High Flow Nasal Cannula vs. Non-Invasive Ventilation in Post-Extubation Pediatric Cardiac Surgery Patients: A Randomized Controlled Trial
Phase: NA
Conditions: Heart Defects, Congenital, Intensive Care Units, Pediatric, Respiration, Artificial, Extubation
Sponsor: Indonesia University

 
NCT Number : 
Date : 02 May 2025 
 
 
 
 
 
 
 
 
 
High Flow Nasal Cannula vs. Non-Invasive Ventilation in Post-Extubation Pediatric 
Cardiac Surgery Patients: A Randomized Controlled Trial 
 
 
 
Yogi Prawira 
Sharfina Fulki Adilla Hidayat 
Rismala Dewi 
Irene Yuniar 
Tartila 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
RESEARCH PROPOSAL 
 
Research Title 
 
 
Research Obejctives: 
This study aims to compare the extubation success rate between the use of 
High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (NIV) in pediatric 
patients post-cardiac surgery at the National General Hospital Dr. Cipto 
Mangunkusumo (RSCM). Additionally, this study seeks to identify factors 
influencing extubation failure in high-risk patient populations, compare CICU 
length of stay, sedation usage and COMFORT scale between patients receiving 
HFNC and those receiving NIV. 
Research Methodology: 
This study is a randomized controlled clinical trial involving two 
intervention groups: one receiving High Flow Nasal Cannula (HFNC) therapy using 
AirvoTM3 Nasal High Flow/HFNC System and the other receiving Non-Invasive 
Ventilation (NIV). The study population consists of pediatric patients admitted to 
the Cardiac Intensive Care Unit (CICU) at Dr. Cipto Mangunkusumo National 
General Hospital (RSCM) following cardiac surgery. A total of 114 subjects will 
be enrolled, with 57 patients allocated to each group. Patients will be monitored for 
24 hours post-extubation to evaluate the incidence of extubation failure and the 
associated risk factors. Reintubation will be performed in cases of respiratory 
failure or other complications requiring airway support. 
Expected Outcomes: 
The use of HFNC is expected to achieve an extubation success rate that is 
comparable to NIV, while offering a lower risk of complications and enhanced 
patient comfort. The findings of this study are anticipated to provide significant 
evidence regarding the differences between these two modalities in preventing 
extubation failure. 
Outcome of Study: 
The expected outcomes include a reduction in reintubation rates at 48 - 72 
hours, 7 days, and 28 days post-extubation in the HFNC group compared to the NIV 
group. Additionally, this study aims to decrease mortality rates in the CICU and 
shorten the length of hospital stay for pediatric patients following cardiac surgery. 
High Flow Nasal Cannula vs. Non-Invasive Ventilation in Post-Extubation 
Pediatric Cardiac Surgery Patients: A Randomized Controlled Trial 

 
 
 
 
CHAPTER 1 Introduction 
1.1. Background 
Congenital heart disease (CHD) is a significant global health concern, with 
a prevalence of 0.8–1.2% of total live births. In developed countries, post-cardiac 
surgery mortality rates among pediatric patients tend to be low. However, data from 
Indonesia, particularly from Dr. Cipto Mangunkusumo National General Hospital 
(RSCM), indicate a significant mortality rate. Over the past 3–5 years, the post- 
cardiac surgery mortality rate among pediatric patients at RSCM has been 
approximately 13.6%, primarily due to complications such as low cardiac output 
syndrome (LCOS), arrhythmias, multi-organ dysfunction, and extubation failure.1 
The incidence of extubation failure in pediatric cardiac surgery patients ranges from 
9.7% to 17.6%.2,3 often associated with airway, neurological, cardiac, 
diaphragmatic, and electrolyte-related factors.4–6 Patients experiencing repeated 
extubation failure have a higher risk of mortality compared to those who either do 
not experience it or fail extubation only once.7 Therefore, identifying effective 
solutions to mitigate the risk of extubation failure is of critical importance. 
Non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) are 
commonly implemented in healthcare centers to reduce the incidence of extubation 
failure. However, the effectiveness of HFNC in minimizing extubation failure 
among high-risk pediatric cardiac surgery patients remains uncertain, particularly 
in Indonesia. At RSCM, the systematic and widespread use of HFNC in managing 
post-cardiac surgery pediatric patients requires further investigation to establish its 
efficacy. This study aims to address this gap by comparing extubation success rates 
between HFNC and NIV at RSCM. 
 
