Optimising success of neonatal extubation: Respiratory support

In this review, we examine lung physiology before, during and after neonatal extubation and propose a three-phase model for the extubation procedure. We perform meta-analyses to compare different modes of non-invasive respiratory support after neonatal extubation and based on the findings, the following clinical recommendations are made

Rescue nasopharyngeal tube for preterm infants non-responsive to initial ventilation after birth

BACKGROUND Physiological changes during the insertion of a rescue nasopharyngeal tube (NPT) after birth are unclear. METHODS Observational study of very preterm infants in the delivery room. Data were extracted at predefined timepoints starting with first facemask placement after birth until 5 min after insertion of NPT. End-expiratory lung impedance (EELI), heart rate (HR) and SpO$_{2}$/FiO$_{2}$-ratio were analysed over time. Changes during the same time span of NIPPV via facemask and NIPPV via NPT were compared. RESULTS Overall, 1154 inflations in 15 infants were analysed. After NPT insertion, EELI increased significantly [0.33 AU/kg (0.19-0.57), p < 0.001]. Compared with the mask period, changes in EELI were not significantly larger during the NPT period [median difference (IQR) = 0.14 AU/kg (-0.14-0.53); p = 0.12]. Insertion of the NPT was associated with significant improvement in HR [52 (33-96); p = 0.001] and SpO$_{2}$/FiO$_{2}$-ratio [161 (69-169); p < 0.001] not observed during the mask period. CONCLUSIONS In very preterm infants non-responsive to initial facemask ventilation after birth, insertion of an NPT resulted in a considerable increase in EELI. This additional gain in lung volume was associated with an immediate improvement in clinical parameters. The use of a NPT may prevent intubation in selected non-responsive infants. IMPACT After birth, a nasopharyngeal tube may be considered as a rescue airway in newborn infants non-responsive to initial positive pressure ventilation via facemask. Although it is widely used among clinicians, its effect on lung volumes and physiological parameters remains unclear. Insertion of a rescue NPT resulted in a considerable increase in lung volume but this was not significantly larger than during facemask ventilation. However, insertion of a rescue NPT was associated with a significant and clinically important improvement in heart rate and oxygenation. This study highlights the importance of individual strategies in preterm resuscitation and introduces the NPT as a valid option

Early prediction of pulmonary outcomes in preterm infants using electrical impedance tomography

INTRODUCTION Electrical impedance tomography (EIT) allows assessment of ventilation and aeration homogeneity which may be associated with respiratory outcomes in preterm infants. METHODS This was a secondary analysis to a recent randomized controlled trial in very preterm infants in the delivery room (DR). The predictive value of various EIT parameters assessed 30 min after birth on important respiratory outcomes (early intubation <24 h after birth, oxygen dependency at 28 days after birth, and moderate/severe bronchopulmonary dysplasia; BPD) was assessed. RESULTS Thirty-two infants were analyzed. A lower percentage of aerated lung volume [OR (95% CI) = 0.8 (0.66-0.98), p = 0.027] as well as a higher aeration homogeneity ratio (i.e., more aeration in the non-gravity-dependent lung) predicted the need for supplemental oxygen at 28 days after birth [9.58 (5.16-17.78), p = 0.0028]. Both variables together had a similar predictive value to a model using known clinical contributors. There was no association with intubation or BPD, where numbers were small. DISCUSSION In very preterm infants, EIT markers of aeration at 30 min after birth accurately predicted the need for supplemental oxygen at 28 days after birth but not BPD. EIT-guided individualized optimization of respiratory support in the DR may be possible

Case report: Intrapulmonary tidal volumes in a preterm infant with chest wall rigidity

BACKGROUND Chest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall. CASE PRESENTATION We present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube. CONCLUSIONS This case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of μ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement

“Harry Potter and the Multitudinous Maladies”: a retrospective population-based observational study of morbidity and mortality among witches and wizards

OBJECTIVES To describe the prevalence of maladies and deaths among witches and wizards in the Harry Potter world, their causes, and associated therapies. DESIGN Retrospective population-based observational study (report analysis) undertaken 10 February - 19 March 2022. SETTING All locations described in the Harry Potter books, predominantly Hogwarts School of Witchcraft and Wizardry, but also selected locations, including Privet Drive No 4, Diagon Alley, the Ministry of Magic, and The Burrow. PARTICIPANTS All witches and wizards mentioned at least once in any of the seven Harry Potter books. MAIN OUTCOME MEASURES Overall numbers of maladies and deaths. Secondary outcomes were changes in morbidity and mortality over time, causes of morbidity and mortality, and treatments. RESULTS A total of 603 wizards or witches named in the Potter books experienced 1541 maladies and injuries (1410 non-fatal) and 131 deaths. Overall morbidity incidence was 471 events per 1000 individuals, and mortality, after adjustment for Lord Voldemort's multi-mortality, was 20.6%. The most frequent causes of morbidity were traumatic injuries during duels or fights (553 cases, 39.2%), magical objects, potions, plants, or creatures (345, 24.5%), and non-combative trauma (221, 15.7%). Most deaths were related to wizarding duels (101 of 131, 77.1%). Treatments were rarely described; the most frequent were jinxes (274, 19.4%) and potions (136, 9.6%). Hospital stays were shorter than a week for almost all non-fatal maladies (1397 of 1410, 99.1%). CONCLUSIONS Morbidity and, in particular, mortality were very high and predominantly caused by magical means. Further investigation into the safety at Hogwarts School of Witchcraft and Wizardry is warranted. The few treatments used had high success rates; rapid recovery was the rule, and hospital stays generally brief. Efforts should be undertaken to identify the magical therapies and interventions used and to introduce these novel remedies into Muggle medicine

