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Principals of Mechanical Ventilation in Neonates: DR Mohd Maghayreh PRTH - Irbid

This document provides information on the principles of mechanical ventilation in neonates. It discusses pulmonary mechanics during assisted ventilation, including compliance, resistance, and time constants. It also covers lung mechanics in different disease states, gas exchange during assisted ventilation focusing on carbon dioxide and oxygen exchange, and different types of mechanical ventilators including volume-cycled, pressure-limited and patient-triggered ventilators. The document concludes with indications for mechanical ventilation in neonates.

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0% found this document useful (0 votes)
87 views78 pages

Principals of Mechanical Ventilation in Neonates: DR Mohd Maghayreh PRTH - Irbid

This document provides information on the principles of mechanical ventilation in neonates. It discusses pulmonary mechanics during assisted ventilation, including compliance, resistance, and time constants. It also covers lung mechanics in different disease states, gas exchange during assisted ventilation focusing on carbon dioxide and oxygen exchange, and different types of mechanical ventilators including volume-cycled, pressure-limited and patient-triggered ventilators. The document concludes with indications for mechanical ventilation in neonates.

Uploaded by

Anonymous 58LGc3
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPT, PDF, TXT or read online on Scribd
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Principals of

mechanical ventilation
in Neonates
Dr Mohd Maghayreh
PRTH -IRBID
Introduction
 Mechanical ventilation is an invasive life-
support procedure with many effects on
the cardiopulmonary system.
 The goal is to optimize both gas
exchange and clinical status at minimum
FiO2 and ventilator pressure. The
ventilator strategy employed to
accomplish this goal depends in part on
the infant’s disease process.
Introduction

 Conventional positive pressure


ventilation remains the mainstay of
assisted ventilation in neonates despite
the development of new ventilatory
techniques.
Pulmonary Mechanics
during Assisted
Ventilation
The mechanical properties of the
respiratory system can be described
according to their elastic and resistive
forces into:
 Compliance
 Resistance
Compliance

 Term used to describe the elastic properties of


a system.
 It is estimated from simultaneous changes in
volume and pressure.

Compliance (mL/cmH2O) = Change in volume (mL)


Change in pressure (cmH2O)
Resistance

 Term used to describe the property of the


lungs that resists airflow.

 The pressure is required to overcome the


elasticity of the respiratory system, to
force gas through the airways (airway
resistance), and to exceed the viscous
resistance of the lung tissue (tissue
resistance).
Resistance (cont.)

Resistance (cmH2O/L/sec) =
Change in pressure (cmH2O)
Change in flow (L/sec)

Time constant of the respiratory


system = Resistance X Compliance
Pulmonary Mechanics
during Assisted
Ventilation (cont.)
 A time period equal to one time constant will
allow a 63% equilibration of pressure (and
volume) throughout the lungs.
 Not much equilibration of pressure and
volume occurs beyond 3 to 5 time constants.

 The time necessary for the lungs to inflate and


deflate will depend on the inspiratory and
expiratory time constants.
Pulmonary Mechanics
during Assisted
Ventilation (cont.)
 Example
 A healthy infant has resistance of 30cm
H2O/L/sec and compliance of 0.004 L/cmH2O.
 One time constant of this infant’s respiratory
system will be 0.12 seconds.
 For complete equilibration of pressure at 5 time
constants or (5 X 0.12 seconds), an inspiratory
or expiratory phase of 0.6 seconds will be
necessary, assuming equal inspiratory and
expiratory time constants.
Pulmonary Mechanics
during Assisted
Ventilation (cont.)
 Infants with RDS typically have a
decreased compliance, and consequently
their time constant and the corresponding
time for pressure and volume
equilibration will be shorter.
 This means that the stiff lung in these
infants (RDS) will complete inflation and
deflation in a shorter time than normal
lungs.
Pulmonary Mechanics
during Assisted
Ventilation (cont.)
 Because infants with RDS have a
decreased time constant, short
inspiratory and expiratory times may be
appropriate during the period of peak
severity of their disease, but the
difference is insignificant after recovery
from RDS when compliance is much
higher and the time constant becomes
longer.
Lung Mechanics in
Disease States
Disease Complian Resistanc Time FRC V/Q Wor
ce e Consta ml/k matchin k
ml/cmH2O cm/H20/ml nt g g
/s sec
Normal 4-6 20- 0.25sec 30 ---- ----
term ml/cmH2O 40cm/H20/ ml/k
ml/s g

