eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Assisted Ventilation of the Newborn

Author: Massimo Bellettato, MD, Director, Neonatal and Paediatric Units, Thiene's Hospital, Italy
Coauthor(s): Wally Carlo, MD, Director, Professor, Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham
Contributor Information and Disclosures

Updated: Mar 19, 2008

Introduction

Hypercapnia is usually caused by severe ventilation/perfusion (V/Q) mismatch or hypoventilation. A substantial proportion of the increased survival rate of preterm infants during the last 30-40 years has been due to the availability of improved ventilatory support.

The primary objective of assisted ventilation is to support breathing until the patient's respiratory efforts are sufficient. Ventilation may be required during immediate care of the infant who is depressed or apneic or during prolonged periods of respiratory failure treatment. Improved survival rates due to advances in neonatal care have resulted in an increased number of infants at risk for chronic lung disease. Although the etiology of lung injury is multifactorial, animal and clinical data indicate that lung injury is affected, in large part, by the ventilatory strategies used. Optimal ventilatory strategies provide the best possible gas exchange, with minimal or no lung injury or other adverse effects.

This article highlights the concepts of pulmonary mechanics, gas exchange, respiration control, and lung injury that can be used to optimize conventional mechanical ventilation (CMV) in order to optimize survival and to minimize adverse effects.

Gas Exchange

Newborns are vulnerable to impaired gas exchange because of their high metabolic rate, propensity for decreased functional residual capacity (FRC), decreased lung compliance, increased resistance, and potential for right-to-left shunts through the ductus arteriosus, foramen ovale, or both. Thus, impaired gas exchange is common in newborns. Hypercapnia and hypoxemia may coexist, although some disorders may affect gas exchange differentially.

Hypercapnia

Optimal V/Q matching occurs when the ratio of the volume of gas to the volume of blood into the lungs approximates 1. Pulmonary venoarterial shunts and alveolar hypoventilation result in V/Q mismatch, which is probably the most important mechanism of gas exchange impairment in infants with respiratory failure due to various causes, including respiratory distress syndrome (RDS). Hypoventilation is frequently seen in infants with apnea of prematurity.

The effect of assisted ventilation on hypercapnia strongly depends on the mechanism of gas exchange impairment. Hypercapnia secondary to severe V/Q mismatch may be treatable with CMV or could require high-frequency ventilation (HFV). Hypercapnia secondary to hypoventilation is usually easily managed with CMV. CO₂ normally diffuses readily from the blood into the alveoli. Elimination of CO₂ from the alveoli is directly proportional to alveolar minute ventilation (see Media file 1), which is determined by the product of tidal volume (minus dead-space ventilation) and frequency. Thus, the alveolar minute ventilation is calculated as follows:

Alveolar Minute Ventilation = (Tidal Volume - Dead Space) X Frequency

Tidal volume is the volume of gas inhaled (or exhaled) with each breath. Frequency is the number of breaths per minute. Dead space is the part of the tidal volume not involved in gas exchange, such as the volume of the conducting airways, and is relatively constant. Thus, increases in either tidal volume or frequency increase alveolar ventilation and decrease the arterial partial pressure of carbon dioxide (PaCO₂).

Because dead-space ventilation is constant, changes in tidal volume appear more effective than frequency changes in altering CO₂ elimination. For example, a 50% increase in tidal volume (ie, 6-9 mL/kg) with a constant dead space (ie, 3 mL/kg) doubles alveolar ventilation (3-6 mL/kg X frequency). In contrast, a 50% increase in frequency increases alveolar ventilation by 50% because dead-space ventilation (dead space X frequency) increases when frequency is increased.

Although increases in minute ventilation achieved via larger tidal volumes are more effective in increasing alveolar ventilation, the use of relatively small tidal volumes and high frequencies is usually preferred to minimize volutrauma.

Hypoxemia

Hypoxemia is usually the result of V/Q mismatch or right-to-left shunting, although diffusion abnormalities and hypoventilation (eg, apnea) may also decrease oxygenation. V/Q mismatch is a major cause of hypoxemia in infants with RDS and other causes of respiratory failure. V/Q mismatch is usually caused by poor ventilation of alveoli relative to their perfusion. Shunting can be intracardiac (eg, congenital cyanotic heart disease), extracardiac (eg, pulmonary or via a patent ductus arteriosus), or both. Diffusion abnormalities typical of interstitial lung disease and other diseases that affect the alveolar-capillary interface are not major mechanisms of severe hypoxemia in neonates. Hypoventilation usually causes mild hypoxemia unless severe hypercapnia develops.

During conventional ventilation, oxygenation is largely determined by the fraction of inspired oxygen (FiO₂) and the mean airway pressure (MAP) (see Media file 2). MAP is the average airway pressure during the respiratory cycle and can be calculated by dividing the area under the airway pressure curve by the duration of the cycle. The formula includes the constant determined by the flow rate and the rate of rise of the airway pressure curve (K), peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), inspiratory time (T_I), and expiratory time (T_E), as follows:

Open table in new window

[ CLOSE WINDOW ]

Table

MAP = K (PIP – PEEP)

TI -------- TI + TE

+ PEEP

MAP = K (PIP – PEEP)

TI -------- TI + TE

+ PEEP

This equation indicates that MAP increases with increasing PIP, PEEP, T_I to T_I + T_E ratio, and flow (increases K by creating a more square waveform).

The mechanism by which increases in MAP generally improve oxygenation appears to be the increased lung volume and improved V/Q matching. Although a direct relationship between MAP and oxygenation is observed, some exceptions are found. For the same change in MAP, increases in PIP and PEEP enhance oxygenation more than changes in the ratio of T_I to T_E (I/E ratio). Increases in PEEP are not as effective once optimal inflation is reached and may not improve oxygenation at all. In fact, an excessive MAP may cause overdistention of alveoli, leading to air trapping and right-to-left shunting of blood in the lungs.

