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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 107/3/696    most recent 90308.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mebrate, Y. Articles by Francis, D. P. PubMed PubMed Citation Articles by Mebrate, Y. Articles by Francis, D. P.

Dynamic CO₂ therapy in periodic breathing: a modeling study to determine optimal timing and dosage regimes

¹International Center for Circulatory Health, St. Mary's Hospital and Imperial College, ²Department of Clinical Engineering, Royal Brompton Hospital, and ³Department of Bioengineering, Physiological Flow Studies Unit, Imperial College, London, United Kingdom

Submitted 22 February 2008 ; accepted in final form 20 July 2009

We examine the potential to treat unstable ventilatory control (seen in periodic breathing, Cheyne-Stokes respiration, and central sleep apnea) with carefully controlled dynamic administration of supplementary CO₂, aiming to reduce ventilatory oscillations with minimum increment in mean CO₂. We used a standard mathematical model to explore the consequences of phasic CO₂ administration, with different timing and dosing algorithms. We found an optimal time window within the ventilation cycle (covering 1/6 of the cycle) during which CO₂ delivery reduces ventilatory fluctuations by >95%. Outside that time, therapy is dramatically less effective: indeed, for more than two-thirds of the cycle, therapy increases ventilatory fluctuations >30%. Efficiency of stabilizing ventilation improved when the algorithm gave a graded increase in CO₂ dose (by controlling its duration or concentration) for more severe periodic breathing. Combining gradations of duration and concentration further increased efficiency of therapy by 22%. The (undesirable) increment in mean end-tidal CO₂ caused was 300 times smaller with dynamic therapy than with static therapy, to achieve the same degree of ventilatory stabilization (0.0005 vs. 0.1710 kPa). The increase in average ventilation was also much smaller with dynamic than static therapy (0.005 vs. 2.015 l/min). We conclude that, if administered dynamically, dramatically smaller quantities of CO₂ could be used to reduce periodic breathing, with minimal adverse effects. Algorithms adjusting both duration and concentration in real time would achieve this most efficiently. If developed clinically as a therapy for periodic breathing, this would minimize excess acidosis, hyperventilation, and sympathetic overactivation, compared with static treatment.

heart failure; Cheyne-Stokes respiration; inhaled carbon dioxide