Biomarkers of Lung Injury in Hyperinflation in the Mechanical Ventilator Versus Manual Hyperinflation

Biomarkers of Lung Injury in the Hyperinflation Maneuver in the Mechanical Ventilator Versus Manual Hyperinflation in Septic Patients: Randomized Clinical Trial

Due to the failure of the respiratory system, many patients admitted to the Intensive Care Units (ICUs) require the institution of invasive mechanical ventilation (MV), aiming at maintaining gas exchange, reversing respiratory muscle fatigue, among other benefits. However, an artificial airway installation may be harmful because of its deleterious capacity to the mucociliary clearance mechanism, predisposing to the accumulation of secretions and consequent respiratory infections. Physiotherapy in patients critical for the purpose of preventing and treating these respiratory complications. In this way, they are techniques that aim at a reexpansion and removal of airborne secretions. An application of manual hyperinflation with the Ambú (HM), applied through compression of the resuscitator (Ambu), an application of hypertension for the use of energy, pulmonary volume. Similar to the goal of manual hyperinflation, a hyperinflation maneuver without mechanical ventilator (HVM) is also widely used and has been shown to be effective. A maneuvering visa re-expansion of collapsed lung areas and increased peak expiratory flow, resulting in the mobilization of secretions. It is known that these techniques can cause deleterious effects to the lungs due to the high volumes administered and the variation in airway depression, predisposing to barotrauma and volutrauma, increasing the lung permeability and consequent pulmonary edema. There may also be a more subtle form of injury, such as a release of lung mediators, initiating a process of local inflammation. This biological response is called biotrauma, and if these mediators translocate into the systemic circulation, it can lead to dysfunction and death. The aim of the present study was to evaluate the biomarkers of pulmonary lesion in the hyperinflation maneuver with mechanical ventilator versus manual hyperinflation with environments in sudden patients under mechanical ventilation.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Device: Hyperinflation with mechanical ventilator; Device: Manual hyperinflation

Detailed Description

This study aims to evaluate the biomarkers of lung injury in the hyperinflation maneuver with mechanical ventilator versus manual hyperinflation with ambu in septic patients under mechanical ventilation through changes in the cellular levels of interleukin 8 (IL-8) and receptor for advanced glycation end products (RAGE). As specific objectives, compare the variables of ventilatory mechanics (dynamic compliance, static complacency, frequency airway resistance) and hemodynamic parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate) before and after each maneuver and between groups. It is characterized as a randomized clinical trial. The binary randomization of the groups will be performed using the electronic application Bracket RTSM (version 2.0.0, Bracket Global), and will be performed by a blind researcher to the groups evaluated. After the eligibility criteria, the selected patients will be randomized and divided into two groups : Hyperinflation group with mechanical ventilator (HVM) and manual hyperinflation group (HM). Triage will be carried out daily in order to detect patients eligible to apply the study through communication with the local multiprofessional team. Once patients are eligible according to the inclusion and exclusion criteria, randomization will be performed to determine the techniques to be employed. Prior to the application of each technique, all patients will be placed in the dorsal decubitus (DD) with the head elevated at 30 degrees and will be aspirated by the nursing team once with probe number nº 14 and with a vacuum of -40cmH2O. Five minutes later, a 4.5 mL blood sample from the study participant for analysis of lung injury biomarkers (IL-8 and RAGE) will be collected in an EDTA tube. Blood samples will be sent to the Molecular and Protein Analysis Unit (UAMP) of the HCPA Experimental Research Center (CPE) in a box cooled by a blind collaborator who is not part of the study and will be stored at -80ºC. The biomarkers will be tested in duplicates through the plasma of the sample collected using the Luminex Human Magnetic Assay kit (R & DSystems, Minneapolis, MN). The results will be transcribed to the datasheet. A period of five minutes will be waited for the start of the initial technique chosen by randomization. When drawn to the HVM group, there will be an increase in initial positive inspiratory pressure until reaching a peak pressure of 40 cmH2O and PEEP equal to 7 cmH2O. During the application of this technique VC will increase significantly in most patients, which may cause and / or increase Auto-PEEP. In order to minimize and / or extinguish this adverse effect the RF should be reduced to allow exhalation. When drawn to the HM group, the manual resuscitation bag will be connected to the oxygen system at five liters per minute. The participant will be disconnected from the ventilator and then initiate a slow inspiration with inspiratory pause followed by abrupt expiration, totaling twelve (12) cycles / minute. Data will be collected on ventilatory mechanics (dynamic compliance, expiratory tidal volume, respiratory rate, peak pressure, plateau pressure, airway resistance) from the ventilator used in the SERVO-s® institution and hemodynamic parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate) in the hemodynamic monitoring device MP60® before and after the application of each technique, and the data will be recorded on an evaluation form. After each maneuver, a period of three hours will be waiting and then a blood sample will be collected again from the patient for the analysis of lung injury biomarkers.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
      • Contact: Nathalia Silva de Oliveira; Phone Number: (51)998090791; Email: nathalia_rondon@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients admitted to the ICPA ICU who have a minimum of 24 hours under mechanical ventilation, coupled to the orotracheal tube (TOT) or tracheostomy (TQT) in pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV) .
• Hemodynamically stable patients with mean arterial pressure equal to or greater than 60 mmHg with Noradrenaline doses of less than 0.5 μg / kg / minute.
• Septic patients.

