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Gentle Ventilation:

A Focus on CPAP

Julie Kessel, MD

UW Madison/Meriter HospitalApril 2013

Objectives

Evidence for continuous positive airway pressure (CPAP) and nasal intermittent mandatory ventilation (IMV).

� Prophylactic CPAP either before/alternative to intubation and

surfactant

� CPAP after surfactant administration to treat RDS/BPD

� High flow nasal cannula and nasal ventilation

Source: Neonatology on the

Web

Proc R Soc Med. 1974 April; 67(4): 245–247.

Gregory Box History

Cohort studies over 25 yrs ago noted benefits of CPAP

2008 Cochrane Review (Ho et al)

� continuous distending pressure vs head box O2 or IPPV (no

PEEP) for RDS in preterm infants

� 3 of 6 with continuous negative pressure

� 4 of 6 studies done in 1970s and excluded < 1000gm

� Low antenatal steroids in 1996 and 2007 trial

� Outcome

� increased pneumothorax

� decreased mortality

Science of CPAP

Benefits (Morely, 2008) � Promotes functional residual capacity

� Decreases airway resistance

Lung architecture and injury� Lambs and baboon studies

� Prevents alveolar collapse

� Preserves endogenous surfactant

� Decreased ventilation perfusion mismatch

� Decrease lung inflammation in lamb and piglets

� Jobe, 2002 and Lampland, 2008

Agrons G A et al. Radiographics 2005;25:1047-1073

CPAP Studies in

Premature Infants

Death or

BPD*

RDS

Intubation+/- surfactant

Extubation

At riskpreemies

recovery

* O2 need at 36 wks post menstrual age

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Cochrane Reviews

1. Prophylactic CPAP

• Prophylactic CPAP for preventing morbidity and mortality in

very preterm infant

• Subramaniam, Henderson-Smart and Davis, 2009, Issue 1

2. CPAP after extubation

� CPAP immediately after extubation for preventing morbidity

in preterm infants

� Davis, Henderson-Smart, 2009, Issue 2

3. CPAP with surfactant

• Early surfactant with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with

or at risk for RDS

• Stevens, Blennow, Meyers and Soll 2008

Prophylactic CPAP

� >32 wks and/or 1500 gm

� Compared:

� Prophylactic CPAP soon after birth regardless of respiratory

status

� “Standard” methods where CPAP/IPPV is used for defined

respiratory condition

� Two Studies

� 230 infants 28-31 wks, antenatal steroids in 80%

� Outcome CPAP

� No differences in death, BPD

CPAP After Extubation

9 RCT, less than 37 wks

Compared

• CPAP (3-7 cm H2O)

• Headbox O2

Outcome CPAP

� Less failure at 1 to 7 days (acidosis, increased O2 or

recurrent minor/single major apnea)

� No difference in oxygen need at 28 days

CPAP with Surfactant6 RCTs

� 1250-2000 gm/<12 hrs with RDS (n=31)

� >1250 gms/<36 wks (n=132)

� <30wks/<6hrs with RDS (n=26)

� 1501-2500gms (n=2700

� 25-35 wks (n=105)

� 25-35 wks (n=68)

Compared

� Early surfactant/brief mechanical ventilation (< 1 hrs)/extubation

� Later surfactant/ventilation

Outcomes CPAP with early surfactant � Decreased BPD, ventilator days and pneumothorax

� Increased surfactant

NEJM takes notice:

NEJM 2008

� Nasal CPAP or Intubation at Birth for Very Preterm Infants

(COIN trial, Morley et al)

NEJM 2010

� Early CPAP versus Surfactant in Extremely Preterm

Infants (SUPPORT Study Group)

Pediatrics 2011

� Randomized trial Comparing Three Approaches To the

Initial Respiratory Management of Neonates (Dunn et al)

COIN Trial: Continuous Positive Airway

Pressure or Intubation at Birth

International RCT of 610 babies at 25 to 28 6/7 wks

� Randomized in delivery room (spontaneous respirations

with RDS)

� CPAP +8 or intubation/ventilation at 5 minutes for

respiratory distress

Outcomes CPAP

� No difference in primary outcome (death or BPD

� Increased pneumothorax (9.1 versus 3%), first 2 days

� Decreased oxygen at 28 days

� Fewer ventilation days

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SUPPORT trial: Surfactant, Positive Pressure

and Pulse Oximetry Randomized Trial

RCT of 1316 infants at 24-27 6/7wks

� Randomlzed before delivery

� Respiratory support

� Intubation/surfactant by 1 hr after birth

� CPAP +5 in the delivery room

� Two target ranges of saturation

� 85-89% versus 91-95%

Outcomes CPAP (36 wks PMA)

