Surfactant Administration via Thin Catheter during Spontaneous Breathing: Randomized Controlled Trial in Alzahra hospital

Document Type: Original Article

Authors

1 Neonatologist, Pediatrics Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Assistant Prof. of Neonatology, Dept. of Pediatrics, Tabriz University of Medical Sciences, Director of Dept. of Neonatal Health, Ministry of Health & Medical Education, Tabriz ,Iran

3 Associated Prof. of Neonatology, Dept. of Pediatrics, Tabriz University of Medical Sciences, Tabriz, Iran

4 Assistant prof. of Neonatology, Isfahan University of Medical Sciences, Isfahan, Iran

5 Master of maternal and neonatal health science, Master of public Health (SDH), Dept. of Neonatal Health, Deputy of Public Health, Ministry of Health and Medical Education, Tehran, Iran

6 Assistant prof. of Neonatology, Boosher University of Medical Sciences, Boosher,Iran

7 PHD of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran

8 MSC of NICU, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Introduction
Respiratory distress syndrome (RDS) is a current cause of morbidity in premature infants resulted from surfactant deficiency. The primary aim of this randomized study was to describe the feasibility of early administration of surfactant via a thin catheter during spontaneous breathing (TEC) and compare its outcomes with the InSurE (Intubate, Surfactant, Extubate) procedure

Materials and Methods
Premature infants with RDS, who were ≤ 32 weeks old and stabilized with nasal continuous positive airway pressure (nCPAP), were randomized to receive surfactant either by the TEC or InSurE technique. Tracheal instillation of 200 mg/kg Curosorf via 5-F catheter during spontaneous breathing under nCPAP was performed in the intervention group (n=38). In the InSurE group (n=40), infants were intubated, received positive pressure ventilation for 30 seconds after surfactant instillation, and placed on nCPAP immediately

Results
Necrotizing enterocolitis rate was significantly lower in TEC group, than InSurE group, [p<0.02, RR=0.49, CI=%95(0.39_0.62)]. But rate of other morbidities did not significant difference between two groups. Although Mechanical ventilation duration did not significant different between two groups (p=0.2), but Total CPAP duration was shorter in TEC group, significantly [P<0.01, RR=8.2, CI=%95 (-37.9_-4.8)]. Need for O2 supplement and mean of total hospital duration was also lower in TEC group, but was not significant, statistically

Conclusion
The TEC technique is feasible for the treatment of respiratory distress syndrome in infants with very low birth weight and decreases total nCPAP duration, significantly. But Judgment of substitution TEC instead of InSurE as a routine technique need to more studies.

Keywords


Introduction

Prematurity remains a leading cause of neonatal morbidity and mortality worldwide, accounting for 60% to 80% of deaths of infants without congenital anomalies. As the risk of neonatal mortality and morbidity near term is low, great attention has been focused on early preterm birth (23 to 32 weeks gestation). Neonatal morbidities that result from prematurity remain a significant clinical problem. These morbidities include RDS, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, patent ductus arteriosus, jaundice, and growth failure, cerebral palsy, disorders of cognition and retinopathy of prematurity.

The risk for these morbidities is directly related to the delivery gestational age and birth weight(1).

RDS is a current cause of morbidity in premature infants resulted from surfactant deficiency. With reducing gestational age, prevalence of RDS increases. The use of CPAP has proved to be a very simple intervention to support the infant in respiratory distress. CPAP technique is simple and cost-effective, and can be used in developing countries. Premature infants who do not respond to nasal CPAP require intubation and ventilator support. Providing ventilator support requires skilled nursing and support staff and laboratory facilities. Surfactant therapy is known to shorten the time needed for assisted ventilation. The studies show that endotracheal surfactant, followed by nasal CPAP, in established cases of RDS can be used effectively. The real goal should be to consider preventive antenatal measures and newer treatment modalities that are less expensive, such as antenatal steroids in preterm labor, implementation of delivery room neonatal resuscitation, early use of CPAP, and other new procedures (1-7).

