Changes in minute ventilation after exposure to 4% sulfur hexafluoride (SF6) in infants

With interest, we read the recent publication by G. Banton et al. Exposure to 4% sulfur hexafluoride (SF6) during multiple breath washout (MBW) in infants was associated with diminished minute ventilation (VE) and increased tidal volume (VT). 1 Infants studied were heterogeneous regarding disease state, age, and use of sedation.Wewondered if changes in breathing pattern are reproducible in a more homogenous cohort of a narrow age range and always measured without sedation. In order to answer this, we took advantage of existing data from our birth cohort and assessed post-hoc breathing pattern encountered during 4% SF6 exposure for MBW. We analyzed tidal breathing and MBWSF6 measurements conducted between 2004 and 2014 in 30 preterm infants with a gestational age at birth between 23.9–35.4 weeks, and in 30 healthy term-born controls. The Ethics Committee of Bern approved the study, written parental informed consent was obtained. Lung functionwasmeasured during natural, quiet sleep as described. Each infant underwent one tidal breathing measurement (dry medical air) lasting 10min, followed by at least two MBWSF6 measurements using an open bypass system (Exhalyzer D, Eco Medics AG, Switzerland). Infants breathed the SF6 gas mixture via face mask until an equilibrium (washin) was established between inand exhaled SF6 fractions. The setup was switched to dry medical air for subsequent washout. Primary outcomes were VT, coefficient of variation of VT (CVVT), respiratory rate, and VE. These were compared (i) between the tidal breathing and MBWSF6 measurements and (ii) within tidal breathing measurements to assess physiological fluctuations. Data distribution was visually assessed and paired t-tests were applied using Stata (Release 11. College Station, TX: StataCorp LP). The mean (range) postmenstrual age was 45 (43–49) weeks at the time of the study. Four percent SF6 induced hypopnea in both preterm and healthy infants. When comparing 100 breaths duringmedical air versus 20 breaths during SF6 washin, VT and VE declined while respiratory rate did not. Mean decrease in VE was 140.0ml/min (95% CI: 70.0–210.1; P< 0.001) in preterm infants and 166.0 ml/min (87.2–244.9; P< 0.001) in healthy controls. The relative mean change of VE was 14% in preterm infants and 10% in healthy controls. Interestingly, VTand VE remained comparably low during SF6 washout (Fig. 1). When comparing the last 20 breaths during medical air versus 20 breaths during SF6 washin, VT and VE also declined. VT decreased by 3.1ml (1.9–4.3; P< 0.001) in preterm infants and 3.1ml (1.5–4.8; P< 0.001) in controls. Accordingly, VE decreased by 196.9ml (137.4–256.4; P< 0.001) in preterm infants and of 117.0ml (46.9–187.0; P1⁄4 0.002) in controls. Comparing the first 20 breaths with the last 20 breaths during medical air to assess physiologic fluctuations, VT andCVVTdid not change systematically. In 90%of infants, reduction of VE upon inhalation of SF6 exceeded their own physiologic variability (mean þ2 standard deviations of changes). This effect was even larger in infants remaining asleep (n1⁄4 41/60) compared to those who woke up between tests irrespective of preterm birth. In contrast to the previous study, in our protocol the setup’s CO2 sensor was only attached for tidal breathing but not for MBW measurements. Therefore, we additionally assessed 10 healthy term born infants with the CO2 sensor insertedalsoduringMBW.All these infants remainedasleep during the testing session. The effect size and direction of change in breathing pattern was akin. Comparing 100 breaths during medical air versus 20 breaths during SF6 washin, VE declined by 198.8ml (97.6–230.0, P1⁄4 0.002) without relevant changes in end-tidal CO2. We reassure that exposure to 4% SF6 during MBW systematically influences breathing pattern in infants. This also supports findings in adults, in whom inhalation of a