If a very high MAP is transmitted to the intrathoracic structures, which may occur when lung compliance is near normal, cardiac output may decrease; thus, even with adequate oxygenation of blood, systemic oxygen transport (arterial oxygen content X cardiac output) may decrease.

Unlike other causes of hypoxemia, shunting is usually unresponsive to oxygen supplementation. Hypoxemia due to V/Q mismatch can be difficult to manage but may be resolved if an increase in airway pressure reexpands atelectatic alveoli. Hypoxemia due to impaired diffusion or hypoventilation usually responds to oxygen supplementation and assisted ventilation.

Blood oxygen content largely depends on oxygen saturation and hemoglobin level. Thus, transfusing packed RBCs to infants with anemia (hemoglobin, <7-10 mg/dL) who are receiving assisted ventilation is common practice. Oxygen delivery also depends on oxygen unloading at the tissue level, which is strongly determined by the oxygen dissociation curve. Acidosis, increases in 2,3-diphosphoglycerate, and adult hemoglobin levels reduce oxygen affinity to hemoglobin and, thus, favor oxygen delivery to the tissues.

Pulmonary Mechanics

Interaction between the ventilator and the infant largely depends on the mechanical properties of the respiratory system.

Pressure gradient

A pressure gradient between the airway opening and the alveoli must be present to drive the flow of gases during both inspiration and expiration. The necessary pressure gradient can be calculated from the following equation:

Pressure = Volume Compliance + Resistance X Flow

Compliance

Compliance describes the elasticity or distensibility of the respiratory structures (eg, alveoli, chest wall, pulmonary parenchyma) and is calculated from the change in volume per unit change in pressure as follows:

Compliance = ΔVolume/ΔPressure

Therefore, the higher the compliance, the larger the delivered volume per unit changes in pressure. Normally, the chest wall is compliant in newborns and does not impose a substantial elastic load compared to the lungs. The range of total respiratory system compliance (lungs + chest wall) in newborns with healthy lungs is 0.003-0.006 L/cm H₂ O, whereas compliance in babies with RDS may be as low as 0.0005-0.001 L/cm H₂ O.

Resistance

Resistance describes the inherent capacity of the air conducting system (eg, airways, endotracheal tube [ETT]) and tissues to oppose airflow. It is expressed as the change in pressure per unit change in flow as follows:

Resistance = ΔPressure/ΔFlow

Airway resistance depends on (1) radii of the airways (total cross-sectional area), (2) length of airways, (3) flow rate, and (4) density and viscosity of gas. Unless bronchospasm, mucosal edema, or interstitial edema decrease their lumina, distal airways normally contribute less than proximal airways to airway resistance because of their larger cross-sectional area. Small ETTs that may contribute significantly to airway resistance are also important, especially when high flow rates that may lead to turbulent flow are used. The range of values for total airway plus tissue respiratory resistance for healthy newborns is 20-40 cm H₂ O/L/s; in intubated newborns this range is 50-150 cm H₂ O/L/s.

Time constant

Compliance and resistance can be used to describe the time necessary for an instantaneous or step change in airway pressure to equilibrate throughout the lungs. The time constant of the respiratory system is a measure of the time necessary for the alveolar pressure to reach 63% of the change in airway pressure, which can be calculated as follows:

Time Constant = Resistance X Compliance

Thus, the time constant of the respiratory system is proportional to the compliance and the resistance.

For example, the lungs of a healthy newborn with a compliance of 0.004 L/cm H₂ O and a resistance of 30 cm H₂ O/L/s have a time constant of 0.12 seconds. When a longer time is allowed for equilibration, a higher percentage of airway pressure equilibrates throughout the lungs. The longer the duration of the inspiratory (or expiratory) time allowed for equilibration, the higher the percentage of equilibration.

For practical purposes, delivery of pressure and volume is complete (95-99%) after 3-5 time constants. The resulting time constant of 0.12 seconds indicates a need for an inspiratory or expiratory phase of 0.36-0.6 seconds. In contrast, lungs with decreased compliance (eg, in RDS) have shorter time constants. Lungs with shorter time constants complete inflation and deflation faster than normal lungs.

The clinical application of the concept of time constant is clear: Very short inspiratory times may lead to incomplete delivery of tidal volume, resulting in lower PIP and MAP and leading to hypercapnia and hypoxemia (see Media file 3). Similarly, insufficient expiratory time may lead to increases in FRC and inadvertent PEEP, which is evidence of gas trapping.

Gas trapping

A short expiratory time, a prolonged time constant, or an elevated tidal volume can result in gas trapping. Gas trapping may decrease compliance and impair cardiac output. Gas trapping during mechanical ventilation may manifest as decreased tidal volume, CO₂ retention, and/or lung hyperexpansion. Although PaO₂ may be adequate during gas trapping, venous return to the heart and cardiac output may be impaired; thus, oxygen delivery can be decreased.

Clinical situations that may suggest the presence of gas trapping include the following: (1) use of a short expiratory time (eg, high ventilatory rates), (2) a prolonged time constant (eg, high resistance), (3) lung overexpansion on radiography, (4) decreased thoracic movement despite high PIP, and (5) impaired cardiovascular function (ie, increased central venous pressure, decreased systemic blood pressure, metabolic acidosis, peripheral edema, decreased urinary output). Values of compliance and resistance differ throughout inspiration and expiration; thus, a single time constant cannot be assumed. Furthermore, with heterogeneous lung diseases such as bronchopulmonary dysplasia (BPD), different lung regions may have different time constants because of varying compliances and resistances, partly accounting for coexistence of atelectasis and hyperexpansion.

