A Primer in
Neonatal Assisted Ventilation
Khalid Altirkawi, MD
King Saud University
College of Medicine
Department of pediatrics
Division of Neonatal Medicine
Introduction
•
•
•
•
Control of breathing
Pulmonary mechanics
Gas exchange mechanisms
Historical synopsis
• Assisted Ventilation Strategies
• Strategies for preventing lung damage
Control of breathing
• Receptors
• Chemoreceptors
• Mechanoreceptors
• Reflexes
Control of Breathing
• Ventilation (CO2 elemination) is maintained by fine
adjustments in tidal volume (VT ) and respiratory rate
(RR) that minimize the work of breathing.
• Motoneurons in the CNS regulate inspiratory and
expiratory muscles activity.
• Chemoreceptors and mechanoreceptors provide feedback to
these neurons to adjust ventilation continuously
Chemoreceptors
• Central (in the brain stem)
• Affected by changes in PaCO2
• And changes in pH (independently of PaCO2 values)
• Peripheral (carotid and aortic bodies)
• Stimulated by hypoxia
• In neonates, acute hypoxia produces a transient
increase in ventilation that disappears quickly
Mechanoreceptors
• Stretch receptors:
• Located in airway smooth muscles
• Respond to changes in tidal volume (VT)
• Mediate:
• Hering-Breuer inflation reflex _ a brief period of decreased or
absent respiratory effort following a good lung inflation
• Head paradoxical reflex _ At slow ventilator rates, large VT
will stimulate augmented inspirations
(may be one of the mechanisms by which caffeine helps weaning from ventilator)
Mechanoreceptors
• Juxtamedullary (J) receptors:
• Located in the interstitium of the alveolar wall
• Stimulated by interstitial edema, fibrosis and by
pulmonary capillary engorgement (CHF).
• Its stimulation increases respiratory rate
Mechanoreceptors
• Baroceptors:
• Located in aortic and carotid sinuses
• Mediate:
• The baroreflex _
Hypertension  hypoventilation or apnea
Hypotension  hyperventilation.
Pulmonary Mechanics
pulmonary mechanics are dynamic, frequently
changing over time
Airway Pressure Gradient
• Gas flows down pressure gradients between
airway opening and alveoli
• Pressure gradient depends on:
• Compliance of lung parenchyma and chest wall
• Resistance to airflow
Compliance
• The elasticity or distensibility of the system
(lungs, chest wall):
Compliance = ∆ volume/∆ pressure
• The chest wall is compliant in neonates and does
not impose a substantial elastic load compared
with the lungs.
Resistance
• The capacity of the air conducting system
(airways, ETT) and tissues to oppose airflow
Resistance = ∆ pressure/∆ flow
• Resistance depends on:
•
•
•
•
Total cross-sectional area of the airways (including ETT)
Length of airways
Flow rate
Density and viscosity of gas breathed
Time constant
• A measure of the time necessary for the alveolar
pressure to reach 63% of the change in airway
pressure.
Time constant = resistance x compliance
Delivery of pressure and volume is complete (95% to 99%) after three to five time
constants
• Different lung regions may have different time
constants due to varying compliance and
resistance
Change in pressure (%)
100
95
99
86
80
60
98
63
40
20
1
2
3
4
Time constant (X)
5
Incomplete inspiration (short Ti)
↓TV
Hypercapnea
↓MAP
hypoxemia
Incomplete expiration (short TE)
Gas trapping
↓Compliance
↓TV
↑MAP
↓TV
↓Cardiac output
Hypercapnia
hyperoxemia
Gas exchange
Hypoxemia and Hypercapnia may coexist,
although some disorders may affect gas
exchange differentially
Gas exchange
• Hypercapnia usually is caused by:
• Hypoventilation
• Severe V/Q mismatch
• Hypoxemia is usually due to:
•
•
•
•
V/Q mismatching (RDS)
R to L shunting (PPHN)
Hypoventilation (apnea)
Diffusion abnormalities
Gas exchange: CO2
• In CMV, elimination of CO2 is directly
proportional to alveolar minute ventilation.