Because of some concerns about morbidities of the routine procedure of surfactant therapy; INtubation SURfactant Extubation (InSurE), new techniques have been suggested. Some studies show administration of surfactant via a thin catheter during spontaneous breathing (TEC) can reduce the need for assisted ventilation and some morbidity (8-11). This randomized clinical trial was carried out to describe the feasibility of administration of surfactant via a thin catheter during spontaneous breathing (TEC) and compare its outcomes with the InSurE technique in alzahra hospital as a level III tertiary care unit of Tabriz city.

Material and Methods

Following the permission of ethics committee of Tabriz University of medical sciences, this randomized clinical trial was done in Alzahra hospital from February 2010 up to November 2012. Preterm infants who were85% (if Pco2

Diagnosis of RDS was based on clinical examination and chest X-ray. Cases with Apgar score less than 6 at the fifth minute of birth or any congenital malformation were excluded. There were 32 infants in intervention group and 40 infants in control group. Necessary cares provided according to Neonatal resuscitation program 2006 (12)and Acute Care atRisk Newborns program (ACoRN)2010(13). The procedures were taken under supervision of Two assisstant professors of neonatology and four neonatology fellows. After data gathering by observation form, SPSS 18 was applied for data analaysis.

Results

Most of the infants born by cesarean section and received antepartum steroid. There was no significant differnce between two groups for Preterm Premature rubture of membrans, Antenatal Steroids, Sex, Gestational age and Birth weight, (table 1). One infant in TEC group (due to pneumothorax) and two infants in InSurE group expired (2 due to sepsis and 1 due to NEC).

Although administration of surfactant via a thin catheter during spontaneous breathing (TEC) causes cough in TEC group, but desaturation was more in InSurE group (p<0.001), (see table 2).

The study show NEC rate was lower in TEC group, comparison to InSurE group,that was statistically significant [p<0.02, RR=0.49, CI=%95(0.39_0.62)]. In comparison other morbidities had no significant difference between two groups, (table 3). Although there was no difference between duration of mechanical ventilation between two groups (p<0.2) mean of total CPAP duration was shorter in TEC group, in contrast to InSurE group, [P<0.01, RR=8.2, CI=%95 (-37.9_-4.8)]. Requirement for O2 supplement and total hospital duration also decreased in TEC group, in comparison to InSurE group, but was not statistically significant.

 

 

 

Tables

 Table 1- Demographic data

P.Value

InSurE

n=42

TEC

n=38

variable

0.2

31(%74)

23(%61)

Caesarean Delivery

0.2

3(%8)

6(%16)

 PProm

0.2

31(%74)

28(%74)

Antenatal Steroids

0.3

SD 2.5 ± 29.6

SD 1.5 ± 30.08

Gestation(Weeks)

0.2

SD 58.3 ± 1383.3

SD 76.6 ±1489.7

Birth weight(gram)

0.7

29(%69)

15(%40)

Male sex

 

 

 

Table 2- procedure data

P.Value

InSurE

TEC

Variable

0.48

4.52

3.83

Age at administration time(h)

0.001

1(%3)

15(%40)

Cough

0.001

23(%55)

4(%11)

Desaturation

0.2

6(%15)

9(%24)

Need for second dose of surfactant

0.6

10(%24)

11(%29)

Need for intubation

         

 

 

 

 

 

Table 3- Neonatal complications

P.Value

InSurE

TEC

Variable

0.3

2(%5)

4(%11)

IVH grade ≥ II

0.028

5(%12)

0

NEC Bell stage II or greater

0.9

11(%27)

10(%27)

Sepsis

0.1

2(%5)

1(%3)

PDA

0.6

2(%5)

1(%3)

ROP

0.4

8(%19)

5(%14)

Mechanical ventilation requirement

0.3

3(%8)

1(%3)

Mortality rate

0.8

4(%10)

4(%11)

BPD

0.9

2(%5)

2(%6)

Pneumothorax

0.2

SEM  4.6± 10.7

SEM 6.5 ± 19.8

Mechanical ventilation duration

0.01

SEM 6.3 ± 56.1

SEM 3.3 ± 35.5

Total CPAP  duration

0.2

25.7SEM±137

SEM 22.54± 92.92

O2 supplement

0.6

SEM 2.8 ± 30.19

SEM 4.42 ± 27.92

Total hospital duration

 

Discussion

The mode of delivery in the most of subjects was caesarian section (67.5%). Afje and Sabzehie`s (2007) study results were similar(6). Respecting to caesarian section as a risk factors of RDS, this indicates necessity of planning for reducing the frequency of this procedure, according to perinatal regionalization program.

