Giuseppe A. Marraro, MD
Director
Department of Anesthesia and Intensive Care
Pediatric Intensive Care Unit
Fatebenefratelli and Ophthalmiatric Hospital
Milano Italy

Correspondence: Corso Porta Nuova 23 - I 20121, Milano, Italy. E-Mail gmarraro@picu.it

Technological and cultural advances, and improvement in care which have taken place over the last 5 years have enabled practitioners to review the possible applications of mechanical breathing assistance, broadening its indications for use, improving its applicability and shortening time of application. The aim of artificial ventilation is not only to support deficient vital function and maintain an adequate gas exchange but essentially to resolve the lung pathology, indirectly aid the resolution of collateral pathologies and stall its progression before a need for highly invasive treatment arises or it evolves towards difficult to treat forms (ARDS). The prevalence and severity of childhood asthma have increased substantially in recent years. Despite continued research and the development of new pharmacological agents, it is one of the leading causes for emergency care requirements; one of the leading causes for missed school, and a cause for considerable morbidity, disability, and occasional mortality at all ages.

Applying mechanical ventilatory support, the advantages of which are both generally recognized and accepted, the undesirable side-effects and damage which may ensue must be borne in mind (barotrauma, volutrauma, atelectrauma, biotrauma) and whatever possible must be done to prevent their appearance. It is no longer possible to speak of unspecified respiratory support being given to a patient presenting respiratory failure; the support provided must take into account the patient's age (e.g. bronchiolitis is characteristic of infants and small children), the severity of the pathology, the patients basic clinical condition (e.g. neuromuscular pathology) and the degree of severity of the pathology when ventilatory support is begun (e.g. precocious or delayed approach).

Mechanical ventilation using positive pressure can need airway invasion using an endotracheal tube or, as is being more frequently seen, non-invasion of airways can be performed (use of facial and nasal masks). Spontaneous breathing can be supported (CPAP, Pressure or Volume Support Ventilation) or ventilation can be totally or partially controlled (Volume and Pressure Controlled Ventilation, Synchronized Intermittent Mandatory Ventilation). Each model has precise indications which allow better application on the one hand, while on the other avoid side effects.

By respiratory failure we mean inability of patient to effect adequate gas exchange following loss of ventilating areas, or inability to introduce air and eliminate it from the lungs, leading to necessity to favor gas exchange artificially.

The main issues concerning mechanical ventilation are: when to start, what type to use and how to apply it (1-4).

When?
The following are required to define when to begin treatment:

• Assessment of work of breathing and energy consumption necessary to obtain gas exchange
  
• Child's residual compensation capacity
  
• Forecast lung pathology evolution (e.g. aspiration syndrome vs. chemical pneumonia (Figure 1), chest trauma vs. ARDS, apnea in
    premature babies vs. severe hypo-ventilation and hypoxia, etc.).

Hemo-gas-analysis (HGA) alone cannot justify mechanical ventilation because in certain clinical situations its deterioration occurs in advanced lung pathology, therefore requiring more invasive methodologies, which are subject to greater risk of complications.

Cyanosis is a late sign usually indicating severe or long-standing hypoxemia.

What?
The model used must be chosen with regard to type of respiratory failure, correlated to difficulty of diffusing gases or to insufficient ventilation (non-effective respiratory drive (Figure 2) and efficacy of patient's ventilation (assess whether only spontaneous breathing support or complete mechanical control of ventilation is necessary).

The type of support to apply is to be chosen in relation to the work of breathing which is required of the child, along with his oxygen consumption and compensation possibilities.

How?
Chosen ventilatory strategy must be applied with regard to severity of pathology to be treated, its possible evolution, aim of such treatment, (e.g. avoid chemical pneumonia after aspiration, etc.) and human and technological resources available.

If an ICU is not available, early non-invasive treatment can be suggested so as to reduce need for invasive treatment (intubation and controlled ventilation). Early initiation of treatment has been shown to be the most important factor in improving the final result.

The fundamental objectives for ventilatory support in acutely ill patients may be viewed physiologically and clinically (1, 5-8):

Physiological objectives

• To support or manipulate pulmonary gas exchange
  
• To normalize alveolar ventilation (PaO2, PaCO2 and pH)
  
• To achieve and maintain PaO2 >60 mm Hg and peripheral Sat O2 > 90%.