minute ventilation = (tidal volume - dead space) X
frequency
• In high frequency ventilation:
CO2 elimination = (tidal volume)2 x frequency
Gas exchange: O2
• Oxygenation is determined by FiO2 and MAP
MAP = K (PIP - PEEP) (TI/TI + TE) + PEEP
• ↑MAP  ↑lung volume and improved V/Q
matching  ↑oxygenation
• Within the physiologic range, MAP is
independent of rate
Assisted Ventilation
Strategies
• The principles
• Historical synopsis
• Continuous Positive Airway Pressure (CPAP)
• Conventional Mechanical Ventilation (CMV)
• High-Frequency Ventilation (HFV)
• Extracorporeal Membrane Oxygenation (ECMO)
CMV Principles
• Gas flows along a pressure gradient
• In spontaneous ventilation, negative intrathoracic
pressure opposes “neutral” atmospheric pressure
• Some mechanical ventilators attempt to mimic
nature (negative extrathoracic pressure) “iron lung”
• In most mechanical ventilators, positive (supraatmospheric) machine-generated pressure vs.
intrathoracic pressure
Characteristics of
Positive Pressure CMV
Cycle to expiration
Pressure
Flow determines rate of
rise and peak pressure
Pressure limited =
“PIP”
Begin inspiration
Time
Ti
Te
In order to prevent uncontrolled over-distention, the PIP is time-limited, pressure-limited
The Oxygenation story:
the North American experience
• Focus on enhancing oxygenation during
spontaneous breathing
• Continuous Positive Airway Pressure (CPAP)
• Continuous Negative Airway Pressure (CNAP)
• Continuous Respiratory Airway Pressure (CRAP)
• Addition to mechanical ventilation a Positive
End Expiratory Pressure (PEEP)
Pressure
Adding PEEP
PEEP
Ti
Time
Te
The Oxygenation story:
Across “The Pond”
• Focus on enhancing oxygenation during
mechanical ventilation
• Systematically explored the “reversed I:E ratio”
• Spontaneous breathing is characterized by a shorter
inspiratory time compared to expiratory time
• Improved oxygenation as one moved from 1:2 to 1:1
to 2:1 to 4:1
Reversed I:E ratio
Pressure
Reversed I:E
Ti
Time
Te
Eureka!
Pressure
Reversed I:E
Raise PIP
Increase flow
Increased PEEP
Ti
Time
Te
Conventional
mechanical ventilation
• The variables
• The modes
• The modalities
CMV variables
• PIP
• Changes in PIP affect both PaO2 (by altering the
MAP) and PaCO2 (by its effects on VT)
• A high PIP may increase the risk of volutrauma, with
resultant air leaks and BPD
• Larger infants tend to have more compliant lungs,
therefore requiring a lower PIP
CMV variables
• PEEP
• Adequate PEEP prevents alveolar collapse, maintains lung
volume at end expiration, and improves V/Q matching.
• ↑ PEEP  MAP and FRC  improving oxygenation.
• Vey high PEEP may decrease venous return, cardiac output,
and increase pulmonary vascular resistance
• Increases in both PIP and PEEP have opposite effects on
CO2 elimination
CMV variables
• Rate:
• In large RCTs, relatively high rates (60 breaths/min)
resulted in a decreased incidence of pneumothorax
in preterm infants who had RDS
• Generally, a high rate, low VT strategy is preferred
CMV variables
• I:E ratio:
• The major effect of an increase in the I:E ratio is to
increase MAP and improve oxygenation.
• Changes in the I:E ratio are not as effective in
increasing oxygenation as are changes in PIP or
PEEP
• Changes in the I:E ratio usually do not alter VT
unless TI and TE become relatively too short
CMV variables
• TI & TE
• A long TI increases the risk of pneumothorax
• Shortening TI is helpful during weaning
• In RCT: limiting TI to 0.5 seconds resulted in a
significantly shorter duration of weaning
• In patients who have CLD a longer TI (around 0.8
sec) may result in improved VT and better CO2
elimination
CMV variables
• FiO2
• During increasing support, increase FiO2 first until it
reaches about 0.6 to 0.7, then increase MAP
• During weaning, decrease FiO2 initially (~ 0.4 to 0.7)
before you decrease MAP
maintaining an appropriate MAP may allow substantial reduction in FiO2
• Reduce MAP before a very low FiO2 is reached
a higher incidence of air leaks has been observed if distending pressures are not
weaned earlier
CMV variables
• Flow:
• Changes in flow have not been well studied in
infants, but they probably affect arterial blood gases
minimally as long as a sufficient flow is used.
