Pediatric and Neonatal Mechanical Ventilation

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Prenatal Development

Embryonic and Fetal

Lung Biology Group, Program of Physiology and Experimental Medicine, Hospital for Sick Children Research Institute. Departments of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada Departments of Laboratory Medicine and Pediatrics, University of Toronto, Toronto, ON, Canada e-mail: [email protected].

Branching Morphogenesis

The first, called domain branching, sprouts daughter branches at specific locations along and around the perimeter of the parent branch. In contrast, localized signaling molecules are involved in the direction of the morphogenetic events themselves (mesenchymal invasion, epithelial budding, etc.).

Differentiation of the Conducting Airway

During pregnancy, lung fluid is secreted by the epithelium into the lumen of future airways. Submucosal glands are observable by week 14, while goblet cells containing mucus are identifiable by week 13 in the trachea and large bronchi, extending into the more proximal intrasegmental bronchi by week 24 (Bucher and Reid 1961.

The Establishment

Basal cells in large airways and Clara cells in bronchioles have been described as early as 10 and 16 weeks of gestation, respectively, although the timing of their maturation is speculative and may not fully mature until the mid-canalicular stage (Bucher and Reid 1961; Jeffery 1998; Jeffery and others 1992. Furthermore, it is estimated that airway epithelial turnover occurs every 30–50 days in adults, although the mechanism of this repopulation is not understood (Crystal et al 2008

Development of the Embryonic and Fetal

The Extrapulmonary Vessels In the development of the pulmonary vasculature,
The Intrapulmonary Vessels and Microcirculation

However, the stem or progenitor cells that act as the source of new epithelial cells have not been definitively determined (Crystal et al. 2008. They suggest that previous studies that used VEGFR-2 (rather than phosphorylated VEGFR-2) to indicate angioblasts (and thus vasculogenesis) (Schachtner et al. 2000) reflect uncommitted pluripotent cells.

Postnatal Lung Development

Postnatal Lung Development
The Formation of the Alveoli
The Regulation of Secondary Septation

Growth Factors
Transcription Factors
Retinoic Acid and Glucocorticoids

The Pulmonary Vascular System in Alveolar
Regulation of Postnatal Vascular Growth

TGF-β is also increased in airway secretions of preterm infants with BPD (Kotecha et al. 1996. Similarly, thyroid transcription factor-1 (TTF-1) is expressed in the epithelium of fetal lung buds, but is restricted to Type II cells after birth (Wert et al. 2002.

Generalities

The Neonatal Neuromechanical Unit: Generalities of Operation

Neural Output
Translation of Muscle Contraction into Pulmonary

Step 1. Force Generation
Step 2. Pressure Generation
Step 3. Lung and Chest Wall Mechanics

Mechanical Constraints and Breathing Pattern

Chest Wall Distortion
Low Resting Volume

Feedback Regulation

Vagal Feedback
Extrapulmonary Ventilatory Reﬂexes
Chemical Feedback

Pulmonary Gas Exchange
Alveolar Ventilation and Alveolar PO 2

On the left side, the compliance of the chest wall (Cw) is similar to that of the lungs (CL). Mortola JP, Sant'Ambrogio G (1978) Movement of the rib cage and the abdomen in tetraplegic patients.

Basics of Gas Exchange

Intrapulmonary Shunt
Dead Space
Blood-Gas Equilibrium
Tissue Oxygenation
Metabolic Rate
Interpretation of Arterial and Venous Blood Gases
Physiology of the Upper Airway and Control in

The structure of the alveolar-capillary interface in the lung is suitable for extremely efficient gas exchange. The rightward shift of the oxygen-hemoglobin dissociation curve represents a compensatory response to improve oxygen delivery under conditions of acidemia or hyperthermia.

The Respiratory System

Introduction: Breathing and the Upper Airway

The upper airway extends from the nose or mouth to the throat (Seikel et al. 2005), but its functions in the context of ventilation extend to the entire airway. This chapter discusses how each structure of the upper airway plays a key role in the dynamic processes of breathing.