Chest wall motion

A technique to estimate time constant that may be helpful in everyday clinical practice is the use of chest wall motion as a semiquantitative estimate of tidal volume. At the bedside, chest wall motion can be measured with appropriately placed heart rate/respiration leads used for routine clinical monitoring (see Media file 4). Careful visual assessment of chest wall motion can also suffice. The shape of the inspiratory and expiratory phases can be analyzed. A rapid rise in inspiratory chest wall motion (or volume) with a plateau indicates complete inspiration. A rise without a plateau indicates incomplete inspiration. In this situation, prolongation of the inspiratory time results in more inspiratory chest wall motion and tidal volume delivery. Inspiratory plateau indicates that inspiratory time may be too long; shortening inspiratory time does not decrease inspiratory chest wall motion or tidal volume delivery and does not eliminate the plateau.

A short expiratory time leads to gas trapping. If gas trapping results from a short expiratory time, lengthening expiration improves ventilation. However, a very prolonged expiratory time does not improve ventilation. Indeed, in the absence of gas trapping, shortening expiratory time allows for more breaths to be provided per minute, which improves ventilation.

Control of Breathing

Important physiologic aspects of control of breathing need to be considered in order to better understand the interaction between the ventilator and the baby's respiratory system. The respiratory drive is servocontrolled by the brain. This serves to minimize variations in arterial blood gases and pH despite physiologic changes in the efficiency of gas exchange and moment-to-moment differences in oxygen consumption and CO₂ production.

Ventilation is maintained by intrinsic fine adjustments in tidal volume and respiratory rate that minimize the work of breathing. This fine adjustment is accomplished by motor neurons in the CNS that receive input largely from the chemoreceptors and mechanoreceptors to regulate inspiratory and expiratory muscles. These 2 components of respiratory control provide feedback to the brain to continuously adjust ventilation. Mechanical ventilation results in changes in chemoreceptor and mechanoreceptor stimulation.

Chemoreceptors

When PaCO₂ changes, ventilation is largely adjusted by the activity of chemoreceptors in the brain stem. An increase in PaCO₂ increases respiratory drive. Because the chemoreceptors most likely sense the hydrogen ion concentration, metabolic acidosis and metabolic alkalosis have strong effects on respiratory drive that are somewhat independent of PaCO₂ values. Most changes in ventilation and respiratory drive produced by PaO₂ changes depend on the peripheral chemoreceptors, which include the carotid bodies and, to a lesser extent, the aortic bodies. In newborns, acute hypoxia produces a transient increase in ventilation that disappears quickly. Moderate or profound respiratory depression can be observed after a couple of minutes of hypoxia, and this decline in respiratory drive is an important cause of hypoventilation, apnea, or both.

Mechanoreceptors

Particularly during neonatal life and infancy, considering the role of mechanoreceptors in the regulation of breathing is also important. Stretch receptors in airway smooth muscles respond to tidal volume changes. For example, immediately following inflation, a brief period of decreased or absent respiratory effort can be detected. This is called the Hering-Breuer inflation reflex; it is usually observed in newborns during conventional ventilation, when a large-enough tidal volume is delivered.

The presence of the Hering-Breuer inflation reflex is a clinical indication that a relatively good tidal volume is delivered, and the reflex is absent if the ventilator tidal volume is very small (eg, if the ETT becomes plugged). The Hering-Breuer reflex is also time related (eg, a longer inspiration tends to stimulate the reflex more). Thus, for the same tidal volume, a breath with a longer inspiratory time elicits a stronger Hering-Breuer reflex and a longer respiratory pause.

At slow ventilator rates, large tidal volumes stimulate augmented inspirations (head paradoxic reflex). This reflex demonstrates improved lung compliance, and its occurrence is increased by methylxanthine administration. This reflex may be one of the mechanisms through which methylxanthines facilitate weaning from mechanical ventilation.

Mechanoreceptors also are altered by changes in FRC. An increase in FRC leads to a longer expiratory time because the next inspiratory effort is delayed. High continuous distending pressure (continuous positive airway pressure [CPAP] or PEEP) can prolong expiratory time and even decrease the respiratory rate because of the intercostal phrenic inhibitory and Hering-Breuer reflexes. Remember that during weaning from a ventilator, a high PEEP may decrease the spontaneous respiratory rate.

Other components of the mechanoreceptor system are the juxtamedullary (J) receptors. These receptors are located in the interstitium of the alveolar wall and are stimulated by interstitial edema and fibrosis as well as by pulmonary capillary engorgement (eg, congestive heart failure). Stimulation of the J receptors increases respiratory rate and may explain the rapid shallow breathing frequently observed in patients with these conditions. Another reflex that affects breathing is the baroreflex. Arterial hypertension can lead to reflex hypoventilation, apnea, or both through aortic and carotid sinus baroceptors. Conversely, a decrease in blood pressure may result in hyperventilation.

Ventilatory Strategies

Continuous positive airway pressure

CPAP has been an important tool in the treatment of newborns with RDS. The mechanisms by which CPAP produces its beneficial effects include increased alveolar volumes, alveolar recruitment and stability, and redistribution of lung water (see below), resulting in an improvement in V/Q matching. However, high CPAP levels may lead to adverse effects (see below).

