Video versus Direct Laryngoscopy for Urgent Intubation of Newborn Infants.

BACKGROUND: Repeated attempts at endotracheal intubation are associated with increased adverse events in neonates. When clinicians view the airway directly with a laryngoscope, fewer than half of first attempts are successful. The use of a video laryngoscope, which has a camera at the tip of the blade that displays a view of the airway on a screen, has been associated with a greater percentage of successful intubations on the first attempt than the use of direct laryngoscopy in adults and children. The effect of video laryngoscopy among neonates is uncertain. METHODS: In this single-center trial, we randomly assigned neonates of any gestational age who were undergoing intubation in the delivery room or neonatal intensive care unit (NICU) to the video-laryngoscopy group or the direct-laryngoscopy group. Randomization was stratified according to gestational age (<32 weeks or ≥32 weeks). The primary outcome was successful intubation on the first attempt, as determined by exhaled carbon dioxide detection. RESULTS: Data were analyzed for 214 of the 226 neonates who were enrolled in the trial, 63 (29%) of whom were intubated in the delivery room and 151 (71%) in the NICU. Successful intubation on the first attempt occurred in 79 of the 107 patients (74%; 95% confidence interval [CI], 66 to 82) in the video-laryngoscopy group and in 48 of the 107 patients (45%; 95% CI, 35 to 54) in the direct-laryngoscopy group (P<0.001). The median number of attempts to achieve successful intubation was 1 (95% CI, 1 to 1) in the video-laryngoscopy group and 2 (95% CI, 1 to 2) in the direct-laryngoscopy group. The median lowest oxygen saturation during intubation was 74% (95% CI, 65 to 78) in the video-laryngoscopy group and 68% (95% CI, 62 to 74) in the direct-laryngoscopy group; the lowest heart rate was 153 beats per minute (95% CI, 148 to 158) and 148 (95% CI, 140 to 156), respectively. CONCLUSIONS: Among neonates undergoing urgent endotracheal intubation, video laryngoscopy resulted in a greater number of successful intubations on the first attempt than direct laryngoscopy. (Funded by the National Maternity Hospital Foundation; VODE ClinicalTrials.gov number, NCT04994652.).

Newborn face mask ventilation training using a standardised intervention and respiratory function monitor: a before and after manikin study.

OBJECTIVE: The International Liaison Committee on Resuscitation has recommended improvements in training for neonatal resuscitation, highlighting the potential role of respiratory function monitors (RFMs). Our objective was to determine whether a manikin-based, standardised face mask ventilation training intervention using an RFM with a simple visual display reduced face mask leak. DESIGN: Multicentre, before and after study. Participants and instructors were blinded to the RFM display during both assessment periods. PARTICIPANTS: Healthcare professionals working or training in a hospital providing maternity and neonatal services. INTERVENTION: All participants underwent a training intervention on positive pressure ventilation using a modified, leak-free manikin and RFM. The intervention consisted of a demonstration of optimal face mask ventilation technique, training in RFM interpretation with corrective strategies for common scenarios and a period of deliberate practice. Each participant performed 30 s of positive pressure ventilation blinded to the RFM display before and after training. MAIN OUTCOME MEASURES: The primary outcome was face mask leak (%) measured after training. Secondary outcome measures included expired tidal volume, inflating pressures and ventilation rate. Adjustments made to technique during training were an important qualitative outcome. RESULTS: Four hundred and fourteen participants were recruited over a 13-month period from April 2022, and 412 underwent analysis. Median (IQR) face mask leak before training was 31% (10-69%) compared with 10% (6-18%) after training (p<0.0001). Improvements were noted across all other ventilation parameters. CONCLUSION: Standardised face mask ventilation training using an RFM with simple visual feedback led to a significant reduction in leak.

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 cmH2O and positive end-expiratory airway pressure of 5 cmH2O. Expired tidal volumes (Vt) were measured with a respiratory function monitor. Target range for Vt 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 Vt of 4.6 (3.3 - 6.2) ml/kg. Median Vt 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).

