Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio-respiratory failure is complex and not clearly delineated. We aimed to examine the clinico-pathological features and suggest how they may be related to outcome, by multi-center review of clinical records and post-mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 x 10(9)/L) with prominent neutrophilia in 9/10. The post-mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co-infection. Pulmonary blood vessels were filled with leukocytes without well-organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin-resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin-sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno-compromise may facilitate co-infection.

NIV was effective in 80% of infants receiving respiratory support for severe bronchiolitis.

IMPORTANCEThe optimal first-line mode of noninvasive respiratory support for acutely ill children is not known.OBJECTIVE To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022. INTERVENTIONS Patients were randomized 1:1 to commence either HFNC at a flow rate based on patient weight (n = 301) or CPAP of 7 to 8 cm H 2 O (n = 299). MAIN OUTCOMES AND MEASURESThe primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which a participant was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio of 0.75. Seven secondary outcomes were assessed, including mortality at critical care unit discharge, intubation within 48 hours, and use of sedation. RESULTSOf the 600 randomized children, consent was not obtained for 5 (HFNC: 1; CPAP: 4) and respiratory support was not started in 22 (HFNC: 5; CPAP: 17); 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis (median age, 9 months; 226 girls [39%]). The median time to liberation in the HFNC group was 52.9 hours (95% CI, 46.0-60.9 hours) vs 47.9 hours (95% CI, 40.5-55.7 hours) in the CPAP group (absolute difference, 5.0 hours [95% CI -10.1 to 17.4 hours]; adjusted hazard ratio 1.03 [1-sided 97.5% CI, 0.86-ϱ]). This met the criterion for noninferiority. Of the 7 prespecified secondary outcomes, 3 were significantly lower in the HFNC group: use of sedation (27.7% vs 37%; adjusted odds ratio, 0.59 [95% CI, 0.39-0.88]); mean duration of critical care stay (5 days vs 7.4 days; adjusted mean difference, −3 days [95% CI, −5.1 to −1 days]); and mean duration of acute hospital stay (13.8 days vs 19.5 days; adjusted mean difference, −7.6 days [95% CI, −13.2 to −1.9 days]). The most common adverse event was nasal trauma (HFNC: 6/295 [2.0%]; CPAP: 18/278 [6.5%]).CONCLUSIONS AND RELEVANCE Among acutely ill children clinically assessed to require noninvasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support.

Aims: To determine whether the use of negative pressure ventilation (NPV) was associated with a lower rate of endotracheal intubation in infants with recurrent apnoea secondary to acute bronchiolitis. Methods: Retrospective review of two paediatric intensive care units (PICU) databases and case notes; one PICU offered NPV. Results: Fifty two infants with bronchiolitis related apnoea were admitted to the two PICUs (31 to the NPV centre). There were no significant differences between infants in the two centres in age and weight on admission, gestational age at birth, birth weight, history of apnoea of prematurity or chronic lung disease, days ill before referral, respiratory syncytial virus status, oxygen requirement before support, and numbers retrieved from secondary care centres. Respiratory support was provided to all 31 infants in the NPV centre (23 NPV, 8 PPV), and 19/21 in the non-NPV centre (18 PPV, 1 CPAP); the NPV centre had lower rates of endotracheal intubation rates (8/31 v 18/21), shorter durations of stay (median 2 v 7 days), and less use of sedation (16/31 v 18/21). In the two years after the NPV centre discontinued use of NPV, 14/ 17 (82%) referred cases were intubated, with a median PICU stay of 7.5 days. Conclusions: The use of NPV was associated with a reduced rate of endotracheal intubation, and shorter PICU stay. A prospective randomised controlled trial of the use of NPV in the treatment of bronchiolitis related apnoea is warranted.