1.2. Relevance to Priority Research Topics 
This research aligns with RSCM’s priority health topics, specifically the 
improvement of intensive care and post-operative recovery in pediatric cardiac 
surgery patients. Investigating respiratory management strategies, such as HFNC 
versus NIV, directly contributes to enhancing healthcare quality at RSCM. If HFNC 
proves to be comparable to NIV in preventing extubation failure, its implementation 
could optimize patient recovery and reduce complication rates. 
 
1.3. Research Problem Statement 
Given the high incidence of extubation failure among pediatric post-cardiac 
surgery patients at RSCM, there is a pressing need to identify a more effective 
approach to prevent extubation failure. This study aims to answer the following 
research question: Is HFNC as effective as NIV in preventing extubation failure 
in pediatric patients following cardiac surgery? 

 
 
 
 
1.4. Research Questions 
1. How does the extubation failure rate compare between HFNC and NIV in 
pediatric patients admitted to the CICU following cardiac surgery? 
2. What factors influence extubation failure in pediatric patients receiving 
HFNC compared to those receiving NIV? 
1.5. Research Objectives 
General Objective: To determine the effectiveness of HFNC compared to 
NIV in preventing extubation failure among pediatric post-cardiac surgery patients 
at RSCM. 
Specific Objectives: 
1. To compare the extubation failure rate between patients receiving HFNC 
and those receiving NIV. 
2. To identify factors influencing extubation success in each intervention 
group. 
 
Secondary Objectives: 
1. To compare CICU length of stay between patients receiving HFNC and 
those receiving NIV.  
2. To compare sedation usage (duration and total dose) between patients 
receiving HFNC and those receiving NIV  
3. To compare COMFORT scale between patients receiving HFNC and those  
receiving NIV  
 
1.6. Research Significance 
This study is expected to provide significant contributions to improving the 
quality of care for pediatric post-cardiac surgery patients at RSCM. The findings 
will generate valid data regarding the effectiveness of HFNC in preventing 
extubation failure, serving as a reference for selecting optimal respiratory therapy 
for these patients. 
For RSCM, this research will facilitate the development of improved 
clinical care standards for pediatric post-cardiac surgery patients, reduce 
complication rates, and enhance recovery outcomes. 
 
1.7. Strategic Research Outcomes 
1.7.1. Internal Implementation at RSCM 
The results of this study are expected to be implemented at RSCM 
in the form of Clinical Practice Guidelines (CPG), Standard Operating 
Procedures (SOPs), or Work Instructions (WIs) for the management of 
pediatric post-cardiac surgery patients. The integration of HFNC as a 
routine care modality will be incorporated into RSCM’s existing clinical 
pathways, supported by internal policies and regulations. 

 
 
1.7.2. Eksternal Adaptability outside RSCM 
The findings of this study have the potential to be adopted by other 
institutions outside RSCM, particularly hospitals that manage pediatric 
cardiac surgery cases. By demonstrating the effectiveness of HFNC, other 
hospitals may implement similar modalities to enhance the quality of care 
for pediatric post-cardiac surgery patients

 
 
CHAPTER II Literature Review 
Pediatric patients undergoing cardiac surgery are at high risk of developing 
respiratory complications, particularly following extubation. Unsuccessful 
extubation can lead to respiratory failure, increasing the need for reintubation and 
further medical interventions. Extubation failure is defined as the necessity for 
reintubation within 72 hours after planned extubation. Several studies have reported 
that the incidence of extubation failure in pediatric post-cardiac surgery patients 
ranges from 9.7% to 17.6%, depending on factors such as cardiopulmonary bypass 
(CPB) duration, congenital heart disease severity, and high inotropic support 
requirements.1 One potential strategy to reduce this rate is the implementation of 
non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) as a transitional 
modality before initiating low-flow oxygen therapy.8,9 However, the effectiveness 
of these approaches remains controversial, particularly in high-risk post-cardiac 
surgery populations. Furthermore, at the RSCM Cardiac ICU, a modified form of 
NIV is still in use, which may not be ideal due to the potential for inadequate airflow 
delivery. 
 
