Non-ventilated Infants Research Articles

PCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.

Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants. This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system. A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117). Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Combination of ketamine and fentanyl (KetaFent) for safe insertion of ultrasound-guided central venous catheters in infants.

Centrally inserted central catheters (CICCs) are placed by ultrasound guided puncture of the internal jugular or brachio-cephalic vein. It is crucial to achieve a good level of sedation and analgesia in order to keep the babies still thus reducing the risk of procedural failure. The aim of this study is to evaluate the efficacy of the combination of ketamine and fentanyl during the CICC placement procedure. We retrospectively collected data from 72 infants who underwent CICC insertion after sedation with KetaFent protocol. The primary outcome was to assess the success of the procedure defined as CICC placement. Secondary outcome was intubation during the procedure in non-ventilated infants (noninvasive ventilation or spontaneous respiration), need for repeat doses of study medications to complete the procedure, time to complete the procedure, the level of analgesia assessed using vital parameters. The procedure was completed in 100% of cases. There were no cases of hypotension during and at the end of the procedure. No intubation was performed on non-ventilated infants. The combination of ketamine and fentanyl for sedation and analgesia in infants requiring insertion of a CICC is 100% successful. It is associated with a low risk of side effect like apnea and intubation. Insertion of a central venous catheter is a painful procedure for infants. Adequate sedation is mandatory to keep the baby still thus reducing the risk of procedural failure.

Persistent Pulmonary Interstitial Emphysema With Respiratory Infection: A Clinicopathological Analysis of Six Cases and Detection of Infectious Pathogens by Metagenomic Next-Generation Sequencing (mNGS).

BackgroundPersistent pulmonary interstitial emphysema (PPIE) is known to be related to mechanical ventilation and preterm. However, PPIE is also reported rarely in non-ventilated and full-term infants. Its relationship with respiratory infection is rarely reported in the literature. PPIE is difficult to diagnose and always mimics other congenital thoracic malformations (CTMs), such as congenital cystic adenomatoid malformation (CCAM).ObjectiveThe objective of this study was to evaluate clinicopathological and radiographic features of PPIE with respiratory infection and to detect the possible infectious pathogens.MethodsFrom January 2011 to December 2019, six cases were confirmed pathologically with PPIE from a large cohort of 477 resected CTMs in West China Hospital of Sichuan University. Clinical and radiographic features were obtained from patients' medical records and follow-up. The present study aimed to analyze clinicopathological and radiographic features and to detect the infectious pathogens by metagenomic next-generation sequencing (mNGS).ResultsThe six PPIE cases included four girls and two boys, ranging from 2 months to 5 years; 100% (5/5) of the available cases were full-term and without mechanical ventilation. CCAM were suspected in 66.7% (4/6) patients; 66.7% (4/6) cases affected a single lobe, and 33.3% (2/6) cases affected both lung lobes. Clinically, all six PPIEs were presented with symptoms of respiratory infection and diagnosed with pneumonia. All six patients were treated by surgery after anti-infective treatment. The pathologic characteristics showed lung cysts with variable size along the bronchovascular bundles, the cysts had a discontinuous fibrotic wall with a smooth inner surface lined with uninucleated and/or multinucleated macrophages. Streptococcus pneumoniae was detected in patient No. 1. Human beta-herpesvirus 5 was detected in patient No. 2. Neisseria mucosa, Neisseria sicca, Prevotella melaninogenica, Prevotella histicola, and Fusobacterium nucleatum were detected in patient No. 5, and no infectious pathogen was detected in 50% (3/6, No. 3, No. 4, and No. 6) of cases.ConclusionSix rare cases of PPIE with respiratory infection were treated by surgery after anti-infective treatment. All five available cases were full-term infants without mechanical ventilation. The histological characteristics of PPIE were the wall of cysts composed of a thin layer of discontinuous fibrous tissue and lined with uninucleated or/and multinucleated macrophages.

Assessment and Correction of Stress in Preterm Infants and Their Mothers.

