Ventilated Preterm Infants Research Articles

Effect of Developmental Care on the Duration of Mechanical Ventilation in Preterm Infants

Effect of Developmental Care on the Duration of Mechanical Ventilation in Preterm Infants

Evaluation of a practice guideline for the management of respiratory distress syndrome in preterm infants: A quality improvement initiative

The use of mechanical ventilation to treat respiratory distress syndrome in preterm infants has been associated with the development of bronchopulmonary dysplasia. As part of a quality improvement initiative to reduce the incidence of bronchopulmonary dysplasia in preterm infants, a new practice guideline for the management of respiratory distress syndrome was developed and adopted into practice in a neonatal intensive care unit in February 2012. To evaluate the effects of implementing the new guideline in regard to the use of mechanical ventilation and surfactant, and the incidence of bronchopulmonary dypslasia. An historical cohort of very preterm infants (gestational age 26(0) to 32(6) weeks) born one year before guideline implementation was compared with a similar cohort of infants born one year following guideline implementation. Data were collected retrospectively from the local neonatal intensive care unit database. A total of 272 preterm infants were included in the study: 129 in the preguideline cohort and 143 in the postguideline cohort. Following the implementation of the guideline, the proportion of infants treated with ongoing mechanical ventilation was reduced from 49% to 26% (P<0.001) and there was a trend toward a reduction in bronchopulmonary dysplasia (27% versus 18%; P=0.07). There was no difference in the proportion of infants treated with surfactant (54% versus 50%). The implementation of the practice guideline helped to minimize the use of ongoing mechanical ventilation in preterm infants.

Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).

Fatal Tension Pneumopericardium in an Extremely Low Birth Weight Infant to Identify the Perforation Site of the Pericardium

A pneumopericardium is a very rare condition and is the least common form of air leak in neonates. A tension pneumopericardium is associated with very high mortality. Neonatal pneumopericardium is usually a complication of mechanical ventilation in premature infants with respiratory distress syndrome. The mechanism of this rare condition and the perforation site of the pericardium have largely been speculative. This case report documents an extremely low birth weight infant who developed fatal tension pneumopericardium, and the autopsy revealed airflow into the pericardial sac through a perforation site of the pericardium near the ostia of the right pulmonary vein. This is a valuable case in which the perforation site of the pericardium was confirmed.

Is the creatine kinase isoenzyme MB level a marker of myocardial ischemia in ventilated premature infants?

INTRODUCTION: It is not clear whether the levels of troponin I (TI) and creatine kinase isoenzyme MB (CK-MB) are changed in premature infants (PI) without evidence of myocardial ischemia (MI). OBJECTIVES: To investigate whether TI and CK-MB change their levels in newborns without MI while on mechanical ventilation (MV). METHODS: We conducted a prospective cohort study in which 165 PI were divided into control group ([CG]; n = 68), mechanical ventilated group ([VG]; n = 21) and a surfactant therapy group ([SG]; n = 76), and had their TI, creatine kinase (CK) and CK-MB levels were determined. After the division, within the first four hours after the introduction of the mechanical ventilation (MV) and one hour after the withdrawal of it, we performed a new measurement of TI, CK and CK-MB to all PI from VG and VS. We used the chi-square test to evaluate the association among qualitative variables and the Kruskall-Wallis test to compare the serum levels of TI, and CK-MB among the groups, before, during and after MV using the statistical package SPSS 16.0 software. RESULTS: TI, CK, and CK-MB serum values before the groups were divided were considered normal. The TI concentration among the groups before and after MV (p > 0.05) did not changed; however, the CK-MB levels were higher in VG when compared to the CG (p = 0.009). CONCLUSION: The increase of CK-MB serum levels in VG and SG seems to indicate an increased work of thoracic skeletal muscle and do not represent a MI signal, which invalidate its use as a marker.

Quicker response results in better SpO2 control - a comparison of 3 FiO2-titration strategies in ventilated preterm infants.

The impact of SpO2 target ranges (TR) has been carefully studied; however, reports suggest a wide variation among infants and centres in maintaining the intended range. Little is known about the effectiveness of different approaches to manual control. Auto-SpO2 controllers are now available which show promise. The aim was to compare two different protocol-driven manual strategies with different response requirements to each other, and a faster automated system (AveaCLiO2, Yorba Linda, CA, USA). In a crossover design, each of the three FiO2/SpO2 approaches was implemented in three randomly assigned consecutive 2.5-hour runs. The two manual strategies (Attentive and Observational) were implemented by a trained operator. The primary endpoints were time in 1) SpO2 TR, 2) < 80% SpO2 and 3) >98% SpO2. Fifteen studies were completed. All three approaches resulted in good control, with time in the target range >60%. CLiO2 use reflected reduced exposure at the two SpO2 extremes. Post hoc analysis determined that the differences were more marked in the infants with more frequent desaturations. Likewise, in this group, the Attentive strategy performed better than the Observative. All three approaches provided excellent control of SpO2 in infants with infrequent desaturations, significantly better than typical routine care. In hard to manage infants with frequent desaturations, faster response appeared to result in better control. The potential of automating the tedious error prone FiO2 adjustment offers significant promise. If manual titration of FiO2 is to remain the usual method of care, additional studies are needed to identify optimal approaches.

Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study.

To evaluate the efficacy of automated control of the fraction of inspired oxygen (FiO2 ) in comparison with manual FiO2 control in maintaining target pulse oxygen saturation (SpO2 ) range. Crossover physiological study involving preterm infants requiring mechanical ventilation and supplemental oxygen. Each infant was studied for two consecutive 12 hours in a random sequence. Outcome measures included the proportion of time with SpO2 within and outside the target range of 90-95%, extreme hypoxaemia (< 80%) and hyperoxaemia (≥ 98%). Complete data set was available in 27 infants. The percentage of time (median, IQR) within the target range was higher during automated control 72.8 (58.8-82.6) compared to manual control 59.6 (49.3-73.3), p = 0.031. Corresponding reduction in per cent time below the target range was 18.1 (12.7-23.6) versus 25.9 (17.8-30.7), p = 0.028, and above the target range 4.8 (3-16) versus 10.1 (6.4-22.5), p = 0.026. Median (IQR) per cent time spent with severe hypoxaemia (SpO2 < 80%) and severe hyperoxaemia (SpO2 ≥ 98%) was 1.3 (0.1-2.9) versus 3.2 (1.4-6.1), p = 0.022 and 0.08 (0.05-0.36) versus 1.7 (0.7-6.8), p = 0.001, respectively. Median number of manual adjustments of FiO2 per 12 hour was 0 and 63, respectively. Automated control of FiO2 significantly improved compliance of oxygen saturation targeting and significantly reduced exposure to hypoxaemia as well as hyperoxaemia.

Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. ClinicalTrials.gov: NCT01022580.

Rescue high-frequency jet ventilation versus conventional ventilation for severe pulmonary dysfunction in preterm infants.

Chronic lung disease (CLD) is a major cause of mortality and morbidity in very low birth weight infants despite increased use of antenatal steroids and surfactant therapy. Ventilator injury and oxygen toxicity are thought to be important factors in the pathogenesis of chronic pulmonary disease. Evidence from animal studies and from adult human studies indicates that high-frequency jet ventilation may reduce the severity of lung injury associated with mechanical ventilation. To compare use of high-frequency jet ventilation (HFJV) versus conventional ventilation (CV) in preterm infants with severe pulmonary dysfunction.Subgroup analyses include the following.• Trials with and without surfactant replacement therapy.• Trials with and without strategies to maintain lung volume.• Trials with infants of different gestational ages and birth weights (specific subgroups to include < 28 weeks' gestation and < 1000 grams).• Trials with and without adequate humidification of inspired gases. The original search included MEDLINE (1966 to August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL; 2005, Issue 3) and EMBASE (1988 to August 2005). We also obtained information from experts in the field and checked cross-references. We updated the electronic search in June 2013 and again in June 2015. We included in this systematic review randomised and quasi-randomised controlled trials of rescue high-frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks' gestation or with birth weight less than 2000 grams in respiratory distress. We used standard methods of the Cochrane Neonatal Review Group, including independent trial assessment and data extraction. We analysed data using risk ratios (RRs) and risk differences (RDs). We included only one trial in the review. Keszler 1991 randomly assigned 166 preterm infants; reported data on 144 infants; and permitted cross-over to the alternate treatment if initial treatment failed. Investigators found no statistically significant differences in overall mortality (including survival after cross-over) between the two groups (RR 1.07, 95% confidence interval (CI) 0.67 to 1.72). In a secondary analysis of infants up to the time of cross-over, rescue treatment with HFJV was associated with lower mortality (RR 0.66, 95% CI 0.45 to 0.97). Researchers reported no significant differences in the incidence of CLD among survivors at 28 days of age, nor in the incidence of intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis. Study authors reported no significant differences in overall mortality between rescue high-frequency jet ventilation and conventional ventilation and presented highly imprecise results for important adverse effects such as intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis.The overall quality of evidence is affected by limitations in trial design and by imprecision due to the small number of infants in the included study. Existing evidence does not support the use of high-frequency jet ventilation as rescue therapy in preterm infants.Studies that target populations at greatest risk and that have sufficient power to assess important outcomes are needed. These trials should incorporate long-term pulmonary and neurodevelopmental outcomes.