� No difference in primary outcome of death or BPD

� No difference in pneumothorax, NEC, Grade 3/4 IVH, severe ROP

� Less intubation and ventilator days

� Less postnatal steroids

� More likely to be alive/free from mechanical ventilation at 7D

Vermont Oxford

NetworkMulticentered randomized trial (27 centers)

� Dunn et al 2011

26-29 wks

� N=648- stopped due to declining enrollment

Compares 3 approaches to initial respiratory management

� Prophylactic surfactant then ETT ventilation

� Prophylactic surfactant with rapid extubation to bubble CPAP (ISX)

� Bubble CPAP than selective surfactant

No difference in death or BPD

The Art of CPAP

Caffeine

� Decreased apnea, extubation failure, ventilator days and CLD

� Schmidt, 2006 NEJM

SUPPORT trial : “Centers with most experience with CPAP also used a higher threshold for intubation”

� Failure/intubation criteria

� Extubation Criteria*

Mode of CPAP delivery

Other: target oxygen saturations

SUPPORT Trial

Lower (85-89%) versus higher 91-95% target range of oxygen saturation

Outcomes for lower target range

� lower rate of severe retinopathy

� higher mortality.

The New Frontier

� Alternative methods for surfactant

� Alternative CPAP

� Biphasic nasal CPAP

� HFNC

� NIPPV

NIPPV

Nasal Intermittent positive pressure ventilation

Started in 1980s

� Increased gastrointestinal perforation

� Garland, Pediatrics, 1985

Three RCTs using Infant Star (synchronized)

Increased use worldwide (Bhandari, 2012)

� About 50% NICUs in UK/Ireland

� Over 98% in Brazil

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NIPPV

NIPPV compatible with Ram (Avea, Draeger, PB, HFOV, Sensor Medics I-servo (with modifications).

� Not compatible with GE Carestation

Several different nasal interfaces/heterogeneous studies

“We suggest that a particular unit use the ones with which they are most comfortable because there are no direct comparisons”

Bhanddari, 2012

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NIPPV Setting

Guidelines

Settings Initial Maximum

Rate (bpm) 40 55

PIP (cm H2o) 20 35

PEEP (cm H20) 5 6

Inspiratory Time 0.5 0.7-1

Post Extubation NIPPV

Cochrane Review NIPPV versus nCPAP for preterm Neonates after Exubation (Davis et al, 2009)

Three RCTs, all with synchronized NIPPV

Outcome NIPPV

Less extubation failure by 48-72hrs

BPD trended less but not significant

No reports of GI perforation

Prophylactic NIPPV

� Intervention Protocol 2009

� Prophylactic NIPPV versus Pro;ylactic nCPAP for preterm infants

� Less than 37 wks

� Primary outcome mortality at 28 days or BPD

� Subgroup analysis > or < 28 wks

NIPPV for RDS

NIPPV versus NCPAP for Preterm Infants with RDS (Meneses et al, Pediatrics, 2012)

Outcomes NIPPV

� Decreased intubation in first 72 hrs (primary outcome)

� No difference in PTX, IVH, NEC, time to full feedings or duration of hospital stay

� No perforations reported

� Trend to less BPD but not significant

HFNC

� Greater than 1 L/min

� 4 studies that investigated HFNC versus CPAP and humidified versus non humidified

� HFNC used post extubation has increased failure compared to CPAP

� Cochrane Review

� “There is insufficient evident to establish the safety or effectiveness of HFNC as a form of respiratory support in

preterm infants”

How should we use CPAP?

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FailedCPAP

Death/ BPD

PTX Post steroids

N=23028-31wks

Prophylactic CPAP after birth

“standard”CPAP/IPPV

N=61025-28 wks

CPAP +8 @ 5 min Intubation @ 5 min equal More CPAP

LessCPAP

N=131624-27wks

CPAP +5 in deliveryroom

Intubation/surfactant within 1 hr

80% equal equal Less CPAP

N=20825-28wks

Early surfactant/CPAP

Later surfactant/CPAP

1/3

N=64626-29

CPAP with or without prophylactic surfactant

Prophylactic surfactant

Summary� Most CPAP studies showed trends but no decrease in BPD or

death� 29-47% compared to 36-51%

� Increase in rate of pneumothorax � 4.8-9.1% to 3-7.4%

� CPAP with early surfactant/brief ventilation may decrease BPD

� Significant failure rates with CPAP at less than 28wks (30-60%) and INSURE (9-50%)

� Tiniest babies (less than 24 wks) rarely escape intubation� 80% in 7 days

� Bigger babies often don’t escape CPAP

Term babies?

