Results
Overall, 131 infants were considered eligible. After four of them were excluded, 127 patients were randomized into the P10 arm (65 patients) and into the P5 arm (62 patients). Three patients (one from the P10 and two from the P5 group) were dropped out after randomization; this was due to the presence of undiagnosed choanal stenosis, to irregular study protocol application and to previously unrecognized congenital immunodeficiency (Figure 1). Patients were enrolled between November 2016 and December 2019. The study was prematurely interrupted thereafter due to low enrollment rate. The study was prematurely ended after the first 127 patients and did not enroll the planned 488 cases due to an almost complete drop in bronchiolitis occurrence in 2020. Table 1 summarizes baseline features of the enrolled patients: age, gestational age, weight, BSS, bacterial coinfection, HFNC support prior to PICU admission and PIM3 score.
Patients were admitted to the PICU after a median time of 1 (0-3) days after hospital admission with no difference between the two groups (p=0.88). HCPAP was started after 13 (6-18) hours in the P5 group and 11 (7-15) in the P10 group (p=0.24). Patients were treated with HCPAP for a median time of 3 days (1-5) and there was no difference between groups (p=0.15). Pathogens responsible of respiratory insufficiency in the two groups are listed in table 1.
All patients survived to PICU discharge.
The overall intubation rate of study population was 18/124 (14.5%). The intubation rates were 9/60 (15%) and 9/64 (14%) in P5 and P10 groups, respectively (OR 0.94, 95% CI 0.36 to 2.46, p=0.99). Of the patients in the P5 group, 47 (78%) were escalated to a PEEP level of 10 cmH2O. Respiratory symptoms were successfully stabilized in 38 of them (81%), while the remaining 9 “escalated” patients were ultimately intubated. In this group, 13 patients who did not require escalation nor intubation. No patient in the P10 group needed de-escalation to a PEEP level of 5 for intolerance. PEEP level was not associated to intubation rate (OR 0.69, 95% CI 0.19 to 2.40, p=0.57), after adjustment for age, gestational age, HFNC application, BSS and PIM3. The intubation rate was heterogeneous across sites (i.e., 37%, 14%, 13.6 % and 3.7%, respectively, among 27, 25, 22 and 50 patients) (Figure 2). However, the initial PEEP level was not significantly associated with intubation in any center. Length of mechanical ventilation was 7 days (5-10) with no difference between groups (p=0.51).
None of the clinical or respiratory parameters differed significantly between groups; however, they all showed a significant improvement over time (p<0.001 in all cases) (Figure 3).
No cases of pneumothorax were described during the study, and the impact of HCPAP on enteral feeding was not significant (2/60 in P5 and 0/64 in P10 group, OR 0.00, 95% CI 0.0- 2.0, p=0.23). Length of PICU stay was similar for both groups, 7 days (5-10) for the P5 group and 7 days (5-8.7) for the P10 group (p=0.94). However, both intubation (OR 1.9; 95% CI 1.5-2.7; p=0.0001) and PEEP escalation (OR 1.27, 95% CI 1.22-1.47; p=0.0003) were associated with PICU length of stay.