Objective: To investigate how skin-to-skin contact influences the stress levels in preterm infants in the neonatal intensive care unit and their mothers. Materials and Methods: The study included 60 preterm infants with gestational age less than 32 weeks, who were treated in the neonatal intensive care unit, and their mothers. The overall design was a baseline-response design. Saliva was collected before (baseline) and after skin-to-skin contact to measure free cortisol by enzyme immunoassay method.Results: Infant baseline salivary cortisol level was 0.587 [0.239; 1.714] μg/dL. It was significantly higher in neonates who had invasive ventilation (1.00 [0.38; 2.44]) μg/dL compared to non-ventilated infants (0.335 [0.156; 1.236]) μg/dL, P = .022 and was positively correlated with the duration of ventilation (r = 0.70; P = .0000). Maternal baseline salivary cortisol level was 0.212 [0.123; 0.378] μg/dL. There was significant decreasing of salivary cortisol after Kangaroo mother care with skin-to-skin contact in infants (0.162 [0.111; 0.231]) μg/dL, P < .001 and mothers (0.096 [0.077; 0.156]) μg/dL, P < .001. Conclusion: Preterm infants in the neonatal intensive care unit and their mothers experience stress which can be confirmed by the increased baseline cortisol levels. Kangaroo mother care with skin-to-skin contact reduces the stress and normalizes salivary cortisol levels in both the infant in the neonatal intensive care unit and the mother.

Bacterial Colonization within the First Six Weeks of Life and Pulmonary Outcome in Preterm Infants

Bronchopulmonary dysplasia (BPD) is a multifactorial disease mainly provoked by pre- and postnatal infections, mechanical ventilation, and oxygen toxicity. In severely affected premature infants requiring mechanical ventilation, association of bacterial colonization of the lung and BPD was recently disclosed. To analyze the impact of bacterial colonization of the upper airway and gastrointestinal tract on moderate/severe BPD, we retrospectively analyzed nasopharyngeal and anal swabs taken weekly during the first 6 weeks of life at a single center in n = 102 preterm infants <1000 g. Colonization mostly occurred between weeks 2 and 6 and displayed a high diversity requiring categorization. Analyses of deviance considering all relevant confounders revealed statistical significance solely for upper airway colonization with bacteria with pathogenic potential and moderate/severe BPD (p = 0.0043) while no link could be established to the Gram response or the gastrointestinal tract. Our data highlight that specific colonization of the upper airway poses a risk to the immature lung. These data are not surprising taking into account the tremendous impact of microbial axes on health and disease across ages. We suggest that studies on upper airway colonization using predefined categories represent a feasible approach to investigate the impact on the pulmonary outcome in ventilated and non-ventilated preterm infants.

Clonidine for pain in non-ventilated infants.

Critically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit.In the critically ill paediatric and neonatal population, clonidine is prescribed as an adjunct to opioids or benzodiazepines aiming to reduce the doses of these drugs that are required for analgesia or sedation, or to facilitate weaning from mechanical ventilation. It has been shownthat clonidine premedication might have a positive effect on postoperative pain in children. To assess the benefit and harms of clonidine for the prevention or treatment of procedural pain; postoperative pain; or pain associated with clinical conditions in non-ventilated neonates. We used the standard search strategy of Cochrane Neonatal to search the CENTRAL, MEDLINE via PubMed, Embase, and CINAHL to December 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We ran an updated search from 1 January 2018 to 11 March 2020 in CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. Randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing clonidine to placebo or no treatment, opioids, paracetamol, dexmedetomidine, or non-pharmacological pain-reducing interventions for the management of procedural pain, postoperative pain, and pain associated with clinical conditions in preterm and term newborns. Two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, modality of administration, and dose of clonidine) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcome considered was pain: for procedural pain, the mean values of each analgesia scale assessed during the procedure and at one to two hours after the procedure; for postoperative pain and for pain associated with clinical conditions, the mean values of each analgesia scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to use the GRADE approach to assess the quality of evidence. Our search strategy yielded 3383 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. We excluded three trials where clonidine was administered for spinal anaesthesia. We did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates.