The use of CPAP instead of assisted ventilation may be a strategy to minimize ventilator-associated lung injury. Several retrospective studies suggest that the decreased need for ventilator support with the use of CPAP may allow lung inflation to be maintained but may prevent volutrauma due to alveolar overdistention, atelectasis, or both. However, 3 multicenter randomized controlled trials that include a total of 459 preterm infants report that prophylactic CPAP does not decrease the incidence or severity of RDS or its complications.¹

Once the diagnosis of RDS is established, the administration of CPAP decreases oxygen requirements, decreases the need for mechanical ventilation, and may reduce mortality. However, the incidence of air leaks is increased among infants who receive CPAP. Optimal time to start CPAP may depend on the severity of RDS. Early CPAP (ie, when PaO2 is approximately <50 mm Hg on a FiO₂ of 0.40 or more) decreases the subsequent need for mechanical ventilation and duration of ventilatory assistance in newborns with RDS.

Initiate CPAP in newborns with RDS when PaO₂ is approximately less than 50 mm Hg on a FiO₂ of 0.40 or more. Studies performed to determine whether CPAP facilitates successful extubation have not demonstrated consistent results. CPAP and nasal intermittent mandatory ventilation (compared with nasal CPAP) reduce extubation failure in small trials and can be an alternative to reintubation.

An effective and maybe less injurious way to recruit the lung in very premature neonates at birth may be a combination of a sustained inflation and early CPAP. This attempt to avoid intubation and mechanical ventilation may reduce lung injury and BPD in preterm infants. Sustained inflation and early nasal CPAP at birth seems justified in extremely preterm infants at risk for RDS, providing early surfactant rescue is given if required.

Conventional mechanical ventilation

A complex interrelationship among the ventilator, the blood gas values, the mechanical characteristics of the respiratory system, and the infant's spontaneous respiratory efforts is observed. Although attention is often focused on the effect of ventilator setting changes on blood gases, the ventilator changes may alter the pulmonary mechanics either acutely (eg, changes in PEEP affect compliance) or chronically (by predisposing to lung injury). Ventilator changes may also affect spontaneous breathing (eg, high PEEP decreases respiratory rate). An understanding of the basic pathophysiology of the underlying respiratory disorder is essential to optimize the ventilatory strategy. Aim for an adequate gas exchange without injuring the lungs; the ultimate goal is a healthy child without chronic lung disease.

A review of the major ventilatory parameters, which can be adjusted on pressure-limited time-cycled ventilators (ie, the most common type of ventilators used for CMV), is useful. These concepts are also applicable to volume ventilators.

Peak inspiratory pressure

Changes in PIP affect both PaO₂ (by altering MAP) and PaCO₂ (by its effects on tidal volume and thus, alveolar ventilation). Therefore, an increase in PIP improves oxygenation and decreases PaCO₂. Use of a high PIP may increase the risk of volutrauma with resultant air leaks and BPD; thus, exercise caution when using high levels of PIP. The level of PIP required in an infant depends largely on the compliance of the respiratory system.

A useful clinical indicator of adequate PIP is gentle chest rise with every breath, which should not be much more than the chest expansion with spontaneous breathing. Although absent breath sounds may indicate inadequate PIP (or a blocked and/or displaced ETT or even ventilator malfunction), the presence of breath sounds is not very helpful in determining optimal PIP. Adventitious sounds, such as crackles, often indicate disorders of lung parenchyma associated with poor compliance (requiring higher PIP), whereas wheezes often indicate increased resistance (affecting the time constant).

Always use the minimum effective PIP. Frequently change PIP in the presence of changing pulmonary mechanics, such as after the administration of surfactant in the management of RDS. Babies with chronic lung disease often have nonhomogeneous lung disease, leading to varying compliance throughout different regions of the lung and, therefore, differing requirements for PIP. This partially accounts for the coexistence of atelectasis and hyperinflation in the same lung.

Positive end-expiratory pressure

Adequate PEEP helps to prevent alveolar collapse, maintains lung volume at end-expiration, and improves V/Q matching. Increases in PEEP usually increase oxygenation associated with increases in MAP. However, in infants with RDS, an excessive PEEP may not further improve oxygenation and, in fact, may decrease venous return, cardiac output, and oxygen transport. High levels of PEEP also may decrease pulmonary perfusion by increasing pulmonary vascular resistance. By reducing d (amplitude) pressure (PIP minus PEEP), an elevation of PEEP may decrease tidal volume and increase PaCO₂.

Although both PIP and PEEP increase MAP and may improve oxygenation, they usually have opposite effects on PaCO₂. Generally, older infants with chronic lung disease tolerate higher levels of PEEP without carbon dioxide retention and with improvements in oxygenation. PEEP also has a variable effect on lung compliance and may affect the PIP required. With RDS, compliance improves with low levels of PEEP, followed by declining compliance at higher levels of PEEP. A minimum PEEP of 4-5 cm H₂ 0 is recommended, since endotracheal intubation eliminates the active maintenance of FRC accomplished with vocal cord adduction and closure of the glottis.

Rate

Changes in frequency alter alveolar minute ventilation and, thus, PaCO₂. Increases in rate and, therefore, increases in alveolar minute ventilation, decrease PaCO₂ proportionally; decreases in rate increase PaCO₂. Frequency changes alone (with a constant I/E ratio) usually do not alter MAP or substantially affect PaO₂. Any changes in inspiratory time that accompany frequency adjustments may change the airway pressure waveform and, thus, alter MAP and oxygenation.

Generally, a high-rate, low-tidal volume strategy is preferred (see below). However, if a very short expiratory time is employed, expiration may be incomplete. The gas trapped in the lungs can increase FRC, decreasing lung compliance. Tidal volume decreases as inspiratory time is reduced beyond a critical level, depending on the time constant of the respiratory system. Thus, above a certain ventilator rate during pressure-limited ventilation, minute ventilation is not a linear function of frequency. Alveolar ventilation actually may fall with higher ventilatory rates as tidal volumes decrease and approach the volume of the anatomic dead space.

