Comparison of the Results of Transcutaneous Carbon Dioxide and Oxygen Pressure in Premature Neonates Who Underwent Minimally Invasive Surfactant Therapy (MIST) Under Heated Respiratory Support With Nasal Cannula High Flow Air Support (HHHFNC) or Nasal Continuous Airway Pressure (CPAP) Methods
Conditions: Premature Birth, Respiratory Distress Syndrome, Surfactant Deficiency Syndrome Neonatal
Sponsor: Hacettepe University

COMPARİSON OF THE RESULTS OF 
TRANSCUTANEOUS CARBONDİOXİDE 
AND OXYGEN PRESSURE İN 
PREMATURE NEONATES WHO 
UNDERWENT MİNİMALLY INVASİVE 
SURFACTANT THERAPY (MIST) 
UNDER HEATED RESPİRATORY 
SUPPORT WİTH NASAL CANNULA 
HİGH FLOW AİR SUPPORT (HHHFNC) 
OR NASAL CONTİNUOUS AİRWAY 
PRESSURE (CPAP) METHODS 
Documented Date: June 20, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Comparison of the Results of Transcutaneous Carbondioxide and Oxygen Pressure in 
Premature Neonates Who Underwent Minimally Invasive Surfactant Therapy (MIST) Under 
Heated Respiratory Support With Nasal Cannula High Flow Air Support (HHHFNC) or Nasal 
Continuous Airway Pressure (CPAP) Methods  
Study Protocol: 
In premature babies (born before 37th week of pregnancy), surfactant production is insufficient since 
lung maturation has not been completed yet. Accordingly, surface tension increases in alveoli and it 
is difficult to keep the alveoli open, gas exchange is insufficient, and as a result, respiratory distress 
syndrome (RDS) occurs in premature babies. Severe respiratory failure occurs in the baby, it must be 
connected to the mechanical ventilator, even if hypoxia cannot be corrected, the baby may be lost. 
Intraracheal surfactant treatment is applied in the treatment of respiratory distress syndrome, which 
develops due to surfactant deficiency. With surfactant treatment, death due to RDS, mechanical 
ventilation requirement, morbidity due to lung disease, hospitalization times in neonatal intensive 
care units have been reduced and survival rates of premature babies have increased. 
Intraracheal surfactant treatment is applied in RDS treatment. In recent clinical studies, two similar 
methods have been studied with a thin catheter without endotracheal intubation in the application 
of surfactant. One of these methods; Developed in Germany, it is LISA (the application of surfactant, 
which is less invasive), which is currently widely used in Europe. In the LISA method, surfactant is 
given after placing a thin flexible catheter into the trachea with the help of a laryngoscope (Magill's 
forceps may or may not be used) while the baby is in CPAP. The second method is the application of 
surfactant, which was developed in Australia and given by using a hard thin vascular catheter into the 
trachea while the baby is being followed up in CPAP only under direct laryngoscope without using 
forceps. This method is called MIST (minimally invasive surfactant treatment). In both methods, the 
aim is to give the surfactant warmed up to body temperature slowly in a few minutes with the help 
of an injector in a baby with spontaneous breathing under CPAP. 
In the current RDS review (2019), it was emphasized that noninvasive respiratory support is the most 
appropriate way to support the breathing of preterm infants. Non invasive methods; CPAP is 
specified as bi-level CPAP, HHHFNC, positive pressure ventilation with nasal interval. CPAP devices 
provide gas flow under controlled pressure with probes firmly placed in the nose. Through the 
distension pressure; Supporting the opening of the upper airway, continued lung expansion and 
prevention of end-expiratory alveolar collapse (lung closure at the end of breath). Thus, it is easier to 
release the endogenous surfactant. 
Heated high flow air support (HHHFNC) moistened with nasal cannula; It has been used as an 
alternative to nasal CPAP since 2013 RDS guideline. The utility mechanism allows the removal of 
carbon dioxide in the nasopharyngeal area, provides the anatomical dead space to be washed with 
air flow, reduces the disadvantage of the anatomical dead space. It also provides CPAP-like support 
thanks to its high flow rates. It reduces breathing work. It helps to reduce the FiO2 level, typically 
using a flow rate of 4-8 L / min. 
According to the RDS review updated in 2019, early surfactant should be applied in infants with RDS. 
According to the latest recommendation, surfactant should be given if the baby's FiO2 (oxygen 
content in inhaled air) need is over 30%. 
In our neonatal intensive care unit, respiratory support is given with nasal CPAP and HHHFNC instead 
of classical invasive (intubated) mechanical ventilation methods. In CPAP method, heated and 
humidified air is given a certain pressure (6-8 cmH2O), while in HHHFNC method, heated humidified 

