Carmen D'Ugard

Multicenter Crossover Study of Automated Control of Inspired Oxygen in Ventilated Preterm Infants

OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (Fio2) adjustment in maintaining arterial oxygen saturation (Spo2) within an intended range for mechanically ventilated preterm infants with frequent episodes of decreased Spo2. METHODS: Thirty-two infants (gestational age [median and interquartile range]: 25 weeks [24–27 weeks]; age: 27 days [17–36 days]) were studied during 2 consecutive 24-hour periods, one with Fio2 adjusted by clinical staff members (manual) and the other by an automated system (automated), in random sequence. RESULTS: Time with Spo2 within the intended range (87%–93%) increased significantly during the automated period, compared with the manual period (40% ± 14% vs 32% ± 13% [mean ± SD]). Times with Spo2 of >93% or >98% were significantly reduced during the automated period (21% ± 20% vs 37% ± 12% and 0.7% vs 5.6% [interquartile ranges: 0.1%–7.2% and 2.7%–11.2%], respectively). Time with Spo2 of <87% increased significantly during the automated period (32% ± 12% vs 23% ± 9%), with more-frequent episodes with Spo2 between 80% and 86%, whereas times with Spo2 of <80% or <75% did not differ between periods. Hourly median Fio2 values throughout the automated period were lower and there were substantially fewer manual Fio2 changes (10 ± 9 vs 112 ± 59 changes per 24 hours; P < .001), compared with the manual period. CONCLUSIONS: In infants with fluctuations in Spo2, automated Fio2 adjustment improved maintenance of the intended Spo2 range led to reduced time with high Spo2 and more-frequent episodes with Spo2 between 80% and 86%.

Effects of Synchronization During Nasal Ventilation in Clinically Stable Preterm Infants

Nasal ventilation is increasingly used to reduce invasive ventilation in preterm infants. The effects of nasal ventilation and the advantages of synchronized nasal ventilation have not been fully evaluated. The objective was to compare the short-term effects of nasal intermittent mandatory ventilation (NIMV) and synchronized NIMV (S-NIMV) with nasal continuous positive airway pressure (NCPAP) on ventilation, gas exchange, and infant-ventilator interaction. Sixteen clinically stable preterm infants requiring NCPAP (GA, 27.6 ± 2.3 wk; birthweight (BW), 993 ± 248 g; and age, 15 ± 14 d) were exposed to NCPAP, NIMV at 20/min, NIMV at 40/min, S-NIMV at 20/min, and S-NIMV at 40/min for 1 h each (Infant-Star ventilator), in random order. Tidal volume, minute ventilation, and gas exchange did not differ significantly between NCPAP, NIMV, and S-NIMV. Inspiratory effort decreased during S-NIMV compared with NCPAP and NIMV, whereas inspiratory effort during NIMV did not differ from NCPAP. Active expiratory effort and expiratory duration increased during NIMV. Chest wall distortion, apnea and hypoxemia spells, abdominal girth, and comfort did not differ. In conclusion, there were no short-term benefits on ventilation and gas exchange of nasal ventilation compared with NCPAP in clinically stable preterm infants. However, synchronized nasal ventilation reduced breathing effort and resulted in better infant-ventilator interaction than nonsynchronized nasal ventilation.

Automated Adjustment of Inspired Oxygen in Preterm Infants with Frequent Fluctuations in Oxygenation: A Pilot Clinical Trial

