Physiological effects of apnoeic oxygenation using high-flow nasal oxygen

In anaesthetic practice, the inability to oxygenate and ventilate patients is a much-feared complication with risk for severe hypoxia-induced adverse outcomes. By administrating oxygen in the absence of spontaneous ventilation, apnoeic oxygenation may overcome these challenges by a prolonged time with sufficient oxygenation. However, the concomitant and continuous increase in systemic carbon dioxide has limited its use. Recently, by using high-flow nasal oxygen (HFNO) during apnoea in anaesthetised patients, there seemed to be some carbon dioxide elimination, which has resulted in increased use of apnoeic oxygenation in clinical practice. From these early observations, this thesis has explored an array of aspects of apnoeic oxygenation with high-flow nasal oxygen by describing gaseous exchange, effects on lung volumes and alterations in biomarkers for organ function and oxidative stress in humans, and finally, by studying advanced haemodynamic parameters and the consequences of different oxygen flow rates in an animal model.

The alterations of arterial oxygen, carbon dioxide and pH have been investigated by using apnoeic oxygenation with HFNO in subjects during general anaesthesia when laryngeal surgery of approximately 30 min duration was performed. Here, an extension of time with sufficient oxygenation was seen throughout the duration of surgery and a lower carbon dioxide rise compared to older studies of apnoeic oxygenation without high-flow oxygen. Also, an increase of arterial-end tidal carbon dioxide levels over time was noted.

Thus, lung volume changes were characterised in subjects randomised to either apnoeic oxygenation with HFNO or mechanical ventilation in patients presenting for laryngeal surgery under general anaesthesia. As determined by electrical impedance tomography, no impedance differences over time or between the groups were seen perioperatively. In the same cohort, biomarkers for oxidative stress and vital organ function were explored to investigate the impact of hyperoxia and the continuously rising hypercapnia during apnoeic oxygenation with HFNO. For both groups, the oxidative stress biomarker MDA increased, and further, a discrete but non-clinically relevant increase in the CNS injury biomarker S100B was described.

Finally, an experimental animal model of apnoeic oxygenation using 10 or 70 L/min of oxygen in a cross-over design with continuous central haemodynamic monitoring was used. Anaesthetised pigs were adequately oxygenated for up to 60 min of apnoea, with a carbon dioxide rise of approximately 0.5 kPa/min during both flow rates. Apnoea generated a continuously increasing, almost doubled mean pulmonary artery pressure. Also, cardiac index, heart rate, arterial blood pressure and cardiopulmonary ratio increased. Importantly, apnoea with no supplementary oxygen or flow resulted in a rapid desaturation to SpO2 < 85 % within 2.5 min.

In summary, apnoeic oxygenation with HFNO enables oxygenation and partial carbon dioxide elimination, thereby extending safe apnoeic time. Perioperative lung volume changes and alterations in biomarkers for vital organ function do not differ from traditional mechanical ventilation. Experimentally, several central haemodynamic parameters were affected during extreme hypercapnia, primarily pulmonary artery pressure. Different oxygen flow rates generated an equal oxygenation and carbon dioxide rise. These findings add essential knowledge of the physiology and use of apnoeic oxygenation with HFNO.

List of scientific papers

I. Apnoeic oxygenation in adults under general anaesthesia using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) - a physiological study. Ida-Maria Gustafsson*, Åse Lodenius*, Jonas Tunelli, Johan Ullman, Malin Jonsson Fagerlund. British Journal of Anaesthesia. 2017;118(4):610-7. *These authors contributed equally.
https://doi.org/10.1093/bja/aex036

II. Lung volume changes in Apnoeic Oxygenation using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) compared to mechanical ventilation in adults undergoing laryngeal surgery. Ida-Maria Forsberg, Johan Ullman, Anton Hoffman, Lars I. Eriksson, Åse Lodenius, Malin Jonsson Fagerlund. ACTA Anaesthesiologica Scandinavica. 2020;64(10):1491-1498.
https://doi.org/10.1111/aas.13686

III. Biomarkers for oxidative stress and organ injury during Transnasal Humidified Rapid-Insufflation Ventilatory Exchange compared to mechanical ventilation in adults undergoing microlaryngoscopy: A randomised controlled study. Ida-Maria Forsberg, Souren Mkrtchian, Anette Ebberyd, Johan Ullman, Lars I Eriksson, Åse Lodenius, Malin Jonsson Fagerlund. ACTA Anaesthesiologica Scandinavica. 2021; 65(9):1276-1284.
https://doi.org/10.1111/aas.13927

IV. Effect of oxygen flow rate on gaseous exchange and central hemodynamics in prolonged apneic oxygenation — a porcine model. Ida-Maria Forsberg, Jonathan Al-Saadi, Albin Sjöblom, Lisa Grape, Johan Petersson, Johan Lundberg, Åse Lodenius, Lars I Eriksson, Malin Jonsson Fagerlund. [Manuscript]