Oral morphine analgesia for preventing pain during invasive procedures in non-ventilated premature infants in hospital: the Poppi RCT

Background Identifying better pain management strategies for painful procedures performed in neonatal care is a clinical priority. Retinopathy of prematurity screening and heel-lance blood tests are essential clinical procedures, but adequate pain relief is not currently provided because of a lack of evidence-based analgesia. Morphine provides effective analgesia in older children and adults, but efficacy in infants is controversial. Morphine is, however, commonly used intravenously for sedation in ventilated infants. Objective The primary objective was to investigate whether or not a single 100 µg/kg morphine sulphate dose administered orally prior to painful clinical procedures provides effective analgesia. Design Single-centre, prospective, randomised controlled trial. Setting John Radcliffe Hospital, Oxford, UK. Participants Thirty-one infants of 34–42 weeks’ gestational age, requiring a heel lance and retinopathy of prematurity screening on the same test occasion. Interventions The study interventions were 100 µg/kg of oral morphine sulphate (intervention arm) or placebo (control arm) 1 hour before the clinically required procedures. Main outcome measures There were two co-primary outcomes: Premature Infant Pain Profile-Revised score (a higher score implies more nociceptive processing) during the 30-second period after retinopathy of prematurity screening, and the magnitude of noxious-evoked brain activity (a higher activity implies more nociceptive processing) following the heel lance. Physiological stability and safety were secondary outcomes. Results After 31 participants were randomised (30 studied and one withdrew), the predefined safety stopping boundary was passed as 3 of the 15 infants who received morphine had apnoeas requiring resuscitation with non-invasive positive-pressure ventilation in the 24 hours after drug administration, compared with 0 of the 15 infants who received placebo [difference in proportion 0.2, 80% confidence interval (adjusted to allow for planned multiple analyses) 0.05 to 1.00; p = 0.085]. The trial was therefore stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. There was no significant difference between the trial arms for either primary outcome (Premature Infant Profile-Revised score following retinopathy of prematurity screening mean score ± standard deviation – morphine: 11.1 ± 3.2; Premature Infant Pain Profile-Revised score following retinopathy of prematurity screening mean score ± standard deviation – placebo: 10.5 ± 3.4; mean difference in Premature Infant Pain Profile-Revised score following retinopathy of prematurity screening score 0.5, 95% confidence interval –2.0 to 3.0, p = 0.66; noxious-evoked brain activity following heel lancing median activity – morphine: 0.99, interquartile range 0.40–1.56; noxious-evoked brain activity following heel lancing median activity – placebo: 0.75, interquartile range 0.33–1.22; and median difference in noxious-evoked brain activity following heel lancing 0.25, 95% confidence interval –0.16 to 0.80, p = 0.25). Limitations The trial lacked power for the primary outcome measures because of early cessation. However, there was a trend across modalities favouring placebo, suggesting that it was unlikely that a clinically significant analgesic benefit would have been detected in the original proposed sample of 156 infants. Conclusions The administration of 100 µg/kg of oral morphine to non-ventilated premature infants has the potential for harm without analgesic benefit. Oral morphine is not recommended for retinopathy of prematurity screening, and caution is strongly advised if this is being considering for other acute painful procedures in non-ventilated premature infants. Future work Further clinical trials are essential to ascertain effective pain management for retinopathy of prematurity screening. Using multimodal measures with detailed physiological recordings provides a rigorous approach to assess analgesic efficacy and adverse effects, leading to greater mechanistic understanding of the drug effects. This is essential in future clinical trials of analgesics in infants. Patient and public involvement The research team worked closely with an on-site charity during the trial design, conduct, oversight and dissemination. Trial registration Clinical Controlled Trials ISRCTN82342359; EudraCT 2014-003237-25. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. Funding was also received for the trial from the Wellcome Trust (reference numbers 095802 and 102076). The report will be published in full in Efficacy and Mechanism; Vol. 6, No. 9. See the National Institute for Health Research’s Journals Library website for further project information.

Use of morphine before retinopathy of prematurity examinations

Use of morphine before retinopathy of prematurity examinations

Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial

SummaryBackgroundInfant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain.MethodsIn this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34–42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile–Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25).FindingsBetween Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI −2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40–1·56) with morphine and 0·75 (0·33–1·22) with placebo (median difference 0·25, 95% CI −0·16 to 0·80; p=0·25).InterpretationAdministration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants.FundingWellcome Trust and National Institute for Health Research.

