NRP 2006: Assisted Ventilation Khalid Aziz, Canadian NRP Committee

Cape Spear from St. John’s, Newfoundland & Labrador

Stitches September 2006

Philosophy Establishing effective ventilation is the primary objective in the management of the apneic or bradycardic newborn infant in the delivery room. ILCOR 2005

Objectives a)To present significant changes to the practice of assisted ventilation b)To explain the relevant ILCOR consensus processes and summarize some of the evidence

Areas of Focus With respect to resuscitation of the newborn: Characteristics of initial assisted breaths Devices used for assisted ventilation Ventilatory needs of the preterm baby

NRP: Importance of Heart Rate In the bradycardic infant, prompt improvement in heart rate is the primary measure of adequate initial ventilation. Check signs of improvement after 30 seconds of PPV. This requires the assistance of another person.

NRP: Importance of Heart Rate Primary Apnea Last Gasp Secondary or Terminal Apnea Onset of Gasping Resuscitation In the bradycardic infant, prompt improvement in heart rate is the primary measure of adequate initial ventilation.

NRP: Optimal Initial Ventilation An initial ventilation pressure of 20 cm H 2 O may be effective (ILCOR). >30-40 cm H 2 O may be necessary in some term babies (ILCOR).

NRP: Optimal Initial Ventilation

NRP: Positive End-Expiratory Pressure If ongoing positive pressure ventilation is required, PEEP of 3-6 cm of water should be used (Canadian NRP 2006). PEEP may be given with a flow-inflating bag or a T-piece resuscitator (Canadian NRP 2006). A self-inflating bag with a PEEP valve is also an acceptable alternative (Canadian NRP 2006).

NRP: Inflation Times There is insufficient evidence to recommend optimal initial and subsequent inflation times (ILCOR 2005).

NRP: Assisted Ventilation Devices A self-inflating bag, a flow-inflating bag, or a T-piece mechanical device designed to regulate pressure as needed can be used to provide bag-valve-mask ventilation to a newborn (ILCOR 2005)

NRP: Assisted Ventilation Devices

NRP: Self inflating bag and PEEP PEEP may be provided using an additional PEEP valve on a self-inflating bag Self-inflating bags cannot provide CPAP

NRP: The T-Piece Resuscitator

The description Advantages and disadvantages Practical use

NRP: Confirming ETT Placement An increasing heart rate and exhaled CO 2 detection are the primary methods for confirming endotracheal tube placement (NRP 2006). CO 2 detector should be used as the primary method for confirming endotracheal tube placement (Canadian NRP 2006).

NRP: Confirming ETT Placement

NRP: Pressures in Preterm Infants Avoid creation of excessive chest wall movement (ILCOR 2005). An initial inflation pressure of cm H 2 O is adequate for most preterm infants (ILCOR 2005).

NRP: Other Preterm Issues Use the lowest pressures necessary to achieve an adequate response Consider giving CPAP (not with a self- inflating bag) Consider giving surfactant if the baby is significantly preterm

The tip of the iceberg

Step 1A.Refine the research question(s) Step 1B.Gather the evidence The ILCOR Consensus Process The ILCOR Consensus Process Step 1: State the Proposal

Step 2A.Determine the level of evidence (levels 1-8) The ILCOR Consensus Process Step 2: Assess the Quality of Each Study

Step 2B.Critically assess each article for quality of design & methods The ILCOR Consensus Process Step 2: Assess the Quality of Each Study

Step 2C.Determine the direction of the results/statistics Step 2D.Cross-tabulate by level, quality and direction; combine & summarize The ILCOR Consensus Process Step 2: Assess the Quality of Each Study

The ILCOR Consensus Process Step 2: Example of result

The ILCOR Consensus Process Step 2: Example of result (Supporting Evidence)

The ILCOR Consensus Process Step 2: Example of result

The ILCOR Consensus Process Step 2: Example of result (neutral or opposing)

The ILCOR Consensus Process Step 3: Determine the Class of Recommendation

The ILCOR Consensus Process Important Areas in Assisted Ventilation Initial Ventilation in Asphyxiated Term Newborns Initial Lung Inflation in Preterm Infants The use of CPAP during resuscitation of Very Premature Infants