Our findings show NEC was lower in TEC group, comparison to InSurE group that was statistically significant. Increasing NEC can be due to more decreasing spo2 in InSurE group. Kribs et al. and Dargaville et al did not report more NEC in InSurE group. In the present study there were no difference in prevalence of BPD, PDA, IVH, pneumothorax, sepsis and ROP between two groups(8, 14). Kribs and Dargaville showed no significant difference between two groups for pneumothorax, sepsis and ROP(8, 14). Dargaville and colleagues showed more BPD and IVH in InSurE group(14). Kribs and colleagues   have reported more PDA and IVH in InSurE group than TEC, that it could be due to increased mechanical ventilation duration in InSurE group(8).

Although mechanical ventilation duration did not differe significantly between two groups (p<0.2) in the present study, total CPAP duration decreased significantly in TEC group, in comparison to InSurE group. But Kribs and kanmaz have reported lower requirement for mechanical ventilation in TEC group and more BPD in InSurE group(8, 15). In the present study requirement for O2 supplement and Total hospital duration also decreased in TEC group, comparison to InSurE group, but was not statistically significant. Kribs and Dargaville reported similar results(8, 14).

Having enough Skill for administration of surfactant via a thin catheter during spontaneous breathing (TEC) accounts one of the limitations of this technique. Cribs and colleagues(2008) during a fourth-year study show the effect of level of   staff’s experience and skill on their results(10).  On the other hand applying a thin catheter leads to slow administration of surfactant. Therefore administration of more amounts of surfactant such as Survanta needs to more time and make it difficult in crowded NICU. 

Now stabilizing with nCPAP and administration of surfactant accepted as a standard technique for treatment of RDS. Pediatricians and neonatologists must be well trained in the use of modern technology and cultivate the sensitivity to the economic implications of NICU care for families.

Our findings show administration of surfactant via a thin catheter during spontaneous breathing (TEC) decreased total CPAP duration, significantly. But Judgment of substitution TEC instead of InSurE as a routine technique needs more studies.

Acknowledgments

The authors appreciate all of the Alzahra hospital staff’s that help them to organizing and performing this research

REFERENCES

1.  Hamvas A MR, Fanaroff AA, Walsh MC. Pathophysiology and Management of Respiratory Distress Syndrome Fanaroff and Martin's Neonatal- Perinatal Medicine. 9th ed. St. Louis: Elsevier Mosby; 2011. p. 1106-11.

2.Turunen R NI, Siitonen S, Repo H, Andersson R  Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics. 2006;117:448–54.

3.Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants [database on the Internet]2001.

4.Donn S, Sinha S. Minimising ventilator induced lung injury in preterm infants. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2006;91(3):F226-F30.

5.Dani C, Bertini G, Pezzati M, Cecchi A, Caviglioli C, Rubaltelli FF. Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants< 30 weeks’ gestation. Pediatrics. 2004;113(6):e560-e3.

6.Afjeh SA SS. The INSURE method in VLBW preterm infant with RDS      Pejouhandeh. 2010;5(15):199-203.

7.Kramer BW IM, Jobe A Intratracheal endotoxin causes systemic inflammation in ventilated preterm lambs. Am J Respir Crit Care Med 2002;165:463-9.

8.Kribs A HC, Kattner E, Vochem M, Kuster H, Moller J, Muller D, Segerer H, Wieg C,Gebauer C, Nikischin W, Wense A, Herting E, Roth B, Gopel W. Surfactant without intubation in preterm infants with respiratory distress: first multi-center data. clin Padiatr 2010;222:13-7.