Nasal Functions in Breathing

Air Conditioning and Vascularity
Nasal Reﬂexes and Protection The nose can sniff out noxious substances and pro-
Nasal Patency and Resistance Nasal breathing in the newborn and infant is the

Nasal obstruction (an extreme example is choanal stenosis) can cause obstructive sleep apnea (OSA) (Marcus 2000). They may have cyanotic episodes, stridor, and hypercapnia; these problems disappear with removal of the nasal lesion (Miller et al. 1987).

Oral Cavity and Pharyngeal Functions in Breathing

Oral Cavity and Pharyngeal Patencies and Obstructive
Sucking, Nutritive Swallowing, and Breathing
Nonnutritive Swallowing, Aspiration, and Swallow

Both this transition to oral breathing and the resumption of nasal breathing after release of the occlusion are delayed by nasal and pharyngeal anesthesia. Postoperative nasal congestion in adults can lead to arterial hypoxemia, apnea, and sleep disturbances, with the latter also occurring in normal volunteers after local anesthesia of the nasal passages (Editorial 1992). Without NNS, “the lungs rapidly fill with these secretions, producing death within days” (Thach 2005).

In summary, patency of the oral cavity and pharynx and coordination with swallowing and inhalation are critical to breathing.

Laryngeal Functions in Breathing and Control

Laryngeal Opening and Closure in Airway Protection and
Laryngeal Intrinsic Muscles and Control in Breathing
Laryngeal and Pump Muscle Breathing Patterns in the

The internal branch of the SLN is sensory, while the external SLN branch is motor to the cricothyroid muscles (right panel) (From O'Connor, D. Reprinted with permission from Myer et al. 1995). The magnitude of abductor activity exceeds that of the adductor muscles as glottic size increases and vice versa, consistent with the relationships between glottic size and flow resistance (Engeland et al. During eupnea, the inspiratory contour of the PCA EMG resembles the flow pattern, while the slope shape of the diaphragm EMG relates to the inspired volume trace (Hutchison et al. 1993).

In the newborn (upper right) the Vr is low compared to that of the adult.

Control of Coordinated Laryngeal and Pump Muscle

Laryngeal Protective, Lower Airway and Chest Wall
Central and Chemical Control Central control of coordinated laryngeal and dia-

In adults, resistive loads applied in the mouth also reduce the expiratory size of the glottis (Brancatisano et al. 1985). In normal adults, voluntary deep inspiration can reduce laryngeal resistance and reduce airway resistance (Sekizawa et al. 1987). This adduction also occurs in adults at the mechanical limits of airway volume (Brancatisano et al. 1983).

In lambs, increased ventilation depends on carotid body input – a sudden decrease in that input triggers expiratory TA activity ( Praud et al. 1992 ).

Mechanics of the Lung, Airways, and the Chest Wall

Background

Passive Tests of Respiratory Mechanics
Dynamic Tests of Respiratory Mechanics

Developmental Considerations

Airway and Lung Development Lung development represents a period of consid-
Sex Differences in Respiratory Mechanics
Periconceptional and Intrauterine Exposures

Mechanical Properties of the Airways, Lung, and Chest Wall

The Airways
The Lungs
The Chest Wall and Respiratory Musculature
Summary

The outward recoil of the chest wall is directly opposed to the inward recoil of the lung. It is important to take the volume dependence into account because ventilation settings can 'push' the pressure-volume curve towards the flattened upper part of the curve (Kano et al. 1994). By simultaneously measuring the transpulmonary pressure and thus the chest wall impedance (Zw), the lung impedance (ZL) can be determined by subtraction.

TLC relationships suggest that increased chest wall stiffness is not fully compensated for by increases in expiratory muscle force over time (Schrader et al. 1988).