Inspiratory and expiratory times

The effects of changes in inspiratory and expiratory times on gas exchange are influenced strongly by the relationships of these times to the inspiratory and expiratory time constants, respectively. An inspiratory time 3-5 times longer than the time constant of the respiratory system allows relatively complete inspiration. A long inspiratory time increases the risk of pneumothorax. Shortening inspiratory time is advantageous during weaning (see below). In a randomized trial, limitation of T_I to 0.5 second, rather than 1 second, resulted in significantly shorter duration of weaning. In contrast, patients with chronic lung disease may have a prolonged time constant. In these patients, a longer inspiratory time (near 0.8 s) may result in improved tidal volume and better carbon dioxide elimination.

Inspiratory-to-expiratory ratio

The major effect of an increase in the I/E ratio is to increase MAP and thus improve oxygenation (see below). However, when corrected for MAP, changes in the I/E ratio are not as effective in increasing oxygenation as are changes in PIP or PEEP. A reversed (inverse) I/E ratio (inspiratory time longer than expiratory time) as high as 4:1 has been demonstrated to be effective in increasing PaO₂; however, adverse effects may occur (see below).

Although a decreased incidence of BPD with the use of reversed I/E ratios may be possible, a large, well-controlled, randomized trial revealed only reductions in the duration of a high inspired oxygen concentration and PEEP exposure with reversed I/E ratios, with no differences in morbidity or mortality. Changes in the I/E ratio usually do not alter tidal volume, unless inspiratory and expiratory times become relatively too short. Thus, carbon dioxide elimination is usually not altered by changes in I/E ratio.

Fraction of inspired oxygen

Changes in FiO₂ alter alveolar oxygen pressure and, thus, oxygenation. Because FiO₂ and MAP both determine oxygenation, they can be balanced as follows:

• During increasing support, first increase FiO₂ until approximately 0.6-0.7, when additional increases in MAP are warranted.
• During weaning, first decrease FiO₂ (to approximately 0.4-0.7) before reducing MAP, because maintenance of an appropriate MAP may allow a substantial reduction in FiO₂.

Reduce MAP before a very low FiO₂ is reached, because a higher incidence of air leaks has been observed if distending pressures are not weaned earlier.

Flow

Although not well studied in infants, changes in flow probably impact arterial blood gases minimally as long as a sufficient flow is used. Flows of 5-12 L/min are sufficient in most newborns, depending on the mechanical ventilator and ETT being used. To maintain an adequate tidal volume, high flows are needed when inspiratory time is shortened.

Pathophysiology-Based Ventilatory Strategies

Respiratory distress syndrome

RDS is characterized by low compliance and low FRC. An optimal conventional ventilation strategy may include conservative indications for conventional ventilation, the lowest PIP and tidal volume required, modest PEEP (4-5 cm H₂ 0), permissive hypercapnia (PaCO₂ 45-60 mm Hg), judicious use of sedation/paralysis, and aggressive weaning.

Chronic lung disease

BPD usually has heterogeneous time constants among lung areas. Resistance may be increased markedly, and frequent exacerbations may occur. A higher PEEP (4-6 cm H₂ 0) is often used, and longer inspiratory and expiratory times with low rates are preferred. Hypercarbia with compensated respiratory acidosis often is tolerated to avoid lung injury secondary to aggressive mechanical ventilation.

Persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn may be primary or associated with aspiration syndrome, prolonged intrauterine hypoxia, congenital diaphragmatic hernia, or other causes. Ventilatory treatment of infants often is controversial and widely varies among centers. In general, adjust FiO₂ to maintain PaO₂ at 80-100 mm Hg to minimize hypoxia-mediated pulmonary vasoconstriction; adjust ventilatory rates and pressures to maintain an arterial pH of 7.45-7.55 (sometimes combined with bicarbonate infusion). Take care to prevent extremely low PaCO₂ (<30 mm Hg), which can cause cerebral vasoconstriction and subsequent neurologic injury. Addition of inhaled nitric oxide to mechanical ventilation reduces the need for extracorporeal membrane oxygenation.

Strategies to Prevent Lung Injury

Emphasis is being placed on evidence that suggests lung injury partially depends on the particular ventilatory strategies used. Ventilator-associated lung injury has traditionally been believed to result from the use of high pressures (hence the term barotrauma). However, recent laboratory-based and clinical research has raised questions about this purported mechanism.

Experimentally, investigators have used high and low volumes and pressures in an attempt to determine if volume or pressure is the major culprit responsible for lung injury in the immature animal. These studies consistently demonstrate that markers of lung injury (pulmonary edema, epithelial injury, hyaline membrane formation) are present with the use of high volumes and low pressures but not with the use of low volumes and high pressures. Thus, many investigators and clinicians prefer the term volutrauma to the more classic term barotrauma.

Lung injury is also caused by repeated collapse (atelectasis) and reopening of the alveoli, which occurs with very low-end expiratory pressures. The heterogeneity of lung tissue involvement in many respiratory diseases predisposes some parts of the lung to volutrauma. Oxidant injury may be another serious cause of lung injury. Immature and developing lungs are particularly susceptible to acquired injury. 

