The Groundbreaking Case at Northwestern University

In a feat that pushes the boundaries of medical science, surgeons at Northwestern University Feinberg School of Medicine achieved what was previously thought impossible: keeping a critically ill patient alive for 48 hours entirely without lungs. This lungless survival breakthrough occurred in spring 2023 when a 33-year-old man from Missouri arrived at Northwestern Memorial Hospital in dire condition. What started as influenza B escalated into necrotizing pneumonia caused by carbapenem-resistant Pseudomonas aeruginosa, leading to liquefied lungs, overwhelming sepsis, and multiple cardiac arrests. The patient's heart stopped upon arrival, requiring immediate cardiopulmonary resuscitation (CPR).

Traditional treatments, including broad-spectrum antibiotics and venoarterial extracorporeal membrane oxygenation (VA-ECMO), failed to control the infection. The lungs had become the primary source of sepsis, making a direct double lung transplant too risky. The Northwestern team, led by thoracic surgeon Ankit Bharat, MD, chief of thoracic surgery and executive director of the Canning Thoracic Institute, made a bold decision: perform a bilateral pneumonectomy—surgical removal of both lungs—to eradicate the infection source, then bridge the patient to transplant using a novel total artificial lung (TAL) system they engineered.

Navigating the Perils of Bilateral Pneumonectomy

Bilateral pneumonectomy is rarely attempted due to profound physiological challenges. Normally, the lungs serve dual roles: gas exchange and hemodynamic buffering. The pulmonary vascular bed acts as a low-resistance capacitor, absorbing the right ventricle's full cardiac output (about 5-8 liters per minute) without overload. Without lungs, blood flow drops resistance dramatically, causing right ventricular distension, failure, and underfilling of the left heart, leading to systemic hypotension and rapid death. Standard ECMO exacerbates risks like recirculation, clotting, and hemorrhage in this empty-chest state.

Historical survival post-bilateral pneumonectomy is dismal, often mere hours even with support. In the US, lung transplants number around 2,500 annually via the United Network for Organ Sharing (UNOS), with over 1,300 patients on the active waitlist. Median post-transplant survival is about 6.1 years, but sepsis-complicated cases like acute respiratory distress syndrome (ARDS) have poorer outcomes. Northwestern's innovation addressed these hurdles head-on, stabilizing the patient long enough for recovery and transplant.

Engineering the Flow-Adaptive Total Artificial Lung System

The TAL system, detailed in a January 2026 Med (Cell Press) publication, mimicked lung functions comprehensively. Key components included:

• A 31F dual-lumen ProtekDuo cannula in the right atrium/main pulmonary artery for venous drainage.
• A Rotaflow centrifugal pump pushing blood through a high-capacity Quadrox-i oxygenator at full cardiac output (>8 L/min).
• A flow-adaptive shunt (14 mm Gore-Tex conduit) from right pulmonary artery to right atrium, recirculating 1.1-6.3 L/min to prevent right heart overload.
• Dual 10 mm Dacron grafts returning oxygenated blood to the left atrium via superior pulmonary veins, ensuring preload.
• Chest stabilization with bovine pericardium reconstruction, saline-filled tissue expanders, and sponges to prevent heart shift and bleeding.

No systemic anticoagulation was needed post-bypass, minimizing clot risks. Targets: mean arterial pressure 60-70 mmHg, lactate <2 mmol/L, SvO2 >65%, urine >0.5 mL/kg/h.

Stabilization and Molecular Insights from the Explanted Lungs

Within 12 hours post-pneumonectomy, vasopressors were weaned, lactate dropped from 8.2 to <1.0 mmol/L by day 1, and sepsis resolved microbiologically. Echocardiography confirmed biventricular function preservation. After 48 hours, donor lungs arrived for successful transplant. At 24 months, forced expiratory volume in 1 second (FEV1) was 75% predicted, diffusing capacity for carbon monoxide (DLCO) 92%, left ventricular ejection fraction (LVEF) >60%.

Northwestern researchers conducted single-cell RNA sequencing (10x Genomics) and spatial transcriptomics (Visium HD, PhenoCycler) on explants, revealing 43 cell types with uniform necrosis, aggressive fibrosis, neutrophil/monocyte macrophage infiltration, absent alveolar type 2 (AT2) repair cells, and profibrotic pathways. This confirmed irreversibility, contrasting recoverable ARDS.Read the full study in Med.

Photo by Joss Broward on Unsplash

Northwestern University's Legacy in Lung Transplant Innovation

Northwestern's Canning Thoracic Institute ranks No. 7 nationally for pulmonology/lung surgery (U.S. News & World Report), performing high-volume transplants (148 in 2024). Ankit Bharat's team has pioneered ECMO bridges, ex vivo lung perfusion, and now TAL. This builds on prior research into ARDS molecular pathology, aiding biomarkers for transplant timing.

The breakthrough underscores university hospitals' role in translational research, where bedside innovation meets advanced analytics like Seurat/Scanpy for omics data.

Challenges in ARDS and Sepsis: A Growing Public Health Crisis

ARDS affects 200,000 US adults yearly (CDC), with 40% mortality. Drug-resistant infections like Pseudomonas rise amid antibiotic overuse. Only 20-30% of severe ARDS patients bridge to transplant successfully on ECMO due to complications. Bilateral pneumonectomy survival pre-TAL was near-zero beyond hours.

This case highlights needs for rapid molecular diagnostics and portable TAL devices, potentially expanding transplant eligibility.UNOS lung transplant data.

Future Directions: Artificial Lungs and Transplant Paradigms

TAL paves ways for implantable lungs, sepsis control pre-transplant, and protocols for "non-recoverable" ARDS. Multicenter trials needed for scalability. Northwestern eyes biomarkers from spatial omics for earlier intervention.

Implications extend to training: Feinberg's residency programs now incorporate TAL simulations, fostering surgeon-researchers.

Stakeholder Perspectives: From Surgeons to Patients

"His lungs were melting... We removed them, and his body started healing," Bharat noted. Patients/families should explore transplants early in refractory cases. Bioethicists praise balancing risks, while donors/transplant networks see efficiency gains.

Photo by Joss Broward on Unsplash

Broader Impacts on Higher Education and Medical Research

This underscores US universities' leadership in biomedicine. Northwestern's NIH-funded labs drive ECMO/TAL evolution. Collaborations with Cell Press amplify discoveries, attracting talent to higher ed jobs in thoracic research.Northwestern press release.

Actionable Insights for Researchers and Clinicians

• Prioritize molecular profiling in ARDS for irreversibility markers.
• Develop portable TAL variants for community hospitals.
• Integrate TAL training in med school curricula.
• Advocate policy for faster donor allocation in sepsis cases.

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