Impact of Volume Guarantee on High-Frequency Oscillatory Ventilation in Preterm Infants: A Randomized Crossover Clinical Trial

Background: High-frequency oscillatory ventilation (HFOV) with volume guarantee (VG) is a new ventilation mode that allows the clinician to set a mean tidal volume to be delivered. Objective: This study aimed to investigate whether HFOV with a VG option may result in constant tidal volume delivery and less fluctuant CO₂ levels compared to HFOV alone in premature infants with respiratory distress syndrome (RDS). Methods: Inborn infants at less than 32 weeks of gestation with RDS requiring invasive mechanical ventilation were eligible. Patients were randomized to receive HFOV + VG or HFOV alone as the initial ventilator mode and then crossed over to the other mode. HFOV was performed with ‘optimal lung volume strategy' during both of the periods. Results: Twenty infants were evaluated. The mean high-frequency tidal volume (VT_hf) and CO₂ diffusion coefficient (DCO₂) were significantly higher in the HFOV + VG mode than HFOV alone. HFOV + VG maintains VT_hf within the target range more consistently than HFOV. The incidences of hypocarbia and hypercarbia were lower in HFOV with VG than HFOV alone. Conclusion: This is the first prospective, randomized, short-term crossover clinical study that compared HFOV with and without VG in infants with acute RDS. Because of the lower VT_hf fluctuation and lower incidences of out-of-target PCO₂ levels, HFOV combined with VG seems to be feasible for preterm infants. However, the results should be interpreted with caution due to the small sample size and short-term crossover design of the study.

Randomized control trial comparing physiologic effects in preterm infants during treatment with nasal continuous positive airway pressure (NCPAP) generated by Bubble NCPAP and Ventilator NCPAP: a pilot study.

Nasal continuous positive airway pressure (NCPAP) is an accepted form of non-invasive ventilation in preterm infants. Few, if any, studies have shown an advantage of one type of NCPAP over another. It has been theorized that bubble-generated NCPAP may be advantageous for the preterm neonate versus traditionally used ventilator-generated NCPAP. The aim of this study was to examine for any short-term differences in physiologic parameters in preterm subjects receiving these two different methods of NCPAP. We conducted a randomized, prospective, cross-over pilot study of preterm infants being treated with NCPAP in the neonatal intensive care unit. Subjects were continuously monitored for several physiologic parameters including heart rate, respiratory rate, oxygen saturation, cerebral tissue oxygen saturation and cerebral fractional oxygen extraction using routine neonatal monitors and near-infrared spectroscopy (NIRS) while on 2 h of bubble NCPAP and 2 h of ventilator NCPAP. Subjects were randomized to be monitored while either starting on bubble NCPAP and then switching to ventilator NCPAP or starting on ventilator NCPAP and switching to bubble NCPAP. Eighteen subjects were included. We found no statistically significant difference in any of the physiologic parameters while subjects were receiving bubble NCPAP versus ventilator NCPAP during the monitoring time periods. While on bubble NCPAP, subjects showed a trend toward decreasing respiratory rate and decreasing cerebral fractional oxygen extraction over time, but this did not reach statistical significance. There appears to be no difference in immediate physiologic effects between bubble NCPAP and ventilator NCPAP. This does not preclude the possibility of potential long-term differences, but any differences seen would likely be based on mechanisms that take more time to develop. A larger prospective trial is warranted to confirm our findings.

Severe retinopathy of prematurity (ROP) is associated with hypocarbia in ventilated preterm infants

Retinopathy of prematurity (ROP) is a leading cause of blindness in children. While excessive oxygen administration has been implicated in the pathogenesis, the potential role of high or low levels of CO2, a highly vasoactive compound, is unclear. Mechanical ventilation may contribute to both hypercarbia (vasodilatation) and hypocarbia (vasoconstriction). We report a case–control study of the relationship between CO2 levels during the first 3 days of life in ventilated preterm infants and the development of ROP.

Comparison of non-synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as post-extubation respiratory support in preterm infants with respiratory distress syndrome: a randomized controlled trial

Objective: To determine whether post-extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS).Methods: In this randomized, controlled, open, prospective, single-center clinical trial, we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation.Results: A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in six (19.3%) of nsNIPPV group compared with nine (28.12%) of NCPAP group and was statistically not significant (p = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.4 ± 39.3 hours versus 111.8 ± 116.4 hours, p = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.9 ± 92.1 hours versus 190.1 ± 140.5 hours, p = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (p = 0.02).Conclusions: Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.

