Administration and monitoring of nitric oxide in ex vivo fluids
Inventors
Potenziano, Jim • Hansell, Douglas R. • Griebel, Jeff • Costa, Eddie • Cooper, Lisa • Newman, David William
Assignees
Mallinckrodt Pharma IP Trading DAC • Therakos Inc • Mallinckrodt Critical Care Finance Inc
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Publication Number
US-10667510-B2
Publication Date
2020-06-02
Expiration Date
Abstract
Described are systems and methods for monitoring administration of nitric oxide (NO) to ex vivo fluids. Examples of such fluids include blood in extracorporeal membrane oxygenation (ECMO) circuits or perfusion fluids used for preserving ex vivo organs prior to transplanting in a recipient. The systems and methods described herein provide for administering nitric oxide to the fluid, monitoring nitric oxide or a nitric oxide marker in the fluid, and adjusting the nitric oxide administration.
Core Innovation
The invention relates to methods of perfusion and preserving a lung in which nitric oxide (NO) or an NO donor is provided during perfusion. The methods include monitoring methemoglobin in the perfusion fluid and adjusting an amount of NO or an NO donor delivered to the lung based on the monitored methemoglobin.
For lung preservation and transplant, an ex vivo lung is perfused with a perfusion fluid including NO or an NO donor. The methods include continuous monitoring of methemoglobin, and in response to the methemoglobin monitored, adjusting an amount of NO or NO donor to maintain NO dosing within a desired range.
In additional embodiments for preserving a lung for transplant, the perfusion fluid is circulated through a perfusion circuit that includes NO or an NO donor from a NO source. The methods include continuously monitoring at least one parameter of the perfusion fluid, where the parameter includes a NO marker, and adjusting the amount of NO or an NO donor to avoid overdosing and underdosing the lung.
Claims Coverage
The document provides three independent inventive methods for lung perfusion and preservation, based on methemoglobin-guided dosing, continuous methemoglobin monitoring to maintain a desired range, and NO-marker-based monitoring to avoid overdosing and underdosing.
Methemoglobin-guided NO dosing during lung perfusion
Perfusing a lung with a perfusion fluid; monitoring methemoglobin in the perfusion fluid; and adjusting an amount of NO or NO donor provided to the lung according to the methemoglobin monitored.
Desired-range NO dosing during ex vivo lung preservation
Perfusing an ex vivo lung with a perfusion fluid including NO or an NO donor; continuously monitoring methemoglobin; and in response to the methemoglobin being monitored, adjusting an amount of NO or an NO donor provided to the lung to maintain NO dosing within a desired range.
NO-marker-based adjustment to avoid overdosing and underdosing during transplant preservation
Perfusing an ex vivo lung with a perfusion fluid circulated through a perfusion circuit, wherein the perfusion fluid includes one of NO or an NO donor provided from a NO source; continuously monitoring at least one parameter of the perfusion fluid, wherein the parameter includes a NO marker; and in response to the parameters being monitored, adjusting an amount of NO or an NO donor provided to the lung to avoid at least one of overdosing and underdosing the lung.
Across the independent claims, the core coverage is control of NO or NO donor delivery to an ex vivo lung using monitored indicators in the perfusion fluid, with methemoglobin used for dosing control and a NO marker used to avoid overdosing and underdosing.
Stated Advantages
Avoid overdosing and underdosing the lung.
Maintain NO dosing to the lung within a desired range.
Adjust NO or an NO donor delivery based on monitored methemoglobin to guide dosing during perfusion and preservation.
Documented Applications
Perfusion and preservation of a lung, including methods for lung preservation for transplant.
Ex vivo lung preservation with NO or NO-donor perfusion and monitoring-based adjustment during lung preservation for transplant.
Transplant preparation involving additional handling steps such as persuffation and flushing [procedural detail omitted for safety].
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