Heated, Humidified High-flow Nasal (HHHFN) Cannula vs Nasal Continuous Positive Airway Pressure in Respiratory Distress in Premature Neonates

1. Objective:

   To compare the clinical efficacy of HFNC and NCPAP, as primary respiratory support in neonates with respiratory distress who are≥28 weeks GA in reducing the need for IMV.

2. Operational definition

   • Efficacy:

Efficacy will be assessed on basis of treatment failure

-Treatment failure: Treatment failure defined as requiring intubation or other non-invasive respiratory support within 72 h of starting intervention.

Mechanical ventilation will be considered when

1. Sustained increase in oxygen requirement: FiO2>0.40 to maintain SpO2 of 90%-94% for more than 2 hour
2. Respiratory acidosis: potential of Hydrogen (pH)≤7.20 and PaCO2>60 mm Hg

3. Frequent or severe apnea despite drug therapy or respiratory support: two or more apnea events requiring bag-mask ventilation within 24 h

   • HFNC:

HFNC will be provided by devices that deliver a blend of heated and humidified gas mixture of air and oxygen at gas flows exceeding 1 L/ min via binasal cannula.

-N-CPAP: NCPAP will be provided by devices with pressure that is measurable and controllable that transport heated and humidified gas via binasal nasal prongs or nasal masks

-Respiratory distress: It will be defined on basis of Silverman Anderson score Primary outcome Our primary outcome is treatment failure within 72hrs of starting intervention Secondary outcomes

1. Nasal injury following either intervention
2. Death before discharge.
3. Surfactant treatment within 72 h after randomization.
4. Duration of both NIV and IMV.
5. Duration of oxygen therapy.
6. Time to achieve full enteral nutrition.
7. Necrotizing enterocolitis.
8. Duration of admission. Hypothesis Alternate hypothesis There is a difference in clinical efficacy of different respiratory supports i.e nCPAP and HHHF in neonates with respiratory distress Null hypothesis There is no difference in clinical efficacy of different respiratory supports i.e NCPAP and HHHF in neonates with respiratory distress

3.Materials and methods

• Study design Randomized controlled trial
• Setting This trial will be conducted at PAF Hospital Islamabad NICU which is a tertiary hospital equipped with ventilators capable of providing HHFN and NCPAP.
• Duration of study 6months
• Sample size The sample size was calculated by using WHO sample size calculator with following parameters Level of significance =5% Power of test=90% Anticipated population proportions, rate of treatment failure in NCPAP group (P1) = 40% and rate of treatment failure in HHHFNC group (P2) = 11.8%.

The sample size turned out to be 50 patients in each group and a total of 100 patients will be included in the study

• Sampling technique Consecutive non probability sampling
• Data collection procedure Before enrolling eligible neonate in our research study informed consent will be taken from guardian. After consent they will be randomly assigned to one of the two groups: the HFNC group, CPAP group. We will assess the respiratory distress using Silverman Andersen Score before starting any respiratory intervention. Surfactant (Curosurf) will be administered to infants with FiO2>0.40 and with evidence of RD syndrome (RDS) on chest x-ray. In nCPAP group, initial PEEP would be 6cm H2O and for HHHF group, initial flow rate will be 6 L/min for all infants ,target Spo2 will be 90-94% for which FiO2 will be adjusted accordingly in both groups .Gas flow of 8L/min in HHFN and PEEP of 8cm H2O for nCPAP will be considered as maximum setting and FiO2 up to 0.40 would be our upper cut off range to ensure adequate oxygenation. Cardiac monitors will be attached continuously and will monitor R/R, Silverman score to assess distress, FiO2 requirement, apneic spells length of stay, duration of respiratory support, initiation of feed in both groups. If infant meet any of pre defined treatment failure criteria, the assigned intervention will be terminated and infant will be put on mechanical ventilation. Non-invasive ventilation failure criteria included acidosis and hypercarbia (pH \<7.20 and pCO2 >65 mmHg), apnea (≥2 episodes/h).Weaning will be started based on clinical status and set protocol i.e when flow rate for infants can be decreased down to 2 L/min in HHHFN group and in CPAP group, pressure for infants can be decreased down to 4 cmH2O.
• Data analysis procedure Data will be analyzed using SPSS software (Version 23) .Descriptive stats will be calculated for both quantitative and qualitative variables Qualitative variables like efficacy , gender, mode of delivery, nasal injury NEC will be measured in term of frequency and percentage Quantitative variables like gestational age, weight, duration of hospital stay, TTN score, need of respiratory support in days , initiation of enteral feeding (hours), duration of respiratory support will be measured in form of mean and standard deviation .Effect modifiers like gestational age, gender, weight and mode of delivery will be controlled through stratification. Post stratification, Independent sample t-test will be used to compare quantitative variables in both groups. P value\< 0.05, will be considered as significant