• To increase lung volume and maintain adequate functional residual capacity (FRC)
  
• To obtain lung expansion and to prevent or treat atelectasis
  
• To improve oxygenation and lung compliance
  
  
• To reduce the work of breathing in presence of high airway resistance and/or reduced compliance, when spontaneous breathing becomes ineffective.

Clinical objectives

• In presence of pathologic lung
Lung pathology may be connected with difficult gas diffusion, particularly concerning alveolar oxygen levels (principally paO2), or with ineffective inhaling and/or exhaling condition, which affect the elimination of CO2 particularly, as well as the acquisition of O2.

Objectives:

• improve lung pathology
  
• reverse hypoxemia, hypercarbia and acute respiratory acidosis
  
• decrease systemic or myocardial oxygen consumption
  
• relieve respiratory distress and reverse ventilatory muscle fatigue
  
• stabilize chest wall in case of rib instability and/or loss of integrity
  

Ventilatory support in cases of lung pathology must:

• prevent appearance of complications connected with artificial supports
  
• avoid appearance of ventilation/perfusion (V/Q) mismatch
  
• prevent or reverse atelectasis-reducing alveolar collapse during expiratory phase and keep alveoli open for as long as possible
        during ventilation.
• In healthy lung
  

Objectives:

• provide adequate gas exchange
  
• permit sedation and/or neuromuscular blockage (e.g. to control seizures or provide general anesthesia)
  
• prevent complications connected with ventilatory support
  
• avoid appearance of atelectasis and ventilation/perfusion (V/Q) mismatch.
  

Mechanical ventilation constitutes the final step in a series of therapeutic man oeuvres of increasing complexity employed in the treatment of respiratory failure. Ventilatory support is indicated in infants and children who cannot breathe adequately without assistance and in those in whom unassisted ventilation will be dangerous or life-threatening.

Advantages:

• Correct ventilation of both lungs and progressive improvement of lung pathology
  
• Improvement of oxygenation and reduction of hypercapnia
  
• Reduction of respiratory fatigue and oxygen consumption
  
• Protection of airways and efficacious bronchosuctioning if tracheal intubation is performed.
  

Absolute indication for intubation and mechanical ventilation are:

• emergency
  
• apnea and severe irregularity of spontaneous breathing
  
• severe respiratory failure
  
• ineffectiveness of oxygen therapy by mask, CPAP or non- invasive ventilation
  

More frequent complications are (9-12):

• reduction of venous return and cardiac output as a consequence of politicization of inhalatory phase. This can be seen mainly in cases of hypovolemia
  
• lung volume and FRC reduction
  
• lung inhomogeneity due to over-expansion of better ventilated areas
  
• small airway closure connected with impossibility to expel secretions and their migration to more declivous and dependent areas (Figure 3a and 3b)
  
• secretion stiffening, loss of ciliary activity and mucus alteration if not well-warmed and humidified gases are used
  
• lung trauma connected with high peak pressure (barotrauma), large volumes (volutrauma) and biological factors (biotrauma) e.g. inflammation
  
• development of infection due to incorrect nursing, insufficient secretion clearance, atelectasis development, etc.
  
• vocal chords and tracheal lesions which can evolve into stenosis if traumatic tracheal intubation is applied - hypoventilation and hypoxia due to technical problems

Use of mechanical ventilation must take the following into account:

1. The underlying physiopathology varies with time and thus mode, settings and intensity of ventilatory support should be frequently
       re-assessed.
2. Mechanical ventilation is associated with a number of adverse consequences and side effects, and as such, measures to minimize
       such complications should be implemented immediately after its application.
3. Alveolar over-distension can cause alveolar damage or air leaks (baro- volutrauma). Hence, man oeuvres to prevent the
       development of excess alveolar (or transpulmonary) pressure should be instituted (protective lung strategies).
4. Dynamic hyperinflation (gas trapping, Auto-PEEP, intrinsic PEEP) often goes unnoticed and should be measured or estimated,
       especially in patients with airway obstruction. Management should be towards limiting the development of dynamic hyperinflation
       and its adverse consequences.

Ventilatory support includes use of artificial breathing devices (ventilator, CPAP system, etc.) and a connector. Prostheses largely used are nasal (Figure 4) and facial masks to perform non-invasive ventilation, and tracheal tubes (Figure 5) for invasive ventilation (13).