High Flow Nasal Cannula (HFNC) 
HFNC is one of the method use to support post-extubation patients to reduce 
the need for invasive intubation. HFNC delivers high-flow oxygen via a nasal 
cannula, equipped with optimal humidification and heating, thereby increasing 
patient comfort and reducing respiratory workload. HFNC also helps improve 
oxygenation and reduce the need for invasive mechanical ventilation.10 Research 
conducted by Mayfield et al. showed that the use of HFNC in pediatric patients with 
bronchiolitis can significantly reduce the need for admission to the pediatric 
intensive care unit (PICU) by up to fourfold compared with the use of low-flow 
oxygen therapy.11 HFNC has also been recognized as a safe modality for use in non- 
ICU settings, including in pediatric wards.11 McKiernan et al. emphasized that 
HFNC can reduce the rate of re-intubation in pediatric patients with bronchiolitis, 
as well as improve oxygen saturation without the risk of side effects such as 
pneumothorax or bradycardia.12 
 
Non-Invasive Ventilation (NIV) 
NIV is a respiratory support technique that utilizes positive pressure 
ventilation without invasive intubation. It is commonly employed in patients with 
acute respiratory distress to maintain airway patency and enhance gas exchange. 
Although NIV has been proven effective in preventing extubation failure in 
pediatric patients, it has several limitations. The use of masks or nasal interfaces in 
NIV can cause discomfort, particularly in infants and younger children, and may 
also increase the risk of air leakage, reducing the efficacy of the therapy.6 A study 
by Thille et al. found that factors such as prolonged cardiopulmonary 

 
 
bypass duration and high inotropic support postoperatively increased the risk of 
extubation failure in patients receiving NIV.6 Additionally, research by Miura et al. 
indicated that neonates experiencing extubation failure due to cardiovascular 
complications were at a higher risk of repeated extubation failure, which further 
elevated mortality risk.3 
 
Comparison of the Effectiveness of HFNC and NIV 
Studies comparing HFNC and NIV in pediatric post-cardiac surgery patients 
have yielded mixed results. Some research supports HFNC as a more comfortable 
and easier-to-implement modality, particularly due to its less invasive nasal cannula 
interface compared to the masks used in NIV. Furthermore, HFNC is considered 
more user-friendly in non-ICU settings.13 Conversely, NIV has been utilized for a 
longer duration in intensive care settings and is known for providing stable positive 
pressure, which helps prevent alveolar collapse and improves gas exchange in 
patients with compromised pulmonary function.8 
A study by Zhou et al. (2024) found that HFNC significantly reduced 
reintubation risk (RR = 0.36, P < 0.00001)14 and shortened ICU stay duration (MD 
= -4.75, P = 0.04). Similarly, research by Elmitwalli et al. (2024) reported that HFNC 
decreased reintubation rates (RR = 0.45, P < 0.01), mortality (RR = 0.31, P < 0.01), 
as well as length of hospital stay (-8.76 days, P < 0.01) and ICU stay (-4.63 days, P 
= 0.04).15 However, compared to conventional oxygen therapy, no significant 
differences were observed in reintubation rates. A study by Kuitunen (2023) 
concluded that there was insufficient evidence to establish a definitive difference in 
reintubation rates and other clinical outcomes between different non-invasive 
ventilation strategies, due to high bias risk and limited study numbers.16 
The debate continues regarding which modality is more effective in 
reducing extubation failure and mortality. HFNC provides benefits for patients with 
moderate-to-severe respiratory failure risk, whereas NIV may be more suitable for 
patients with severe pulmonary conditions. Further research is required to 
determine the optimal post-extubation strategy for pediatric post-cardiac surgery 
patients.