air is given at a certain flow rate (6-8 L / min).  This study was planned to compare the results of 
infants who were given surfactant with MIST method under CPAP or HHHFNC support in the 
treatment of respiratory distress syndrome in premature babies. No blood will be collected from the 
babies included in this study, and nothing that will not be applied to babies who are not included in 
the study. If these babies need surfactant according to the chest X-ray and oxygen demand in the 
breathing air, surfactant support will be given by MIST method. In the follow-up of these babies, 
after the surfactant application, the follow-up application for each baby will be carried out; Blood gas 
will be taken in the second and sixth hour, and a chest radiograph will be taken in the sixth hour. The 
mechanical ventilation settings of the patient are made according to the values here. For example, 
the pressure given in case of insufficient oxygenation, the amount of oxygen is increased, the 
pressure given in case of hypercarbia is increased, the pressure is decreased in case of hypocarbia. 
This measurement shows only partial carbon dioxide (PCO2) and partial oxygen (PO2) pressures in 
that instant blood gas. It is of great importance to protect the premature babies being monitored in 
the intensive care unit from hypoxia and hypercarbia, as well as the pressure, volume, oxygen-
related trauma and injuries given by iatrogenically invasive or non-invasive respiratory support. 
Unnecessarily high supply of oxygen can cause oxygen radical damage and increase the risk of 
diseases associated with oxygen radical damage (premature retinopathy, necrotizing enterocolitis, 
bronchopulmonary dysplasia, periventricular leukomalacia). With the improvement of lung 
compliance and recovery of gas after surfactant treatment, carbon dioxide excretion may accelerate 
and hypocarbia may develop. Hypocarbia can cause intraventricular hemorrhage and periventricular 
leukomaliasis in premature babies. 
During surfactant application, babies will be monitored (as in all babies in the NICU) saturation, peak 
heart rate, perfusion index (the ratio of nonpulsatile flow in the capillary bed) and t values will be 
recorded. For all these reasons, monitoring of PI, PVI and continuous transcutaneous PCO2 and PO2 
values are of great importance for the prevention of mortality and morbidity, as well as monitoring 
of oxygen saturation values with pulse oximetry in premature babies.  
Research Method: 
In our hospital, it was planned to take a total of 40 patients born under 32 weeks and less than 1500 
grams (20 patients being in the HHHNFC, 20 patients in the CPAP group). Patients will be 
consecutively distributed to two groups until they reach the specified number of patients. 
In this study, it was aimed to monitor continuous oxygen saturation, PI, PVI, transcutaneous PO2 and 
PCO2 measurements just before, during and after the surfactant application and to compare the 
results of babies who received nCPAP and HHHFNC support. 
At the end of the study, all data will be entered in an SPSS file and study statistics will be made. A 
database will be created using SPSS software. A p value of <0.05 was determined as the limit of 
significance.  
Inclusion criteria 
• Premature babies under 37 weeks of sleep at Hacettepe University Neonatal Intensive Care Unit, 
• Infants who have been diagnosed with respiratory distress syndrome in the first 24 hours of life, 
who have received surfactant treatment under the nCPAP or HHHFNC method using the MIST 
method, 
• Babies whose informed consent was obtained from their mothers and / or fathers 

Exclusion criteria 
• Term babies born 37 weeks and over 
• Babies monitored for intubation due to severe respiratory failure 
• Babies with hemodynamically unstable, severe hypotension 
Major congenital anomalies (severe congenital heart disease, congenital diaphragmatic hernia etc.) 
• Babies with chromosomal disorders 
• Babies with hereditary metabolic disease 
• Babies whose informed consent form could not be obtained from their mothers and / or fathers 
• Babies whose mothers have early membrane rupture or chorioamnionitis 
• Diabetic mother babies 
• Families who want their children to leave the work at any time of the study 
• Babies whose study data cannot be collected completely