This randomized controlled trial compared the Take Care technique of administering surfactant via thin catheter during spontaneous breathing to the InSurE technique of intubation and brief ventilation. The study found the Take Care technique significantly reduced the need for mechanical ventilation in the first 72 hours and had a lower rate of bronchopulmonary dysplasia compared to InSurE. However, the study had limitations including being conducted at a single center and having insufficient power to detect differences in chronic lung disease. Further research is still needed to establish the generalizability and applicability of the Take Care technique in clinical practice.

1. Journal Club
Surfactant administration via thin catheter during
spontaneous breathing : Randomized controlled
trial
GOPAKUMAR HARIHARAN
REGISTRAR , ROYAL HOBART HOSPITAL
TASMANIA , AUTRALIA

3. Presentation
 Back ground information ( RDS and BPD )
 Rationale for study
 The article and the findings
 Critical analysis of article
 Discussion

4. INTRODUCTION
 Respiratory distress syndrome (RDS) is the
most important cause of mortality and morbidity in
preterm infants – surfactant deficiency
 Conventional management
Intubation,mechanical ventilation, and surfactant
administration
 Long term morbidity ( mech vent and oxygen toxicity
)– BPD –oxygen Requirement at 36 weeks corrected
age

5. Mechanical ventilation and BPD
 Few large mechanical breaths may cause lung injury and
blunt the effect of subsequent surfactant treatment and
increase risk of BPD
 Efforts to reduce BPD - by restricting mechanical
ventilation
 Surfactant – Successful in treatment of RDS . Does not
reduce the incidence of BPD bronchopulmonary
dysplasia (BPD)

6. Ways of reducing mechanical ventilation related
to surfactant administration
 Adverse effects of MV and Oxygen therapy - Trend towards
noninvasive methods – early use nasal continuous positive
airway pressure (nCPAP)
 Early nCPAP with early surfactant significantly reduces BPD,
MV need, and air leaks compared with nCPAP with late
surfactant ( Metanalysis of 6 studies )
 Two components of current research – Early surfactant
and avoidance of intubation and MV
 InSurE Technique
 Minimal invasive surfactant therapy
 Nasopharyngeal instillation
 Aerosolised method

7. AIM
To assess the efficacy and the feasibility of the Take
Care technique and
To compare its short- and long-term effects with the
InSurE procedure, especially on the requirement of
intubation and MV in the first 72 hours of life, which
are known to be the major contributing factors for
BPD

8. Inclusion criteria
 Preterm infants, who were less than 32 weeks -
stabilized with nasal continuous positive airway
pressure (nCPAP) in the delivery room
 Patients with signs of RDS and requiring FiO2 more
than 0.4 in first 2 hours of life to maintain SpO2
levels between 85% to 92%, were randomized to
receive surfactant treatment either by the Take Care
or InSurE procedure.
 Sequentially numbered sealed opaque envelopes
stratified by GA (less than 28 weeks and 29 to 32
weeks) - used for randomization.

9. RDS diagnosis
• Need for supplemental oxygen
• Tachypnea
• Grunting, and intercostal
retractions
• Confirmed by typical x-ray and
blood gas findings

10. Exclusion criteria
 Infants with major congenital anomalies
 No parental consent
 Who required PPV or intubation in the delivery room
 Babies not resuscitated by trial investigators

11. Sample size calculation
.
Previous experiences with the InSurE technique - 50%
of patients required intubation and MV in first 72
hours of life
To reduce the need for MV treatment with this new Take Care
technique from 50% to 30%, sample size estimated was 100 for
each group to yield .80% power.20

12. Trial profile
Randomization

13. Methodology – Surfactant administration
Take care group - Tracheal instillation of 100 mg/kg
poractant via 5-F catheter during spontaneous
breathing under nCPAP
InSurE - intubated, received positive pressure
ventilation for 30 seconds after surfactant instillation,
and placed on nCPAP immediately.

