Management of Neonatal Respiratory Distress Syndrome European Consensus Guidelines 2010 UpdateOla 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 Ancona, Italy Gorm Griesen Copenhagen, Denmark Henry Halliday Belfast, UK Mikko Hallman Oulu, Finland Eren Ozek Istanbul, Turkey Richard Plavka Prague, Czech Republic Ola Saugstad Oslo, Norway Umberto Simeoni Marseille, France Christian Speer Wurzburg, Germany David Sweet Belfast, UK (Secretary)

Updated Guidelines: 2010What 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?

Role of antenatal steroids Which steroid? How many courses? Who should get them?

Role of tocolytic agents Allow steroids to take effect or time to transfer

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 self-inflating 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 SurfactantsComparison of Animal Derived SurfactantsSurfacta

ntPreparation/ Preparation/ CompositionComposition

PhospholiPhospholipidspids

Plasma Plasma logens logens

*mol %*mol %

SP- B SP- B mg/mlmg/ml

SP- C SP- C mg/mlmg/ml

Survanta Survanta (S(S)

Minced Bovine Minced Bovine Lung Extract/ Lung Extract/

DPPC, Palmitic DPPC, Palmitic Acid, Acid,

TripalmitinTripalmitin

84 %84 % 1.51.5Total <1mg/mlTotal <1mg/ml

0 - 1.3 0 - 1.3 ((µg/µmol µg/µmol

PL)PL)

1 – 20 1 – 20 ((µg/µmol PL)µg/µmol PL)

Infasurf Infasurf (I)(I)

Bovine Lung Bovine Lung Lavage/DPPC, Lavage/DPPC,

CholesterolCholesterol 95 %95 %NANA

0.260.26 0.440.440.90.9(Alveofact)(Alveofact)

CurosurfCurosurf

(C)(C)

Minced Porcine Minced Porcine Lung Lung

Extract/DPPC, Extract/DPPC, Polar lipids Polar lipids

(Liquid Gel (Liquid Gel Chromatography)Chromatography)

99 %99 % 3.83.8 0.450.45 0.550.55

* High Plasmalogen content is associated with lower BPD rate. Rudiger et al. AJP 2005

Tracheal Aspirates with High Levels of Tracheal Aspirates with High Levels of Plasmalogens Associated with Lower Plasmalogens Associated with Lower

BPD RatesBPD Rates

• Aspirates were collected Aspirates were collected

prospectively prospectively from preterm from preterm

infants ≤32 wks GA intubated infants ≤32 wks GA intubated

within 1hr of birthwithin 1hr of birth

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

5

4

3

2

1

BPD

XX

X

X

X

XX

X

X

X

non BPD

P<0.001

% D

MA

s on

all

Fat

ty A

cid

s

Comparison of Animal Derived Surfactants

Curosurf vs. Survanta (5 studies) Trials (6-10) Surfactant N Type Patient

sResults

Speer

1995

Curosurf vs. Survanta

73 Tx 700-1500 g

Curosurf: Lower FiO2, PIP & MAP @ 12-24 h

Baroutis

2003

Curosurf vs. Survanta vs.

Alveofact

80 Tx < 2000 g

Curosurf: Fewer days on O2 & PPV; Decreased LOS

Ramanathan

2004

Curosurf vs. Survanta

293 Tx 750-1750 g

Curosurf: Lower FiO2, Fewer doses, Decreased

Mortality < 32 wks

Malloy

2005

Curosurf vs. Survanta

58 Tx < 37 wks

Curosurf: Lower FiO2 up to 48 h, Fewer doses, lower

volume

Fujii, 2010 Curosurf vs. Survanta

52 Tx < 30 wks

Curosurf: Faster weaning, Less Air-Leaks, PDA & MV

at 72 hrs

Curosurf

(n= 33)

Survanta

(n = 40)PIE 3 % 10 %

PTX 6.1 % 12.5 %

IVH Total 21.2 % 35 %

IVH Gr. III-IV 3 % 12.5 %

O2 @ 36 wks PCA

12.5 % 11.4 %

Mortality 3 % 12.5 %

Speer C et al. Arch Dis Child 1995; 72: F8-F13No Difference in Death or BPD

Curosurf vs. Survanta – Rescue Trial (6)