• In general, flows of 8 to 12 L/min are sufficient in
most neonates.
• High flows are needed when inspiratory time is
shortened to maintain an adequate tidal volume.
CMV Modalities
(Target Variable)
• Volume controlled:
• Set tidal volume is delivered, VT is pressure-limited
• Pressure controlled:
• Constant inspiratory pressure, ie. decelerating
variable flow
• Time or flow cycled: method by which inspiration is
started/ended
• Volumes vary with lung compliance
Modes of CMV
Untriggered
Triggered
• IPPV:
• SIMV
• Machine rate faster than
spontaneous
• IMV:
• Slower than spontaneous and
asynchronous
• SIPPV or Assist/Control
• Pressure Supported
Ventilation (PSV)
• Volume Guaranteed
(VG)
Problems in CMV
• Problem:
• Asynchrony:
• Ineffective ventilation and oxygenation
• Fluctuation in BP (associated with IVH)
• Solutions:
• Paralysis and sedation
• Synchronized ventilation
Synchronizing
Means of detecting the
initiation of a breath
• Thoracic impedance
• Abdominal movement
• Change in esophageal
pressure
• Change in airway
pressure
• Change in airway flow
Problems
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•
•
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Artifact
“auto triggering”
Antiphasic triggering
Delayed response time
Lack of response
Triggered (Synchronous) Ventilation
• SIMV
• Only “X” breaths per minute are supported with
“machine breaths” in synchrony
• SIPPV
• Every sensed breath is supported by “machine breath”
• PSV
• Every sensed breath is supported by fixed pressure, but
patient controls flow and TI
• VG
• Preset volume delivered every time
Volume Guarantee (VG)
• The ventilator delivers a specified expired
volume (VT) with the lowest possible pressure
• The preferred mode in which to use VG is PSV
• Best use is when mechanics are rapidly changing
• Do NOT use VG if the leak is > 40%
Volume Guarantee (VG)
• The Problem
• Preset volume delivered may be excessive or
inadequate in a rapidly changing clinical setting
• The Solution
• Over several breaths, records volume achieved and
pressure generated to achieve that volume
• Target “new” pressure computed to achieve predefined set volume
Characteristics of Triggered CMV
“Support” in
untriggered
phase
Machine’s
Support
Frequency
of support
A/C
Preset flow, Ti,
PIP, PEEP
All sensed breaths
Set rate
“guaranteed”
SIMV
Preset flow, Ti,
PIP, PEEP
All sensed breaths in
rated-defined
“window”
CPAP
Set rate
“guaranteed”
Preset PIP, PEEP
Patient’s flow, Ti
All sensed breaths
+/- SIMV or
CPAP
PSV
Clinical Use of Triggered CMV
Typical Setting
Advantage
Disadvantage
Critically ill, unstable,
paralyzed
Control
Control is an
illusion
SIMV
Stable, spontaneously
breathing but not with
consistent rate or MV
Increased
dependence on
patient =
“wean”
Increased
dependence on
patient = “wean”
PSV
Actively attempting to
decrease ventilatory
support
Greatest
synchronization
A/C
Draeger: no
SIMV
A/C and PSV vs. SIMV
High frequency
ventilation
HFV
Characteristics of HFV
• Continuous distending pressure
• Small VT (less than anatomic dead space)
• Rapid ventilator rates
HFV: Examples in Nature
• Humming bird
• ~250 bpm while at rest
• One-way flow via
parabronchi and air sacs
(NOT tidal)
• Panting dog
• VT less than deadspace
• Very high respiratory rate
HFV: Impediment to Gas Flow
Impedance
Airway
frequency
impedance
HFV: Impediment to Gas Flow
Alveolae
frequency
HFV: Impediment to Gas Flow
impedance
Airway
Airway + Alveolae
Alveolae
frequency
impedance
HFV: Resonant Frequency
“Sweet spot”
frequency
So… In High Frequency Ventilation
• Ventilation is controlled by frequency and
(VT)2
• Frequency and VT are
inversely related
 frequency =  ETT resistance,  VT
HFV: The Design
HFOV
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•
•
•
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Diaphragm or piston
Active expiration
Single control of Paw
Single device
Optimum volume, low
pressure
• Air trapping
• Fixed (rigid) circuit
HFJV
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•
•
•
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High pressure jet
Passive expiration
Multiple controls of Paw
CMV in series
Low volume, low
pressure
• Air trapping
• Triple lumen ET tube
HFV: The Strategy
HFOV
• Severe homogeneous lung
disease
• RDS
• Early-onset pneumonia
• PPHN (in concert with
iNO)
Target: RDS
HFJV
• Severe heterogeneous lung
disease
• MAS
• Late-onset pneumonia
• Airleak syndromes
• Pneumothorax
• PIE
Target: barotrauma
Comparative Pressure Profiles
Common Starting Points
Starting CMV
• Choose mode (SIMV, PSV, ….)
