GOPAKUMAR HARIHARANREGISTRAR , ROYAL HOBART HOSPITAL

TASMANIA , AUTRALIA

Journal Club Surfactant administration via thin catheter

during spontaneous breathing : Randomized controlled trial

Presentation

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

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

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)

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

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

AIM

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.

RDS diagnosis

• Need for supplemental oxygen• Tachypnea• Grunting, and intercostal

retractions• Confirmed by typical x-ray and

blood gas findings

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

Sample size calculation

.

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

Previous experiences with the InSurE technique - 50% of patients required intubation

and MV in first 72 hours of life

Trial profile Randomization

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.

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 NICUShorter catheter length, and no need for forceps during applicationNo premedication or sedation

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.

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.

Study population

Participant Population

357 infantsAssessed for eligibility

254 infants had RDS

200 Randomized

Randomization

Intervention

Take Care

Comparison

InsurE

100100 100

Base line charecteristics

No significant difference between the groups

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.

Secondary outcomes

Repeated surfactant therapyDuration of respiratory supportRates of pneumothorax Patent ductus arteriosus requiring medical or surgical

treatmentIntraventricular hemorrhage (grade .2 according tothe

Papille classification)Retinopathy of prematurity greater than stage 2 Necrotizing enterocolitis with Bells stage 2 or greaterLength of hospitalizationBPD or death.

Observations

Immediate •Reintubation and MV •Pneumothorax , Duration of resp support, PDA , IVH ,NEC

Late •Chronic lung disease •ROP , Length of hospitalisation , Death

FiO2 trend

No significant difference

Alteration of PEEP over time

Results – Primary

The MV requirement ( nCPAP failure in first 72 hours of life )

30% vs 45%, P = .02, RR –0.52, 95% CI – 0.94 to –0.29) (Table 3).

Significantly lower in the Take Care group when compared with the InSurE group

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

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 attempt18% 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.

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

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.

Critical Analysis

Study

Appropriate comparison group Baseline charecteristics match Randomization technique appropriate –

Sealed opaque envelope Subgroup analysis made

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

Trial profile

Of the babies considered as candidates , a majority of babies Fit into the criteria , which is unlike in clinical practice . ? Population difference

Randomization

Limitation - All infants who might have been eligible for the study - not enrolled because of concern for standardization

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

No significant difference – But difference in CLD ? Other factors? Slow reduction in FiO2 - Usually associated with rapid reduction in FiO2

after surfactant

successful reduction in BPD rate (10.3%) in comparison with the InSurE (20.2%) method.

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.

Chronic Lung disease

CLD No CLD

Take Care 9 91 100

Insure 17 83 100

26 174 200

Insufficient power to detect CLD

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

Technique

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

?Generalisation of the technique

HobartTechnique

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.

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

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

Limitations ( Authors )

Limitations – Authors • Only one agent used -

poractant alpha • Single centre study • Insufficient power to detect

BPD

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

Thank you