March 5, 2007Manitoba NRP Advisory Group Use of Oxygen during Resuscitation of Neonates John Baier.

March 5, 2007 Manitoba NRP Advisory Group

Use of Oxygen during Resuscitation of Neonates

John Baier


Objectives

• Review CPS recommendations regarding use of oxygen during resuscitation of newborn infants

• Review the normal postnatal changes in oxygen saturation during transition to extra-uterine life

• Review scientific evidence for oxygen being harmful during resuscitation

• Review clinical trials and experience with room air resuscitation

• Provide a practical approach to CPS recommendations


CPS Recommendations

• Positive-pressure ventilation should be initiated with air (21% oxygen).

• Supplemental oxygen should be used if the baby remains cyanotic or heart rate is less than 100 bpm at 90 seconds of age.

• Blended gases should be available in the delivery room and during transport to the NICU.

• To avoid hyperoxemia pulse oximetry should be available in rooms designated for delivery of babies <33 weeks gestation. Even though, there is no clear definition of what is hyperoxia for preterm infant, it seems reasonable to avoid saturations above 95% when supplemental oxygen is used.


Normal postnatal changes in oxygen saturation

during transition to extra-uterine life


Transitions

• Fetal PaO2 is 20 mm Hg– SaO2 ~60%

• At birth– Infant starts to breath– Lungs expand

• Pulmonary vascular resistance decreases• Pulmonary blood flow increases

– Removal of placental circulation • Systemic vascular resistance increases

– Fetal circulatory pattern starts to convert to normal extra-uterine pattern

– PaO2 increases


Transitions

• How long does this take?

• How good are we at detecting cyanosis?


Rabi et al J Pediatrics 2006

Normal postnatal change in oxygen saturation



Rabi et al J Pediatrics 2006



Kamlin et al J Pediatrics 2006


Evidence that resuscitation with 100%

oxygen may harm


Abstracts on use of oxygen for Resuscitation at PAS-SPR

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2000 2001 2002 2003 2004 2005 2006


Animal Models: Cardiovascular

• Variety of species and models• Compared to RA resuscitation with 100%

results in:– Increased pulmonary arterial contractility in vitro

(newborn lambs)– Similar effects on pulmonary and systemic vascular

resistances (piglet)– No difference in cardiac output (piglets)– No differences in regional blood flow (piglets)– Similar or less myocardial protection – troponin

(piglets)


• Compared to RA resuscitation with 100% results in:– Increased time of apnea (rat)

• Slower resolution of acidosis (piglets)• Similar resolution of acidosis (lambs)• More rapid resolution of hyperlactatemia (piglets)

– Increased evidence of pulmonary injury (lamb, piglet)• Decreased anti-oxidant levels• Increased lipid peroxidation• Increased neutrophil activation (MPO)• Increased MMP-2, MMP-9• Increased cytokines (IL-8)• Increased gene expression (immunosupression)

Animal Models: Pulmonary


Animal Models: CNS

• Compared to RA resuscitation with 100% results in:– No changes in regional blood flow (rabbits)– Increased CNS lipid oxidation and worse neurological

outcome (adult dogs)– Increase in CNS apoptosis –cell death (piglets)– Increased in CNS MMP-2 (piglets)– Increase in CNS IL-1 and TNF (lambs)– No improvement in neurobehavioural outcomes or

brain histology (rats)– No differences in brain pathology (piglets)


Animal Models: Other effects

• Compared to RA resuscitation with 100% results in:– Increased platelet aggregation (piglets)


Evidence of harmful effects of resuscitation with 100% oxygen in newborn infants


Copyright ©2001 American Academy of Pediatrics

Vento, M. et al. Pediatrics 2001;107:642-647

Anti-oxidant status in resuscitated infants


• RA resuscitation resulted in less oxidant stress (GSH/GSSG ratio) at 48 hours of life than did resuscitation with 100% oxygen

• Superoxide dismutase (SOD) activity was less in infants resuscitated with room air than with 100% oxygen