RDS ↓ ↓ ↓ ↓ ↓ ↑

MAS ↓ ↑ ↑ ↑ ↓ ↑
Lung Mechanics in
Disease States (cont.)
Diseas Complianc Resistance Time FRC V/Q Wor
e e cm/H20/ml/ Consta ml/k matchi k
ml/cmH2O s nt g ng
sec
BPD ↑/ ↓ ↑ ↑ ↑ ↓ ↑

Air ↓ ↑ ↑ ↑ ↓ ↑
leak

VLBW ↓ ↓ ↓ ↓ ↓ ↑
apnea
Gas Exchange during
Assisted Ventilation
 Carbon dioxide (CO2)
 Diffuses rapidly from the blood into the alveoli.
 Its elimination depends largely on the total
amount of gas that goes through the alveoli =
alveolar ventilation.
 Alveolar ventilation per minute is calculated as:
 Minute alveolar ventilation= (Tidal volume –
Dead space) X Frequency
Gas Exchange during
Assisted Ventilation
(cont.)
 Tidal volume (for a given compliance) is
determined by the pressure gradient
between inspiration and expiration, i.e.
peak inspiratory pressure (PIP) minus
positive end expiratory pressure (PEEP).
Gas Exchange during
Assisted Ventilation
(cont.)
 Inspiratory duration may partially determine the
tidal volume; very short inspiratory time may
not allow pressure to be equilibrated
throughout the respiratory system in infants
with normal lungs and with relatively long time
constants, resulting in decreased tidal volume.
So tidal volume can be decreased by
shortening the inspiratory time.

 Changes in ventilator frequency have a strong


effect on CO2 elimination.
Gas Exchange during
Assisted Ventilation
(cont.)
 Oxygen
 Oxygen exchange depends largely on
the matching of perfusion with ventilation.
 During assisted ventilation, oxygenation
is largely determined by the mean airway
pressure applied.
Gas Exchange during
Assisted Ventilation
(cont.)
 Mean airway pressure is a measure of
the average pressure to which the lungs
are exposed during the respiratory cycle
and may be calculated as:
 Paw = (PIP –PEEP) [Ti/ (Ti +Te)] +
PEEP
 where Ti and Te are inspiratory and
expiratory times respectively
Gas Exchange during
Assisted Ventilation
(cont.)
 Mean airway pressure is affected by
different ventilator parameters shown in
the graph below: (1) Flow rate (2) Peak
inspiratory pressure (PIP) (3) Inspiratory
time (4) Positive end expiratory airway
pressure (PEEP).
Gas Exchange during
Assisted Ventilation
(cont.)
Gas Exchange during
Assisted Ventilation
(cont.)
 Mean airway pressure will be
augmented by
 increasing any of the following:

 Inspiratory flow.
 PIP.
 Ratio of Ti to Te (I/E ratio).
 PEEP.
 Frequency (or rate) by shortening Te.
Gas Exchange during
Assisted Ventilation
(cont.)
 Special notes (cont.)
 Very high Paw may cause over-distention of airways
and alveoli, leading to an increase in dead space and
right-to-left shunting of blood in the lungs.