9.Kribs A, Pillekamp F, Hünseler C, Vierzig A, Roth B. Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age≤ 27 weeks). Pediatric Anesthesia. 2007;17(4):364-9.

10.Kribs A, Vierzig, A., Hünseler, C., Eifinger, F., Welzing, L., Stützer, H. and Roth,B Early surfactant in spontaneously breathing with nCPAP in ELBW infants – a single centre four year experience. Acta Paediatrica 2008;97:293-8.

11.Kattwinkel J, Robinson M, Bloom BT, Delmore P, Ferguson JE. Technique for intrapartum administration of surfactant without requirement for an endotracheal tube. Journal of Perinatology. 2004;24(6):360-5.

12.Kattwinkel J. Textbook of neonatal resuscitation  5th ed: AAP; 2006.

13.Society AN. Acute Care at Risk Newobrns (ACoRN) 2010. Available from: http://www.acornprogram.net/.

14.Dargaville PA, Aiyappan A, De Paoli AG, Kuschel CA, Kamlin COF, Carlin JB, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2013;98(2):F122-F6.

15.Kanmaz G EO, Canpolat E,Mutlu B,Dilmen U. Surfactant Administration via Thin Catheter During Spontaneous Breathing: Randomized Controlled Trial. Pediatrics 2013;131:502-9.

 

1.  Hamvas A MR, Fanaroff AA, Walsh MC. Pathophysiology and Management of Respiratory Distress Syndrome Fanaroff and Martin's Neonatal- Perinatal Medicine. 9th ed. St. Louis: Elsevier Mosby; 2011. p. 1106-11.

2.Turunen R NI, Siitonen S, Repo H, Andersson R  Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics. 2006;117:448–54.

3.Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants [database on the Internet]2001.

4.Donn S, Sinha S. Minimising ventilator induced lung injury in preterm infants. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2006;91(3):F226-F30.

5.Dani C, Bertini G, Pezzati M, Cecchi A, Caviglioli C, Rubaltelli FF. Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants< 30 weeks’ gestation. Pediatrics. 2004;113(6):e560-e3.

6.Afjeh SA SS. The INSURE method in VLBW preterm infant with RDS      Pejouhandeh. 2010;5(15):199-203.

7.Kramer BW IM, Jobe A Intratracheal endotoxin causes systemic inflammation in ventilated preterm lambs. Am J Respir Crit Care Med 2002;165:463-9.

8.Kribs A HC, Kattner E, Vochem M, Kuster H, Moller J, Muller D, Segerer H, Wieg C,Gebauer C, Nikischin W, Wense A, Herting E, Roth B, Gopel W. Surfactant without intubation in preterm infants with respiratory distress: first multi-center data. clin Padiatr 2010;222:13-7.

9.Kribs A, Pillekamp F, Hünseler C, Vierzig A, Roth B. Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age≤ 27 weeks). Pediatric Anesthesia. 2007;17(4):364-9.

10.Kribs A, Vierzig, A., Hünseler, C., Eifinger, F., Welzing, L., Stützer, H. and Roth,B Early surfactant in spontaneously breathing with nCPAP in ELBW infants – a single centre four year experience. Acta Paediatrica 2008;97:293-8.

11.Kattwinkel J, Robinson M, Bloom BT, Delmore P, Ferguson JE. Technique for intrapartum administration of surfactant without requirement for an endotracheal tube. Journal of Perinatology. 2004;24(6):360-5.

12.Kattwinkel J. Textbook of neonatal resuscitation  5th ed: AAP; 2006.

13.Society AN. Acute Care at Risk Newobrns (ACoRN) 2010. Available from: http://www.acornprogram.net/.

14.Dargaville PA, Aiyappan A, De Paoli AG, Kuschel CA, Kamlin COF, Carlin JB, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2013;98(2):F122-F6.

15.Kanmaz G EO, Canpolat E,Mutlu B,Dilmen U. Surfactant Administration via Thin Catheter During Spontaneous Breathing: Randomized Controlled Trial. Pediatrics 2013;131:502-9.