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in neonatal sepsis.

BACKGROUND: Efficient and accurate diagnosis of neonatal sepsis is challenging. The potential impact for a reduction in morbidity and mortality as well as antibiotic usage has stimulated the ongoing search for biomarkers of early sepsis. The objective of this pilot study was to quantify the levels of sTREM-1 and correlate with blood cultures and inflammatory markers in neonates evaluated for sepsis. METHODS: Neonates with suspected sepsis were enrolled (n = 83; Preterm n = 35; Term n = 48). Routine bloods for sepsis evaluation were included and plasma sTREM-1 levels were quantified by ELISA. RESULTS: Term and preterm neonates (n = 83; Preterm n = 35; Term n = 48) were enrolled and 16 neonates had positive blood cultures (preterm n = 15; term n = 1). sTREM-1 levels were not significantly different in infants with culture-positive or culture-negative sepsis (356 ± 218 pg/mL and 385 ± 254 pg/mL respectively). The immature-to-total granulocyte (I/T) ratio showed a significant positive correlation with sTREM-1 in the preterm group with positive blood cultures. Additionally, sTREM-1 showed a positive correlation with CRP in the preterm group with negative blood cultures. CONCLUSIONS: sTREM-1 was associated with traditional markers of inflammation (I/T ratio and CRP). However, in this cohort sTREM-1 did not improve the early detection of neonatal culture-positive sepsis.

Effects of tactile stimulation on spontaneous breathing during face mask ventilation.

OBJECTIVE: We sought to determine the effect of stimulation during positive pressure ventilation (PPV) on the number of spontaneous breaths, exhaled tidal volume (VTe), mask leak and obstruction. DESIGN: Secondary analysis of a prospective, randomised trial comparing two face masks. SETTING: Single-centre delivery room study. PATIENTS: Newborn infants ≥34 weeks' gestation at birth. METHODS: Resuscitations were video recorded. Tactile stimulations during PPV were noted and the timing, duration and surface area of applied stimulus were recorded. Respiratory flow waveforms were evaluated to determine the number of spontaneous breaths, VTe, leak and obstruction. Variables were recorded throughout each tactile stimulation episode and compared with those recorded in the same time period immediately before stimulation. RESULTS: Twenty of 40 infants received tactile stimulation during PPV and we recorded 57 stimulations during PPV. During stimulation, the number of spontaneous breaths increased (median difference (IQR): 1 breath (0-3); padj<0.001) and VTe increased (0.5 mL/kg (-0.5 to 1.7), padj=0.028), whereas mask leak (0% (-20 to 1), padj=0.12) and percentage of obstructed inflations (0% (0-0), padj=0.14) did not change, compared with the period immediately prior to stimulation. Increased duration of stimulation (padj<0.001) and surface area of applied stimulus (padj=0.026) were associated with a larger increase in spontaneous breaths in response to tactile stimulation. CONCLUSIONS: Tactile stimulation during PPV was associated with an increase in the number of spontaneous breaths compared with immediately before stimulation without a change in mask leak and obstruction. These data inform the discussion on continuing stimulation during PPV in term infants. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry (ACTRN12616000768493).

Time to desaturation in preterm infants undergoing endotracheal intubation.