 Very high Paw can be transmitted to the intrathoracic


structures, causing decreased cardiac output
secondary to decreased venous return and increased
pulmonary vascular resistance. Thus despite
adequate PaO2 and oxygen content, oxygen transport
may decrease.
Types of Mechanical
Ventilators
 Volume-cycled ventilators.
 Pressure-limited, time-cycled,
continuous-flow ventilators .
 Patient–triggered ventilators (PTV ).
Volume-Cycled
Ventilators
 Less frequently used attempting to ventilate
neonates.
 Deliver a fixed volume irrespective of pressure
generated unless pressure limits are set.
 The tidal volume (generally 7-10 ml/kg but 4-7
is usually adequate) delivered to the patient is
obtained by adjusting the flow rate to
determine the time over which it is delivered,
thus determining the I:E ratio.
Volume-Cycled Ventilators
(cont.)
 In patients with RDS showing markedly
diminished compliance, the delivery of a
normal tidal volume requires a very high
PIP.
Pressure-Limited, Time-
Cycled, Continuous-Flow
Ventilators
 Peak inspiratory pressure (pressure-
limited), and inspiratory timing (time-
cycled) are selected.
 Continuous flow of fresh heated
humidified gas is delivered to the patient
throughout the respiratory cycle.
 It allows the infant to make spontaneous
respiratory efforts between ventilator
breaths (Intermittent Mandatory
Ventilation (IMV).
Pressure-Limited, Time-
Cycled, Continuous-Flow
Ventilators (cont.)
 Spontaneously breathing infants who
breathe out of phase with too many IMV
breaths thus fighting the ventilator may
receive inadequate ventilation and are at
an increased risk of air leak.
Patient–Triggered
Ventilators (PTV)
 Modification of conventional ventilation in
which the patient is able to initiate
ventilator breaths.
 There is a detector of thoracoabdominal
movement, airflow, or airway pressure to
indicate the onset of the inspiratory
efforts, and so triggering the ventilator
setting.
Patient–Triggered
Ventilators (PTV) (cont.)
 If the infant does not generate an
adequate inspiratory effort during a
preset period, the ventilator will deliver a
non triggered breath.

 Result in improved tidal volume and


blood gases but may lead to
hyperventilation in tachypneic infants.
Patient–Triggered
Ventilators (PTV) (cont.)
 PTV is used in two modes:
 Synchronized Intermittent Mandatory
Ventilation (SIMV)
 A single triggered breath is given in equal
windows of time, with the other patient
breaths occurring during each window not
assisted.
 This way the rate can be slowly reduced
with all assisted breaths well-synchronized.
Patient–Triggered
Ventilators (PTV) (cont.)
 Assist / Control mode (A/C)
 All breaths are triggered, the patient
controls the ventilator rate, and weaning is
accomplished by reducing the PIP.
 Advantage is reduction in cerebral blood
flow variability.
 Weaning from ventilator is facilitated in both
A/C and SIMV.
 These ventilators reduce the duration of
assisted ventilation and facilitate weaning.
Indications of Mechanical
Ventilation
 Absolute indications
 If any of the following is present:

 Severe hypoxemia with PaO2 less than 50


mmHg despite FiO2 of 0.8.
 Respiratory acidosis with pH of less than 7.20
to 7.25, or PaCO2 above 60 mmHg.
 Severe prolonged apnea.
Indications of Mechanical
Ventilation (cont.)
 Relative indications
 Frequent intermittent apnea
unresponsive to drug therapy.
 Early treatment when use of mechanical
ventilation is anticipated because of
deteriorating gas exchange.
 Relieving work of breathing in an infant
with signs of respiratory difficulty.
 Initiation of exogenous surfactant therapy
Effects of Specific
Interventions on Blood
Gases
 Peak inspiratory pressure (PIP):
 Changes in PIP will determine the pressure gradient
between the onset and end of inspiration and thus
affect alveolar ventilation.
 Increase in PIP will:
 Increase tidal volume.
 Increase CO2 elimination and decrease PaCO2.
 Raise Paw and thus improve oxygenation.
Peak Inspiratory Pressure
(PIP)
 Clinical assessment of chest movement should
be performed before and after changes in PIP.
 High levels of PIP can cause:
 An increased risk of barotraumas with resultant air
leaks.
 An increased risk of bronchopulmonary dysplasia.
 Impaired cardiac function.
 The magnitude of the tidal volume, rather than
that of PIP, correlates best with lung injury.
Positive End-Expiratory
Pressure (PEEP)
 Adequate PEEP will increase PaO2 by:
 Preventing alveolar collapse.
 Maintaining lung volume at the end of
expiration.
 Improving the ventilation-perfusion
relationship
Positive End-Expiratory
Pressure (PEEP- cont.)
 Elevation of PEEP will decrease tidal volume and
consequently increase PaCO2 by:
 Altering the pressure gradient between inspiration
and expiration, and consequently affecting CO2
elimination.
 Use of a PEEP of more than 5-6 cmH2O may
decrease lung compliance, leading to a decrease in
tidal volume and to alveolar hypoventilation, and
consequently causing an increase PaCO2.
Positive End-Expiratory
Pressure (PEEP- cont.)
 For the same magnitude of pressure change,
decrease in PEEP has a larger effect on tidal
volume than increase in PIP.

