A novel external artificial lung system sustained an adult man for approximately 2 days after his irreversibly diseased lungs were removed in advance of a double lung transplant. Two years after the successful surgery, the patient showed excellent cardiopulmonary function, according to a team led by Ankit Bharat, MD, chief of thoracic surgery and executive director of the Northwestern Medicine Canning Thoracic Institute, Chicago. The details were published in Med, a Cell Press journal.

Pursuing the development of a total artificial lung (TAL) system is critical, Bharat told Medscape Medical News.

“We currently face a therapeutic dead end for patients with severe acute respiratory distress syndrome (ARDS) complicated by necrotizing pneumonia and septic shock; the mortality rate for these patients exceeds 80%,” he said. Although conventional support measures such as extracorporeal membrane oxygenation or mechanical ventilation can support gas exchange, they do not address the underlying problem of sepsis in the native lungs that drives refractory shock, Bharat explained.

“Lung transplantation is rarely an option in this setting because the patient is too unstable and infected,” Bharat said. “This [TAL] system allows us to perform a bilateral pneumonectomy — providing definitive source control — while maintaining hemodynamic stability, effectively bridging patients who would otherwise be considered non-transplantable to a successful outcome,” he said.

Shunting, Success, and Surprises

The primary physiologic challenge in the procedure was managing the loss of the pulmonary vascular bed, said Bharat. “The native lungs act as a capacitor that accommodates fluctuations in right ventricular output. When you remove the lungs, you remove that reservoir, placing the right ventricle at high risk for acute distension and failure,” he told Medscape Medical News. To overcome this hurdle, Bharat and colleagues engineered a flow-adaptive shunt between the pulmonary artery and the right atrium. “Calculating the precise resistance for this shunt to allow it to autoregulate — diverting excess flow when necessary while maintaining adequate system flow — was the most critical and technically demanding aspect of the design,” he said.

“The most remarkable observation was the speed of hemodynamic stabilization once the infected lungs were removed,” Bharat told Medscape Medical News. “Prior to the procedure, the patient was in refractory septic shock with rising lactate levels despite maximal support. Following the bilateral pneumonectomy and initiation of the TAL support, vasopressor requirements declined rapidly and were discontinued within approximately 12 hours,” he said. Within 24 hours, serum lactate dropped from 8.2 mmol/L to less than 1.0 mmol/L, he added. These outcomes were “a powerful confirmation that the lungs were indeed the driver of the systemic instability, and that the TAL system could effectively restore physiologic balance,” Bharat added.

Following the procedure, Bharat identified two main avenues for future research. First, multicenter registries are needed to validate the TAL approach and refine management protocols, particularly regarding anticoagulation strategies, he said. “We successfully managed this patient without systemic heparinization,” he noted. Second, more research to identify biomarkers that can distinguish between recoverable injury and end-stage fibrosis will help determine when lung injury in patients with ARDS is truly irreversible, Bharat said. “Identifying these markers early would allow us to refer appropriate patients for this salvage strategy before they deteriorate past the point of no return,” he added.

Treating the Untreatable

The researchers highlighted that patients with severe ARDS complicated by necrotizing pneumonia and septic shock are rarely candidates for lung transplantation because of infection, hemodynamic instability, and uncertainty about lung recovery, said Kartik Shenoy, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“A [TAL] system addresses this gap by providing both gas exchange and hemodynamic buffering, making it possible to safely remove infected lungs and stabilize patients who would otherwise die,” Shenoy told Medscape Medical News. “This creates a potential lifesaving bridge to transplantation for a previously untreatable/very-high-risk-for-transplant population,” he said

“One of the most surprising findings was how rapidly and completely hemodynamics stabilized after initiation of the [TAL] system,” said Shenoy, who was not involved in the project. “Vasopressors were discontinued within hours, lactate levels normalized, and end-organ perfusion improved despite the complete absence of native lungs,” he noted.

“Equally unexpected was the uniform and irreversible nature of lung injury revealed by single-cell and spatial transcriptomic analysis,” said Shenoy. “Rather than showing patchy or potentially reversible ARDS, all lung regions demonstrated molecular hallmarks of end-stage fibrosis, supporting that recovery was biologically impossible and perhaps validating the decision to proceed with transplantation,” he noted.

Engineering and Physiologic Challenges

Shenoy agreed with the researchers that maintaining cardiovascular stability while removing the diseased lungs was the most challenging aspect of the procedure. Once the pulmonary vascular bed is removed, patients are at high risk for acute right ventricular failure and circulatory collapse, he said. “Designing a system that could dynamically adapt to fluctuating blood flow, prevent ventricular overload, maintain continuous left-sided filling, and function without systemic anticoagulation in a septic patient represented a major physiologic and engineering challenge. Successfully overcoming this was central to the system’s success,” he added.

In order to make this procedure more accessible, future steps include the optimization of longer-term TAL support and refinement of the device’s design so it could be used outside of highly specialized centers, Shenoy told Medscape Medical News. “Ultimately, integrating artificial lung technology with precision biologic diagnostics could transform how clinicians decide when to pursue transplantation vs recovery-focused care,” he said. 

The study was funded by the National Institutes of Health. Bharat and Shenoy disclosed no financial conflicts of interest.