• Select PEEP based upon lung disease to achieve
optimal inflation
• Select PIP or volume to generate VT = 4-6 ml/kg
• Start with rate 30-40
• Blood gases in 30 minutes to determine baseline
Starting HFOV
• Frequency
• 10 to 12 Hz for infants >1500g, 15 Hz if <1500 g
• IT
• 33% of cycle
• Amplitude (P)
• Perceptible vibration movement down to groin
• Paw
• Equal to CMV if restrictive disease
• 2-3 cm H2O above CMV if atelectatic disease
Starting HFJV
• Frequency (jet)
• 420 (LBW), 240 - 360 (term or long time constant)
• 3-5 CMV breaths
• IT
• 0.02 seconds
• PIP (Jet)
• To vibrate chest (~PIP on CMV)
• PEEP (CMV)
• To maintain Paw for optimal inflation
HFV: Therapeutic strategies
• Blood gas 20-30 minutes after initiation
• Chest radiograph within 4 hrs after initiation,
and whenever lung over-inflation is suspected
• Adjust Paw to maintain optimal lung volume
• After improvement
• Decrease Paw to maintain FiO2 0.3-0.4
• Decrease VT if PaCO2 lower than target
HFV: Therapeutic strategies
• Atelectasis?
• Increase Paw by 1-2 cm H2O until O2 requirement
• Hypercarbia with high lung volumes?
• Consider air trapping/inadvertent PEEP
HFV: Pitfalls and Complications
• HFV is more effective at ventilation, so the risk
of hypocarbia is greater.
Hypocarbia is clearly correlated with PVL
• Lung overdistention  airleak
• Air trapping  Hypercarbia
• Increased intrathoracic pressure  Reduced
systemic venous return Hypotension
HFV vs. CMV in prophylaxis
• There is no evidence that elective use of HFV (
HFOV or HFFI) provides any greater benefit to
premature infants who have RDS than CMV
• Data are limited and results are mixed as to whether
HFJV may reduce the incidence of CLD
• Preferential use of HFV as the initial mode of
ventilation to treat RDS in premature infants is not
supported
HFV vs. CMV in rescue therapy
• There is no evidence that HFV provides any longterm benefit over CMV in patients who have
respiratory failure
• No RCTs to support the use of HFV over CMV in
the treatment bronchopleural or tracheo-esophageal
fistula
• HFV in this population appears to diminish the
amount of continuous air leak and improve patient
stabilization
Take Home Generalizations
• “A high frequency ventilator can ventilate a
stone.”