 Thus a decrease in PEEP should be


considered when CO2 retention occurs,
especially if oxygenation is not a problem.
Positive End-Expiratory
Pressure (PEEP)
 Adequate PEEP will increase PaO2 by:
 Preventing alveolar collapse.
 Maintaining lung volume at the end of
expiration.
 Improving the ventilation-perfusion
relationship
Positive End-Expiratory
Pressure (PEEP- cont.)
 Increase in PEEP will raise Paw and
improve oxygenation, but use of very
high PEEP does not benefit oxygenation
more and can cause:
 Impaired venous return.
 Decreased cardiac output.
 Decreased oxygen transport.
Positive End-Expiratory
Pressure (PEEP- cont.)
 A minimum PEEP of 3 to 4 cmH2O is
recommended because endotracheal
intubation eliminates the active
maintenance of functional residual
capacity done by the infant by vocal cord
adduction.
Frequency (Rate)
 Changes alter alveolar ventilation and thus PaCO2
(decrease PaCO2).
 Use of a moderately high frequency (60 breaths per
minute) allows for a reduction in PIP and leads to about
a 50% decrease in the incidence of pneumothorax in
infants with RDS.
 Most neonates can tolerate high frequencies (60-70
breaths per minute) and short expiratory times without
marked gas trapping as they have short time
constants.
Frequency (Rate) – cont.
 Ventilation with high frequency (> 60 breaths per
minute) may facilitate the synchronization of patient
effort to ventilator rate while reducing ventilator fighting
and the need for sedation or paralysis.
 When high frequency is used in conventional
ventilators, the resultant short Ti may decrease tidal
volume.
 Frequency changes alone, with constant I/E ratio,
usually do not alter Paw, and so do not alter PaO2.
Ratio of Inspiratory to
Expiratory Time
 The major effect of changes in I:E ratio is
on Paw and thus oxygenation.

 Reversed I/E ratios (longer Ti than Te)


may increase PaO2 and may also lead to
an increase in the incidence of
pneumothorax.
Ratio of Inspiratory to
Expiratory Time
 For the same changes in Paw, changes
in I:E ratio do not increase oxygenation
as much as changes in PIP or PEEP.
 Changes in I/E ratio do not usually alter
tidal volume (unless Ti or Te become too
short, and inspiration or expiration
become incomplete), so CO2 elimination
is usually not altered by changes in the
I:E ratio.
Inspiratory and Expiratory
Times
 The effect of changes in Ti and Te largely
depends on the time constants.
 Absolute durations of Ti vary in different
disease processes and depend on the
inspiratory time constant.
 Ti of 1.0 second or longer leads to active
expiration, fighting the ventilator, slower
weaning, and a high incidence of
pneumothorax.
Inspiratory and Expiratory
Times (cont.)
 Prolonged Ti may impede venous return and impair
oxygen transport.
 Inspiratory times shorter than 0.2 to 0.3 seconds can
lead to incomplete inspiration.
 In very short expiratory time (Te), expiration may be
incomplete and gas trapping in the lungs increases,
leading to lung overdistention and decreased
compliance
Inspiratory and Expiratory
Times (cont.)
 Gas trapping will produce inadvertent
PEEP which results in a reduction in the
pressure gradient between inspiration
and expiration, leading to a decrease in
tidal volume and elevation of PaCO2,
and increases the risk of pneumothorax.
Inspired Oxygen
Concentration (FiO2)
 Increase in FiO2 alters alveolar oxygen tension,
provides a larger diffusion gradient, and improves
oxygenation.
 Oxygen and Paw should be balanced to minimize lung
damage.
 During weaning, maintenance of appropriate Paw
allows reduction in FiO2, however Paw should be
reduced before a very low FiO2 is reached. If
distending pressure is not decreased until a low FiO2 is
reached, a high incidence of air leak is observed.
Flow

 Flow rates of 5-10 L/min are sufficient


under most circumstances in neonates.
 Higher inspiratory flows are needed when
Ti is shortened in larger infants to ensure
an adequate pressure rise and delivery of
the desired PIP.
 High flows can lead to turbulence, an
increase in resistance, and gas trapping
Effects of Ventilator
Setting Changes on Blood
Gases Effect
Ventilator setting PaCO2 PaO2
changes
Increase PIP Decrease Increase
Increase PEEP Increase Increase
Increase rate Decrease Increase
Increase I:E ratio -------- Increase
Increase FiO2 ------- Increase
Increase flow Decrease Increase
Starting Ventilator
Setting
 Intubate infant with an endotracheal tube
according to body weight.