Exclusion Criteria:

• Patients with contraindications to increased positive pressure (non-drained pneumothorax and hemothorax, subcutaneous emphysema).
• Patients with a diagnosis of adult respiratory distress syndrome (ARDS).
• Neurosurgical patients who are under intracranial pressure monitoring (ICP);
• Patients with Peak inspiratory pressure (PIP) = 40 cmH2O and / or PEEP> 10 cmH2O.
• Post-surgical patients
• Patients submitted to extracorporeal circulation (ECC)
• Chronic renal patients
• Patients without relatives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group HVM; When randomized to the Hyperinflation with mechanical ventilator (HVM) group, there will be an increase in initial positive inspiratory pressure until reaching a peak pressure of 40 cmH2O and PEEP equal to 7 cmH2O	Device: Hyperinflation with mechanical ventilator; increase in initial positive inspiratory pressure until reaching a peak pressure of 40 cmH2O and PEEP equal to 7 cmH2O
Experimental: Group HM; When randomized to the Manual hyperinflation (HM) group, the manual resuscitation bag will be connected to the oxygen system at five liters per minute. The participant will be disconnected from the ventilator and then initiate a slow inspiration with inspiratory pause followed by abrupt expiration, totaling twelve (12) cycles / minute.	Device: Manual hyperinflation; the manual resuscitation bag will be connected to the oxygen system at five liters per minute. The participant will be disconnected from the ventilator and then initiate a slow inspiration with inspiratory pause followed by abrupt expiration, totaling twelve (12) cycles / minute.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin 8 (IL-8)	A sample of 4.5 mL of blood from the study participant for analysis of lung injury biomarkers will be collected in an EDTA tube and then analyzed using the Luminex Human Magnetic Assay kit	variation in 3 hours
Receptor for advanced glycation end products (RAGE)	A sample of 4.5 mL of blood from the study participant for analysis of lung injury biomarkers will be collected in an EDTA tube and then analyzed using the Luminex Human Magnetic Assay kit	variation in 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	will be verified through the Philips MP60® hemodynamic monitoring device	variation in 3 hours
Diastolic blood pressure	will be verified through the Philips MP60® hemodynamic monitoring device	variation in 3 hours
Heart rate	will be verified through the Philips MP60® hemodynamic monitoring device	variation in 3 hours
Mean arterial pressure	will be verified through the Philips MP60® hemodynamic monitoring device	variation in 3 hours
Respiratory rate	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours
Dynamic compliance (cdyn)	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours
Static compliance (cst)	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours
Peak inspiratory pressure (PIP)	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours
Plateau pressure (PP)	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours
Airway resistance (Raw)	value obtained from the ventilator used in the institution SERVO-s®	variation in 3 hours

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Silvia Regina Rios Vieira, Federal University of Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2018
• Primary Completion (Anticipated): September 10, 2019
• Study Completion (Anticipated): December 20, 2019

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: biomarkers; sepsis; lung injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Lung Injury
• Other Study ID Numbers: 170580

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No