Harry Potter and the Multitudinous Maladies: a retrospective population-based observational study of morbidity and mortality among witches and wizards

Objectives: To describe the prevalence of maladies and deaths among witches and wizards in the Harry Potter world, their causes, and associated therapies. Design: Retrospective population-based observational study (report analysis) undertaken 10 February - 19 March 2022. Setting: All locations described in the Harry Potter books, predominantly Hogwarts School of Witchcraft and Wizardry, but also selected locations, including Privet Drive No 4, Diagon Alley, the Ministry of Magic, and The Burrow. Participants: All witches and wizards mentioned at least once in any of the seven Harry Potter books. Main outcome measures: Overall numbers of maladies and deaths. Secondary outcomes were changes in morbidity and mortality over time, causes of morbidity and mortality, and treatments. Results: A total of 603 wizards or witches named in the Potter books experienced 1541 maladies and injuries (1410 non-fatal) and 131 deaths. Overall morbidity incidence was 471 events per 1000 individuals, and mortality, after adjustment for Lord Voldemort's multi-mortality, was 20.6%. The most frequent causes of morbidity were traumatic injuries during duels or fights (553 cases, 39.2%), magical objects, potions, plants, or creatures (345, 24.5%), and non-combative trauma (221, 15.7%). Most deaths were related to wizarding duels (101 of 131, 77.1%). Treatments were rarely described;the most frequent were jinxes (274, 19.4%) and potions (136, 9.6%). Hospital stays were shorter than a week for almost all non-fatal maladies (1397 of 1410, 99.1%). Conclusions: Morbidity and, in particular, mortality were very high and predominantly caused by magical means. Further investigation into the safety at Hogwarts School of Witchcraft and Wizardry is warranted. The few treatments used had high success rates;rapid recovery was the rule, and hospital stays generally brief. Efforts should be undertaken to identify the magical therapies and interventions used and to introduce these novel remedies into Muggle medicine

Tidal volumes during delivery room stabilization of (near) term infants

BACKGROUND We sought to assess tidal volumes in (near) term infants during delivery room stabilization. METHODS Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH$_{2}$O and positive end-expiratory airway pressure of 5 cmH$_{2}$O. Expired tidal volumes (V$_{t}$) were measured with a respiratory function monitor. Target range for V$_{t}$ was defined to be 4 - 8 ml/kg. RESULTS Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 - 39.0) weeks received 1828 inflations with a median V$_{t}$ of 4.6 (3.3 - 6.2) ml/kg. Median V$_{t}$ was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25-27) % of the inflations were in the target rage over the duration of PPV while 42 (25 - 65) % and 10 (3 - 33) % were above and below target range. CONCLUSIONS Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. TRIAL REGISTRATION This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493)

Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma

Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107) Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We sought to examine the effects of different combinations of these NPS and NPSR1 variants on downstream signaling and genetic risk of asthma. In transfected cells, the magnitude of NPSR1-induced activation of cAMP/PKA signal transduction pathways and downstream gene expression was dependent on the combination of the NPS and NPSR1 variants with NPS-Val(6)/NPSR1-Ile(107) resulting in strongest and NPS-Leu(6)/NPSR1-Asn(107) in weakest effects, respectively. One or two copies of the NPS-Leu(6) (rs4751440) were associated with physician-diagnosed childhood asthma (OR: 0.67, 95% CI 0.49-0.92, p = 0.01) and together with two other linked NPS variants (rs1931704 and rs10830123) formed a protective haplotype (p = 0.008) in the Swedish birth cohort BAMSE (2033 children). NPS rs10830123 showed epistasis with NPSR1 rs324981 encoding Asn(107)Ile (p = 0.009) in BAMSE and with the linked NPSR1 rs17199659 (p = 0.005) in the German MAGIC/ISAAC II cohort (1454 children). In conclusion, NPS variants modify asthma risk and should be considered in genetic association studies of NPSR1 with asthma and other complex diseases.Peer reviewe