 
 
CHAPTER III Theoretical Framework, Conceptual Framework, and 
Operational Definitions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Image 1. Theoretical Framework 
Pediatric Post-Cardiac Surgery Patients 
Respiratory Dysfunction 
Hemodynamic 
Instability 
High-flow oxygen 
therapy with 
Positive Pressure 
Support 
HFNC 
   NIV 
Reduction of extubation 
failure 
Improved Oxygenation 
Prevention of alveolar 
collapse, improved gas 
exchange, and reduced 
risk of respiratory 
failure 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Image 2. Conceptual Framework 
 
 
 
Table 1. Operational Definitons 
 
Variable 
Definition 
Scale 
Measurement 
Criteria 
Age 
Age <12 months 
Patient age categorized as less than 
12 months. 
Categorical 
Medical 
history, 
medical records 
Age >12 months 
Patient age categorized as more 
than 12 months. 
Categorical 
Medical 
history, 
medical records 
Weight 
Weight 
Patient weight measured using a 
scale before intervention. 
Numeric 
Weight measurement 
(kg) 
RACHS 
RACHS 
Risk stratification for cardiac 
surgery. 
Categorical 
Ordinal 
Based on RACHS 
Classification 
in 
Medical Records 
Operation Type 
Off CPB 
Surgery without the use of 
cardiopulmonary bypass. 
Categorical 
Based 
Records 
on Surgical 
CPB 
Surgery without the use of 
cardiopulmonary bypass. 
Categorical 
Based 
Records 
on Surgical 
Gender 
Male 
Male patient. 
Categorical 
Medical 
history, 
medical records 
Female 
Female patient. 
Categorical 
Medical 
history, 
medical records 
Malnutrition 
Yes 
Patient 
diagnosed 
with 
malnutrition based on clinical 
assessment. 
Categorical 
Clinical Assessment 
No 
Patient 
not 
diagnosed 
with 
malnutrition  based  on  clinical 
assessment. 
Categorical 
Clinical Assessment 
Respiration 
Diagnosis 
at 
Extubation 
Pneumonia 
Patient diagnosed with pneumonia 
at the time of extubation. 
Categorical 
Based on Clinical 
Evaluation 
Effusion 
Patient diagnosed with pleural 
effusion at the time of extubation. 
Categorical 
Based on Clinical 
Evaluation 
Pediatric post-cardiac surgery patients 
with congenital heart disease (CHD), 
intubation > 48 hours 
Extubation 
HFNC Group 
NIV Group 
Successful extubation 
 
Extubation failure 

 
 
 
 