Effects of Synchronization during Noninvasive Intermittent Mandatory Ventilation in Preterm Infants with Respiratory Distress Syndrome Immediately after Extubation

Background: Noninvasive ventilation is increasingly used in very-low-birth-weight infants (VLBWI) to reduce complications that occur with invasive ventilation. However, the physiological effects of synchronization during noninvasive nasal intermittent mandatory ventilation (IMV) have not been tested in VLBWI immediately after extubation. Objective: We aimed to study the short-term effects of synchronized nasal IMV (S-NIMV) compared to nonsynchronized nasal IMV (NIMV) on breathing effort as measured by phasic esophageal pressure (Pe) deflection, spontaneous respiratory rate (RR), gas exchange, cerebral tissue oxygen saturation (StO₂) and intermittent episodes of bradycardia or hypoxemia in VLBWI recovering from respiratory distress syndrome (RDS). Methods: Fourteen VLBWI recovering from RDS were studied using a randomized cross-over design during both S-NIMV and NIMV (of 2 h each) immediately after extubation. Results: Phasic Pe deflection, spontaneous RR and transcutaneous PCO₂ decreased significantly while transcutaneous PO₂ and synchrony rate (defined as peak ventilator pressure delivered within the first half of spontaneous inspiration) increased significantly during S-NIMV compared to during NIMV. There was no difference in blood pressure, average arterial oxygen saturation (SpO₂), cerebral StO₂, fractional tissue oxygen extraction of the brain and severe bradycardia (defined as time with a heart rate <100 beats/min lasting ≥10 s) and in hypoxemic episodes (SpO₂ <80%) between the two modes. Conclusion: Synchronization during nasal ventilation immediately after extubation in VLBWI recovering from RDS improved gas exchange and decreased the respiratory effort, and it could therefore be considered to provide a more efficient respiratory support and synchrony.

Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial

Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. Deutsche Forschungsgemeinschaft.

Role of serine proteases in the regulation of interleukin-877 during the development of bronchopulmonary dysplasia in preterm ventilated infants.

RationaleThe chemokine interleukin-8 is implicated in the development of bronchopulmonary dysplasia in preterm infants. The 77-amino acid isoform of interleukin-8 (interleukin-877) is a less potent chemoattractant than other shorter isoforms. Although interleukin-877 is abundant in the preterm circulation, its regulation in the preterm lung is unknown.ObjectivesTo study expression and processing of pulmonary interleukin-877 in preterm infants who did and did not develop bronchopulmonary dysplasia.MethodsTotal interleukin-8 and interleukin-877 were measured in bronchoalveolar lavage fluid from preterm infants by immunoassay. Neutrophil serine proteases were used to assess processing. Neutrophil chemotaxis assays and degranulation of neutrophil matrix metalloproteinase-9 were used to assess interleukin-8 function.Main ResultsPeak total interleukin-8 and interleukin-877 concentrations were increased in infants who developed bronchopulmonary dysplasia compared to those who did not. Shorter forms of interleukin-8 predominated in the preterm lung (96.3% No-bronchopulmonary dysplasia vs 97.1% bronchopulmonary dysplasia, p>0.05). Preterm bronchoalveolar lavage fluid significantly converted exogenously added interleukin-877 to shorter isoforms (p<0.001). Conversion was greater in bronchopulmonary dysplasia infants (p<0.05). This conversion was inhibited by α-1 antitrypsin and antithrombin III (p<0.01). Purified neutrophil serine proteases efficiently converted interleukin-877 to shorter isoforms in a time- and dose-dependent fashion; shorter interleukin-8 isoforms were primarily responsible for neutrophil chemotaxis (p<0.001). Conversion by proteinase-3 resulted in significantly increased interleukin-8 activity in vitro (p<0.01).ConclusionsShorter, potent, isoforms interleukin-8 predominate in the preterm lung, and are increased in infants developing bronchopulmonary dysplasia, due to conversion of interleukin-877 by neutrophil serine proteases and thrombin. Processing of interleukin-8 provides an attractive therapeutic target to prevent development of bronchopulmonary dysplasia.

Sustained inflation at birth did not alter lung injury from mechanical ventilation in surfactant-treated fetal lambs.

BackgroundSustained inflations (SI) are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation.HypothesisA 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs.MethodsThe head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline). Fetal lambs were randomized to one of four 15 minute interventions: 1) PEEP 8 cmH2O; 2) 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3) mechanical ventilation with 7 ml/kg tidal volume; or 4) 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention.ResultsSI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP) 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury.ConclusionIn surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation.

