Physiological based CPAP for preterm infants at birth

Preterm infants are currently supported with 5-8 cmH2O continuous positivie airway pressure (CPAP) at birth. This pressure range is predominantly extrapolated from CPAP support later on the neonatal intensive care unit, while the underlying physiology during the transition at birth is considarably different. Based on literature- and retrospective studies, we hyptothesized that preterm infants may benefit from physiological-based (PB)-CPAP, wherein CPAP levels change following the pulmonary physiological changes during transition. PB-CPAP consists of an initial 15 cmH2O CPAP that promotes lung aeration, but that is later decreased to 8 cmH2O CPAP to maintain lung aeration. In animal studies, we demonstrated that PB-CPAP improves lung aeration and decreases the risk of apnea, without causing lung over-expansion when CPAP levels are decreased appropriately. In a randomized trial, we showed that PB-CPAP improves heart rates of preterm infants when compared to 5-8 cmH2O, which also implies improved lung aeration. Despite its benefits, the current PB-CPAP strategy is too complex for caregivers to combine with standard care. Future studies will focus on automatization or simplification of PB-CPAP to improve CPAP support for preterm infants at birth. LUMC / Geneeskund

Feasibility and effect of physiological-based CPAP in preterm infants at birth

Background: Preterm infants are commonly supported with 5-8 cmH(2)O CPAP. However, animal studies demonstrate that high initial CPAP levels (12-15 cmH(2)O) which are then reduced (termed physiological based (PB)-CPAP), improve lung aeration without adversely affecting cardiovascular function. We investigated the feasibility of PB-CPAP and the effect in preterm infants at birth.Methods: Preterm infants (24-30 weeks gestation) were randomized to PB-CPAP or 5-8 cmH(2)O CPAP for the first 10 min after birth. PB-CPAP consisted of 15 cmH(2)O CPAP that was decreased when infants were stabilized (heart rate >= 100 bpm, SpO(2) >= 85%, FiO(2) <= 0.4, spontaneous breathing) to 8 cmH(2)O with steps of ~2/3 cmH(2)O/min. Primary outcomes were feasibility and SpO(2) in the first 5 min after birth. Secondary outcomes included physiological and breathing parameters and short-term neonatal outcomes. Planned enrollment was 42 infants.Results: The trial was stopped after enrolling 31 infants due to a low inclusion rate and recent changes in the local resuscitation guideline that conflict with the study protocol. Measurements were available for analysis in 28 infants (PB-CPAP n = 8, 5-8 cmH(2)O n = 20). Protocol deviations in the PB-CPAP group included one infant receiving 3 inflations with 15 cmH(2)O PEEP and two infants in which CPAP levels were decreased faster than described in the study protocol. In the 5-8 cmH(2)O CPAP group, three infants received 4, 10, and 12 cmH(2)O CPAP. During evaluations, caregivers indicated that the current PB-CPAP protocol was difficult to execute. The SpO(2) in the first 5 min after birth was not different [61 (49-70) vs. 64 (47-74), p = 0.973]. However, infants receiving PB-CPAP achieved higher heart rates [121 (111-130) vs. 97 (82-119) bpm, p = 0.016] and duration of mask ventilation was shorter [0:42 (0:34-2:22) vs. 2:58 (1:36-6:03) min, p = 0.020]. Infants in the PB-CPAP group required 6:36 (5:49-11:03) min to stabilize, compared to 9:57 (6:58-15:06) min in the 5-8 cmH2O CPAP group (p = 0.256). There were no differences in short-term outcomes.Conclusion: Stabilization of preterm infants with PB-CPAP is feasible but tailoring CPAP appeared challenging. PB-CPAP did not lead to higher SpO(2) but increased heart rate and shortened the duration of mask ventilation, which may reflect faster lung aeration.Developmen

Repetitive versus standard tactile stimulation of preterm infants at birth - A randomized controlled trial

Development and application of statistical models for medical scientific researc

The effect of initial oxygen exposure on diaphragm activity in preterm infants at birth

Background: The initial FiO(2) that should be used for the stabilization of preterm infants in the delivery room (DR) is still a matter of debate as both hypoxia and hyperoxia should be prevented. A recent randomized controlled trial showed that preterm infants [gestational age (GA) < 30 weeks] stabilized with an initial high FiO(2) (1.0) had a significantly higher breathing effort than infants stabilized with a low FiO(2) (0.3). As the diaphragm is the main respiratory muscle in these infants, we aimed to describe the effects of the initial FiO(2) on diaphragm activity.Methods: In a subgroup of infants from the original bi-center randomized controlled trial diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG), using three skin electrodes that were placed directly after birth. Diaphragm activity was compared in the first 5 min after birth. From the dEMG respiratory waveform several outcome measures were determined for comparison of the groups: average peak- and tonic inspiratory activity (dEMG(peak) and dEMG(ton), respectively), inspiratory amplitude (dEMG(amp)), area under the curve (dEMG(AUC)) and the respiratory rate (RR).Results: Thirty-one infants were included in this subgroup, of which 29 could be analyzed [n = 15 (median GA 28.4 weeks) and n = 14 (median GA 27.9 weeks) for the 100 and 30% oxygen group, respectively]. Tonic diaphragm activity was significantly higher in the high FiO(2)-group (4.3 +/- 2.1 mu V vs. 2.9 +/- 1.1 mu V; p = 0.047). The other dEMG-parameters (dEMG(peak), dEMG(amp), dEMG(AUC)) showed consistently higher values in the high FiO(2) group, but did not reach statistical significance. Average RR showed similar values in both groups (34 +/- 9 vs. 32 +/- 10 breaths/min for the high and low oxygen group, respectively).Conclusion: Preterm infants stabilized with an initial high FiO(2) showed significantly more tonic diaphragm activity and an overall trend toward a higher level of diaphragm activity than those stabilized with an initial low FiO(2). These results confirm that a high initial FiO(2) after birth stimulates breathing effort, which can be objectified with dEMG.Developmen