Vasoactive- 
Inotropic 
Score 
before Extubation 
VIS 
Vasoactive-Inotropic Score (VIS) 
to 
assess 
inotropic 
and 
vasoconstrictor therapy before 
extubation. 
Numeric 
VIS 
Calculation 
based 
on 
Drug 
Dosage 
ABG 
1 
hour 
before extubation 
pH 
Arterial blood pH measured 1 hour 
before extubation. 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PCO2 
Partial pressure of carbon dioxide 
(PaCO2) in blood, measured 1 hour 
before extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PaO2 
Partial pressure of oxygen (PaO2) 
in blood, measured 1 hour before 
extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
BE (Base Excess) 
Base excess or deficit in blood, 
measured 1 hour before extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
HCO3 
Bicarbonate 
concentration 
in 
blood, measured 1 hour before 
extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PF ratio 
Ratio of PaO2 to FiO2, measured 1 
hour before extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
OI/OSI 
Oxygenation Index (OI) or Oxygen 
Saturation Index (OSI), measured 1 
hour before extubation 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
Weaning Method 
Pressure Support 
Ventilator weaning method with 
pressure support. 
Categorical 
Medical Records on 
the Method Used 
T-piece 
Ventilator weaning method using a 
T-Piece without pressure support. 
Categorical 
Medical Records on 
the Method Used 
ABG 1 hour after 
NIV/HFNC 
pH 
Arterial blood pH measured 1 hour 
after initiation of NIV or HFNC. 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PCO2 
Partial pressure of carbon dioxide 
(PaCO2) in blood, measured 1 hour 
fater initiation of NIV or HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PaO2 
Partial pressure of oxygen (PaO2) 
in blood, measured 1 hour fater 
initiation of NIV or HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
BE (Base Excess) 
Base excess or deficit in blood, 
measured 1 hour fater initiation of 
NIV or HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
HCO3 
Bicarbonate 
concentration 
in 
blood, measured 1 hour fater 
initiation of NIV or HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
PF ratio 
Ratio of PaO2 to FiO2, measured 1 
hour fater initiation of NIV or 
HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
OI/OSI 
Oxygenation Index (OI) or Oxygen 
Saturation Index (OSI), measured 
1 hour fater initiation of NIV or 
HFNC 
Numeric 
Arterial Blood Gas 
(ABG) Measurement 
Successful 
Extubation 
No Reintubation 
in 72 hours 
Patient 
does 
not 
require 
reintubation within 72 hours after 
extubation 
Categorical 
Based on Clinical 
Observation 
Extubation Failure 
Reintubation 
within 72 hours 
Patient requires reintubation within 
72 hours after extubation 
Categorical 
Based  on  Clinical 
Observation 
Reintubation 
Reintubasi at 72 
hours, 7 days and 
28 Days 
Frequency of patients requiring 
reintubation at 72 hours, 7 days and 
28 days 
Categorical 
Based on Clinical 
Observation 
Mortality in CICU 
Mortality During 
CICU Stay 
Number of patient deaths during 
CICU hospitalization 
Categorical 
Based on Mortality 
Records 
Length of CICU 
Stay  
Total Length of 
CICU Stay (in 
Days)  
Total length of CICU stay measured 
in days  
Numeric  
Based on Hospital 
Records  
Length of Hospital 
Stay  
Total Length of 
Hospital Stay (in  
Days)  
Total length of hospital stay 
measured in days  
Numeric  
Based on Hospital 
Records  
Sedation usage  
Duration of 
sedation (in Hours) 
and total dosage  
Total duration of sedation after 
extubation measured in hours and 
total dosage  
Numeric  
Based on Hospital 
Records  
COMFORT scale  
Patient’s comfort 
during sedation post 
extubation  
Patient’s comfort measured in 
COMFORT behavioral scale  
Categoric  
COMFORT 
behavioural scale 
assessmen  

 
 
CHAPTER IV Research Methodology 
4.1. 4.1. Study Design 
This study employs a Randomized Controlled Trial (RCT) design to 
compare two intervention groups: patients receiving oxygen therapy 
using Non-Invasive Ventilation (NIV) and those receiving therapy 
with High Flow Nasal Cannula (HFNC) using AirvoTM3 Nasal High 
Flow/HFNC System. Patients will be monitored for the incidence of 
extubation failure and other clinical parameters throughout their 
hospitalization. 
 
4.2. Study Setting and Duration 
This study will be conducted in the Cardiac Intensive Care Unit 
(CICU) at Dr. Cipto Mangunkusumo National General Hospital 
(RSUPN Cipto Mangunkusumo), Jakarta. The study period will run 
from January 2025 to December 2025. 
 
4.3. Population and Sample 
The study population consists of pediatric patients undergoing 
post-cardiac surgery and receiving care in the CICU at RSUPN 
Cipto Mangunkusumo, Jakarta. The study sample will be selected 
based on predefined inclusion and exclusion criteria, with the total 
sample size determined using an appropriate statistical estimation 
formula. The sample size estimation will be calculated using the 
following formula: 
 