Depending on connecting prosthesis, mechanical ventilation is defined:

• non-invasive ventilation when inferior airways are not invaded to introduce external gases into lungs
• invasive ventilation when tracheal intubation or tracheostomy are used to connect patient to ventilator.

Mechanical ventilation can be applied both invasively or non-invasively in the following ways:

1. Assisted spontaneous breathing: Continuous Positive Airway Pressure (CPAP)
   
2. Supported spontaneous breathing: Pressure or volume support in spontaneous breathing: Pressure Support Ventilation and
       Volume Support Ventilation
   
3. Mixed respiratory support: Intermittent Mandatory Ventilation and Synchronized Intermittent Mandatory Ventilation
   
4. Controlled mechanical ventilation: Pressure controlled Ventilation, Volume Controlled Ventilation, Pressure Regulated Volume
        Controlled Ventilation, High Frequency Ventilation
   

1. ASSISTED SPONTANEOUS BREATHING
1.1 Continuous Positive Airway Pressure (CPAP): CPAP is a mode of ventilation, which enables the elevation of end-expiratory pressure to levels above atmospheric pressure to increase total lung volume, and functional residual capacity, thus favoring improved oxygenation (Figure 6) (14-19).

This method presents several advantages because of:

• increased lung volume and FRC and improve in ventilation/perfusion ratio
  
• preventing and resolving atelectasis
  
• reduced work of breathing and prevention of muscle fatigue
  
• Reduced sternum and chest deformities and normalization of respiratory frequency
  

CPAP is indicated in:

• recurrent apnea, not from CNS origin, connected with exhaustion and muscle fatigue
  
• Moderate Idiopathic Respiratory Distress Syndrome of premature baby (RDS), transient tachypnea, pulmonary edema and not     severe pneumonia and bronchopneumonia
  
• Weaning from the ventilator and when reduction of intubation is desired.
  

CPAP is not advisable in:

• high risk patients
  
• apnea prolonged over 20 sec or recurrent, complicated by bradycardia
  
• insufficient spontaneous breathing from different origins
  
• severe respiratory effort to maintain ventilation
  
• hypercapnia (PaCO2 > 50 mm Hg).

2. SUPPORTED SPONTANEOUS BREATHING
Assisted modes of ventilation are those in which part of the breathing pattern is contributed or initiated by the child. The work of breathing performed by the child is never abolished.

2.1 Pressure Support Ventilation (PSV) : Pressure support ventilation (PSV) is designed to support spontaneous breaths during inspiratory phase. It is primarily designed to assist spontaneous breathing and therefore the patient should have an intact respiratory drive (20-22).

The patient triggers each breath by opening the demand valve of the ventilator. A supplementary gas flow is delivered to the inspiratory circuit to produce positive inspiratory pressure at a pre-set value. Cycles are pressure limited and there is no pre-set tidal volume. The patient triggers assisted breathing and regulates respiratory rate, inspiratory and expiratory time and tidal volume.

Advantages:

• minimizes work of breathing
  
• reduces respiratory muscle fatigue and oxygen consumption
  
• hemodynamic stability favored as breathing is triggered spontaneously
  
• can be used to compensate for extra work produced by endotracheal tube and demand valve (23).

Disadvantages
Tidal volume is uncontrolled and variable and depends on respiratory mechanics, cycling frequency and synchrony between patient and ventilator.

• If pressure support is high, the patient tends to reduce his respiratory rate and tidal volume. The risk of baro- and volutrauma is increased    and ventilated gases may not be adequately warmed and   humidified.
  
• If pressure support is low, patient tends to increase respiratory frequency and reduce tidal volume. In   such case oxygen consumption and    work of breathing are increased.
  
• In cases of inhomogeneous lung pathology, PSV tends to favor ventilation of better-aerated areas   without affecting collapsed or atelectatic    areas.
  

PSV needs continuous and careful adaptation of respiratory support to avoid the aforementioned undesirable effects (increased support from health workers).

Indications:

- Intensive care

• Weaning from ventilation after improvement in lung pathology
• Weaning from long term ventilation
• Weaning of patients with chronic obstructive pulmonary disease e.g. infants with severe BPD
• To promote respiratory muscle training
• To compensate for high resistance of endotracheal tubes during CPAP.