The increased risk of impaired cerebral blood flow autoregulation and intracranial hemorrhage in neonates with hypercapnia is concerning. However, hypercapnic acidosis increases cerebral oxygen delivery, and the CO ₂ -induced alterations in cerebral blood flow appear to be reversible. A retrospective study of 849 infants who weighted 1,250 g or less revealed that severe hypocapnia, severe hypercapnia, and wide fluctuations in PaCO ₂ were associated with increased risk of hemorrhage.² The randomized, controlled trials of permissive hypercapnia in neonates have not reported an increase in intracranial hemorrhage.³

Hypercapnia may play a role in the development of retinopathy of prematurity (ROP) through retinal vessel vasodilation, increased oxygenation, and subsequent formation of oxygen-derived free radicals. However, the randomized trials in neonates that tested for the presence of ROP or long-term visual outcomes reported no difference in the control group compared with the hypercapnia groups.⁴

Permissive hypercapnia

Permissive hypercapnia, or controlled mechanical hypoventilation, is a strategy for the treatment of patients receiving ventilatory assistance (see below). When using this strategy, prioritize the prevention or limitation of overventilation rather than maintenance of normal blood gases and the high alveolar ventilation that is frequently used. Respiratory acidosis and alveolar hypoventilation may be an acceptable price for the prevention of pulmonary volutrauma. Experimental data show that therapeutic hypercapnia reduces lung and brain injury and attenuates hypoxic brain injury in newborn rats.⁵ In preterm lambs, hypercapnia is associated with improved compliance and lung volume.

A multicenter trial of 841 adult patients with acute RDS revealed that low tidal volume and hypercapnia resulted in a large reduction in mortality (40% to 31%) in the gentle ventilation group. Three trials in preterm infants have attempted to minimize lung injury by tolerating hypercapnia and reducing tidal volume and minute ventilation. A small pilot randomized trial revealed that permissive hypercapnia (target PaCO₂ of 45-55 mm Hg) during the first 4 days in infants who weighed 601-1250 g resulted in greater number of infants weaned from mechanical ventilation (P < 0.005).³

A second small trial did not confirm the potential benefits of permissive hypercapnia. A multicenter trial of infants who weighed less than 1000 g reported that permissive hypercapnia (target PaCO₂ >50 mm Hg) during the first 10 days of life led to a trend for reduced BPD or death at 36 weeks' postconceptional age (PCA) (68% vs 63%).

Furthermore, the strategy of permissive hypercapnia reduced the severity of BPD, as evidenced by a decreased need of ventilator support at 36 weeks' PCA from 16% to 1% (P < 0.005). Hypercapnia was well tolerated and no apparent side effects were reported in a study of infants with persistent pulmonary hypertension managed with PaCO₂ values of up to 60 mm Hg. In nonrandomized studies, infants with congenital diaphragmatic hernia also appear to benefit from permissive hypercapnia.^6,7 Gentle ventilator strategy of small tidal volumes, higher rates, and permissive hypercapnia may reduce BPD in very preterm infants.

Low tidal volume ventilation

Ventilatory strategies for CMV in infants should focus on prevention of overdistention, use of relatively small tidal volumes, maintenance of adequate FRC, and use of sufficient inspiratory and expiratory times. Because high maximal lung volume appears to correlate best with lung injury, selection of an appropriate PIP and FRC (or operating lung volume) is critical for the prevention of lung injury during pressure-limited ventilation. With the recognition that large tidal volumes lead to lung injury, relatively small tidal volumes are now recommended.

Studies in healthy infants report tidal volume ranges of 5-8 mL/kg, whereas infants with RDS have tidal volumes of 3-6 mL/kg. In infants with severe pulmonary disease, ventilation with small tidal volumes may be preferable because lung heterogeneity and unexpanded alveoli lead to overdistention and injury of the most compliant alveoli if a normal tidal volume is used. Maintenance of an adequate FRC is also necessary.

Strategies Based on Alternative Modes of Ventilation

Technologic advances have resulted in better ventilators. Patient-triggered ventilation (PTV), synchronized intermittent mandatory ventilation (SIMV), volume-targeted ventilation, and other new ventilator modes are increasingly used in newborns. HFV is another mode of ventilation that may reduce lung injury and may improve pulmonary outcomes, although available studies fail to demonstrate consistent benefits.

Patient-triggered ventilation

The most frequently used ventilators in newborns are time-triggered at a preset frequency; however, because of the available bias flow, the patient can also take spontaneous breaths. In contrast, PTV, which is also called assist/control, uses spontaneous respiratory effort to trigger the ventilator. During PTV, changes in airway flow or pressure, chest wall or abdominal movements, or esophageal pressure are used as an indicator of the onset of the inspiratory effort. Once the ventilator detects inspiratory effort, it delivers a ventilator breath at predetermined settings (PIP, inspiratory duration, flow).

Although improved oxygenation has been observed, PTV may occasionally have to be discontinued in some very immature infants because of weak respiratory efforts. A back-up (control) rate may be used to reduce this problem. Despite short-term benefit, large randomized controlled trials report that patient-triggered ventilation does not improve long-term outcomes in infants with RDS, although it may reduce the cost of care.^8,9

Synchronized intermittent mandatory ventilation

This mode of ventilation achieves synchrony between the patient and the ventilator breaths. Synchrony easily occurs in most newborns because strong respiratory reflexes during early life elicit relaxation of respiratory muscles at the end of lung inflation. Furthermore, inspiratory efforts usually start when lung volume is decreased at the end of exhalation. Synchrony may be achieved by nearly matching the ventilator frequency to the spontaneous respiratory rate or by simply ventilating at relatively high rates (60-120 min). Triggering systems can be used to achieve synchronization when synchrony does not occur with these maneuvers. SIMV is as effective as CMV; however, no major benefits were observed in a large randomized controlled trial.