Initial Ventilation in Asphyxiated Term Newborns Step 1. State the Proposal 5 Hypotheses: IPPV alone is effective Best indicator of adequate initial ventilation is heart rate Chest movement assesses initial ventilation; pressure >30cm H 2 O may be required Prolonged/sustained inflations are needed (>1sec) for initial inflation of asphyxiated term infant Optimal IPPV is breaths per minute (728 articles reviewed / 20 included)

Initial Ventilation in Asphyxiated Term Newborns Step 2. Assess the Quality of Each Study 2A. Determine the level of evidence 2B. Critically assess each article (research design/methods) 2C. Determine direction of results statistics (+/- neutral) 2D. Cross-tabulate

Initial Ventilation in Asphyxiated Term Newborns Step 3. Determine the Class of Recommendations Class I Class IIa ClassIIb Class III Indeterminate

Initial Ventilation in Asphyxiated Term Newborns Hypothesis I Positive pressure alone is effective in the resuscitation of asphyxiated newly born infants. Animal Studies: Mature fetal lambs and rhesus monkeys Artificial ventilation alone was effective in resuscitating the majority of animals following the last spontaneous gasp, provided the mean arterial BP was greater than 15mmHg (Dawes 1963)

Initial Ventilation in Asphyxiated Term Newborns In all species “ventilation of the lungs...effects a rapid & complete restoration of the cardiovascular condition to normal” (Cross 1966)

Initial Ventilation in Asphyxiated Term Newborns Criteria of Effective Treatment: Gasping returns only after recovery of the circulation The increase in heart rate (if maintained at a reasonable level) is a reliable guide to this recovery (Cross 1966) IPPV is much more effective than hyperbaric O 2 in newborn rabbits – 85% recovered with IPPV alone ~ 4mins....or IPPV and cardiac massage (Campbell 1966)

Initial Ventilation in Asphyxiated Term Newborns 12 fetal rhesus monkeys asphyxiated under controlled conditions: –6/12 - rapid response to IPPV alone –remaining 6 – prompt response to chest compressions and IPPV –mean arterial BP lower in those who required CPR (Adamsons 1964) Fetal and newborn rabbits under controlled asphyxia: “...surest sign that lung inflation was going to succeed was an increase in heart rate and BP” (Godfrey 1968)

Initial Ventilation in Asphyxiated Term Newborns Hypothesis II Observing an increase in heart rate within 30 seconds is the primary measure of adequate initial ventilation. Human Studies: 31 full term infants, delivered by c-section, required intubation and ventilation –“IPPV through an endotracheal tube is at least as effective in producing lung expansion as is spontaneous respiration” (Ditchburn 1966) Demonstrated that prompt increase in heart rate ≥ 130/min. was proof of adequate ventilation (Palme-Kilander 1993)

Initial Ventilation in Asphyxiated Term Newborns Hypothesis III Observing chest wall movement assesses the adequacy of initial ventilation – pressures in excess of 30cm H 2 O may be required Hypothesis IV Prolonged or sustained inflations (>1 second) are needed for the initial inflation of asphyxiated term infants

Initial Ventilation in Asphyxiated Term Newborns Several studies looked at pressure and volume changes in healthy term newborns with the onset of spontaneous respirations: Babies produce large negative intrathoracic pressures of up to 50cm H 2 O before lung expansion occurs 7/11 babies had formed FRC at the end of the first breath (Karlberg 1960)

Initial Ventilation in Asphyxiated Term Newborns 20 healthy infants immediately after C-section delivery –The pattern of breathing immediately after delivery is very irregular –FRC obtained with the first breath is proportional to the previous inspired volume (Mortola 1982)

15 babies – elective c-section –5/11 had formed FRC 35 babies – born vaginally –20/21 had formed FRC Initial Ventilation in Asphyxiated Term Newborns Studied the first breath of 50 babies: Possible explanations: 1)Vaginal birth canal squeeze 2)Vaginal delivery – babies make a strong expiratory effort (expiratory pressures in c/s group were 25% smaller) 3)Balance of fluid dynamics within the lungs: - no opening pressure - inspiratory pressure & volume same - expiratory pressure lower in c/s group (Vyas 1981)

Initial Ventilation in Asphyxiated Term Newborns Studied the establishment of FRC: 34 term babies vaginally delivered: recorded ~ the first 30 seconds (≥ 3 breaths) Looked at: –Magnitude of the birth canal squeeze –Interval between delivery of the chest and the onset of the first breath –Inspiratory pressure changes –Expiratory pressure changes –Gaseous FRC at the end of the first breath

