Francesco Cavigioli

Does Sustained Lung Inflation at Birth Improve Outcome of Preterm Infants at Risk for Respiratory Distress Syndrome

Background: Sustained lung inflation (SLI) applied at birth has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity in animal studies. Objectives: To verify if the application of SLI in preterm infants at birth may reduce the need for mechanical ventilation and improve their respiratory outcome. Methods: We prospectively studied 89 infants with respiratory distress (gestational age (GA) 28.1 ± 2.2 weeks) treated at birth with a SLI (25 cm H2O, sustained for 15 s) in addition to AAP recommendations versus a historical control group (n = 119; GA 28.1 ± 2.0 weeks) treated without SLI with the same device (controlled positive end-expiratory pressure of 5 cm H2O). Results: The SLI group had less need for (51 vs. 76%, p < 0.0001) and shorter duration of mechanical ventilation (5 ± 11 vs. 11 ± 19 days, p = 0.008), a more frequent occurrence of exclusive nasal continuous airway pressure support (49 vs. 24%, p < 0.0001) and INtubation-SURfactant-Extubation (INSURE) treatment (16 vs. 3%, p = 0.01), less need for surfactant (45 vs. 61%, p = 0.027) and postnatal steroids (10 vs. 25%, p = 0.01), a shorter duration of oxygen therapy (21 ± 27 vs. 31 ± 31 days, p = 0.016), and, finally, a lower occurrence of bronchopulmonary dysplasia in survivors (7 vs. 25%, p = 0.004). Multiple regression analysis showed that 23–27 weeks of GA and birth weight <750 g increased the risk of mechanical ventilation, while a clinical risk index for babies (CRIB) score <3 as well as INSURE strategy and SLI treatment in the delivery room decreased it. Conclusions: The application of a SLI at birth in preterm infants with respiratory distress may decrease the need for mechanical ventilation without inducing evident adverse effects.

Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants.

OBJECTIVE To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. STUDY DESIGN Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. RESULTS The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. CONCLUSIONS A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. TRIAL REGISTRATION ISRCTN 56626482.

Volume guarantee versus high frequency ventilation: lung inflammation in preterm infants

Background: Appropriate ventilation together with improvement of clinical care of premature babies can contribute to reducing lung inflammation, known to represent the “primum movens” of bronchopulmonary dysplasia (BPD). High-frequency oscillatory ventilation (HFOV) and volume-guarantee (VG) ventilation are effective in the treatment of neonatal respiratory distress syndrome (RDS). Objective: To assess the potential of HFOV and VG to prevent BPD in the acute phase of RDS, by a randomised clinical study evaluating lung inflammation in premature infants. Study design: Forty infants (gestational age 25–32 weeks) with RDS were assigned to assist-control ventilation plus VG (Vt = 5 ml/kg) or HFOV (both with a Dräger Babylog 8000 plus ventilator). Levels of interleukin (IL) 6, IL8 and tumour necrosis factor were determined in tracheal aspirate on days 1, 3 and 7 of life. Results: In the HFOV group IL6 levels were significantly higher on day 3 (0.5 (0.2) vs assisted-control ventilation plus VG group 0.1 (0.2) ng/ml) and oxygen dependency was significantly longer (36 (23) vs assisted-control ventilation plus VG group 19 (11) days). Conclusion: VG ventilation is an effective lung-protective strategy to be used in acute RDS, inducing a lower expression of early inflammation markers than HFOV. Whether the use of this initial ventilatory strategy contributes to the prevention of BPD requires further studies.

Bronchoalveolar lavage with diluted porcine surfactant in mechanically ventilated term infants with meconium aspiration syndrome.

