Physiological Response in Lung Transplant Recipients Undergoing Neurally Adjusted Ventilatory Assist (TRANS-NAVA)

Physiological Response to Different Levels of Support in Lung Transplant Recipients Undergoing Neurally Adjusted Ventilatory Assist (NAVA)

Primary Graft Dysfunction (PGD) respresents the leading cause of mortality in early post-operative period of Lung Tranplantation (LTx). Protective ventilatory strategy could potentially reduce the risk of PGD in these patients. Neurally Adjusted Ventilatory Assist (NAVA) is an assisted ventilation mode that could allow to adopt this strategy. Aim of the study is to assess the feasibility of NAVA in the early post-LTx phase and to describe the breathing pattern and the physiological relationship between neural respiratory drive and different levels of ventilatory assist, in the absence of pulmonary vagal afferent feedback.

Study Overview

• Status: Unknown
• Conditions: Ventilator-Induced Lung Injury; Lung Transplant; Complications; Work of Breathing; Neurally Adjusted Ventilatory Assist
• Intervention / Treatment: Device: NAVA ventilation

Detailed Description

Lung transplantation (LTx) is an important treatment option for select patients with end-stage pulmonary disease. Primary Graft Dysfunction (PGD) is the main cause of death; in the early period following LTx a protective ventilatory strategy (tidal volume - Vt of 6 mL/Kg + Positive End Expiratory Pressure) could potentially reduce the risk of PGD in these patients. Neurally Adjusted Ventilatory Assist (NAVA) is an assisted ventilation mode in which neural inspiratory activity is monitored through the continuous recording of electrical activity of the diaphragm (EAdi). Actually, Guidelines about the adoption of a protective ventilatory strategy in the early post-opeartive period are lacking.

NAVA, because of its intrinsic properties (proportionality between respiratory drive and level of assist, prevention of diaphragm atrophy), could allow to reach the afore mentioned ventilatory strategy. So, aim of the study, is the evaluation of patients' neural breathing pattern during NAVA, in early post-operative period of LTx

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Ospedale Maggiore Policlinico
• Switzerland
  • Lausanne, Switzerland, 10111
    • Recruiting
    • University Hospital of Lausanne
    • Contact: Lise Piquilloud, MD; Phone Number: +41 21 314 1632; Email: Lise.Piquilloud@chuv.ch

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:

• Age > 18 y.o.
• Admission to ICU for post-operative monitoring after LTx
• Presence of spontaneous breathing activity
• Sedation titrated to a target RASS between 0 and -2
• Written informed consent obtained

Exclusion Criteria:

• Contraindication to nasogastric tube insertion (gastroesophageal surgery in the previous 3 months, gastroesophageal bleeding in the previous 30 days, history of esophageal varices, facial trauma)
• Increased risk of bleeding with nasogastric tube insertion, due to severe coagulation disorders and severe thrombocytopenia ( i.e., INR > 2 and platelets count < 70.000/mm3)
• Severe hemodynamic instability (noradenaline > 0.3 μg/kg/min and/or use of vasopressin)
• Postoperative extracorporeal respiratory support (ECMO)
• Pre-operative reconditioning of the transplanted lungs by means of ex-vivo lung perfusion (EVLP)
• Lung retransplantation
• Failure to obtain a stable EAdi signal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAVA group; NAVA ventilation	Device: NAVA ventilation; Assisted Ventilation Mode, synchronized, through EAdi catheter, with patient's inspiratory effort and proportional to respiratory drive

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the variations of Electrical Activity of the Diaphragm in response to different levels of ventilatory assist at different degrees of lung inflation (different Positive End Expiratory Pressure values)	Electrical Activity of the Diaphragm (EAdi) (microVolt)	One hour after the recovery of spontaneous breathing
Evaluation of the variations of Neuro-Mechanical Coupling (expressed as microVolt of EAdi /cmH2O of airway pressure Ratio) in response to different levels of ventilatory assist at different degrees of lung inflation	Neuro-Mechanical Coupling (NMC) (microvolt/cmH2O)	One hour after the recovery of spontaneous breathing
Evaluation of the variations of Neuro-ventilatory Efficiency (expressed as microvolt of EAdi / mL of Tidal Volume Ratio) in response to different levels of ventilatory assist at different degree of lung inflation	Neuro-Ventilatory Efficiency (NVE) (microvolt/mL)	One hour after the recovery of spontaneous breathing
Evaluation of the changes in the patient's neural breathing pattern (expressed as mL of Tidal Volume) at different levels of ventilatory assist	Tidal Volume (mL)	One hour after the recovery of spontaneous breathing
Evaluation of the changes in the patient's neural breathing pattern (expressed as respiratory rate) at different levels of ventilatory assist	Respiratory rate (Breaths/min)	One hour after the recovery of spontaneous breathing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the feasibility of Plateau Pressure during NAVA	Plateau Pressure (Pplat)	One hour after the recovery of spontaneous breathing, with inspiratory hold manoeuvres
Ultrasound assessment of the changes of Diaphragm's Thickening Fraction at different levels of Positive End Expiratory Pressure and at different NAVA gains	Diaphragm's Thickening Fraction (TF)	One hour after the recovery of spontaneous breathing
Assesment of the total asynchrony index (double triggering + missed efforts + inspiratory trigger delay +short cycling + prolonged cycling)	Total Asinchrony Index	One hour after the recovery of spontaneous breathing

Collaborators and Investigators

• Sponsor: Policlinico Hospital
• Collaborators: University of Lausanne Hospitals
• Investigators: Principal Investigator: Chiara Abbruzzese, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Principal Investigator: Luigi Castagna, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Principal Investigator: Nicola Bottino, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Principal Investigator: Alberto Zanella, MD, University of Milan; Principal Investigator: Nadia Corcione, MD, Fondazione IRCCS Ca' Granda; Principal Investigator: Antonio Pesenti, Prof, University of Milan

Publications and helpful links

General Publications

• Grasselli G, Castagna L, Abbruzzese C, Corcione N, Bottino N, Guzzardella A, Colombo SM, Carlesso E, Mauri T, Rossetti V, Palleschi A, Scaravilli V, Zanella A, Pesenti A. Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation. Br J Anaesth. 2021 Jul;127(1):143-152. doi: 10.1016/j.bja.2021.03.010. Epub 2021 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2017
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: TRANS-NAVA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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