� NRP instructor update, Spring/Summer 2012

Beyond BPD-

Neurodevelopmental Outcomes

2012

� Neurodevelopmental Outcomes in Early CPAP and Pulse

Oximetry Trial (Support Study Group)

� Evaluations at 18-22 months

� No difference in neurodevelopmental impairment

� 27.9 versus 29.9 %

� Baley (BSID-III) less than 70

� Gross motor function classification system > 2

� Moderate/severe cerebral palsy

� Bilateral visual handicap

Life expectancy has increased to 76.7 years-

everyone deserves a good start

reference

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References

� Carlo et al, Gentle Ventilation: new evidence from the SUPPORT, COIN, VON CURPAP, Colombian Network and Neocosur Network Trials, Early Human Development, 2012.

� Morely et al, Current Opinion Pediatrics, 2004

� Morley and Davis, Continuous Positive Airway Pressure: Scientific and clinical Rationale, Curr Op pediatrics, 2008

� Pfister and Soll, Perinatology Clinics, 2012

� Bhandari, Noninvasive Respiratory Support in the Preterm Infant, Perinatology Clinics, 2012

� Ramanathan, Nasal Respiratory Support through the Nares, Its Time has Come, J Perinatology, 2009.

Range of Failure Criteria� Time range

� 48 hr to 7 days

� Oxygen:

� 50% needed to maintain saturation greater than 88% for 1 hr

� 60-80%

� Increased 15-20% over baseline

� Blood gas (some require 2)

� PCO2 greater than 65 documented 1 hr before intubation

� pCO2 greater than 50-65, pH < 7.2-7.25

� Clinical

� Hemodynamic instability: low BP/perfusion needing volume/pressors > 4 hrs

� Progressive atelectasis or respiratory distress

� Severe A/B

� Apnea (recurrent minor or 1 major)

� One major/frequent minor A/B events

� 3 or more episodes of apnea needing stimulation or 1 needing IPPV

� >3 apnea needing moderate stimulation in 12 hrs or 2 apnea needing vigorous stimulation in 8 hrs.

SUPPORT trial Intubation Criteria (any)

� FIO2 > 0.5 to maintain saturation > 88% for 1 hours

� PaCO2 >65 mmHg within 1 hr of intubation

� Hemodynamic instability

Extubation Criteria (all)

� PaCO2 < 65 mm HG with pH > 7.2

� SpO2 above 88% with FIO2 < 0.5

� Mean airway pressure < 10 cm H2O

� IMV < 20 breaths/minute

� Amplitude less than 2X MAP (high frequency)

� Absence of clinically significant PDA

NIPPV Weaning

GuidelinesParamet

erAmount Frequency Minimal

Settings

PIP 1-2 Q 6-12 hrs 10-12

RATE 2 Q 6-12 hrs 12-20

PEEP 1 NA <5

FiO2 NA NA <30%

Order of weaning:1) Wean PIP first until at 10-12, then begin to wean the rate

1) Wean PEEP last or if CXR shows hyperexpansion

1) Once on minimal NIPPV setting, can change to CPAP 5, routine

nasal cannula, or room air based on attending discretion

Blood Gas Checks During

NIPPVas Recommended by Dr. Ramanathan

Acute Phase: Q 12-24hrs

Weaning Phase: Q 24-48hrs, biweekly if stable

Escalation of Care: Q 1-2hrs after change made

-Adapted from LAC-USC 2011 Guidelines

Initial Management of RDS< 26 wks +

incomplete betamethasone

< 26 wks + complete betamethasone*

OR

29-31 wks and/or

<1500gms

>32 wks

CPAP±rate in DRInterface:Ram Cannula or

mask

CPAP±rate in DRInterface:Ram Cannula or

mask

Observe vs. CPAP±rate if sxs in DR

Interface: Ram Cannula or mask

Give surfactant for (1) or (2)(1) Intubated for

resuscitation or RDS(2) Prophylaxis

Give surfactant if (1) or (2):(1) intubated for

resuscitation or respiratory distress

(2) FiO2 >0.35 on optimal

NIPPV settings

**Give surfactant if (1) or (2) :(1) intubated for resuscitation or

respiratory distress

(2) FiO2 >0.4

Caffeine upon admission Caffeine upon admission Caffeine if symptomatic

Extubate to NIPPV Extubate to NIPPV Extubate , manage routinely

*Complete betamethasone defined as >2 doses and 24hrs prior to last dose

**Curosurf dosing range 100-200mg/kg, if >32wks use 100mg/kg dose

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Considerations for

Intubation

& Surfactant Administration

Parameters

Respiratory

Acidosis

pH <7.2-7.25

CO2 Retention >60-65

FiO2 >35%

Apneas + BMV >1-2/ 24-hr period

Spells +

Stimulation

>2-3/ hr

Must meet ONE or MORE of the above criteria