- Postoperative care

1. To preserve or reactivate spontaneous breathing
2. 2. To resolve atelectasis after surgery.

Contraindications:

1. Deep sedation and muscle paralysis
2. Severe neurological disorders
3. Hypoventilation syndromes
4. Patients who may be unable to activate trigger demand valve.

2.2 Volume Support Ventilation (VSV) : VSV is a new means of assisting spontaneous breathing which avoids the disadvantages deriving from pressure support ventilation which needs frequent adaptation by medical staff. The ventilator, breath by breath, adapts inspiratory pressure support to changes in the mechanical properties of the lung and the thorax in order to ensure that the lowest possible pressure is used to deliver pre-set tidal and minute volume that remain constant. Inspiratory pressure is constant and flow is decelerated (4, 24, 25).

When the patient is able to ventilate pre-set tidal volume, the ventilator does not support the breath. At this stage, extubation may be performed with safety. In cases of apnea the ventilator automatically switches to PRVC. The initial values for expected tidal and minute volume should be set as should all parameters to be used in PRVC in the presence of apnea ventilation. Indications and contraindications are similar to PSV. The main advantages of VSV vs. PSV is the possibility of maintaining stable tidal volume, being protected should apnea occur and being able to recognize when the patient no longer requires pressure support to ventilate pre-set tidal volumes (extubation can safely be performed).

3. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION - SIMV
SIMV combines a pre-set number of ventilator-delivered mandatory breaths of predetermined tidal volume with the facility for intermittent patient-generated spontaneous breaths. The ventilators on the market offer the possibility of delivering pressure-or volume-targeted breaths during mandatory cycles. Child with SIMV can activate mandatory breaths but if child trigger is not efficacious, ventilator can deliver a mandatory breath. Pressure or Volume Support can be applied during non-mandatory support.

Advantages:

• possibility to maintain spontaneous breathing and avoid muscle atrophy, especially in neuromuscular   patients who rapidly lose ability to    breath spontaneously
  
• progressive reduction of controlled breaths can favor return to complete spontaneous breathing.

The method is difficult to apply in cases of acute and severe lung pathology, in compromised clinical status and in cases of neurological disorders than can interfere with ventilation drive. In these cases children could adapt completely to control breathing furnished from ventilator that could be insufficient to maintain adequate gas exchange (26-29).

4. CONTROLLED MECHANICAL VENTILATION - CMV

This mode of ventilation controls the patient's respiratory activity completely. Introduction of gases into the lung, inspiration, is obtained using positive pressure, which pushes gases into the lung (30). This method is completely different from spontaneous breathing in which introduction of gases into the lung occurs as a result of negative pressure inside the lung. As a consequence, venous return and cardiac output can be reduced.

The expiratory phase is passive and is regulated by the opening of expiratory valve at end of inspiration. This valve is opened when a prefixed pressure or tidal volume is achieved in the lung.

4.1. Constant Pressure Generators (Pressure Controlled Ventilators): The pressure ventilator delivers a volume of gas at constant pressure to the lung during set inspiratory time. Volume received by patient is determined by set inspiratory pressure, respiratory rate and inspiratory time. Pressure remains constant during inspiration, while flow decelerates.

Advantages:

• flow rate is geared to reach Peak Inspiratory Pressure (PIP) as quickly as possible and flow will exceed patient's demand, improving    patient ventilator synchrony and decreasing work of breathing;
  
• using decelerating flow pattern and square-wave pressure pattern; distribution of gas within the lung can be improved.
  

Disadvantages:-

• pressure remains constant while tidal volume will vary, according to changes in compliance and airway resistance
  
• any thorax and diaphragmatic compression reduces tidal volume, which can be insufficient to maintain adequate gas exchange.
  

This mode of ventilation has been proposed to protect the lung from barotrauma but instability of tidal volume and PEEP can create inhomogeneity of lung. Hypoventilation or hyperventilation may occur: e.g. in infants with RDS, with low compliance and normal airway resistance, pressure ventilation may lead to insufficient tidal volume and hypoventilation.

4.2. Constant Flow Generators (Preset Volume Controlled Ventilators): The generator delivers the same preset tidal volume with each breath. During inspiratory time pressure will be slowly increased while flow pattern produces a square wave.

