Respiratory Support in Meconium Aspiration Syndrome: A Practical Guide

Meconium aspiration syndrome (MAS) is a complex respiratory disease of the term and near-term neonate. Inhalation of meconium causes airway obstruction, atelectasis, epithelial injury, surfactant inhibition, and pulmonary hypertension, the chief clinical manifestations of which are hypoxaemia and poor lung compliance. Supplemental oxygen is the mainstay of therapy for MAS, with around one-third of infants requiring intubation and mechanical ventilation. For those ventilated, high ventilator pressures, as well as a relatively long inspiratory time and slow ventilator rate, may be necessary to achieve adequate oxygenation. High-frequency ventilation may offer a benefit in infants with refractory hypoxaemia and/or gas trapping. Inhaled nitric oxide is effective in those with pulmonary hypertension, and other adjunctive therapies, including surfactant administration and lung lavage, should be considered in selected cases. With judicious use of available modes of ventilation and adjunctive therapies, infants with even the most severe MAS can usually be supported through the disease, with an acceptably low risk of short- and long-term morbidities

Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support

Background: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed. // Methods: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated. // Results: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm. // Conclusion: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials

Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates : a randomized clinical trial

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. Design, Setting, and Participants: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks’ gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Interventions: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Main Outcomes and Measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Results: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, −6.5 [95% CI, −1.2 to −11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. Conclusions and Relevance: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures

Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants

Background: Compared to very low gestational age (\u3c32 weeks, VLGA) cohorts, very low birth weight (\u3c1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. Results: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (\u3c1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and \u3c32 weeks, AUC 0.60-0.62). Conclusion: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking

Regional tidal ventilation and compliance during a stepwise vital capacity manoeuvre

PURPOSE: To determine whether, during mechanical ventilation, an optimal positive end-expiratory pressure (PEEP) can be identified by measurement of regional tidal volume and compliance [V (T(reg)), C (RS(reg))]. METHODS: Sixteen anaesthetized intubated neonatal piglets underwent a stepwise vital capacity manoeuvre performed during pressure control ventilation, with 5 cmHO PEEP increments to 25 cmHO, and decrements to 0 cmHO. Peak inflating pressure was 10 cmHO above PEEP throughout. The manoeuvre was performed in the normal lung, after repeated saline lavage and after surfactant therapy. Global V (T) and C (RS) were measured at the airway opening; V (T(reg)) and C (RS(reg)) were measured in the ventral, medial and dorsal lung using electrical impedance tomography (EIT). RESULTS: Most uniform distribution of regional tidal ventilation was noted during PEEP decrements after lung recruitment, at varying PEEP levels. In the lavaged and surfactant-treated lung the PEEP optimal for ventilation distribution was also associated with highest mean V (T(reg)) [lavaged: 95 +/- 9.3% of maximum, mean +/- standard deviation (SD); surfactant-treated: 92 +/- 17%] and global V (T) (96 +/- 10%; 96 +/- 15%). Regional C (RS) plots clearly demonstrated co-existent ventral overdistension and dorsal recruitment, particularly during PEEP increments; whereas during PEEP decrements, peak C (RS(reg)) values showed considerable interregional concordance [e.g. peak C (RS(reg)) in the lavaged left lung; ventral: 0.017 +/- 0.0036; medial: 0.016 +/- 0.0054; dorsal: 0.017 +/- 0.0073 cmHO(1); P = 0.98, analysis of variance (ANOVA)]. CONCLUSIONS: After lung recruitment, a PEEP level can be identified by EIT at which tidal ventilation is uniformly distributed, with associated concordance in compliance between lung regions. Bedside monitoring of regional tidal ventilation and compliance using EIT may thus aid in PEEP selection

Regional pulmonary effects of bronchoalveolar lavage procedure determined by electrical impedance tomography

Abstract Background The provision of guidance in ventilator therapy by continuous monitoring of regional lung ventilation, aeration and respiratory system mechanics is the main clinical benefit of electrical impedance tomography (EIT). A new application was recently described in critically ill patients undergoing diagnostic bronchoalveolar lavage (BAL) with the intention of using EIT to identify the region where sampling was performed. Increased electrical bioimpedance was reported after fluid instillation. To verify the accuracy of these findings, contradicting the current EIT knowledge, we have systematically analysed chest EIT data acquired under controlled experimental conditions in animals undergoing a large number of BAL procedures. Methods One hundred thirteen BAL procedures were performed in 13 newborn piglets positioned both supine and prone. EIT data was obtained at 13 images before, during and after each BAL. The data was analysed at three time points: (1) after disconnection from the ventilator before the fluid instillation and by the ends of fluid (2) instillation and (3) recovery by suction and compared with the baseline measurements before the procedure. Functional EIT images were generated, and changes in pixel electrical bioimpedance were calculated relative to baseline. The data was examined in the whole image and in three (ventral, middle, dorsal) regions-of-interest per lung. Results Compared with the baseline phase, chest electrical bioimpedance fell after the disconnection from the ventilator in all animals in both postures during all procedures. The fluid instillation further decreased electrical bioimpedance. During fluid recovery, electrical bioimpedance increased, but not to baseline values. All effects were highly significant (p < 0.001). The fractional changes in individual regions-of-interest were posture-dependent. The regional fall in electrical bioimpedance was smaller in the ventral and larger in the dorsal regions after the fluid instillation than after the initial disconnection to ambient pressure in supine animals (p < 0.001) whereas these changes were of comparable amplitude in prone position. Conclusions The results of this study show a regionally dissimilar initial fall in electrical bioimpedance caused by non-uniform aeration loss at the beginning of the BAL procedure. They also confirm a further pronounced fall in bioimpedance during fluid instillation, incomplete recovery after suction and a posture-dependent distribution pattern of these effects