OBJECTIVE To assess the efficacy of a system for automated fraction of inspired oxygen (FiO(2)) adjustment in maintaining oxygen saturation (SpO(2)) within an intended range in preterm infants with spontaneous fluctuations in SpO(2). STUDY DESIGN Sixteen infants (gestational age, 24.9 +/- 1.4 weeks; birth weight, 678 +/- 144 g; age, 33 +/- 15 days) with frequent hypoxemia episodes underwent two 4-hour periods of FiO(2) adjustment by clinical personnel (routine) and the automated system (automated). RESULTS Compared with the routine period, the percent time within intended SpO(2) range (88%-95%) increased during the automated period (58% +/- 10% versus 42% +/- 9%; P < .001), whereas the percent time with SpO(2) higher than the intended range and >or=98% were reduced (9% +/- 10% versus 31% +/- 8% [P < .001] and 3% +/- 5% versus 16% +/- 9% [P < .001], respectively). Percent time with SpO(2) < 88% increased during the automated period (33% +/- 7% versus 27% +/- 9%; P = .003) because of more frequent episodes, whereas the time with SpO(2) < 75% did not differ. The 4-hour median FiO(2) was lower during the automated period (29% +/- 4% versus 34% +/- 5%; P < .001). CONCLUSION Automated FiO(2) adjustment improved maintenance of SpO(2) within the intended range and reduced hyperoxemia and FiO(2). These findings should be examined in longer periods with standard clinical conditions and, eventually, in the context of randomized trials powered to detect clinically important effects on outcome.

Effects of Pressure Support during an Acute Reduction of Synchronized Intermittent Mandatory Ventilation in Preterm Infants

BACKGROUND:During weaning of synchronized intermittent mandatory rate in preterm infants, the spontaneous breaths must overcome the resistance of the endotracheal tube and the disease-induced respiratory loads. Pressure Support (PS) can be used as an adjunct to synchronized intermittent mandatory ventilation (SIMV) to partially unload the spontaneous breaths.OBJECTIVE:To evaluate the effects of two levels of PS as an adjunct to SIMV on gas exchange and breathing effort during an acute reduction in SIMV rate in preterm infants.METHODS:In all, 15 infants (birth weight 793±217 g, gestational age 26.4±1.5 weeks, postnatal age 15±16 days). Ventilatory support consisted of SIMV with peak inspiratory pressure (PTP) 16.3±1.3 cmH2O, positive end-expiratory pressure (PEEP) 4.3±0.6 cmH2O, and fraction of inspired oxygen (FiO2) 0.26±0.06. Infants were studied during four 30-minute periods: Two baseline SIMV periods and two periods of SIMV plus PS, in random order. During SIMV+PS, SIMV rate was lowered by 10 breaths per minute (b/minute) and PS was set at 3 and 6 cmH2O (SIMV+PS3 and SIMV+PS6, respectively).RESULTS:SIMV rate was reduced during SIMV+PS from 21.4±6.6 to 11.4±6.6 b/minute. Arterial oxygen saturation, transcutaneous carbon dioxide tension and FiO2 remained unchanged. Minute ventilation, total respiratory rate and mean airway pressure were higher during SIMV+PS. Per-breath inspiratory effort was lower during SIMV+PS and this was more striking during SIMV+PS6. Spontaneous inspiratory effort per minute increased during SIMV+PS3, but this increase was averted during SIMV+PS6.CONCLUSION:Assistance of the spontaneous breaths with pressure support maintained gas exchange. PS of 6 cm H2O prevented an increase in breathing effort during an acute 50% reduction in SIMV rate.

A Randomized Controlled Trial of Two Nasal Continuous Positive Airway Pressure Levels after Extubation in Preterm Infants