Curosurf vs. Survanta – Rescue Trial (6)

Changes in FiO2 , PIP & MAP

FiO2

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

PIP & MAP

Faster Weaning

**

Data : Mean SEM *,* = p < 0.05

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

0 15’ 30’ 2 h 6 h

FiO

2

Ramanathan R et al. AJP 21:109-119; 2004

Faster Weaning

41

20

0

8

1

49

15

4

27

0

20

40

60

2 Doses 3 Doses 4 Doses

Curosurf 100

Curosurf 200

Survanta 100

% I

nfa

nts

% of Infants Requiring Additional Doses of Surfactant #8

*

* p < 0.05 36 % (C200) vs. 68 % (S100) received 2 or more doses

Fewer Doses

15

76

28

50

39

4

1519

0

32

16

3529

4

16

8

0

10

20

30

40

50

60

70

80

Air Leaks PDA PDA-Ligation

BPD ROP II-IV IVH II-IV NEC Mortality

Beractant Poractant AlfaP = 0.002

%

Curosurf vs. Survanta (n=50): (Rescue Trial # 10)

Less Air Leaks & PDA with Curosurf

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

P = 0.047

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

OR ( 95 % C.I. )

PTX 0.54 0.19, 1.53

O2 @ 36 wks 1.03 0.61, 1.74

PDA 1.29 0.79, 2.08

Pulmonary Hge 1.01 0.32, 3.21

IVH Gr. I-II 1.39 0.65, 2.96

IVH GR.III-IV 0.65 0.28, 1.53

Neonatal Mortality

0.35 0.13, 0.92

(* Speer et al. & *Ramanathan et al.) Halliday HL. Biol Neonate 2005; 87:317-22

Ramanthan et al Journal of Perinatology (2011), 1–7 

Mortality of 3 different surfactants

Ramanthan et al Journal of Perinatology (2011), 1–7

Mortality of 3 different surfactants

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

Cost per patient: Curosurf vs. Survanta

0,00

200,00

400,00

600,00

800,00

1 000,00

1 200,00

1 400,00

1 600,00

1 800,00

2 000,00

Model 1 Model 2 Model 3 Model 4

SurvantaCurosurf

Cos

t / P

atie

nt

($)

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

53% ($ 950)

46% ($ 618)

20% ($ 220) 20% ($

200)

Cost Effective

Surfactant for RDS: Evidence Based Surfactant for RDS: Evidence Based ApproachApproach

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

PhospholipidsLowering Surface Tension

& Better anti-inflammatory effects

2. Phosphotidylcholine molecular species closely resembles human surfactant

Better interaction with SP-B

3. Highest amount of SP-B Rapid adsorption of Phospholipids

4. Highest amount of Plasmalogens

Highest anti-oxidant activity

5. Highest amount of PUFA in a smaller volume and lower Viscosity

Rapid distribution and less reflux

Guidelines for Surfactant Treatment of RDS < 28 wk 29-31 wk > 32 wk

NIPPV in DR, Early Rescue (<30’) in DR or NICU with 200 mg/kg of Poractant Alfa

Early CPAP/NIPPV

Surfactant if intubated for resuscitation

Observe

CPAP/NIPPV if respiratory

distress

Extubate to NIPPV as soon as possible (> 24 wk).

•Start Caffeine

Early Rescue with

100-200 mg/kg if FiO2 > 0.30 + white CXR.

•Start Caffeine

Delayed Rescue with

100 mg/kg if FiO2 > 0.40

+ white CXR

•Caffeine if symptomatic

Redosing:

FiO2 > 0.30

How soon: 2-12 hrs from the 1st dose

Redosing:

FiO2 > 0.35

How soon: 12 hrs from the 1st dose

Redosing:

FiO2 > 0.40

How soon: 12 hrs from the 1st dose

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 Should we resuscitate extremely low birth weight extremely low birth weight

infants with a low FiOinfants with a low FiO22??

