Evaluation of Perioperative Recovery With a Spontaneous Breathing-Preserving Strategy in Older Lung Transplant Recipients: A Prospective Multicenter Single-Arm Cohort Study

This prospective, multicenter, single-arm cohort study (BREATH-Elderly) is designed to evaluate the clinical effectiveness and safety of an anesthesia-surgical strategy intended to preserve spontaneous breathing in adult lung transplant recipients aged 70 years and older. The primary objective is to characterize early postoperative recovery under this standardized pathway, with a focus on (1) postoperative invasive mechanical ventilation (IMV) requirement, (2) postoperative length of hospital stay (LOS), and (3) perioperative survival (from the start of transplantation to hospital discharge or postoperative day 30, whichever occurs first).

Eligible participants are adults aged ≥70 years who are listed for allogeneic lung transplantation and meet prespecified perioperative safety thresholds (e.g., not receiving ongoing invasive mechanical ventilation or ECMO preoperatively; acceptable baseline cardiac and renal function; no evidence of active infection; and adequate rehabilitation potential and caregiver support). Key exclusions include retransplantation or multi-organ transplantation, recent major cardiovascular/cerebrovascular events, severe end-organ failure, active malignancy, extreme body habitus (e.g., BMI <16 or ≥35 kg/m²), ongoing substance use, and scenarios judged by the anesthesia team to make a preserved spontaneous-breathing pathway unsafe (e.g., predicted difficult airway or inability to safely manage the airway with a laryngeal mask-based approach).

All enrolled participants will undergo lung transplantation using a standardized preserved spontaneous-breathing anesthesia-surgical pathway, typically based on total intravenous anesthesia with airway management using a laryngeal mask airway and continuous monitoring of oxygenation and ventilation. The protocol includes predefined rescue escalation criteria and standardized procedures for conversion when clinically indicated. Triggers for conversion may include, but are not limited to: persistent hypoxemia (e.g., SpO₂ <85% despite assisted ventilation), severe hypercapnia with acidosis and accompanying hemodynamic/arrhythmic instability (e.g., PaCO₂ ≥80 mmHg with repeated pH <7.25 and circulatory/arrhythmic changes), unstable surgical field due to marked mediastinal movement refractory to adjustment, major intraoperative bleeding impairing operative safety, and abnormal airway secretions (e.g., increased or bloody sputum with a >30% reduction in tidal volume or elevated airway pressure when assisted ventilation is required). If conversion is required, the protocol specifies intubation approach options (e.g., single-lumen tube plus bronchial blocker or double-lumen tube when lung isolation is necessary) and immediate initiation of lung-protective ventilation. Postoperative care, including immunosuppression and infection prevention, follows routine standards at each participating transplant center and is recorded in the case report form. Participants are assessed throughout the index hospitalization, with key postoperative complications captured through discharge and up to 30 days after surgery, and additional follow-up items (e.g., 90-day survival/readmission/interventions) recorded where applicable.

The primary endpoint is a composite of three early recovery indicators (reported both as a composite and as individual components): (1) postoperative IMV requirement in the early postoperative period (including events such as re-intubation/tracheostomy and/or new or escalated extracorporeal respiratory support as defined in the protocol), (2) postoperative LOS, and (3) perioperative survival to discharge or postoperative day 30. Secondary endpoints include intraoperative and anesthesia-related measures (e.g., operative/anesthesia time, blood loss, perioperative medication exposure, success rate of removing the airway device in the operating room, time to first effective communication), ICU length of stay, in-hospital resource utilization/cost categories, and a prespecified list of postoperative complications (e.g., primary graft dysfunction graded at standard time points, respiratory support escalation events, infections, bleeding requiring re-intervention, AKI and renal replacement therapy, major cardiovascular/cerebrovascular events, rejection episodes, and thrombotic events). Outcomes will be summarized descriptively and compared against each center's historical outcomes under conventional intubated strategies using appropriate one-sample methods; multivariable models may be used to adjust for important clinical factors (e.g., diagnosis, intraoperative ECMO use, and procedural complexity) when warranted.

The study is expected to demonstrate that, in carefully selected recipients aged ≥70 years, a standardized preserved spontaneous-breathing strategy is feasible and can be implemented with structured rescue pathways, and may be associated with a higher proportion of patients avoiding postoperative IMV, a shorter postoperative hospital stay, and maintained perioperative survival within an acceptable safety profile. These findings are intended to support broader implementation guidance and inform the design of subsequent comparative studies in elderly lung transplant populations.