14. Take Care technique procedure
 Used 5F, flexible, sterile nasogastric tube shortened at
33-cm depth from the catheter hub.
 Desired depths of insertion beyond the vocal cords for
preterm infants of 25 to 26, 27 to 28, and 29 to 32 weeks
GA were 1.0, 1.5, and 2.0 cm, respectively
 After catheter placement, the laryngoscope was removed.
 CPAP support not disrupted throughout the procedure
Shorter duration (30 to 60 seconds) of a single type of surfactant (poractant a)
Administered by only experienced physicians in the NICU
Shorter catheter length, and
no need for forceps during application
No premedication or sedation

15. Procedure
 Control arterial blood gas samples were taken∼2
hours after the procedure.
 CPAP pressure was titrated according to work of
breathing and oxygen requirement, with SpO2 target
of 85% to 92%.
 If the patient did not respond to treatment or
deteriorated after 6 hours of first application
(FiO2.0.4, partial pressure of carbon dioxide .60 mm
Hg), a second dose of surfactant of 100 mg/kg was
repeated and the same procedure was used as during
the first surfactant instillation.

16. Reintubation
 Maximum acceptable settings were sustained CPAP pressure
of beyond 7-cm H2O along with an FiO2 of 0.6. Infants
exceeding these limits were intubated, and a further dose of
surfactant was given if clinically indicated.
 Need for MV during the first 72 hours of life in infants who
had initially been managed with nCPAP was classified as
failure of nCPAP.
 Other indications for intubation were sustained respiratory
acidosis (pH,7.2) and apnea requiring repeated episodes of
PPV.

17. Study population
357 infants
Assessed for
eligibility
254 infants had RDS
Participant
Population
200 Randomized

18. Randomization
Intervention Comparison
Take Care InsurE
100 100
100

19. Base line charecteristics
No significant difference between the groups

20. Primary Outcomes
Effects of the Take Care technique on the need for
intubation and MVin the first 72 hours (and
thereafter) of life in addition to feasibility of the
technique.

21. Secondary outcomes
 Repeated surfactant therapy
 Duration of respiratory support
 Rates of pneumothorax
 Patent ductus arteriosus requiring medical or surgical
treatment
 Intraventricular hemorrhage (grade .2 according tothe
Papille classification)
 Retinopathy of prematurity greater than stage 2
 Necrotizing enterocolitis with Bells stage 2 or greater
 Length of hospitalization
 BPD or death.

22. Observations
• Reintubation and MV
• Pneumothorax , Duration of resp
Immediate support, PDA , IVH ,NEC
• Chronic lung disease
• ROP , Length of hospitalisation ,
Late Death

23. FiO2 trend
No significant difference

24. Alteration of PEEP over time

26. Results – Primary
The MV requirement ( nCPAP failure in first 72 hours
of life )
Significantly lower in the Take Care group when
compared with the InSurE group
30% vs 45%,
P = .02,
RR –0.52, 95%
CI – 0.94 to –0.29) (Table 3).

27. Mean duration of both nCPAP and MV were
significantly shorter in the Take Care group (P values
.006 and .002, respectively).

28. Results
Peridosing adverse events
Coughing and gagging (11%) and bradycardia and desaturation (17%) were recorded as peridosing
adverse events in the Take Care group.
Failure of first attempt
18% of patients in the Take Care group and 10% in the InSurE group ( not statistically significant
(P = .07) )
Bradycardia and desaturation
not statistically different between groups (18% vs 17%, P = .35).
Surfactant reflux during the attempt
Significantly higher in the Take Care group in contrast to the In- SurE group (21% vs 10%, P =
.002).
Severe apnea and bradycardia
Twelve percent (n = 12) of patients had severe apnea lasting.20 seconds and bradycardia
(,100/min) required PPV with a T-piece device during the procedure in the Take Care
group, whereas all patients in the InSurE group received PPV.

30. Secondary outcomes – Other Neonatal
Morbidies
Patent ductus arteriosus (28% vs 32%),
Necrotizing enterocolitis (5% vs 6%),
Intraventricular hemorrhage (10% vs 16%), and
Retinopathy of prematurity (3% vs 4%)
Similar between groups

31. Conclusion
This single-center prospective
randomized controlled trial
demonstrated that bolus surfactant
administration during spontaneous
breathing via a thin nasogastric
tube, dubbed the Take Care
technique, was feasible and it
successfully reduced the MV
requirement in first 72 hours of life,
shortened MV duration, and
resulted in a lower BPD rate when
compared with the InSurE
technique.

33. Study
 Appropriate comparison group
 Baseline charecteristics match
 Randomization technique appropriate – Sealed
opaque envelope
 Subgroup analysis made

34. Research Question
Does take Care Procedure in babies less than 32 weeks
of gestation reduce need for mechanical ventilation
and thereby incidence of bronchopulmonary dysplasia
compared to babies managed by InSurE technique
Hypothesis

35. Limitation - All
infants who
Trial profile might have been
Randomization eligible for the
study - not
enrolled because
of concern for
standardization
Of the babies considered as candidates , a majority of babies
Fit into the criteria , which is unlike in clinical practice . ?
Population difference

36. Inclusion Criteria
Patients with signs of RDS, who were under nCPAP
treatment and required fraction of inspired oxygen
(FiO2) 0.4 in first 2 hours of life to maintain SpO2
levels between 85% to 92%, were randomized to
receive surfactant treatment either by the Take Care or
InSurE procedure.
Rapid rise of FiO2 to 0.40 at 2 hours ? – Not generally seen in RDS ?
Different popluation with associated morbidity or racial difference

37. successful reduction in
BPD rate (10.3%) in
comparison with the
InSurE (20.2%) method.
No significant difference – But difference in CLD ? Other factors
? Slow reduction in FiO2 - Usually associated with rapid reduction in FiO2 after
surfactant

38. Respiratory indices before and after minimally invasive surfactant therapy (MIST) – all
infants.
Dargaville P A et al. Arch Dis Child Fetal Neonatal Ed
2011;96:F243-F248
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

40. Chronic Lung disease
CLD No CLD
Take Care 9 91 100
Insure 17 83 100
26 174 200
Mortality 16 % and 13% respectively
Total number – 100 . After excluding babies died - 84 in Take care &
Insure – 87
Percen of BPD = 9/100 = 0.09 ; 9/84 = 10.7
% of BPD ( InSurE = 17/100 = 0.17 ; 17/87 = 19.5
Relative risk – 0.09 / 0.17 = 0.52
Insufficient power to detect CLD

42. Technique
Hobart
Technique
Dargaville PA, Aiyappan A, Cornelius A,Williams C, De Paoli AG. Preliminary
evaluationof a new technique of minimally invasive
surfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011;96(4):F243–F248
?Generalisation of the technique

43. Alternative ways of surfactant administration
without PPV – MIST
Administration of surfactant via a thin catheter during
spontaneous breathing with CPAP - used since 2001.
Catheter placed with Magill forceps into the trachea
under direct laryngoscopy and surfactant is applied
over a period of 1 to 3 minutes.

44. Peridosing events
Dargaville et al ( Hobart Technique ) - use of a more
stable vascular catheter for the procedure, which
allowed placement without use of the Magill forceps.
Fewer peridosing events with take care ,such as failure
of the first attempt of catheterization, bradycardia,
surfactantreflux, and PPV requirement, by usingthis
technique in comparison with Dargaville et al’s report.
? Study conducted by single experienced Neonatologist – Difficulty in
Generalisation of the result

45. Reintubation - fio2 60% ( not generally practised )
Single centre study

46. Limitations ( Authors )
Limitations – Authors
• Only one agent used - poractant
alpha
• Single centre study
• Insufficient power to detect BPD

47. Applicability in practice
 The population studied appears to be very different –
appears to be more sick , Rapid rise in FiO2 req
, Low PH and clinical status
 Technique - ? Feasible by experienced physicians
 Single centre study
 Needs more research for wider applicability