BACKGROUND: Neonatal endotracheal intubation is often associated with physiological instability. The Neonatal Resuscitation Program recommends a time-based limit (30 s) for intubation attempts in the delivery room, but there are limited physiological data to support recommendations in the neonatal intensive care unit (NICU). We aimed to determine the time to desaturation after ceasing spontaneous or assisted breathing in preterm infants undergoing elective endotracheal intubation in the NICU. METHODS: Observational study at The Royal Women's Hospital, Melbourne. A secondary analysis was performed of video recordings of neonates ≤32 weeks' postmenstrual age undergoing elective intubation. Infants received premedication including atropine, a sedative and muscle relaxant. Apnoeic oxygenation time (AOT) was defined as the time from the last positive pressure or spontaneous breath until desaturation (SpO2 <90%). RESULTS: Seventy-eight infants were included. The median (IQR) gestational age at birth was 27 (26-29) weeks and birth weight 946 (773-1216) g. All but five neonates desaturated to SpO2 <90% (73/78, 94%). The median (IQR) AOT was 22 (14-32) s. The median (IQR) time from ceasing positive pressure ventilation to desaturation <80% was 35 (24-44) s and to desaturation <60% was 56 (42-68) s. No episodes of bradycardia were seen. CONCLUSIONS: This is the first study to report AOT in preterm infants. During intubation of preterm infants in the NICU, desaturation occurs quickly after cessation of positive pressure ventilation. These data are important for the development of clinical guidelines for neonatal intubation. TRIAL REGISTRATION NUMBER: ACTRN12614000709640.

Physiological responses to facemask application in newborns immediately after birth.

OBJECTIVE: Application of a face mask may induce apnoea and bradycardia, possibly via the trigeminocardiac reflex (TCR). We aimed to describe rates of apnoea and bradycardia in term and late-preterm infants following facemask application during neonatal stabilisation and compare the effects of first facemask application with subsequent applications. DESIGN: Subgroup analysis of a prospective, randomised trial comparing two face masks. SETTING: Single-centre study in the delivery room PATIENTS: Infants>34 weeks gestational age at birth METHODS: Resuscitations were video recorded. Airway flow and pressure were measured using a flow sensor. The effect of first and subsequent facemask applications on spontaneously breathing infants were noted. When available, flow waveforms as well as heart rate (HR) were assessed 20 s before and 30 s after each facemask application. RESULTS: In total, 128 facemask applications were evaluated. In eleven percent of facemask applications infants stopped breathing. The first application was associated with a higher rate of apnoea than subsequent applications (29% vs 8%, OR (95% CI)=4.76 (1.41-16.67), p=0.012). On aggregate, there was no change in median HR over time. In the interventions associated with apnoea, HR dropped by 38bpm [median (IQR) at time of facemask application: 134bpm (134-150) vs 96bpm (94-102) 20 s after application; p=0.25] and recovered within 30 s. CONCLUSIONS: Facemask applications in term and late-preterm infants during neonatal stabilisation are associated with apnoea and this effect is more pronounced after the first compared with subsequent applications. Healthcare providers should be aware of the TCR and vigilant when applying a face mask to newborn infants. TRIAL REGISTRATION NUMBER: ACTRN12616000768493.

Interfaces for non-invasive neonatal resuscitation in the delivery room: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review of trials comparing interfaces for delivering non-invasive PPV to a newborn in the delivery room (DR). METHODS: MEDLINE, PUBMED, EMBASE, CINAHL and COCHRANE databases were searched on March 1, 2020 and 2826 articles were screened. The review was conducted using the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary outcomes were intubation in the DR and mortality. Secondary outcomes were chest compressions, intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC) and mask leak. RESULTS: Five randomized-control trials were eligible for inclusion. Sample size and gestational age varied amongst the trials, ranging from 56 to 617 infants and 24-39 weeks' respectively. Three trials compared nasal cannulae (NC) with face masks (FMs). Pooled analysis showed that NC were associated with a decreased use of chest compressions (RR 0.2 (95% CI 0.08-0.47). A reduction in rate of intubation in the DR was statistically significant only in the trial in which bi-nasal rather than single nasal cannulae were used (RR 0.10, 95% CI 0.02-0.44). However, there was no important difference in mortality (RR 0.72, 95% CI 0.47-1.13). Two trials compared different FM models (Laerdal versus Fisher & Paykel and Laerdal versus Resusi-sure) and both found no significant difference in primary and secondary outcomes. CONCLUSION: There is little high-quality evidence to guide clinicians choosing an interface to provide PPV during newborn resuscitation. Nasal interfaces, particularly binasal cannulae, appear to offer some advantages over FMs but need further testing in larger, well designed trials. STUDY REGISTRATION: PROSPERO CRD42020151870.