Initial Ventilation in Asphyxiated Term Newborns Results: –No evidence of opening pressure –All babies had a marked positive pressure during expiration - in 13/16 this exceeded 50cm H 2 O –All except 1 formed FRC following the first breath –* Significant correlation between inspiratory volume and FRC * emerged above all other factors in the formation of FRC (Vyas 1986)

Initial Ventilation in Asphyxiated Term Newborns Studied IPPV in depressed term infants: Ventilating pressures of 30cm H 2 O provide adequate lung ventilation: FRC Formation: (Hull 1969)

Initial Ventilation in Asphyxiated Term Newborns (Hull 1969)

Initial Ventilation in Asphyxiated Term Newborns (Hull 1969)

Initial Ventilation in Asphyxiated Term Newborns (Hull 1969)

Initial Ventilation in Asphyxiated Term Newborns Respiratory reflex responses: –Strong expiratory effort (“rejection response”) –Inspiratory efforts (paradoxical reflex of Head) (Hull 1969)

Initial Ventilation in Asphyxiated Term Newborns Responses to prolonged and slow rise inflation – 9 babies studied:

Initial Ventilation in Asphyxiated Term Newborns Results: –Physiologic responses –Inflation mean 33.6mL ( mL) –Formation of FRC – all 9 babies formed FRC at the end of the first inflation –Opening pressure: »only seen in 1 infant with slow rise »in square wave apparent between 10-25cm H 2 O (Vyas 1981)

Initial Ventilation in Asphyxiated Term Newborns (Milner 1982)

Initial Ventilation in Asphyxiated Term Newborns Summary: No randomized studies IPPV in depressed term newborns: –Limited numbers –Mostly C-section deliveries –Initial respiratory pressures were highly variable »18-60cm H 2 O (mean 30-40cm H 2 O) –Chest movement mentioned in Upton et al »Indicator of adequate ventilation –Palme-Kilander »2/3 infants required PIP >50cm H 2 O –Subsequent breaths PIPs somewhat less »29 (14-42cm H 2 O) –Generally variable inspiratory time »0.5 – 2 secs. –Based on limited available data

Initial Ventilation in Asphyxiated Term Newborns

Initial Lung Inflation in Preterm Newborns Step 1. State the Proposal Hypothesis: Methods of achieving initial lung inflation during resuscitation of term infants are inappropriate for use in preterm infants Gather evidence: 47 articles from human studies 13 articles from animal studies

Step 2. Assess the Quality of Each Study 2ADetermine the level of evidence 2BCritically assess each article (research design/methods) 2CDetermine direction of results statistics (+/- neutral) 2DCross-tabulate * different endpoints Initial Lung Inflation in Preterm Newborns

Step 3.Determine the class of Recommendations Class I Class II IIa IIb Class III Indeterminate Initial Lung Inflation in Preterm Newborns

Animal Studies: 44 premature rabbits: - ventilated with standardized tidal volume of 10mL/kg of standardized insufflation pressures of 35cm H 2 O from minutes: Necrosis and degeneration of bronchiolar epithelium appeared in animals ventilated for 5 min. or more (Nilsson 1980) 16 premature lambs, 8 received 4 sustained inflations for 5 seconds SI did not improve lung function (Klopping-Ketelaars 1994) Initial Lung Inflation in Preterm Newborns

5 pairs of premature lamb siblings: - one of each pair given 6 manual inflations, mL/kg (“bagging”) - all lambs given surfactant at 30 min. of age: Histological lung injury Impairment of compliance Inhibited the response to surfactant Why did a few large breaths have such a deleterious effect on lung function? –High airway pressure during bagging –The size of the breaths –The time at which they were given –The surfactant deficiency in the lungs (Bjorklund 1997) Initial Lung Inflation in Preterm Newborns

21 premature lambs: - IPPV for 30 min. after birth (tidal volumes of 5mL/kg, 10mL/kg and 20mL/kg) - then at 30 min. - given surfactant and ventilatedx 6hrs: The group with tidal volumes of 20mL/kg: Lower compliance Difficult to ventilate Depressed surfactant recovery Increased protein recovery (Wada 1997)