 
𝑛1 = 𝑛2 = ( 
2 
𝑍𝛼√2𝑃𝑄+𝑍𝛽√𝑃1𝑄1+𝑃2𝑄2) 
𝑃1−𝑃2 
Description: 
n1 = n2 = Sample size 
Za = Standard deviation for Type I error = 5% = 1,96 
Zb = Standard deviation for Type II error = 20% = 0,84 
P1 − P2 = Minimum significant difference in proportion = 0,25 
P2 = Extubation failure rate with HFNC based on literature is 17% 
or equivalent to 0.17. 
Q2 = 1 − 0,17 = 0,83 
P1 = P2 + 0,25 = 0,17 + 0,25 = 0,42 
Q1 = 1 − P1 = 1 − 0,42 = 0,58 
P = (P1 + P2)/2 = (0,42 + 0,17)/2 = 0,295 
Q = 1 − P = 1 − 0,295 = 0,705 
 

 
 
𝑛1 = 𝑛2 =  (1,96√2𝑥0,295𝑥0,705 + 0,84√0,42𝑥0,58 + 0,17𝑥0,83
0,42 −0,17
)
2
 
= 51 
 
 
Meanwhile, when estimating the sample size based on the outcome 
of  reintubation  rate  reduction,  the  calculation  is  as  follows 
 
2 
𝑍𝛼√2𝑃𝑄 + 𝑍𝛽√𝑃1𝑄1 + 𝑃2𝑄2 
𝑛1 = 𝑛2 = ( 
𝑃1 − 𝑃2 
) 
 
Description: 
P1 (HFNC) = 0.37 (HFNC reintubation rate) 
P2 (NIV) = 0.15 (NIV reintubation rate) 
P1 - P2 = 0.25 (Difference to be detected) 
Q1 = 1 - P1 = 1 - 0.37 = 0.63 
Q2 = 1 - P2 = 1 - 0.15 = 0.88 
P = (P1 + P2) / 2 = (0.37 + 0.17) / 2 = 0.245 
Q = 1 - P = 1 - 0.245 = 0.755 
 
𝑛1 = 𝑛2 =  (1,96√2𝑥0,245𝑥0,755 + 0,84√(0,37𝑥0,63) + (0,12𝑥0,88)
0,25
)
2
 
= 45.22 ~ 46 subjects 
 
Similarly, when estimating the sample size based on the outcome of 
mortality reduction, the calculation is as follows: 
 
𝑛1 = 𝑛2 = ( 
Description: 
2 
𝑍𝛼√2𝑃𝑄 + 𝑍𝛽√𝑃1𝑄1 + 𝑃2𝑄2 
𝑃1 − 𝑃2 
) 
P1 (HFNC) = 0.1 (Mortality rate with HFNC) 
P2 (NIV) = 0.35 (Mortality rate with NIV) 
P1 − P2 = 0.25 (The difference to be detected) 
Q1 = 1 - P1 = 1 - 0.1 = 0.9 

 
 
 
 
Q2 = 1 - P2 = 1 – 0,35 = 0,65 
P = (P1 + P2) / 2 = (0.1 + 0,33) / 2 = 0,225 
Q = 1 - P = 1 – 0,225 = 0,77
 
 
 
 
𝑛1 = 𝑛2 =  (1,96√2𝑥0,225𝑥0,775 + 0,84√(0,1𝑥0,9) + (0,35𝑥0,65)
0,25
)
2
 
= 42.54 ~ 43 subjek 
 
Based on these calculations, the required sample size is 51 subjects 
per group, resulting in a total of 102 subjects for both groups. 
Considering an additional 10% to account for loss to follow-up, 
the  adjusted  sample  size  is  calculated  as  follows: 
Additional subjects: 
10%×102=10,2 
Total subjects after addition: 
102+10,2=112,2~113 subjek 
57 subjects/group 
 
Thus, this study requires 57 subjects per group, with a total of 114 
subjects. 
 