Educational Perspectives: Toward More Effective Neonatal Resuscitation: Assessing and Improving Clinical Skills.

Newborn deaths following birth asphyxia remain a significant global problem, and effective resuscitation by well-trained professionals may reduce mortality and morbidity. Clinicians are often responsible for teaching newborn resuscitation to trainees. Multiple educational methods are used to teach these skills, but data supporting their efficacy are limited. Mask ventilation and chest compressions are considered the basics of resuscitation. These technical motor skills are critically important but difficult to teach and often not objectively assessed. Teaching more advanced skills such as neonatal intubation is challenging, because teaching opportunities and working hours of learners have declined. Videolaryngoscopy appears to be an effective teaching tool that allows instruction during clinical practice. There is also emerging recognition that effective resuscitation requires more than individual clinical skills. The importance of teamwork and leadership is now recognized, and teamwork training should be incorporated because it improves these nontechnical skills. Simulation training has become increasingly popular as a method of teaching both technical and nontechnical skills. However, there are unanswered questions about the validity, fidelity, and content of simulation. Formal resuscitation programs usually incorporate a mixture of teaching modalities and appear to reduce neonatal mortality and morbidity in low- and middle-income countries. Emerging teaching techniques such as tele-education, video debriefing, and high-frequency training warrant further investigation.

Respiratory monitors to teach newborn facemask ventilation: a randomised trial.

OBJECTIVE: The International Liaison Committee on Resuscitation has found that there is a need for high-quality randomised trials of training interventions that improve the effectiveness of resuscitation skills. The objective of this study was to determine whether using a respiratory function monitor (RFM) during mask ventilation training with a manikin reduces facemask leak. DESIGN: Stratified, parallel-group, randomised controlled trial. Outcome assessors were blinded to group allocation. SETTING: Thirteen hospitals in Australia, including non-tertiary sites. PARTICIPANTS: Consecutive sample of healthcare professionals attending a structured newborn resuscitation training course. INTERVENTIONS: An RFM providing real-time, objective, leak, flow and volume information was attached to the facemask during 1.5 hours of newborn ventilation and simulation training using a manikin. Participants were randomised to have the RFM display visible (intervention) or masked (control), using a computer-generated randomisation sequence. MAIN OUTCOME MEASURES: The primary outcome was facemask leak measured after neonatal facemask ventilation training. Tidal volume was an important secondary outcome measure. RESULTS: Participants were recruited from May 2016 to November 2017. Of 402 eligible participants, two refused consent. Four hundred were randomised, 200 to each group, of whom 194 in each group underwent analysis. The median (IQR) facemask leak was 23% (8%-41%) in the RFM visible group compared with 35% (14%-67%) in the masked group, p<0.0001, difference (95% CI) in medians 12 (4 to 22). CONCLUSIONS: The display of information from an RFM improved the effectiveness of newborn facemask ventilation training. TRIAL REGISTRATION NUMBER: ACTRN12616000542493, pre-results.

Smaller facemasks for positive pressure ventilation in preterm infants: A randomised trial.

