Modified oxygen mask to induce target levels of hyperoxia and hypercarbia during radiotherapy: A more effective alternative to carbogen

Abstract

Purpose: Carbogen has long been under investigation as an adjuvant to radiotherapy of tumors. A major factor confounding its evaluation is its inconsistency in raising blood partial pressure of CO₂ (pCO₂). We investigated whether a new partial rebreathing method would provide better control of pCO₂ than carbogen.

Methods and materials: We compared the efficacy of each method in 10 healthy volunteers. Volunteers breathed 1.5, 3 and 5% carbogen in 5-min stages via the usual non-rebreathing circuit. All the volunteers then breathed 100% O₂ through a commercial sequential gas delivery (SGD) circuit modified by attaching a reservoir to its exhalation port. Hypercarbia was induced by step reductions in oxygen flow to the SGD circuit. We monitored minute ventilation and end-tidal pCO₂ (ETpCO₂) as a surrogate for its arterial value.

Results: Inhalation of 1.5 and 3% carbogen did not increase ETpCO₂ from baseline (40 ± 1.5 mmHg); 5% carbogen increased ETpCO₂ to 45 ± 1.6 mmHg (p < 0.001). With the SGD circuit, reducing O₂ flow to 4.3 ± 0.7 l/min increased ETpCO₂ in all subjects from 41 ± 2.0 mmHg (baseline) to 46 ± 2.1 mmHg (p < 0.001). Voluntary hyperventilation reduced ETpCO₂ with 5% carbogen but not with SGD (p = 0.379).

Conclusions: We confirm previous observations that carbogen inhalation does not result in a predictable rise in ETpCO₂ and suggest that a precise and stable target ETpCO₂ can instead be induced by simply controlling O₂ flow into a modified SGD circuit. We hoped that the reliable control of pCO₂ will enable studies that address first, the efficacy of raising ETpCO₂ on specific tumor blood flow, and eventually, its benefit as an adjuvant to radiotherapy.

Keywords:

• Radiosensitizers
• hypoxia
• carbogen
• tumor oxygenation
• hypercarbia
• rebreathing

Abbreviations
SGD	=	sequential gas delivery
pCO2	=	partial pressure of carbon dioxide
pO2	=	partial pressure of oxygen
ETpCO2	=	end-tidal partial pressure of CO2
ETpO2	=	end-tidal partial pressure of O2
Hypercarbia	=	increased carbon dioxide concentration in the blood
Hyperoxia	=	increased oxygen concentration in the blood
End-tidal FO2	=	fractional concentration of end-tidal oxygen

Abbreviations
SGD	=	sequential gas delivery
pCO2	=	partial pressure of carbon dioxide
pO2	=	partial pressure of oxygen
ETpCO2	=	end-tidal partial pressure of CO2
ETpO2	=	end-tidal partial pressure of O2
Hypercarbia	=	increased carbon dioxide concentration in the blood
Hyperoxia	=	increased oxygen concentration in the blood
End-tidal FO2	=	fractional concentration of end-tidal oxygen