Proportional assist ventilation

Unless they are flow-cycled, both modes of patient-initiated mechanical ventilation discussed above (PTV, SIMV) are designed to synchronize only the onset of the inspiratory support. In contrast, proportional assist ventilation (PAV) matches the onset and duration of both inspiratory and expiratory support. Ventilatory support is in proportion to the volume and/or flow of the spontaneous breath. Thus, the ventilator selectively can decrease the elastic and/or resistive work of breathing. The magnitude of the support can be adjusted depending on the patient's needs. When compared with CMV and PTV, PAV may reduce ventilatory pressures while maintaining or improving gas exchange. Randomized clinical trials are needed to determine if PAV leads to major benefits when compared to CMV.

Volume-targeted ventilation

Volume-targeted ventilators self-adjust in an attempt to maintain the tidal volume set by the clinician. This ventilatory strategy may be effective in maintaining tidal volume despite changes in respiratory mechanics. Modern neonatal ventilators with very sensitive and accurate flow sensors make adjustments to the PIP or inflation time from inflation to inflation to try to deliver the set volume. Although little information is available regarding the optimal tidal volume for preterm infants, typical VT is 4-6 mL/kg.

A meta-analysis of trials in preterm infants reported no significant differences in mortality between volume-targeted and pressure-limited groups but found some clinically important benefits of volume-targeting, including significant reductions in duration of intermittent positive pressure ventilation, rates of pneumothorax, and severe intraventricular hemorrhage.¹⁰

Volume-targeted ventilation may be particularly helpful in patients with heterogeneous lung disease because the differing time constants throughout the lung parenchyma when pressure-limited ventilation is used may result in suboptimal tidal volume delivery.

Tracheal gas insufflation

The added dead space of the ETT and the ventilator circuit that connects to the machine contribute to the anatomic dead space, reducing alveolar minute ventilation and resulting in reduced carbon dioxide elimination. In smaller infants or in those with increasingly severe pulmonary disease, dead space becomes the largest proportion of the tidal volume. With tracheal gas insufflation (TGS), gas delivered to the distal part of the ETT during exhalation washes out this dead space and the accompanying CO₂. TGS results in a decrease in PaCO₂ and/or PIP. If proven safe and effective, TGS should be useful in reducing tidal volume and the accompanying volutrauma, particularly in very premature infants and infants with very decreased lung compliance.

High-frequency ventilation

HFV may improve blood gases because, in addition to the gas transport by convection, other mechanisms of gas exchange may become active at high frequencies (variable velocity profiles of gas during inspiration and exhalation, gas exchange between parallel lung units, increased turbulence and diffusion). Extensive clinical use of the various HFVs has occurred in newborns. High-frequency positive-pressure ventilators use standard ventilators modified with low-compliance tubing and connectors. Thus, an adequate tidal volume may be delivered despite very short inspiratory times.

High-frequency jet ventilation (HFJV) is characterized by the delivery of gases from a high-pressure source through a small-bore injector cannula. The fast gas flowing out of the cannula possibly produces areas of relative negative pressure that entrain gases from their surroundings.

High-frequency flow interruption (HFFI) also delivers small tidal volumes by interrupting the flow of the pressure source; however, in contrast to jet ventilation, HFFI does not use an injector cannula.

High-frequency oscillatory ventilation (HFOV) delivers very small volumes (even smaller than dead space) at extremely high frequencies. Oscillatory ventilation is unique because exhalation is generated actively, as opposed to other forms of HFV, in which exhalation is passive.

HFOV, HFFI, and HFJV have been evaluated in many randomized controlled trials, including trials of more than 3000 preterm infants.^{11,12,13,14,15} Although the results between the trials have been heterogenous, meta-analysis reveals no clear evidence that HFV is superior to conventional ventilation as the initial mode of ventilatory support. Trends for reduction in mortality and BPD have been seen, despite a significant increase in air leaks with HFOV.

In addition, trends for an increase in grades 3 and 4 intraventricular hemorrhage and periventricular leukomalacia have been seen; however, the results are inconsistent in a subgroup meta-analysis of all trials using optimized respiratory care, including high use of antenatal steroids, surfactant replacement, lung volume recruitment, and high rate of conventional ventilation. Heterogeneity among trials of elective HFV compared with CMV in preterm infants may be due to differences in ventilatory strategies. Long-term outcome studies do not show an advantage of high-frequency ventilation over conventional ventilation. HFJV in preterm infants with pulmonary interstitial emphysema led to a more frequent and faster resolution of pulmonary interstitial emphysema but no reduction in mortality or other adverse outcomes.

In a randomized study of a population of infants born at less than 28 weeks' gestation, the initial mode of ventilation had no impact on respiratory or neurodevelopmental morbidity at age 2 years.¹⁶ HFOV and CMV appear equally effective for the early treatment of RDS.

Summary

Many advances in neonatal care have led to increased survival of smaller and critically ill infants. CMV is being used on smaller and more ill infants for longer durations. Sound application of the basic concepts of gas exchange, pulmonary mechanics, and control of breathing is necessary to optimize mechanical ventilation. The use of pathophysiology-based ventilatory strategies, strategies to prevent lung injury, and alternative modes of ventilation should result in further improvement in neonatal outcomes.