OBJECTIVE To compare extubation failure rate with two ranges of nasal continuous positive airway pressure (NCPAP) in oxygen dependent preterm infants. STUDY DESIGN Preterm infants of birth weight 500-1000 g and gestational age 23-30 weeks, extubated for the first time during the first 6 weeks while requiring fraction of inspired oxygen ≥ 0.25, were randomly assigned to a NCPAP range of 4-6 (low NCPAP) or 7-9 (high NCPAP) cmH2O. RESULTS Infants were randomized to low (n = 47) or high NCPAP (n = 46) at day 16.3 ± 14.7 and 15.5 ± 12.4, respectively. Rates of extubation failure per criteria (24% vs 43%, P = .04, OR and 95% CI: 0.39 [0.16-0.96]) and re-intubation (17% vs 38%, P = .023, 0.33 [0.016-0.85]) within 96 hours were significantly lower in the high- compared with the low NCPAP group. This was mainly due to a strikingly lower failure rate in the 500-750 g birth weight strata. Duration of ventilation, bronchopulmonary dysplasia, or severe bronchopulmonary dysplasia did not differ significantly. No infant developed pneumothorax during 96 hours post-extubation. CONCLUSIONS Extubation failure in preterm infants with residual lung disease was lower with NCPAP range of 7-9 compared with 4-6 cmH2O. These findings suggest the need for higher distending pressure post-extubation in the more immature infants who are still oxygen dependent.

Effects of instrumental dead space reduction during weaning from synchronized ventilation in preterm infants.

Objective:A majority of the modalities of synchronized ventilation in preterm infants require the use of flow sensors that can increase dead space and may adversely affect ventilator weaning. The objective of this study was to assess the effects of flow sensor dead space during synchronized intermittent mandatory ventilation (SIMV) weaning in preterm infants.Study Design:Twelve preterm infants (gestational age 25±2 weeks, birth weight 705±158 g, age: 31±186 days, SIMV rate: 25±8 breaths min–1, peak inspiratory pressure 18±2 cm H2O, positive end-expiratory pressure: 5±0.5 cm H2O, pressure support: 9±3 cm H2O, fraction of inspired oxygen: 34±6%) underwent two 2.5-h weaning periods during which SIMV rate was reduced twice by 5 breaths min–1 at 30-min intervals as tolerated, with and without reduction of flow sensor dead space, in random sequence. A 30-min baseline was obtained before each weaning period. Dead space was reduced by flushing the flow sensor with a continuous gas leak flow in the endotracheal tube connector.Result:Transcutaneous CO2 tension during SIMV weaning periods without and with reduced dead space did not differ from baseline, whereas total minute ventilation and tidal volume were lower during the SIMV weaning period with reduced dead space. Three infants did not tolerate SIMV weaning without while one infant did not tolerate weaning with reduced dead space.Conclusion:SIMV weaning elicited a compensatory rise in spontaneous ventilation. When flow sensor dead space was reduced during SIMV weaning, gas exchange was maintained with lower minute ventilation. Instrumental dead space imposes a ventilatory burden during SIMV weaning in small preterm infants.

Acute effects of inhaled nitric oxide on pulmonary and cardiac function in preterm infants with evolving bronchopulmonary dysplasia.

BACKGROUND: Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance by preferential vasodilation in ventilated lung units. In experimental animals, iNO also reduces airway resistance by smooth muscle relaxation. Hence, there may be a therapeutic role for iNO in evolving bronchopulmonary dysplasia (BPD).OBJECTIVE: To evaluate the acute effects of low-dose iNO on lung mechanics, ventilation distribution, oxygenation, and cardiac function in preterm infants with evolving BPD.METHODS: Measurements of lung compliance (CL), airway resistance (RL), ventilation-distribution (N2 clearance in multiple-breath washout), oxygenation (SpO2), left ventricular ejection fraction (LVEF) and right ventricular shortening fraction were obtained before and during 2 hours of iNO (10 ppm) in a group of ventilated preterm infants with evolving BPD.RESULTS: A total of 13 preterm infants with (mean±SD) BW: 663.8±116 g, GA: 24.9±1.2 weeks, age: 32±14 days, mean airway pressure: 6.7±0.9 cmH2O and fraction of inspired oxygen: 0.35±0.06 were studied. iNO did not affect CL, RL or N2 clearance. There was a small increase in LVEF. Mean SpO2 remained unchanged, but the duration of spontaneous hypoxemic episodes increased during iNO.CONCLUSION: Low-dose iNO had no acute effects on lung function, cardiac function and oxygenation in evolving BPD.