 During intubation, infants require


fractional inspired oxygen FiO2 that is
10% higher than what they were
receiving before mechanical ventilation.
Guidelines for
Endotracheal Tube Size
Infant weight(gm) Endotracheal tube
internal diameter
< 1,000gm 2.5mm

1,000 - 2,000 3.0mm

2,000 - 3,000 3.5mm

> 3,000 3.5 - 4.00mm


Initial Setting of
Mechanical Ventilation
 PIP is determined by hearing good breath sounds and
good lung expansion.
 FiO2 is determined according to patient need.
 Ti should not be prolonged because of risk of alveolar
over-distention. Start with 0.25 seconds and do not
exceed 0.5 seconds (unless there are special
indications).
 Respirator rate should not ordinarily exceed 80
breaths/min to allow sufficient time for exhalation.
Initial Setting of
Mechanical Ventilation
(cont.)
Initial settings

Fio2 As indicated
Systemic flow 8-10l/min
Rate 60 breaths / min
Ti/Te 1:1.25 - 1:4
PIP 18 - 22cm H20
Good breath sounds
PEEP 3 - 5cm H20
Subsequent Settings of
Mechanical Ventilation
 Measure arterial blood gases half an
hour after the initial setting and adjust the
setting accordingly. (Table)

 Although it is tempting to try to lower


PaCO2 by increasing the respiratory rate
rather than by adjusting ventilatory
pressure, data suggest that this can not
be without risk.
Subsequent Settings of
Mechanical Ventilation
(cont.)
 This is because as respiratory rate increases, the
absolute time for expiration decreases, and if it
decreases to less than three time constants for
expiration, gas trapping and alveolar over-distension
may occur.
 The entire cardiopulmonary status of the infant must be
kept in mind as vigorous attempts to control PaCO2
may result in worsened lung injury.
Subsequent Settings of
Mechanical Ventilation
(cont.)
 One can allow the PaCO2 to increase to 45- 55 torr or
above in infants with severe respiratory distress.
 Infants with poor pulmonary blood flow because of
hypotension, hypovolemia, cardiac failure, or high
pulmonary vascular resistance may have low PaO2,
and treatment should be directed to improve pulmonary
blood flow, blood pressure and volume, and cardiac
output.
Subsequent Settings of
Mechanical Ventilation
(cont.)
Subsequent PEEP PIP
settings
Low PaO2 , Increase
Low PaCo2
Low PaO2 , Increase
High PaCo2
High PaO2 , Decrease
High PaCo2
High PaO2 , Decrease
Low PaCo2
Monitoring The Infant
during Mechanical
Ventilation
 Obtain an initial blood gas within 15-30
minutes of starting mechanical
ventilation.
 Obtain a blood gas within 15-30 minutes of any
change in ventilator settings.
 Obtain a blood gas every 6 hours unless a
sudden change in the infant's condition occurs.
 Continuous monitoring of the O2 saturation level
as well as the HR and RR is necessary.
Deterioration during
Mechanical Ventilation
 Sudden clinical deterioration
 Mechanical or electrical ventilator failure.
 Disconnected tube or leaking connection.
 Endotracheal tube displacement or
blockage.
 Pneumothorax.
Deterioration during
Mechanical Ventilation
(cont.)
 Gradual deterioration
 Inappropriate ventilator setting.
 Intraventricular hemorrhage.
 Baby fighting against ventilator.
 PDA.
 Anemia.
 Infection.
Paralysis and Sedation
 The use of neuromuscular blockade is not routinely
indicated.

 It has been advocated in infants requiring mechanical


ventilation with a high rate or pressure, and who
become increasingly agitated when their spontaneous
respiration is out of phase with the ventilator, resulting
in decreased effectiveness of mechanical support.
Paralysis and Sedation
(cont.)
 Paralysis may worsen oxygenation in infants with RDS
as it may result in decreased dynamic lung compliance,
increased airway resistance, and the removal of the
infant’s respiratory effort contribution to tidal breathing.