Advantages of volume controlled ventilation:

• supply of constant minute volume
• maintenance of preset tidal volume with variation of compliance and/or pulmonary resistance.

Disadvantages:

• atelectatic areas are not re-ventilated, as they require higher pressure in order to be re
• opened
  - less damaged areas tend to be hyperventilated
• using uncuffed tubes, a large part of preset tidal volume can be lost leading to inadequate ventilation.
  

This ventilatory mode, using small tidal volume and high respiratory frequency to maintain stable minute volume, has been demonstrated to be effective in reducing Ventilation Associated Lung Injury (VALI), morbidity and mortality in ARDS. The best results have been obtained when PEEP levels have been maintained over inferior flex point and lung expansion under superior inflection point of volume/pressure curve (31-33).

4.3 Pressure Regulated Volume Controlled Ventilation –PRVC: PRVC ventilation delivers controlled tidal and minute volume in a pressure-limited manner using lowest possible pressure, kept constant during inspiratory phase. Gas flow is decelerated and pressure and flow constantly vary, breath by breath, in order to achieve pre-set tidal volume at minimum peak inspiratory pressure. The ventilator tests the first breath at 5 cm H2O above PEEP and calculates pressure-volume ratio. Inspiratory pressure changes breath by breath until preset tidal volume is reached at a maximum of 5 cmH2O below set upper pressure limit. At this stage measured tidal volume corresponds to preset value and pressure remains constant. If measured tidal volume increases above preset level, inspiratory pressure is reduced until set tidal volume is reached (34-37).

Advantages of PRVC ventilation

• improvement of respiratory mechanics and gas exchange
  
• reduction of barotrauma connected with Peak Inspiratory Pressure (PIP)
• reduction of oxygen toxicity due to possibility of using reduced FiO2 to maintain adequate gas exchange as compared with
  conventional mechanical ventilation
• opening of closed areas of lung connected with use of decelerated and laminar flow
• immediate reduction of PIP in presence of a rapid change of compliance and resistance as   surfactant, bronchodilators, nitric oxide,
  etc. are used.

Indications:

• when lung compliance and resistance vary rapidly
• If there is an initial requirement of high flow in order to re-open closed pulmonary areas (e.g.   atelectasis, etc.)
• to reduce high ventilatory peak pressure (e.g. in premature infants, interstitial emphysema, etc.)
• to control ventilatory pressures from the moment non-ventilated alveoli and bronchioles are re-  opened (e.g. surfactant, theophylline or nitric oxide administration, etc.)
• in presence of broncho- and bronchiole-spasms (e.g. asthma, bronchiolitis, etc.)
• in all patients in whom PEEP levels must be reduced in order to avoid hemodynamic complications.

Clinical controlled trials are required to evaluate real benefits of PRVC ventilation in acute phase of lung pathology (need of peak pressure to reopen non ventilating areas), in ventilation of healthy lungs (i.e., neurosurgical patients) and during weaning from ventilator.

1. High Frequency Ventilation – HFV: High-frequency ventilation (HFV) has been one of the most studied ventilation techniques, apart from Positive Pressure Ventilation, over the past two decades. Despite its theoretical benefits it has not received unanimous consensus and has not been widely used.

The most fundamental difference between high frequency ventilation (HFV) and intermittent positive pressure ventilation (IPPV) is that with HFV the tidal volume (Vt) required is approximately 1-3 ml/kg body weight, compared with 6-10 ml/kg with intermittent positive pressure ventilation (IPPV). The increase in ventilation rate to frequencies of 60 b.p.m. or more in HFV is obviously mandatory if even comparable minute volume ventilation is to result.

Three models are currently under investigation: High-frequency positive pressure ventilation (HFPPV), high-frequency jet ventilation (HFJV) and high-frequency oscillatory ventilation (HFOV). The first two are no longer used in intensive care therapy due to their poor results in trials compared to conventional mechanical ventilation. HFJV has found an important place in tracheo-bronchial surgery. HFOV is proving highly successful, mainly because adequate equipment capable of solving the problem of humidification of ventilated gases is now available (38, 39).

