Continuous Endogenous Exhaled CO Monitoring by Laser Spectrometer in Human EVLP Before Lung Transplantation

Abstract

Endogenous production of carbon monoxide (CO) is affected by inflammatory phenomena and ischemia-reperfusion injury. Precise measurement of exhaled endogenous CO (eCO) is possible thanks to a laser spectrometer (ProCeas® from AP2E company). We assessed eCO levels of human lung grafts during the normothermic Ex-Vivo Lung Perfusion (EVLP). ProCeas® was connected in bypass to the ventilation circuit. The surgical team took the decision to transplant the lungs without knowing eCO values. We compared eCO between accepted and rejected grafts. EVLP parameters and recipient outcomes were also compared with eCO values. Over 7 months, eCO was analyzed in 21 consecutive EVLP grafts. Two pairs of lungs were rejected by the surgical team. In these two cases, there was a tendency for higher eCO values (0.358 ± 0.52 ppm) compared to transplanted lungs (0.240 ± 0.76 ppm). During the EVLP procedure, eCO was correlated with glucose consumption and lactate production. However, there was no association of eCO neither with edema formation nor with the PO₂/FiO₂ ratio per EVLP. Regarding post-operative data, every patient transplanted with grafts exhaling high eCO levels (>0.235 ppm) during EVLP presented a Primary Graft Dysfunction score of 3 within the 72 h post-transplantation. There was also a tendency for a longer stay in ICU for recipients with grafts exhaling high eCO levels during EVLP. eCO can be continuously monitored during EVLP. It could serve as an additional and early marker in the evaluation of the lung grafts providing relevant information for post-operative resuscitation care.

Keywords: carbon monoxide; cavity enhanced laser absorption spectroscopy; ex-vivo lung perfusion; gasotransmitters; ischemia-reperfusion; lung inflammation; lung transplant; spectroscopy.

FIGURE 1

Overview of the setup of EVLP preparation with the XPS^TM device on the right and the ProCEAS® in the background, monitoring eCO in real-time. In the front plane is the ventilated and perfused ex-vivo lung.

FIGURE 2

CO endogenous production monitored in real -time during ex-vivo lung perfusion. Time origin corresponds to the ventilation start. Before the connection to the lung, the analyzer measures CO concentration in ambient air. A strong release of eCO is observed at the beginning of the lung opening period (wine arrow). During inter-recruitment periods (orange arrows), lungs are ventilated with a FiO₂ of 21% and a PEEP of 5 cmH2O. During each recruitment period (purple arrow), the FiO₂ is increased to 100% (pink box), while the PEEP is increased to 10 cmH2O only during the first 10 min (green box) and then set back to 5 cmH2O.

FIGURE 3

Zooms-in of eCO measurements presented in Figure 2 (Data from one EVLP procedure, displayed as example) Left: entire first recruitment period. Right: zoom on the last minutes of the recruitment phase. The respiratory cycles can be distinguished, allowing the identification of maximum (red) and minimum (green) CO values to derive the lungs’ endogenous CO production.

FIGURE 4

Data from two EVLP procedures displayed as examples of eCO monitoring of “standard” lungs (left) and eCO monitoring of “hemorrhagic” lungs (right). Among the total of 21 EVLP procedures that we monitored, only 3 pairs of lungs had an “hemorrhagic profile” like the one shown on the right part of this figure. Although these 3 pairs of lungs were transplanted by the surgeons without problems for the recipients, we decided to exclude a priori these 3 pairs of lungs from the eCO data analysis.

FIGURE 5

Flow chart. Abbreviations: DCD: Donor after Circulatory Death, BDD: Brain Dead Donors.

FIGURE 6

eCO and metabolism. Glucose consumption is estimated as the difference in glucose concentration in perfusate between the two first recruitment maneuvers. When removing the outlier point (lung #18), the correlation is still significant (p < 0.05; ρ = 0.49) between eCO and glucose consumption, but not anymore with lactate concentration.

FIGURE 7

eCO and length of stay in ICU. Patients receiving lungs exhaling “high” eCO levels (>0.235 ppm) at 1st EVLP evaluation, have a trend to stay longer in ICU.