INTRODUCTION

Surfactant therapy is applied through two different techniques in order to treat respiratorydistress syndrome (RDS). The INSURE (intubate, surfactant, extubate) method is the most commonway for surfactant treatment.¹ Recently, a newmethod, minimally invasive surfactant therapy (MIST), has been developed to administersurfactant. Surfactant administration via a thinendotracheal catheter during spontaneousbreathing with continuous positive airwaypressure (CPAP) has come into clinical use withthis method.²,⁵ However, not enough data andexperience exist on how MIST and INSURE techniques affect pain perception in newborns.

It is difficult to evaluate pain perception in infants. Presently, pain and/or discomfortassessment is mainly based on behavioral painscales. However, these scoring systems are basedon items like facial movements, body movements, or comfort ability and therefore subjected tosignificant inter- and intra-observer variability.⁶,⁹

Recent studies indicated that sympathetic and parasympathetic influences in response topainful or stressful stimulus can be measured byvariations of RR heart rate intervals. It has beenshown that the Newborn Infant Parasympathetic Evaluation (NIPE) index could assess theparasympathetic tone and evaluate prolongedpain, acute pain, discomfort, and comfortablestimulations. In this study, we aimed to comparethe pain perceptions of preterm infants treatedwith different surfactant administrationtechniques using heart rate variability (HRV) asmeasured by the NIPE index and PIPP score.

METHODS

This prospective randomized controlled study was conducted in the neonatal intensive care unit (NICU) of Zekai Tahir Burak Maternity Teaching Hospital between May and June 2015. Preterminfants with 26-32 weeks of gestational age and ≤1250 g birthweight who suffered from RDS wereenrolled. This trial was approved by the Zekai

Tahir Burak Maternity and Teaching Hospital Ethics Committee, and written parental consentwas obtained from the parents of each infant.

Preterm infants requiring surfactant therapy for RDS were randomly assigned to either INSURE or MIST groups when they wereadmitted to the NICU. NIPE monitor (Mdoloris Medical Systems, France) was attached toeach infant before surfactant administration. Infants with major congenital anomalies; PPV orintubation in the delivery room; structural cardiacanomalies; exposure to painful procedures likevenipuncture, suctioning, blood sampling, orheel prick 30 minutes before assessment; andlack of parental consent were excluded. RDS wasdiagnosed in infants exhibiting the followingsymptoms: need for supplemental oxygen, tachypnea, grunting, and intercostal retractions; it was confirmed by typical x-ray and bloodgas findings. A suggested protocol would be totreat infants ≤26 weeks' gestation when Fi O₂requirements > 0.30 and infants >26 weeks' when Fi O₂ requirements > 0.40.

RESULTS

Fourteen infants were enrolled in the study: INSURE: n = 7; MIST: n = 7 (Figure 1). Mean ± SD) gestational age of the infants was 29.1 ± 1.5 inthe INSURE group and 29.4 ± 1.2 in the MIST group (p > 0.05). Mean (± SD) birthweights of theinfants were 1107 ± 103 g in the INSURE groupand 1127 ± 85 g in the MIST group (p > 0.05). Demographic characteristics of the groups wereshown in Table 1.

Figure 1 Flowchart of study infants 

Table 1 Demographic characteristics of the groups 

The PIPP scores and HRV variables of the groups are presented in Table 2. The median PIPP scores were 10 (10-13) and 10 (8-12) inthe INSURE and MIST groups, respectively. PIPP scores did not differ between infants inthe INSURE and MIST groups (p = 0.053). Astatistically significant difference in the median HRV of infants during surfactant administrationwas observed between the INSURE and MIST groups (52 vs. 56, p = 0.03). HRV analyses beforeand after surfactant administration were similarin both groups (Table 2). HRV index and PIPP score of each infant are shown in Table 3. Therewas a significant correlation between NIPE valuesand PIPP scores during surfactant administration (r² = -0,811, p < 0.0001).

Table 2 Comparison of HRV index and PIPP scores 

Table 3 NIPE index and PIPP score of each infant 

DISCUSSION

In our study, we observed that the NIPE index was significantly higher during the surfactantadministration in infants treated with MIST technique and also correlated with PIPP scores.

There is consensus that the endotracheal intubation procedure should be performedwhile the infant is adequately sedated.¹⁰,¹¹ However, there is ongoing debate about whetheror not sedation should be used during MIST, as the presence of spontaneous breathing is aprerequisite for the procedure. In the studiesevaluating MIST technique no sedation wasused.¹² In our study we found that the MIST technique group had less pain compared to INSURE group. So, we suggested that surfactantadministration with the MIST technique, thus, may be more comfortable for preterm infantswith RDS.

Alexandre et al. compared HRV before and after standardized cocooning phases associatedwith the human voice and carried out: 1) bythe mother and 2) by a third person. HRV wasassessed and expressed as an index reflectingthe parasympathetic tone. They showed that cocooning associated with the human voice enhances HRV in the preterm infant, indicatingan increase in parasympathetic activity.¹³

Our study is strong in terms of revealing the stress levels of preterm infant treated withsurfactant. Pain was assessed by both the PIPP scores and NIPE index, while different surfactantadministration techniques were applied to theinfants. PIPP score is a powerful scale that hasbeen used in the objective assessment of painin premature infants. Scarce information isavailable in the literature about the pain sensationthat MIST practice can produce, and our trialpresents results that will help illuminate this areaof inquiry. In addition, current trial is the firststudy to compare PIPP score with NIPE index inpreterm infants.

Our study has some limitations. First, HRV is controlled by the autonomic nervous systemoutflow, which can be altered by numerousfactors, including maturation, environmentalconditions, and/or drugs. Second it is a smallsample sized study.

CONCLUSION

Our findings suggest that surfactant administration using the MIST technique mightbe more comfortable for preterm infants with RDS.