Volume Guarantee Ventilation: Effect on Preterm Infants with Frequent Hypoxemia Episodes.

Background: Preterm infants on mechanical ventilation have spontaneous hypoxemia episodes (HE) triggered by decreases in lung volume and tidal volume (VT). Volume guarantee (VG) is a mode where the ventilator peak pressure is adjusted to keep the exhaled VT at a target level. The effect of VG on HE under routine clinical conditions has not been fully evaluated. Objective: To evaluate the effect of VG on HE in preterm infants in comparison to pressure control (PC) ventilation under routine clinical conditions. Methods: Twenty-four mechanically ventilated preterm infants with ≥4 HE of arterial oxygen saturation (SpO2) <75% over 8 h were enrolled. They were studied over 2 consecutive 24-hour periods of VG and PC, in random order. Results: While the frequency of HE (SpO2 <85% for ≥20 s) did not differ, their duration was reduced during VG. The frequency or duration of severe HE (SpO2 <75% for ≥20 s) did not differ between PC and VG. The proportion of time in severe hypoxemia (SpO2 <75%) during VG did not differ from PC [median: 4.4 (IQR 2.9-5.0) vs. 5.0% (IQR 3.9-6.9), p = 0.44]. The fraction of inspired oxygen (FiO2) was lower during VG compared to PC. Conclusion: The use of VG during routine clinical conditions resulted in a modest reduction in the duration of HE (SpO2 <85%) and FiO2 compared to PC. The use of VG did not reduce the more severe HE.

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial

Objective To evaluate in a randomized, double‐blind, placebo‐controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Study design Preterm infants born at 23‐30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Results Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10‐41 days) and control groups (median, 20 days; IQR, 9‐43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Conclusions Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. Trial Registration ClinicalTrials.gov: NCT01751724.

Hypoxemia Episodes during Day and Night and Their Impact on Oxygen Saturation Targeting in Mechanically Ventilated Preterm Infants

Background: Hypoxemia episodes (HE) occur frequently in ventilated preterm infants and hinder the achievement of arterial oxygen saturation (SpO2) targets. These episodes may increase the risk for retinopathy of prematurity and neurodevelopmental disability. There are no data on the variation in HE and SpO2 targeting between day and night. Objective: The aim of this study was to evaluate the difference between day and night on the frequency and severity of HE and achievement of SpO2 targets. Methods: Twenty-four mechanically ventilated preterm infants with ≥4 episodes of SpO2 <75% over an 8-h period were enrolled. The fraction of inspired oxygen (FiO2), SpO2, and ventilator parameters were recorded over 24 h. Data from the day (9 a.m. to 5 p.m.) were compared to the night (9 p.m. to 5 a.m.) for the frequency of HE and proportion of time within and outside the target SpO2 range (90-95%). Results: The frequency of severe HE (SpO2 <75, ≥20 s) and prolonged severe HE (SpO2 <75, ≥60 s) was lower during the night compared to the day (1.6 ± 1.0 vs. 2.4 ± 1.3 episodes/h, p = 0.008, and 0.53 ± 0.35 vs. 0.90 ± 0.54 episodes/h, p = 0.018). There was no difference in mean episode duration. The frequency and duration of mild HE (SpO2 <85, ≥20 s) were lower during the night compared to the day (5.9 ± 2.7 vs. 7.1 ± 2.5 episodes/h, p = 0.003, and 72 ± 15 vs. 87 ± 25 s, p = 0.01, respectively). The proportion of time in severe hypoxemia (SpO2 <75%) was smaller, whereas time in hyperoxemia (SpO2 >95%) was greater, during the night compared to the day. The mean FiO2 did not differ between day and night. Conclusion: In this group of infants with frequent HE, nighttime was associated with fewer episodes when compared to daytime. This is likely due to less handling and sensory stimulation during the night. The increase in time spent with hyperoxemia during the night is likely to be due to more tolerance of high SpO2 with less proactive weaning of FiO2.