High-CPAP does not impede cardiovascular changes at birth in preterm sheep

Objective: Continuous positive airway pressures (CPAP) used to assist preterm infants at birth are limited to 4-8 cmH(2)O due to concerns that high-CPAP may cause pulmonary overexpansion and adversely affect the cardiovascular system. We investigated the effects of high-CPAP on pulmonary (PBF) and cerebral (CBF) blood flows and jugular vein pressure (JVP) after birth in preterm lambs.Methods: Preterm lambs instrumented with flow probes and catheters were delivered at 133/146 days gestation. Lambs received low-CPAP (LCPAP: 5 cmH(2)O), high-CPAP (HCPAP: 15 cmH(2)O) or dynamic HCPAP (15 decreasing to 8 cmH(2)O at similar to 2 cmH(2)O/min) for up to 30 min after birth.Results: Mean PBF was lower in the LCPAP [median (Q1-Q3); 202 (48-277) mL/min, p = 0.002] compared to HCPAP [315 (221-365) mL/min] and dynamic HCPAP [327 (269-376) mL/min] lambs. CBF was similar in LCPAP [65 (37-78) mL/min], HCPAP [73 (41-106) mL/min], and dynamic HCPAP [66 (52-81) mL/min, p = 0.174] lambs. JVP was similar at CPAPs of 5 [8.0 (5.1-12.4) mmHg], 8 [9.4 (5.3-13.4) mmHg], and 15 cmH(2)O [8.6 (6.9-10.5) mmHg, p = 0.909]. Heart rate was lower in the LCPAP [134 (101-174) bpm; p = 0.028] compared to the HCPAP [173 (139-205)] and dynamic HCPAP [188 (161-207) bpm] groups. Ventilation or additional caffeine was required in 5/6 LCPAP, 1/6 HCPAP, and 5/7 dynamic HCPAP lambs (p = 0.082), whereas 3/6 LCPAP, but no HCPAP lambs required intubation (p = 0.041), and 1/6 LCPAP, but no HCPAP lambs developed a pneumothorax (p = 0.632).Conclusion: High-CPAP did not impede the increase in PBF at birth and supported preterm lambs without affecting CBF and JVP.Developmen

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC).METHODS: Preterm rabbits delivered at 29/32 days (similar to 26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing similar to 2 cm H2O/min) for up to 10 min after birth.RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates.CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O.Developmen

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Reflexes that impact spontaneous breathing of preterm infants at birth: a narrative review

Some neural circuits within infants are not fully developed at birth, especially in preterm infants. Therefore, it is unclear whether reflexes that affect breathing may or may not be activated during the neonatal stabilisation at birth. Both sensory reflexes (eg, tactile stimulation) and non-invasive ventilation (NIV) can promote spontaneous breathing at birth, but the application of NIV can also compromise breathing by inducing facial reflexes that inhibit spontaneous breathing. Applying an interface could provoke the trigeminocardiac reflex (TCR) by stimulating the trigeminal nerve resulting in apnoea and a reduction in heart rate. Similarly, airflow within the nasopharynx can elicit the TCR and/or laryngeal chemoreflex (LCR), resulting in glottal closure and ineffective ventilation, whereas providing pressure via inflations could stimulate multiple receptors that affect breathing. Stimulating the fast adapting pulmonary receptors may activate Head's paradoxical reflex to stimulate spontaneous breathing. In contrast, stimulating the slow adapting pulmonary receptors or laryngeal receptors could induce the Hering-Breuer inflation reflex or LCR, respectively, and thereby inhibit spontaneous breathing. As clinicians are most often unaware that starting primary care might affect the breathing they intend to support, this narrative review summarises the currently available evidence on (vagally mediated) reflexes that might promote or inhibit spontaneous breathing at birth.Developmen

Technology in the delivery room supporting the neonatal healthcare provider's task

Very preterm infants are a unique and highly vulnerable group of patients that have a narrow physiological margin within which interventions are safe and effective. The increased understanding of the foetal to neonatal transition marks the intricacy of the rapid and major physiological changes that take place, making delivery room stabilisation and resuscitation an increasingly complex and sophisticated activity for caregivers to perform. While modern, automated technologies are pro-gressively implemented in the neonatal intensive care unit (NICU) to enhance the caregivers in providing the right care for these patients, the technology in the delivery room still lags far behind. Diligent translation of well-known and promising technological solutions from the NICU to the delivery room will allow for better support of the caregivers in performing their tasks. In this review we will discuss the current technology used for stabilisation of preterm infants in the delivery room and how this could be optimised in order to further improve care and outcomes of preterm infants in the near future.Developmen

Time to achieve desired fraction of inspired oxygen using a T-piece ventilator during resuscitation of preterm infants at birth

Developmen