Arjan B. te Pas

A randomized, controlled trial of delivery-room respiratory management in very preterm infants.

BACKGROUND. Initial ventilation strategy may play an important role in the development of bronchopulmonary dysplasia in very preterm infants. Early nasal continuous positive airway pressure is an accepted approach, but randomized clinical trials are lacking. Our aim was to determine whether early nasal continuous positive airway pressure, preceded by a sustained inflation, is more effective and less injurious in very preterm infants than conventional intervention. METHODS. Two hundred seven very preterm infants were assigned randomly in the delivery room to either a sustained inflation through a nasopharyngeal tube followed by early nasal continuous positive airway pressure (early functional residual capacity intervention) or repeated manual inflations with a self-inflating bag and mask followed by nasal continuous positive airway pressure, if necessary, after arrival at the NICU. The primary outcome measure was intubation <72 hours of age and bronchopulmonary dysplasia at 36 weeks was used as secondary outcome. This trial was registered as an early functional residual capacity intervention trial (ISRCTN 12757724). RESULTS. In the early functional residual capacity intervention group, fewer infants were intubated at <72 hours of age or received >1 dose of surfactant, and the average duration of ventilatory support was less. Infants in the early functional residual capacity intervention group developed bronchopulmonary dysplasia less frequently. CONCLUSIONS. A sustained inflation followed by early nasal continuous positive airway pressure, delivered through a nasopharyngeal tube, is a more efficient strategy than repeated manual inflations with a self-inflating bag and mask followed by nasal continuous positive airway pressure on admission to the NICU.

Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs

•  Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying reason is not known. •  In a new preterm lamb study we investigated whether delayed cord clamping until ventilation had been initiated improved pulmonary, cardiovascular and cerebral haemodynamic stability. •  We demonstrated that ventilation prior to cord clamping markedly improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped, thus further stabilising the cerebral haemodynamic transition. •  These results show that delaying cord clamping until after ventilation onset leads to a smoother transition to newborn life, and probably underlies previously demonstrated benefits of delayed cord clamping.

Effect of Sustained Inflation Length on Establishing Functional Residual Capacity at Birth in Ventilated Premature Rabbits

The effect of inflation length on lung aeration pattern, tidal volumes, and functional residual capacity (FRC) immediately after birth was investigated. Preterm rabbits (28 d), randomized into four groups, received a 1-, 5-, 10-, or 20-s inflation (SI) followed by ventilation with 5 cm H2O end-expiratory pressure. Gas volumes were measured by plethysmography and uniformity of lung aeration by phase contrast x-ray imaging for 7 min. The first inspiratory volume significantly (p < 0.001) increased with inflation duration from a median (IQR) of 0.2 (0.1–3.1) mL/kg for 1-s inflation to 23.4 (19.3–30.4) mL/kg for 20-s SI. The lung was uniformly aerated, and the FRC and tidal volume fully recruited after 20-s SI. A 10-s SI caused a higher FRC (p < 0.05) at 7 min, and a 20-s SI caused a higher FRC (p < 0.05) at 20 s and 7 min than a 1- or 5-s SI. The mean (SD) time for 90% of the lung to aerate was 14.0 (4.1) s using 35 cm H2O peak inflation pressure. In these rabbits, 10- and 20-s SI increased the inspiratory volume and produced a greater FRC, and a 20-s SI uniformly aerated the lung before ventilation started.

Reducing lung injury during neonatal resuscitation of preterm infants.

