Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS.

BACKGROUND: Low-dose inhaled carbon monoxide (iCO) has demonstrated significant therapeutic potential in preclinical studies, and its safety has been established in human studies. However, the safety of delivering personalized iCO concentrations of 200 to 500 ppm in ventilated patients with pneumonia and ARDS, targeting 7% HbCO at 90 min of exposure, remains unknown. METHODS: Personalized iCO concentrations needed to reach a plasma HbCO of 7% at 90 min were determined using a Coburn-Forster-Kane (CFK) calculator, utilizing baseline and 20-minute (20-min) arterial HbCO measurements at an iCO test concentration of 200 ppm. The personalized iCO concentration was administered for the remainder of the 90 min with HbCO measurements performed at 60-, 75-, and 90-minutes. RESULTS: There were no safety incidents observed during the study, and all exposed subjects were alive and well at 6-month follow-up. Surprisingly, we found significant deviations between measured and predicted HbCO levels at 90 min for individualized exposures with iCO of 220 to 425 ppm (p < 0.001), which were more discrepant at higher iCO doses. However, fitting the CFK model to the 20- to 90-minute HbCO measurements confirmed the validity of the CFK model and revealed significant deviations for baseline HbCO (p < 0.001), suggesting pulmonary vascular responses to iCO during the 20-min test exposure, confirmed by observed changes in DLCO. CONCLUSIONS: Pulmonary vasodilation in response to iCO can affect early HbCO kinetics, which is relevant to refining protocols for reliable, personalized iCO administration that optimize pulmonary iCO concentrations, thereby increasing the benefits of therapeutic iCO administration in lung diseases.