Vento et al 2005 AJRCCM

Anti-oxidant status in resuscitated infants

**p < 0.01 versus control; #p <0.05 versus RAR.**p < 0.01 versus control; #p <0.05 versus RAR.

http://ajrccm.atsjournals.org/content/vol172/issue11/images/large/200412-1740OCf1.jpeg


Renal injury in resuscitated infants

• NAG urine excretion expressed in IU/mmol creatinine, in the first 14 d of postnatal life in asphyxiated newborn infants resuscitated with room air (RAR) or 100% oxygen (OxR). *p < 0.05 versus RAR.

• Normal values for non asphyxiated control infants are below the limit of 10 IU/mmol creatinine




Relationships between oxidant status and injury biomarkers

• Both troponin (myocardial injury) and NAG (renal injury) were directly related to degree of oxidant stress (oxidized glutathione)




Clinical Trials and Experience with Room Air

Resuscitation


Clinical Trials comparing Resuscitation with room air and 100% oxygen

• Vento et al 1991 – Spain (40 infants)

• Ramji et al 1993– India (84 infants)

• Saugstad et al 1998, 2003– India and Europe (609 infants)

• Ramji et al 2003– India (431 infants)

• Bajaj et al 2005– India (204 infants)

• Vento et al 2005– Spain (39 infants)


Vento et al 1991

• Term Infants (40)• Clinical and biochemical signs of

asphyxia (moderate)– hypotonia and apnea, which were

nonresponsive to external stimuli– Apgar score at 1 minute in both groups

ranged from 3 to 5

• Resuscitating team was unaware of the type of gas (RA or 100%)


Vento, M. et al. Pediatrics 2001;107:642-647

Time needed for the onset of a sustained respiratory pattern

** p<0.01 vs. controls# p<0.05 vs. the RAR group.

Copyright ©2001 American Academy of Pediatrics


Extended experience with Room Air Resuscitation (Vento 2001)


Saugstad et al 1998

• Multicenter Study– Mainly in developing countries

• Entry criterion– apnea or gasping with heart rate <80 beats per minute at birth

necessitating resuscitation• Exclusion criteria

– Birth weight <1000 g– Lethal anomalies– Hydrops– cyanotic congenital heart defects– Stillbirth

• Quasi randomized– even dates were resuscitated with room air (room air group), and

those born on odd dates were resuscitated with 100% oxygen (oxygen group)

• Not Blinded• Infants in the room air group who had bradycardia (heart rate

<80) and/or central cyanosis 90 seconds after birth was switched over to 100%


Saugstad et al 1998

• Treatment failure (ie cyanosis or HR<80 at 90 seconds

05

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Room Air 100%


Saugstad et al 1998

• Primary outcome: Death within 1 week and/or presence of grade II or III HIE


Bajaj et al 2005

• 204 infants– India

• Entry criterion– apnea or gasping with heart rate <100 beats per minute at birth

necessitating resuscitation• Exclusion criteria

– Birth weight <1000 g– Lethal anomalies– Hydrops

• Quasi randomized– Odd dates were resuscitated with room air (room air group), and

those born on even dates were resuscitated with 100% oxygen (oxygen group)

• Not Blinded• Infants in the room air group who had bradycardia (heart rate

<100) and/or central cyanosis 90 s after birth was switched over to 100%


Bajaj et al 2005

• Primary Outcome: HIE and/or death before discharge


Blood Gases


Overall Mortality in studies

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Mortality

RA 100% Oxygen Number of Resuscitated Number Died

Source Room Air Oxygen Room Air Oxygen

Ramji 1993 42 42 3 4

Saugstad 1998 288 321 40 61

Vento 2001 19 21 0 0

Vento 2001 16 1 14 6

Ramji 2003 210 221 26 40

Bajaj 2005 107 97 17 17

Vento 2005 17 22 2 4

Totals 657 683 99 128

15.1% 18.7%


Metanalysis of Trials: Death at 1 week

Rabi et al 2007 (in press)


Metanalysis of Trials: Death at 1 month

Rabi et al 2007 (in press)


Metanalysis of Trials: HIE


Practical Considerations

• CPS Guideline:– Supplemental oxygen should be used if

the baby remains cyanotic or heart rate is less than 100 bpm at 90 seconds of age.