Influence of Gestational Age on Dead Space and Alveolar Ventilation in Preterm Infants Ventilated with Volume Guarantee

Background: Ventilated preterm infant lungs are vulnerable to overdistension and underinflation. The optimal ventilator-delivered tidal volume (V_T) in these infants is unknown and may depend on the extent of alveolarisation at birth. Objectives: We aimed to calculate respiratory dead space (V_D) from the molar mass (MM) signal of an ultrasonic flowmeter (V_D,MM) in very preterm infants on volume-targeted ventilation (V_T target, 4-5 ml/kg) and to study the association between gestational age (GA) and V_D,MM-to-V_T ratio (V_D,MM/V_T), alveolar tidal volume (V_A) and alveolar minute volume (AMV). Methods: This was a single-centre, prospective, observational, cohort study in a neonatal intensive care unit. Tidal breathing analysis was performed in ventilated very preterm infants (GA range 23-32 weeks) on day 1 of life. Results: Valid measurements were obtained in 43/51 (87%) infants. Tidal breathing variables were analysed using multivariable linear regression. V_D,MM/V_T was negatively associated with GA after adjusting for birth weight Z score (p < 0.001, R² = 0.26). This association was primarily influenced by the appliance dead space. Despite similar V_T/kg and V_A/kg across all studied infants, respiratory rate and AMV/kg increased with GA. Conclusions:V_D,app rather than anatomical V_D is the major factor influencing increased V_D,MM/V_T at a younger GA. A volume guarantee setting of 4-5 ml/kg in the Dräger Babylog® 8000 plus ventilator may be inappropriate as a universal target across the GA range of 23-32 weeks. Differences between measured and set V_T and the dependence of this difference on GA require further investigation.

The role of surfactant and non-invasive mechanical ventilation in early management of respiratory distress syndrome in premature infants.

Surfactant replacement therapy has been used for few decades for the treatment of respiratory distress syndrome (RDS) and has significantly improved morbidity and mortality in premature infants. Non-invasive respiratory support has recently emerged as a strategy in the early management of RDS. In this review, we discuss the different strategies of early management of RDS. A literature search of PubMed database was conducted to review the subject. The quality of evidence of key clinical studies was graded according to a modified grading system of the international GRADE group. Continuous positive airway pressure (CPAP) with selective surfactant is a safe alternative to routine intubation, surfactant and mechanical ventilation in preterm infants with spontaneous breathing, and such an approach has been associated with decreased risk of death and bronchopulmonary dysplasia. There is a risk of pneumothorax when using a high pressure of CPAP (≥8 cm of H2O), a high partial pressure of carbon dioxide (PCO2 >75 mm of Hg), and a high fraction of inspired oxygen (FiO2 >0.6) as a threshold for intubation while on CPAP. Not all preterm infants need surfactant treatment, and non-invasive respiratory support is a safe and effective approach.

Low-Flow Oxygen for Positive Pressure Ventilation of Preterm Infants in the Delivery Room

Background: The recent newborn resuscitation guidelines have recommended that a pulse oximeter and oxygen blender be used to keep oxygen saturation (SpO₂) within the target range. However, an oxygen blender and compressed air are not generally available in delivery rooms. Objectives: To determine whether using low-flow oxygen at 0.5-1 liters/min for positive pressure ventilation (PPV) via a self-inflating bag (SIB) without a reservoir is effective and able to maintain SpO₂ within the target range. Methods: Infants with a gestational age (GA) ≤32 weeks who initially required PPV after birth were enrolled. PPV was performed with low-flow oxygen at 0.5-1 liters/min via an SIB without a reservoir, and the flow was adjusted in a stepwise manner (from 0.5 to 0.8 to 1 liters/min) to keep SpO₂ in the target range. If the heart rate was still <100/min or SpO₂ was <70% at 3 min or chest compression was needed, then 100% oxygen was provided. Results: Forty-seven infants were enrolled in the study with a median (interquartile range) GA and birth weight of 28 (27-30) weeks and 1,060 (770-1,360) g, respectively. Twelve infants were initially intubated and switched to 100% oxygen (n = 12) due to ineffective ventilation, which occurred predominately in lower GA infants with intrapartum fetal distress. Thirty infants were successfully resuscitated with low-flow oxygen PPV (success rate 85.7%, 30/35), and >80% of their SpO₂ distribution during PPV was between the 3rd and 97th percentiles of the reference range. Conclusion: Low-flow oxygen for PPV via an SIB used in this study should be sufficient for providing oxygen in resuscitation of preterm infants as long as adequate ventilation is evident. This technique is simple and could be useful in a resource-limited setting.