The benefits and drawbacks of CPAP or high-positive end-expiratory pressure in infants with RDS is as follows:

• Benefits
  • Increased alveolar volume and functional residual capacity
  • Alveolar recruitment
  • Alveolar stability
  • Redistribution of lung water
  • Improved V/Q matching
• Drawbacks
  • Increased risk for air leaks
  • Overdistention
  • CO ₂ retention
  • Cardiovascular impairment
  • Decreased compliance
  • May increase pulmonary vascular resistance

The benefits and drawbacks of high-rate, low tidal volume (low PIP) are as follows:  

• Benefits
  • Decreased air leaks
  • Decreased volutrauma
  • Decreased cardiovascular adverse effects
  • Decreased risk of pulmonary edema
• Drawbacks
  • Gas trapping or inadvertent positive end-expiratory pressure
  • Generalized atelectasis
  • Maldistribution of gas
  • Increased resistance

The benefits and drawbacks of high I/E ratio/long inspiratory time are as follows:  

• Benefits
  • Increased oxygenation
  • May improve gas distribution in lungs with atelectasis
• Drawbacks
  • Gas trapping and inadvertent positive end-expiratory pressure
  • Increased risk of volutrauma and air leaks
  • Impaired venous return
  • Increased pulmonary vascular resistance

The benefits and drawbacks of permissive hypercapnia in neonates are as follows:  


• Benefits
  • Decreased volutrauma and lung injury
  • Decreased duration of mechanical ventilation
  • Reduced alveolar ventilation
  • Reduced side effects of hypocapnia
  • Increased oxygen unloading
• Drawbacks
  • Cerebral vasodilation
  • Hypoxemia
  • Hyperkalemia
  • Decreased O ₂ uptake by hemoglobin
  • Increased pulmonary vascular resistance

The benefits and drawbacks of short inspiratory time are as follows:  

• Benefits
  • Faster weaning
  • Decreased risk for pneumothorax
  • Allows use of higher ventilator rate
• Drawbacks
  • Insufficient tidal volume
  • May need high flow rates

Multimedia

(Enlarge Image)

Media file 1: Relationships among ventilator-controlled variables (shaded circles) and pulmonary mechanics (unshaded circles) that determine minute ventilation during pressure-limited time-cycled ventilation. The relationships between the circles joined by solid lines are described by simple mathematical equations. The dashed lines represent relationships that cannot be calculated precisely without considering other variable such as pulmonary mechanics. Thus, simple mathematical equations determine the time constant of the lungs, the pressure gradient, and the inspiratory time. In turn, these determine the delivered tidal volume, which, when multiplied by the respiratory frequency, provides the minute ventilation. Alveolar ventilation can be calculated from the product of tidal volume and frequency when dead space is subtracted from the former (Adapted from Chatburn RL, Lough MD).

[ CLOSE WINDOW ]



Relationships among ventilator-controlled variables (shaded circles) and pulmonary mechanics (unshaded circles) that determine minute ventilation during pressure-limited time-cycled ventilation. The relationships between the circles joined by solid lines are described by simple mathematical equations. The dashed lines represent relationships that cannot be calculated precisely without considering other variable such as pulmonary mechanics. Thus, simple mathematical equations determine the time constant of the lungs, the pressure gradient, and the inspiratory time. In turn, these determine the delivered tidal volume, which, when multiplied by the respiratory frequency, provides the minute ventilation. Alveolar ventilation can be calculated from the product of tidal volume and frequency when dead space is subtracted from the former (Adapted from Chatburn RL, Lough MD).

(Enlarge Image)

Media file 2: Determinants of oxygenation during pressure-limited time-cycled ventilation. Shaded circles represent ventilator-controlled variables. Solid lines represent the simple mathematical relationships that determine mean airway pressure and oxygenation, whereas dashed lines represent relationships that cannot be quantified in a simple mathematical way (From Carlo WA, Greenough A, Chatburn RL).

[ CLOSE WINDOW ]



Determinants of oxygenation during pressure-limited time-cycled ventilation. Shaded circles represent ventilator-controlled variables. Solid lines represent the simple mathematical relationships that determine mean airway pressure and oxygenation, whereas dashed lines represent relationships that cannot be quantified in a simple mathematical way (From Carlo WA, Greenough A, Chatburn RL).

(Enlarge Image)

Media file 3: Effects of incomplete inspiration (A) or incomplete expiration (B) on gas exchange. An incomplete inspiration leads to decreases in tidal volume and mean airway pressure. Hypercapnia and hypoxemia may result. An incomplete expiration may lead to decreases in compliance and tidal volume and an increase in mean airway pressure. Hypercapnia with a decrease in PaO2 may result. However, gas trapping and its resulting increase in mean airway pressure may decrease venous return, decreasing cardiac output and impairing oxygen delivery (From Carlo WA, Greenough A, Chatburn RL).

[ CLOSE WINDOW ]



Effects of incomplete inspiration (A) or incomplete expiration (B) on gas exchange. An incomplete inspiration leads to decreases in tidal volume and mean airway pressure. Hypercapnia and hypoxemia may result. An incomplete expiration may lead to decreases in compliance and tidal volume and an increase in mean airway pressure. Hypercapnia with a decrease in PaO2 may result. However, gas trapping and its resulting increase in mean airway pressure may decrease venous return, decreasing cardiac output and impairing oxygen delivery (From Carlo WA, Greenough A, Chatburn RL).

(Enlarge Image)

Media file 4: Estimation of optimal inspiratory and expiratory times based on chest wall motion (From Ambalavanan N, Carlo WA).

[ CLOSE WINDOW ]



Estimation of optimal inspiratory and expiratory times based on chest wall motion (From Ambalavanan N, Carlo WA).

Keywords

assisted ventilation of the newborn, assisted ventilation of the neonate, respiratory support, breathing support, neonatal care, chronic lung disease, pulmonary mechanics, gas exchange, lung injury, control of breathing, conventional mechanical ventilation, CMV, hypercapnia, ventilation/perfusion, V/Q, hypoventilation, venoarterial shunts, apnea of prematurity, respiratory distress syndrome, RDS, high-frequency ventilation, HFV, hypoxemia, congenital cyanotic heart disease, patent ductus arteriosus, interstitial lung disease, gas trapping, metabolic acidosis, metabolic alkalosis

• Search for CME/CE on This Topic »