Perioperative Recovery Outcomes With a Spontaneous Breathing Strategy in Severely Underweight Lung Transplant Recipients

Official title

Evaluation of Perioperative Recovery Outcomes of a Spontaneous Breathing-Preserving Strategy in Severely Underweight Lung Transplantation: A Prospective, Multicenter, Single-Arm Clinical Study

Overview

The goal of this prospective, multicenter, single-arm clinical study is to learn whether a spontaneous breathing-preserving perioperative management strategy can improve recovery and is safe in lung transplant recipients with very low body weight (body mass index \[BMI\] \<16 kg/m²). The main questions it aims to answer are whether, in lung transplant recipients with very low body weight (BMI \<16 kg/m²), a spontaneous breathing-preserving anesthesia-surgical strategy combined with standardized nutritional optimization and a prehabilitation program can improve early postoperative recovery and perioperative survival. Specifically, the study will assess the proportion of participants who require postoperative invasive mechanical ventilation, postoperative length of hospital stay, and perioperative survival within the protocol-defined time window (e.g., through hospital discharge). Participants will undergo lung transplantation using a perioperative strategy that preserves spontaneous breathing whenever clinically appropriate, with predefined criteria for conversion to endotracheal intubation and mechanical ventilation if needed. They will receive standard postoperative monitoring and supportive care, with respiratory support events and perioperative complications assessed during the index hospitalization (and up to 30 days after surgery, if specified in the protocol). Key outcomes will be collected from routine clinical care, including postoperative ventilatory support status, length of hospital stay, and major safety events.

Detailed description

This prospective, multicenter, single-arm clinical study will evaluate the clinical effectiveness and safety of a spontaneous breathing-preserving anesthesia-surgical strategy, integrated with standardized nutritional optimization and a structured prehabilitation program, in lung transplant recipients with very low body weight (body mass index \[BMI\] \<16 kg/m²). The overall purpose is to determine whether this bundled perioperative approach can enhance early postoperative recovery while maintaining acceptable perioperative survival in this high-risk population.

Eligible participants will be enrolled consecutively across participating centers and managed according to a standardized perioperative pathway. The intervention bundle includes: (1) preoperative nutritional optimization and prehabilitation tailored to severe low BMI status, and (2) an intraoperative anesthesia-surgical management strategy designed to preserve spontaneous breathing whenever clinically appropriate, with predefined criteria for escalation/conversion to endotracheal intubation and invasive mechanical ventilation (IMV) if safety thresholds are exceeded. Postoperatively, participants will receive standard monitoring and supportive care per institutional lung transplant practice, with protocolized collection of key respiratory support events and perioperative complications. Outcomes will be assessed during the index hospitalization and, where specified by the protocol, through a defined perioperative follow-up window (e.g., up to 30 days after surgery).

The primary clinical outcomes focus on early recovery and perioperative survival: (1) the proportion of participants requiring postoperative IMV, (2) postoperative length of hospital stay, and (3) perioperative survival within the protocol-defined time window (e.g., through hospital discharge and/or up to 30 days). Additional safety and recovery measures may include intensive care unit length of stay, re-intubation or tracheostomy, new or escalated extracorporeal support, primary graft dysfunction grading at prespecified time points, infections, airway complications, bleeding requiring re-intervention, acute kidney injury and renal replacement therapy, major cardiovascular/cerebrovascular events, and rejection episodes. Analyses will primarily be descriptive and estimation-focused, reporting event rates, central tendencies for length-of-stay outcomes, and survival estimates with confidence intervals; where appropriate, findings may be contextualized against prespecified benchmarks or contemporaneous historical outcomes.

The study is expected to generate high-quality prospective evidence on the feasibility and clinical signals of benefit of a spontaneous breathing-preserving perioperative strategy in severely underweight lung transplant recipients. It is hypothesized that the bundled approach will be associated with a lower need for postoperative IMV and shorter postoperative hospitalization, while maintaining acceptable perioperative survival and safety profiles in this vulnerable population. Results are intended to inform standardized perioperative pathways and support broader implementation and future comparative studies.