• Each underlying disease has a pathophysiology
that suggests the ventilator-of-choice
• Diffuse, homogeneous vs. dishomogenous
• Presence or absence of barotrauma
• Underlying cardiovascular compromise
Strategies to Prevent
Lung Injury
Strategies to Prevent Lung
Injury
• Permissive Hypercapnia
• Low Tidal Volume Ventilation
• Alternative Modes of Ventilation:
•
•
•
•
•
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Patient-triggered Ventilation
Synchronization
High-frequency Ventilation
Liquid ventilation
Proportional Assist Ventilation
Tracheal Gas Insufflation
Ventilator-associated lung injury
• Biotrauma:
• Barotrauma (high pressure, low volume)
• Volutrauma (high volume, low pressure)
• Markers of lung injury are present with the use of high volume and
low pressure, but not with the low volume and high pressure
• The heterogeneity of lung tissue involvement in many diseases
predisposes some parts of the lung to volutrauma
• Oxidant injury
Permissive hypercapnia
• Priority is given to the prevention or limitation
of over-ventilation rather than to maintenance
of normal blood gases
• Two large retrospective studies:
• Hypocapnia during the early neonatal course resulted
in an increased risk of lung injury
Permissive hypercapnia
• RCT:
•
•
•
•
Surfactant-treated infants
BW = 854+163 g, GA = 26+1.4 wks
Assissted ventilation during the first 24 hours
Two groups; Permissive hypercapnia (PaCO2 = 45 - 55 mm
Hg) or normocapnia (PaCO2 = 35 - 45 mm Hg)
• Results: the number of patients receiving assisted ventilation
during the intervention period was lower in the permissive
hypercapnia group (P =0.005)
When to avoid hypercapnia
• IVH risk starts to rise when PaCO2 ~ 53-57
• Since IVH is an early phenomenon, we need to
change upper limit of PaCO2 target range after
risk period has ended
i.e. for Premature infants in first two weeks of life, PCO2 goal is 45 – 55
mm Hg. after two weeks of life, PCO2 goal is 55 – 65 mm Hg as long as
pH > 7.20
Proportional Assist Ventilation
• PAV matches the onset and duration of both
inspiratory and expiratory support
• Support is in proportion to the volume and flow
of the spontaneous breath (decrease the elastic
or resistive work of breathing selectively)
• RCTs are needed
Tracheal gas insufflation
• The added dead space of the ETT  ↑anatomic
dead space  ↓minute ventilation  ↑ PaCO2
• Gas delivered to the distal part of ETT during
exhalation washes out this dead space and the
accompanying CO2
Continuous positive airway
pressure
CPAP
CPAP
PROS
• ↑ alveolar volume &
FRC
• Alveolar recruitment
• Alveolar stability
• Improved V/Q matching
• Redistribution of lung
water
CONS
• Increased risk for air
leaks
• Overdistention
• CO2 retention
• CVS impairment
• Decreased compliance
• Potential to increase
PVR
Early CPAP
• Rescue therapy of established RDS
• Decreases O2 requirements
• Decreases the need for mechanical ventilation
• May reduce mortality
• The optimal time to start CPAP depends on the
severity of RDS (PaO2~ 50 torr, FiO2 ~ 0.4)
Prophylactic CPAP
• Does not decrease the incidence or severity of
RDS
• Does not reduce the rate of complications or
death
Non-invasive
ventilation
NIV
NIV – the rationale
• One of the initial forms of respiratory support
used in preterm infants with RDS
• Recently it has been reintroduced for initial
management of RDS and indications such as
apnea and to improve extubation success after
invasive ventilation
NIV – the mechanism
• The intermittently increased nasal pressure:
• Is transmitted to the lower airways enhancing VT
• Via the nose may act as a stimulus and reduce apnea
episodes
• Increases MAP  better alveolar recruitment and
higher lung volume
• Clears the exhaled gas from the upper airway and thus
reducing the anatomical dead space.
NIV – the Modalities
• Initially, NIV was accomplished using conventional IMV mode (N-IMV)
• By adding triggering, other modalities became
available: N-A/C (aka N-SIPPV), N-PSV, NSIMV
• There are no data on what are the best settings
during NIV
NIV and apnea
• Effects of NIV on apnea:
• Not consistent
• Greater among infants who present with a more
frequent apnea while on N-CPAP
• May be more effective in those infants with poorer
lung function and on N-CPAP
• May not always lead to improved ventilation and gas
exchange, but can partially reduce work of breathing
The End
Suggested Reading
• Goldsmith and Karotkin. Assisted Ventilation of the
Neonate 2003: 183-202
• Froese and Kinsella. High Frequency Oscillatory
Ventilation: Lessons from the neonatal/pediatric
experience. Critial Care Medicine 2005;33:S115-121
• Keszler. High Frequency Ventilation: Evidence-based
Practice and Specific Clinical Indications NeoReviews
2006;7:e234-241
Optimizing Lung Volume
• Lung hysteresis refers to the fact that lung volume and
compliance at a given transpulmonary pressure is higher in
deflation than in inflation
Froese AB: Neonatal and
Pediatric Ventilation:
Physiological and clinical
perspectives. In Marini JJ,
Slutsky AS (eds):
Physiological Basis of
Ventilatory Support. New
York, Marcel Dekker, 1998.
P. 1346