AIM: Facial measurements of preterm infants indicate that standard diameter facemasks used during positive pressure ventilation are too large, which may lead to mask leak and compromise resuscitation. We aimed to determine whether the use of a facemask that better complies with the dimensions of preterm faces, compared with a standard facemask, reduces facemask leak. METHODS: Parallel group, randomised controlled trial. Preterm infants ≤32 weeks' gestation receiving facemask ventilation prior to intubation in the neonatal intensive care unit, and those 28-32+6 weeks' receiving facemask ventilation in the delivery room were eligible. Infants were randomised to receive ventilation via a standard (50mm) (control), or a smaller (35mm or 42mm) diameter facemask (intervention), stratified by gestation (≤26 weeks'; 35mm, 27-32+6; 42mm). The primary outcome was leak between the mask and the infants face. RESULTS: Of 298 eligible infants, 139 were randomised and 131 were included in the final analysis; 66 in the intervention group and 65 in the control group. The median (IQR) leak was 42% (13-69%) in the intervention group compared with 39% (22-66%) in the control group P=0.43. The median (IQR) lowest oxygen saturation was similar in both groups [intervention 70% (34-93%) vs. control 71% (40-93%) P=0.75]. One infant crossed over from the intervention to the control group due to poor response to ventilation with the intervention facemask. CONCLUSIONS: Smaller facemasks did not reduce mask leak in preterm facemask ventilation. All facemasks had high leak, particularly in infants ≤26 weeks' gestation. CLINICAL TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12614000709640, www.anzctr.org.au.

Suction Mask vs Conventional Mask Ventilation in Term and Near-Term Infants in the Delivery Room: A Randomized Controlled Trial.

OBJECTIVE: To compare the suction mask, a new facemask that uses suction to create a seal between the mask and the infant's face, with a conventional soft, round silicone mask during positive pressure ventilation (PPV) in the delivery room in newborn infants >34 weeks of gestation. STUDY DESIGN: Single-center randomized controlled trial in the delivery room. The primary outcome was mask leak. RESULTS: Forty-five infants were studied at a median gestational age of 38.1 weeks (IQR, 36.4-39.0 weeks); 22 were randomized to the suction mask and 23 to the conventional mask. The suction mask did not reduce mask leak (49.9%; IQR, 11.0%-92.7%) compared with the conventional mask (30.5%; IQR, 10.6%-48.8%; P = .51). The suction mask delivered lower peak inspiratory pressure (27.2 cm H2O [IQR, 25.0-28.7 cm H2O] vs 30.4 cm H2O [IQR, 29.4-32.5 cm H2O]; P < .05) and lower positive end expiratory pressure (3.7 cm H2O [IQR, 3.1-4.5 cm H2O] vs 5.1 cm H2O [IQR, 4.2-5.7 cm H2O ]; P < .05). There was no difference in the duration of PPV or rates of intubation or admission to the neonatal intensive care unit. In 5 infants (23%), the clinician switched from the suction to the conventional mask, 2 owing to intermittently low peak inspiratory pressure, 2 owing to failure to respond to PPV, and 1 owing to marked facial bruising after 6 minutes of PPV. CONCLUSIONS: The use of the suction mask to provide PPV in newborn infants did not reduce facemask leak. Adverse effects such as the inability to achieve the set pressures and transient skin discoloration are concerning. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12616000768493.

Identification of dysregulated genes in cutaneous squamous cell carcinoma.

Carcinogenesis is a multi-step process resulting from the accumulation of genetic mutations and subsequently leading to dysregulated genes, but the number and identity of differentially expressed genes in cutaneous squamous cell carcinoma (SCC) is unknown at present. In order to identify dysregulated genes, we examined the relative mRNA expression present in cutaneous SCC and its precursor lesion actinic keratosis (AK) by comparison to normal skin. Snap frozen biopsies from 20 specimens of normal skin, 10 AK, and 10 cutaneous SCC were examined. Total-RNA was extracted, reversely transcribed, and 14 genes were investigated using gene-specific intron-flanking primers and quantitative real-time reverse transcription PCR. Specificity was confirmed by sequencing of the PCR amplicons. Ten of 14 genes were significantly dysregulated in AK and/or cutaneous SCC by comparison to normal skin. The genes CNN2, COX4I1, COX5B, COX7C, CRLF3, CTSC, NDRG1, and LMNA showed increased expression in skin cancer (p < 0.02), while RPL15 and LGTN were down-regulated (p < 0.03). The genes differentially expressed during skin carcinogenesis may prove useful in order to understand the origin and progression of cutaneous SCC and for diagnostic approaches.