CO and NO pulmonary diffusing capacity during pregnancy: Safety and diagnostic potential

Abstract

This paper reviews the scientific evidence for the safety of carbon monoxide (CO) and nitric oxide (NO) inhalation to measure pulmonary diffusing capacity (DL(CO) and DL(NO)) in pregnant women and their fetuses. In eight earlier studies, 650 pregnant women had DL(CO) measurements performed at various times during pregnancy, with a minimum of two to four tests per session. Both pregnant subjects that were healthy and those with medical complications were tested. No study reported adverse maternal, fetal, or neonatal outcomes from the CO inhalation in association with measuring DL(CO). Eleven pregnant women, chiefly with pulmonary hypertension, and 1105 pre-term neonates, mostly with respiratory failure, were administered various dosages of NO (5-80ppm for 4 weeks continuously in pregnant women, and 1-20ppm for 15min to 3 weeks for the neonates). NO treatment was found to be an effective therapy for pregnant women with pulmonary hypertension. In neonates with respiratory failure and pulmonary hypertension, NO therapy improved oxygenation and survival and has been associated with only minor, transient adverse effects. In conclusion, maternal carboxyhemoglobin ([Hb(CO)]) levels can safely increase to 5% per testing session when the dose-exposure limit is 0.3% CO inhalation for <or=3min, and for NO, 80ppm for <or=3min. The risk of late fetal or neonatal death from increased Hb(CO) from diffusion testing is considerably less than the risk of death from all causes reported by the Centers for Disease Control, and is therefore considered "minimal risk".

Fig. 1

The predicted maternal and fetal [Hb_CO] when a mother breaths 50 ppm CO for 16 h, followed by an 8 h period in which no CO was inspired. The level of CO exposure is equivalent to smoking about 1–1.5 packs of cigarettes per day, followed by an 8 h sleep period. Figure modified by Longo (1977) based on the mathematical model by Hill et al. (1977).

Fig. 2

Changes in maternal and fetal [Hb_CO] during and after a 24 h exposure to 68 ppm CO and a 4 h exposure to 300 ppm CO. If the maternal value of 10% Hb_CO were obtained at equilibrium (point A), the fetal [Hb_CO] would be equal to about 11%. If the sample was taken at point B during the washout phase, the fetal [Hb_CO] would be about 14%. However, if the blood sample was taken during the uptake phase (point C), the fetal [Hb_CO] would be 2%. Not only is it impossible to predict fetal [Hb_CO] on the basis of a single maternal blood sample, but the length of time necessary to reduce the fetal [Hb_CO] depends on whether the concentration has already peaked or is still rising. In the case of lung diffusing testing, which could require up to about 3 min of 3000 ppm CO inhalation, the maternal [Hb_CO] may increase to 5%, but the fetal Hb_CO would hardly increase. This is typified by the enhanced “Detail” on the right panel in figure. Figures reproduced from Longo (1977).