Late (≥ 7 days) inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence. We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I2 statistic 73% and 86%, respectively). Furthermore, inhalation steroids did not impact total duration of mechanical ventilation or oxygen dependency. There was a trend toward a reduction in the use of systemic corticosteroids in infants receiving inhalation corticosteroids (TRR 0.51, 95% CI 0.26 to 1.00; 4 studies, 74 infants; very low-quality evidence). There was a paucity of data on short- and long-term adverse effects. Our results should be interpreted with caution because the total number of randomised participants is relatively small, and most trials differed considerably in participant characteristics, inhalation therapy, and outcome definitions. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Impact of feeding method on diaphragm electrical activity and central apnea in preterm infants (FEAdi study)

BackgroundIn preterm infants, it is unknown whether feeding affects neural breathing pattern. ObjectivesBy measuring the diaphragm electrical activity (Edi) waveform, we evaluated the effect of enteral feeding and compared the effects of feeding methods on neural breathing pattern and central apnea in very low birth weight preterm infants. MethodsIn a prospective, randomized, crossover study, ten non-ventilated preterm infants with birth weights<1250g and tolerating full feeds were randomized to either bolus feeding (BF) or slow infusion feeding (SF) over 90min, followed by crossover to the other method at the next feed. Edi was continuously measured by a feeding catheter with miniaturized sensors. Five 15-min epochs were chosen [Baseline (BL), first 15min and 90min after BF/SF started] for breath-by-breath analyses of neural breathing pattern, including Edi peak, Edi min (end-expiratory), neural inspiratory and expiratory times, neural respiratory rate, and central apnea. Primary outcome was change in Edi min with feed. Secondary outcomes include change in Edi peak, frequency and duration of central apnea with feeding. ResultsAlthough intrasubject coefficient of variation was not significantly different, individual responses to feeding and feeding method were variable. No significant difference in Edi timing, Edi min, Edi peak, or apnea was observed for the different epochs. ConclusionsIn this study cohort, neural breathing pattern does not appear to be consistently affected by enteral feeding or the feeding method. Compared with BF, SF does not appear to reduce the number or duration of apneas.

Impact of warmed inhaled gas from the mechanical ventilator on esophageal temperature during therapeutic whole body hypothermia

During therapeutic whole body cooling (WBC), the core temperature is usually monitored with an esophageal probe. Most infants receive mechanical ventilation while being cooled. As the temperature in the esophagus responds rapidly to changes in the ambient temperature, inhalation of warmed gas from ventilator may lead to overestimation of ventilated patients' actual temperature, causing automated cooling devices to overcool patients well below the desired set temperature targets. To determine if the esophageal temperature recordings during therapeutic WBC differ between ventilated and non-ventilated infants. Twenty-two consecutively cooled infants had simultaneous esophageal and rectal temperatures recorded every 4 h during 72 h of WBC. Other clinical monitoring and treatment during hypothermia were provided under an established protocol. Fourteen infants received mechanical ventilation throughout the duration of cooling. The remaining eight infants were initially ventilated but were extubated later and were not on ventilator between 32 and 72 h of WBC. The esophageal temperatures across every 4 h time points during the 32-72 h interval of WBC did not differ between the ventilated and non-ventilated infants. The magnitude (median, interquartile range) of the difference between esophageal and rectal temperatures was also similar between the two groups. Warmed inhaled gas does not interfere with the esophageal temperature during WBC.

Effect of intubation and mechanical ventilation on exhaled nitric oxide in preterm infants with and without bronchopulmonary dysplasia measured at a median postmenstrual age of 49 weeks

BackgroundExhaled nitric oxide (eNO) is a marker of established airway inflammation in adults and children, but conflicting results have been reported in preterm infants when postnatal eNO is measured during tidal breathing. This study investigated the extent to which intubation and mechanical ventilation (MV) affect eNO and NO production (V’NO) in preterm infants with and without bronchopulmonary dysplasia (BPD).Patients and methodsA total of 176 very low birth weight (VLBW) infants (birth weight <1500 g), including 74 (42%) with and 102 (58%) without BPD, were examined at a median postmenstrual age of 49 weeks. Of the 176 infants, 84 (48%) did not require MV, 47 (27%) required MV for <7 days and 45 (26%) required MV for ≥7 days. Exhaled NO and tidal breathing parameters were measured in sleeping infants during tidal breathing, respiratory mechanics were assessed by occlusion tests, and arterialized capillary blood gas was analyzed.ResultseNO was significantly correlated with tidal breathing parameters, while V’NO was correlated with growth parameters, including age and body length (p < 0.001 each). Infants who were intubated and received MV for <7 days had significantly lower eNO (p < 0.01) and V’NO (p < 0.01) than non-ventilated infants. In contrast, eNO and V’NO did not differ significantly in non-ventilated infants and those receiving MV for ≥7 days. Multivariate analysis showed that independent on the duration of MV eNO (p = 0.003) and V’NO (p = 0.018) were significantly increased in BPD infants comparable with the effects of intubation and MV on eNO (p = 0.002) and V’NO (p = 0.017).ConclusionsPreterm infants with BPD show only weak postnatal increases in eNO and V’NO, but these changes may be obscured by the distinct influences of breathing pattern and invasive respiratory support. This limits the diagnostic value of postnatal eNO measurements in the follow-up of BPD infants.

