Clinical trial NCT03905837: Impact of Lidocaine Administration on Postoperative Complications During Lung Resection Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lung Diseases
Lung Inflammation
Lung Injury, Acute
Postoperative Complications
Keywords: lidocaine
postoperative complications
thoracic surgery
Lead sponsor: Hospital General Universitario Gregorio Marañon
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2019-04-05
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Eligibility 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.

Primary outcomes:
measure: Postoperative complications
timeFrame: up to 30 days after intervention
Secondary outcomes:
measure: gas exchange
timeFrame: 24 hours
measure: 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.
timeFrame: up to 24 hours of intervention
measure: Analgesic requirements of opioids in the first 24 hours after the surgery
timeFrame: 24 hours
measure: Special Care Units stay
timeFrame: up to 30 days after intervention
measure: Hospital stay
timeFrame: up to 30 days after intervention
measure: Re-admissions in Special Care Units
timeFrame: up to 30 days after intervention
measure: Postoperative cognitive dysfunction measure by mini mental state examination
timeFrame: up to 3 days after intervention
measure: Neuro-inflammatory response measure by the synthesis of protein S-100 beta in serum
timeFrame: up to 24 hours after intervention
measure: Neuro-inflammatory response measure by the synthesis of neuronal specific enolase in serum
timeFrame: up to 24 hours after intervention
measure: Neuro-inflammatory response measure by the synthesis of glial fibrillary acidic protein
timeFrame: up to 24 hours after intervention
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
Study officials:
affiliation: Hospital Gregorio Maranon
name: Francisco de la Gala, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.