To investigate the clinical efficacy and safety of caffeine citrate combined with heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) for prevention of extubation failure in premature infants with respiratory distress syndrome (RDS).

From September 2017 to February 2019, a total of 72 premature infants with RDS (28 weeks≤gestational age<32 weeks) who were prepared for noninvasive mechanical ventilation after a period of invasive mechanical ventilation with an endotracheal tube in neonatal intensive care unit of the Affiliated Xuzhou Hospital of Southeast University, were chosen as research subjects. They were randomly divided into two groups by random digits table method. In the combined treatment group (n=47), they were given caffeine citrate 24 h before extubation combined with HHHFNC after extubation for prevention of extubation failure; and in the control group (n=43), they were given NCPAP after extubation without caffeine citrate for prevention of extubation failure. The general clinical data, incidence of extubation failure, duration of noninvasive ventilation and total duration of oxygen inhaling, the days of achieving adequate oral feeding and related complications of noninvasive mechanical ventilation between two groups of premature infants were compared by independent-samples t test or chi-square test. The study was reviewed and approved by the Medical Ethics Committee of the Affiliated Xuzhou Hospital of Southeast University (Approval No. 2017-13), and clinical research informed consents were signed by the guardians of all premature infants.

① There were no significant differences between two groups in general clinical data including gender composition ratio, gestational age, gravidity, birth weight, and the rate of premature rupture of membranes, cesarean section rate, composition ratio of conception, glucocorticoid application rate 24 h to 7 d before delivery, incidence rate of hypertensive disorders complicating pregnancy of mother, incidence of grade Ⅲ RDS, 1 min and 5 min Apgar scores of RDS premature infants after birth, usage rate of pulmonary surfactant (PS) and duration of invasive mechanical ventilation (P>0.05). ② The incidence of extubation failure, duration of noninvasive ventilation and total duration of oxygen inhaling, length of hospitalization, times of apnea in combined treatment group were 8.1% (3/37), 3.5 d (1.0-15.0 d), 11.0 d (4.0-28.0 d), 15.5 d (6.0-29.0 d) and 11.0 times (7.0-15.0 times), respectively, which were significant less or lower or shorter than those in control group 20% (7/35), 6.5 d (2.5-18.0 d), 15.0 d (6.0-32.0 d), 22.0 d (7.0-36.0 d) and 18.0 times (8.0-25.0 times), and all the differences were statistically significant(χ²=4.712, P=0.030; Z=-2.030, P=0.018; Z=-2.129, P=0.012; Z=-2.889, P=0.008; Z=-2.105, P=0.022). The time for children in the combination treatment group to achieve adequate oral feeding was shorter than that in control group which were 10.0 d (6.0-20.0 d) and 16.0 d (8.0-28.0 d), respectively, and the difference was statistically significant (Z=—2.857, P=0.010). ③The incidence rates of nasal injury, abdominal distention and head shaping in combined treatment group were 10.8% (4/37), 10.8% (4/37) and 8.1% (3/37), respectively, which were significant lower than those in control group, 22.9% (8/35), 28.6% (10/35) and 31.4% (11/35), and all the differences were statistically significant (χ²=4.782, 5.140, 5.982; P=0.028, 0.021, 0.012).

Compared with the application of NCPAP alone, caffeine citrate combined with HHHFNC for prevention of extubation failure in premature infants with RDS can reduce the incidence of extubation failure, nasal injury, and abdominal distension, and shorten the duration of noninvasive mechanical ventilation and oxygen inhaling. It′s a safe and effective respiratory support model for premature infants with RDS.