The Hering-Breuer Reflex in Bilateral Lung Transplant Patients

Overview

The goal of this clinical trial (non-pharmacologic, single-center) is to determine whether the Hering-Breuer inflation reflex is preserved-and how it is modulated by end-expiratory pressure-in adult intensive-care patients who have undergone bilateral lung transplantation. The study will enroll men and women ≥ 18 years admitted to the ICU during the early weaning phase and will include a comparison group of intubated ICU patients after major non-thoracic surgery. The main questions it aims to answer are: * Is the Hering-Breuer reflex (measured as the ratio THBR/TSPONT) absent or attenuated in double-lung-transplant recipients? * Does changing the level of positive end-expiratory pressure (PEEP 8 vs 12 cmH₂O) influence the reflex? Comparison group: Researchers will compare the transplant arm (post-bilateral lung transplantation) with the control arm (post-operative, non-thoracic surgery patients) to see whether loss or blunting of the reflex-and its response to PEEP-differs between the two cohorts. Participants will: * Have a nasogastric catheter with embedded electrodes positioned to record the electrical activity of the diaphragm (EAdi). * Be ventilated in pressure-support mode at two preset PEEP levels (8 cmH₂O and 12 cmH₂O) during the weaning phase. * Receive one standardized high-volume insufflation at \~30 cmH₂O in each PEEP condition to elicit the reflex, while EAdi, airway pressures, inspiratory/expiratory times, and tidal volumes are recorded for 10 minutes per level.

Interventions

• Device Nasogastric tube placement and elicitation of Hering-Breuer reflex
  Enrolled patients will have a nasogastric tube placed, through which diaphragmatic electrical activity will be measured. Patients will be ventilated in pressure support mode with an expansion breath delivered at a maximum pressure of approximately 30 cmH2O in order to elicit the Hering-Breuer Reflex. Diaphragmatic electrical activity, timing, volumes and pressures will then be analyzed before and after the expansion breath over a 10 minute period, testing two levels of PEEP (8 and 12 cmH2O).

Primary outcome measures

• THBR/TSPONT ratio [Time frame: At the enrollment]

Secondary outcome measures (1)

• The variation of the THBR/TSPONT ratio as a function of PEEP [Time frame: At the enrollment]

Eligibility criteria

Inclusion criteria

• Age >18 years;
• Both sexes;
• For group 1: patients admitted to the Intensive Care Unit after undergoing bilateral lung transplantation, during respiratory weaning;
• For group 2: patients admitted to the Intensive Care Unit for support or monitoring after non-thoracic surgery, who will arrive intubated.

Exclusion criteria

For group 1, patients meeting at least one of the following criteria will be excluded:

• Re-transplantation or single-lung transplantation;
• Urgent lung transplantation;
• Post-transplant respiratory system compliance < 30 mL/cmH₂O;
• Hemodynamic instability (defined as the presence of one or more of the following: plasma lactate > 4 mmol/L, need for vasoactive support with norepinephrine and/or epinephrine at a dose > 0.05 mcg/kg/min, systolic arterial pressure < 80 mmHg);
• Increased risk of bleeding related to the placement of a nasogastric tube due to coagulopathy or severe thrombocytopenia (INR > 2 and platelets < 70,000);
• Pregnancy

For group 2, patients presenting with one or more of the following criteria will be excluded:

• Postoperative respiratory system compliance < 30 mL/cmH₂O;
• Hemodynamic instability (defined as the presence of one or more of the following: plasma lactate > 4 mmol/L, need for vasoactive support with norepinephrine and/or epinephrine at a dose > 0.05 mcg/kg/min, systolic arterial pressure < 80 mmHg);
• Contraindications to nasogastric tube placement (gastroesophageal surgery within the last 3 months, gastroesophageal bleeding in the previous 30 days, esophageal varices, facial trauma);
• Increased risk of bleeding related to the placement of a nasogastric tube due to coagulopathy or severe thrombocytopenia (INR > 2 and platelets < 70,000);
• History of lung transplantation or major thoracic surgery;
• Pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Italy · 1 center

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan

Identifiers

NCT: NCT07280611 · ID 5483

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