4.4. Inclusion and Exclusion Criteria 
Inclusion Criteria: 
• Patients under 18 years of age. 
• Post-cardiac surgery patients in the CICU of RSUPN. 
• Patients at high risk of extubation failure (e.g., young age, 
open sternotomy, mechanical ventilation >48 hours). 
• Patients who pass the extubation readiness test and 
spontaneous breathing trial. 
Exclusion Criteria: 
• Diaphragmatic paralysis. 
• Decreased consciousness. 
• Neuromuscular disease. 
• Pneumothorax without drainage. 
• Airway obstruction. 
• Patients with a tracheostomy. 
• Unplanned extubation. 
• Patient received PEEP >7 prior to extubation 

 
 
 
4.5. Sample Size Estimation 
The sample size calculation follows the formula for unpaired 
categorical analytical studies. Based on the literature, the extubation 
failure rate with HFNC is 17%, and the minimum significant 
difference in proportion is 25%. The estimated sample size for each 
group is 57 patients, with a total of 114 patients for both groups. 
 
4.6. Sampling Method 
Sampling is conducted consecutively from pediatric post-cardiac 
surgery patients who meet the inclusion criteria during the study 
period in the CICU of RSUPN Cipto Mangunkusumo. Subjects 
meeting the inclusion and exclusion criteria will be randomized into 
two intervention groups: the High Flow Nasal Cannula (HFNC) 
group and the Non-Invasive Ventilation (NIV) group, using a simple 
randomization method. Block randomization was employed to 
ensure balanced allocation between the intervention and control 
groups. Subject assignment within each block was conducted 
randomly using statistical software (e.g., SPSS or Excel), with 
allocation concealed from investigators involved in data collection 
to minimize potential bias. 
 
4.7. Data Collection Technique 
Data is collected through clinical observation and measurement of 
patients' respiratory parameters before and after therapy. A blood 
sample of 0.5–1.0 mL is taken one hour before and after therapy. 
Monitoring is conducted by a trained medical team, and data on 
extubation failure, vital parameters, and patients' clinical conditions 
are continuously recorded during hospitalization. 
 
4.8. Data Analysis 
Data will be processed using statistical software and analyzed 
through univariate and multivariate analyses. 
• Univariate analysis will be used to describe subject 
characteristics. 
• Multivariate analysis using binary logistic regression will be 
performed to identify factors influencing extubation failure. 

 
 
 
 
 
4.9. The Research Flowchart includes input, process, output, and 
outcome components based on the achievement indicators. 
 
 
Image 3. Research Flowchart 
INPUT 
Pediatric post-cardiac surgery patients 
with PIM, intubation >48 hours 
Screening and Randomization 
Spontaneous Breathing Trial 
High-risk Extubation Profile 
Informed Consent 
ABG Test 1 hour before extubation 
Extubation 
ABG Test 1 hour after extubation 
Devices applied to patients continuously 
for 24 hours. If the patient remains 
stable, device settings are adjusted 
based on the patient's condition 
Standard Intensive Care Unit Monitoring 
(Electrocardiogram, Oxygen Saturation, 
PaCO₂) 
Monitoring of Extubation Failure 
Incidents 

 
 
 
 
 
Image 4. NIV Group Procedure  
   
 
Image 5. HFNC Group Procedure 
HFNC applied in 
patients using AirvoTM3 
Nasal High Flow/HFNC 
System 
+ Interface: oronasal/ full 
face mask, nasal pronge 

 
 
 
 
 
4.10. Research Timeline 
 
No 
Action Plan 
Month 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
1. 
Preparation and Ethical 
Approval Submission 
2. 
Patient Recruitment and 
Randomization 
3. 
Intervention 
Implementation (HFNC and 
NIV) 
4. 
Data Collection and 
Monitoring 
5. 
Data Analysis and Report 
Writing 
 