Mechanical Ventilation Drives Inflammation in Severe Viral Bronchiolitis

IntroductionRespiratory insufficiency due to severe respiratory syncytial virus (RSV) infection is the most frequent cause of paediatric intensive care unit admission in infants during the winter season. Previous studies have shown increased levels of inflammatory mediators in airways of mechanically ventilated children compared to spontaneous breathing children with viral bronchiolitis. In this prospective observational multi-center study we aimed to investigate whether this increase was related to disease severity or caused by mechanical ventilation.Materials and MethodsNasopharyngeal aspirates were collected <1 hour before intubation and 24 hours later in RSV bronchiolitis patients with respiratory failure (n = 18) and non-ventilated RSV bronchiolitis controls (n = 18). Concentrations of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α.ResultsBaseline cytokine levels were comparable between ventilated and non-ventilated infants. After 24 hours of mechanical ventilation mean cytokine levels, except for MIP-1α, were elevated compared to non-ventilated infected controls: IL-1α (159 versus 4 pg/ml, p<0.01), IL-1β (1068 versus 99 pg/ml, p<0.01), IL-6 (2343 versus 958 pg/ml, p<0.05) and MCP-1 (174 versus 26 pg/ml, p<0.05).ConclusionsUsing pre- and post-intubation observations, this study suggests that endotracheal intubation and subsequent mechanical ventilation cause a robust pulmonary inflammation in infants with RSV bronchiolitis.

Safety and Effectiveness of Skin-to-Skin Contact in the NICU to Support Neurodevelopment in Vulnerable Preterm Infants

Skin-to-skin contact (SSC) is a cornerstone of neurodevelopmentally supportive and family-oriented care for very low-birth-weight preterm infants (VPIs). However, performing SSC with unstable and/or ventilated VPIs remains challenging for caregiving teams and/or controversial in the literature. We first aimed to assess the safety and effectiveness of SSC with vulnerable VPIs in a neonatal intensive care unit over 12 months. Our second aim was to evaluate the impact of the respiratory support (intubation or not) and of the infant's weight (above or below 1000 g) on the effects of SSC. Vital signs, body temperature, and oxygen requirement data were prospectively recorded by each infant's nurse before (baseline), during (3 time points), and after their first or first 2 SSC episodes. We compared the variations of each parameter from baseline (analysis of variance for repeated measures with post hoc analysis when appropriate). We studied 141 SSCs in 96 VPIs of 28 (24-33) weeks' gestational age, at 12 (0-55) days of postnatal age, and at a postmenstrual age of 30.5 (±1.5) weeks. During SSC, there were statistically significant increases in oxygen saturation (Sao2) (P < .001) with decreases in oxygen requirement (P = .043), a decrease in heart rate toward stability (P < .01) but a transient and moderate decrease in mean axillary temperature following the transfer from bed to mother (P < .05). Apneas/bradycardias requiring minor intervention occurred in 19 (13%) SSCs, without need for SSC termination. These variations were similar for intubated newborns (18%) as compared with newborns on nasal continuous positive airway pressure (52%) or breathing room air (30%). However, ventilated infants exhibited a significant increase in transcutaneous partial pressure of carbon dioxide (TcPco2) (P = .01), although remaining in a clinically acceptable range, and a greater decrease in oxygen requirements during SSC (P < .001) than nonventilated infants. Skin-to-skin contact in the neonatal intensive care unit seems safe and effective even in ventilated VPIs. Recording physiologic data of infants before, during, and after SCC provides data needed to secure changes of practice in SCC.