AbstractBackground: To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). Methods: Eight consecutive mechanically ventilated term infants with severe ARDS due to MAS underwent BAL with 15 mL/kg of diluted (5.3mg phospholipid/mL) surfactant saline suspension (porcine surfactant [Curosurf®]). Treatment was administered slowly in aliquots of 2.5mL. The mean age of neonates at treatment was 3.5 (range 1–8) hours. Heart rate, systemic blood pressure and oxygen saturation were monitored continuously. Arterial blood gases were measured immediately before treatment, and again at 3 and 6 hours post-treatment. Chest x-rays were taken 6 and 24 hours after treatment. Results: Radiological improvement was evident in all eight patients 6 hours post-treatment. Compared with pre-BAL values, significant improvements (p < 0.05) in mean values for partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, arterial/alveolar O2 ratio and oxygenation index were documented at 3 and 6 hours after BAL. In all patients, tracheal fluids that had been meconium-stained prior to BAL were clear of meconium after BAL. Only one patient required nitric oxide therapy for transient pulmonary hypertension. No adverse sequelae of treatment occurred during the study. Conclusions: BAL with dilute porcine surfactant administered slowly in 2.5mL aliquots improved oxygenation and chest x-ray findings, without causing major adverse effects, in mechanically ventilated term infants with ARDS due to MAS.

Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome.

Preterm infants need the achievement of adequate lung volume. Lung recruitment maneuver (LRM) is applied during high-frequency oscillatory ventilation. We investigated the effect of an LRM with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in infants conventionally ventilated for respiratory distress syndrome (RDS). Preterm infants in assisted controlled ventilation+volume guarantee for RDS after surfactant randomly received an LRM (group A) or did not (group B). LRM entailed increments of 0.2 cm H (2)O PEEP every 5 minutes, until fraction of inspired oxygen (Fi O(2))=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve. When saturation of peripheral oxygen fell and Fi O(2) rose, we reincremented PEEP until Sp O(2) became stable. Group A ( N=10) and group B ( N=10) infants were similar: gestational age 25 ± 2 versus 25 ± 2 weeks; body weight 747 ± 233 versus 737 ± 219 g; clinical risk index for babies 9.8 versus 8.1; initial Fi O(2) 56 ± 24 versus 52 ± 21, respectively. LRM began at 86 ± 69 minutes of age and lasted for 61 ± 18 minutes. Groups A and B showed different max PEEP during the first 12 hours of life (6.1 ± 0.3 versus 5.3 ± 0.3 cm H (2)O, P=0.00), time to lowest Fi O(2) (94 ± 24 versus 435 ± 221 minutes; P=0.000) and O(2) dependency (29 ± 12 versus 45 ± 17 days; P=0.04). No adverse events and no differences in the outcomes were observed. LRM led to the earlier lowest Fi O(2) of the first 12 hours of life and a shorter O (2) dependency.

Alveolar recruitment in the delivery room

Most preterm babies with a gestational age less than 23–27 weeks need a respiratory support in the delivery room (DR); the aim of ventilation is to create and maintain a functional residual capacity (FRC); to facilitate gas exchange and to minimize acute lung injury. The application of a continuous positive airway pressure (CPAP) from the first breaths helps in obtaining a lung volume stabilization. Efficacy and safety of the application of a sustained lung inflation (SLI) at birth is still under careful evaluation. The prompt increase of the hearth rate and oxygen saturation in the preliminary studies at the moment available in the literature are signs of the good efficacy of the manoeuvre but the effects of the SLI on oxygenation and hemodynamics are undetermined. When preterm infants need respiratory assistance in the DR, respiratory function monitoring is desirable to apply adequate and gentle resuscitation manoeuvres. Clinical large trials taking place in the DR are needed but they are also extremely difficult to be designed and performed.

Effectivity of ventilation by measuring expired CO2 and RIP during stabilisation of preterm infants at birth