References 
1. 
Murni IK, Djer MM, Yanuarso PB, Putra ST, Advani N, Rachmat J, et al. Outcome 
of pediatric cardiac surgery and predictors of major complication in a developing 
country. Ann Pediatr Cardiol. 2019;12(1):38–44. 
2. 
Miura S, Jardim PV, Butt W, Namachivayam SP. Extubation Failure and Major 
Adverse Events Secondary to Extubation Failure Following Neonatal Cardiac 
Surgery*. Pediatr Crit Care Med. 2020 Dec;21(12):e1119–25. 
3. 
Miura S, Butt W, Thompson J, Namachivayam SP. Recurrent Extubation Failure 
Following Neonatal Cardiac Surgery Is Associated with Increased Mortality. 
Pediatr Cardiol. 2021 Jun;42(5):1149–56. 
4. 
Rooney SR, Mastropietro CW, Benneyworth B, Graham EM, Klugman D, Costello 
J, et al. Influence of Early Extubation Location on Outcomes Following Pediatric 
Cardiac Surgery∗. Pediatr Crit Care Med. 2020;21(10):E915–21. 
5. 
Simeonov L, Pechilkov D, Kaneva A, McLellan MC, Jenkins K. Early extubation 
strategy after congenital heart surgery: 1-year single-centre experience. Cardiol 
Young. 2022;32(3):357–63. 
6. 
Thille AW, Boissier F, Ghezala H Ben, Razazi K, Mekontso-Dessap A, Brun- 
Buisson C. Risk factors for and prediction by caregivers of extubation failure in ICU 
patients: A prospective study. Crit Care Med. 2015;43(3):613–20. 
7. 
Morales Acevedo JA, Muñoz Rodríguez CM, Garcia Iturbide R, Rodriguez Sanchez 

 
 
 
 
JR, Mejia Perez SI. Clinical variables associated to extubation failure in mexican 
pediatric patients: Associated variables to failure in extubation. Trends Anaesth Crit 
Care. 2021;37(xxxx):55–9. 
8. 
Chang CJ, Chiang LL, Chen KY, Feng PH, Su CL, Hsu HS. High-Flow Nasal 
Cannula versus Noninvasive Positive Pressure Ventilation in Patients with Heart 
Failure after Extubation: An Observational Cohort Study. Can Respir J. 2020;2020. 
9. 
Demoule A, Chevret S, Carlucci A, Kouatchet A, Jaber S, Meziani F, et al. 
Changing use of noninvasive ventilation in critically ill patients: trends over 15 
years in francophone countries. Intensive Care Med. 2016;42(1):82–92. 
10. 
Doshi P, Whittle JS, Bublewicz M, Kearney J, Ashe T, Graham R, et al. High- 
Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized 
Clinical Trial. Ann Emerg Med. 2018 Jul;72(1):73-83.e5. 
11. 
Mayfield S, Bogossian F, O’Malley L, Schibler A. High-flow nasal cannula oxygen 
therapy for infants with bronchiolitis: Pilot study. J Paediatr Child Health. 
2014;50(5):373–8. 
12. 
McKiernan C, Chua LC, Visintainer PF, Allen H. High Flow Nasal Cannulae 
Therapy in Infants with Bronchiolitis. J Pediatr. 2010 Apr;156(4):634–8. 
13. 
McQueen M. Safety and Long Term Outcomes with High Flow Nasal Cannula 
Therapy in Neonatology: A Large Retrospective Cohort Study. J Pulm Respir Med. 
2014;04(06). 
14. 
Zhou, S. J., Chen, X. H., Liu, Y. Y., Chen, Q., Zheng, Y. R., & Zhang, Q. L. (2024). 
Comparison of high-flow nasal cannula oxygenation and non-invasive ventilation 
for postoperative pediatric cardiac surgery: a meta-analysis. BMC Pulmonary 
Medicine, 24(1), 92. 
15. 
Elmitwalli, I., Abdelhady, E., Kalsotra, S., Gehred, A., Tobias, J. D., & Olbrecht, 
V. A. (2024). Use of high‐flow nasal cannula versus other noninvasive ventilation 
techniques or conventional oxygen therapy for respiratory support following 
pediatric cardiac surgery: A systematic review and meta‐analysis. Pediatric 
Anesthesia, 34(6), 519-531. 
16. 
Kuitunen, I., & Uimonen, M. (2024). Noninvasive respiratory support preventing 
reintubation after pediatric cardiac surgery—A systematic review. Pediatric 
Anesthesia, 34(3), 204-211.