Raquel E et al Pediatrics May 2008

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

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

0 3 6 9 12 1550

100

150

200low FiO2

High FiO2

Raquel E et al Pediatrics May 2008

min after birth

bea

ts p

er m

in

SpO2 in extremely low gestational age neonates

0

20

40

60

80

100

120

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

Sp

O2

(%)

Hox group (n=41)

Lox group (n=37)

Vento et al, Pediatrics 2009

Isofurans

**

**

Suggested level for administration of oxygen0

10

20

30

40

50

60

70

80

90

100

Oxy

gen

satu

ratio

n(%

)

0 1 2 3 4 5 6 7 8 9 10

Minutes after birth

10th 25th 50th 75th 90th

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

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

TRANSITIONAL OXYGEN TRACKING SYSTEMTRANSITIONAL OXYGEN TRACKING SYSTEMAllowing to individualize FiO2 avoiding hyper/hypoxiaAllowing to individualize FiO2 avoiding hyper/hypoxia

Rich W et al non published data 2010

50%

10%

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 GA w/BW g Study design High SaO2 Low SaO2

STOP ROP 2000 Mean 25.4 w Randomized 96-99 89-94

Tin 2001 <28 weeks Observational 88-98 70-90

Sun 2002 500-1000gr Survey >95 ≤ 95

BOOST 1 2003 <30 weeks Randomized 95-98 91-94

Chow 2003 500-1500 gr Observational 90-98 85-93

VanderVeen 2006 ≤28 weeks≤ 1250 gr

Historical control

87-97 85-93

Deulofeut 2006 ≤ 1250 gr Historical control

92-100 85-93

Noori 2009 < 1000 gr Historical control

89-94 83-89

SUPPORT 2010 24-28 weeks Randomized 91-95 85-89

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

Relative Risk .2 .5 1 2

Study Relative Risk (95% CI)

Randomized trials

STOP ROP, 2000 0.64 ( 0.40, 1.03)

Askie, 2003 0.71 ( 0.59, 0.86)

Support, 2010 0.91 ( 0.79, 1.05)

Subtotal 0.79 ( 0.64, 0.97)

Observational studies

Tin, 2001 0.40 ( 0.22, 0.69)

Sun, 2002 0.66 ( 0.57, 0.76)

Deulofeut, 2006 0.69 ( 0.55, 0.85)

Noori, 2009 1.04 ( 0.79, 1.36)

Subtotal 0.70 ( 0.54, 0.91)

Overall 0.74 ( 0.63, 0.87)

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

BPD and SpO2

Relative Risk .03 .1 .25 .5 1 2

Study Relative Risk (95% CI)

Randomized trials

Support, 2010 0.48 ( 0.34, 0.68)

Subtotal 0.48 ( 0.34, 0.68)

Observational studies

Tin, 2001 0.40 ( 0.22, 0.69)

Sun, 2002 0.66 ( 0.57, 0.76)

Chow, 2003 0.22 ( 0.05, 0.85)

Deulefeut, 2006 0.64 ( 0.27, 1.46)

VanderVeen, 2006 0.32 ( 0.12, 0.80)

Noori, 2009 0.28 ( 0.18, 0.42)

Subtotal 0.42 ( 0.27, 0.65)

Overall 0.44 ( 0.31, 0.61)

ROP and SpO2

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

Terms and Conditions

Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trialWolfgang Göpel, 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 Möller, MD, Christoph Härtel, MD, Sebastian Haller, MD, Bernhard Roth, MD, Egbert Herting, PhD and on behalf of the German Neonatal Network

The Lancet September 30, 2011

Randomized studieshigh 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

High SpO2 • 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

SpO2 85-89% Vs 91-95 %

BPD 25%

ROP 50%

Mortality 20%

SpO2 ?

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

What is the ”right” balance between mortality and morbidity?

Oxygen saturation in ELBWIs revisitedOxygen saturation in ELBWIs revisited Updated recommendationsUpdated 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)

ConclusionsConclusions

•It is best to initiate resusctiation of term babies It is best to initiate resusctiation of term babies with airwith air

•Low SaOLow SaO22 (85%) beyond the DR (85%) beyond the DR

probably reduces BPD and ROPprobably reduces BPD and ROPBut may increase mortalityBut may increase mortality Do not target SaODo not target SaO22 between 85-89% between 85-89%

•The optimal FiOThe optimal FiO22 for resuscitation of ELGANs is for resuscitation of ELGANs is

not known. But do not use 100% oxygen, start low not known. But do not use 100% oxygen, start low with 21 or 30%with 21 or 30%

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