A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants.

CONTEXT

Conventional nasal continuous positive airway pressure (NCPAP) had been known to improve the rate of successful extubation in preterm neonates and can be provided via a short binasal prongs that fit snugly into the infant's nose. To be effective, however, the prong has to be maintained in place in a way that it can deliver the positive distending pressure to the upper airway with minimal leak.

Several NCPAP devices are available, but all can cause nasal trauma. Damage to the skin often is mild and resolves with the cessation of NCPAP but may be a cause of unexplained septicemia in the preterm population. More significant trauma can result in permanent disfigurement and long-term functional sequelae.

Heated Humidified High-Flow Nasal Cannulae (HHHFNC) seems to be well tolerated in patients and easy to apply, leading to increased use around the world. In a number of reports, authors describe the use of HHHFNC as a mode of respiratory support in premature infants.[12]

MATERIALS AND METHODS

Study design

This is a single center randomized controlled trial done in Royal Women's Hospital, Melbourne, Victoria, Australia from January 1, 2009 to July 31, 2011.

Outcome

The primary outcome is extubation failure within the 7 days after extubation and was defined as follows:

Apnea (respiratory pause >20 seconds), more than six episodes in 6 hours or one requiring intermittent positive pressure ventilation

Acidosis, pH < 7.25 and PCO2 > 66 mmHg

And >15% sustained increase in FiO2 from extubation.

Extubation failure was deemed to have occurred if any single criterion was met in any one of the 7 days after extubation

Population

Inclusion

Infants born at less than 32 weeks’ gestation

Who required endotracheal intubation and positive pressure ventilation

Were considered ready for extubation by the clinical team.

Exclusion

Suspected upper airway obstruction

Congenital airway malformations

Or major cardiopulmonary malformations.

Intervention

HHHFNC via Vapotherm with 1.5-mm external diameter nasal cannulae (Vapotherm Inc, Stevensville, MD). Infants allocated to this group were extubated to a flow rate of 8 L/min. Flow rate was weaned to a minimum of 4 L/min.

NCPAP via Hudson binasal prongs, 3.7-4.6 mm external diameter (Hudson Respiratory Care Inc, Temecula, CA). Infants randomized to NCPAP were extubated to a positive end-expiratory pressure (PEEP) of 8 cm H2O if the fraction of inspired oxygen (FiO2) >0.3 or a PEEP of 7 cm H2O if FiO2 < 0.3. PEEP was weaned to a minimum of 5 cm H2O.

The same fixation method was used for both nasal interfaces (Sticky Whiskers Beevers Manufacturing and Supply, McMinville, OR). A nasal trauma score was adapted from Kaufman et al. and nasal trauma scores were recorded three times daily for the 7 days after extubation.

Oxygen saturation targets were 85-92% for both groups and all infants received a loading dose of 20 mg/kg caffeine citrate before extubation and a maintenance dose of 10 mg/kg/day until 34 completed weeks of gestation.

Randomization and allocation

A random number sequence was generated with STATA Statistical Software (Release 10.0, 2001; Stata Corp, College Station, TX) and was stratified by gestational age into less than 28 weeks’ gestation and 28.0-31.6 weeks’ gestation.

A variable block size was used for treatment allocation. Allocation was matched by the use of sequentially numbered, sealed opaque envelopes that were opened immediately before the subjects were extubated.

Statistical analyses

Review of data from the study center over a 2-year period (2004-2006) revealed 50% of infants <32 weeks’ gestation who required mechanical ventilation met the study extubation failure criteria in the 7 days after extubation with a reintubation rate of 35%.

A sample size of 130 provided 80% power to detect a reduction in extubation failure from 50-25% (alpha = 0.05).

Analysis was by intention to treat. Mean values and proportions between groups were analyzed by Student t-test or 2-sample test of proportions, respectively. All statistical analyses were performed using STATA Statistical Software: (Release 10.0. Stata Corp).

RESULTS

A total of 132 infants were enrolled between January 1, 2009 and July 31, 2011. All infants were followed for the first 7 days after extubation, and 121 infants were followed until their discharge home.

The baseline demographic and ventilation characteristics of enrolled infants with the exception of sex were similar. There were more males in the NCPAP group n = 41 (63%) compared with n = 33 (49%) of those assigned HHHFNC. There was no interaction of sex with the primary outcome variable of extubation failure (P = 0.5).

There were no differences in rates of extubation failure or BPD between the two groups. There were no differences in extubation failure rates in either gestational age stratum. Infants assigned to HHHFNC had significantly less nasal trauma than those assigned to NCPAP (P < 0.001) [Table 1].

Table 1

Primary outcome for infants assigned to receive either Vapotherm HHHFNC or NCPAP for postextubation respiratory support and by subgroup

Seven infants assigned to HHHFNC and eight in the NCPAP group were reintubated in the first week after extubation, having met the failure criteria. Two infants assigned to HHHFNC and seven assigned to NCPAP were changed to nasal intermittent mandatory ventilation (NIMV). At parental request, one infant's therapy was changed from NCPAP to HHHFNC; consent was retained for the use of primary outcome data.

A total of 13 (20%) of infants assigned to NCPAP were changed to HHHFNC as the result of nasal trauma in the first 7 days after extubation. These infants had a mean nasal trauma score of 22 (SD 10.1) compared with a mean score of 7.4 (SD 6.7) in those who remained on NCPAP (P < 0.001) and a mean score of 3.1 (SD 7.2) in those assigned to HHHFNC.

CONCLUSION

There was no difference in the rates of extubation failure between infants randomized to HHHFNC or NCPAP in the first 7 days after extubation. However, HHHFNC was associated with significantly less nasal trauma compared with NCPAP.

COMMENTARY

Evidence is accumulating addressing the efficacy of HHHFNC utilization in the management of preterm infants. To date, most of the studies comparing NCPAP to HHHFNC were of small size and included larger preterm infants.

Evidence suggests the HHHFNC is comparable to NCPAP as a weaning method off conventional ventilation. The largest study to date was conducted in Australia and presented at the Pediatric Academic Society (PAS) meeting, 2013 in Washington DC. The study included 300 preterm infants. HHHFNC was found to be noninferior to NCPAP for extubation failure in VLBW infants. The study failed to show noninferiority for infants less than 26 weeks. This new method of respiratory support in preterm infants was found to be more convenient to apply and results in less nasal trauma as compared with NCPAP.

We believe that evidence is still not conclusive especially for the smallest preterm infants less than 26 weeks and that more data are needed. A head to head comparison of the two available devices with regard to efficacy is also needed.

Abstracted from

Collins CL, Holberton JR, Barfield C, Davis PG. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr 2013;162:949-54.