Objective To measure tidal volume, plethysmography changes and gas exchange during respiratory support at birth. Design The following parameters were measured: (1) expired tidal volumes (Vte (mL/kg)) using respiratory function monitoring, (2) changes in plethysmography (AU/kg) per breath using respiratory inductance plethysmography (bands placed around rib cage (RC) and abdomen (AB)) and (3) expired CO2 (ECO2) levels using a volumetric CO2 monitor. For respiratory support, a T-piece resuscitator and facemask were used with peak inspiratory pressure (PIP) 25 cm H2O and positive end expiratory pressure 5 cm H2O. Data were analysed during the sustained inflation (SI), positive pressure ventilation (PPV) and breathing on continuous positive airway pressure (CPAP). Setting The delivery rooms of the Leiden University Medical Center, Leiden, and V. Buzzi, Milan. Patients: 15 preterm infants with a gestational age 28 (27–31) weeks and a birth weight of 1080 (994–1300) g. Results Vte for PPV inflations, PPV inflations with breathing and spontaneous breathing were significantly different (4.4 (2.5–8.6) vs 8.8 (5.7–11.4) vs 5.7 (3.3–9.8); p<0.0001)). Spontaneous breathing led to the highest ECO2 levels and during PPV, ECO2 levels were higher when the inflations coincided with breathing (32 (23–38) vs 20 (13–25) vs 2 (3–11) mm Hg; p<0.0001). Little change in plethysmography amplitude occurred during the SI, PPV and breathing at the RC. There was gain in plethysmography amplitude at the AB during the SI, PPV, but most with breathing. Conclusions While Vte during breathing on CPAP was lower compared with PPV coinciding with breathing, breathing on CPAP was most effective in gas exchange and plethysmography amplitude gain compared with PPV and PPV coinciding with breathing.

ELBW infants: to intubate or not to intubate in the delivery room?

Few years ago, elective tracheal intubation in the delivery room was considered as the routine approach in managing respiratory failure in extremely-low-birth-weight infants (ELBW), at least in terms of surfactant administration. Over recent years, the indications and principles of neonatal resuscitation of ELBW infants have been partially reviewed: many randomized clinical trials (RCT) have demonstrated that these infants do not die quickly without intubation in the delivery room, and many infants only need a little help in completing foetal-neonatal transition through the use of lung recruitment manoeuvres in the delivery room (e.g. sustained lung inflation, CPAP) and then only non-invasive ventilation support. Tracheal intubation and mechanical ventilation can be reserved solely for depressed or ELBW, although further RCTs are needed to provide additional information and to provide a conclusive response to the eternal debate as to whether intubation at birth can influence outcome for ELBW infants.

Effects of Breathing and Apnoea during Sustained Inflations in Resuscitation of Preterm Infants

Background: A sustained inflation (SI) at birth in preterm babies may be ineffective unless the infants breathe. Gain in lung volume is associated with breathing during delivery room non-invasive management. Objective: To describe the breathing patterns of preterm infants during an SI and correlate to a calculated gain in lung volume. Methods: Retrospective observational study. Data collected from a respiratory function monitor during SI (25 cmH2O for 15 s then PEEP at 5 cmH2O) through a face mask in preterm infants (gestational age [GA] ≤31 weeks). Spontaneous breaths, inspiratory time (TI), inspiratory/expiratory tidal volume (Vti/Vte), and gain in lung volume were determined. Results: 30 SIs in 20 infants (mean GA 27 weeks; birth weight 825 g) were analysed and stratified in 2 groups according to spontaneous breathing: SIs without spontaneous breaths (apnoea: n = 11) and SIs with spontaneous breaths (breathing: n = 19). Mean GA was lower in the apnoea group versus the breathing group (25 vs. 27+5 weeks; p = 0.01). Mean birth weight was lower in the apnoea group versus the breathing group (683 vs. 860 g; p = ns). In the breathing group, the mean number of spontaneous breaths was 4 with a mean TI of 0.52 min, the mean Vti/kg was 5.9 mL/kg, and the mean Vte was 2.7 mL/kg. The calculated mean gain in lung volume was 7.5 mL/kg in the apnoea group and 17.8 mL/kg in the breathing group (p = 0.039). Conclusions: Actively breathing infants during an SI at birth showed a gain in lung volume higher than apnoeic infants. Spontaneous breathing during SI seems to be related to GA.

Ventilatory management of asphyxiated infant during hypothermia

Hypothermia is used for its neuroprotective effect in perinatal asphyxia. Mechanical ventilation is often used as a supportive therapy for severe asphyxiated infants who can present various degrees of respiratory failure. Animal studies demonstrated a protective effect of cooling on the lungs due to reduced ventilatory requirements. Even if actual knowledge on the effects of hypothermia and rewarming on respiratory parameters during mechanical ventilation is limited, nevertheless human studies seem to demonstrate that hypothermia is safe and does not cause significant changes in the level of respiratory supports.