NAVA vs PSV Ventilation During Weaning From Mechanical Ventilation in Children After Liver Transplantation (NAVIGATE)

The Use of Neurally Adjusted Ventilator Assist Versus Pressure Support Ventilation durIng weaninG From Mechanical ventilAtion in pediaTric Patients After livEr Transplantation. A Physiologic Cross-over Controlled Trial. NAVIGATE Study

Liver transplantation is the treatment of choice for acute and chronic end-stage liver disease. Neurally Adjusted Ventilator Assist (NAVA) may be a feasible solution to guide the liberation from mechanical ventilation reducing asynchronies between patient and ventilator, and optimizing ventilator cycling. Cardiovascular and respiratory effects during NAVA ventilation are very limited after major abdominal surgery. The purpose of this application is to explore the efficacy of NAVA to reduce the asynchronies between the ventilator and pediatric patient admitted in Pediatric Intensive Care Unit (PICU) after major abdominal surgery, and the relationship between an optimal level of NAVA and cardiac and pulmonary function.

Study Overview

• Status: Unknown
• Conditions: Weaning From Mechanical Ventilation; Pediatric Liver Transplantation
• Intervention / Treatment: Procedure: Weaning from mechanical ventilation

Detailed Description

Twelve pediatric patients underwent liver transplantation and admitted during postoperative period in PICU will be studied. They will be endotracheally intubated and spontaneously triggering the mechanical ventilator. In each patient enrolled a specially manufactured nasogastric tube will be inserted. This nasogastric tube is equipped with ten electrodes. The correct position of the nasogastric tube (and of electrodes) will be confirmed checking the good quality of Edi trace with the P waves displayed by the central electrodes on monitor of Servo I Ventilator (Maquet). All the patients will be ventilated using ventilators with NAVA option (Servo-I, Maquet Critical Care, Sweden). After a stabilization period in Pressure Support Ventilation (PSV) according with the attending physician, each patient will be studied for a duration of 2 hours, divided in three trials of 40-minutes (first 30 minutes to washout from the effects of previous ventilation mode and during the last 10 minutes the results will be recorded). Each patient will be randomized for ventilation mode sequence (PSV/NAVA/PSV or NAVA/PSV/NAVA). The patient tracings of flow, airway pressure, electrical activity of diaphragm for the patient-ventilator interaction analysis, blood gas analysis and cardiovascular parameters will be recorded during each trial.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrizio Chiusolo, MD; Phone Number: +390668592397; Email: fabrizio.chiusolo@opbg.net

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00165
      • Recruiting
      • Fabrizio Chiusolo
      • Contact: Fabrizio Chiusolo, MD; Phone Number: +390668592397; Email: fabrizio.chiusolo@opbg.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Liver recipients (from cadaveric or living donor)
• Invasive Mechanical ventilation

Exclusion Criteria:

• Neurological impairment
• Neuromuscular, mitochondrial, metabolic, or chromosomal diseases with baby hypotonia
• Lesions of medulla
• Hemodynamic instability requiring inotropes/vasopressors (dopamine > 6 mcg/kg/min, norepinephrine, epinephrine, dobutamine, milrinone) or volume load.
• Congenital cardiovascular disease
• Patient extubated
• Need of controlled mechanical ventilation
• Intravenous infusion of benzodiazepines or propofol
• Pneumonia, pneumothorax, massive pleural effusion
• Patient placed on extracorporeal circuit
• Contraindications to insert nasogastric tube
• Not expected to survive beyond 24 hours
• Parental/legal guardian refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NAVA/PSV/NAVA; 6 patients	Procedure: Weaning from mechanical ventilation; Cross over study: 3 periods of 40 minutes in ventilation mode (NAVA or PSV); to register ventilator traces and cardiopulmonary parameters during the last 10 minutes of each period.
Active Comparator: PSV/NAVA/PSV; 6 patients	Procedure: Weaning from mechanical ventilation; Cross over study: 3 periods of 40 minutes in ventilation mode (NAVA or PSV); to register ventilator traces and cardiopulmonary parameters during the last 10 minutes of each period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asynchrony Index	Asynchrony Index (ratio between the number of asynchronous breathing events and the total respiratory rate, expressed as percentage) will be measured in the last 10 minutes of each ventilatory trial of 40 minutes.	last 10 minutes of each ventilatory trial, NAVA or PSV
Left and right ventricle function	Evaluation of left and right ventricular function variation during each ventilation mode. It will be measured by trans-thoracic echocardiogram in the last 10 minutes of each ventilatory trial of 40 minutes.	last 10 minutes of each ventilatory trial, NAVA or PSV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
arterial partial pressure of oxygen (PaO2)	millimeters of mercury (mm Hg)	last 10 minutes of each ventilatory trial, NAVA or PSV
arterial partial pressure of carbon dioxide	mm Hg	last 10 minutes of each ventilatory trial, NAVA or PSV
oxygen index	{[mean airway pressure in centimeters of water × fraction of inspired oxygen × 100] ÷ PaO2 in mm Hg}	last 10 minutes of each ventilatory trial, NAVA or PSV
respiratory rate	breaths per minute	last 10 minutes of each ventilatory trial, NAVA or PSV
lactate	millimole/liter	last 10 minutes of each ventilatory trial, NAVA or PSV
heart rate	beats per minute (bpm)	last 10 minutes of each ventilatory trial, NAVA or PSV
cardiac index	{cardiac output [stroke volume (milliliter) x heart rate (bpm)] / body surface area (BSA; weight in kilograms and height in centimeters will be combined to report BSA in m^2)} in liters/minute/m^2	last 10 minutes of each ventilatory trial, NAVA or PSV
mean arterial pressure	mm Hg	last 10 minutes of each ventilatory trial, NAVA or PSV
central venous pressure	mm Hg	last 10 minutes of each ventilatory trial, NAVA or PSV
systemic vascular resistance	[(mean arterial pressure - central venous pressure) x 79.92 / cardiac index] in dynes/seconds/cm^-5	last 10 minutes of each ventilatory trial, NAVA or PSV