 As a result, it is necessary to increase ventilator


pressure after initiation of neuromuscular blockade.
Paralysis and Sedation
(cont.)
 Sedation is useful when agitation
interferes with ventilatory support and
when infants fight the ventilator.
 Phenobarbital decreases the variability in
mean arterial pressure and intracranial
pressure associated with endotracheal
suctioning.
Weaning
 When the patient is stable, FiO2 and PIP are weaned
first.
 Decrease PIP as tolerated and as chest rise
diminishes.
 When PIP is around 20, attention is directed to FiO2
and then to the respiratory rate alternating with each
other, in response to assessment of chest excursion,
blood gas results, and oxygen saturation.
Weaning (cont.)

 As frequency is decreased, Te should be


prolonged.
 For larger infants, weaning to
endotracheal CPAP may begin when PIP
has been stable between 15-18 cmH2O,
and FiO2 is less than 0.4.
 The infant can be weaned to oxygen
hood when he/she requires less than 4
cmH2O of end expiratory pressure.
Weaning (cont.)
 For infants weighing less than 1,750 gm, when PIP is
less than 15 cmH2O and FiO2 is less than 0.3, start to
decrease the respiratory rate gradually to 15-20
breaths/min and then wean directly to nasal CPAP if
available.

 In most infants, when ventilator frequency of


approximately 15 breaths per minute is tolerated,
endotracheal CPAP may be tried for a short period
before extubation.
Weaning (cont.)
 Atelectasis after extubation is common in preterm
infants recovering from RDS. Use of nasal CPAP may
prevent atelectasis.
 Steroids are not routine before estuation, but if there
was prolonged intubation or previous failed attempts of
extubation, a short course of steroids may facilitate
extubation.
 If strider caused by laryngeal edema develops after
extubation, racemic epinephrine aerosols and steroids
may be helpful.
Physiotherapy and
Suctioning
 Tracheal suctioning and chest physiotherapy should be
minimized in infants with HMD in the first few days after
birth because their secretions are scant.
 Physiotherapy and suctioning should be done to
prevent the development of atelectasis, especially in
premature infants. However, some infants show acute
deterioration of blood gases.
Physiotherapy and
Suctioning (cont.)
 Continuous monitoring of O2 saturation
by pulse oximetry is recommended if
physical therapy is prescribed.

 During suction, the catheter should not


be inserted beyond the lower end of the
endotracheal tube to prevent damage to
airways.
Physiotherapy and
Suctioning (cont.)
 During accompanying bagging (periods of manual
ventilation), FiO2 may be increased by 10% over the
infant’s current requirement.
 A pressure manometer (if available) must be in place
to ensure comparable pressures maintained off-
ventilator.
 It is better to use endotracheal adapters that allow
suctioning without interrupting assisted ventilation.
Complications of
Mechanical Ventilation
 Endotracheal tube complications and
 tracheal lesions
 Accidental displacement of the
endotracheal tube into main stem
bronchus, hypopharynx, or esophagus.
 Accidental extubation.
 Obstruction of endotracheal tube.
Complications of
Mechanical Ventilation
(cont.)
 Airway injury
 Subglottic stenosis.
 Edema of the cords after extubation (may
result in hoarseness and stridor).
 Prolonged use of orotracheal intubation
associated with palatal groove formation.
 Necrotizing tracheobronchitis.
Complications of
Mechanical Ventilation
(cont.)
Infection
Pneumonia and systemic infections with
Staphylococcus epidermidis, Candida
organism, gram-negative organisms, and
Staphylococcus aureus.
Complications of
Mechanical Ventilation
(cont.)
 Chronic lung disease / Oxygen toxicity
 Bronchopulmonary dysplasia (BPD),
related to increased airway pressure and
changes in lung volume.

 Other contributing factors are oxygen


toxicity, anatomic and physiologic
immaturity, and individual susceptibility.
Complications of
Mechanical Ventilation
(cont.)
Air leak
Pneumothorax, pulmonary interstitial
emphysema (PIE), and
pneumomediastinum directly related to
increased airway pressure occurring
frequently at MAP >14 cmH2O.
Complications of
Mechanical Ventilation
(cont.)
 Miscellaneous
 Intraventricular hemorrhage.
 Decreased cardiac output.
 Feeding intolerance

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