A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs
Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health.
METHODS:A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2).
RESULTS:Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group.
CONCLUSIONS:The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This multicentre pilot study randomised rejected lungs to ex-vivo perfusion (EVLP), EVLP with gaseous nitric oxide (gNO) introduced directly into the perfusate (n=16) or inhaled NO via the ventilator (iNO; n=4). Lungs with gaseous NO demonstrated improved aggregate scores in markers of lung physiology (delta PO2, static compliance and pulmonary vascular resistance), with lower lung weights. No difference was seen in the iNO group. No differences were seen in the assessment of transplantability between groups by any of the observers. As an experimental study, the design was good with randomisation and blinding of outcome assessment in the gNO subgroup (the iNO subgroup was unblinded). The limitations are small numbers (especially in the iNO subgroup) and the discarded nature of the organs which are therefore not comparable to those used in clinical transplantation. Nonetheless, these results warrant further investigation, in particular with regards to post-transplant clinical outcomes of NO delivery during EVLP. |
Methodological quality
| Jadad score | 2 |
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| Allocation concealment | NO |
| Data analysis | PER PROTOCOL |
Study Details
| Aims: | This study aimed to evaluate whether administering exogenous nitric oxide during ex vivo lung perfusion (EVLP) improves lung health. |
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| Interventions: | Donor lungs were randomised to receive either gaseous nitric oxide (gNO) plus perfusate or perfusate alone. |
| Participants: | 20 bilateral lungs (16 were included in blinded study and 4 in the open-label study). |
| Outcomes: | The primary outcomes were overall score for lung physiology indicators and total duration of stable EVLP time. The secondary outcomes were measurements of transplantation suitability, lung weight and left atrium partial pressure of oxygen (LAPO2). |
| Follow Up: | 10 hours. |
Metadata
| Funding: | Industry funding |
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| Publication type: | Randomised Controlled Trial |
| Organ: | Lung |
| Language: | English |
| Author email: | matthew.hartwig@duke.edu |
| MeSH terms: | Lung Transplantation |