High Inspired CO2 Target Accuracy in Mechanical Ventilation and Spontaneous Breathing Using the Additional CO2 Method

Cerebrovascular Reactivity Imaging (CVR) is a diagnostic method for assessment of alterations in cerebral blood flow in response to a controlled vascular stimulus. The principal utility is the capacity to evaluate the cerebrovascular reserve, thereby elucidating autoregulatory functioning. Over the past decade, CVR has accumulated large interest, emerging as an expanding research field and application in a diverse spectrum of patient populations. In CVR, CO2 gas challenge is the most prevalent method, which elicits a vascular response by alterations in inspired CO2 concentrations. While several systems have been proposed in the literature, only a limited number have been devised to operate in tandem with mechanical ventilation, thus constraining the majority CVR investigations to spontaneous breathing individuals. We have developed a new method, denoted Additional CO2, designed to enable CO2 challenge in ventilators. The central idea is the introduction of an additional flow of highly concentrated CO2 into the respiratory circuit, as opposed to administration of the entire gas mixture from a reservoir. By monitoring the main respiratory gas flow emanating from the ventilator, the CO2 concentration in the inspired gas can be manipulated by adjusting the proportion of additional CO2. We evaluated the efficacy of this approach in controlled settings: 1) in a ventilator coupled with a test-lung and 2) in spontaneous breathing healthy volunteers. Additionally, we made a comparative analysis using a conventional method employing a gas reservoir containing a blend of O2, N2, and CO2 in varying concentrations. The methods were evaluated by assessment of the precision in attaining target inspired CO2 levels and examination of their performance within a Magnetic Resonance Imaging (MRI) environment. Our investigations revealed that the Additional CO2 method consistently achieved a high degree of accuracy in reaching target inspired CO2 levels in both mechanical ventilation and spontaneous breathing. We anticipate that these findings will lay the groundwork for a broader implementation of CVR assessments in mechanically ventilated patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was made possible through funding from the Swedish Research Council (Grant 2022-02886), theSwedishBrainFoundation(GrantFO2022-0109),andRegionO ̈stergo ̈tland(ALFgrant). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Swedish Ethical Review Authority gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors