Management of Neonatal Respiratory Distress Syndrome

European Consensus Guidelines 2010 Update

Ola Didrik Saugstad, MD Department of Pediatric Research Oslo University Hospital, University of Oslo, Norway

Kiev, Nov 30th 2011

European Guidelines on RDS: 2010

European panel of experts convened under auspices of EAPM to develop evidence-based guidelines on management of RDS. Supported by an unrestricted educational grant from Chiesi Farmaceutici but none of the panel members received honoraria for their contributions.
HLH and CPS are consultants to Chiesi ODS and VPC members of the Chiesi Advisory Board

European Consensus Guideline Panel

Virgilio Carnielli Gorm Griesen Henry Halliday Mikko Hallman Eren Ozek Richard Plavka Ola Saugstad Umberto Simeoni Christian Speer David Sweet

Ancona, Italy Copenhagen, Denmark Belfast, UK Oulu, Finland Istanbul, Turkey Prague, Czech Republic Oslo, Norway Marseille, France Wurzburg, Germany Belfast, UK (Secretary)

Updated Guidelines: 2010 What is New?

Guidelines contain new evidence from recent Cochrane reviews and the literature since 2007. Many of the previous recommendations on surfactant and CPAP are now more firmly evidence-based. The section on delivery room stabilisation has been considerably expanded. New recommendations on delaying cord clamping and a new section on avoiding or reducing duration of mechanical ventilation, including recommendations on caffeine therapy, nasal ventilation, permissive hypercarbia and the role of newer ventilator modalities. A new miscellaneous section has also been added covering aspects of RDS management that arise infrequently

Aims

Discuss controversies in RDS management Examine the evidence for best practice Develop consensus guidelines from evidence available up to end of 2009 Publish the consensus recommendations on management of RDS in 2010, updating those of 2007

RDS - Definition

Pulmonary insufficiency starting at birth Mainly confirmed to preterm babies Caused by lack of alveolar surfactant Presents with respiratory distress Development of respiratory failure Natural course is death or recovery after 3-4 days Classical X-Ray appearances

Ground glass appearance Air bronchograms

Chest radiograph before and after surfactant

RDS - Treatment

Oxygen CPAP Mechanical ventilation Surfactant replacement Supportive Care

RDS Aims of Management

Maximise numbers of survivors Minimise potential adverse effects of disease or therapy Many interventions have been studied in randomised controlled clinical trials and systematic reviews

Grades of Evidence and Levels of Recommendation

A = Meta-analysis or high quality RCT B = Smaller RCT or systematic review of case/ control studies C = Good quality case-control or cohort study D = Case series or expert opinion Modified from SIGN guidelines handbook www.sign.ac.uk/guidelines/fulltext/50

European Guidelines on RDS: 2010

Prenatal Care Delivery Room Stabilisation Surfactant Therapy Oxygen Supplementation Beyond Stabilisation Role of CPAP Mechanical Ventilation (MV) Strategies Avoiding or Reducing Duration of MV Prophylactic Treatment for Sepsis Supportive Care: thermal, fluid and nutrition, tissue perfusion, ductus arteriosus Miscellaneous Considerations

Management of RDS can be influenced before birth

Consider place of delivery Role of infection in initiation of preterm labour

Role of antibiotics? Which steroid? How many courses? Who should get them? Allow steroids to take effect or time to transfer

Role of antenatal steroids

Role of tocolytic agents

Prenatal Care Recommendations: 2010

Mothers at high risk should be transferred to a perinatal centre (C) Single course of prenatal steroids should be given if threatened preterm labour from 23 to 35 wk gestation (A) Antibiotics should be given to mothers with PPROM (A) Consider short-term tocolytics to allow transfer in utero or time to complete course of steroids (A) Consider a second course of steroids if risk of RDS outweighs uncertainty about long-term adverse effects (D). Multiple pregnancy might be an example (C).

Delivery Room Stabilisation

Babies with RDS have difficulty maintaining FRC and alveolar aeration. Traditionally, many are resuscitated with bag & mask using 100% oxygen and there is emerging evidence that 100% oxygen may be harmful Many are intubated for prophylactic surfactant Uncontrolled tidal volumes are also detrimental to the immature lung and early CPAP is being advocated Delayed clamping of the cord may confer benefits Hypothermia should be avoided

Delivery Room Stabilisation Recommendations - 1

If possible, delay cord clamping for at least 30-45 sec (A). Oxygen should be controlled with a blender and the lowest possible concentration should be used (~30%), provided there is an adequate heart rate response (B). 30% oxygen to start and titrate using pulse oximetry but note normal sats may be 40-60%, reaching 50-80% by 5 min but should be >85% by 10 min. Avoid hyperoxia (B). If spontaneous breathing, stabilise with CPAP of 5-6 cm water via mask or prongs (B). If breathing is insufficient consider a sustained inflation rather than IPPV (B). Ventilation with a T-piece device is preferable to a selfinflating or flow-inflating bag to generate PEEP (C).

Delivery Room Stabilisation Recommendations - 2

If PPV is needed avoid excessive tidal volumes and maintain PEEP (D). Reserve intubation for babies not responding to PPV or those requiring surfactant (D). Verify correct position of the endotracheal tube using colorimetric CO2 detection (D). Plastic bags or occlusive wrapping under radiant warmers should be used for babies < 28 weeks gestation (A).

Surfactant Therapy

Surfactants have revolutionised respiratory care over past 2 decades, and when given prophylactically or as rescue therapy reduce death and pulmonary airleaks in RDS Many RCTs have been performed to determine the best surfactant, and the optimal timing of dosing and redosing However, most trials were in the era of low prenatal steroid and CPAP use

Surfactant Therapy dosing and redosing

At least 100 mg/kg phospholipid is required and 200 mg/kg may be better for established RDS Administration by bolus results in better distribution Prophylaxis reduces mortality and air leaks, but more babies end up being treated Surfactant can be given whilst avoiding mechanical ventilation using INSURE technique A second (and occasionally a third) dose is sometimes required

Surfactant Therapy - Recommendations

Babies with or at high risk of RDS should be given a natural surfactant preparation (A). Prophylaxis for most babies < 26 weeks gestation. Prophylaxis also if intubation required (A). Early rescue for untreated babies if evidence of RDS such as increasing oxygen requirement (A). Poractant alfa 200 mg/kg is better than 100 mg/kg (of poractant or beractant) for moderate to severe RDS (B). Consider early extubation to CPAP if stable (B). A 2nd/ 3rd dose should be given if ongoing evidence of RDS such as persistent oxygen or MV need (A).

Comparison of Animal Derived Surfactants

Surfacta nt
Preparation/ Composition Phospholi pids Plasma logens *mol % SP- B mg/ml SP- C mg/ml

Survanta Minced Bovine Lung Extract/ (S)

Total <1mg/ml

DPPC, Palmitic Acid, Tripalmitin

84 %

1.5
NA

0 - 1.3
(g/mol
PL)

1 20 (g/mol PL)

Infasurf (I)

Bovine Lung Lavage/DPPC, Cholesterol

95 %

0.9
(Alveofact)

0.26

0.44

Curosurf Minced Porcine

(C)

Lung Extract/DPPC, Polar lipids

(Liquid Gel Chromatography)

99 %

3.8

0.45

0.55

* High Plasmalogen content is associated with lower BPD rate. Rudiger et al.

Tracheal Aspirates with High Levels of Plasmalogens Associated with Lower BPD Rates
P<0.001
X X

5
X

% DMAs on all Fatty Acids

4
X

Aspirates were collected prospectively from preterm infants 32 wks GA intubated within 1hr of birth

3 2 1

X X X X

BPD

non BPD

Rdiger M, et al. Critical Care Med. 2000;28:1572-1577

Comparison of Animal Derived Surfactants Curosurf vs. Survanta (5 studies)

Trials (6-10) Surfactant N Type Patient s Results Curosurf: Lower FiO2, PIP & MAP @ 12-24 h

Speer 1995 Baroutis 2003

Curosurf vs. Survanta Curosurf vs. Survanta vs. Alveofact

73

Tx

7001500 g

80

Tx

< 2000 Curosurf: Fewer days on O2 & PPV; Decreased LOS g

Ramanathan 2004

Curosurf vs. Survanta

293

Tx

7501750 g

Curosurf: Lower FiO2, Fewer doses, Decreased Mortality < 32 wks

Curosurf: Lower FiO2 up to 48 h, Fewer doses, lower volume Curosurf: Faster weaning, Less Air-Leaks, PDA & MV

Malloy 2005 Fujii, 2010

Curosurf vs. Survanta Curosurf vs. Survanta

58

Tx

< 37 wks < 30 wks

52

Tx

Curosurf vs. Survanta Rescue Trial (6)

Curosurf (n= 33)
PIE PTX 3% 6.1 %

Survanta (n = 40)
10 % 12.5 %

IVH Total
IVH Gr. III-IV

21.2 %
3%

35 %
12.5 % 11.4 %

O2 @ 36 wks 12.5 % PCA Mortality 3% No Difference in Death or BPD

12.5 %

Speer C et al. Arch Dis Child 1995; 72: F8-F13

Curosurf vs. Survanta Rescue Trial (6) Changes in FiO2 , PIP & MAP
FiO2

PIP & MAP

Faster Weaning
Speer C et al. Arch Dis Child 1995; 72: F8-F13

FiO2 vs. Time curves after the first dose of Surfactant (n=293) Trial #8 0.7
0.65 0.6 0.55

Faster Weaning

Survanta Curosurf 100 Curosurf 200

FiO2

0.5 0.45 0.4 0.35 0.3 0.25 0.2

* *

Data : Mean SEM *,* = p < 0.05

15

30 2h 6h Ramanathan R et al. AJP 21:109-119; 2004

% of Infants Requiring Additional Doses of Surfactant #8 60

49 41
40
% Infants

Fewer Doses

Curosurf 100 Curosurf 200 Survanta 100

27 20
20

15 8 0 1
4 Doses

0
2 Doses 3 Doses

* p < 0.05

36 % (C200) vs. 68 % (S100) received 2 or more doses

Curosurf vs. Survanta (n=50): (Rescue Trial # 10) Less Air Leaks & PDA with Curosurf
80 70 60 50 76

Beractant
P= 0.002
50 35 28 16 39 29

Poractant Alfa

40
P= 30 0.047 20 15

32

15 16 4 4

19 8

10 0 0
Air Leaks PDA PDALigation BPD

ROP II-IV IVH II-IV

NEC

Mortality

Fujii AM et al. J Perinatol, 1-6; March 2010

Meta-analysis Curosurf vs Survanta Trials (6&8)*

OR
PTX

( 95 % C.I. ) 0.19, 1.53

0.54

O2 @ 36 wks
PDA Pulmonary Hge IVH Gr. I-II IVH GR.III-IV Neonatal Mortality

1.03
1.29 1.01 1.39 0.65 0.35

0.61, 1.74
0.79, 2.08 0.32, 3.21 0.65, 2.96 0.28, 1.53 0.13, 0.92

(* Speer et al. & *Ramanathan et al.) Halliday HL. Biol Neonate 2005;

Mortality of 3 different surfactants

Ramanthan et al Journal of Perinatology (2011), 17

Mortality of 3 different surfactants

Ramanthan et al Journal of Perinatology (2011), 17

Cost per patient: Curosurf vs. Survanta

2 000,00 1 800,00

Cost / Patient ($)

1 600,00 1 400,00 1 200,00 1 000,00 800,00 600,00 400,00 200,00 0,00

53% ($ 950) 46% ($ 618) 20% ($ 220) 20% ($ 200)

Survanta Curosurf

Model 1 Model 2 Model 3 Model 4

Cost Effective

Model 1: Speer et al (mean wt, single-use vial) Model 2: Ramanathan et al. (mean wt, single-use vial) Model 3: Ramanathan et al. (Actual wt, single-use vial) p=<0.01 Model 4: Ramanathan et al. (Actual wt, Survanta

as multi-use vial)

p=0.018

Marsh W, Smeeding J, York JM, Ramanathan R, Sekar K. JPPT 9:113-121; 2004

Surfactant for RDS: Evidence Based Approach

1. Animal Derived Surfactants: Faster weaning of O2, and MAP, Fewer air leaks, and Decreased Mortality when compared to synthetic Surfactants. 2. Among Animal Derived Surfactants, Porcine surfactant, Curosurf provides Faster Weaning, Rapid Extubation, Less PDA, Survival Advantage & Cost-effectiveness when compared to Bovine surfactants, Survanta or Infasurf 3. Best Timing: < 60 minutes of Age

Why Poractant Alfa (Curosurf)?

1. Highest amount of Phospholipids
2. Phosphotidylcholine molecular species closely resembles human surfactant

Lowering Surface Tension & Better antiinflammatory effects Better interaction with SP-B

3. Highest amount of SP-B

4. Highest amount of

Plasmalogens
5. Highest amount of PUFA in a smaller volume and

Rapid adsorption of Phospholipids Highest anti-oxidant activity Rapid distribution and less reflux

Guidelines for Surfactant Treatment of RDS

< 28 wk
NIPPV in DR, Early Rescue (<30) in DR or NICU with 200 mg/kg of Poractant Alfa Extubate to NIPPV as soon as possible (> 24 wk). Start Caffeine

29-31 wk
Early CPAP/NIPPV Surfactant if intubated for resuscitation Early Rescue with 100-200 mg/kg if FiO2 > 0.30 + white CXR. Start Caffeine

> 32 wk
Observe CPAP/NIPPV if respiratory distress Delayed Rescue with 100 mg/kg if FiO2 > 0.40 + white CXR Caffeine if symptomatic

Redosing: FiO2 > 0.30 How soon: 2-12 hrs

Redosing: FiO2 > 0.35 How soon: 12 hrs

Redosing: FiO2 > 0.40 How soon: 12 hrs

Oxygen supplementation beyond stabilisation

Currently no firm evidence to guide optimal oxygen saturations in NICU Suggestions to target between 85% and 93% and not exceed 95% to reduce ROP and BPD Long-term neuro-developmental outcomes are unknown Hyperoxia can occur following surfactant therapy Fluctuations in oxygen saturations may also increase the risk of ROP Optimal saturation targets currently being studied in BOOST-II, COT and SUPPORT

Oxygen supplementation beyond stabilisation

In oxygen, saturations should be maintained at all times between 85 and 93% (D). After surfactant, avoid a hyperoxic peak, which is associated with IVH, by rapid reduction in oxygen (C). Avoid fluctuations in oxygen saturations in the postnatal period (D).

What is new and why this topic?

Stabilisation/Resuscitation:

How to titrate FiO2 if oxygen is needed?

Optimal FiO2 for preterm infants is not known Oxygen saturation beyond the DR in ELBWI: New data on mortality has created uncertainty of safety

A too low SpO2 reduces ROP and BPD but increases mortality
Consequences for clinical practice
Previous reccommendations of SpO2 targets should perhap be changed

Should we resuscitate extremely low birth weight infants with a low FiO2?

High (90% Vs low (30%) FiO2 Resuscitating ELBWIs

Raquel E et al Pediatrics May 2008

Heart rate in ELBWI (< 28 w) resuscitated with high or low O2 aiming at SaO2 of 85%
200

low FiO2 High FiO2

beats per min

150

100

50 0 3 6 9 12 15

min after birth

Raque l E e t al Pe diatrics M ay 2008

SpO2 in extremely low gestational age neonates

120 100

SpO2 (%)

80
60 40 20 0 0 5 10 15 20 Time after birth (min) 25 30 35

Hox group (n=41) Lox group (n=37)

Vento et al, Pediatrics 2009

Isofurans

50

**

ng/mg creatinine

40

**

30

20

10

0 da y 1 da y 7

How could SpO2 centiles be used to inform decision making in the DR?

100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 Suggested level for administration of oxygen

Minutes after birth

10th 25th 50th 75th 90th

Dawson, Vento, Finer, Rich, Saugstad, Morley, Davis J Pediatrics 2011

TRANSITIONAL OXYGEN TRACKING SYSTEM Allowing to individualize FiO2 avoiding hyper/hypoxia

50% 10%

Rich W et al non published data 2010

High or Low Saturation for ELBWIs?

Effect on BPD and ROP At least 9 studies have been published investigating the effect on BPD and ROP of low or high oxygen saturation in VLBWI or ELBWIS. Of these 3 only are randomized

Studies regarding high or low SpO2 targets in VLBWI or ELBWIs Characterisation of Studies

Study
STOP ROP 2000 Tin 2001 Sun 2002 BOOST 1 2003 Chow 2003

GA w/BW g
Mean 25.4 w <28 weeks 500-1000gr <30 weeks 500-1500 gr

Study design High SaO2

Randomized Observational Survey Randomized Observational 96-99 88-98 >95 95-98 90-98

Low SaO2
89-94 70-90 95 91-94 85-93

VanderVeen 2006

28 weeks 1250 gr 1250 gr

Historical control Historical control Historical control Randomized

87-97

85-93

Deulofeut 2006

92-100

85-93

Noori 2009

< 1000 gr

89-94

83-89

SUPPORT 2010

24-28 weeks

91-95

85-89

Saugstad and Aune, Neonatology 2010;100:1-8.

BPD and SpO2

Study Randomized trials STOP ROP, 2000 Askie, 2003 Support, 2010 Subtotal Observational studies Tin, 2001 Sun, 2002 Deulofeut, 2006 Noori, 2009 Subtotal Overall 0.40 ( 0.22, 0.69) 0.66 ( 0.57, 0.76) 0.69 ( 0.55, 0.85) 1.04 ( 0.79, 1.36) 0.70 ( 0.54, 0.91) 0.74 ( 0.63, 0.87) 0.64 ( 0.40, 1.03) 0.71 ( 0.59, 0.86) 0.91 ( 0.79, 1.05) 0.79 ( 0.64, 0.97) Relative Risk (95% CI)

.2

.5

1 Relative Risk

Saugstad and Aune, Neonatology 2010;100:1-8.

ROP and SpO2

Study Randomized trials Support, 2010 Subtotal Observational studies Tin, 2001 Sun, 2002 Chow, 2003 Deulefeut, 2006 VanderVeen, 2006 Noori, 2009 Subtotal Overall 0.40 ( 0.22, 0.69) 0.66 ( 0.57, 0.76) 0.22 ( 0.05, 0.85) 0.64 ( 0.27, 1.46) 0.32 ( 0.12, 0.80) 0.28 ( 0.18, 0.42) 0.42 ( 0.27, 0.65) 0.44 ( 0.31, 0.61) 0.48 ( 0.34, 0.68) 0.48 ( 0.34, 0.68) Relative Risk (95% CI)

.03

.1

.25

.5

1 Relative Risk

Saugstad and Aune, Neonatology 2010;100:1-8.

Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial
Wolfgang Gpel, MD, Angela Kribs, MD, Andreas Ziegler, PhD, Reinhard Laux, MD, Thomas Hoehn, MD, Christian Wieg, MD, Jens Siegel, MD, Stefan Avenarius, MD, Axel von der Wense, MD, Matthias Vochem, MD, Peter Groneck, MD, Ursula Weller, MD, Jens Mller, MD, Christoph Hrtel, MD, Sebastian Haller, MD, Bernhard Roth, MD, Egbert Herting, PhD and on behalf of the German Neonatal Network

The Lancet September 30, 2011

Terms and Conditions

Randomized studies high or low SpO2 for ELBWI

SUPPORT BOOST 2 (UK, Australia, New Zealand) COT
High 91-95 % Low 85- 89%

Mortality at 36 weeks PMA in High or Low SpO2 - Support + BOOST 2

Stenson B et al, NEJM, April 28, 2011 p 1681

Summary
Postnatal oxygenation of ELBWIs

Increases severe ROP and BPD Fluctuations should be avoided especially first 5 days Should not exceed 95%
Low SpO2 increases mortality Is a SpO2 at 85% too low ?
How to find the right balance of SpO2 between: 1) lowest mortality rate 2) lowest incidence of morbidity (BPD, ROP)? Randomized controlled trials are needed and one more large study is underway However, new studies would probably be needed

High SpO2

SpO2 85-89% Vs 91-95 %

BPD 25% ROP 50%

Mortality

20%

What is the right balance between mortality and morbidity?

SpO2

89-93% ?? 91-95 % ??

Oxygen saturation in ELBWIs revisited Updated recommendations

This means that SpO2 of ELBWIs should not be targeted at 85-89 % until further data become available. This recommendation may be controversial knowing that even if mortality is slightly reduced it may lead to considerably higher rates of severe ROP and BPD.

The SpO2 targets describing the optimal balance between mortality on one hand and complications such as ROP and BPD on the other is therefore presently not known.
In fact, it may take several years until more precise information is available to guide clinical practice.
Saugstad, Halliday, Speer, Neonatology, October 2011 (editorial)

Conclusions
It is best to initiate resusctiation of term babies with air

The optimal FiO2 for resuscitation of ELGANs is not known. But do not use 100% oxygen, start low with 21 or 30% Low SaO2 (85%) beyond the DR probably reduces BPD and ROP But may increase mortality
Do not target SaO2 between 85-89%

CPAP - Recommendations

CPAP should be started from birth in all babies at risk of RDS, such as those <30 wk not needing MV, until clinical status can be assessed (D). Short binasal prongs should be used rather than a single prong and a pressure of at least 6 cm water should be used (A). CPAP with early rescue surfactant should be considered in babies with RDS to reduce MV (A).

Mechanical Ventilation Recommendations

MV should be used to support babies with respiratory failure as this improves survival (A). Avoid hypocarbia, as this is associated with increased risks of BPD and PVL (B). Settings of MV should be adjusted frequently with the aim of maintaining optimum lung volume (C). Duration of MV should be minimised to reduce injurious effect on the lung (B).

Avoiding or Reducing Duration of MV

Clear links between MV and development of BPD and neurological sequelae Interventions to avoid or shorten MV include: caffeine, CPAP or NIPPV with or without surfactant, INSURE technique, permissive hypercarbia and aggressive weaning with early extubation

Avoiding or Reducing Duration of MV: Recommendations: 2010

Caffeine should be used to treat apnoea and to facilitate weaning from MV (A). It should also be considered for those at high risk of MV (e.g. <1250 g on CPAP or NIPPV) (B). CPAP or NIPPV should be used if possible to avoid MV through an endotracheal tube (B). Weaning from MV - reasonable to tolerate moderate hypercarbia provided pH > 7.22 (D). Synchronised and targeted tidal volume modes with aggressive weaning should be used (B).

Prophylactic Treatment for Sepsis: Recommendations: 2010

Antibiotics should be started in all babies with RDS until sepsis is ruled out. Penicillin or ampicillin with an aminoglycoside is commonest but units need to develop local protocols (D). Protocols should also be developed for antifungal prophylaxis in very preterm babies based on local incidence and risk factors (D).

Supportive Care

Temperature Control Fluid and Nutritional Management Maintenance of Tissue Perfusion Management of Persistent Ductus Arteriosus Support of the Family

Temperature Control

All efforts should be made to reduce heat loss Use of polythene bags < 28 weeks reduces heat loss and may improve survival Incubators reduce insensible water losses compared to radiant warmers Servo-controlled temperature decreases mortality

Recommendation: 2010 Maintain axillary temp 36.5 37.5 oC at all times (C)

Very preterm

baby being
placed in a

plastic bag

Fluid and Nutrition Management: Recommendations: 2010

Most babies should be started on 70-80 mL/kg/day and nursed in high humidity (D). Fluid and electrolyte therapy should be tailored individually allowing a 2.5-4% daily weight loss (15% total) over first 5 days (D). Sodium intake should be restricted over first few days and initiated after onset of diuresis with careful monitoring of fluid and electrolyte levels (B). Full parenteral nutrition can be started on day 1 (A). May include protein 3.5 g/kg/day and lipid 3 g/kg/day in 10% dextrose. Minimal enteral feeding should be started from the first day (B). Early aggressive feeding is popular but level A evidence is lacking.

Maintenance of Tissue Perfusion: Recommendations: 2010

Treatment of hypotension is recommended when confirmed by evidence of poor tissue perfusion (C). Volume expansion with 10-20 mL/kg normal saline as first line if myocardial dysfunction excluded (D). Dopamine (2-10 ug/kg/min) if volume expansion fails (B). Dobutamine (10-20 ug/kg/min) as first line and epinephrine (0.01-0.5 ug/kg/min) if low systemic blood flow and myocardial dysfunction need to be treated (D). Hydrocortisone (1 mg/kg 8 hourly) in cases of refractory hypotension when conventional therapy has failed (B). Echo may help decisions when to start treatment for hypotension and what drug to use (B).

Management of the Ductus Arteriosus

PDA may cause clinical problems for preterm babies with RDS Insufficient data on long-term outcomes when treating PDA with indomethacin, ibuprofen or surgical ligation. Treatment must be based on individual assessment

Recommendations: 2010 If decision to try to close PDA then indomethacin or ibuprofen are equally effective (B). Pharmacological or surgical treatment of PDA must be based on assessment of clinical signs and echo findings suggesting poor tolerance of the PDA (D).

Miscellaneous Considerations

Babies at or near term, especially if born by elective caesarean section, can develop severe RDS. Some term babies with RDS may have genetic disorders (SP-B or ABCA3 deficiency). If pulmonary hypertension is present iNO may help, otherwise not. If pulmonary haemorrhage occurs surfactant may help at least transiently. Later surfactant therapy has not been shown to reduce or modify course of BPD.

Miscellaneous Considerations: Recommendations: 2010

Elective caesarean section in low risk pregnancies should not be done < 39 wk (B). Inhaled NO is not beneficial in management of babies with RDS unless pulmonary hypertension is present in near term infants (A). Surfactant improves oxygenation in babies with pulmonary haemorrhages (C). Surfactant cannot be recommended for prevention of evolving BPD (C).

Summary Management of RDS

Prenatal Care Delivery Room Stabilisation Surfactant, CPAP and Mechanical Ventilation Temperature Control Fluid Management Nutritional Support Management of PDA and Poor Tissue Perfusion Miscellaneous Considerations

Thank You