Neonatologists are familiar with the concept of ventilator-induced lung injury (VILI) 1,2 and are increasingly careful in the neonatal intensive care unit (NICU) to apply positive-pressure ventilation (PPV) strategies that are gentle to the lungs. 3 Although PPV also is commonly used in the delivery room (DR), clinicians appear less aware that the same gentle approach should be applied to reduce lung injury during the first few minutes of life. To achieve adequate gas exchange after delivery, lung fluid is cleared and replaced with air, and functional residual capacity (FRC) is established. Mechanical ventilation requires an appropriate minute volume to achieve adequate gas exchange. Clinical signs are used to evaluate the response to ventilation during neonatal resuscitation. The tidal volume (V T ) delivered is rarely measured; thus, airway pressure is not adjusted to optimize V T and reduce volutrauma or underventilation. 4,6 The use of end-expiratory pressure, considered essential to avoid lung injury in the NICU, is still not uniformly applied in the DR. PPV may cause lung injury through various mechanisms, including high airway pressure (barotrauma), high V T and overdistention (volutrauma), repeated alveolar collapse and reexpansion (atelectrauma), and infection and inflammation (bio-trauma).1 These injuries cause leakage of proteinaceous fluid and blood into the airways, alveoli, and lung interstitium, inhibiting surfactant function, interfering with lung mechanics, and contributing to lung injury.1 In this review, we describe what is known about the causes of neonatal lung injury, based on animal and human research. Although human data are scanty, and randomized control trials are needed, we suggest ways in which current practice might be changed to help minimize lung injury during neonatal resuscitation.

Respiratory monitoring of neonatal resuscitation

Video observations and recordings of respiratory signals from mannequin studies and delivery room (DR) resuscitations are described. This article discusses the uses of a respiratory function monitor (RFM) during training and resuscitations along with potential pitfalls and limitations. It adds objectivity to the clinical assessment. A respiratory function monitor provides real-time quantitative information including tidal volume and leak. It may be used to teach correct mask hold and positioning techniques during simulation-based mannequin. Examples demonstrating its potential usefulness during resuscitations are provided. However, further studies are needed to investigate whether it can help improve short-term and long-term outcomes.

Breathing Patterns in Preterm and Term Infants Immediately After Birth

There is limited data describing how preterm and term infants breathe spontaneously immediately after birth. We studied spontaneously breathing infants ≥29 wk immediately after birth. Airway flow and tidal volume were measured for 90 s using a hot wire anemometer attached to a facemask. Twelve preterm and 13 term infants had recordings suitable for analysis. The median (interquartile range) proportion of expiratory braking was very high in both groups (preterm 90 [74–99] vs. term 87 [74–94]%; NS). Crying pattern was the predominant breathing pattern for both groups (62 [36–77]% vs. 64 [46–79]%; NS). Preterm infants showed a higher incidence of expiratory hold pattern (9 [4–17]% vs. 2 [0–6]%; p = 0.02). Both groups had large tidal volumes (6.7 [3.9] vs. 6.5 [4.1] mL/kg), high peak inspiratory flows (5.7 [3.8] vs. 8.0 [5] L/min), lower peak expiratory flow (3.6 [2.4] vs. 4.8 [3.2] L/min), short inspiration time (0.31 [0.13] vs. 0.32 [0.16] s) and long expiration time (0.93 [0.64] vs. 1.14 [0.86] s). Directly after birth, both preterm and term infants frequently brake their expiration, mostly by crying. Preterm infants use significantly more expiratory breath holds to defend their lung volume.

An Initial Sustained Inflation Improves the Respiratory and Cardiovascular Transition at Birth in Preterm Lambs

A sustained inflation (SI) facilitates lung aeration after birth but may impair the neonatal cardiovascular transition. We aimed to determine the effect of an initial SI on pulmonary arterial and carotid blood flow (PBF and CBF) after preterm birth. Fetal sheep were instrumented at ∼122 d of gestation (d). Lambs were delivered at ∼127 d and received either an initial SI (40 cm H2O for 1 min or until a volume of 20 mL/kg was administered) followed by ventilation for 30 min (SI; n = 7) or ventilation for 30 min (non-SI; n = 6). At 10 min after ventilation onset, inspired O2 content increased from 21 to 100% for 10 min. PBF, CBF, pulmonary arterial and carotid pressures, tidal volume, and inspiratory pressures were recorded. PBF was greater during the SI (p < 0.05) but thereafter was similar between groups. Non-SI lambs were hypoxemic and had higher CBF than SI lambs (p < 0.05). Cerebral oxygen delivery was constant in SI lambs but increased ∼4-fold in non-SI lambs during ventilation with 100% O2 (p < 0.05). Lung compliance and respiratory status were better in SI than non-SI lambs (p < 0.05). A SI improved lung function without adverse circulatory effects, seemed to stabilize neonatal cerebral O2 delivery, and may protect against cerebral hyperoxia.

Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth

At birth, the initiation of pulmonary gas exchange is dependent on air entry into the lungs, and recent evidence indicates that pressures generated by inspiration may be involved. We have used simultaneous plethysmography and phase-contrast X-ray imaging to investigate the contribution of inspiration and expiratory braking maneuvers (EBMs) to lung aeration and the formation of a functional residual capacity (FRC) after birth. Near-term rabbit pups (n = 26) were delivered by cesarean section, placed in a water plethysmograph, and imaged during the initiation of spontaneous breathing. Breath-by-breath changes in lung gas volumes were measured using plethysmography and visualized using phase-contrast X-ray imaging. Pups rapidly (1-5 breaths) generate a FRC (16.2 +/- 1.2 ml/kg) by inhaling a greater volume than they expire (by 2.9 +/- 0.4 ml.kg(-1).breath(-1) over the first 5 breaths). As a result, 94.8 +/- 1.4% of lung aeration occurred during inspiration over multiple breaths. The incidence of EBMs was rare early during lung aeration, with most (>80%) occurring after >80% of max FRC was achieved. Although EBMs were associated with an overall increase in FRC, 34.8 +/- 5.3% of EBMs were associated with a decrease in FRC. We conclude that lung aeration is predominantly achieved by inspiratory efforts and that EBMs help to maintain FRC following its formation.

Cardiovascular transition at birth: a physiological sequence

The transition to newborn life at birth involves major cardiovascular changes that are triggered by lung aeration. These include a large increase in pulmonary blood flow (PBF), which is required for pulmonary gas exchange and to replace umbilical venous return as the source of preload for the left heart. Clamping the umbilical cord before PBF increases reduces venous return and preload for the left heart and thereby reduces cardiac output. Thus, if ventilation onset is delayed following cord clamping, the infant is at risk of superimposing an ischemic insult, due to low cardiac output, on top of an asphyxic insult. Much debate has centered on the timing of cord clamping at birth, focusing mainly on the potential for a time-dependent placental to infant blood transfusion. This has prompted recommendations for delayed cord clamping for a set time after birth in infants not requiring resuscitation. However, recent evidence indicates that ventilation onset before cord clamping mitigates the adverse cardiovascular consequences caused by immediate cord clamping. This indicates that the timing of cord clamping should be based on the infant’s physiology rather than an arbitrary period of time and that delayed cord clamping may be of greatest benefit to apneic infants.

Leak and obstruction with mask ventilation during simulated neonatal resuscitation

Objectives To evaluate mask technique during simulated neonatal resuscitation and test the effectiveness of training in optimal mask handling. Study design Seventy participants(consultants, registrars and nurses) from neonatal units were asked to administer positive pressure ventilation at a flow of 8 l/min and a frequency of 40–60/min to a modified leak free, term newborn manikin (lung compliance 0.5 ml/cm H2O) using a Neopuff T-piece device. Recordings were made (1) before training, (2) after training in mask handling and (3) 3 weeks later. Leak was calculated. Obstruction (tidal volume <60% of optimal tidal volume) and severe obstruction (<30% of optimal tidal volume) were calculated when leak was minimal. Results For the 70 participants, median (IQR) leak was 71% (32–95%) before training, 10% (5–37%) directly after training and 15% (4–33%) 3 weeks later (p<0.001). When leak was minimal, gas flow obstruction was observed before, directly after training and 3 weeks later in 46%, 42% and 37% of inflations, respectively. Severe obstruction did not occur. Conclusions Mask ventilation during simulated neonatal resuscitation was often hampered by large leaks at the face mask. Moderate airway obstruction occurred frequently when effort was taken to minimise leak. Training in mask ventilation reduced mask leak but should also focus on preventing airway obstruction.