1.1 High Frequency Oscillatory Ventilation (HFOV): Tidal volume is delivered via normal sized tracheal tubes and both inspiration and expiration are active and of approximately equal power, such as would occur with an oscillating piston or loud speaker-based ventilator. Frequencies range from 2 Hz to more than 100 Hz (6000 c.p.m.). The ventilator is usually a reciprocating pump of the piston variety or a loudspeaker system driven by an electronic oscillator.

There are a number of mechanisms proposed to explain gas exchange in HFOV. Direct alveolar ventilation, asymmetric velocity profiles, Taylor dispersion, pendeluft, cardiogenic mixing, accelerated diffusion and acoustic resonance appear to participate in gas exchanges both individually and/or together.

Theoretical advantages:

• maintaining airways open
• smaller phasic volume and pressure change
• gas exchange at significantly lower airway pressures
• less involvement of cardiovascular system
• less depression of endogenous surfactant production.

HFOV is recommended in order to reduce lung barotrauma and consequent lung injury in non-homogeneous lung pathology, air leaks, Persistent Pulmonary Hypertension of Newborn (PPHN) and ventilation of premature babies.

Contraindications:

• pulmonary obstruction from fresh meconium aspiration
• bronchopulmonary dysplasia
• RSV bronchiolitis
• intracranial hemorrhage.

Complications:

• lung overinflation in obstructive lung diseases
• intracranial hemorrhages - reduction in heart rate attributed to increased vagal activity
• bronchopulmonary dysplasia due to inhomogeneous lung ventilation (Figure 7)
• necrotizing tracheobronchitis, increased permeability of lung epithelium and insufficient humidification of tracheo-bronchial secretions.

While HFOV can maintain adequate gas exchange for prolonged periods in many situations, there is as yet no clearly defined clinical role for this mode of ventilation in pediatric patients. Despite the absence of any clearly defined clinical niche for HFOV, there seems little doubt that it will continue to be used extensively in bench testing and animal experimentation (40, 41).

2. Non-Invasive Positive Pressure Ventilation – NIPPV: The feasibility of applying a ventilatory mode capable of avoiding airway invasion has been evaluated and tested over time. Two modes using different methodologies to attain respiration have had large consensus: 1) Negative Pressure Ventilation by means of either iron lung or chest cuirass (42-44), and 2) Positive Pressure Ventilation in spontaneous breathing, with CPAP, or Non-invasive Positive Pressure Ventilation with mask (45-47). A new ventilatory mode has been recently introduced in clinical practice, which uses biphasic negative and positive external pressure to obtain gas exchange (Figure 8).

Most tested indications:

• to treat neuromuscular and chronic obstructive pulmonary disease
• to reduce respiratory fatigue and rest respiratory muscles
• home assistance.

General criteria for NPPV application in pediatric age:

• Moderate or severe dyspnea
• Use of accessory muscles and paradoxical abdominal respiration
• Severe deterioration of gas exchange with PaCO2 >45 and/or pH < 7.35 or PaO2/FiO2 < 300.

Eligibility criteria:

• awake and collaborative child
• hemodynamic stability
• no abundant secretions
• presence of airway protective reflexes
• absence of facial trauma or anatomical malformation
• no gastrointestinal bleeding.

Exclusion criteria (48) :

• unconsciousness, not collaborating or agitated patient
• respiratory arrest
• hemodynamic instability (hypotension, arrhythmia, etc.)
• insufficient protection of airways (lack of cough, abundant secretions)
• airway obstruction
• vomiting
• trauma, burns and face malformation.

There is high evidence-based efficacy in treatment of chronic lung disease, in cardiogenic pulmonary edema, immunocompromised patients, difficult weaning from ventilator and restrictive lung pathology.

There is moderate evidence-based efficacy in cystic fibrosis, asthma, postoperative respiratory failure and “do not intubate” patients. Extubation failure, ARDS and pneumonia have shown evidence-based efficacy.

Indispensable factors resulting in NPPV efficacy:

1. Patient selection
2. Early treatment
3. Comfortable ventilator-patient interface
4. Psychological patient support
5. Continuous monitoring
6. Skilled and motivated team.

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Marraro G A.Practical Guidelines for Mechanical Ventilation.Pediatric Oncall [serial online] 2005 [cited 2005 January 1];2. Available from:
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PEDIATRIC_EMERGENCIES/mechanical_ventilation.asp