Effect of Body Position on Ventilation Distribution in Ventilated Preterm Infants

Positioning is considered vital to the maintenance of good lung ventilation by optimizing oxygen transport and gas exchange in ventilated premature infants. Previous studies suggest that the prone position is advantageous; however, no data exist on regional ventilation distribution for this age group. To investigate the effect of body position on regional ventilation distribution in ventilated and nonventilated preterm infants using electrical impedance tomography. Randomized crossover study design. Neonatal ICU. A total of 24 ventilated preterm infants were compared with six spontaneously breathing preterm infants. Random assignment of the order of the positions supine, prone, and quarter prone. Ventilation distribution was measured with regional impedance amplitudes and global inhomogeneity indices using electrical impedance tomography. In the spontaneously breathing infants, regional impedance amplitudes were increased in the posterior compared with the anterior lung (p < 0.01) and in the right compared with the left lung (p = 0.03). No differences were found in the ventilated infants. Ventilation was more inhomogeneous in the ventilated compared with the healthy infants (p < 0.01). Assessment of temporal regional lung filling showed that the posterior lung filled earlier than the anterior lung in the spontaneously breathing infants (p < 0.02) whereas in the in the ventilated infants the right lung filled before the left lung (p < 0.01). In contrast to previous studies showing that ventilation is distributed to the nondependent lung in infants and children, this study shows that gravity has little effect on regional ventilation distribution.

Monitoring Apnea of Prematurity: Validity of Nursing Documentation and Bedside Cardiorespiratory Monitor

To compare apnea events recorded by bedside cardiorespiratory monitor and nursing documentation with those detected by visual inspection of continuous electronic cardiorespiratory waveform. In a prospective observational study, 20 nonventilated infants of 28 to 33 weeks' gestational age were monitored for apnea during the first 2 postnatal weeks. Apnea was defined as a respiratory pause > 20 seconds or > 15 seconds if associated with a heart rate < 80/min or oxygen saturation < 85%. True apnea was defined as one for which visual inspection of continuous electronic cardiorespiratory waveform on the central monitor verified apnea. The number of apnea episodes recorded by nursing documentation and bedside monitors were 207 and 418, respectively. Only 7.7% of apnea events recorded by nursing documentation were confirmed as true apnea compared with 50.4% of apnea recorded by bedside monitors and the difference was statistically significant. Of true apnea (n = 211) episodes recorded on central monitors, 99% were recorded by bedside monitors but only 7.6% of apnea occurrences were recorded by nursing personnel. Nursing documentation does not provide accurate monitoring of apnea. Although bedside monitors have better sensitivity and specificity than nursing documentation, future research should be directed to improve the specificity of bedside monitoring.

Massive pneumatic expansion of lymphatic vessel resulting in cystic lesions in the pulmonary parenchyma: A rare case of persistent interstitial pulmonary emphysema in a non-ventilated infant

We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment.

1106 Impact of Warmed Inhaled Gas from the Mechanical Ventilator on Esophageal Temperature During Whole Body Hypothermia for Hypoxic-Ischemic Encephalopathy

During whole body cooling (WBC), the core temperature is monitored with either an esophageal or a rectal probe. Most infants are usually on mechanical ventilation while receiving hypothermia. As the...

Specific increase in local IL‐17 production during recovery from primary RSV bronchiolitis

Although Respiratory syncytial virus (RSV) bronchiolitis is the most important cause of hospital admission for infants during the winter season, the pathogenesis is largely unknown. Interleukin-17 (IL-17) concentrations were studied in nasopharyngeal aspirates from 21 non-ventilated and 17 ventilated infants admitted to hospital with RSV bronchiolitis at time of admission and discharge from the hospital. On admission, nasopharyngeal concentrations of most cytokines and chemokines were lower in non-ventilated infants than in ventilated infants, reaching statistical significance for Eotaxin, IL-1α, and IL-6. During course of disease, nasopharyngeal concentrations of most cytokines and chemokines decreased, reaching statistical significance for IL-6 and IP-10. However, nasopharyngeal IL-17 concentrations were higher at discharge than at admission in children with non-ventilated RSV disease (209-101 pg/ml, P = 0.008), a response pattern not observed in ventilated RSV patients nor for other cytokines or chemokines. It is speculated that local IL-17 production may be involved during convalescence from RSV bronchiolitis in non-ventilated patients by facilitating innate and adaptive antiviral immune responses. The role of IL-17 in the pathogenesis of RSV bronchiolitis is to be explored further.