Interventions

• Procedure Lung transplantation that preserves spontaneous breathing function
  This intervention uses a spontaneous-breathing-preserving anesthesia strategy during lung transplantation, which differs from conventional management based on endotracheal intubation and invasive mechanical ventilation. A supraglottic airway (laryngeal mask airway) is used when feasible instead of endotracheal intubation to maintain spontaneous breathing throughout the procedure. Neuromuscular blocking agents are minimized, and regional nerve blocks (such as intercostal nerve blocks or paraverte

Primary outcome measures

• Number of Participants Requiring Postoperative Invasive Mechanical Ventilation (IMV) During Index Hospitalization [Time frame: From ICU admission immediately after leaving the operating room until hospital discharge or in-hospital death, assessed up to 90 days postoperatively (if hospitalization extends beyond 90 days, events after day 90 will not be counted for this outcome).]
• Postoperative Hospital Length of Stay (Days) During Index Hospitalization [Time frame: From end of surgery (postoperative Day 0) until hospital discharge or in-hospital death (index hospitalization), assessed up to 90 days.]
• Rate of Perioperative Survival [Time frame: From start of transplant surgery through hospital discharge or postoperative Day 30, whichever occurs first.]

Eligibility criteria

\[1\] Inclusion Criteria

• Age and informed consent: Age ≥18 years; able to understand the study and provide written informed consent; willing and able to comply with follow-up.
• Transplant candidacy: Listed in CLuTR or the participating center's lung transplant waiting list and scheduled to undergo allogeneic lung transplantation.
• Low body weight definition (core cohort criterion): Preoperative BMI <16 kg/m², calculated using the most recent traceable preoperative height and weight within the evaluation window.
• Preoperative support status: Not receiving ongoing invasive mechanical ventilation (endotracheal intubation or tracheostomy) and not on ECMO or other extracorporeal life support preoperatively.
• Minimum acceptable end-organ function: LVEF ≥40%; eGFR ≥40 mL/min/1.73 m²; no evidence of acute liver failure or decompensated cirrhosis/portal hypertension; American Society of Anesthesiologists (ASA) physical status ≤ IV.
• Infection and transmissible diseases: No evidence of active infection; no active tuberculosis; HIV/HBV/HCV status meeting center transplant requirements (e.g., undetectable viral load, where applicable).
• Rehabilitation and support: Demonstrated potential for postoperative rehabilitation (able to participate in training) and reliable caregiving support (at least one primary caregiver).

\[2\] Exclusion Criteria

• Consent/compliance: Refusal or withdrawal of informed consent; investigator judgment that follow-up cannot be completed or presence of recurrent severe non-adherence.
• Transplant type: Retransplantation, multi-organ transplantation, or planned lobar lung transplantation.
• Recent major cardiovascular/cerebrovascular events: Acute coronary syndrome/myocardial infarction or stroke within the past 30 days.
• Severe organ dysfunction/acute failure: LVEF <40%; eGFR <40 mL/min/1.73 m²; acute liver failure or decompensated cirrhosis/portal hypertension; acute renal failure requiring dialysis with low likelihood of recovery; significant preoperative neuropsychiatric disorder or altered mental status.
• High-risk/severe infection: Septic shock; active extrapulmonary or disseminated infection; active tuberculosis; detectable HIV viral load (or otherwise not meeting center transplant standards).
• High bleeding risk: Severe bronchiectasis not treated with preoperative vascular intervention or not readily correctable.
• Malignancy: Active malignancy or malignancy with high risk of recurrence or cancer-related mortality.
• Severe chest wall or spinal deformity: Definitively diagnosed severe thoracic cage deformity or spinal deformity.
• Substance use/dependence: Current use of cigarettes, e-cigarettes, inhaled cannabis, or intravenous drugs.
• Tubeless/spontaneous breathing-preserving strategy not safely feasible: Determined by the anesthesia team to have a difficult airway or unsafe supraglottic/non-intubated airway management (e.g., anticipated intraoperative airway difficulty, pharyngeal/laryngeal narrowing not suitable for a laryngeal mask airway), including but not limited to: Mallampati class >III, mouth opening <3 cm, thyromental distance <5 cm, or significant airway anatomic variants (e.g., aberrant right upper lobe bronchial takeoff in a planned right lung transplant) deemed difficult to manage safely with an LMA or single-lumen tube.
• Donor/donor lung limitations: Donor age >60 years; donor mechanical ventilation >14 days; positive donor airway microbiology deemed unacceptable by the transplant team.
• Protected populations: Pregnant or breastfeeding women.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07384572 · BREATHE-LowWt

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