10 premature newborn lambs: - 2 received surfactant before birth - 2 before the first breath - 2 recruitment maneuvers – 5 breaths, 8mL/kg * - 2 recruitment maneuvers – 5 breaths, 16mL/kg * - 2 recruitment maneuvers – 5 breaths, 32mL/kg * * followed by surfactant »Decreased inspiratory capacity »Decreased compliance »Decreased FRC »Decreased surfactant response »More lung injury (Bjorklund 2001) Initial Lung Inflation in Preterm Newborns

(Bjorklund 2001)

Initial Lung Inflation in Preterm Newborns (Bjorklund 2001)

Initial Lung Inflation in Preterm Newborns (Bjorklund 2001)

Study A. 12 preterm lambs: Group 1 – 5 lung inflations at birth → surfactant Group 2 – surfactant followed immediately by 5inflations Group 3 – surfactant followed by inflations after 10min. Group 4 – surfactant followed by inflations after 60min. * Inflations were 16mL/kg sustained x 5seconds Study B. 10 pairs of twin preterm lambs: - all received surfactant before the first breath - one of each pair got 5 inflations immediately after - the other got 5 inflations 10-15min. after (Ingimarsson 2004) Initial Lung Inflation in Preterm Newborns

“late” compared to “early” inflations: –Lower pressures generated –Easier to ventilate –Better inspiratory capacity, compliance and FRC –Histology showed “satisfactory” response to surfactant (Ingimarsson 2004)

Initial Lung Inflation in Preterm Newborns Suggests: Preceding surfactant does not protect the lungs against the harmful effects of large inflations The “sensitive” period is probably very short (~ 10 min.) (Ingimarsson 2004)

Initial Lung Inflation in Preterm Newborns Human Studies: 21 preterm infants, intubation and IPPV at birth (mean inflation pressure 27cm H 2 O) (Hoskyns 1987) 70 preterm infants, (median pressure for adequate chest wall expansion = 22.8cm H 2 O): - never required >30cm H 2 O (Hird 1991)

651 infants – multi-center randomized trial: a)compared an immediate surfactant bolus b) post-ventilatory aliqout strategy ~ 10min. No difference in survival Less chronic lung disease – O 2 supplement at 36 weeks in (b) Could be due to the vigorous bagging in the immediate group? (Kendig 1998) Initial Lung Inflation in Preterm Newborns

123 preterm infants (retrospective cohort study): 2 different delivery room policies 1994 vs ELBW infants intubated immediately for respiratory distress NP tube inserted – continuous inflation 20-25cm H 2 O (15-20 sec.) → CPAP 4-6cm. Mean initial pressure requirement = 25cm H 2 O More infants in 1996 never intubated (25% vs. 7%) Mortality & morbidity were the same (Lindner 1999) Initial Lung Inflation in Preterm Newborns

“Human” Element: Physicians unable to detect blocked ETT Nurses with experience relied less on manometers but were also less accurate in controlling PIP without the devices Junior doctors could not assess tidal volume visually in relation to inflation pressure NEOPUFF device – more consistent (Spears 1991) (Howard-Glenn 1990) (Stenson 1995) (Finer 2001) Initial Lung Inflation in Preterm Newborns

Summary: Greater emphasis on improving heart rate Less emphasis on good chest wall movement –Encourages large, potentially damaging inflations to preterm infants at a time when their lungs are most susceptable to injury

Initial Lung Inflation in Preterm Newborns

Use of CPAP in the Delivery Room Step 1.State the Proposal Hypotheses: CPAP is a safe and effective intervention in newborn resuscitation compared to Endotracheal Intubation CPAP during resuscitation of very preterm infants will reduce oxygen requirements and the need for ventilation The use of CPAP will decrease oxygen dependency at 36 wks. gestation Gather evidence: 27 articles from human studies 3 articles from animal studies

Use of CPAP in the Delivery Room Step 2.Assess the Quality of Each Study –2ADetermine the level of evidence –2BCritically assess each article (research design/methods) –2CDetermine direction of results statistics (+/- neutral) –2DCross-tabulate * different endpoints

Use of CPAP in the Delivery Room Step 3.Determine the class of Recommendations –Class I –Class II IIa IIb –Class III –Indeterminate

Use of CPAP in the Delivery Room (Finer 2004))

Use of CPAP in the Delivery Room Recommendation: Class B Acceptable & useful Fair evidence