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute
• Collaborators: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Fabrizio Chiusolo, MD, Bambino Gesù Hospital and Research Institute

Publications and helpful links

General Publications

• Antonelli M, Conti G, Bufi M, Costa MG, Lappa A, Rocco M, Gasparetto A, Meduri GU. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA. 2000 Jan 12;283(2):235-41. doi: 10.1001/jama.283.2.235.
• Esteban A, Ferguson ND, Meade MO, Frutos-Vivar F, Apezteguia C, Brochard L, Raymondos K, Nin N, Hurtado J, Tomicic V, Gonzalez M, Elizalde J, Nightingale P, Abroug F, Pelosi P, Arabi Y, Moreno R, Jibaja M, D'Empaire G, Sandi F, Matamis D, Montanez AM, Anzueto A; VENTILA Group. Evolution of mechanical ventilation in response to clinical research. Am J Respir Crit Care Med. 2008 Jan 15;177(2):170-7. doi: 10.1164/rccm.200706-893OC. Epub 2007 Oct 25.
• Esquivel CO, Iwatsuki S, Gordon RD, Marsh WW Jr, Koneru B, Makowka L, Tzakis AG, Todo S, Starzl TE. Indications for pediatric liver transplantation. J Pediatr. 1987 Dec;111(6 Pt 2):1039-45. doi: 10.1016/s0022-3476(87)80053-7.
• Ulukaya S, Arikan C, Aydogdu S, Ayanoglu HO, Tokat Y. Immediate tracheal extubation of pediatric liver transplant recipients in the operating room. Pediatr Transplant. 2003 Oct;7(5):381-4. doi: 10.1034/j.1399-3046.2003.00072.x.
• Fullington NM, Cauley RP, Potanos KM, O'Melia L, Zurakowski D, Bae Kim H, Seefelder C, Vakili K. Immediate extubation after pediatric liver transplantation: a single-center experience. Liver Transpl. 2015 Jan;21(1):57-62. doi: 10.1002/lt.24036.
• Coisel Y, Chanques G, Jung B, Constantin JM, Capdevila X, Matecki S, Grasso S, Jaber S. Neurally adjusted ventilatory assist in critically ill postoperative patients: a crossover randomized study. Anesthesiology. 2010 Oct;113(4):925-35. doi: 10.1097/ALN.0b013e3181ee2ef1.
• Moulin D, Clement de Clety S, Reynaert M, Carlier MA, Veyckmans F, Claus D, Buts JP, de Hemptinne B, Otte JB. Intensive care for children after orthotopic liver transplantation. Intensive Care Med. 1989;15 Suppl 1:S71-2. doi: 10.1007/BF00260893.
• Chidini G, De Luca D, Conti G, Pelosi P, Nava S, Calderini E. Early Noninvasive Neurally Adjusted Ventilatory Assist Versus Noninvasive Flow-Triggered Pressure Support Ventilation in Pediatric Acute Respiratory Failure: A Physiologic Randomized Controlled Trial. Pediatr Crit Care Med. 2016 Nov;17(11):e487-e495. doi: 10.1097/PCC.0000000000000947.
• Scharf SM, Caldini P, Ingram RH Jr. Cardiovascular effects of increasing airway pressure in the dog. Am J Physiol. 1977 Jan;232(1):H35-43. doi: 10.1152/ajpheart.1977.232.1.H35.
• Vieillard-Baron A, Loubieres Y, Schmitt JM, Page B, Dubourg O, Jardin F. Cyclic changes in right ventricular output impedance during mechanical ventilation. J Appl Physiol (1985). 1999 Nov;87(5):1644-50. doi: 10.1152/jappl.1999.87.5.1644.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): January 30, 2022

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: mechanical ventilation; pediatric; liver transplantation; weaning; pressure support ventilation; neurally adjusted ventilatory assist
• Other Study ID Numbers: 1695_OPBG_2018

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