Respiratory Mechanics in Neonatal Pathologies

Acute Neonatal Lung Disease The predominant neonatal acute respiratory dis-

Transient Tachypnea of the Newborn
Respiratory Distress Syndrome Like TTN, RDS is predominantly a disease of the
Meconium Aspiration Syndrome
Persistent Pulmonary
Congenital Diaphragmatic Hernia

Chronic Neonatal Lung Disease

Bronchopulmonary Dysplasia BPD is most commonly considered as the chronic
Bronchial Hyperresponsiveness Several studies have evaluated the effect of bron-

Although compliance is also low (increased elasticity), tissue resistance is disproportionately greater, resulting in mechanical disconnection of the parenchyma and increased hysteresivity (ratio of tissue resistance to tissue elasticity) (Pillow et al. 2001a, 2005). Like prenatal steroids, postnatal steroids also increase respiratory system compliance (Durand et al. 1995). In preterm infants, respiratory system compliance (Crs) increases in relation to body weight during the first two years of life, while an initially high respiratory system resistance (Rrs) decreases over the same period (Baraldi et al. 1997a).

Infants with BPD do not show an improvement in airway resistance (Raw, measured by plethysmography) over a 4-month period (Shao et al. 1998).

Respiratory Mechanics in Pediatric Diseases

Restrictive Lung Disease

Restrictive Ventilatory Defect of Pulmonary Origin
Restrictive Defect Arising in the Chest Wall

Obstructive Lung Disease

Childhood Asthma and Wheezing Disorders
Cystic Fibrosis (CF)
Long-Term Sequelae of Neonatal Lung Disease
Obstructive Airway Disease Following Hematopoietic Stem

Neuromuscular Disease (NMD)

A concave shape of the F/V curve can be observed as a result of small airway obstructions (Pellegrino et al. 2005). A decrease in CL could be related to diffuse microatelectase in a few patients (Estenne et al. 1993). Inspiratory muscle strength can easily be assessed by SNIP in children with NMD (Stefanutti et al. 2000).

PImax indicates predominant expiratory muscle weakness, a characteristic of children with type 2 and 3 SMA (Carter et al. 1995).

Introduction
Physiological Effects

Hemodynamic Changes
Respiratory Changes
Neurological Effects

Speciﬁ c Difﬁ culties and Complications

Indications for Intubation
Complications

Recommendations for Clinical Practice

Intubation Route
Premedication Use
Tube Positioning

Introduction

However, unsuccessful intubation is frequent, particularly in the delivery room reaching a rate of 38% in a recent study (O'Donnell et al. 2006. Dempsey EM et al. (2006) Facilitation of neonatal endotracheal intubation with mivacurium and fentanyl in the neonatal intensive care unit Roberts WA et al (1995) Use of capnography for recognition of esophageal intubation in the neonatal intensive care unit.

Stow PJ et al (1988) Anterior fontanel pressure responses to tracheal intubation in the awake and anesthetized child.

Oxygen Supplementation,

Oxygen delivery is a vital component of patient care within pediatric and neonatal intensive care units. Thus, reduced oxygen delivery may result from inadequate cardiac output, low arterial oxygen saturation, insufficient hemoglobin concentration, or low PaO2 as a minor contributor (secondary to the 0.003 factor in the formula described above). In this chapter, we will review the variety of mechanisms by which clinicians can improve the patient's oxygen supply to meet the metabolic demands involved in various pathophysiologic processes.

Delivery, and Physiologic Effects

Oxygen Delivery Systems

Low-Flow Devices

Nasal Cannulae
Simple Face Mask
Venturi Face Mask or Tracheostomy Collar

High-Flow Devices

High-Flow Nasal Cannulae
Non-rebreather Face Masks
Partial Rebreather Face Masks This mask is essentially the same setup as the
Oxyhood
Noninvasive Ventilation (NIV) This mode of ventilation and oxygen delivery can
Oxygen Delivery via Invasive Mechanical Ventilation
Hyperbaric Oxygen

If the gas flow is insufficient, the FiO2, on the other hand, is likely to be variable and inadequate as the patient entrains room air. High-flow devices provide a more reliable concentration of inspired oxygen to the patient regardless of respiratory effort. In the neonatal intensive care unit (NICU), high-flow nasal cannula (HFNC) (>1 L/min for the neonatal population) has been introduced as an alternative to nasal continuous positive airway pressure (NCPAP), which has been the traditional standard of care for infants with respiratory distress syndrome (RDS) or apnea.

