frame: 24 hours ]
    Compare the gas exchange (PaO2 / FiO2) at 24 hours after the intervention between the three groups of the study.

  2. 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. [ Time Frame: up to 24 hours of intervention ]
    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

  3. Analgesic requirements of opioids in the first 24 hours after the surgery [ Time Frame: 24 hours ]
    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.

  4. Special Care Units stay [ Time Frame: up to 30 days after intervention ]
    To compare the average stay (measure in hours) in Special Care Units among the three groups of the study

  5. Hospital stay [ Time Frame: up to 30 days after intervention ]
    To compare the average hospital stay (measure in days) among the three groups of the study

  6. Re-admissions in Special Care Units [ Time Frame: up to 30 days after intervention ]
    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.

  7. Postoperative cognitive dysfunction measure by mini mental state examination [ Time Frame: up to 3 days after intervention ]
    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.

  8. Neuro-inflammatory response measure by the synthesis of protein S-100 beta in serum [ Time Frame: up to 24 hours after intervention ]
    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

  9. Neuro-inflammatory response measure by the synthesis of neuronal specific enolase in serum [ Time Frame: up to 24 hours after intervention ]
    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

  10. Neuro-inflammatory response measure by the synthesis of glial fibrillary acidic protein [ Time Frame: up to 24 hours after intervention ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905837


Contacts
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Contact: Francisco de la Gala, MD PhD 0034915868367 francisco.gala@salud.madrid.org
Contact: Ignacio Garutti, MD PhD 0034915868367 ignacio.garutti@salud.madrid.org

Locations
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Spain
Hospital Gregorio Maranon Recruiting
Madrid, Spain, 28007
Contact: Francisco de la Gala, MD PhD    0034915868367    francisco.gala@salud.madrid.org   
Contact: Ignacio Garutti, MD PhD    0034915868367    ignacio.garutti@salud.madrid.org   
Sponsors and Collaborators
Francisco Andres de la Gala
Instituto de Salud Carlos III
Investigators
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Principal Investigator: Francisco de la Gala, MD PhD Hospital Gregorio Maranon

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Francisco Andres de la Gala, Anesthesiologist. MD. PhD, Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier: NCT03905837     History of Changes
Other Study ID Numbers: IGMFGG-2016
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Francisco Andres de la Gala, Hospital General Universitario Gregorio Marañon:
lidocaine
postoperative complications
thoracic surgery
Additional relevant MeSH terms:
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Lung Diseases
Lung Injury
Pneumonia
Acute Lung Injury
Inflammation
Postoperative Complications
Pathologic Processes
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries
Respiratory Tract Infections
Lidocaine
Remifentanil
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Analgesics