Non-invasive high-frequency ventilation in newborn infants with respiratory distress

Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress.

To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress.

We searched CENTRAL, MEDLINE, Embase, CINAHL and three trial registries in April 2023.

Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation.

Two authors independently selected the trials for inclusion, extracted data, assessed the risk of bias, and undertook GRADE assessment.

We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46 term infants. nHFV compared to invasive respiratory therapy for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 0.67, 95% CI 0.20 to 2.18; 1 study, 80 infants) or the incidence of CLD (RR 0.38, 95% CI 0.09 to 1.59; 2 studies, 180 infants), both very low-certainty. ET intubation, death or CLD, severe intraventricular haemorrhage (IVH) and neurodevelopmental disability (ND) were not reported. nHFV vs nasal continuous positive airway pressure (nCPAP) used for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 1.00, 95% CI 0.41 to 2.41; 4 studies, 531 infants; very low-certainty). nHFV may reduce ET intubation (RR 0.52, 95% CI 0.33 to 0.82; 5 studies, 571 infants), but there may be little or no difference in CLD (RR 1.35, 95% CI 0.80 to 2.27; 4 studies, 481 infants); death or CLD (RR 2.50, 95% CI 0.52 to 12.01; 1 study, 68 participants); or severe IVH (RR 1.17, 95% CI 0.36 to 3.78; 4 studies, 531 infants), all low-certainty evidence. ND was not reported. nHFV vs nasal intermittent positive-pressure ventilation (nIPPV) used for initial RS nHFV may result in little to no difference in mortality before hospital discharge (RR 1.86, 95% CI 0.90 to 3.83; 2 studies, 84 infants; low-certainty). nHFV may have little or no effect in reducing ET intubation (RR 1.33, 95% CI 0.76 to 2.34; 5 studies, 228 infants; low-certainty). There may be a reduction in CLD (RR 0.63, 95% CI 0.42 to 0.95; 5 studies, 307 infants; low-certainty). A single study (36 infants) reported no events for severe IVH. Death or CLD and ND were not reported. nHFV vs high-flow nasal cannula (HFNC) used for initial RS We are very uncertain whether nHFV reduces ET intubation (RR 2.94, 95% CI 0.65 to 13.27; 1 study, 37 infants) or reduces CLD (RR 1.18, 95% CI 0.46 to 2.98; 1 study, 37 participants), both very low-certainty. There were no mortality events before hospital discharge or severe IVH. Other deaths, CLD and ND, were not reported. nHFV vs nCPAP used for RS following planned extubation nHFV probably results in little or no difference in mortality before hospital discharge (RR 0.92, 95% CI 0.52 to 1.64; 6 studies, 1472 infants; moderate-certainty). nHFV may result in a reduction in ET reintubation (RR 0.42, 95% CI 0.35 to 0.51; 11 studies, 1897 infants) and CLD (RR 0.78, 95% CI 0.67 to 0.91; 10 studies, 1829 infants), both low-certainty. nHFV probably has little or no effect on death or CLD (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 966 infants) and severe IVH (RR 0.80, 95% CI 0.57 to 1.13; 3 studies, 1117 infants), both moderate-certainty. We are very uncertain whether nHFV reduces ND (RR 0.92, 95% CI 0.37 to 2.29; 1 study, 74 infants; very low-certainty). nHFV versus nIPPV used for RS following planned extubation nHFV may have little or no effect on mortality before hospital discharge (RR 1.83, 95% CI 0.70 to 4.79; 2 studies, 984 infants; low-certainty). There is probably a reduction in ET reintubation (RR 0.69, 95% CI 0.54 to 0.89; 6 studies, 1364 infants), but little or no effect on CLD (RR 0.88, 95% CI 0.75 to 1.04; 4 studies, 1236 infants); death or CLD (RR 0.92, 95% CI 0.79 to 1.08; 3 studies, 1070 infants); or severe IVH (RR 0.78, 95% CI 0.55 to 1.10; 4 studies, 1162 infants), all moderate-certainty. One study reported there might be no difference in ND (RR 0.88, 95% CI 0.35 to 2.16; 1 study, 72 infants; low-certainty). nHFV versus nIPPV following initial non-invasive RS failure nHFV may have little or no effect on mortality before hospital discharge (RR 1.44, 95% CI 0.10 to 21.33); or ET intubation (RR 1.23, 95% CI 0.51 to 2.98); or CLD (RR 1.01, 95% CI 0.70 to 1.47); or severe IVH (RR 0.47, 95% CI 0.02 to 10.87); 1 study, 39 participants, all low- or very low-certainty. Other deaths or CLD and ND were not reported.

For initial RS, we are very uncertain if using nHFV compared to invasive respiratory therapy affects clinical outcomes. However, nHFV may reduce intubation when compared to nCPAP. For planned extubation, nHFV may reduce the risk of reintubation compared to nCPAP and nIPPV. nHFV may reduce the risk of CLD when compared to nCPAP. Following initial non-invasive respiratory support failure, nHFV when compared to nIPPV may result in little to no difference in intubation. Large trials, particularly in high-income settings, are needed to determine the role of nHFV in initial RS and following the failure of other non-invasive respiratory support. Also, the optimal settings of nHVF require further investigation.