This device allows for high-flow oxygen delivery to an enclosed space surrounding the patient's head while allowing easy access for patient care.

Physiologic Effects of Oxygen Breathing

Breathing Control
Pulmonary Vasodilatation
Absorption Atelectasis
Pulmonary Oxygen Toxicity Animal studies have demonstrated that expo-
Non-respiratory Effects of Oxygen

Hemodynamic Effects
Oxygen Consumption
Retinopathy of the Prematurely Born Infant (ROP)

Hyperbaric Oxygen Therapy (HBO)

CO Poisoning
Wound Healing
Air Emboli
Toxicity/Complications

Efferent nerves extend to the diaphragm, intercostal muscles, and accessory muscles of the neck. Thus, gas can diffuse from the alveoli into the blood resulting in rapid alveolar collapse. Oxygen delivery to body tissues and organs can be optimized by supplementing.

Therefore, the retinal vasculature is incomplete and vulnerable in premature infants.

History of NCPAP

Although its use is based on strong physiological principles, more data are still needed on its beneficial short- and long-term effects and on possible complications. In this chapter we describe the main methods of delivering NCPAP that are currently in use. We then discuss the NCPAP studies conducted to date and classify them by level of evidence.

Finally, we will draw some conclusions based on the evidence presented and suggest areas for future investigation.

Nasal CPAP: An Evidence-Based Assessment

Description of NCPAP Devices

Continuous Flow
Variable Flow
Bi-level CPAP
Nasal Intermittent Positive Pressure Ventilation (NIPPV)

Assessing the NCPAP Data

NCPAP Used at Resuscitation
NCPAP Used Early or Prophylactically
NCPAP Used in Conjunction with Exogenous Surfactant
NCPAP for Extubation
NCPAP Used for Apnea

Comparative Studies of NCPAP Devices

Model and Animal Studies

High-ﬂ ow Nasal Cannula
Conclusions and Future Directions

There were no differences in the need for intubation or reintubation between groups (Bober et al. 2013. Liptsen E, Aghai ZH, Pyon KH et al (2005) Breathing during nasal continuous positive airway pressure in preterm infants: a comparison of air bubble vs. devices with variable flow.O'Brien K, Campbell C, Brown L et al (2013) Biphasic nasal continuous positive airway pressure (BP-NCPAP) vs.

Further H, Robertson B, Greisen G et al (1994) Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome.

Mechanical Ventilation

Conventional Mechanical Ventilation

Classiﬁcation of Mechanical Ventilators

Mechanical Ventilators
Continuous-Flow Systems
Variable-Flow Systems
Constant-Flow Systems

Patient–Ventilator Interface

Effects of the Patient Circuit The patient circuit consists of tubing which con-
Apparatus Dead Space
Imposed Work of Breathing and Pressure-Support
Summary

Ventilator Modes

Controlled Ventilation .1 Waveforms

When the ventilator's exhalation valve closes during inspiration, the bias flow is diverted to the patient and the lungs are active. Inappropriate circuit flow can result in rheotrauma (Donn and Sinha 2006), a component of ventilator-induced lung injury (Attar and Donn 2002). Here the inspiration time will be the sum of the inspiration flow time and the inspiration holding time.

During flow cycling, the actual inspiratory time will be less than the set inspiratory time when inﬂation is terminated by the flow change (Prinainak et al. 2003). When the patient starts a spontaneous breath, there is a slight acceleration of the flow in the proximal airway. In the center of the transducer there is a diaphragm which is distorted proportionally to the amount of flow.