• How much Oxygen????

• How to switch between RA and Oxygen????


How much Oxygen??

• No Data– Clinical Trials

switched back to 100% oxygen if poor response after 90 seconds of room air resuscitation 0

510152025303540

Room Air 100%


How much Oxygen??

• No Data– Clinical Trials switched back to 100%

oxygen if poor response after 90 seconds of room air resuscitation

• CPS recommendation is to use 100% oxygen


Resuscitation using an Anesthesia Bag

• Situation 1: Blended oxygen is available in delivery suite:

• Bag is connected to a blender and FiO2 turned to 21%

• If no response, then FiO2 is increased using blender.


Resuscitation with Self Inflating Bag

• Situation 1: Blended oxygen is available in delivery suite:– Bag (with reservoir attached) is

connected to blender and FiO2 turned to 21%

– If no response after 90 seconds, then FiO2 is increased using the blender.


Resuscitation with Self Inflating Bag

• Situation 2: Only 100% oxygen is available– Bag (with reservoir attached) is

connected to 100% oxygen source and flow is turned off

– If no response after 90 seconds, then flow is turned on


What if there is no medical air in the delivery room?

• A compressor in the delivery room could be used to deliver room air– Still needs to be blended with 100%

oxygen source


What if there is no blender

• CPS Guideline:– Blended gases should be available in

the delivery room and during transport to the NICU This means all deliveries.

• Not recommended but gases can be tee’d together to adjust effective FiO2


Blending gases without blender


Additional Considerations

• Infants <33 weeks gestation• Resuscitation in patients in NICU who

are ventilated or already receiving oxygen


CPS recommendation

• To avoid hyperoxemia pulse oximetry should be available in rooms designated for delivery of babies <33 weeks gestation. Even though, there is no clear definition of what is hyperoxia for preterm infant, it seems reasonable to avoid saturations above 95% when supplemental oxygen is used.

• How to titrate oxygen in preterm infants?


Oxygen administration

• Pulse oximetry must be considered an essential component of resuscitation

• Should be placed as soon as possible in an infant who requires resuscitation or appears in need of supplemental oxygen

• Consider use of new technology signal extraction monitors that will perform adequately in low perfusion situations.


Infants <33 weeks gestation

• Start resuscitation with room air as for term infants– If bradycardic/cyanotic at 90 sec

increase oxygen incrementally• Gradual increase in saturation to 90%• Avoid saturation >95%• How?


Titrating oxygen in infants < 33 weeks

• Blended oxygen source

• Titrate FiO2 to saturation and heart rate– HR >100 – Slow increase to

~90%– Saturation <90%

PPV with room air

Increase FiO2 to 0.40

Increase FiO2 to 0.60

etc

HR <100 or

Sat<80

HR <100 or

Sat<80

HR <100 or

Sat<80

60 secs

60 secs

60 secs


Titrating oxygen in infants < 33 weeks

• Self inflating bag attached to 100% oxygen

• Endpoints– HR >100 – Slow increase to

~90%– Saturation <90%

PPV with no reservoir and no flow

Turn on flow(40%)

Attach reservoir

HR <100 or

Sat<80

HR <100 or

Sat<80

60 secs

60 secs


Infants who need resuscitation on ventilators or on oxygen• Most likely have pulse oximetry already

established• Start with oxygen concentration patient

was receiving before need for resuscitation occurred

• Example: Infant was on 30% oxygen for resolving HMD and has a severe apnea and profound bradycardia needing bag mask ventilation– Start at 30% and provide adequate

ventilation for 90% before increasing oxygen

March 5, 2007Manitoba NRP Advisory Group Use of Oxygen during Resuscitation of Neonates John Baier.

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